XLVII CONGRESSO SOCIETÀ ITALIANA DI NEUROLOGIA Venezia, 22-25 Ottobre 2016 Polo Congressuale – Lido di Venezia

Programma scientifico

22 OTTOBRE 2016

CORSI DI AGGIORNAMENTO A NUMERO CHIUSO 1 (RICHIESTO ACCREDITAMENTO A NUMERO CHIUSO) ORE 11.00 – 17.00 Urgenze in neurologia Moderatori: E.C. AGOSTONI (Milano), G. MICIELI (Pavia) PRIMA PARTE • Acuzie nei disturbi del movimento A. BERARDELLI (Roma) • Disturbi “funzionali” a esordio acuto C. SERRATI (Genova) Trattamento endovascolare: cambierà la gestione del paziente con ictus acuto? • Le evidenze D. TONI (Roma) • L’organizzazione E.C. AGOSTONI (Milano) • Crisi epilettiche e stato di male in Pronto Soccorso F. Minicucci (Milano) • Disturbi parossistici notturni non epilettici R. MANNI (Pavia) SECONDA PARTE Moderatori: G. TEDESCHI (Napoli), B. GIOMETTO (Padova) • Rabdomiolisi e dolori muscolari acuti A. TOSCANO (Messina) • Crisi miasteniche A. EVOLI (Roma)

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• Neuropatie motorie acute C. BRIANI (Padova) • Patologie neurologiche acute: il setting neurologico è più vantaggioso? G. MICIELI (Pavia) TAVOLA ROTONDA • Modelli organizzativi per la neurologia d’urgenza Moderatore: F.A. DE FALCO (Napoli)

CORSI DI AGGIORNAMENTO A NUMERO CHIUSO 2 (RICHIESTO ACCREDITAMENTO A NUMERO CHIUSO) ORE 11.00 – 17.00 Ruolo della Risonanza Magnetica convenzionale e avanzata nella diagnosi e prognosi delle principali patologie neurologiche Moderatori: M. FILIPPI (Milano), G. TEDESCHI (Napoli) PRIMA PARTE • Sclerosi Multipla M. ROCCA (Milano) • Malattie vascolari A. BOZZAO (Roma) • Tumori A. FALINI (Milano) • Vasculiti del sistema nervoso centrale N. DE STEFANO (Siena) SECONDA PARTE Moderatori: N. DE STEFANO (Siena), M. ROCCA (Milano) • Malattia di Alzheimer A. PADOVANI (Brescia) • Demenza fronto-temporale F. AGOSTA (Milano) • Sclerosi Laterale Amiotrofica F. TROJISI (Napoli) • Malattia di Parkinson A. QUATTRONE (Catanzaro)

CORSI DI AGGIORNAMENTO A NUMERO CHIUSO 3 (RICHIESTO ACCREDITAMENTO A NUMERO CHIUSO) ORE 11.00 – 14.00 I criteri diagnostici per le demenze Moderatori: D. GALIMBERTI (Milano), M. MUSICCO (Milano) • I criteri del National Institute of Aging A. CAGNIN (Padova) • I criteri dell’International Working Group D. PERANI (Milano) • Discussione: convergenze e divergenze tra i due criteri • Demenza con corpi di Lewy e Parkinson L. BONANNI (Chieti)

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• Demenze frontotemporali D. GALIMBERTI (Milano)

CORSI DI AGGIORNAMENTO A NUMERO CHIUSO 4 (RICHIESTO ACCREDITAMENTO A NUMERO CHIUSO) ORE 11.00 – 14.00 Avanzamenti clinici e biomolecolari nella Doppler myocardial imaging Moderatore: G. MEOLA (San Donato Milanese, MI) • Abnormal splicing in myotonic dystrophy D. FURLING (Paris, F) • Fatica e disturbi del sonno G. SICILIANO (Pisa) • Imaging muscolare M. GARIBALDI (Roma - Nice, F) • Biomarkers in Doppler myocardial imaging C. ANGELINI (Padova) • Translational research in Doppler myocardial imaging: current approaches towards novel therapies G. BASSEZ (Creteil, F)

CORSI DI AGGIORNAMENTO A NUMERO CHIUSO 5 (RICHIESTO ACCREDITAMENTO A NUMERO CHIUSO) ORE 11.00 – 14.00 Semeiotica dei disordini del movimento Moderatori: G. ABBRUZZESE (Genova), P. CORTELLI (Bologna) • Distonia G. DE FAZIO (Bari) • Tremore A. BERARDELLI (Roma) • Disturbi funzionale del movimento M. TINAZZI (Verona) • Le ipocinesie P. BARONE (Napoli)

CORSI DI AGGIORNAMENTO A NUMERO CHIUSO 6 (RICHIESTO ACCREDITAMENTO A NUMERO CHIUSO) ORE 11.00 – 14.00 Disordini di coscienza legati a gravi cerebrolesioni acquisite Moderatori: P. BRAMANTI (Messina), P.M. ROSSINI (Roma) • Neuroepidemiologia ed inquadramento diagnostico dei disordini di coscienza P.M. ROSSINI (Roma) • I percorsi P. BRAMANTI (Messina) • Trattamento riabilitativo L. SALTUARI (Bolzano) • Problematiche etiche e legislative G.L. GIGLI (Roma)

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CORSI DI AGGIORNAMENTO A NUMERO CHIUSO 7 (RICHIESTO ACCREDITAMENTO A NUMERO CHIUSO) ORE 11.00 – 14.00 La sindrome di Guillain Barrè Strohl 100 anni dopo: cosa c’è di nuovo? Moderatori: G. CAVALETTI (Milano), A. SCHENONE (Genova) • Inquadramento clinico terapeutico, fattori di rischio e misure di outcome E. NOBILE ORAZIO (Milano) • Le nodo-paranodopatie immunomediate A. UNCINI (Chieti) • La sindrome di Guillain Barrè cronica: una definizione errata o una realtà clinica da chiarire? D. COCITO (Torino) • Le plessopatie infiammatorie C. BRIANI (Padova)

CORSI DI AGGIORNAMENTO A NUMERO CHIUSO 8 (RICHIESTO ACCREDITAMENTO A NUMERO CHIUSO) ORE 11.00 – 14.00 Nuove frontiere della stimolazione cerebrale non invasiva in neurologia Moderatori: C. CALTAGIRONE (Roma), G. KOCH (Roma) • Il contributo della coregistrazione TMS-EEG (Stimolazione Magnetica Transcranica-Elettroencefalogramma) nell’esplorazione del connettoma corticale umano C. MINIUSSI (Brescia) • Integrazione globale della funzione cerebrale nei pazienti con disturbi dello stato di coscienza M. MASSIMINI (Milano) • La malattia di Alzheimer: un disturbo della plasticità corticale G. KOCH (Roma) • Stimolazione cerebrale non invasiva integrata con la robotica nella riabilitazione dell’ictus V. Di Lazzaro (Roma)

CORSI DI AGGIORNAMENTO A NUMERO CHIUSO 9 (RICHIESTO ACCREDITAMENTO A NUMERO CHIUSO) ORE 11.00 – 14.00 Esame liquorale Moderatori: D. FRANCIOTTA (Pavia), G.L. MANCARDI (Genova) • Fisiopatologia e diagnostica neuro-immunologica generale D. FRANCIOTTA (Pavia) • Le malattie infettive P. CINQUE (Milano) • Le encefaliti immuno-mediate B. GIOMETTO (Padova) • Le malattie degenerative L. PARNETTI (Perugia)

14.00-15.00 PAUSA PRANZO

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SIMPOSIO ORE 15.00 – 17.00 Riconoscere e gestire i problemi iatrogeni nell’anziano in collaborazione con la Società Italiana di Neurogeriatria Moderatori: C. CALTAGIRONE (Roma), E. COSTANZO (Catania) • Concetti di neurofarmacologia clinica nell’anziano S. CUZZOCREA (Messina) • Disturbi del movimento indotti da farmaci F.E. PONTIERI (Roma) • Disturbi cognitivi indotti da farmaci C. SERRATI (Genova) • Disturbi dello stato di coscienza iatrogeni G. BELELLI (Milano), M. MUSICCO (Milano) • Sintesi generale e conclusioni G. FABBRINI (Roma)

SIMPOSIO ORE 15.00 – 17.00 Neurosonologia in collaborazione con SINSEC- Società Italiana di NeuroSonologia Emodinamica Cerebrale Moderatori: C. BARACCHINI (Padova), S. Ricci (Città di Castello – PG) • Stenosi carotidea asintomatica: stima del rischio C. FINOCCHI (Genova) • Patologia ostruttiva del circolo posteriore: servono gli ultrasuoni? C. BARACCHINI (Genova) • TCD/TCCD: Revisione di accuratezza diagnostica S.CENCIARELLI (Città di Castello – PG) • Stroke mimics: soluzioni mediante ultrasuoni G.GIUSSANI ( Lecco)

WORKSHOP 1 ORE 15.00 – 17.00 Le urgenze Neurologiche in gravidanza: organizzazione dei percorsi di cura Moderatori: G. GIUSSANI (Milano), A. PROTTI (Milano) • La gestione delle urgenze tra territorio e ospedale R. ZANINI (Verona) • Le emergenze neurochirurgiche e neurointerventistiche M. PIANO (Milano) • La cefalea acuta nella donna gravida G. BONO (Pavia) • Presentazione del volume: Neurological Emergency during Pregnancy A. PROTTI (Milano)

WORKSHOP 2 ORE 15.00 – 17.00

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Nuovi scenari nella stimolazione cerebrale profonda Moderatori: L. LOPIANO (Torino), F. VALZANIA (Modena) • Il Parkinson dopo la Deep Brain Stimulation: una nuova malattia? F. CONTARINO (Leiden, D) • Deep Brain Stimulation e urgenze G. COSSU (Cagliari) • Impatto nella pratica clinica delle recenti innovazioni M.C. SENSI (Ferrara) • Sostituzione del generatori d’impulsi: continuità terapeutica, durata e rimborsabilità M.G. RIZZONE (Torino) 1

WORKSHOP 3 ORE 15.00 – 17.00 Ritmi circadiani e patologie neurologiche: insights fisiopatologici e implicazioni cliniche Moderatori: R. FERRI (Troina - EN), F. PIZZA (Bologna) • Ritmi circadiani e timing degli attacchi emicranici: implicazioni cliniche e fisiopatologiche M. DE TOMMASO (Bari) • I ritmi circadiani contano nell’epilessia? Occorrenza delle crisi e target terapeutici R. MANNI (Pavia) • Sonno, ritmi circadiani e patogenesi della malattia di Alzheimer B. GUARNIERI (Città Sant’Angelo, PE) • Sonno, stroke e modulazione circadiana della pressione arteriosa C. LOMBARDI (Milano)

WORKSHOP 4 ORE 15.00 – 17.00 La neuropsicologia nella prassi della neurologia clinica Moderatori: G. MICELI (Rovereto, TN), M.C. SILVERI (Roma), D. QUARANTA (Roma) • La neuropsicologia a letto dell’ammalato D. GROSSI (Napoli) • La neuropsicologia in sala operatoria C. PAPAGNO (Milano) • La neuropsicologia in tribunale A. STRACCIARI (Bologna) • La neuropsicologia e le neuroimmagini D. PERANI (Milano) • La neuropsicologia in riabilitazione A. MAZZUCCHI (Parma)

WORKSHOP 5 ORE 15.00 – 17.00 I luoghi assistenziali neurologici Moderatori: V. NAPOLETANO (Bari), R. DI FEDE (Bari), M. NOTARIELLO (Foggia)

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• Introduzione G. TEDESCHI (Napoli) • L’integrazione Ospedale Territorio nei cambiamenti dell’organizzazione dell’assistenza alle malattie del Sistema Nervoso V. NAPOLETANO (Bari), L. PROVINCIALI (Ancona) • UVM (Unità di Valutazione multidisciplinare)– PAI (Piano assistenziale individuale)– SMANDI ( Scuola valutazione multidimensionale disabili)– ICF (Classificazione Internazionale del Funzionamento) e cure domiciliari quale alternativa a RSA(Residenze Sanitarie Assistenziali) ed RSSA (Residenza Socio Sanitaria Assistenziale)– come fare un PAI (Piano assistenziale individuale) A. RUSSELLO (Lecce) • Il PTA ( Piano Terapeutico Aziendale) : quando le cure in Hospice, RSA (Residenze Sanitarie Assistenziali) ed RSA1 (Residenze Sanitarie Assistenziali) S. GEMMA (Foggia) • Il modello HUB and Spoke, un servizio per la complessità organizzativa e assistenziale nelle macroaree regionali per le malattie neurodegenerative R. ELEOPRA (Mestre), R. QUATRALE (Udine) • I luoghi fisici della Ricerca tra Presidio Ospedaliero e Presidio Territoriale di Assistenza M.R. TOLA (Ferrara), E. MONTANARI (Fidenza) 10.30-ffff

WORKSHOP 6 ORE 15.00 – 17.00 Trattamenti in neuroncologia: casi clinico complessi Moderatori: A. SILVANI (Milano), V. VILLANI (Roma) • Gliomatosis cerebri o malattia demielinizzante A. SALMAGGI (Lecco) • Encefalite o neoplasia gliale? E. MARCHIONI (Pavia) • Disturbi neurologici in pazienti con tumore della mammella R. RUDÀ (Torino) • Lesione espansiva nel paziente anziano: glioblastoma o linfoma? A. SILVANI (Milano)

17.00-17.30 PAUSA CAFFÈ

CERIMONIA DI INAUGURAZIONE 17.30 SALUTO DELLE AUTORITÀ 18.30 LETTURA MAGISTRALE From Plague control in the republic of Venice to the new WHO (world health organitation) International health regulations

L. BERTINATO (Venezia)

23 OTTOBRE 2016

SESSIONE PLENARIA ORE 8.30 – 10.30 Contributo dei neurologi italiani all’estero Moderatori: C. FERRARESE (Milano), C. SERRATI (Genova), G. TEDESCHI (Napoli) • Trauma cranico R. SAVICA (Rochester, USA)

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• Nuovi modelli assistenziali nel trattamento della fase avanzata della Malattia di Parkinson A. FASANO (Toronto, CAN) • Sclerosi Multipla O. CICCARELLI (Londra, UK) • Ictus ischemico ed emorragico sono malattie trattabili: la rivoluzione della neurochirurgia endovascolare I. LINFANTE (Miami, USA) 10.30-11.00 PAUSA CAFFÈ 11.00-13.00 SESSIONI DI COMUNICAZIONI ORALI SUI SEGUENTI ARGOMENTI Casi clinici 1 ( vedi descrizione pagina 21), disordini del movimento 1 neuroimmunologia, cefalee 1, malattie cerebrovascolari 1, malattie del motoneurone, malattie neuromuscolari,1 Sclerosi multipla 1, demenza 1 Saranno presentate 8 comunicazioni libere per ciascun argomento, che avranno come obiettivo l’aggiornamento sulle singole patologie Elenco relatori a pag 21 13.00-14.30 PAUSA PRANZO 13.30-14.30

CONFERENZE DIDATTICHE ORE 13.00 – 14.30 Le mieliti Progressi nel percorso dalla sindrome alla malattia Moderatore: P. ANNUNZIATA (Siena) • Le mieliti acute traverse: alla ricerca di nuovi marcatori di diagnosi e prognosi P. ANNUNZIATA (Siena) • Mieliti autoimmuni e post infettive E. Marchioni (Pavia) • Mieliti e malattie infiammatorie del connettivo M. Zoccarato (Padova)

Patologie emergenti Moderatore: B. GIOMETTO (Padova) • Role of the WFN (World Federation of Neurology) toward world wide education to improve neurological care W. GRISOLD (Vienna, A) • Transient Neuro-Epidemiology in Africa: from infectious to vascular and degenerative factors A. GALLO DIOPP (Dakar, SN) • Encefalite erpetica ed Ac anti-NMDAR (The N-methyl-D-aspartate receptor): relazione tra infezione ed autoimmunità B. GIOMETTO (Padova)

LETTURA ORE 14:00 – 14:30 Disturbo del controllo degli impulsi e malattia di Parkinson In collaborazione con UCB Moderatori: P.Stanzione ( Roma ) Icarus: i risultati di uno studio osservazionale italiano • A. ANTONINI (Milano)

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SIMPOSIO ORE 14.00-15.00 Rivaroxaban in Neurologia: evidenze ed esperienze In collaborazione con Bayer Moderatori: G. MICIELI (Pavia) • Evidenze nel paziente impegnativo e conferme nella vita reale M. DEL SETTE (Genova) • Esperienza pratica clinica M. PACIARONI (Perugia)

SIMPOSIO ORE 14.00-15.00 Spasticità, plasticità e riabilitazione nella Sclerosi Multipla In collaborazione con Almirall Moderatori: G. COMI (Milano), P.BRAMANTI (Messina) • Basi neurobiologiche degli interventi riabilitativi D.CENTONZE (Roma)

• Terapia fisica e farmacologia nel management della spasticità in neuroriabilitazione M. Rovaris (Milano) • Discussione sui temi trattati nel simposio

SIMPOSIO ORE 14.30-16.30 La medicina di genere e le malattie neurologiche e alle malattie neurologiche Moderatori: C. PACI (San Benedetto del Tronto, AP), M.G. PISCAGLIA (Ravenna) • Introduzione L. PROVINCIALI (Ancona) • Epidemiologia delle malattie neurologiche in relazione al sesso E. BEGHI (Milano) • Sclerosi Multipla e medicina di genere C. TORTORELLA (Bari) • Demenze e medicina di genere P. MERLO (Bergamo) • Medicina di genere e medicina di precisione A. PROTTI (Milano) • La normativa sulla medicina di genere P. BOLDRINI (Roma) • Discussione (La discussione si baserà sugli argomenti tratti nel simposio)

SIMPOSIO ORE 14.30-16.30 Demenze degenerative e vascolari: ha ancora un senso una distinzione netta? Moderatori: C. CALTAGIRONE (Roma), M. SILVESTRINI (Ancona) • Introduzione

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C. CALTAGIRONE (Roma) • Inquadramento nosografico e impatto epidemiologico delle forme miste A. PADOVANI (Brescia) • Il contributo del neuroimaging alla diagnosi di deterioramento cognitivo vascolare L. PANTONI (Firenze) • I fattori di rischio comuni M. SILVESTRINI (Ancona)

SIMPOSIO ORE 15.00 -16.00 Nuovo approccio nel trattamento della depressione: “la multimodalità” In collaborazione con Lundbeck Moderatori:

L. PROVINCIALI

(Ancona)

• La multimodalità: nuovo approccio farmacologico per il trattamento della depressione maggiore N.NICOLETTI (Roma) • I sintomi cognitivi nel paziente depresso: impatto, diagnosi e cura A.PADOVANI (Padova)

SIMPOSIO ORE 15.00 -16.00 Teriflunomide: dagli studi registrativi, alle nuove evidenze, alla “real life”

Moderatori: M.G. MARROSU (Cagliari) • Teriflunomide alla luce dell’evoluzione dei “treatment goals” in Sclerosi Multipla D.CENTONZE (Roma) • “Brain Atrophy” e progressione della disabilità P. GALLO (Padova) • La definizione del profilo scientifico di un farmaco: ruolo della “real life” L. TROJANO (Bari)

SIMPOSIO ORE 15.00-17.00 Nuove frontiere per l’ictus acuto tra innovazioni terapeutiche e vincoli organizzativi in collaborazione con Italiana Stroke Organization - ISO Moderatori: A. CAROLEI (L’Aquila) • Registro SITS (Safe Implementation of Treatment in Stroke) e Registro endovascolare D. TONI (Roma), S. MANGIAFICO (Firenze) • Nuovi trial clinici: risultati, revisioni sistematiche e meta-analisi I. LINFANTE (Miami, USA) • Nuovi trial di confronto diretto D. TONI (Roma) • Documento di consenso E.C. AGOSTONI (Milano)

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SIMPOSIO ORE 16.00 -17.00 Il futuro della Sclerosi Multipla:evidenze e prospettive In collaborazione con Merck Moderatori:

G. COMI

(Milano) - M. TROJANO (Bari)

• Immunità cellulare: nuovi target terapeutici R. FURLAN (Milano) • Efficacia delle nuove opzioni terapeutiche: Evidenze dagli studi clinici G. COMI (Milano) • Il profilo di sicurezza delle nuove opzioni terapeutiche F. PATTI (Catania)

17.00-17.30 PRESENTAZIONE DEL VOLUME “CONDIVISIONE MULTIDISCIPLINARE DEL PERCORSO ASSISTENZIALE DELLA

SCLEROSI MULTIPLA” A. FRANCIA (Roma) 17.00-17.30 PAUSA CAFFÈ

WORKSHOP 7 ORE 17.30 – 19.30 Comorbilità nella Sclerosi Multipla Moderatore: G.M. MARROSU (Cagliari) • Nuovi criteri diagnostici di Risonanza Magnetica M. FILIPPI (Milano) • Rilevanza delle comorbilità nei trattamenti farmacologici A. LUGARESI (Bologna) • Impatto economico delle comorbilità R. BERGAMASCHI (Pavia) • Gestione delle comorbilità nel setting clinico E. COCCO (Cagliari)

WORKSHOP 8 ORE 17.30 – 19.30 Cefalea cronica quotidiana Moderatori: P. CORTELLI (Bologna), A. RUSSO (Napoli) • Diagnosi e classificazione delle cefalee croniche primarie M. RUSSO (Parma), P. TORELLI (Parma) • Nuovi approcci diagnostici nelle cefalee croniche secondarie M.R. MAZZA (Catanzaro), F. BONO (Catanzaro) • Terapie farmacologiche e non delle cefalee croniche G. COPPOLA (Roma), F. PIERELLI (Latina)

WORKSHOP 9 ORE 17.30 – 19.30 Terapia sintomatica nella grave disabilità neurologica Moderatori: C.A. DEFANTI (Gazzaniga, BG), A. CONTE (Roma)

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• “Sintomatico” o “palliativo”: due termini per la stessa cura o approcci diversi? A. SOLARI (Milano) • Dolore e spasticità nella Sclerosi Multipla C. SOLARO (Genova) • Dispnea e insufficienza respiratoria nella Sclerosi Laterale Amiotrofica F.O. LOGULLO (Macerata) • Gestione sintomatica del paziente con ictus nella STROKE UNIT D. INZITARI (Firenze), V. CRESPI (Monza) • Discussione (Discussione sui temi trattati nella sessione)

WORKSHOP 10 ORE 17.30 – 19.30 Misurazione dell’atrofia in neurologia: stato dell’arte Moderatori: G. ARABIA (Catanzaro), M.A. ROCCA (Milano) • Misurazione dell’atrofia: aspetti tecnici e variabili fisiologiche A. GIORGIO (Siena) • Sclerosi multipla A. GALLO (Napoli) • Demenze F. AGOSTA (Milano) • Disturbi del movimento G. ARABIA (Catanzaro)

WORKSHOP 11 ORE 17.30 – 19.30 Le demenze leucoencefalopatiche non vascolari Moderatori: F. AGOSTA (Milano), M. MUSICCO (Milano) • Introduzione F. TAGLIAVINI (Milano) • Meccanismi cellulari, metabolici e molecolari nelle leucodistrofie e leucopatie su base genetica M. BUGIANI (Amsterdam, NL) • Quadri di imaging delle leucodistrofie e leucopatie VAN DER KNAPP (Amsterdam, NL) • La leucoaraiosi è sempre di origine vascolare? L. PANTONI (Firenze) • Il caso del Cadasil A. FEDERICO (Siena) • Il caso dell’angiopatia amiloide cerebrale F. PIAZZA (Milano) • Profili neuropsicologi e clinici da danno della sostanza bianca nelle demenze S. CAPPA (Pavia)

WORKSHOP 12 ORE 17.30 – 19.30 Paraparesi spastiche familiari: aggiornamenti sugli aspetti diagnostici e terapeutici

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Moderatori: F. SANTORELLI (Pisa), A. TOSCANO (Messina) • Clinica e diagnostica delle forme autosomico dominanti G. DE MICHELE (Napoli) • Clinica e diagnostica delle forme autosomico recessive C. CASALI (Latina) • Come procedere alla diagnosi genetica M.T. BASSI (Bosisio Parini, MI) • Terapia: presente e futuro M.T. DOTTI (Siena) 10.30-ffff

WORKSHOP 13 ORE 17.30 – 19.30 Eredoatassie e dintorni. Dedicato alla memoria di Stefano Di Donato Moderatori: D. DIODATO (Roma), M. ZEVIANI (Cambridge, UK) • Stefano di Donato: neurologo, scienziato e maestro A. FEDERICO (Siena) • Eredoatassie: inquadramento clinico A. FILLA (Napoli) • Genetica molecolare e diagnostica avanzata delle eredoatassie F. TARONI (Milano) • Atassia di Friedreich: dai meccanismi molecolari alla terapia sperimentale M. PANDOLFO (Bruxelles, B) • La complessità genetica e patogenetica della malattia di Huntington E. CATTANEO (Milano) 10.30-ff

WORKSHOP 14 ORE 17.30 – 19.30 Taupatie: disturbi della mente e del movimento Moderatori: R. CERAVOLO (Pisa), F. MORGANTE (Messina) • Aspetti clinici e classificazione C. COLOSIMO (Roma, Terni) • Aspetti clinici della FTD (Demenza Frontotemporale) E. SCARPINI (Milano) • Neuropatologia delle taupatie P. PARCHI (Bologna) • Neurofisiopatologia delle taupatie M. BOLOGNA (Roma)

WORKSHOP 15 ORE 17.30 – 19.30 10.30-ffff L’ictus, i nuovi movimenti, gli stakeholders ed il filo rosso delle evidenze scientifiche Moderatori: V. PIRAS (Cagliari), S. RICCI (Città di Castello, PG) • 118/PS P. CANDELARESI (Milano)

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• Neuroradiologo E. CICERI (Verona) • Giovane neurologo V. OPPO (Milano) • Neurologo A. CICCONE (Mantova) • Utente-Caregiver A. MALAGUTTI (Mantova) • Riabilitatore M. TARICCO (Bologna) • Il decisore V. PANELLA (Roma)

