Treatment of Focal Dystonia Amit Batla, MD, DM (Neurology) Maria Stamelou, MD, PhD Kailash P. Bhatia, MD, DM (Neurology), FRCP *

Current Treatment Options in Neurology (2012) 14:213–229 DOI 10.1007/s11940-012-0169-6 Movement Disorders (O Suchowersky, Section Editor) Treatment ...
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Current Treatment Options in Neurology (2012) 14:213–229 DOI 10.1007/s11940-012-0169-6

Movement Disorders (O Suchowersky, Section Editor)

Treatment of Focal Dystonia Amit Batla, MD, DM (Neurology) Maria Stamelou, MD, PhD Kailash P. Bhatia, MD, DM (Neurology), FRCP* Address *The National Hospital for Neurology and Neurosurgery Queen Square, Box 13, London, WC1N 3BG, UK Email: [email protected] Published online: 14 March 2012 * Springer Science+Business Media, LLC 2012

Keywords Focal dystonia

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Treatment

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Botulinum toxin

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Anticholinergics

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Deep brain stimulation

Opinion statement Dystonia is characterized by repetitive twisting movements or abnormal postures due to involuntary muscle activity. When limited to a single body region it is called focal dystonia. Examples of focal dystonia include cervical dystonia (neck), blepharospasm (eyes), oromandibular dystonia, focal limb dystonia, and spasmodic dysphonia, which are discussed here. Once the diagnosis is established, the therapeutic plan is discussed with the patients. They are informed that there is no cure for dystonia and treatment is symptomatic. The main therapeutic option for treating focal dystonias is botulinum toxin (BoNT). There have been several attempts to characterize the procedure, the type of toxin, dosage, techniques, and combination with physical measures in each of the focal dystonia forms. The general treatment principles are similar. The affected muscles are injected at muscle sites based on evidence and experience using standard dosages based on the type of toxin used. The injections are repeated after 3 to 6 months based on the individual response duration. In the uncommon event of nonresponse with BoNT, the dose and site are reassessed. Oral drug treatment could be considered as an additional option. Once the condition is thought to be medically refractory, the opinion from the deep brain stimulation (DBS) team for the suitability of the patient for DBS is taken. The successful use of DBS in cervical dystonia has led to increased acceptance for trial in other forms of focal dystonias. DBS surgery in focal dystonias other than cervical is, however, still experimental. The patients may be offered the surgery with adequate explanation of the risks and benefits. Patient education and directing the patients towards dystonia support groups and relevant websites that provide scientific information may be useful for long-term compliance and benefit.

Introduction Dystonia is an involuntary, sustained, patterned, and often repetitive muscle contraction of opposing muscles, causing twisting movements or abnormal postures [1]. Dystonia is classified by distribution into

focal (single body part only), segmental (two or more contiguous body parts), multifocal (two or more noncontiguous body parts), hemidystonia (one side of the body and generalized dystonia (92 contiguous body

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parts plus the trunk)), or generalized [2]. By age at onset, it is classified into young-onset (G20–30 years) and adult-onset dystonia. By etiology it is classified into primary (where dystonia with or without tremor are the only symptoms and signs); dystonia-plus syndromes (where signs other than dystonia are present without secondary cause or neurodegeneration); secondary dystonia (in which a clear secondary cause such as brain injury or drug exposure is present); and heredo-degenerative dystonia (where dystonia is part of a neurodegenerative syndrome, such as Wilson’s disease) [2].

Here we discuss the symptomatic treatment of primary focal dystonias, the most common of which is cervical dystonia followed by blepharospasm, oromandibular, spasmodic dysphonia, and focal limb dystonia. Botulinum toxin (BoNT) remains the mainstay of symptomatic treatment in most conditions [3]. Deep brain stimulation (DBS) may be useful in carefully selected, medically refractory cases. Oral medications have a limited role. BoNT therapy and DBS are discussed in greater detail for cervical dystonia as an example to cover procedures, contraindications and adverse events applicable to all forms of primary focal dystonia.

Treatment Cervical dystonia & &

Cervical dystonia (CD) is characterized by abnormal posturing or spasms simulating a tremor affecting the neck and shoulder muscles [2]. The main treatment option is BoNT, and DBS may be considered in refractory cases.