WORKSHOP 16 ORE 17.30 – 19.30 Variabilità delle lesioni nelle malattie neurodegenerative: stadi di malattia o eterogeneità fenotipica? Moderatori: M.B.A. MELONE (Napoli), E. PEGORARO (Padova) • Malattia di Alzheimer e taupatie G. GIACCONE (Milano) • Parkinson e sinucleinopatie S. FERRARI (Roma) • Corea di Huntington F.R. FUSCO (Roma) • Sclerosi Laterale Amiotrofica e TDP43 (TAR DNA-binding protein) M.T. GIORDANA (Torino)

24 OTTOBRE 2016

08.00-10.00 SESSIONE PLENARIA Organizzazione dell’assistenza neurologica Moderatori: E.C. AGOSTONI (Milano), L. LOPIANO (Torino), L. PROVINCIALI (Ancona) • Nuovi orientamenti per fronteggiare la crisi sanitaria F. SPANDONARO (Roma) • Il ruolo delle Aziende di alta specialità nell’urgenza neurologica A. ZOLI (Milano) • Modelli di integrazione Ospedale-Territorio M. FABI (Parma) • Sostenibilità del sistema sanitario nazionale: un approccio value - based in neurologia N. CARTABELLOTTA (Bologna) 10.00-11.00 ASSEMBLEA DEI SOCI SIN 11.00-11.15 PAUSA CAFFÈ

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- SOCIETA’ ITALIANA DI NEUROLOGIA

11.15-12.30 SESSIONI DI COMUNICAZIONI ORALI SUI SEGUENTI ARGOMENTI Casi Clinici 2 ( vedi descrizione pagina 21), Disordini del movimento 2, Neuropsicologia clinica, Cefalee 2, Malattie cerebrovascolari 2, malattie degenerative, dolore, malattie neuromuscolari 2 Saranno presentate 8 comunicazioni libere per ciascun argomento, che avranno come obiettivo l’aggiornamento sulle singole patologie. Elenco relatori a pag 21

12.30-14.30 PAUSA PRANZO

Lettura ORE 12.30-13.30 Gestione del trattamento anticoagulante nei pazienti con fibrillazione atriale in ambito neurologico In collaborazione con Pfizer & Bristol Myers Squibb G. MICIELI (Pavia)

Simposio ORE 12.30-13.30 Sclerosi Multipla oggi: una toria che sostiene il presente e guarda al futuro In collaborazione con Teva Moderatore: G. COMI (Milano) • Copaxone, la storia continua G. COMI (Milano) • Dati real life: scelta dell’algoritmo terapeutico M. TROJANO (Bari) • Il carico gestionale nel trattamento della Sclerosi Multipla L. PROVINCIALI (Ancona)

13.00-13.30 BREAKING NEWS Risultati dalla Consensus Conference internazionale sulla Epilessia frontale notturna P. TINUPER (Bologna)

Lettura ORE 13.30 – 14.00 Malattia di Parkinson: identificare la fase avanzata e il corretto processo di referral In collaborazione con Abbvie Moderatore: L. LOPIANO (Torino) Relatore: A. ANTONINI (Padova)

SIMPOSIO ORE 13.30-15.30 Cambiare la storia di malattia del paziente SMRR (Sclerosi Multipla Remittente Recidivante): quale approccio? In collaborazione con Biogen Italia

• Introduzione P. GALLO (Padova) Moderatori: M.P. AMATO (Firenze) • Strategie di trattamento per il paziente mild-to-moderate: Peginterferone beta-1a e dimetilfumarato, approcci innovativi nella gestione del paziente di I linea P. PERINI (Padova)

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Moderatori: P. GALLO (Padova) • Strategie di trattamento per il paziente highly-active: Natalizumab: “A decade of difference” Daclizumab, un nuovo traguardo della ricerca scientifica A.UCCELLI (Genova) • Discussioni (La discussione si baserà sugli argomenti tratti nel simposio)

• Conclusioni M.P. AMATO (Firenze)

SIMPOSIO ORE 13.45-15.30 La neuroinfiammazione nelle patologie neurologiche acute e croniche: nuove prospettive terapeutiche? In collaborazione con Epitech group Moderatori: C. Caltagirone (Roma), C Ferrarese (Milano), F. Orzi (Roma) • Meccanismi di neuroinfiammazione F. NICOLETTI (Roma) • Il ruolo delle citochine P.BOSSU’ (Roma) • La neuroinfiammazione nell’ ictus ischemico G.DE SIMONI (Milano) • La neuroinfiammazione nelle malattie neurodegenerative L.TREMOLIZZO (Milano) • Nuove prospettive terapeutiche S. CUZZOCREA (Messina)

SIMPOSIO ORE 14.30-16.00 SYMPOSIUM OF THE ITALIAN NeuPSIG Moderatore: G. CRUCCU (Roma) • Chronic leg and back pain: the problems entailed by mixed pain R. BARON (Kiel, D) • The role of topical treatments: lidocaine versus capsaicin S. TAMBURIN (Verona) • Combination therapy: contrasting views G. CRUCCU (Roma) • New European guidelines on central stimulation therapy for chronic pain A. TRUINI (Roma)

SIMPOSIO ORE 14.30-16.00 Leber’s Hereditary Optic Neuropathy – Aspetti clinici, diagnostici e terapeutici In collaborazione con Santhera Moderatore: A. Toscano (Messina) Co-Moderatore: P. Morandi Treu (Roma)

• Bisogni dei pazienti LHON (Leber’s Hereditary Optic Neuropathology ) e il valore dell’Associazione dei pazienti

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P. MORANDI TREU (Roma) • Neuropatia ottica ereditaria di Leber (LHON - Leber’s Hereditary Optic Neuropathology) : diagnostica differenziale, conferma genetica ed inquadramento clinico terapeutico V. CARELLI (Bologna) • Impiego clinico di Raxone nell’ambito della LHON: i risultati della “Consensus on guidelines for idebenone Administration in Leber’s hereditary optic neuropathy C. LA MORGIA (Bologna) • The clinical Development of Raxone for the LHON indication G.METZ (Germania) • Malattie Mitocondriali e Registri Nazionali e internazionali P. SANTANTONIO (Roma)

SIMPOSIO ORE 14.30-16.30 Network italiano per le forme autosomiche dominanti di malattia di Alzheimer e demenza frontotemporale Moderatori: S. CAPPA (Milano), • Introduzione G. FRISONI (Milano) • Procedure standardizzate per la valutazione delle forme genetiche di malattia di Alzheimer e demenza frontotemporale M. PIEVANI (Brescia) • Registro e biobanca per le forme genetiche di malattia di Alzheimer e demenza frontotemporale F. TAGLIAVINI (Milano), D. GALIMBERTI (Milano) • La consulenza genetica nelle forme familiari di malattia di Alzheimer e demenza frontotemporale A.C. BRUNI (Lamezia Terme), S. SORBI (Firenze) • Una rete sinergica per lo studio delle forme genetiche di malattia di Alzheimer e demenza frontotemporale A. PADOVANI (Brescia)

SIMPOSIO ORE 14.30-16.30 Le tecniche neurofisiologiche nella prognosi delle patologie neurologiche Moderatori: V. DI LAZZARO (Roma), L. LEOCANI (Milano) • Stroke V. DI LAZZARO (Roma) • Malattie del motoneurone A. QUARTARONE (Messina) • Sclerosi Multipla L. LEOCANI (Milano) • Disturbi del Movimento A. BERARDELLI (Roma)

SIMPOSIO ORE 15.30 -16.30 Genitorialità e Sclerosi Multipla In collaborazione con Merck Moderatori:

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A. BERTOLOTTO (Orbassano

- TO) - G. TEDESCHI (Napoli)

• “Genitori si può, anche con la Sclerosi Multipla” L. LAVORGNA (Napoli) • Genitorialità e SM: le esigenze dei pazienti e il ruolo dell’associazione (AISM) M. BATTAGLIA (Genova) • Genitorialità e SM: le esigenze dei pazienti e il ruolo del clinico M.G. MARROSU (Cagliari)

SIMPOSIO ORE 16.30 - 17.30 La strategia di induzione: esperienze a confronto Moderatori: G. COMI (Milano) • Introduzione G. COMI (Milano) • Esperienze a confronto L.MOIOLA (Milano), A.BERTOLOTTO (Torino), M.G. MARROSU (Cagliari) • Discussione (La discussione si baserà sugli argomenti tratti nel simposio)

16.30-17.30 PAUSA CAFFÈ

WORKSHOPS 17 ORE 17.30-19.30 La terapia nella fase avanzata della malattia di Parkinson Moderatori: A. ALBANESE (Milano), R. ELEOPRA (Udine) • Quale terapia per quale paziente? U. BONUCCELLI (Pisa) • DBS (Deep Brain Stimulation): attualità e innovazioni future M. ZIBETTI (Torino) • Stimolazione Dopaminergica continua, con infusione intestinale A. ANTONINI (Venezia)

WORKSHOPS 18 ORE 17.30-19.30 Malattie “semplici”, malattie “complesse” e target terapeutici comuni per il progresso della ricerca Moderatori: L. OTTOBONI (Milano), M. SALVETTI (Roma) • Malattie diverse, fisiopatologie condivise M.G. MARROSU (Cagliari) • Single gene mutations come modelli per autoimmunità multifattoriale G. MATARESE (Napoli) • Demielinizzazione centrale e periferica: target terapeutici condivisi? C. TAVEGGIA (Milano) • Terapie cellulari: sempre lo stesso grado di complessità? L. OTTOBONI (Milano) • Alterazioni sinaptiche immunomediate nella SM (Sclerosi Multipla) e in malattie orfane del SNC (Sistema Nervoso Centrale)

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R. MANTEGAZZA (Milano) • Verso un supporto “trasversale” alla ricerca clinica? P. ZARATIN (Genova)

WORKSHOPS 19 ORE 17.30-19.30 10.30-ffff Global Burden of Disease: un nuovo approccio alla definizione e allo studio delle malattie neurologiche nel mondo globale Moderatori: E. BALDIN (Bologna), G. LOGROSCINO (Bari) • Overview on Global Burden Diseases L. MONASTA (Trieste) • Epilessia in GBD (Global Burden Diseases) E. BEGHI (Milano) • Stroke in GBD (Global Burden Diseases) S. RICCI (Città di Castello, PG) • L’esperienza dei nefrologi nel GBD (Global Burden Diseases): cosa può insegnare ai neurologi? G. Remuzzi (Milano) • Demenza in GBD (Global Burden Diseases) G. LOGROSCINO (Bari) • Questions and answers E. BALDIN (Bologna)

WORKSHOPS 20 ORE 17.30-19.30 10 Miopatie e malattie multisistemiche Moderatori: G. SICILIANO (Pisa), L. VERCELLI (Torino) • Il muscolo bersaglio del disturbo endocrino C. RODOLICO (Messina) • Miopatie infiammatorie e disordini reumatologici: quale sovrapposizione? M. MIRABELLA (Roma) • Critical illness e insufficienza multi organo M. FILOSTO (Brescia) • Ageing patologico e sarcopenia G. SICILIANO (Pisa)

WORKSHOPS 21 ORE 17.30-19.30 La SLA (Sclerosi Laterale Amiotrofica): una malattia multisistemica Moderatori: J. MANDRIOLI (Modena), N. TICOZZI (Milano) • Eterogeneità genetica nella SLA (Sclerosi Laterale Amiotrofica) F.L. CONFORTI (Cosenza) • SLA (Sclerosi Laterale Amiotrofica) ed eterogeneità clinica: i sintomi non motori A. CALVO (Torino) • Approcci innovativi di imaging nelle malattie del motoneurone F. AGOSTA (Milano) • Dall’eterogeneità dei meccanismi patogenetici a nuovi target terapeutici G. LAURIA (Milano)

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WORKSHOPS 22 ORE 17.30-19.30 Difficoltà interpretative nella diagnosi strumentale Moderatori: D. LIUZZI (Bari), R. PELLICCIARI (Bari) • Certezze ed interpretazioni della neurografia L. SANTORO (Napoli) • L’EEG (Elettroencefalografia) nella diagnosi delle epilessie. Fatti, artefatti e misfatti P. TINUPER (Bologna) • Il neuroimaging nelle sindromi parkinsoniane: istruzioni per l’uso R. CERAVOLO (Pisa) • Il liquor cerebrospinale: dalla fisiopatologia della risposta immunitaria alla diagnostica in neuroimmonologia C. AVOLIO (Foggia)

WORKSHOPS 23 ORE 17.30-19.30 Mancata diagnosi in epilessia Moderatori: U. AGUGLIA (Catanzaro), A. COPPOLA (Napoli) • Introduzione S. STRIANO (Napoli) • Epilessie generalizzate A. GAMBARDELLA (Catanzaro) • Epilessie parziali P. TINUPER (Bologna) • Casi clinici esemplificativi: sessione video C. DI BONAVENTURA (Roma), E. FERLAZZO (Catanzaro) (I video dei casi clinici tratteranno argomenti inerenti la diagnosi dell’epilsessia)

WORKSHOPS 24 ORE 17.30-19.30 Neurologia, arte e storia Moderatori: G. ZANCHIN (Padova), F. PALADIN (Venezia) • Le neuroscienze a Venezia F. PALADIN (Venezia) • Bisturi e pennelli: la pinacoteca di Antonio Scarpa (1752-1832) G. ZANCHIN (Padova), F. MAGGIONI (Padova) • Arte e melanconia: i miti, i simboli D. CASSANO (Nocera Inferiore, SA) • La neurologia e l’immagine in movimento: il ruolo del cinema L. LORUSSO (Chiari, BS) • L’attacco della valchiria: l’emicrania di Wagner F. MAINARDI (Venezia), C. LISOTTO (San Vito al Tagliamento, PN), G. ZANCHIN (Padova)

WORKSHOPS 25 ORE 17.30-19.30 Le neuroscienze affettive in neurologia clinica Moderatori: A. PADOVANI (Brescia), D. PERANI (Milano)

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• Introduzione C. CALTAGIRONE (Roma) • Il ruolo del cervelletto nella regolazione delle emozioni M. LEGGIO (Roma) • I disturbi affettivi nella FTD (FrontoTemporale Disease) e nella AD (Alzheimer Disease) S. CAPPA (Milano) • I disturbi affettivi nell’epilessia temporale prima e dopo trattamento chirurgico S. MELETTI (Modena) • L’apatia nelle patologie neurodegenerative D. GROSSI (Napoli)

25 OTTOBRE 2016

SESSIONE PLENARIA ORE 9.00 – 11.00 Aggiornamenti nelle terapie Moderatori: R. ELEOPRA (Udine), G.L. MANCARDI (Genova), A. QUATTRONE (Catanzaro) • Malattie acute D. TONI (Roma) • Malattie croniche ed evolutive U. BONUCCELLI (Pisa) • Trattamento riabilitativo G. ABBRUZZESE (Genova) • Terapie palliative G. MORETTO (Verona) 11.00-11.30 PAUSA CAFFÈ 11.30-13.30 SESSIONI DI COMUNICAZIONI ORALI SUI SEGUENTI ARGOMENTI Epilessia, Sclerosi Multipla 2, Neuroimmagini, Neurofisiologia clinica, Neurogenetica, Demenze 2, Neurooncologia, riabilitazione neurologica Saranno presentate 8 comunicazioni libere per ciascun argomento, che avranno come obiettivo l’aggiornamento sulle singole patologie Elenco relatori a pag 21

13.30-15.00 PAUSA PRANZO ORE 15.00 CHIUSURA DEI LAVORI CONGRESSUALI E

RAZIONALE pag. 21

La Clinica Neurologica di Ancona e la comunità neurologica delle Marche si sentono particolarmente gratificate dall’incarico di organizzare il XLVII Congresso della Società Italiana di Neurologia nell’anno 2016. La scelta di realizzare l’evento a Venezia, testimonia la sinergia fra due sedi affacciate sul mare Adriatico, nelle quali è particolarmente vivace la tradizione neurologica. Venezia offre una testimonianza illustre e feconda della cura delle malattie e dell’assistenza rivolta alle persone colpite da danni a carico del Sistema Nervoso, sia per gli aspetti della fase acuta che per gli impegni della postacuzie e della riabilitazione neurologica. Già in passato importanti eventi scientifici a valenza internazionale e nazionale sono stati organizzati a Venezia da neurologi italiani e il fascino della sede può enfatizzare la visibilità della comunità nazionale nelle sue espressioni scientifiche, assistenziali e didattiche. A fronte di un crescente impegno nella ricerca neurologica, testimoniata da una posizione di rilievo nel ranking internazionale, i neurologi italiani affrontano con crescente disagio le difficoltà correlate all’organizzazione assistenziale. Dopo anni di costante riduzione delle risorse, realizzata in maniera talora indiscriminata, si è chiamati a testimoniare l’impegno culturale e organizzativo teso a migliorare le condizioni della popolazione affetta da compromissione del Sistema Nervoso. In molte Regioni Italiane si sono realizzati tentativi di razionalizzazione dell’organizzazione assistenziale, ma la sproporzione fra domanda dell’utenza ed offerta assistenziale specifica favorisce spesso risposte assistenziali non competenti, con conseguente danno ai pazienti e spreco di risorse. L’immagine rappresentata nell’annuncio potrebbe testimoniare il fervore dell’attività richiesta alla competenza neurologica per le numerose malattie d’interesse. E’ chiaro che negli ultimi anni non è più giustificabile l’atteggiamento di esaltazione del ruolo diagnostico isolato a fronte di una rassegnazione unita a “nichilismo terapeutico”, che ha caratterizzato in passato la Neurologia Clinica, quando una diagnosi corretta rappresentava l’obiettivo precipuo, e spesso finale, dell’impegno dei neurologi. Al giorno d’oggi l’assistenza si estrinseca, anche e soprattutto, attraverso l’impiego di farmaci innovativi in grado di modificare il decorso delle malattie, di trattamenti palliativi capaci di migliorare la qualità di vita in corso di malattia e di approcci riabilitativi destinati ad ottimizzare le possibilità di recupero dell’autonomia nelle attività della vita quotidiana. Alla luce di questi presupposti, le malattie neurologiche hanno perso le caratteristiche d’ineluttibilità legate alle difficoltà diagnostiche e alle carenze assistenziali, dato che le competenze disponibili consentono possibilità concrete di trattamento o di miglioramento della qualità di vita. Tali obiettivi richiedono una lucida ridistribuzione delle risorse destinate alle strutture neurologiche degli ospedali e del territorio, al fine di renderle adeguate all’attuale epidemiologia delle malattie del Sistema Nervoso e delle condizioni di disabilità ad esse correlate. Il XLVII Congresso della Società Italiana di Neurologia fornirà un palcoscenico ricco d’interesse e fascino ai neurologi, alle associazioni e a tutti gli operatori sanitari coinvolti nell’assistenza alle persone colpite da malattie acute e croniche del Sistema Nervoso. Tutte le condizioni d’interesse neurologico saranno trattate per gli aspetti più innovativi e per le caratteristiche di impiego nella pratica clinica. Particolare risalto sarà dato alle risorse terapeutiche recentemente disponibili e ai percorsi assistenziali codificati al fine di modificare l’andamento delle molteplici malattie neurologiche.

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Professioni alle quali si riferisce l'evento formativo:

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COMUNICAZIONI ORALI DEI GIORNI 23 - 24 - 25 OTTOBRE 2016

23/10/2016 CASI CLINICI 1 A NOVEL MAPT DELETION AS CAUSE OF SPORADIC SPEECH APRAXIA EVOLVING TO CORTICOBASAL SYNDROME G. Mazzon, T. Cattaruzza, A. Menichelli, A. Fabretto, P. Manganotti 1

Neurological Clinic, Department of Medical, Surgical and Health Sciences, University of Trieste (Trieste); Neuropsychology Unit, Department of Rehabilitation Medicine, University of Trieste (Trieste); 3Department of Advanced Diagnostic and Clinical Trials- Medical Genetics, IRCCS Burlo Garofolo (Trieste) 2

Background: Speech apraxia is a disorder of speech motor planning/programming leading to slow rate, articulatory distortion, distorted sound substitutions and syllables segmentation. It can be isolated or a component of a degenerative syndrome such as Progressive Supranuclear Palsy or Corticobasal Syndrome. These diseases are often sporadic, but little is known about their genetic basis. Case Report: A 74-year-old right-handed man was referred to our Ambulatory Care for Memory Disorders with a 1-year history of progressive isolated articulation impairment, without any other cognitive, motor or behavioural symptoms. His family and past medical history were unremarkable except for depressive disorder. On first neurological evaluation, mild dysphonia and articulatory apraxia with sound distortion and slow speech rate were found, confirmed as the prevailing deficit on neuropsychological testing. Complete blood tests including thyroid hormones, vitamin B12 and folate were within normal range. Brain Magnetic Resonance Imaging (MRI) showed mild cortical atrophy, particularly in bilateral (left greater than right) temporopolar and parietal regions. During the following two years, speech disorder slightly worsened, while mild segmental (not axial) bradykinesia, ideomotor apraxia and saccades fragmentation without vertical gaze impairment appeared. Dysautonomic, behavioural or cognitive symptoms were denied. On neuropsychological follow-up, slow progressing speech apraxia, lately associated with impairment on verbal/written production and visuospatial search speed was found, with only subtle impairment of short-term memory and executive functions. Brain Single Photon Emission Tomography (SPECT) with DaTSCAN revealed normal basal ganglia uptake; Brain Perfusion SPECT showed slight asymmetric hypoperfusion in temporopolar and temporomesial regions. Cerebrospinal Fluid biomarkers (Aβ-42, Tau and PTau) analysis showed values within normal range. In the suspicion of FTD-spectrum syndrome, not fitting any clinical diagnostic criteria, gene sequencing of MAPT, PGRN and C9ORF72 genes was performed, revealing a 5bp deletion (c.105119del,p.Gln35_Asp40delinsHis) in MAPT gene, not yet described in literature (HMGD professional®), and probably disease causing in accordance with prediction softwares (Mutation Taster® and Polyphen® ). A final diagnosis of speech apraxia leading to possible corticobasal syndrome was therefore made. Conclusions: We describe the clinical profile evolution of a patient presenting with slowly progressive isolated speech apraxia, supporting the idea that this rare speech disorder can be the first presentation of Corticobasal Syndrome. Moreover, a novel probably disease-causing MAPT mutation never described before was found, underlying the importance of genetic analysis – particularly in selected atypical cases - for in vivo understanding of possible pathophysiological disease process. References: − Rossi, G. & Tagliavini, F. Frontotemporal lobar degeneration: old knowledge and new insight into the pathogenetic mechanisms of tau mutations. Front. Aging Neurosci. (2015);7:192 − Rossi, G. et al. The G389R mutation in the MAPT gene presenting as sporadic corticobasal syndrome. Mov. Disord. Off. J. Mov. Disord. Soc. (2008);23:892–895 − Josephs, K. A. et al. The evolution of primary progressive apraxia of speech. Brain J. Neurol. 1(2014);37: 2783– 2795

GENETIC AND ENVIRONMENTAL FACTORS AFFECT BRAIN DIFFERENTLY IN DM1 MONOZYGOTIC TWINS: THE EFFECT ON SOCIAL COGNITION AND DECISION-MAKING ABILITIES L. Serra1, M. Bruschini1, A. Petrucci2, G. Meola3, M. Bozzali1 1

Neuroimaging Laboratory, Santa Lucia Foundation IRCCS (Roma); 2UOC Neurologia e Neurofisiopatologia, AO San Camillo Forlanini (Roma); 3Department of Neurology, IRCCS Policlinico San Donato, University of Milan (Milano) pag. 25

Aims: Myotonic dystrophy type-1 (DM1) is a genetic multisystem disorder (1) in which both social cognition deficits (2) and brain abnormalities are currently recognised (3). Genetics and environmental factors modulate the brain development, thus accounting for brain resilience. Here, investigated the heritability traits of DM1 brain features and corresponding cognitive profiles. Methods: Two monozygotic twins with a adult DM1 onset (LV and SV, 29 years old, Females, 11 years of education) were investigated using an extensive assessment including social cognition (Theory of Mind, Emotional processing, Socialsituation test, moral-and-conventional knowledge), executive functions (Iowa-Gambling Task, Wisconsin-Card Sorting test, Trial-Making Test, Tower of London, Raven’s Coloured Progressive Matrices, Cognitive Estimation Task), and Intelligent quotient (IQ). Patients underwent 3T MRI including T1-weighetd volumes for voxel-based morphometry (VBM). Ten gender-matched healthy subjects (HS) were used as controls for brain volumetric comparisons in either patient. Results: Both patients reported a normal IQ. LV showed an extensive impairment of emotion processing underlying her social cognition abilities, while SV showed a remarkable impairment in the cognitive aspects of social cognition. Both patients revealed similar deficits in decision-making. VBM revealed similarities, but also differences in regional grey matter (GM) atrophy distribution between LV and SV. In both cases GM atrophy was present in the posterior cingulate cortex (BA23/31) and precuneus (BA7), and in the striatum. SV (but not LV) showed additional GM atrophy in her right dorsolateral prefrontal cortex (BA46). With respect to white matter (WM), both patients revealed regional atrophy distributed to the thalamus and the uncinate fasciculus. Discussion: This study in monozygous DM1 twins indicates that emotional and cognitive components of social cognition can be differently impaired across DM1 patients (2). These impairments are consistent with their different patterns of regional brain atrophy. GM atrophy in most posterior brain areas (connected with the limbic system) accounts for the emotional dysfunction observed in LV. GM atrophy in the dorsolateral prefrontal cortex accounts for the cognitive deficits in social cognition observed in SV (2). The overlapping atrophy in the striatum (structure implicated in reward mechanisms) might account for patients’ common deficits in decision-making. Overall, our DM1 twins showed differences in GM but not in WM volumes. We speculate that WM might be more affected by genetics, while GM may be modulated by specific environmental factors, such as education and social events experienced during lifetime (3). Interestingly these two environmental factors seem to have impacted differently on individual patients’ dysfunctions. References: 1. G. Meola, R. Cardani, “Myotonic dystrophies: An update on clinical aspects, genetic, pathology, and molecular pathomechanisms”. Biochimca et Biophysica Acta (2015);1852:594-606 2. Serra L, Cercignani M, Bruschini M, Cipolotti L, Mancini M, Silvestri G, Petrucci A, Bucci E, Antonini G, Licchelli L, Spanò B, Giacanelli M, Caltagirone C, Meola G, Bozzali M. "I Know that You Know that I Know": Neural Substrates Associated with Social Cognition Deficits in DM1 Patients.” PLoS One (2016) Jun 3;11(6):e0156901 3. Serra L, Petrucci A, Spanò B, Torso M, Olivito G, Lispi L, Costanzi-Porrini S, Giulietti G, Koch G, Giacanelli M, Caltagirone C, Cercignani M, Bozzali M. How genetics affects the brain to produce higher-level dysfunctions in myotonic dystrophy type 1. Funct Neurol. (2015) Jan-Mar;30(1):21-31