Treatment with botulinum toxins & &

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Botulinum toxins are derived from Clostridium botulinum. The mechanism of action is chemical denervation that is topical, reversible, and dose-dependent [3]. There are seven serotypes of BoNT labelled A through G. The types A and B are available for clinical use in dystonia. Each serotype binds to a serotype-specific acceptor site on presynaptic nerve terminals, and each selectively cleaves a specific protein involved in vesicle fusion and neurotransmitter release. BoNT A cleaves synaptosomalassociated protein of 25 kD (SNAP 25), and BoNT B cleaves vesicular associated membrane protein (VAMP) called synaptobrevin [4]. Recently, there has been further understanding of the precise modes of action of BoNT [4] but it is beyond the scope of this review. The evidence from several Class I and class II studies (Table 1) has led to a level A recommendation for use of BoNT in CD as a first line treatment of by the American academy of Neurology [5] and European federation [6••, 7]. Both Serotypes A or B have been systematically evaluated against placebo in randomized trials. There appears to be no difference in the efficacy or safety. The European guidelines recommend that BoNT B may be used if there is resistance to BoNT A [6••]. A Cochrane review has assessed the evidence for safety and efficacy of BoNT A in CD based on 13 studies including 680 patients. The metaanalysis found significant improvements on objective rating scales

Pappert 2008 [16]

Poewe 1998 [17]

Truong 2005 [18]

Benecke 2005 [19]

Brans 1996 [20]

I

I

Botulinum toxin I A (Dysport)

Botulinum toxin II type A (BoNT A) and NT-201 (Xeomin) Botulinum toxin I A (Dysport)

Greene 1990 [21]

Randomized, doubleblind design vs tri hexyphenidyl(THP)

Comella 2005 [15]

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Botulinum toxin I A (Botox)

Double-blind noninferiority trial

Brin 1999 [14]

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Randomized, doubleblind

TWSTRS

TWSTRS

TWSTRS

TWSTRS

11.0 (BoNT B) 8.8 (BoNT A)

3.3 (placebo) 11.6 (2500 U) 12.5 (5000 U) 16.4 (10,000 U) 4.3 (Placebo) 9.3 (5000 U) 11.7 (10,000 U) 2.0 (placebo) 11.1 (10,000U) 10.2 (BoNT B) 9.3(BoNT A)

Benefit on scores

Dysphagia 14% (BoNT B) 15% (BoNT A) Dry mouth 37% (BoNT B) 35% (BoNT A) No significant differences in the occurrence of injection site pain and dysphagia Neck weakness (n=14) Dysphagia (n=16) Dry mouth (n=13)

Dysphagia (n=13)

Dysphagia (n=13)

Dysphagia (n=16) Dry mouth (n=14)

Significant adverse events reported

Modification 20%–32% at 4 weeks on of the scale Tsui scale. Overall improvement in 79% used by patients Tsui et al. TWSTRS 3.8 (placebo) 9.9 (500 U) Neck weakness 16%, Dysphagia 16%, Dry mouth 22%, Blurred vision 14% 11 in both at 28 days Dysphagia 8.2% (BoNT A) 420 patients TWSTRS (213 NT201 On follow up 6.6 10.8% (NT201) and 207 (NT 201) 6.4 (Botox) Botox) Neck weakness (n=3) 66 (33) TWSTRS On Tsui scale 0 (THP) 5 Blurred vision (n=6) Dry (Disability) (BTA). On TWSTRS (dis mouth (n=9) ability) 93 points in and Tsui Scale 18.8% (THP) 42.8% (BTA) 55 Result Scale 61% patients improved Dysphagia (n=3) Capability Scale and Pain Scale

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139 BoNT A, TWSTRS n=74;BoNT B, n=65

77 (39)

109 (73)

122 (92)

Score No. of used patients (treatment group)

75 (54) Placebo controlled double blind dose ranging study with 250/500 or 1000 Units Double-blind, placebo- 80 (37) controlled

Randomized, doubleblind, noninferiority trial

Brashear 1999 [13]

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Botulinum toxin B (NeuroBloc) BotulinBm toxin B (NeuroBloc) Botulinum toxin type A (BoNT A) and type B (BoNT B) Botulinum toxin type A (BoNT A) and type B (BoNT B) Botulinum toxin A (Dysport)

Double-blind, placebocontrolled safety and efficacy study Double-blind, placebocontrolled Double-blind, placebocontrolled Randomized, doubleblind, parallel-arm

Trial design

Lew 1997 [12]