NOVEL COMPOUND HETEROZYGOUS MUTATIONS IN THE CLN6 GENE ASSOCIATED WITH AUTOSOMAL RECESSIVE KUFS DISEASE G. Borzì1, L. Mumoli1, F. Abate1, S. Cavalli1, A. Labate1,2, A. Gambardella1,2 1

Institute of Neurology, Department of Medical and Surgical Sciences, University Magna Graecia (Catanzaro); 2Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR) (Catanzaro) Purpose: Autosomal recessive Kufs disease (KD) type A is a rare form of neuronal-ceroid-lipofuscinosis presenting with progressive myoclonus epilepsy that starts around the age of 30 years. The phenotype seems to be more heterogeneous than previously assumed, so the diagnosis is markedly delayed or missed. Recessive mutations in CLN6 seem to be the major cause of the disorder. Here, we report clinical and genetic findings in a KD family with two affected individuals. Materials and methods: The two probands are a brother (40 y) and sister (42 y), with non-consanguineous parents. Since their twenties, both of them experienced vibrating jerks of the mouth and upper limbs, induced by voluntary movements or visual stimuli. In the following years, rare generalized tonic-clonic seizures also occurred. They were diagnosed juvenile myoclonic epilepsy and received levetiracetam, which reduced myoclonus. In the following 5-10 years, myoclonus progressively worsened, becoming a dominant symptom and causing severe motor impairment. They also experienced progressive unsteadiness, difficulty in writing, speech and cognitive slowing. EEG/polygraphic recordings showed pag. 26

generalized spike-waves and photo-paroxysmal response with a high sensitivity to low-frequency photic stimulation, with 1:1 spike to 1-Hz stimuli. Visual and auditory evoked potentials were normal, while somatosensory evoked potentials revealed a large cortical potential, associate with C-reflex. In both patients, brain MRI showed cortical and subcortical atrophy over both hemispheres with white matter abnormalities. The two patients, their unaffected mother and brother underwent a genetic molecular study to search mutations of CLN6 (NM_017882.2). Results: Gene sequencing of CLN6 identified both probands to be compound heterozygous for a c.721 A>G, P. M241V mutation in exon 7; and c.814 C>G, P. L272V in exon 7. The healthy brother did not carry any mutation, the mother was a carrier of the single c.721 A> G; P. M241V variant. These two variants are very rare and predicted to be damaging. Conclusions: The results of this family further highlight the major role of the CLN6 gene for recessive KD type A. As its diagnosis is challenging and is compounded by the relative rarity of the disorder, the CLN6 mutation screening should now be considered as an initial diagnostic step in patients with adult-onset myoclonus, allowing early detection and avoiding other costly and invasive investigations. In our family, early and very characteristic electro-clinical manifestations of KD type A related to CLN6 mutations were massive and segmental myoclonus, as also low-frequency photo paroxysmal response. References: − Arsov T, Smith KR, Damiano J, Franceschetti S, Canafoglia L, Bromhead CJ, Andermann E, Vears DF, Cossette P, Rajagopalan S, McDougall A, Sofia V,Farrell M, Aguglia U, Zini A, Meletti S, Morbin M, Mullen S, Andermann F, Mole SE, Bahlo M, Berkovic SF. Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6. Am J Hum Genet. (2011) May 13;88(5):566-73 − Canafoglia L, Gilioli I, Invernizzi F, Sofia V, Fugnanesi V, Morbin M, Chiapparini L, Granata T, Binelli S, Scaioli V, Garavaglia B, Nardocci N, Berkovic SF, Franceschetti S. Electroclinical spectrum of the neuronal ceroid lipofuscinoses associated with CLN6 mutations. Neurology (2015) Jul 28;85(4):316-24 − Franceschetti S, Michelucci R, Canafoglia L, Striano P, Gambardella A, Magaudda A, Tinuper P, La Neve A, Ferlazzo E, Gobbi G, Giallonardo AT, Capovilla G, Visani E, Panzica F, Avanzini G, Tassinari CA, Bianchi A, Zara F; Collaborative LICE study group on PMEs. Progressive myoclonic epilepsies: definitive and still undetermined causes. Neurology (2014) Feb 4;82(5):405-11

ACUTE HEMICHOREA AN UNUSUAL FIRST MULTIPLE SCLEROSIS PRESENTATION: TWO CASE REPORTS F. Cavallieri, G. Giovannini, E. Menozzi, S. Meletti, A. Chiari, J. Mandrioli, D. Ferraro, S. Contardi, P. Nichelli, F. Valzania Department of Neuroscience, S. Agostino-Estense Hospital and University of Modena and Reggio Emilia (Modena) Introduction: Hyperkinetic movement disorders, in particular chorea, has been rarely reported in patients with Multiple Sclerosis (MS) and almost never represent the first clinical manifestation. The few cases reported in the literature had basal ganglia (mainly striatum) demyelinating plaques. We report two patients with acute hemichorea as the presenting symptoms of MS. Case reports: Patient 1: A 39 year-old woman acutely developed subcontinuous, choreic movements in her right limbs occasionally associated to ballistic movements and abnormal dystonic postures. Moreover continuous peribuccal and tongue involuntary movements were noted. Brain MRI revealed a tumefactive, T2/FLAIR hyperintense, T1 hypointense contrastenhancing demyelinating lesion in the left cerebral peduncle, extending to the substantia nigra and subthalamic nucleus (STN). Multiple others non-contrast-enhancing demyelinating lesions were also found. Isoelectric focusing (IEF) revealed nine cerebrospinal fluid (CSF) oligoclonal bands (OB). A diagnosis of MS was made and the patient was treated with highdose methylprednisolone with improvement of symptoms. Patient 2: An 18 year-old man acutely developed intermittent choreic and choreoathetoid movements associated with a dystonic posture of the left limbs, mostly involving the left hand, dysarthric speech and mental slowing. Brain MRI revealed a right subthalamic T2/FLAIR hyperintense, contrast-enhancing demyelinating lesion extending to the homolateral cerebral peduncle. Multiple non-contrast-enhancing demyelinating lesions involved the left part of the pons-mesencephalic passage, the homolateral superior cerebellar peduncle, and the corpus callosum. IEF revealed five CSF OB. A MS diagnosis was made and the patient was treated with high-dose methylprednisolone with involuntary movements resolution in six days. Discussion: Choreoathetosis, with different degrees of dystonia, represents the clinical manifestation of peak-dose levodopa-induced dyskinesia in advanced Parkinson’s Disease (PD) that are possibly associated with STN hypoactivity, as suggested by the occurrence of dyskinesias in MPTP monkeys and by the occurrence of hemichorea-hemiballism in around pag. 27

15% of PD patients after subthalamotomy or during Deep Brain Stimulation (DBS). Historically, contralateral hemichorea has been described in relation to subthalamic or thalamic lesions. In our case, the occurrence of demyelinating lesions in basal ganglia could be explained by the presence of myelinated fibers within the subcortical grey nuclei. These observations, the presence of contrast-enhancing STN lesions and the clinical improvement following steroid treatment, suggest a direct relationship between the occurrence of the demyelinating lesions and the onset of the involuntary movements. Aside from common cases induced by metabolic or vascular lesions, in young subjects this clinical picture could suggest an unusual onset of a demyelinating disease. References: − Mehanna R, Jankovic J. Movement disorders in multiple sclerosis and other demyelinating diseases. J. Neurol Sci (2013);328:1-8 − Lee MS, Marsden CD. Movement disorders following lesions of the thalamus or subthalamic region. Mov Disord. (1994);9:493-507 − Guridi J, González-Redondo R, Obeso JA. Clinical features, pathophysiology, and treatment of levodopa-induced dyskinesias in Parkinson’s disease. Parkinsons Dis. (2012);2012:943159

LIMB-SHAKING: AN EXCLUSIVE EPILEPTIC ORIGIN? F. Notturno1, C. Tiseo1, D. Degan1, R. Ornello1, M. Lobene2, M. Pinelli3, A. Carolei1 1

Department of Neurology and Stroke Unit, Avezzano Hospital, University of L’Aquila (L’Aquila); 2Department of Radiology, Avezzano Hospital, ASL1 AZ-SU-AQ (Avezzano, AQ); 3Department of Angiology, Avezzano Hospital, ASL1 AZ-SU-AQ (Avezzano, AQ)

Background: Limb-shaking syndrome is a rare presentation of internal carotid artery (ICA) occlusion. The syndrome is characterized by brief and paroxysmal movements of the limbs, mainly observable with postural changes and is frequently misdiagnosed as focal epileptic seizures. Methods: A 74-year old male patient complained of involuntary and intermittently present left limbs movements, described as shaking and trembling, lasting from few seconds to three minutes. Consciousness, speech, sensory and motor functions were normal, during and after the attacks. The episodes mainly occurred after standing up from the supine position or during a prolonged laughter. Results: Arterial blood pressure was 110/70 mmHg in both supine and standing positions. A bruit over the right ICA was revealed. Doppler ultrasound examination showed occlusion of the right ICA and near-occlusion of the right external carotid artery (ECA). Transtemporal window insonation of the right middle cerebral artery (MCA) showed a typical post-occlusive flow with reduction of peak systolic and diastolic velocities. Breath-holding test documented an exhausted cerebrovascular reserve in the right hemisphere. Brain magnetic resonance imaging, including diffusion weighted images, was normal. CT-angiography confirmed the occlusion of the right ICA, a near-occlusion of the right ECA, and poor collateral circulation. CT-perfusion showed an extensive perfusion deficit involving the whole right anterior circulation territory. The electroencephalogram did not show any epileptic or focal slow waves activities. The patient was not eligible to revascularization procedure because of the occlusion of the right ICA. In order to improve cerebral blood flow the ongoing antihypertensive treatment was stopped. On day 2 limb-shaking movements resolved and the patient remained completely asymptomatic during the 6-month followup period. Discussion: The patient was diagnosed as affected by limb-shaking syndrome. This is a rare form of hemodynamic transient ischemic attack, determined by stenosis or occlusion of the ICA, causing a chronic cerebral hypoperfusion. Involuntary limbs movements are the result of a focal critical reduction of cerebral blood flow occurring in the vascular watershed territories of the anterior circulation. Because of the altered vasomotor reactivity, conditions that may further and transiently compromise cerebral perfusion, such as rising, exercising, coughing, or laughing, favor the development of symptoms. The absence of Jacksonian march, the spear of the face muscles, the absence of epileptiform activity are in favor of the vascular origin of the symptoms. Early recognition of this syndrome is crucial for the timely improvement of cerebral perfusion by carotid revascularization or blood pressure increase.

CEREBRAL SUPERFICIAL SIDEROSIS FOLLOWING CHRONIC INTRACRANIAL HYPOTENSION E. Ferrante1, F. Rubino2, V. Prone1, A. Guccione1, A. Piperno3, S. Pelucchi3, E. Agostoni1 1

Neuroscience Department, Niguarda Cà Granda Hospital (Milano); 2Anaesthesiology Department, Niguarda Cà Granda Hospital (Milano); 3Internal Medicine 2 Department, S. Gerardo Hospital Monza, Milano-Bicocca University (Milano) pag. 28

Introduction: Superficial siderosis (SS) is a radiological and pathological condition in which hemosiderin is deposited in the subpial layer of the central nervous system, which leads to slowly progressive neurological dysfunction. The distinct clinical features are characterized by deafness, hyposmia, cerebellar ataxia, pyramidal signs, cognitive decline and bladder disturbance. Case Report: In February 2010 a 48 years old man presented a dislocation of the right shoulder while skiing. After 4 months he presented hyposmia, bilater hearing loss and tinnitus, vertigo and nuchal stiffness without headache. After December 2011 the patient showed also imbalance. He was hospitalized in another neurological department and brain MRI showed a diffuse cerebellar superficial siderosis with atrophy and without diffuse pachymeningeal enhancement (DPE). The CSF exam and the spinal-MRI were normal. 4 years after the trauma a myelo-CT showed a C2-T11 anterior epidural CSF collection without localization the real CSF leak site. In August 2015 the patient was admitted in our department. The neurological examination showed anosmia, severe ipoacusia and mild imbalance at the tightrope walking test. Spinal myeloMRI showed anterior epidural CSF collection from C2 to T11 and brain MRI was unchanged. The lumber puncture showed clear CSF with opening pressure of 5 cm H2O, protein 50 mg/dl, ferritine 71 ng/ml (n.v. 3.9-6.4) and some erythrocytes. The intracranial hypotension (IH) was diagnosed and an epidural lumbar blood patch (EBP) was performed with imbalance improvement and nuchal stiffness disappearance. In May 2016 a spinal myelo-MRI and CSF exam were unchanged. Radionuclide cysternography at 4th hours showed a tracer increased uptake at anterior epidural cervical-thoracic junction level, indicating the approximate CSF leak site and early tracer accumulation in the bladder, indirect sign of CSF leakage. A thoracic targeted EBP at T3-T4 level was performed with recovered of the imbalance and improvement of the tinnitus. Discussion: SS is a rare disease. The aetiology in about 50% of the cases is unknown. The principal cause might be the chronic venous microbleeding. The microbleedings would caused by the breaking of the cerebellar bridge veins for the brain sagging, the epidural and pial venous plexus engorgment that accompanies CSF hypotension, sclerosis of the epidural venous plexus by choronic siderosis, leading to venous pial plexus hypertension with secondary prominent engorgement with blood exudation. Conclusion: In the cryptogenic cases of SS with an epidural fluid collection at spinal-MRI it might suspect IH also in atypical cases without headache and DPE, treatable with EBP. References: − Cheng CY, Chen MH, Wang SJ, Lin KP A proposed mechanism of superficial siderosis supported by surgical and neuroimaging findings. Med Hypotheses (2011) Jun;76(6):823-6 − Ferrante E, Arpino I, Citterio A, Wetzl R, Savino A. Epidural blood patch in Trendelenburg position pre-medicated with acetazolamide to treat spontaneous intracrania lhypotension. European Journal of Neurology (2010);17:715–9

REVERSIBLE ATAXIA WITH CEREBELLUM HYPERINTENSITY DUE TO HYPOMAGNESEMIA AND THIAMINE DEFICIENCY: A CASE REPORT D. Baroncini1, P. Annovazzi1, S. Baldini1, G. Minonzio2, A. Ghezzi1, G. Comi3, M. Zaffaroni1 1

Multiple Sclerosis Study Center, ASST Valle Olona (Gallarate-VA); 2Neuroradiology Department, ASST Valle Olona (Gallarate-VA); 3Department of Neurology and Institute of Experimental Neurology, University Vita-Salute San Raffaele (Milano) Objective: We present the case of a patient with a subacute reversible ataxia with evidence of cerebellar hyperintensity on brain MRI. Materials and Methods: Single patient case report. Case Report: A 41 years-old man with an unremarkable family history presented to our hospital with a subacute onset of slurred speech, oscillopsia, diffuse paresthesia and intermittent limb tremors. Past medical history included cigarettes smoking, type II diabetes mellitus, arterial hypertension and a loss of 22 Kg in the past 3 months due to a low-calorie diet. Ongoing medications were sitagliptin, metformin, bisoprolol, valsartan and omeprazole. In emergency care unit blood exams showed severe sodium, potassium and magnesium depletion. Brain CT scan, EEG and EKG were normal. Electrolytes supplementation led to full improvement of all symptoms except for dysarthria. Neurological consultation was then requested: the clinical examination showed mild confusion, severe slurred speech, mild “no-no” head tremor, mild dysdiadochokinesia, positive Romberg sign and difficulty in walking heel-to-toe. Brain MRI scans showed a T2 and DWI hyperintensity in vermis and anterior cerebellar lobe. The patient was then admitted to our neurological department. General blood exams, vitamin E and B12, celiac-related/classic onconeural/anti-GAD antibodies were normal. Folate levels were low. Cerebral spinal fluid examination was unremarkable, with no oligoclonal bands. Extensive total body imaging (CT, PET) and endoscopic exams were also negative. Intramuscular thiamine administration led to an initial partial recovery. We pag. 29

repeat blood electrolytes finding again a severe magnesium deficiency. The combined parenteral supplementation of thiamine and magnesium led finally to an almost complete recovery, with a full regression of the cerebellar hyperintensity on MRI. Discussion: In the clinical picture of Wernicke encephalopathy cerebellar ataxia is often present, but only rarely cerebellar alterations on brain MRI scans have been described (1). Furthermore, hypomagnesemia has been associated with a reversible vermian cerebellar ataxia with nodulus involvement (2). Although we did not dose blood thiamine levels in the acute phase, loss of weight due to diet restriction, exclusion of other causes and improvement after thiamine supplementation support the diagnosis. Hypomagnesemia could have foster this atypical cerebellar presentation, as magnesium is a crucial cofactor in thiamine metabolism and severe hypomagnesemia may lead to a refractory response to thiamine until magnesium is given (3). Conclusion: In the diagnostic work-up of patients with cerebellar ataxia hypomagnesemia and thiamine deficiency are extremely important to unveil due to their potential correction. References: 1. Jung Eun Kim, Tae Hyung Kim, In Kyu Yu, et al. Diffusion-Weighted MRI in Recurrent Wernicke’s Encephalopathy: a Remarkable Cerebellar Lesion. J Clin Neurol (2006); 2(2):141-145 2. Santos AF, Sousa F, Rodrigues M, et al. Reversible cerebellar syndrome induced by hypomagnesemia. Neurology and Clinical Neuroscience (2015);3:190–191 3. Sechi G., Serra A. Wernicke’s encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol (2007);6:442–55

MIDBRAIN HEMIATROPHY IN A PATIENT WITH EARLY ONSET HEMIPARKINSONISM A. Lupo1, G. Barbagallo1, G. Arabia1, L. Manfredini1, U. Sabatini2, A. Quattrone3 1

Institute of Neurology, University Magna Græcia (Catanzaro); 2Institute of Neuroradiology, University Magna Graecia (Catanzaro); 3Institute of Neurology; Neuroimaging Research Unit, Institute of Molecular Bioimaging and Physiology, University Magna Graecia; National Research Council (Catanzaro) Introduction: A rare form of secondary parkinsonism has been recently reported as hemiparkinsonism-hemiatrophy syndrome (HPHA). This condition is defined by the occurrence of a body hemiatrophy with features of an ipsilateral, early onset, slowly progressive, levodopa-responsive hemiparkinsonism. The underlying pathogenesis is not well understood, but perinatal cerebral insults seem to play a crucial role. Magnetic resonance imaging (MRI) may be normal or it can show a controlateral brain asymmetry, ventricle asimmetry, hyperintense lesions in midbrain with or without nigral involvement [1]. Case description: A 58-years-old man presented with a 12-year nonprogressive history of levodopa-responsive brachiocrural slowness and decrease in dexterity on the left side, with ipsilateral hand tremor. His past history was negative for birth-related problems, even if since early childhood he had some clumsiness to the left upper and lower limbs and he was aware of the asymmetry between the left and the right side. Neurological examination revealed slight brachio-crural atrophy with mild rigidity and bradykinesia of his left side, rest and postural tremor in the ipsilateral hand. He did not show other atypical hallmarks, such us autonomic disturbances, pyramidal signs and cognitive impairment. PINK1, Parkin, and DJ-1 mutations were negative. MRI 3T showed a right midbrain atrophy with the rarefaction of the substantia nigra, that was not recognizable as the band of signal hypointensity on T2 sequence, laterally to the red nucleus. Dopamine transporter singlephoton emission computed tomography (DAT-SPECT) scan with 123I-ioflupane (FP-CIT) revealed a strictly unilateral reduced striatal binding on the right side. Discussion: Here we describe an early-onset, nonprogressive, levodopa-responsive hemiparkinsonism on the left side associated with an ipsilateral body hemiatrophy. Furthermore, MRI showed an atrophy of the right midbrain combined with an ipsilateral rarefaction of the substantia nigra. In according with these MRI findings, DAT-SPECT showed a significant reduced uptake of FP-CIT only in the right striatum. In our patient, pure left hemiparkinsonism, ipsilateral brachio-crural atrophy that was by himself recognized, and controlateral midbrain atrophy suggest a diagnosis of HPHA. The history of cerebral injury occurring at birth or first few years of life is reported in nearly half of patients, although it has not been documented in all cases of HPHA [2]. To our knowledge, this case represents the first description of a possible HPHA associated to midbrain hemiatrophy and absence of the substanti nigra. References: 1. Wijemanne S, Jankovic J. Hemiparkinsonism-hemiatrophy syndrome. Neurology (2007);69:1585-94 2. Giladi N, Burke RE, Kostic V, et al. Hemiparkinsonism-hemiatrophy syndrome: clinical and neuroradiologic features. Neurology (1990);40:1731–1734 pag. 30

DISORDINI DEL MOVIMENTO 1 CLINICAL, NEUROPHYSIOLOGICAL AND IMAGING FEATURES OF ESSENTIAL TREMOR-PARKINSON DISEASE (ET-PD) SYNDROME G. Arabia1, A. Lupo1, L. Manfredini1, M. Caligiuri2, R. Nisticò2, G. Barbagallo1, I. Martino1, F. Novellino2, M. Salsone2, A. Quattrone1 1 Institute of Neurology, University "Magna Graecia" (Catanzaro); 2Neuroimaging Research Unit, IBFM, National Research Council (Catanzaro)

Objective: The relationship between essential tremor (ET) and Parkinson’s disease (PD) is strongly controversial. Some authors have proposed a coincidental co-occurrence of ET and PD, whereas others suggested that ‘‘ET-PD’’ syndrome may represent a distinct entity.1-3 The aim of the present study was to investigate the clinical, neurophysiological and imaging features of patients with ET-PD in comparison with patients affected by ET, ET with resting tremor (r-ET) and tremordominant PD (t-PD). Methods: A total of 122 patients referring to our Movement Disorders Center for tremor were included in this study. Eighteen patients were affected by ET-PD, 40 patients with ET, 23 patients with r-ET, and 41 patients by t-PD. All patients were classified according to the standardized clinical criteria. Clinical, neurophysiological, neuropsychological, and imaging features of the included patients were analysed. Results: No statistical differences were found in the comparisons among the study groups in terms of age, sex, family history for tremor and/or PD, and cognitive status performances. Age at onset and disease duration of ET were similar in ET, r-ET and ET-PD patients (p=0.56, Kruskal-Wallis test followed by pairwise Wilcoxon rank sum test and Bonferroni correction). ET-PD and r-ET patients showed resting tremor with an EMG synchronous pattern, whereas the pattern was alternating in t-PD patients. DAT-scan uptake was preserved in ET and r-ET patients (4.27 ± 0.59 and 4.46 ± 0.62, respectively) and reduced in t-PD patients (2.12 ± 0.43). ET-PD patients showed moderately reduced uptake values (3.19 ± 1.02). MIBG scintigraphy uptake was abnormal in t-PD and preserved in ET and r-ET. In ET-PD patients, MIBG uptake was only slightly reduced, suggesting a mild sympathetic cardiac denervation in these patients. Conclusions. Our findings suggested that ET-PD might be considered a distinct clinical entity. Indeed, our study showed that ET-PD patients, after a long history of ET, developed a parkinsonism with clinical, neurophysiological, and imaging features differential from the classical PD. References: − Pahwa R, Koller WC. Is there a relationship between Parkinson’s disease and essential tremor? Clin Neuropharmacol (1993);16:30-35 − LaRoia H, Louis ED. Association between essential tremor and other neurodegenerative diseases: what is the epidemiological evidence. Neuorepidemiology (2011);37:1-10 − Fekete R, Jankovic J. Revisiting the relationship between essential tremor and Parkinson’s disease. Mov Disord (2011);26:391-398

IMPAIRED HEART RATE VARIABILITY BY LONG TERM ECG RECORDING IN PARKINSON’S DISEASE: A CASE-CONTROL STUDY V. Arnao1, A. Cinturino1, G. Lanza1, G. Bellavia1, S. Mastrilli1, V. Perini1, S. Realmuto1, F. Valentino1, C. Buttà2, C. Maida2, A. Tuttolomondo2, M. D'Amelio1 1 Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo (Palermo); 2Biomedical Department of Internal and Specialistic Medicine, University of Palermo (Palermo)

Introduction: Parkinson's disease (PD) is associated with autonomic dysfunction, controlled by circadian regulation. Impaired cardiovascular autonomic regulation is an autonomic symptom of Parkinson’s disease (PD) and it may increase long-term morbidity. Heart rate variability (HRV) decreases in PD and it can be considered a marker for cardiovascular dysautonomia. 24-hour Holter recording could be a valid tool to characterizing cardiac autonomic state.

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Objective: To evaluate the presence of autonomic symptoms in PD patients and to perform a time-domain assessment of HRV by a long term 24-hour Holter recording. Method: This is an observational, cross-sectional, comparative study. Patients with idiopathic PD and without comorbidity impairing the HRV, and age-matched healthy persons were recruited at the Neurological Department starting from January 2013 to May 2015. Patient with suspected atypical or secondary parkinsonism were excluded. The levodopa Equivalent Daily Dose (LED) has been calculated and medications have been recorded as Comorbidities have been recorded, using the Cumulative Illness Rating Scale (CIRS). Each patient underwent an extensive evaluation including Hoehn & Yahr stage (H&Y), Unified Parkinson’s Disease Rating Scale (UPDRS), and Scale for Outcomes in PD for autonomic symptoms (SCOPA-AUT). A Time domain analysis of heart rate variability (HRV) using 24-hour ambulatory ECG was also performed. Results: A total of 18 patients with PD were identified (mean age was 55,6 ±8,8, disease duration: 5,01± 4,7); none of patients and of the 18 age and sex matched controls was on anti-hypertensive, antiarrhythmic and mineral corticoid drugs. Mean SCOPA-AUT scale score was 10,12 ± 7,34. PD patients were on HY stage 1-2 and mean LED was 311 ± 239,9. At univariate analysis, compared to healthy controls, in 24-hour ambulatory ECG evaluation, SDNNindex (ISDNN) was significantly lower (p 0,01) in PD patients. ISDNN significantly correlated with age (Rho -0.69, p B 0.02), LED (Rho -0.60, p B 0.01), Levodopa dosage (Rho -0.57, p B 0.02) and SCOPA-AUT scale scores (Rho -0.47, p B 0.05). At multivariate analysis (adjusted for age, LED and levodopa dosage and SCOPA-AUT score), older age (ORa 1.209, 1.18–1.493, p = 0.005), levodopa therapy (ORa 1.006, 1.003–1.014, p = 0.005) LED (ORa 1.09, 1.003–1.0155, p = 0.003) and SCOPAAUT scores (ORa 1.038, 1.002–1.299, p = 0.005) were independently associated with lower ISDNN value. Conclusion: This study highlights the importance of autonomic dysfunction in PD. In our population characterized by mild to moderate disease severity, most of patients had autonomic system involved and time-domain assessment of HRV could be a potential tool to characterizing cardiovascular dysautonomia. Both cardiac sympathetic and parasympathetic dysfunction are commonly reported in PD patients. Decrease of iSDNN in HRV may demonstrate overall sympathetic and parasympathetic function in PD. References: − Verbaan D, Marinus J, Visser M, van Rooden SM, Stiggelbout AM, van Hilten JJ. Patient-reported autonomic symptoms in Parkinson disease. Neurology (2007) Jul 24;69(4):333-41 − Visser M, Marinus J, Stiggelbout AM, Van Hilten JJ. Assessment of autonomic dysfunction in Parkinson's disease: the SCOPA-AUT. Mov Disord. (2004) Nov;19(11):1306-12 − Brisinda D, Sorbo AR, Di Giacopo R, Venuti A, Bentivoglio AR, Fenici R. Cardiovascular autonomic nervous system evaluation in Parkinson disease and multiple system atrophy. J Neurol Sci. (2014) Jan 15;336(1-2):197-202

DOPAMINE D2 RECEPTOR MEDIATED NEUROPROTECTION IN A LRRK2 GENETIC MODEL OF PARKINSON DISEASE A. Mancini1, A. Tozzi2, A. de Iure1, V. Durante1, M. Tantucci1, P. Mazzocchetti1, M. Di Filippo1, P. Calabresi1 1

Neurology Clinic, Department of Medicine, University of Perugia (Perugia); 2Section of Physiology and Biochemistry, Department of Experimental Medicine, University of Perugia (Perugia) Objectives: Parkinson Disease (PD) is a neurodegenerative disease in which genetic and environmental factors synergistically lead to a loss of midbrain dopamine (DA) neurons. Mutations of Lrrk2 gene are responsible for the majority of inherited cases of PD and can be also found in sporadic cases. The pathophysiological role of this kinase has yet to be fully understood (1). Thus, we investigated possible alterations of striatal medium spiny neurons (MSNs) activity in a genetic mouse model of PD carrying the G2019S knock-in (KI) mutation, which enhances Lrrk2 kinase activity (2,3). We also evaluated in this model neuronal vulnerability to rotenone, a mitochondrial complex I inhibitor, known to be involved in PD pathogenesis. Materials and methods: Basal membrane properties and glutamatergic excitatory postsynaptic currents (EPSCs) were recorded, by patch-clamp experiments, in MSNs from brain slices of mice carrying the Lrrk2 mutation observed in PD patients (G2019S-KI) and control C57Bl/6 mice. Striatal DA release was measured by constant potential amperometry. Neuronal vulnerability to rotenone was tested by measuring the progressive reduction of striatal field potential amplitude (FPA). Results: The amperometric analysis showed reduced striatal DA levels by 49% (p= 50% reduction of seizure was achieved. Results: All seizures are focal and focal with secondary generalization. Prior to the initiation of treatment with IvIg, seizure frequency was 100 monthly crisis in patient n°1, 90 monthly crisis in patient n°2 and 35 monthly crisis in patient n°3. Previously, all patients had taken more than three antiepileptic drugs without any benefit. Following treatment with IvIg , the following outcomes were noted: patient n°1 had a 81 % reduction of monthly frequency of crisis , patient n°2 had 58 % reduction, patient n°3 had a 85 % reduction. All three patients had a positive clinical response to treatment from baseline. In addition a psychocognitive improvement has been also registered in school environment and in relationships with peers. IvIgs were well tollerated by all children and a good safety profile was observed as reported in literature. Discussions: We registered a global reduction of seizure frequency after six monthly cycles of IvIg as reported in literature, without showing phisical or cognitive side effects (considering age of development of our patients). Intravenous immunoglobulin are able to reduce multiple seizure types in a variety of epilepsy etiologies, including those of unknown cause. A good profile of tolerability and safety was observed as reported in literature. Conclusions: Human normal immunoglobulin can be considered as a valid and safe therapeutical alternative in selected cases of drug-resistent epilepsy in pediatric population when politherapy failed, above all where antiepileptic drugs can negatively influence cognitive development. References: − Kwan P, Schacter SC, Brodie MJ. Drug-resistant epilepsy. N.Engl. J. Med. (2011);365(10):919-926 − Walker L1, Pirmohamed M, Marson AG. Immunomodulatory interventions for focal epilepsy syndromes.Cochrane Database Syst Rev. (2013) Jun 27;(6):CD009945. − Mikati MA, Kurdi R, EL-Khoury Z, Rahi A, Raad W.Intravenous immunoglobulin therapy in intractable childhood epilepsy: Open-label study and review of the literature. Epilepsy&Behavior (2010);1:90-94 pag. 39

A MULTICENTER STUDY ON THE DIAGNOSTIC SIGNIFICANCE OF A SINGLE CEREBROSPINAL FLUID IGG BAND D. Ferraro1, A. Simone1, E. Cocco2, M. Santangelo3, P. Immovilli4, M. Calabrese5, M. Di Filippo6, R. Orlandi1, R. Bedin1, F. Vitetta1, A. Gallina6, C. Solaro7, C. Gasperini8, M. Rodegher9, P. Sola1 1

Department of Neurosciences, University of Modena and Reggio Emilia (Modena); 2Department of Public Health, Clinical and Molecular Medicine, University of Cagliari (Cagliari); 3Neurology Unit, Ramazzini Hospital (Carpi-MO); 4Neurology Unit, Department of Specialistic Medicine, G. da Saliceto Hospital (Piacenza); 5Department of Neurological and Movement Sciences, University Hospital of Verona (Verona); 6Neurology Unit, Medicine Department, University of Perugia (Perugia); 7 Neurology Unit, PA Micone Hospital (Genova); 8Neurology Unit, San Camillo Forlanini Hospital (Roma); 9Neurology Unit, IRCSS Policlinico San Donato (Milano) Introduction: The finding of a single cerebrospinal fluid (CSF) Immunoglobulin G (IgG) band is rare and only few studies have explored its frequency and diagnostic significance. Our aim was to establish 1) the diagnoses associated with the finding of a single CSF IgG band, 2) the proportion of patients with a single IgG band who will be diagnosed with Multiple Sclerosis (MS) within the following 2 years and 3) whether there are differences in the CSF characteristics of patients subsequently diagnosed with MS compared to those with alternative diagnoses, in a multicenter study. Methods: We collected clinical and CSF data of patients who showed a single CSF-restricted IgG band, with or without an associated “mirror pattern”, at CSF isoelectric focusing (IEF) analysis, carried out for any reason, from 2005 onwards. Results: Out of 8156 CSF IEF analyses, 113 showed a single CSF IgG band (1.4%). In another cohort of 500 CSF analyses carried out for suspected MS, only 2 showed a single CSF IgG band (0.4%). A definite diagnosis was established in 98 patients. MS was diagnosed in 26 (27%) patients, other central nervous system (CNS) demyelinating diseases in 20 (20%), CNS infections in 7 (7%), inflammatory peripheral nervous system (PNS) diseases in 6 (6%), CNS autoimmune/paraneoplastic diseases in 5 (5%), cerebral tumours in 3 (3%), and other diagnoses in 31 (32%), including CNS/PNS degenerative diseases (6%), spondylomyelopathy (3%), idiopathic intracranial hypertension (2%), headache (2%), Tolosa-Hunt syndrome, reversible cerebral vasoconstriction syndrome, hereditary spastic paraparesis, DYT1-positive dystonia and cerebral venous thrombosis. Patients who acquired a diagnosis of MS were significantly younger (38±13 versus 46±18 years; p=0.03) than those with other diagnoses. There were no differences in CSF data (cell number and type, proteins, Link’s Index, CSF/serum albumin ratio, presence of additional “mirror pattern”) between the two groups. Discussion and Conclusion: MS was the single most frequent diagnosis in patients with a single CSF IgG band. Nevertheless, the majority of patients with a single CSF IgG band have neurological diseases other than MS or CNS demyelinating diseases, the most frequent being CNS infections, inflammatory PNS diseases, CNS autoimmune/paraneoplastic diseases and cerebral tumours. Patients with a subsequent diagnosis of MS are significantly younger than those with other neurological diseases. HUMAN HYPOCRETIN RECEPTOR 2 ANTIBODIES ARE RARELY FOUND IN IDIOPATHIC NARCOLEPSY M. P. Giannoccaro1, P. Waters2, F. Pizza3, R. Liguori4, G. Plazzi4, A. Vincent2 1

Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum, University of Bologna (Bologna); 2Nuffield Department of Clinical Neurosciences, Oxford University (Oxford-UK); 3IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital (Bologna); 4IRCCS Institute of Neurological Sciences of Bologna, University of Bologna (Bologna) Objectives: Narcolepsy (NC) is caused by loss of hypothalamic hypocretin-secreting cells, and has been proposed to be autoimmune, although no clear evidence of autoimunnity has been provided to date. Recently NC has been recognized more commonly in children following H1N1 vaccination with Pandemrix. In 2015 Ahmed et al. [1] proposed a cross-reactivity between H1N1 influenza virus and the hypocretin receptor 2 (HCRTR2), and identified HCRTR2 autoantibodies in 85% of post-vaccination NC patients using a cell based ELISA (CBE). We established a cell-based assay (CBA) to test a group of idiopathic NC patients for this antibody. Methods: We studied 61 patients (41 adults, 20 children), including 50 narcolepsy type 1 (NT1, narcolepsy with cataplexy) and 11 type 2 (NT2, without cataplexy), 22 patients with other sleep disorders and 11 healthy controls. Human embryonic kidney cells were transiently transfected with a HCRTR2 construct. 36 hours post-transfection, live cells were incubated with patients’ sera for 1 hour at 1:20 dilution, then fixed and incubated with secondary anti-human IgG (H + L chain or anti Fc). For some sera, antibodies against the four IgG subclasses were used as secondary antibodies. A semi-quantitative pag. 40

scoring system was used from 0 to 4 as in previous publications; samples scoring ≥ 1 were considered positive. Results: Only 3/61 NC (5%) showed a score ≥ 1; anti-IgG Fc confirmed that the antibody was IgG. Anti-subclass identified IgG3 in two patients and IgG1 and IgG2 in one. Sera from five additional narcolepsy patients and one patient with idiopathic hypersomnia scored 0.5. Positive patients included one NT1 patient with associated psychotic features, one NT2 patient and a patient with cataplexy but normal Hcrt CSF levels. Discussion: Compared with previous findings [1], there were only a few NC patients with HCRTR2 antibodies. The difference may be related to the test used (CBE vs live CBA) or to the population included (post-vaccine vs idiopathic NC). Interestingly, one patient presented a peculiar phenotype with cataplexy and normal levels of Hypocretin-1 in the CSF. Conclusions: Antibodies against HCRTR2 are rare in patients with idiopathic narcolepsy, they have been detected in patients with widely heterogeneous phenotypes and their significance is unclear. Reference: − Ahmed SS, Volkmuth W, Duca J, Corti L, Pallaoro M, Pezzicoli A, Karle A, Rigat F, Rappuoli R, Narasimhan V, Julkunen I, Vuorela A, Vaarala O, Nohynek H, Pasini FL, Montomoli E, Trombetta C, Adams CM, Rothbard J, Steinman L. Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2. Sci Transl Med. (2015);7(294):294ra105

SARCOIDOSIS OF THE SPINAL CORD: CLINICAL AND RADIOLOGICAL CHARACTERISTICS G. Dalla Costa1, L. Sarro1, D. De Feo1, F. Sangalli1, B. Colombo1, L. Moiola1, N. Anzalone2, A. Falini2, G. Comi1, V. Martinelli1 1 Department of Neurology, San Raffaele Hospital (Milano); 2Department of Neuroradiology, San Raffaele Hospital (Milano)

Background Sarcoidosis of the spinal cord is a rare disease and its differential diagnosis is challeging as it often mimics other inflammatory demyelinating syndromes both clinically and on neuroimaging results. Methods: This is a case series on four patients presenting with a spinal cord syndrome ultimately confirmed as sarcoidosis at histopathological examination. The aim of this study is to describe the typical features of spinal cord sarcoidosis. Results: Four patients (mean age 50 years) have been followed-up over a median of 12 months after the onset of an isolated myelitis. Two patients were females and two were males, and all of them had an unremarkable previous medical history. All patients presented with sensory symptoms at the limbs, while two of them had motor deficit associated. Both the cervical and dorsal tracts of the spinal cord were involved in three patients, while one patient presented with an extensive involvement of the dorsal tract alone. The cerebrospinal fluid (CSF) showed elevated protein level (median 70 mg/dl) and elevated white cell count (median 45/mm(3). Oligoclonal bands were present in two patients. Thoracic lymphnodes enlargement, detected at CT and/or at PET examinations, not at clinical onset, but after repeated evaluations during the follow up, eventually lead to the histopathologic confirmation of granuloma formations with lymphocytic infiltrates typical of sarcoidosis in all cases. Of prominence, all patients presented with an initial linear leptomeningeal pattern of enhancement and after each relapse of the disease progressive parenchymal involvement was observed. The patients experienced clinical improvement with corticosteroids and/or immunosuppressive treatment. Conclusions: Symptoms due to intramedullary cervical lesions can be the first manifestation of neurosarcoidosis. The clinical course and neuroradiologic findings can mimic lynphoproliferative and demyelinating diseases. In neurosarcoisosis the spread of the typical leptomeningeal inflammatory process to the Virchow-Robin spaces is believed to result in parenchymal involvement, causing the centripetal involvement of the spinal cord at longitudinal assessments. SCLEROSI MULTIPLA 1 BODY MASS INDEX AND SLOW TITRATION ARE PROTECTIVE FACTORS FOR DIMETHYL FUMARATE GASTROINTESTINAL EVENTS IN A RELAPSING REMITTING MULTIPLE SCLEROSIS CLINICAL SETTING D. Paolicelli, A. Manni, A. Iaffaldano, V. Di Lecce, C. Tortorella, S. Zoccolella, M. Messina, P. Iaffaldano, R. Cortese, M. Trojano Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro (Bari) Background: The short-term safety profile for dimethyl fumarate (DMF) in the phase 3 trials was highly favorable and longpag. 41

term data from ENDORSE study confirmed a good benefit/risk ratio. However, the most frequent adverse events (AEs) in patients receiving DMF include flushing, gastrointestinal (GI) events and a certain incidence of leukopenia and lymphopenia. Objective: We tried to correlate demographic and anthropometric measures to the most common safety and tolerability issues in a cohort of 111 Relapsing Remitting Multiple Sclerosis (RRMS) patients treated with oral DMF 120 mg BID for 7 days (standard titration) or for 2-4 weeks (slower titration), and then increased to 240 mg BID. Methods: At the time of DMF first prescription, anthropometric measures were performed. Lymphocyte and leukocyte counts at baseline (T0) and after 3 (T3), 6 (T6) and 12 months (T12) of therapy were assessed by flow cytometry method. Any AEs were reported immediately upon the occurrence or during the scheduled follow-up. Results: The observation period was 10.3±5 months; 62% of subjects were female. The mean age at DMF beginning was 39.5 ± 11 years. The mean Body Mass Index (BMI) was 23.6±4.38. Seven patients interrupted the drug for AEs, one more patient for lack of efficacy. Among our patients 45% experienced GI side effects and 68% flushing. The multivariate analysis showed that a lower BMI (p/=1 relapse) to prior therapy at baseline (CARE-MS II; NCT00548405) demonstrated greater improvements in relapse rate and various MRI outcomes with alemtuzumab versus subcutaneous interferon beta-1a (SC IFNB-1a) over 2 years. In addition to the superior impact of alemtuzumab on reducing lesion activity vs SC IFNB-1a, MRI efficacy outcomes also included significant slowing of BVL. An extension study (NCT00930553) showed durable efficacy of alemtuzumab through 6 years in the absence of continuous treatment. Here we evaluate the effect of alemtuzumab on BVL over 6 years. Materials: MRI scans were obtained at baseline and annually thereafter. BVL was derived by relative change in brain parenchymal fraction. Methods: In the CARE-MS studies, patients received 2 alemtuzumab 12 mg/day courses (5 consecutive days at baseline and 3 consecutive days 12 months later). Patients completing the studies could enter the extension, with as-needed alemtuzumab for relapse or MRI activity. Alternate disease-modifying therapy (DMT) could be provided per investigator discretion. Results: 349 (95%) CARE-MS I and 393 (93%) CARE-MS II alemtuzumab-treated patients entered the extension. Through 6 years, 325/349 (93%) CARE-MS I and 344/393 (88%) CARE-MS II patients remained on study. In CARE-MS I patients, alemtuzumab slowed median yearly BVL over 2 years compared with SC IFNB-1a, and BVL remained low in Years 3-6 (Year 1: -0.59%, Year 2: -0.25%, Year 3: -0.19%, Year 4: -0.14%, Year 5: -0.20%, Year 6: -0.17%). In CARE-MS II patients, median yearly BVL significantly decreased over 2 years compared with SC IFNB-1a, and remained low in Years 3-6 (Year 1: -0.48%, Year 2: -0.22%, Year 3: -0.10%, Year 4: -0.19%, Year 5: -0.07%, Year 6: -0.10%). These effects were achieved with 63% (CARE-MS I) and 50% (CARE-MS II) of patients receiving no alemtuzumab retreatment after the initial 2 alemtuzumab courses and no other DMT through Year 6. Discussion: Slowing of BVL with alemtuzumab was maintained over 6 years. Median annual BVL was /=50% of patients receiving no additional treatment since the initial 2 alemtuzumab courses. CONCLUSION: Based on these findings, alemtuzumab may provide uniquely durable efficacy in the absence of continuous treatment for RRMS patients. Study Support: Sanofi Genzyme and Bayer HealthCare Pharmaceuticals. Aspects of the work described in this abstract were submitted at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), September 14-17, 2016, London, United Kingdom. The authors would like to acknowledge Dr Daniel Pelletier for his interpretation of the data and for his critical review of the abstract content.

CEFALEE 1 FEATURES OF MIGRAINE WITH AURA IN PEDIATRIC AGE M. Balestri1, D. Maiorani2, A. Capuano1, S. Tarantino1, R. Frusciante1, L. Papetti1, F. Vigevano1, M. Valeriani1 1

Headache Center, Neurology, Bambino Gesù Hospital (Roma);

2

Pediatric Unit, Hospital of Viterbo (Viterbo)

Objective: Though common in pediatric age, migraine with aura (MA) has been scarcely studied in children. Our aims were to investigate: 1) the clinical characteristics of the aura in a cohort of MA children, and 2) the features of the headache associated with the aura. Methods: The present study was based on data retrospectively collected from 164 MA children referred to our 3rd level Headache Centre. Results: In our patients, the visual symptoms were far more frequent (93%) than the somatosensory, motor, and speech disturbances. The aura anticipated the headache onset in most cases (69.1%) and its duration ranged from 5 to 60 minutes. When we divided our patients in 4 different age groups (less than 7 years, between 7 and 10 years, between 11 and 14 years, more than 14 years), no difference in the aura characteristics was found between the groups. On the other hand, when the headache type was classified according to the ICHD-IIIb criteria, migraine was diagnosed only in 40.2% of patients and the diagnosis remained undetermined in 4.3% of MA children. However, if headache duration was not considered, the migraineurs raised to 67% of patients and in no child the diagnosis was undetermined. pag. 44

Discussion: Our pediatric population showed aura features that did not depend on the age and were similar to those of adult patients. However, the headache could be difficult to be classified if headache duration was considered. Conclusions: ICHD-IIIb criteria for aura are suitable also for children and adolescents.

FACTORS ASSOCIATED TO FREQUENT RELAPSE INTO MEDICATION OVERUSE IN CHRONIC MIGRAINE PATIENTS: A 3-YEAR RETROSPECTIVE EVALUATION L. Grazzi, A. Raggi Neurology Public Health and Disability Unit, IRCCS Foundation Neurological Institute C. Besta (Milano) Introduction: Chronic migraine (CM) is a negative evolution of migraine course characterized by headaches occurring 15 or more days per month. It is often cause of medication overuse (MO). The treatment of CM with MO requires withdrawal of overused drugs, prescription of individualized prophylaxis, and advice and education to prevent relapse into MO. A subgroup of patients can be considered as “frequent relapsers” (FR), requiring two or more structured withdrawals over three years. There are relatively few studies that specifically addressed the possible predictors of relapse. Aim: To characterize FR patients in terms of disease features and associated psychosocial aspects. Methods: A sample of 194 adult patients with CM-MO according to Silberstein’s criteria attending our Headache Center to perform a withdrawal treatment were consecutively recruited between June 2011 and December 2012. They completed standardized clinical interview which included previous withdrawal treatments, living situation, employment, as well as questionnaires measuring disability (WHODAS 2.0), headaches frequency, depressive symptomatology (BDI-II). FR patients were defined as those with at least one structured withdrawals in the three years before the current hospitalization. Baseline differences between FR and non-FR were assessed using Chi-Squared and Student’s t-test. Results: Complete information was available for 188 patients; 58 were considered as FR (30.8%). The mean number of days with headache in 3 months was 63.9 in FR and 55.1 in non FR patients (P=.010); mean BDI-II score was 19.4 and 15.3 (P=.005); WHODAS 2.0 score was 34.8 and 29.1 (P=.005), respectively. Furthermore, 22% of FR and 10% of non-FR were living alone (P=.023), and 48.3% of FR and 65.4% of non-FR had low education (P=.027). No differences were found for gender, employment status, age, overuse of triptans vs. NSAIDS. Discussion: In this retrospective study we found that several aspects related either to the clinical presentation of headache or to psychosocial domains were significantly more common in those who undergo repeated withdrawal treatments, i.e. FR, namely: higher frequency of headaches, living alone, having a lower education, higher disability scores, and higher depression scores. Our data may contribute to the management of CM with MO and will be useful to guide future prospective studies. COGNITIVE DYSFUNCTIONS AND PSYCHOLOGICAL SYMPTOMS IN MIGRAINE WITHOUT AURA: A CROSS-SECTIONAL STUDY A. De Mase1, A. Russo2, G. Santangelo3, L. Trojano3, F. Falco3, L. Marcuccio2, M. Siciliano3, F. Conte2, F. Garramone3, A. Tessitore2, G. Tedeschi2 1

Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples (Napoli); Headache Center, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples (Napoli); 3Department of Psychology, Second University of Naples (Caserta) 2

Objective: The aim of the study was to characterize the cognitive profile and psychological symptoms (i.e. depression, anxiety and apathy) in drug-naïve migraine without aura (MwoA) patients. Background: The occurrence of cognitive dysfunctions and psychological symptoms, as well as their mutual relationships, in migraine patients are still debated. Methods: Seventy-two consecutive MwoA patients, referred to the Italian University Headache Clinic and 72 healthy subjects (HCs) were enrolled. Patients, during an attack-free period, and HCs completed Montreal Cognitive Assessment (MoCA), Beck Depression Inventory-II (BDI-II), Selfversion of Apathy Evaluation Scale (AES-S) and State and Trait Anxiety Inventory (STAI-Y-1 and 2). Clinical parameters of disease severity (i.e. disease duration, migraine attacks per month, mean pain intensity during migraine attacks, migraine disability and impact on daily life) were recorded. Results: Although performance of MwoA patients on MoCA was above Italian cut-off threshold (45 g of alcohol) and lightmoderate drinkers or non-drinkers. We constructed multivariable logistic regression models including demographics, conventional vascular risk factors, and antithrombotic drugs as covariates. Based on the observation that hemorrhage location (deep hemispheric versus lobar) is an important clue to etiology, analyses were performed separately for lobar and deep ICH subjects versus control subjects. Results: A total of 3,173 cases (mean age 75.79 ±9.65 years; males, 55.5%) and 3,155 controls (mean age 73.18 ±7.28 years; males, 55.4%) were enrolled. The prevalence of excessive alcohol consumers was similar between ICH cases and controls (14.2%vs13.2 %, p=0.232), and alcohol intake was not associated with the overall risk of ICH after adjusting for potential confounders (OR 1.09, 95% CI, 0.93–1.29; p=0.29). Conversely, excessive alcohol consumption was associated with disease risk in the group of patients with deep ICH (OR 1.30, 95% CI, 1.05–1.6; p=0.01), as well as in that of people in the fourth quartile of age (> 80 years; OR, 1.75; 95% CI, 1.14-2.69; p=0.01).The highest disease risk associated to excessive alcohol intake was detected in patients aged over 80 years with deeply located hematomas (OR, 2.56; 95% CI, 1.38-4.75, pag. 54

p=0.003), whereas no effect was found for lobar ICH. Within the group of patients at highest risk, untreated hypertension was strongly associated to excessive alcohol consumption (OR, 5.01; 95% CI, 2.31-10.84; p≤0.001). Conclusion: In people aged ≥ 55 years, excessive alcohol consumption increases the risk of deeply located ICH, especially in older subjects with untreated hypertension. This suggests a prominent role for alcohol in the vascular pathologies underlying deep ICH, but not in cerebral amyloid angiopathy causing bleeding in the lobar brain regions.