Class of First author evidence

Botulinum toxin I B (NeuroBloc)

Intervention

Table 1. Studies assessing treatment of cervical dystonia with botulinum toxin and deep brain stimulation

Treatment of Focal Dystonia Batla et al. 215

Hung 2007 [34] Cacciola 2010 [35••]

II

II

II

IV IV

Bilateral GPi-DBS

Bilateral GPi-DBS

Bilateral GPi-DBS

Bilateral GPi-DBS Bilateral GPi-DBS

Pretto 2008 [33]

Kiss 2007 [32]

Skogseid 2011 [31••]

Class of First author evidence

Intervention

Table 1 (Continued)

Open label

Prospective, singlecenter study with blinded evaluation Open label

Prospective, singlecenter study with blinded evaluation Prospective, singleblind, multicenter study

Trial design

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TWSTRS

TWSTRS

TWSTRS

4

10

TWSTRS

TWSTRS

10

8

Score No. of used patients (treatment group)

Significant adverse events reported

70% on severity scale after Reversible right 2.5 year hemiparesis and aphasia occurred in one patient 43% from baseline 14.7 to Mild and transient 8.4 at 12 months on dysphagia dysarthria severity scale and facial weakness in one patient each Transient post-operative Baseline 12.8 to a mean bronchospasm and postoperative score of confusion in one 7.5 54.8%, on Severity score Lead infection in one and transient dysarthria in 2 68.1% on Severity score 2 infections and 1 lead breakage

Benefit on scores

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& &

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for dystonia [8]. The benefit with BoNT A is more and its use is associated with lesser side effects than oral treatment with the anticholinergic trihexyphenidyl [9]. The evidence of use of BoNT B in CD has been evaluated in a Cochrane review. This included 308 patients from three studies. BoNT B was found to be more effective than placebo [10]. BoNT B has been found to be as effective as BoNT A [11] and both toxin serotypes are useful in treatment of CD [12–21]. The various forms of BoNT A (Abobotulinum toxin A [Dysport®] and Onabotulinum toxin A [Botox®]) have similar effect [22, 23]. Incobotulinum toxin A (Xeomin®) has been compared with Botox® in a noninferiority trial and showed similar efficacy [19]. Regarding dosage equivalence, ratios of 3:1 to 5:1 for Dysport® to Botox® can be used but this cannot be translated using a simple dose conversion [22, 23]. The dose for Xeomin® is equivalent to Botox® [19]. The dose comparison of BoNT B and BoNT A can be guided by two studies directly comparing BoNT A (Botox®) and BoNT B (Myobloc®/ NeuroBloc®) in 1:40 [15 Class I] and 1:66.6 [16 Class I] ratios. Both studies found no difference in the treatment response with either type of toxin.

BoNT There is no consensus or studies guiding the muscle selection; however, most studies use similar muscles. The guiding principles for muscle selection are as follows:

For the rotation (torticollis), ipsilateral splenius/semispinalis capitis, contralateral sternocleidomastoid and trapezius are injected. For the lateral tilt (laterocollis), the ipsilateral sternocleidomastoid and splenius/semispinalis capitis are usually injected. The ipsilateral scalene complex, levator scapulae, posterior paravertebrals may additionally be injected. For shoulder elevation, ipsilateral levator scapulae and trapezius are injected. The extension of the head backwards (retrocollis) may require bilateral splenius/semispinalis capitis and bilateral upper trapezius injections. The flexion of the head forwards (anterocollis) is treated with injections in the bilateral sternocleidomastoid. The bilateral scalene complex and submental complex may be additionally injected for anterocollis [24]. Standard dose

Dosage guidance is available for individual brands. When injecting children care must be taken to limit the total dose to less than 12 units⁄kg or 400 units (for Botox®), whichever is the lower [5].

Repeat injections

The mean duration of effect of BoNT A has been reported as 95 days [17, Class I]. The time between treatment and the return of Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score to within 10% of baseline has been found to range from 9 to 89 weeks with a mean of 20.0 weeks. [18, Class I]. With BoNT B, the time to return to the baseline TWRTRS total score was about 16 weeks in three Class I studies [12, 13, 17].