MALATTIE DEL MOTONEURONE THE UTILITY OF MULTIMODAL IMAGING IN THE DIAGNOSIS OF ALS F. Agosta1, P. Ferraro1, N. Riva2, M. Copetti3, Y. Falzone2, A. Chiò4, G. Sorarù5, A. Falini6, G. Comi2, M. Filippi1 1

Neuroimaging Research Unit, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University (Milano); 2Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University (Milano); 3Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza (San Giovanni Rotondo-FG); 4 ALS Center, “Rita Levi Montalcini”, Department of Neuroscience, University of Torino (Torino); 5Department of Neurosciences, University of Padova (Padova); 6Department of Neuroradiology, San Raffaele Scientific Institute, VitaSalute San Raffaele University (Milano) Objectives: To develop an automated method for identification of individual patients with amyotrophic lateral sclerosis (ALS) using multimodal advanced structural Magnetic Resonance Imaging (MRI) data and to test the validity of our approach in patients at onset with clinical syndromes suggestive of ALS, but not meeting criteria for ALS based on revised El Escorial/Awaji criteria. Materials and methods: 3D T1-weighted and diffusion tensor (DT) MRI were obtained from 113 sporadic (probable, probable-laboratory supported, definite) ALS patients, 20 patients with ALS mimic disorders, and 40 healthy controls. The diagnostic accuracy of precentral cortical thickness measures and DT MRI metrics of the corticospinal tract and motor callosal fibers were assessed in a testing cohort and externally proved in a validation cohort using a random forest analysis. Results: In the testing set (64 randomly selected sporadic ALS patients and healthy controls), precentral cortical thickness showed 0.85 accuracy, 0.76 sensitivity, 1.00 specificity in differentiating ALS patients from healthy controls, while DT MRI measures distinguished the two groups with 0.77 accuracy, 0.84 sensitivity, 0.65 specificity. In the same group, the combination of cortical thickness and DT MRI metrics improved the classification pattern as follows: 0.87 accuracy, 0.88 sensitivity, 0.84 specificity. In the validation cohort (remaining 49 sporadic ALS vs mimic disorders), the best diagnostic accuracy was reached by DT MRI (0.99 accuracy, 1.00 sensitivity, 0.94 specificity) while cortical thickness measures provided the following discrimination values: 0.73 accuracy, 0.82 sensitivity, 0.56 specificity. The combined approach distinguished ALS from mimic syndromes with 0.87 accuracy. Discussion and Conclusions: A multimodal imaging approach that incorporates motor cortical and white matter alterations yields statistically significant improvement in accuracy over using each modality separately in the individual ALS patient classification. In order to distinguish ALS from mimic disorders, DT MRI represents the most powerful tool. This study provides a roadmap for translation of MRI predictors of ALS into clinical daily practice. Funded by: AriSLA (MacLearnALS Project).

DISEASE PROGRESSION IN SBMA: IS SERUM CREATININE A RELIABLE BIOMARKER? G. Querin1, E. Da Re1, I. Martinelli1, L. Bello1, C. Bertolin1, D. Pareyson2, C. Mariotti2, E. Pegoraro1, G. Sorarù1 1

Department of Neurosciences, University of Padova (Padova); 2Clinic of Central and Peripheral Degenerative Neuropathies Unit, Department of Clinical Neurosciences, IRCCS Foundation, C. Besta Neurological Institute (Milano)

Background: Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, X-linked, lower motor neuron disease caused by a CAG repeat expansion within the androgen receptor gene. No reliable index of disease progression has been established so far and, nevertheless, there is a critical need for biomarkers discovery and validation in order to improve the diagnostic process and organization of clinical trials (1). Objective: We investigated if creatinine serum levels, a common used biomarker in neuromuscular diseases, could be a pag. 55

reliable index of disease progression in SBMA. Methods: We studied 65 SBMA patients. They underwent biochemical analysis including creatinine and CK serum levels and completed a clinical protocol including 6 minute walk test (6MWT), functional scale (ALS-FRSr), ADL grade scale and respiratory evaluation (fVC) at baseline and after 1 year. Spearman’s coefficient was used to assess correlations and a linear regression was used to fit the obtained results. Student t test were used to compare means. Results: A significant decrease of 6MWT values (p =0.003) and creatinine serum levels (p= 0.0031) was observed between baseline and 12 months evaluation. Creatinine serum levels at baseline didn’t correlate with age of the patients, disease duration and age of symptoms onset. They correlated with 6MWT (p=0.0006), total ALSFRS score (p< 0.001) and with upper and lower limbs subscores at baseline (p< 0.001). A correlation was found also with the ADL grade (p50% of patients had tongue and palatal movements preserved. At first speech evaluation dysarthria was globally considered mild in 52% of patients, moderate in 19.3%, severe in 18% of patients. Time from disease onset to dysarthria onset was inversely correlated with survival (p80% sustained mean knockdown of serum TTR and was considered generally well tolerated in patients with hATTR-PN (1,2). Additionally, data from the Phase 2 open-label extension study demonstrated evidence for potential disease stabilization at 18 months (2). Materials and Methods: APOLLO is a Phase 3 international, randomized (2:1), double-blind study (NCT01960348) evaluating the efficacy and safety of patisiran 0.3mg/kg IV or placebo once every 3 weeks in symptomatic patients hATTRPN (neurological impairment score [NIS] of 5-130). Select exclusion criteria included: prior liver transplantation, current tetramer stabilizer use, PND score >3b, and NYHA class >2. The primary endpoint is change from baseline at 18 months in

pag. 66

the mNIS+7 composite neurologic impairment score; secondary endpoints include assessments of QOL and changes in mBMI, motor/autonomic function. Results: 225 patients with hATTR-PN were enrolled at 44 sites (19 countries) and representative of the global patient population (EU: 51%; N. America: 21%; Asia Pacific: 20%; LatAm: 8%). Median age: 62 years (24-82); males: 74%; Val30Met TTR mutation: 42%; non-V30M mutations: 58% (including 73 TTR genotypes); and previously TTR tetramer stabilizer use: 53%. Measures of baseline disease severity showed - FAP Stage 1: 46%; FAP Stage 2: 53%; and mean mBMI: 978.7 kg/cm2g/L (522-1530). Mean baseline NIS and mNIS+7 were 59.3 (6.0-141.6) and 78.8 (8.0-165.0), respectively. NIS and mNIS+7 were highly correlated with FAP Stage and PND score. Echocardiographic evidence of cardiac involvement noted in 54% of patients; with mean NT-proBNP and troponin levels of 1461 ng/L (40-7895) and 0.1 ng/mL (0.1-1.0), respectively. Discussion and Conclusions: Baseline demographics demonstrate that the Phase 3 APOLLO study enrolled hATTR-PN patients with a wide range of TTR genotypes and neuropathy severity, including >50% with cardiac involvement. This is the largest, controlled study of patients with hATTR-PN to date and is representative of the global patient population.

References: 1. Suhr OB, Coelho T, Buades J, et al. Efficacy and safety of patisiran for FAP: a phase II multi-dose study. Orphanet J Rare Dis. (2015);10:109 2. Adams D, Suhr OB, Conceicao I, et al. Phase 2 OLE study of patisiran, an RNAi Therapeutic for FAP. Neurology (2016); 86(16):S38.003

RETREATMENT WITH RITUXIMAB IN ANTI-MAG POLYNEUROPATHY: IS THE B-CELL-ACTIVATING FACTOR (BAFF) A NEGATIVE PROGNOSTIC FACTOR? M. Garnero1, D. Franciotta2, C. Briani3, M. Campagnolo3, M. Grandis1, S. Fabbri1, A. Beronio4, G. Mancardi1, A. Schenone1, L. Benedetti1 1

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa (Genova); 2Laboratory of Neuroimmunology, C. Mondino National Neurological Institute, University of Pavia (Pavia); 3 Department of Neurosciences, University of Padua (Padova); 4Department of Neurology, S. Andrea Hospital (La Spezia) Introduction: The B-cell depleting anti-CD20 monoclonal antibody Rituximab is the main therapeutic choice for antimyelin-associated glycoprotein (MAG) polyneuropathy. B-cell-activating factor (BAFF) is a key costimulatory molecule for B-cell survival, proliferation and immunoglobulin production. BAFF induced furthermore modifications on B-cell homeostatic regulation, in particular the increase of the numbers of long lived plasmacells, Ig- producing, compared to the short lived plasmacells. As previously reported, serum BAFF values > 1665 pg/ml can predict the lack of response or the precocity of relapse in Rituximab-treated patients with anti-MAG polyneuropathy. Analogously, higher serum BAFF levels were associated with resistance to Rituximab in patient with lymphoma or Sjogren syndrome. Patients and Methods: Nineteen patients with anti-MAG polyneuropathy responding to rituximab, 375 mg/sq for four consecutive weekly infusions, were prospectively studied for 6-13 years (average 9 years). Clinical deterioration was defined as worsening by one point in at least two scales including MRC sumscore, INCAT Disability Scale and INCAT sensory sumscore and required additional Rituximab cycles. BAFF concentrations were measured in serum samples before and after the first and subsequent admistrations of Rituximab by a commercial ELISA. The kit employed a monoclonal antibody specific for BAFF, and a peroxide-linked anti-BAFF polyclonal antibody. Results: Four patients maintained the improvement through the last follow-up. Among the fifteen patients deteriorating a total of thirteen patients received multiple courses of Rituximab. Retreatment cycles were generally administered in an interval time never less than 2 years. Nine of thirteen patients receiving multiple courses of Rituximab improved their clinical status again while in three the results were less satisfactory than those following the first treatment. Drug resistance was recorded in one patient after the fourth cycle. In these last four patients we recorded that the values of BAFF increased progressively after each cycle of Rituximab. Conclusion: We observed that serum BAFF concentration progressive increase after repeated cycles of Rituximab and this correlates with a reduced clinical benefit as if it develops a resistance to the retreatment. These findings confirm what has already been observed by Dalakas et al. (Neurology 2008) that Rituximab may be associated with anti-BAFF agents in order to prevent the development of resistance to the treatment. Targeting BAFF could be beneficial, given the consequent reduction in the survival of BAFF-dependent, rituximab-insensitive long-lived plasma cells.

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DEFLAZACORT TREATMENT AND SPP1 RS8357094 GENOTYPE IMPACT OPN PROTEIN LEVEL IN PRIMARY MUSCLE CELLS OF DUCHENNE MUSCULAR DYSTROPHY PATIENTS L. Bello1, S. Vianello1, B. Pantic1, E. Galletta1, D. Borgia1, B. Gavassini1, G. Soraru'1, L. Vitiello2, E. Pegoraro1 1

Department of Neurosciences, University of Padua (Padova); 2Department of Biology, University of Padua (Padova)

Aims: Osteopontin (OPN), the protein product of the SPP1 gene, plays a role in Duchenne muscular dystrophy (DMD) pathophysiology as a modulator of muscle inflammation and regeneration. A polymorphism in the SPP1 promoter (rs28357094) has been recognized as a genetic modifier of disease severity, and possibly of response to glucocorticoid (GC) treatment, with a dominant effect. We aimed to study SPP1 mRNA and OPN protein expression in primary human myoblasts and myotube cultures, both normal and dystrophin-deficient, in basal conditions and in response to GCs. Materials and Methods: DMD proliferating primary myoblasts and differentiated myotubes, derived from muscle biopsies of 12 DMD patients and 9 controls with defined rs28357094 genotypes (TT versus TG), were treated for 72h with the GC drug deflazacort (DFZ). SPP1 mRNA was quantified by rtPCR, and OPN protein was quantified by Western Blot. OPN protein was detected as two 55/50 kDa bands (confirmed by siRNA gene silencing). Results: There was a trend towards higher SPP1 mRNA expression with the TT genotype. No significant difference in OPN mRNA or protein was detected in DFZ-treated DMD myoblasts or myotubes compared to control cells. However, when DMD cells were stratified according to rs28357094 genotype, DFZ treatment resulted in a significant increase in OPN protein in both myoblasts and myotubes carrying the TG genotype, with a significant interaction term between treatment and genotype. We did not observe a strong linear correlation between mRNA expression and protein levels. Both healthy and DMD myoblasts and myotubes expressed high levels of OPN protein. A shift towards the 50 kDa protein band was observed in the transition from myoblast to myotube and to mature muscle. Increase in OPN protein was observed in DMD myotubes carrying TG genotype at rs28357094. Discussion: Expression data confirmed that the T allele at rs28357094 renders the SPP1 promoter more active in basal conditions. Conversely, the G allele seems to enhance gene expression when GCs are administered. There is a complex regulation of OPN protein expression, which involves post-transcriptional mechanisms as well as post-translational modifications, ultimately leading to greater OPN abundance in DMD myotubes carrying the rs28357094 TG genotype. Conclusions: These findings are in concordance with clinical studies showing a stunted long-term effect of GC treatment in carriers of the G allele at 28357094, suggesting that this SNP is a pharmacogenetic predictor of poorer GC response, rather than a modifier of disease progression per se. CLENBUTEROL AMELIORATES THE PHENOTYPE OF SPINAL AND BULBAR MUSCULAR ATROPHY MICE AND PATIENT-DERIVED MYOTUBES G. Soraru1, C. Milioto2, A. Malena1, M. Polanco2, D. Borgia1, E. Pegoraro1, E. Maino2, M. Pennuto2 1

Department of Neurosciences, University of Padua (Padova); 2Dulbecco Telethon Institute, Centre for Integrative Biology, University of Trento (Trento)

Objectives: Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease characterized by the loss of lower motor neurons. SBMA is caused by the expansion of a polyglutamine tract in the gene coding for androgen receptor (AR). Expression of polyglutamine-expanded AR causes damage not only to motor neurons, but also to skeletal muscle cells. Here we investigated the effect of beta-agonist stimulation in SBMA muscle cells and knock-in mice. Materials and Methods: We treated C2C12 myotubes expressing polyglutamine-expanded AR, knock-in SBMA mice, and SBMA patient-derived myotubes with the beta-agonist clenbuterol. Results: We showed that treatment of C2C12 myotubes expressing polyglutamine-expanded AR with the beta-agonist clenbuterol increases myotube width. This effect was associated with activation of the phosphatidylinositol-3-kinase (PI3K)/Akt and adenylyl cyclase (AC)/protein kinase A (PKA) pathways, suggesting that clenbuterol induces SBMA myotube hypertrophy through activation of these pathways. Notably, clenbuterol treatment decreased the accumulation of polyglutamine-expanded AR. Treatment of SBMA mice with clenbuterol started at disease onset ameliorated motor function, extended survival, and improved muscle pathology. Clenbuterol reduced the glycolytic-to-oxidative fiber-type switch occurring in SBMA glycolytic muscles and induced hypertrophy of both glycolytic and oxidative fibers. Importantly, clenbuterol induced hypertrophy of primary myotubes derived from SBMA patients. Discussion and Conclusion: These results indicate that beta-agonist stimulation with clenbuterol is a novel therapeutic strategy for SBMA.

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AN ITALIAN MULTICENTER DATABASE FOR THE DIAGNOSIS AND THERAPY OF CHRONIC INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY (CIDP) AND ITS VARIANTS G. Liberatore1, D. Cocito2, M. Filosto3, S. Jann4, M. Clerici5, A. Cortese6, G. Lauria7, G. Cavaletti8, M. Carpo9, R. Fazio10, G. Antonini11, M. Luigetti12, M. Ruiz13, E. Peci2, A. Todeschini3, E. Verrengia4, L. Piccolo6, E. Beghi14, E. Nobile Orazio1 1

IRCCS Humanitas Clinical and Research Center, Milan University (Milano); 2Department of Neuroscience, Città della Salute e della Scienza Hospital (Torino); 3Neurology Clinic, Spedali Civili Hospital (Brescia); 4Department of Neuroscience, Niguarda Cà Granda Hospital (Milano); 5Department of Neuroscience, Fondazione Macchi Hospital (Varese); 6Mondino National Neurological Institute, IRCCS Fondazione Mondino (Pavia); 73rd Neurology Unit, IRCCS Carlo Besta Neurological Institute (Milano); 8Department of Neurology, Milano Bicocca University, S. Gerardo Hospital (Monza); 9Neurology Unit, Treviglio Hospital (Treviglio-BG); 10Neurological Institute, IRCCS San Raffaele Hospital (Milano); 11Department of Neuroscience, S. Andrea Hospital, Univesity of Rome (Roma); 12Institute of Neurology, Policlinico Universitario Agostimo Gemelli, UCSC (Roma); 13Institute of Neurology, University of Padua (Padova); 14 Department of Neuroscience, IRCCS Mario Negri Institute (Milano) Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic and disabling disease that often improves with immune therapy. Several variants of CIDP have been reported including purely motor, sensory, distal, asymmetric or focal forms. The relation of these variants to CIDP remains unclear also considering that some of them may have a different response to therapy. The lack of clear diagnostic criteria for these variants may also explain the different proportion and response to therapies among different series of patients. Methods: We implemented a web-based database to collect the data from large series of patients with CIDP followed by Italian Centers with expertise on CIDP in order to determine the frequency and characteristic of these variants, the diagnostic criteria used for the diagnosis, the possible evolution into typical CIDP, the association with specific anti-nerve antibodies, and their response to therapy. The association of CIDP and variants with antecedent events, life and dietary habits and concomitant diseases will be also examined. All the patients will be evaluated at the time of inclusion and tested for the presence of different anti-nerve antibodies. Patients will be followed for two years to monitor their outcome and response to therapy. Results: The study started on October 2015 and by May 31, 2016 we included 160 patients with CIDP and variants (95 men, 65 women), aged 18-86 years (median 62). Almost half of the patient had a purely motor (19%) or sensory (28%) presentation but, at the time of inclusion after a mean disease duration of 7.9 years (range 0.5-38 years), 87% had a sensorimotor impairment while only few remained with purely sensory (6%) or motor (7%) symptoms. A consistent proportion of patients developed fatigue (71%) and pain (38%). The diagnosis of CIDP was confirmed by the EFNS/PNS criteria in 84% of patients. CIDP was typical in 90% and atypical in 10%. CSF studies were diagnostic in 80% of the patients while nerve biopsy or imaging (US or NMR) in 62% and 60%. Improvement after one or more therapies was reported by 87% of the patients with a positive response to IVIg (85%), steroids (47%), plasma exchange (71%) and immunosuppressant (33%). Conclusions: These preliminary data confirm that studies with multicenter database can be very useful in providing information on the natural history, course, diagnosis and response to therapy in patients with CIDP and variants. LIPOMATOSIS INCIDENCE AND CHARACTERISTICS IN AN ITALIAN COHORT OF MITOCHONDRIAL PATIENTS E. Barca1, O. Musumeci1, C. Lamperti2, G. Comi3, M. Moggio4, T. Mongini5, G. Siciliano6, M. Filosto7, E. Pegoraro8, S. Servidei9, D. Ronchi3, L. Vercelli5, D. Orsucci6, L. Bello8, G. Primiano9, M. Zeviani10, M. Mancuso6, A. Toscano1 1 Department of Clinical and Experimental Medicine, Neurology and Neuromuscolar Disease Unit, Messina University (Messina); 2Unit of Molecular Neurogenetics, The Foundation "Carlo Besta" Institute of Neurology (Milano); 3Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan (Milano); 4 Neuromuscular Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, and Dino Ferrari Centre, University of Milan (Milano); 5Department of Neuroscience, University of Turin (Torino); 6Neurological Clinic, University of Pisa (Pisa); 7Neurological Clinic, University Hospital Spedali Civili, University of Brescia (Brescia); 8Neurological Clinic, University of Padova (Padova); 9Institute of Neurology, Catholic University of the Sacred Heart (Roma); 10Mitochondrial Biology Unit, Medical Research Council (Cambridge-UK)

Introduction: Lipomas have often been associated with mtDNA mutations and were mainly observed in patients with mutation in mitochondrial tRNA lysine which is also the most frequent mutation associated with MERRF. Up to date, no pag. 69

systematic studies have been developed in order to assess the incidence of lipomas in large cohorts of mitochondrial patients. The aim of this study is to analyze the incidence and characteristics of lipomas among an Italian cohort of patients with mitochondrial diseases. Methods: Retrospective, database-based study (Nation-wide Italian Collaborative Network of Mitochondrial Diseases) of patients with lipomas. Results: A total of 17 patients with lipomas have been identified among the 1086mitochondrial patients,enrolled in the Italian database. About 20% showed a classical MERRF syndrome whereas the others disclosed myopathy (40%), one CPEO and other two only an isolated lipomatosis. Lactate was elevated in almost all the examined patients. Muscle biopsy was available in 10/17 patients: in all of them mitochondrial abnormalities were present. 90% had mutations in mtDNA coding for tRNA lysine. Interestingly,two patients had multiple mitochondrial DNA deletions in muscle. Lipomas were multiple in 11 out of 17 patients and in about 50% were symmetric. In all patients, lipomas were localized along the cervical-cranial-thoracic region. Conclusion: Our data confirm the strong association between multiple lipomas and lysine tRNA mutations, although the presence of two patients with muscle mtDNA multiple deletions confirm that mutation in other genes may lead to a similar phenotype. References: − Altmann J, et al. Expanded phenotypic spectrum of the m.8344A>G "MERRF" mutation: data from the German mitoNET registry. J Neurol. (2016); 263(5):961-72 − Sawyer SL, et al. Homozygous mutations in MFN2 cause multiple symmetric lipomatosis associated with neuropathy. Hum Mol Genet. (2015); 24(18):5109-14 − Mancuso M, et al. Phenotypic heterogeneity of the 8344A>G mtDNA "MERRF" mutation. Neurology (2013); 80(22):2049-54

DISEASE PROGRESSION AND CLINICAL HISTORY IN 246 PATIENTS FROM THE FSHD ITALIAN REGISTRY L. Vercelli1, G. Ricci2, M. Cao3, E. Rolle1, V. Ponzalino1, L. Ruggiero4, F. Mele5, M. Govi5, A. Nikolic5, L. Villa6, E. Bucci7, R. Di Giacomo8, M. Scarlato9, B. Pasanisi10, G. Tomelleri11, M. Filosto12, L. Maggi10, S. Previtali9, C. Rodolico13, A. Di Muzio8, G. Antonini7, M. Moggio6, L. Santoro4, C. Angelini14, E. Pegoraro3, R. Tupler5, T. Mongini1 1

Department of Neurosciences, Center for Neuromuscular Diseases, University of Turin (Torino); 2Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa (Pisa), 3Department of Neurosciences, University of Padua (Padova); 4Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples (Napoli); 5Department of Life Sciences, University of Modena and Reggio Emilia (Modena); 6Neuromuscular Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Dino Ferrari Center (Milano); 7Department of Neuroscience, Mental Health and Sensory Organs, S. Andrea Hospital, University of Rome "Sapienza" (Roma); 8Center for Neuromuscular Disease, CeSI, University "G. D'Annunzio" (Chieti); 9Neuromuscular Repair Unit, INSPE and Division of Neuroscience, IRCSS San Raffaele Scientific Institute (Milano); 10IRCCS Foundation C. Besta Neurological Institute (Milano); 11Department of Neurological, Neuropsychological, Morphological and Movement Sciences, University of Verona (Verona); 12Neurology Clinic, ‘‘Spedali Civili’’ Hospital (Brescia); 13Department of Neurosciences, Policlinico "G. Martino", University of Messina (Messina); 14IRCCS San Camillo (Venezia) Objective: Facio-Scapulo-Humeral muscular dystrophy (FSHD) is a rare genetic disorder, with a distinctive and peculiar phenotype: a progressive asymmetric facial, shoulder girdle and pectoral muscle weakness and atrophy, with a descending progression to involve the distal lower extremity muscles before affecting the hip girdle muscles. The Italian Network for FSHD designed a longitudinal study to assess disease progression on a long-term period because FSHD is known having a slowly disease deterioration but literature is poor about long follow up in these pathology or study have few cases. Materials and Methods: The study was performed by collecting data from the Italian FSHD Registry, based on a nationwide collaboration. We have selected the patients, genetically confirmed, with a follow up at least 5-years long (first evaluation 2007-2011; second one 2013-2016). We have used MRC scale, FSHD clinical score in both examinations and the new concept of Comprehensive Clinical Evaluation Form (CCEF)*, a tool which defines various clinical categories by the combination of different features, typical or atypical for FSHD. Results: The patients were 246 (110 females, 136 males, aged 12-84 years, with a D4Z4 allele ≤41kb). We have observed a limited decline in FSHD disease: the mean deterioration was 1 point to FSHD clinical score but index cases have worsened more than relatives while incomplete phenotypes (B categories) or carriers with a FSHD score equal to 0 (C categories) did

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not progress in 5-years. 4% subjects have lost ambulation and 3% became NIMV-dependent cases. Patients with an intermediate FSHD score worsened more than the other groups. Discussion: FSHD is one of the most common muscular dystrophies but despite a great number of clinical studies, little is known about the real progression over the years and about the natural history of the disease. Our Italian study is the first longitudinal study with a large cohort of patients We need FSHD patients with complete phenotype (A categories) and index cases for design a potential therapeutic future study because in these categories we observe the greatest decline than the other groups. Conclusions: Our data stress the importance to rely on more sensitive outcome measures, specifically designed to monitor disease progression in view of future clinical trials. Reference: − G Ricci, L Ruggieri, L Vercelli et al. A novel clinical tool to classify facioscapulohumeral muscular dystrophy phenotypes. J Neurol (2016);263:1204–1214

24/10/2016 CASI CLINICI 2 CEREBRAL AMYLOID ANGIOPATHY-RELATED INFLAMMATION WITH PSEUDOTUMORAL PRESENTATION: CLINICORADIOLOGICAL FEATURES AND COURSE IN A PATIENT C. Piantadosi, M. Bassetti, A. Casini, A. Cobianchi, A. Salerno, L. Bove Neurology Unit, San Giovanni-Addolorata Hospital (Roma) Background: Cerebral Amyloid Angiopathy-related inflammation (CAA-ri) is a less frequent manifestation of Cerebral Amyloid Angiopathy (CAA) and results from an inflammatory response to β-amyloid protein in the blood vessel walls [1]. Objectives: To describe the clinicoradiological features and to point out the course in a patient with CAA-ri. Case report: A 74-year-old woman, after the death of the husband, began to have memory impairment and agitation, treated with neuroleptics at medium-high dosage. A cerebral CT scan showed minor abnormalities. About five months later, slowly progressive right hemiparesis presented; a generalized seizure also occurred and the patient was promptly transported to our hospital. At admission brain CT scan revealed diffuse left hemispheric edema. The neurological examination detected a confused and disorientated patient and right hemiparesis. An EEG recorded abundant delta waves and epileptiform abnormalities, bilaterally located but prevailing on left side. A cerebral neoplastic disorder was suspected and intravenous dexamethasone (8 mg/day for 40 kg body-weight) and levetiracetam were soon started. Routine blood tests (including ESR ) were all normal as well as the tumor markers and tests for anti-phospholipid and anti-thyroid antibodies, systemic lupus erythematosus and other connective tissue diseases. Brain MRI (performed under sedation) showed: diffuse left hemispheric hyperintesity on FLAIR sequences (consistent with vasogenic edema); no enhancement on postcontrast T1-weighted images; microbleeds on gradient echo sequences (T2*-GRE). The microbleeds were distributed in cerebral lobes and were very numerous with a starry-sky appearance. The diagnosis of probable CAA-ri was made according to the recently published criteria [2]. Dexamethasone was switched to oral prednisone (50 mg/day for a month and tapered within three months), levetiracetam was continued. Control MRI showed marked reduction of edema. The right hemiparesis regressed, walking became stable, no more seizures happened but memory loss did not improve with persistent disorientation and need of supervision. Discussion: CAA-ri can mimic a brain tumor for clinical and radiological aspects [3]. Cerebro-meningeal biopsy can be dangerous to elderly patients and not informative. It has become crucial for the diagnosis of CAA-ri to perform brain MRI with also T2*-GRE or susceptibility-weighted imaging (SWI) as reported in recently validated criteria [2]. Nonetheless, it is advisable to carry out further studies which should better clarify treatment, course and prognosis of CAA-ri. Conclusions: Cerebro-meningeal biopsy is no longer required for diagnosis of CAA-ri. Dissolving inflammatory edema, the corticosteroid treatment can improve different symptoms of CAA-ri but the prognosis remains that of underlying CAA. References: 1. Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry (2012);83(2):124-37 2. Auriel E, Charidimou A, Gurol ME, Ni J, Van Etten ES, Martinez-Ramirez S, Boulouis G, Piazza F, DiFrancesco JC, Frosch MP, Pontes-Neto OV, Shoamanesh A, Reijmer Y, Vashkevich A, Ayres AM, Schwab KM, Viswanathan A, Greenberg SM. Validation of Clinicoradiological Criteria for the Diagnosis of Cerebral Amyloid pag. 71

3.

Angiopathy-Related Inflammation. JAMA Neurol (2016);73(2):197-202 Ronsin S, Deiana G, Geraldo AF, Durand-Dubief F, Thomas-Maisonneuve L, Formaglio M, Desestret V, Meyronet D, Nighoghossian N, Berthezène Y, Honnorat J, Ducray F. Pseudotumoral presentation of cerebral amyloid angiopathy-related inflammation. Neurology (2016);86(10):912-9

THE TRICKY DIAGNOSIS OF ADULT-ONSET ALEXANDER DISEASE L. Marcuccio1, A. Tessitore1, A. Giordano1, M. Cirillo2, G. Tedeschi1 1

Department of Medical, Surgical Neurological, Metabolic and Aging Sciences, Second University of Naples (Napoli); Neuroradiology Unit, Department of Clinical and Experimental Medicine and Surgery, Second University of Naples (Napoli) 2

Case: We report a 60-year-old woman referred to our hospital for a progressive 7 years history of speech and swallow disturbances, walking difficulties, imbalance and episodic falls. Family and personal clinical histories were unremarkable. Phenomenology: Neurological examination revealed broad-based and shuffling gait with freezing (in starting and in turning), gaze evoked nystagmus, hypermetric saccades without slowing of vertical saccades, dysarthria, dysphagia and dysphonia, bradykinesia (right >left) and axial rigidity, bilateral hyperactive deep tendon reflexes. The patient needs aid for walking or for daily life activities. Investigations: General blood examinations, thyroid, vit B12 and folic acid, VDRL/TPHA were unremarkable. Cerebrospinal fluid (CSF) analysis was negative. Electrophysiological evaluation (EMG and MEP) was normal. Neuropsychological evaluation showed no cognitive impairment. Brain and spinal MRI showed marked atrophy from the medulla oblongata to the cervical spinal cord, involving midbrain tegmentum and sparing the pontine base (“tadpole sign”), mild cerebellar atrophy with enlargement of the fourth ventricle and symmetrical striatal lesions. Discussion and results: Several differential diagnosis were considered (multiple sclerosis, motor neuron disease, MSA, SCA and cervical myelopathy); moreover Alexander disease was suspected. Genetic testing revealed one heterozygous mutation on exon 1 of the GFAP (glial fibrillary acidic protein) gene (c.221T>C, p.Met74Thr), mutation associated to the adult forms of Alexander disease. Conclusion: Although very rare, adult onset of Alexander disease should be considered (and genetic testing performed) in the differential diagnosis of parkinsonism plus syndrome when typical MRI findings were observed even in absence of a positive familiar history. References: − Pareyson D, Fancellu R, Mariotti C, Romano S, Salmaggi A, Carella F, Girotti F, Gattellaro G, Carriero MR, Farina L, Ceccherini I, Savoiardo M. Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature. Brain (2008) Sep;131(Pt 9):2321-31 − Namekawa M, Takiyama Y, Honda J, Shimazaki H, Sakoe K, Nakano I. Adult-onset Alexander disease with typical "tadpole" brainstem atrophy and unusual bilateral basal ganglia involvement: a case report and review of the literature. BMC Neurol. (2010) Apr 1;10:21 − Farina L, Pareyson D, Minati L, Ceccherini I, Chiapparini L, Romano S, Gambaro P, Fancellu R, Savoiardo M. Can MR imaging diagnose adult-onset Alexander disease? AJNR Am J Neuroradiol. (2008) Jun;29(6):1190-6

ACTION AND STIMULUS-INDUCED FOCAL MYOCLONUS ASSOCIATED WITH BREAST CANCER: A CASE REPORT OF AN ATYPICAL PARANEOPLASTIC SYNDROME D. Baroncini1, S. Baldini1, P. Annovazzi1, G. Minonzio2, A. Ghezzi1, G. Comi3, M. Zaffaroni1 1

Multiple Sclerosis Study Center, ASST Valle Olona (Gallarate-VA); 2Department of Neuroradiology, ASST Valle Olona (Gallarate-VA); 3Department of Neurology and Institute of Experimental Neurology, University Vita-Salute San Raffaele (Milano) Objective: To present the case of an action/stimulus-induced focal myoclonus in a woman with breast cancer. Materials and Methods: Single patient case report. Case Report: A 50 years-old woman presented to our attention with a 2 months history of involuntary movement in the left foot, worsened by movement and walking, and improved by rest. She also complained brief episodes of general stiffness pag. 72

and trismus, without loss of consciousness. Past medical history included bilateral cheratoconus and arterial hypertension. She was previously investigated in another Hospital (EMG-ENG, routine blood exams, chest radiograph, EEG, brain and spinal cord MRI) with no definite diagnosis. She received clonazepam and oral prednisone, with minimum benefits, and also neuroleptics in the suspect of a psychogenic movement disorder. After few weeks she complained also a mild dysartria and right hand movement clumsiness. She was then admitted to our department. Neurological examination showed an action and stimulus-induced (tactile plantar stimulation) myoclonus of the left foot with a mild diffusion on the leg, slight dysarthria, prevalence of DTRs on lower left limb and an incorrect left cutaneous plantar response. Walking worsened the myoclonus. Brain/thoracic spinal cord MRI, evoked potential and video-EEG were unremarkable. Autoantibodies (ANA, ANCA, antiphospholipid, anti-GAD, celiac disease-related) were negative. CSF examination (including oligoclonal bands) resulted normal. Suspecting a paraneoplastic syndrome we requested a total body CT scan that revealed a left breast cancer, with linfonodal metastasis. Classic and non-classic (anti-AMPA, anti-GABA, anti-LG1, anti-CASPR2, anti-VGKC) onconeural antibodies were negative. After surgical removal of breast tumor the myoclonus was reduced, but after few weeks it worsen again. We then treated the patient with high dose intravenous steroid, with a substantial improvement. At now the patient is still on neurological and oncological follow-up and she is receiving oral steroid therapy. Discussion: Isolated myoclonus has been rarely described in the spectrum of paraneoplastic syndrome [1]. In this case, the episodes of diffuse stiffness and the mild dysarthria were the clues that lead us to think about a paraneoplastic/autoimmune disorder. Although classic and non-classic onconeural antibodies were negative, the presence of breast cancer, the initial improvement after its surgical removal and the rapid response to intravenous steroid therapy support the diagnosis of a paraneoplastic syndrome (“possible” according to Graus criteria) [2]. Conclusion: Diagnosis of paraneoplastic disorders need a higher level of suspicion, especially if the presentation eludes from the so-called classic syndromes. References: 1. Salsano E, Ciano C, Romano S et al. Propriospinal myoclonus with life threatening tonic spasms as paraneoplastic presentation of breast cancer. J Neurol Neurosurg Psychiatry (2006) Mar;77(3):422-4 2. F Graus, J Y Delattre, J C Antoine et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry (2004);75:1135–1140

RUBRAL OR PSYCHOGENIC TREMOR? T. Bocci1, D. Barloscio1, A. De Rosa1, L. Parenti1, A. Priori2, F. Sartucci1 1 2

Department of Clinical and Experimental Medicine, Cisanello Neurology Unit, Pisa University Medical School (Pisa); Department of Neurological Sciences, Fondazione IRCCS Ospedale Maggiore Policlinico, University of Milan (Milano)

Objectives: Rubral tremor is a rare kind of hyperkinetic movement disorder, clinically characterized by irregular, monolateral, high-amplitude jerks, sharing a quite similar frequency with those observed in Parkinson’s disease. It may be caused by mesencephalic lesions, ranging from midbrain infarctions to traumatic injury and neoplasias; it has been also reported after thalamic stroke, likely emerging from lesions upstream of the rubral and nigral outflow system. Lesions of the superior cerebellar peduncle, midbrain tegmentum or posterior part of the thalamus may cause this peculiar tremor; probably, lesions of the red nucleus itself are not sufficient for its production. We report the case of a man referred to our attention because of an atypical ipsilateral hand tremor. Materials and Methods: A video report was made. Patient presented a combined resting-postural-kinetic tremor. We bilaterally performed a surface polymyography from the extensor digitorum communis (EDC) and flexor carpi radialis (FCR) muscles. Brainstem reflexes were also assessed; in particular, we evaluated the habituation phenomenon of the blink reflex (BR). Motor Evoked Potentials (MEPs) were recorded from the abductor digiti minimi (ADM) of the right hand. Results: At the first clinical evaluation, tremor showed the classical features of a rubral tremor. Neuroimaging revealed an intracranial dermoid cyst at the right pontocerebellar angle with brainstem dislocation. However, both the spontaneous variability of tremor frequency and frequency entrainment induced by contralateral rhythmic tasks do not suggest an organic aetiology. Polymyography revealed: 1) a paradoxical increase of tremor amplitude with mass loading; 2) jerks’ synchronization between antagonistic muscles during voluntary contralateral motor performances; 3) tremor inhibition while asking the patient to make a ballistic movement. The BR habituation was preserved. During motor imagery, MEPs were paradoxically smaller than at rest, as extensively reported in psychogenic movement disorders. Discussion: To our knowledge, intracranial dermoid cyst was never reported elsewhere as a potential cause of rubral tremor. More important, however, jerks were very atypical in our patient. In particular, basing both on clinical and pag. 73

neurophysiological findings, we may suggest a complete psychogenic genesis or, at least in part, a possible co-existence of a rubral tremor with psychogenic traits. Conclusions: Tremor diagnosis should be based on a careful clinical, neurophysiological and radiological assessment. Our case strengthen the importance of surface electromyography in tremors; at the same time, our results prompt further studies to re-define electrodiagnostic criteria in hyperkinetic movement disorders, possibly updating the floating border between organic and psychogenic disease. A CASE OF RAPIDLY PROGRESSIVE DEMENTIA: WHIPPLE DISEASE OF CNS M. E. Pessa1, A. Baldi2, S. D'Anna2 1

Clinic of Neurology and Neurorehabilitation, University of Udine (Udine); 2Neurology, San Tommaso dei Battuti Hospital (Portogruaro, VE) A 72-year old woman came to our attention for worsening within few weeks of confusion, aphasia, ataxia and urinary incontinence. She had suffered for 4-5 months of mild cognitive impairment with short-time memory loss, disorientation and mood depression. Her medical history was remarkable for hypertension, diabetes mellitus II and Whipple Disease, diagnosed in 1985 and treated from the last relapse (2011) with trimethoprim–sulfamethoxazole (160+800mg/day). During hospitalization she became drowsy and aphasic,she developed partial status epilepticus and oculomasticatory myorhythmia (a characteristical sign of WD of CNS). MRI signs were nonspecific with severe cortical atrophy and expansion of subarachnoid spaces and ventricular cavities, but CSF analysis revealed 34 cells/mm (70% lymphocytes) with PCR positive for Tropheryma Whippelii (TW). Antimicrobial treatment was started with ceftriaxone, doxycycline, hydroxycholoroquine and trimethoprim–sulfamethoxazole i.v, with mild gradual improvement in the level of consciousness (she began to answer simple questions and to interact with those around her). We reported a case of Whipple Disease with CNS involvement after about 30 years from diagnosis. This eventuality is not frequent, but really also not so rare, especially after so many years of illness (10). Whipple’s disease (WD) is a multi-systemic chronic relapsing infection due to Tropheryma Whippelii, a grampositive bacterium ubiquitously present in the environment. It is a very rare disease (approximate annual incidence 1/1.000.000) that characteristically affects middle-aged Caucasian subjects (1).The infection occurs through human to human transmission and is often asymptomatic or results in self-limiting gastroenteritis,but in predisposed individuals probably an immune deficiency allows the survival of TW that, over the course of many years, spreads systemically (3). CNS involvement is observed in 20% to 40% of cases. Our patient presented a frequent clinical picture of WD of CNS with rapidly progressive dementia associated with oculomasticatory myorhythmia (that is a characteristic sign of WD) (10). We would emphasize the importance of considering also WD in cases of rapidly progressive cognitive impairment (especially with medical history of recurrent arthralgias, diarrhea, weight loss) because it is a potentially treatable cause of dementia and is probably underestimated due to its difficult diagnosis. References: 1. Gerard A, Sarrot-Reynauld F, Liozon E, et al. Neurologic presentation of Whipple disease: report of 12 cases and review of the literature. Medicine (Baltimore) (2002);81:443-457 2. Schneider T, Moos V, Loddenkemper C et al. Whipple’s disease: new aspects of pathogenesis and treatment. Lancet Infect Dis (2008) 8:179–190 3. Moos V, Kunkel D, Marth T et al. Reduced peripheral and mucosal Tropheryma whipplei-specific Th1 response in patients with Whipple’s disease. J Immunol (2006)177:2015–2022

EXPANDING CLINICAL PHENOTYPES OF FRAGILE X-ASSOCIATED TREMOR/ATAXIA L. I. Manfredini1, G. Arabia1, A. Lupo1, G. Mastroianni1, M. Mancini1, G. Barbagallo1, M. Morelli1, M. Salsone2, A. Quattrone2 1 2

Institute of Neurology, Department of Medical and Surgical Sciences, University of Magna Graecia (Catanzaro); Neuroimaging Research Unit, Institute of Molecular Bioimaging and Physiology, National Research Council (Catanzaro)

Background: The fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder consisting of progressive intention tremor and cerebellar ataxia recently described in men with the premutation (55 to 200 CGG repeats) in the promoter region of the fragile X mental retardation 1 (FMR1) gene and with grandchildren with fragile X syndrome (FXS). The most frequent magnetic resonance imaging (MRI) features are cerebral, cerebellar atrophy and periventricular white matter iperintensities. During the last decade, additional clinical features have been described, such as orthostatic, pag. 74

post-prandial hypotension and peripheral neuropathy. We present here a patient carrying an FMR1 premutation allele, without a family history for FXS, whom clinical features expand the FXTAS phenotype. Clinical case: A 49 years-old man referred to our clinic with a 6-years history of tremor of the limbs and gait ataxia, associated with occasional syncopal episodes, occurring after meals and prolonged standing position. Neurological examination showed rest, postural and intention tremor of the upper and lower estremities and ataxic gait. Mild bradykinesia and rigidity of the limbs were also present. Autonomic tests showed an orthostatic and post-prandrial hypotension. In standing position, a marked decrease of systolic blood pressure (SBP) of 34 mmHg (normal values up to 20 mmHg) occured. After a standardized meal, the diastolic blood pressure (DBP) had a decrease of 14 mmHg (normal values up to 10 mmHg). The patient also performed a 24-hour non invasive ambulatory recording of blood pressure. The patient’s blood pressure profile showed a circadian rhythm with marked decrease of pressure values during the night (SBP, minimum value: 80 mmHG; DBP, minimum value: 45 mmHg). This pattern characterized by a reduction over 20 % of the night average systolic pressure compared to the average daytime pressure is defined as “extreme dipper”. Brain MRI demonstrated a marked cerebellar and cerebral atrophy. Genetic analysis revealed FMRI premutation with 57 CGG expansions. Discussion: Our case report expanded the clinical spectrum of FXTAS, presenting a new sign of nocturnal dysautonomia. In patients with FXTAS, autonomic dysfunction has been reported mainly in terms of impotence, hypertension, bladder dysfunction and orthostatic hypotension. Here, we reported for the first time a marked nocturnal hypotension, defined “extreme dipper” in a patient with FXTAS. Circadian dysautonomia may be underdiagnosed. Our case suggested that the noctural non-invasive ambulatory recording of blood pressure may be a useful testing to accurately investigate the autonomic disfunction of patients with FXTAS. References: − P. Pugliese, G. Annesi, N. Cutuli, G. Arabia, G. Nicoletti, F. Annesi, P. Tarantino, A. Gambardella, P. Valentino, M. Zappia, A. Quattrone, MD. The fragile X premutation presenting as postprandial hypotension. Neurology (2004); 63 (11): 2188-2189 − Deborah A Hall, Rachael C Birch, Mathieu Anheim, Aia E Jønch, Elizabeth Pintado, Joanne O’Keefe, Julian N Trollor, Glenn T Stebbins, Randi J Hagerman, Stanley Fahn, Elizabeth Berry-Kravis and Maureen A Leehey. Journal of Neurodevelopmental Disorders (2014);6:31 ACUTE CONFUSIONAL MIGRAINE (ACM) IN CADASIL: ROLE OF ELECTROENCEPHALOGRAM (EEG) E. P. Verrengia, E. Ferrante, S. Jann, S. Meregalli, E. Agostoni Niguarda Hospital, Bicocca University (Milano) Purpose: ACM (Acute Confusional Migraine) can represent a clinical manifestation of CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). EEG (electroencephalogram) can represent a useful tool to evaluate this condition. Material and methods: We report two stereotypic confusional events in migraine in the same CADASIL patient. Results: A 54-year-old woman with diagnosis of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) was admitted to our Hospital in February 2016. Patient history includes recurrent stroke, chronic headache since childhood classified as migraine with visual aura, typical neuroimaging findings. She has no family history of stroke and dementia. The assumption of no cognitive decline was based on her ability to perform business activity. The diagnosis was confirmed by mutation in Notch3 gene in 2006. In December 2015 she was hospitalized in London with a severe headache associated with visual impairment (migraine with aura), agitation and speech disturbance. Patient confusion lasted four days. Brain computed tomography (TC) in acute phase was negative and EEG, performed five days after the clinical event, was normal. In absence of new ischemic lesions on DWI-MRI (Diffusion Weighted ImagingMagnetic Resonance), she was treated with Levetiracetam 500 mg twice a day. In February 2016 she was evaluated in our Emergency Department with a similar episode compared to the one of London 2015. The patient presented a prolonged duration visual aura migraine since early morning. During this episode, she presented agitation associated with an inability to communicate and to comprehend spoken words. Agitation was treated with benzodiazepines with a resolution in 24 hrs, but she presented an alteration of cognitive/behavioral status for seven days. In acute phase, in absence of new lesions on TC scan, an EEG revealed a disorganized track with slow bilateral activity, non-reactivity to algic stimuli, no epileptiform figures. Her brain DWI-MRI revealed pre-existing infarcts, leukoencephalopathy, hemosiderin foci, but no recent ischemic lesions. Based on basal features and subsequent improvement of EEG, we decided to discontinue antiepileptic therapy. In June 2016 the patient was able to perform her work activities in absence of ACM events. Discussion and conclusions: We describe two episodes of ACM in the same CADASIL patient, lasted four and seven days respectively. EEG shows a typical pattern in acute phase ACM and excludes seizure related to pre-existing cerebral infarcts. Further data are required to support the role of EEG to qualify this phenomenon. pag. 75

References: − Swati Sathe, Edgar DePeralta, Gregory Pastores, Edwin H. Kolodny. Acute Confusional Migraine May Be a Presenting Feature of CADASIL. Headache (2009);49:590-596 − Cheng-Tsung Hsiao, Yun-Chung Chen, Yo-Tsen Liu, Bing-Wen Soong, Yi-Chung Lee. Acute simultaneous multiple lacunar infarcts as the initial presentation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Journal of the Chinese Medical Association (2015);78:424-426 − Liem MK, Oberstein SA, van der Grond J, Ferrari MD, Haan J. CADASIL and migraine: A narrative review. Cephalalgia (2010) Nov;30(11):1284-9 A CASE-REPORT OF MIGRAINE “SINE HEADACHE” A. Taga, M. Russo, A. Genovese, M. Trapasso, G. Manzoni, P. Torelli Department of Clinical and Experimental Medicine, University of Parma (Parma) Background and objectives: We describe a case of a female patient whose typical migraine attacks transformed into migraine attacks with a full spectre of associated symptoms but without headache. Case report: A 53-year old woman was evaluated in May 2016, complaining of a long history of migraine without aura (MO), with onset at 16 years old, characterized by unilateral, pulsating, severe headache attacks, associated with photophobia, phonophobia, osmophobia, nausea and inconstantly vomiting. She used successfully triptans (sumatriptan or rizatriptan) as abortive therapy. The patient recognized some migraine triggers, including weekend and the menstrual window; the mean attacks frequency was two or three per month. Her past medical history was unremarkable and didn’t include the so-called “childhood periodic syndromes” [1]; she had a family history of MO (mother and a sister). Since November 2015, in concomitance with premenopausal menstrual dysregulation, the patient reported the occurence of episodes of nausea and vomiting, associated with photophobia, phonophobia, osmophobia but without headache. Similarly to her “typical” migraine attacks, these episodes lasted one to three days when untreated; they responded well to the triptans, but not to the common antiemetics (metoclopramide and domperidone); the reported triggers and the frequency were the same of the previous migraine attacks. The patient reported also some residual but infrequent migraine attacks with headache. Alternative diagnoses were excluded through extensive laboratory tests (including endocrine, metabolic and infective screening), gastrointestinal examinations (including gastroscopy, colonoscopy and abdominal US) and urologic evaluations; a brain MRI scan excluded CNS abnormalities. Discussion and conclusions: To date, there aren’t literature data on otherwise typical migraine attacks without headache. A similar eventuality has been described only for cluster headache [2]. On the other hand, the current IHS classification [1] recognizes some syndromes historically noted to occur in childhood (previously kown as "childhood periodic syndromes"), but which occur in adults, too, and which include among the others: recurrent gastrointestinal disturbance and cyclic vomiting syndrome. However, our case is not comparable to these entities for the absence of the abdominal pain and for the unpredictable temporal pattern of nausea and vomiting episodes. We hypothesize that a functional dysregulation of the hypothalamo-brainstem connectivity [3] (which is a supposed to be a generator of migrainous pain and associated symptoms) may generate migraine attacks with a full spectre of associated symptoms, but without headache. References: 1. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia (2013);33:629–808 2. Dilli E, Dodick DW. Extracephalic cluster (cluster sine headache). Neurology (2008);70(16):1362-3 3. Schulte LH, May A. The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain (2016) (published ahed of print, doi: http://dx.doi.org/10.1093/brain/aww097)

DISORDINI DEL MOVIMENTO 2 CLINICAL, ELECTROPHYSIOLOGICAL AND MRI FINDINGS IN ESSENTIAL TREMOR WITH AND WITHOUT RESTING TREMOR R. Nisticò1, M. Caligiuri1, G. Arabia2, F. Novellino1, M. Salsone1, M. Morelli2, G. Barbagallo2, A. Lupo2, A. Cherubini1, A. Quattrone2 1

Institute of Molecular Imaging and Physiology (IBFM-CNR), National Research Council (Catanzaro); 2Institute of Neurology, University Magna Graecia (Catanzaro) pag. 76

Background: The etiopathogenesis of essential tremor (ET) is still debated, since the predominant role of circuit dysfunction or brain degenerative changes has not been clearly established. The relationship with Parkinson's Disease (PD) is also controversial and resting tremor occurs in up to 20 % of rET.(1) The aim of this study was to evaluate brainstem interneuronal excitability by blink reflex recovery cycle (BRrc ) (2) in patients with rET compared with patients with ET. In addition we used probabilistic tractography and network analysis to investigate the structural integrity of the motor circuit in classical ET, rET and healthy controls (HC). Methods: We investigated 25 patients with ET (14 female, mean age 65.1 ± 10.4), 22 patients with rET (10 female, mean age 64.9 ± 13.4) and 25 age and sex matched HC. All patients underwent to BRrc, and MRI protocol incuding whole-brain 3D T1-weighted and diffusion-weighted MRI. The following regions, known to be part of the motor circuit, were automatically identified on T1 images: putamen, caudate nucleus, globus pallidus, thalamus, cerebellum, precentral cortex and supplementary motor area (SMA). Probabilistic tractography between these nodes was performed on diffusion data in network-mode, in order to reconstruct connections in the motor circuit and to obtain connectivity matrices necessary for computing connectomics measures. Results: All patients with rET had an increased R2-BRrc while all patients with ET had a normal BRrc comparable to that of control subjects. Network analysis revealed increased nodal efficiency of the cerebellum in ET and in rET compared to HC. Patients with rET showed increased nodal efficiencies in bilateral globus pallidus, left precentral cortex and left caudate compared to both ET and HC. Thalamic nodal efficiency was increased in rET compared to HC. Discussion: Our results help clarify both electrophysiological and structural differences of two different phenotypes of ET. Patients with rET had an increased R2 recovery component of BRrc whereas patients with ET had a normal BRrc comparable to that of control subjects. The pallidal dysfunction, mainly related to its connection to the thalamus, was identified as a possible neuroimaging correlate of resting tremor in ET. Conclusions: Our findings indicate the possible clinical usefulness of BRrcc for differentiating rET from ET. In ET and rET, dysfunction of both the globus pallidus and the thalamus may play an important role in explaining different clinical presentations of the disease. References: 1. Nicoletti V, Cecchi P, Frosini D et al. Morphometric and functional MRI changes in essential tremor with and without resting tremor. J Neurol. (2015) Mar;262(3):719-28. doi: 10.1007/s00415-014-7626-y. Epub 2015 Jan 9 2. Nisticò R, Pirritano D, Novellino F et al. Blink reflex recovery cycle in patients with essential tremor associated with resting tremor. Neurology (2012) Oct 2;79(14):1490-5. doi: 10.1212/WNL.0b013e31826d5f83. Epub 2012 Sep 19

THALAMIC PROTON MAGNETIC RESONANCE SPECTROSCOPY CAN DISTINGUISH ESSENTIAL TREMOR WITH RESTING TREMOR FROM TREMOR-DOMINANT PARKINSON'S DISEASE: A PILOT STUDY G. Barbagallo1, A. Cherubini2, G. Arabia1, F. Novellino2, M. Salsone2, R. Nisticò2, M. Caracciolo2, F. Rocca2, I. Martino1,2, C. Chiriaco2, A. Quattrone1,2 1

Institute of Neurology, University Magna Graecia (Catanzaro); 2Neuroimaging Research Unit, Institute of Molecular Bioimaging and Physiology, National Research Council (Catanzaro)

Background: Several pathological, surgical, electrophysiological, and imaging studies have shown that the thalamus plays an important role in tremor generation [1]. Distinguishing Essential Tremor with resting tremor (rET) from tremor-dominant PD (tPD) may be challenging especially in the first stages of the diseases, in the absence of DAT-SPECT investigation. Aims: The aims of the study were (1) to investigate the presence of metabolic alterations in the thalamus of patients with rET and tPD using proton magnetic resonance spectroscopy (1H-MRS), and (2) to evaluate the possible usefulness of the 1H-MRS for differentiating subjects with tPD from those with rET. Materials and Methods: Thirteen patients with tPD, 10 with rET and 10 healthy controls participated in this study. After conventional MR imaging, single-voxel 1H-MRS (TR=2000 ms; TE=28 ms) was performed by using a PROBE-SV system implemented on a 3 tesla scanner (GE, General Electric Medical Systems, Milwaukee, WI). A voxel of 10 × 10 × 15 mm was acquired in each thalamus of all subjects. Peak areas of N-acetyl-aspartate with N-acetyl-aspartyl-glutamate (NAA), creatine with phosphocreatine (Cr), and glycerophosphocholine with phosphocholine (Cho), were calculated using a version 6.3-1K of the fitting program LCModel for each voxel [2]. Comparative and discriminant analyses were performed on the mean values of the bilateral NAA/Cr, a neural density marker, and Cho/Cr, a membrane marker.

pag. 77

Results: Patients with tPD showed a significant reduction of NAA/Cr and Cho/Cr ratios, compared to rET and healthy controls. Remarkably, logistic regression and receiver operating characteristic (ROC) curves showed that the combination of both spectroscopic markers (i.e. NAA/Cr and Cho/Cr) was able to obtain a 100% accuracy in distinguishing patients with tPD from those with rET. Discussion and Conclusions: Our study demonstrates that thalamic 1H-MRS may help to distinguish tPD from rET, showing its potential usefulness for differentiating these diseases characterized by the presence of resting tremor. References: 1. Helmich RC, Hallett M, Deuschl G, Toni I, Bloem BR. Cerebral causes and consequences of parkinsonian resting tremor: a tale of two circuits? Brain (2012);135:3206-26 2. Provencher SW. Automatic quantitation of localized in vivo 1H spectra with LC Model. NMR in biomedicine (2001);14(4):260-264

PREDICTION OF COGNITIVE WORSENING IN DE NOVO PARKINSON DISEASE: USE OF BIOMARKERS IN CLINICAL SETTING D. Arnaldi1, F. De Carli2, A. Brugnolo1, N. Girtler1, A. Picco1, M. Ferrara1, L. Proietti1, M. Bauckneht3, S. Morbelli3, F. Nobili1 1

DINOGMI, IRCCS San Martino IST, University of Genoa (Genova); 2Institute of Bioimaging and Molecular Physiology, National Research Council (Genova); 3DISSAL, IRCCS-San Martino IST, University of Genoa (Genova) Objective: To define the best predictors of future cognitive worsening among clinical and neuropsychological features, resting EEG and dopamine transporter (DAT) imaging in a group of patients with newly diagnosed Parkinson disease (PD). Methods: Fifty-four de novo, drug naïve PD patients were prospectively evaluated by clinical and neuropsychological assessment, resting EEG and 123I-FP-CIT-SPECT. The patients were classified into mainly motor, diffuse/malignant and intermediate PD subtypes according to Fereshtehnejad et al [1]. Follow-up cognitive outcome was defined by identifying cognitively stable or worsened patients after an average time of five years (4.8±2.2). The best predictors of cognitive outcome were evaluated by logistic regression on baseline clinical, neuropsychological, demographic, quantitative EEG (qEEG) and 123I-FP-CIT-SPECT data. Cross-validated, receiver operator characteristic (ROC) analysis was used to measure the accuracy of the baseline predictors of cognitive outcome. qEEG and 123I-FP-CIT-SPECT cut-point values to be used in single subject were also computed. Results: The best predictors of future cognitive worsening were the posterior mean qEEG frequency (82% accuracy; cutpoint 8.3 Hz) and the 123I-FP-CIT-SPECT specific to non-displaceable binding ratio (SBR) at caudate level (80% accuracy; cut-point 2.3) (pposterior). No longitudinal changes were observed in the infratentorial regions. In MSA-p, the progressive involvement of corpus callosum, external capsule, and long-range associative WM pathways was associated with the worsening of cognitive deficits and behavioral changes. Discussion: In MSA-p patients, the progression of WM microstructural damage is prominent compared to cortical damage and it is related to the worsening of cognitive and behavioural symptoms. Conclusions: This is the first longitudinal, multimodal MRI study of MSA-p patients. In MSA-p patients, WM changes were detected mainly in supratentorial regions and showed a significant impact on MSA-p clinical features. Conversely, cortical damage was only modest. DT MRI has the potential to offer promising biomarkers for monitoring MSA-p and predicting the clinical evolution. References: − Gilman S, Wenning GK, Low PA et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology (2008);71: 670–6 − Stefanova N, Bücke P, Duerr S, Wenning GK. Multiple system atrophy: an update. Lancet Neurol. (2009) Dec;8(12):1172-8

PROGNOSTIC INDICATORS OF SURVIVAL IN 136 MULTIPLE SYSTEM ATROPHY PATIENTS G. Giannini1, G. Calandra-Buonaura1, M. Bacchi-Reggiani2, F. Provini1, P. Cortelli1 1

IRCCS Institute of Neurological Sciences of Bologna, Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum, University of Bologna (Bologna); 2Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna (Bologna) Objective: To determine the predictive value of different clinical factors on shortened survival in a cohort of multiple system atrophy (MSA) patients referred to a tertiary centre. Materials and Method: We retrospectively identified all patients with a final clinical diagnosis of MSA referred to our Department between 1991 and 2014 and evaluated at least once a year during the disease course. Diagnosis of MSA was independently confirmed by three neurologists expert in movement disorders from data available at the last follow-up evaluation according to international criteria. Clinical data were collected from medical records and updated at every follow-up visit. Survival data were defined based on time to death from the disease onset and calculated using Kaplan-Meier curves. To identify variables associated with survival in MSA, univariate and multivariable Cox regression analyses were performed. The following variables were studied: age at disease onset, sex, predominant clinical phenotype (parkinsonian vs. cerebellar), presence of stridor, type of disease onset (cerebellar, parkinsonian or autonomic) and mode of autonomic onset (orthostatic hypotension vs. urinary dysfunction). Statistical analyses were performed using the statistical software STATA®, version 14.0. A p-value less than 0.05 (2-sided) was considered significant. Results: A total of 136 MSA patients were included (88 males; 68 MSA with predominant Parkinsonism), 113 were deceased at the time of the study. The mean ± standard deviation age at disease onset was 57.26 ± 8.70 years and the median (interquartile range) of disease duration was 7 years (5-9). On Kaplan-Meier curve the median duration of illness was 7.84 years. The univariate Cox regression analyses of the influence of clinical factors on survival showed that neither MSA subtype, sex, age at disease onset nor presence of stridor were significantly associated with survival. The autonomic disease onset and the mode of autonomic onset (orthostatic hypotension) were associated with shortened survival in a univariate analysis and remained independent predictors of mortality in the multivariable model (HR= 1.70, CI 95%= 1.12-2.58, p= 0.013 and HR= 1.74, CI 95%= 1.09-2.76, p= 0.019 respectively).

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Conclusions: The study showed that autonomic disease onset and, in particular, the onset with orthostatic hypotension predicted unfavourable survival in patients with MSA. These results could be useful in optimizing therapy and clinical management. THE EFFECT OF L-DOPA/CARBIDOPA INTESTINAL GEL IN PARKINSON'S DISEASE ASSESSED USING NEUROPHYSIOLOGICAL TECHNIQUES D. Belvisi1, M. Bologna1, A. Latorre2, F. Di Biasio1, A. Conte1,2, N. Modugno1,2, A. Berardelli1,2, G. Fabbrini1,2 1

IRCCS Neuromed Institute, Sapienza, Università di Roma (Pozzilli-IS); 2Department of Neurology and Psychiatry, Sapienza University of Rome (Roma)

Introduction: Continuous dopaminergic stimulation is a therapeutic option in the advanced stages of Parkinson’s disease (PD). L-Dopa/Carbidopa intestinal gel (LCIG) delivered to the proximal jejunum allows a stable and smooth plasmatic concentration of L-Dopa. Despite the evidence of the efficacy of LCIG on motor and non-motor symptoms in PD, no studies have objectively investigated the effects of LGIG on motor and non-motor abnormalities by using neurophysiological techniques. Methods: We studied 11 with advanced PD patients in therapy with LCIG and 11 age-matched healthy subjects. Motor impairment was measured by kinematic recording of repetitive finger movements (finger tapping), recorded using a 3D optoelectronic system (SMART). Patients were instructed to tap the index finger against the thumb repeatedly as rapidly and with as large amplitude as possible for 15 seconds. Movement amplitude, velocity and rhythm were measured. Sensory abnormalities were evaluated using the somatosensory tactile discrimination threshold (STDT). STDT was tested by delivering paired stimuli starting with an interstimulus interval of 0 ms (simultaneous pair), and progressively increasing interstimulus intervals in 10 ms steps. STDT was evaluated in two different body regions bilaterally: the index finger (‘hand’) and the periorbital region (‘eye’). All patients were studied in OFF and ON phase. Results: The kinematic analysis of finger tapping showed that PD patients in the OFF medication condition had a markedly lower amplitude and velocity and impaired rhythm than HS and no progressive reduction in both movement kinematics during finger tapping. Similar results were obtained when comparing PD patients ON medication and HS thus indicating that LCIG did not normalize the kinematic variables analyzed. However, movement amplitude and velocity were improved upon LCIG infusion as showed by the significant difference of the kinematic variables between the OFF and ON condition. STDT values were significantly higher PD patients OFF and ON medication in comparison to HS independently from the medication status, the body side and region tested. In PD patients STDT values tested in ON medication condition improved, but did not normalize, in comparison to those obtained in OFF medication condition. Conclusions: Continuous dopaminergic stimulation improves but does not normalize motor and sensory abnormalities in advanced PD. LCIG is able to reverse, at least in part, functional abnormalities causing motor and sensory deficit, but is not able to compensate alternative mechanisms, possibly including anatomical abnormalities of basal ganglia nuclei and cortical areas resulting in bradykinesia and sensory deficits in advanced PD.

PAIN THRESHOLD AND PAIN TOLERANCE IN FUNCTIONAL AND IDIOPATHIC DYSTONIA A. Matinella1, F. Morgante2, E. Andrenelli3, C. Allegra2, C. Terranova2, P. Girlanda2, M. Tinazzi1 1

Department of Neurological and Movement Sciences, Neurology Unit, University of Verona (Verona); 2Department of Clinical and Experimental Medicine, University of Messina (Messina); 3Department of Experimental and Clinical Medicine, Neurorehabilitation Clinic, "Politecnica delle Marche" University (Ancona) Objectives: Pain is often experiences by patients affected by functional dystonia, sometimes at a degree which is disproportionate to the extent of motor symptoms and occur in body segments not affected by involuntary movements. Painful sensations are also experienced by patients with idiopathic cervical dystonia in the affected body part. Aim of the present study was to assess pain threshold and pain tolerance in patients with functional and idiopathic dystonia. Methods: We enrolled 10 patients with idiopathic cervical dystonia, 10 patients with functional dystonia and 14 age- and gender matched healthy controls. Pain threshold and pain tolerance were assessed giving square wave electrical pulses of increasing intensity delivered to the index finger of each hand through skin ring electrodes. The lowest intensity of stimulus (0.5 mA) was increased by 0.5 mA steps until the subjects perceived the electrical stimulus (tactile threshold). Then, the intensity of electrical stimulus was increased by 0.5 mA steps until the subjects reported a change in sensation from unpainful to ‘‘faintly painful’’ (pain threshold, P-Th). Finally, the intensity was increased by 1 mA steps until the subjects pag. 80

reported an ‘‘intolerable’’ painful sensation (pain tolerance, P-Tol). Results: In functional dystonia patients we recorded a significant increase of P-Th (p < 0.01) and P-Tol (p< 0.0001) compared to idiopathic cervical dystonia and control healthy subjects. The increase of P-Th and P-Tol did not correlate with disease duration. Discussion: We demonstrate that patients with functional dystonia a marked increase of pain threshold and pain tolerance compare to patients with idiopathic dystonia and healthy control subjects. We might hypothesize that the abnormal connectivity between the motor and the limbic system which characterized functional dystonia might account for increased pain perception. That is, increased pain thresholds might be linked to an alteration of the emotional aspect of pain processing in functional dystonia. Conclusion: Pain processing is different in patients with functional and idiopathic dystonia, with significant increase of pain thresholds in functional dystonia. ORTHOSTATIC HYPOTENSION INCREASES THE RISK OF FALLS IN IDIOPATHIC PARKINSON'S DISEASE PATIENTS M. Sarchioto1, M. Zibetti1, S. Maule2, V. Milazzo2, E. Montanaro1, A. Romagnolo1, A. Merola1, L. Lopiano1 1 Dipartimento di Neuroscienze, Università di Torino (Torino); 2Dipartimento di Scienze Mediche, Università di Torino (Torino)

Objective: Orthostatic hypotension (OH) is believed to contribute to cause falls in Parkinson's disease (PD) patients, but few studies have assessed it directly. In this work we evaluated the correlation between falls and OH in patients with PD. Materials: Thirty six consecutive patients diagnosed with idiopathic PD were recruited. Patients who presented atypical parkinsonian features, older than 80 years or having positive history for diabetes mellitus, chronic renal failure, atrial fibrillation or other arrhythmias were excluded. Methods: Motor features were scored using Unified Parkinson’s Disease Rating Scale part III (UPDRS III) and Hoen and Yahr’s (H&Y) staging. Patient’s global postural assessment was evaluated using a 4-item axial motor subscore, calculated using the sum of MDS-UPDRS motor examination items from 3.27 to 3.30 and three more tests: Time Up and Go (TUG), Push and Release (P&R) and Freezing of Gate Questionnaire (FOG). A brief cognitive screening was performed using Montreal Cognitive Assessment (MoCa). Patient’s autonomic functions were studied using postural blood pressure test for orthostatic hypotension (OH). Anamnestic data for falls were collected by asking patients for any falls occurred in the previous 12 months. They were also followed up for falls in the next 6 months. Results: The mean age was 63.7 (SD 9.6) years and the mean disease duration was 6.5 (SD 3.5) years. A statistically significant association was found between falls and OH (p=0.04). Falls also inversely correlated with the value of systolic blood pressure reduction measured at the 1st and 3rd minute during tilt test (p=0.01 for both conditions) and directly correlate with the systolic blood pressure reduction between supine and 1st minute orthostatic measurement (∆p) (p=0.02). A multiple regression model taking into account possible confounding variables of axial symptoms and cognitive status (MoCA) showed that ∆p remained a significant predictor of falls (t = 2.6, p=0.01). Discussion: Our data demonstrate a role of OH as a risk factor for falls in patients with idiopathic PD. Data suggest that there is a strict correlation between sistolic blood pressure values and falls, infact the lower is the value of it the greater is the probability of falls for patients. Data also demonstrate that higher is the gap between sistolic and diastolic blood pressure values, the higher is the chance of falls. Conclusions: Careful monitoring of supine and orthostatic blood pressure may be useful for detecting individuals with PD at risk of falls and may be a significant modifiable factor for falls prevention. References: − Kerr GK, Worringham CJ, Cole MH, Lacherez PF, Wood JM, Silburn PA. Predictors of future falls in Parkinson disease. Neurology (2010) Jul 13;75(2):116-24 − Vikas Kotagal, Roger L. Albin, Martijn L.T.M. Müller, Robert A. Koeppe, Kirk A. Frey, Nicolaas I. Bohnen. Modifiable cardiovascular risk factors and axial motor impairments in Parkinson disease. Neurology (2014);82:1514–1520 − Palma JA, Gomez-Esteban JC, Norcliffe-Kaufmann L, Martinez J, Tijero B, Berganzo K, Kaufmann H. Orthostatic hypotension in Parkinson disease: how much you fall or how low you go? Movement Disorders (2015) Apr 15;30(5):639-45

NEUROPSICOLOGIA CLINICA

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ITEM CONSISTENCY IN RETRIEVING PERSON-SPECIFIC SEMANTIC INFORMATION FROM FACES AND VOICES: AN EXPLORATORY STUDY IN HEALTHY SUBJECTS C. Piccininni1, G. Gainotti1, L. Trojano2, S. Luzzi3, C. Papagno2, G. Carlesimo4, C. Marra1, D. Quaranta1 1

Research Center for Neuropsychology, Institute of Neurology, Catholic University (Roma); 2Department of Psychology, Second University of Naples (Caserta); 3Department of Clinical and Experimental Medicine, Polytechnic University of Marche (Ancona); 4Laboratory of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation (Roma) Objectives: Faces and voices are the most important stimuli for the recognition of familiar people, but their efficacy is not symmetrical. Previous evidence has shown an advantage of face over voice in semantic information retrieval. These findings are at variance with models assuming that semantic information is stored in an unitary fashion. As proposed by previous authors [1], a further clarification of this issue could come from the assessment of consistency across modalities (face and voice) for individual test items. In fact, an unitary amodal person-specific semantic system would correspond to a high level of consistency across modalities, whereas low levels of consistency would favour the hypothesis of a multi-modal system. The aim of the present study was to evaluate item consistency across modalities in healthy subjects who underwent the Famous People Recognition Battery (FPRB), a standardized test [2] devised to assess familiarity and semantic information retrieval from face and voice. Materials: We enrolled 155 healthy subjects who underwent the FPRB. The FPRB consists of two subtests in which subjects are requested to recognize the same 40 famous persons through their faces and voices, distinguishing them from 20 unknown people, and assessing identification of persons recognized as familiar. Identification is estimated with a semantic score ranging 0-3. Methods: Consistency between scores obtained in the face and voice modalities was assessed by the intraclass correlation coefficient (ICC) between the semantic score obtained for voices and faces. Only scores obtained by subjects who experienced a familiarity feeling for both modalities were taken into account. Results: For most of the stimuli (26/40, 65%) the familiarity feeling was more easily evoked from faces. The total semantic scores from voices and faces were significantly different (69.81±24.326 vs 101.06±15.288; p165 U did not show a significant reduction in headache days compared the group who received 155 U (P ≥0.306). Conclusions: Our preliminary findings show sustained benefit of BoNT-A in the majority of CM patients with and without MO. The follow-the-pain strategy may not offer additional benefits compared to the standard paradigm. A comparison between larger series of patients treated with 155U vs patients treated with 185U may be required before implementing our findings in clinical practice. RESTING STATE CONNECTIVITY BETWEEN DEFAULT MODE NETWORK AND INSULA ENCODES PAIN INTENSITY DURING SPONTANEOUS MIGRAINE ATTACKS G. Coppola1, A. Di Renzo1, E. Tinelli2, C. Di Lorenzo3, V. Parisi1, F. Pierelli4 1

Department of Neurophysiology of Vision and Neurophthalmology, G.B. Bietti Foundation-IRCCS (Roma); 2Department of Neurology and Psychiatry, Neuroradiology Section, Sapienza University of Rome (Roma); 3Neurology Section, Don Carlo Gnocchi Onlus Foundation (Milano); 4Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino (Latina) Background: Previous functional magnetic resonance imaging (MRI) studies have revealed that greater ongoing clinical pain in different chronic pain populations, such as fibromyalgia and chronic low-back pain, is associated with proportional greater resting default mode network (DMN) connectivity to insula. Here, we investigated seed-based resting state DMNinsula connectivity during the acute head pain that characterizes spontaneous recurrent migraine attacks. Method: Thirteen patients with untreated migraine without aura (MI) underwent 3T MRI scans during the initial 6 hours of a spontaneous full-blown migraine attack and were compared to a group of 19 healthy volunteers (HV). We collected seedbased resting state data in the four core regions consistently identified in the DMN: medial prefrontal cortex (MPFC),

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posterior cingulate cortex (PCC), and left and right inferior parietal lobules (IPLs). Moreover, we collected seed-based resting state data from the insula bilaterally. Results: Compared to HV, MI patients showed stronger bilateral insula connectivity to the medial prefrontal cortex (MPFC) region of interest. In MI, the strength of insula-MPFC connectivity, as measured by calculating the Spearman's rank correlation coefficient, was negatively correlated with pain intensity (visual analogue scale) during migraine (r= -0.566, p= 0.05). Conclusion: To sum up, we documented for the first time that greater subjective intensity of pain during migraine is associated with proportional weaker DMN-insula connectivity. Notably, this finding seems to be specific to acute migraine head pain since it was dissimilar to that reported in previous studies investigating the association between chronic extracephalic painful conditions and DMN-insula connectivity. MODIFICATIONS OF GRAY MATTER VOLUME IN MIGRAINE PATIENTS OVER FOUR YEARS: A TENSOR-BASED MORPHOMETRY STUDY R. Messina1, B. Colombo1, E. Pagani2, A. Falini3, G. Comi1, M. Filippi2, M. Rocca2 1 Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University (Milano); 2Neuroimaging Research Unit, INSPE, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University (Milano); 3Department of Neuroradiology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University (Milano)

Background: Previous studies have shown diffuse gray matter (GM) abnormalities in regions involved in pain and visual processing in migraine patients. A longitudinal study found GM atrophy of sensory-discriminative brain regions in these patients after one year. Objectives: To explore longitudinal GM changes over a four-year follow up in migraine patients and their association with patients’ clinical characteristics and disease activity. Methods: Using a 3.0 Tesla scanner, brain dual-echo and 3D T1-weighted scans were acquired from 25 patients with migraine and 25 healthy controls at baseline and after 4 years (range of follow-up years: controls 1.7-6.6, patients: 2.9-5.6). Tensor-Based Morphometry and SPM12 were used to assess longitudinal changes of GM volumes in migraine patients after 4 years and according to the disease duration and attack frequency and their changes. Results: Eight patients (32%) reported an increased number of migraine attacks at follow up. At baseline, compared to controls, migraine patients showed cerebellar GM atrophy and higher volume of regions of the right fronto-temporo-parietal lobes. At follow up, compared to controls, migraine patients had an increased volume of fronto-parietal regions, which was related to a higher number of migraine attacks at baseline (r=0.58, p40 years). Conclusions: We believe such systematic assessment of rare diseases prevalence is needed to develop speciphic plans of public health intervention. Furthermore cooperation of different clinical centers should be encouraged to gather uniform information and relevant series for planning clinical intervention. References: − Pandolfo M. Friedreich ataxia: the clinical picture. J Neurol (2009);256(Suppl.1):3–8 − Wedding IM, Kroken M, Henriksen SP, Selmer KK, Fiskerstrand T, Knappskog PM, Berge T, Tallaksen CM. Friedreich ataxia in Norway - an epidemiological, molecular and clinical study. Orphanet J Rare Dis. (2015) Sep 4;10:108 − Hamza W, Ali Pacha L, Hamadouche T, Muller J, Drouot N, Ferrat F, Makri S, Chaouch M, Tazir M, Koenig M, Benhassine T. Molecular and clinical study of a cohort of 110 Algerian patients with autosomal recessive ataxia. BMC Med Genet. (2015) Jun 12;16:36 LTP-LIKE CORTICAL PLASTICITY IS INDEPENDENTLY FROM AGE OF ONSET

DISRUPTED

IN

ALZHEIMER’S

F. Di Lorenzo, V. Ponzo, S. Bonnì, C. Motta, M. Bozzali, C. Caltagirone, A. Martorana, G. Koch Fondazione Santa Lucia, Tor Vergata University (Roma)

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DISEASE

PATIENTS

Objective: Early Onset Alzheimer Disease (EOAD) shares the same pathological features of Late Onset Alzheimer disease (LOAD). However it is unknown if AD pathology induces in EOAD similar modification in synaptic functions as those described in LOAD. We used transcranial magnetic stimulation tools to investigate the mechanisms of cortical plasticity and sensory-motor integration in AD patients with a wide range of disease onset. Materials and Methods: We evaluated newly diagnosed sporadic AD (n=54) in comparison with healthy age-matched controls (HS n=24). Cortical plasticity mechanisms of long-term potentiation (LTP) or of long-term depression (LTD) were assessed using respectively intermittent (iTBS) or continuous theta burst stimulation (cTBS) protocols. Sensory-motor integration was evaluated by means of short afferent inhibition (SAI) protocol. Results: AD showed an impairment of LTP-like cortical plasticity that was reversed to a paradoxical LTD after iTBS in comparison to HS. LTD-like cortical plasticity was similar across groups. LTP-like cortical plasticity did not correlate with age. AD patients presenting with more altered LTP-like cortical plasticity had more severe cognitive decline at 18 months. SAI was impaired in AD and showed a strong correlation with the individual age of subjects rather than with disease age of onset. Discussion: Cortical LTP disruption is a central mechanism of AD that is independent from age of onset. AD can be described primarily as a disorder of LTP-like cortical plasticity not influenced by physiological ageing and associated with a more severe cognitive decline. Conclusions: LTP impairment is AD-dependent, and could be considered as a neurophysiological marker of disease, while the SAI dysfunction is age-dependent thus representing more likely a marker of the interaction between physiological and pathological ageing. RIGHT SEMANTIC DEMENTIA IN RIGHT-HANDEDNESS: A CASE REPORT A. Dell'Edera, F. Caso, R. Cardamone, R. Santangelo, G. Cecchetti, S. Mazzeo, M. Falautano, V. Martinelli, G. Comi, G. Magnani Department of Neurology, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University (Milano) Objective: To describe clinical, genetic and neuroanatomical features of a patient with the right temporal lobe variant (RTLV) of the semantic variant of primary progressive aphasia (svPPA). SvPPA has been classically associated with left anterior temporal damage. Nevertheless, almost 25% of svPPA patients show prominent right-sided damage and behavioral disturbances, (mainly in emotional processing), in addition to language deficits. Thus, the differential diagnosis between this syndrome and the behavioral variant of frontotemporal dementia (bvFTD) is usually challenging. Currently, no consensus criteria exist for the RTLV of svPPA [1]. Materials: A 60-years-old right-handed woman was admitted to our Hospital in 2016. The husband reported in the last year difficulties in the comprehension of low-frequency words, reduction of empathy, rigid and obsessive behavior. Recently, she had working troubles due to her difficulties in social interaction with colleagues. Her father was affected by unclassifiable dementia. Methods: The patient underwent neurological and neuropsychological examination, Edinburgh handedness questionnaire (EHQ), blood and cerebrospinal fluid (CSF) screening, electroencephalogram, brain MRI and 18FDG-PET. A genetic analysis for the main genes associated with FTLD was performed. Results: EHQ scores indicated strong right-handedness. General neurological exam was normal except for the presence of glabellar and snout reflexes. Neuropsychological evaluation revealed deficits with abstract reasoning, especially in emotional relevant setting. Regards to language, word-finding and naming deficits, and mildly impaired single words comprehension were detected. Her CSF profile was congruent with non-AD pathology. EEG was unremarkable. MRI revealed severe atrophy in right temporal regions mildly extended to dorsolateral prefrontal cortex (DLPFC). Consistently, 18FDG-PET showed severe hypomethabolism in right temporal pole and milder involvement also of left temporal pole, right DLPFC, right orbital cortex and bilateral medial frontal gyrus. Discussion: We described a rare case of RTLV of svPPA, characterized by affected emotion processing, including abnormal social cognition and aspect of theory of mind [2], language dysfunction, and severe right temporal damage. This picture is different from the bvFTD cases that usually present with prominent frontal damage, deficits in working memory, executive function and increased apathy [1]. The different presentation is more evident at disease onset than after the spread of the underlying pathological process. Conclusions: Distinguishing the RTLV of svPPA from bvFTD is critical, given the likely different underlying neuropathology involving syndrome-specific networks and the potential patients’ enrollment in protein-specific treatments as they become available. References: pag. 101

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González-Caballero, Abellán-Miralles, Sáenz-Sanjuan, Right temporal lobe variant of frontotemporal dementia. Journal of Clinical Neuroscience (2015);22:1139–1143 Irish, Hodge, Piguet, Right anterior temporal lobe dysfunction underlies theory of mind impairments in semantic dementia. Brain (2014);137:1241–1253

DOPAMINE IMBALANCE IN HUNTINGTON'S DISEASE: WHEN THE INHIBITION OF AUTOPHAGY CAN LEAD TO CELL CATASTROPHE M. A. Melone1, C. Vidoni2, A. Castiglioni2, C. Seca2, C. Isidoro2 1

Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale & Centro Interuniversitario di Ricerca in Neuroscienze (CIRN), Seconda Università di Napoli (Napoli); 2Department of Health Sciences, Laboratory of Molecular Pathology and Nanobioimaging, Università del Piemonte Orientale “A. Avogadro” (Novara) Background: Huntington Disease (HD) is a neurodegenerative condition caused by abnormal expansions (>37) of a polyglutamine (PolyQ) tract in the huntingtin protein (Htt). Dopamine (DA) induces oxidative stress and causes toxicity in neurons. DA may exacerbate neuronal loss in the striatum. Autophagy is a lysosomal degradation pathway known to clear protein aggregates. We hypothesized that DA could induce toxicity in Htt-expressing dopaminergic neurons by inhibiting the clearing activity of the autophagy system. Materials and Methods: Normal and mutant Htt were ectopically expressed in dopaminergic human neuroblastoma SHSY5Y cells. The autophagic activity and Htt expression were studied by Western blotting and immunofluorescence. Apoptosis was assessed by FACS analysis, Propidium Iodide (PI) staining and Western blotting. Results: Hyper-expression of mutant Htt “per se” reduced cell proliferation and induced cell death. These effects were associated with impairment of the autophagy pathway. DA caused apoptotic and necrotic cell death in SH-SY5Y cells expressing the mutant Htt. In the latter cells, DA further reduced the formation of autophagosome, thus preventing the degradation of Htt aggregates. DA induced oxidative stress at mitochondrial level with generation of anion superoxide ROS. Conclusions: DA causes the death of neurons expressing the mutant Htt through the inhibition of the autophagy degradation pathway. We suggest that DA-induced mitochondrial oxidative stress promotes the generation of ROS that inhibit ATG4, the enzyme needed for the LC3 I to LC3 II conversion. Our data help explain why alterations in DA function conjugate to the inhibition of autophagy system may play a significant role in the motor and cognitive symptoms of HD. Acknowledgements MIUR (PRIN contract #20109MXHMR_004, to MABM)

ABRUPT WITHDRAWAL OF IMMUNOSUPPRESSIVE DRUGS: A POTENTIAL TRIGGER FOR CAA-RI I. Colombo1, G. Calabrese1, B. Bordo1, L. Chiapparini2, S. Auricchio3, F. Piazza4, M. Longoni4, I. Santilli1 1

Neurology Unit, Hospital of Desio, ASST Monza (Desio-MB);
2Neuroradiology Unit, Fondazione C. Besta (Milano); 
3Nephrology Unit, Hospital of Desio, ASST Monza (Desio-MB)
4School of Medicine and Surgery, Milan Center for Neuroscience (NeuroMi), University of Milano-Bicocca (Monza) Objectives: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare but potentially treatable cause of dementia, secondary to an inflammatory response to beta-amyloid (Ab) in cerebral vessels. Acute-onset cognitive behavioral abnormalities, focal deficits, seizures, or headache are the most common presentations. MRI tipically shows asymmetric T2 or FLAIR hyperintensities, minimal gadolinium enhancement, and microbleeds at cortico-subcortical junction. During the acute phase, anti-Ab autoantibodies are increased (1). CAA-ri usually responds to steroids. According to the proposed diagnostic criteria (2), it may be possible to diagnose patients based on clinical and MRI findings alone, obviating the need for brain biopsy. We report the first case of CAA-ri occurring after immunosuppressive withdrawal.
Materials and methods: A 53-year-old man, affected with polycistic disease and late-stage uremia, underwent kidney allotransplantation. Eleven years later light cell cancer was detected on the transplanted kidney, which was excised. Immunosuppressive drugs, including cyclosporine and mycophenolate, were abruptly withdrawn and hemodialysis started. After one month drowsiness and apathy were observed and interpreted as reactive depression. Three months later he was admitted in our department due to right hemianopsia and aphasia. Complex partial seizures occurred and were treated with antiepileptic drugs. EEG showed diffuse delta activity. A brain MRI demonstrated FLAIR hyperintensities in left parasagittal parieto-temporal and temporo-occipital regions, suggesting brain edema, together with minute hemosiderin depositions at Gradient- sequences. No contrast enhancement was observed. CAA-ri was suspected. At cerebrospinal fluid examination proteins were 162 mg/dl and anti-Abeta autoantibodies resulted positive. The patient was treated with 1 mg/kg pag. 102

prednisone with progressive resolution of symptoms within four weeks. Five months later disappearance of edema was the main feature at MRI. Six months after steroids start, tapering is still ongoing, remaining the patient asymptomatic.
Discussion and conclusions: It is likely that in our patient mood changes were the first presentation of CAAri and no MRI was performed at that time. It is remarkable that neurological and psychiatric onset occurred just one month after immunosuppressive withdrawal. We argue that this abrupt change in the modulation of immune system was the trigger for CAA-ri. Thus, in CAA-ri patients both cerebral amyloid angiopathy and inflammation of blood vessels coexist. Our case report reinforces the idea that autoimmunity plays a role in the causation of this vasculitis. References: 1. Greenberg SM, Savoiardo M, et al. Anti-amyloid β autoantibodies in cerebral amyloid angiopathy-related inflammation: implications for amyloid-modifying therapies. Ann Neurol. (2013) Apr;73(4):449-58 2. Auriel E, Charidimou A, Gurol ME, et al. Validation of Clinicoradiological Criteria for the Diagnosis of Cerebral Amyloid Angiopathy-Related Inflammation. JAMA Neurol. (2016) Feb 1;73(2):197-202

DOLORE EXPECTATION TO FEEL MORE PAIN DISRUPTS LASER-PAIN AND LASER EVOKED POTENTIAL AMPLITUDES HABITUATION C. Pazzaglia1, E. Testani2, R. Giordano2, L. Padua1,2, M. Valeriani3 1

Department of Neurology, Don Carlo Gnocchi Onlus Foundation (Milano); 2Department of Neuroscience, Catholic University of Sacred Heart (Roma); 3Neurology Unit, Ospedale Pediatrico Bambino Gesù, IRCCS, Center for SensoryMotor Interaction, Aalborg University (Roma, Aalborg, DK) Objective: Increased pain perception due to the expectation to feel more pain is called nocebo effect. The present study aimed at investigating whether: 1) the mere expectation to feel more pain after the administration of an inert drug may affect the laser-pain rating and the laser evoked potential (LEP) amplitude, and 2) the learning potentiates the nocebo effect. Materials: Eighteen healthy volunteers were told that an inert cream, applied on the right hand, would increase the laserpain and LEP amplitude to right hand stimulation. Methods: Subjects were randomly assigned to either “verbal session” or “conditioning session”. In the “verbal session”, LEPs to both right and left hand stimulation were recorded at the same intensity before (baseline) and after cream application. In the “conditioning session”, after an initial cream application the laser stimulus intensity was increased surreptitiously to make the subjects believe that the treatment really increased pain sensation. Then, the cream was reapplied and LEPs were recorded at the same stimulus intensity as at the baseline. Results: It was found that the verbal suggestion to feel more pain disrupted the physiological habituation of the laser-pain rating and LEP amplitude to treated (right) hand stimulation. Discussion: Unlike it was previously demonstrated for the placebo effect, the learning did not potentiate the nocebo effect. Conclusions: That the mere expectation to feel more pain has evident consequences on both psychophysical and neurophysiological level can be relevant from a clinical point of view.

THE DIAGNOSTIC ACCURACY OF LASER EVOKED POTENTIALS IN DIABETIC SMALL FIBRE NEUROPATHY E. Galosi, S. La Cesa, G. Di Stefano, C. Leone, A. Fasolino, A. Pepe, A. Di Lionardo, S. Piroso, A. Truini, G. Cruccu Department of Neurology and Psychiatry, University La Sapienza (Roma) Although laser evoked potential (LEP) recording is the most widely agreed neurophysiological tool for investigating nociceptive pathway in patients with neuropathic pain, the diagnostic accuracy of this technique has not yet been documented. In this clinical and neurophysiological study we aimed at assessing sensitivity and specificity of LEPs in a representative neuropathic pain condition, i.e. diabetic small fibre neuropathy. We have carried out 288 LEP recordings from face, hand and foot in 73 healthy subjects to collect age-corrected normative ranges for face, hand and foot. After having screened 172 patients with diabetic neuropathy, we have selected 23 patients with possible pure small fibre neuropathy. In these patients, using the skin biopsy as a gold standard we have calculated sensitivity and specificity of LEPs. In healthy participants LEP amplitude decreased from face to foot. While age strongly influenced normative ranges pag. 103

for all LEP variables, gender did not affect LEP amplitude. By applying age-corrected normative ranges for LEPs, we found that LEPs have a sensitivity and specificity of 76% and 80%. Our clinical and neurophysiological study providing agecorrected normative ranges for the main LEP data and their diagnostic accuracy, helps to improve the clinical reliability of LEPs as a diagnostic tool, and indicates that this technique might be an alternative diagnostic tool to the skin biopsy for a definite diagnosis of diabetic small fibre neuropathy. References: − Valeriani M, Pazzaglia C, Cruccu G, Truini A. Clinical usefulness of laser evoked potentials. Neurophysiol Clin. (2012) Oct;42(5):345-53 − Truini A, Galeotti F, Romaniello A, Virtuoso M, Iannetti GD, Cruccu G. Laser-evoked potentials: normative values. Clin Neurophysiol. (2005) Apr;116(4):821-6 − Truini A, Biasiotta A, La Cesa S, Di Stefano G, Galeotti F, Petrucci MT, Inghilleri M, Cartoni C, Pergolini M, Cruccu G. Mechanisms of pain in distal symmetric polyneuropathy: a combined clinical and neurophysiological study. Pain (2010) Sep;150(3):516-21

PERIPHERAL NERVE STIMULATION OF THE UPPER LIMB FOR NEUROPATHIC PAIN AFTER NERVE INJURIES: A LONG-LASTING EFFICACY IN PAIN RELIEF G. Devigili1, C. Lettieri1, S. Rinaldo1, G. Stevanato2, R. Eleopra1 1

Department of Neurology, Santa Maria della Misericordia University Hospital (Udine); 2Neurosurgery Unit, Dell'Angelo Hospital (Mestre-VE) Introduction: The peripheral nerve stimulation showed good efficacy in treatment of peripheral neuropathic pain (NP) after nerve injuries. However, the evidences of the long-term efficacy and safety are still lacking. The aim of study was to evaluate the long-term outcome in patients after PNS implants. Therefore we designed an OFF-ON stimulation paradigm in order to evaluate the timing of effects on pain relief and changing in sensory profiles. Methods: We prospectically evaluate 12 patients with severe intractable pain after nerve of upper limb or brachial plexus injuries. All underwent surgical implant a quadripolar electrode lead for PNS placed on the sensory nerve fibers of the nerve mainly involved in pain symptoms. All patients underwent the neuroalgological evaluation and quantitative sensory testing and pain questionnaries at baseline and at follow-up evaluation (after 1, 6, 12 months and every year after implant). In all the parameters of stimulation were placed with a subliminal sensation not perceived. During the follow-up the patients performed a blinded switch OFF of stimulation and neuroalgological evaluation and QST was performed. Then the stimulator was switch ON and a second neuroalgological and QST evaluation was performed. Results: All the patients experienced pain relief after implant (mean of 76.2% improvement NRS) and positive phenomena like allodynia were almost disappeared. All the patients showed a persistent pain relief during the follow-up period range from 1.4 months to 9 years. During the blinded OFF stimulation in all the pain reappeared with the same quality of pain present at the onset, regardless of the duration of PNS. The reappearance of pain in all was less then the minute (mean of 38 seconds). After 1 hour also the autonomic symptoms (skin flushing and swelling) occurred. The patients experience pain relief after around one minute to the turning ON the stimulation. No significant adverse events occurred. The warm and cold thresholds were reduced only in patients with peripheral nerve lesion, distally to the brachial plexus. Conclusion: The results support the long lasting efficacy in pain relief of PNS for peripheral neuropathic pain supported by the blinded paradigm of evaluation. The surgical technique is safety with poor risk of lead dislocation.

MOTOR CORTEX TRNS AMELIORATES PAIN, ANXIETY, DEPRESSION AND COGNITIVE IMPAIRMENT IN PATIENTS WITH FIBROMYALGIA: PRELIMINARY RESULTS OF A RANDOMIZED SHAMCONTROLLED TRIAL G. La Bianca1, M. Curatolo2, M. Romano2, M. Sorce2, B. Fierro1, F. Brighina1 1 2

Department of Experimental Biomedicine and Clinical Neuroscience (BIONEC), University of Palermo (Palermo); Neurology Unit, Hospitals Villa Sofia-Cervello (Palermo)

Objective: Fibromyalgia (FMS) is a complex clinical syndrome characterized by widespread muscoloskeletal pain, chronic fatigue, cognitive deficit, sleep and mood disorders. Most pharmacological therapies based on antidepressants, painkillers pag. 104

and muscle relaxants showed limited effectiveness in this disease. For this reason, it’s very important to search and improve new therapeutic means can act directly on the neural circuits responsible for the processing of pain and involved in the typical cognitive impairment, called ‘fibrofog’ (1). Many studies have shown motor cortex transcranial direct-current stimulation (tDCS) and motor cortex repetitive transcranial magnetic stimulation (rTMS) are able to reduce perceived pain levels and number of tender points. Instead, stimulation of dorsolateral prefrontal cortex (DLPFC) was correlated to reduction of anxiety and depression (2) and cognitive improvement (3). Recently a new transcranial electrical stimulation approach, random noise stimulation (tRNS), based on fastly and random frequency changing alternating current, likely acting through stochastic resonance activation mechanisms, was found effective in ameliorate working memory and pain in limited series (3). Here we aimed to explore clinical and neuropsychological effects of primary motor cortex (M1) tRNS in FMS patients. Materials and methods: Twenty female patients with FMS between the ages of 26 and 67 were randomized into two treatment groups undergoing daily stimulation sessions for two weeks (weekend free): one received active, real tRNS and the other one sham, placebo tRNS. Each patient was evaluated, before and after treatment, through Visual Analogue Scale (VAS), Fibromyalgia Impact Questionnaire (FIQ), Mini-Mental State Examination (MMSE), Hospital Anxiety and Depression Scale (HANDS) and other specific neurophychological tests, such as Trail Making Test (TMT), Rey Auditory Verbal Learning Test (AVLT), Forward and Backward Digit Span. Results: M1 active tRNS, compared to sham, induced a general improvement of FMS clinical picture: pain, depression and anxiety scores showed significant and relevant reduction (about 40%) and consistent improvement was also reported in working memory and QoL scores. Discussion and conclusions: These findings suggest M1 tRNS can be very effective in relieving symptoms of fibromyalgia. Differently from motor cortex tDCS, tRNS seems able to counteract not only pain but also cognitive disturbance in these patients. This could follow to the invoked mechanism of stochastic resonance that would bring to a synchronization of neural firing so inducing more spreading and lasting effects. References: 1. Howard M. Kravitz, Robert S. Katz Fibrofog and fibromyalgia: a narrative review and implications for clinical practice, Rheumatology Int (2015);35:1115-1125 2. Hou WH, Wang TY, Kang JH. The effects of add-on non-invasive brain stimulation in fibromyalgia: a metaanalysis and meta-regression of randomized controlled trials. Rheumatology (Oxford) (2016) May 5 3. Mulquiney PG, Hoy KE, Daskalakis ZJ, Fitzgerald PB. Improving working memory: exploring the effect of transcranial random noise stimulation and transcranial direct current stimulation on the dorsolateral prefrontal cortex. Clin Neurophysiol. (2011) Dec;122(12):2384-9

DIAGNOSING AND ASSESSING PAIN IN NEUROREHABILITATION: FROM TRANSLATIONAL RESEARCH TO THE CLINICAL SETTING. RESULTS AND RECOMMENDATIONS OF THE ITALIAN CONSENSUS CONFERENCE ON PAIN IN NEUROREHABILITATION (ICCPN) S. Tamburin1, C. Porro2, A. Truini3, V. Tugnoli4, E. Alfonsi5, L. Berliocchi6, C. Cacciatori1, M. Lacerenza7, F. Magrinelli1, P. Marchettini8, P. Sacerdote9, M. Valeriani10, G. Sandrini5 1

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona (Verona); 2Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia (Modena); 3Department of Neurology and Psychiatry, University Sapienza (Roma); 4Neurology Unit, University Hospital of Ferrara (Ferrara); 5 Department of Brain and Behavioral Sciences, University of Pavia (Pavia); 6Department of Health Sciences, University Magna Graecia of Catanzaro (Catanzaro); 7Pain Medicine Center, Casa di Cura San Pio X, Opera San Camillo Foundation (Milano); 8Pain Medicine Center, Hospital San Raffaele (Milano); 9Department of Pharmacological and Biomolecular Sciences, University of Milan (Milano); 10Division of Neurology, Ospedale Pediatrico Bambino Gesù, IRCCS (Roma) Background and aims: Pain is very common in neurorehabilitation, where it may either be a target for treatment or have a negative effect on rehabilitation procedures and outcomes. Guidelines or consensus on diagnosis and assessment of pain, and translational evidence from animal models are largely lacking in this setting. Methods: The Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) collected evidence on animal models for the treatment of pain, potential predictive biomarkers for response to treatment in preclinical models, the definition and diagnostic criteria for nociceptive and neuropathic pain (NP), screening tools and questionnaires, and diagnostic clinical and instrumental techniques for separating nociceptive from NP and for the assessment of pain in the field of neurorehabilitation. Results: Promising preliminary preclinical data support some therapeutic approaches to pain, but there is a strong need of pag. 105

adequate preclinical models, experimental settings, outcome measures, and biomarkers that could be more relevant for pain in neurorehabilitation field. Data on diagnosis and assessment of nociceptive and NP are very scanty in neurorehabilitation, but those from other contexts can be adapted and translated in this specific setting. Discussion and Conclusions: The present ICCPN recommendations may give information on the relevance of current preclinical models, and be helpful for ameliorating pain diagnosis and assessment, which are prerequisites for better application and tailoring of current pharmacological and non-pharmacological treatments for pain in neurorehabilitation. They may also be useful for future studies aimed to fill the knowledge gaps on these topics.

CEREBELLAR DIRECT CURRENT STIMULATION MODULATES PAIN PERCEPTION AND ITS CORTICAL CORRELATES IN HUMANS T. Bocci1, D. Barloscio1, L. Parenti1, M. Bartolotta1, A. De Rosa1, R. Ferrucci2, A. Priori2, M. Valeriani3, F. Sartucci1 1

Department of Clinical and Experimental Medicine, Cisanello Neurology Unit, Pisa University Medical School (Pisa); Department of Neurological Sciences, Fondazione IRCCS Ospedale Maggiore Policlinico, University of Milan (Milano); 3 Division of Neurology, Ospedale Bambino Gesù, IRCCS (Roma) 2

Introduction: The cerebellum is involved in a wide number of integrative functions, ranging from working memory and associative learning to motor control, but its role in pain perception and nociceptive processing is poorly understood. We evaluated the effects of transcranial cerebellar direct current stimulation (tcDCS) by studying the changes in perceptive threshold (PT), pain intensity (VAS) and laser evoked potentials (LEPs) variables (amplitude and latency of both N1 and N2/P2 responses). Materials and Methods: Fifteen subjects were studied before and after anodal, cathodal and sham tcDCS. LEPs were obtained using a Nd:YAP laser (wavelength 1.04 µm, pulse 164 duration 2–20 ms, maximum energy 7 J). The laser beam was transmitted from the generator to the stimulating probe via a 10m length optical fibre; signals were then amplified, band pass filtered (0.1–200 Hz, time analysis 1000 ms). The dorsum of the left hand was stimulated by laser pulses (individual variability: 3.89–15.75 J/cm2) with short duration (5 ms) and small diameter spots (5 mm). VAS was evaluated by delivering laser pulses at two different intensities, respectively two and three times the PT. Results: Cathodal polarization dampened the PT and increased the VAS score, while the anodal one had opposite effects (p