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Movement Disorders (O Suchowersky, Section Editor) We repeat the injections in 3 to 6 months’ time depending on patient’s response. Contraindications

Hypersensitivity to any form of BoNT or infection at the proposed injection site are absolute contraindications (applicable to all focal dystonias). Caution is advised when injecting [25]. The presence of pre-existing muscle neuromuscular weakness due to disorders such as amyotrophic lateral sclerosis, myopathies, motor polyneuropathies, and myasthenia gravis or Lambert-Eaton syndrome and concurrent use of aminoglycoside antibiotics or other neuromuscular blocking agent. Bleeding disorders, or regular use of anticoagulants. Special population: Safety and efficacy are not established in patients less than 16 years of age for the treatment of CD, and in patients less than 12 years of age for the treatment of blepharospasm and strabismus. There are insufficient data to allow use of BoNT in pregnancy and lactation.

Main side effects

Excessive weakness of muscles injected. Spread to adjacent muscles causing weakness. Fatigue, flu-like symptoms, a dry mouth, dizziness, and a skin rash. Local pain or bruising at injection site is common side effects irrespective of the site of focal dystonia [24, 25]. The common adverse events with BoNT A in CD were found to be neck weakness (number needed to harm [NNH]=8), dysphagia (NNH=10), and dry mouth/sore throat (NNH= 10) [8, Class I]. The common adverse events with BoNT B were found to be dry mouth (NNH=6) and dysphagia (NNH=8) [10, Class I].

Cost/cost-effectiveness

The cost-effectiveness of BoNT has been evaluated in a large clinical series recently [26•]. The daily cost of BoNT A injections were €0.95±0.30 for blepharospasm and €2.85±0.86 for CD. Per session cost of Dysport® injections in CD was €289±87 (range, 54–682) with benefit lasting 14.3± 6.7 weeks [26•].

Nonresponders

Some patients never respond to treatment with BoNT (primary nonresponders), whereas some stop responding later in the course of treatment (secondary nonresponders). The primary nonresponders (less than 25% following the first and, at least, the second consecutive treatments) may constitute 15% to 30% of the cases of CD [27]. The causes for BoNT treatment failure in either case may be inadequate dosing, inappropriate muscle selection, inaccessible dystonic muscles, or contracture [27]. In the cases with secondary failure, 35.7% were demonstrated to have neutralizing antibodies [28].This study brought about the awareness of the protein load associated risk of developing antibodies leading to a reduction of protein load of Botox® preparation used for this study from 25 to 5 nanograms per 100 units. The evaluation with the new formulation demonstrated none of the treated patients developed secondary resistance [29]. In a more recent study using Dysport® for other indication, none of the 1554 patients developed neutralizing antibodies [30••].

Treatment with deep brain stimulation &

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DBS is a useful option if the treatment with BoNT fails to provide adequate improvement (level B) [7]. The recommendation level is level A for primary generalized and segmental dystonia [7]. This is mainly based on evidence from a few class II studies [31••, 32–34, 35••] (Table 1). As of now there is no evidence to support use of DBS in CD as a first line treatment and its use must be reserved for cases not responding to BoNT.

Treatment of Focal Dystonia

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There is evidence to suggest that bilateral globus pallidus interna (GPi) is the preferred site if DBS is considered in CD and was used in all of the class II studies. The complications rate is similar to DBS procedures done for other conditions (See Table 1 for details).

DBS Standard procedure

The DBS device consists of three components: a lead with four electrodes (contacts) that is implanted within the deep brain target, usually the GPi in this case, and a programmable pulse generator, which is used to deliver the therapeutic current. This is usually implanted in the chest wall. After lead implantation, the pulse generator can be programmed transcutaneously from the chest wall. The current accepted target of DBS for CD is the GPi. Microelectrode recording, with or without intraoperative MRI guidance, can be used to refine the targeting of the leads. The device is activated 7 to 14 days after implantation. The amplitude, pulse width, frequency, and choice of the active contacts can be regulated. There is no consensus regarding the optimal settings for treatment of dystonia. Wide pulses (210–400 μsec) and high frequencies (130 Hz or higher) are preferred. Using lower settings prolongs battery life, therefore requiring fewer battery replacement surgeries. With availability of batteries with longer lives or options of recharge, this may not be a problem. The duration of effect varies in different studies. There is an immediate lesioning effect and CD improves but returns in a week. Significant benefit has been noted at 3 months using TWSTRS [38], and the improvement may continue beyond the first year and has been reported as 64.5%, 65.5%, and 75.8% at 3, 6, and 12 months, respectively, after surgery [37••].

Contraindications

Psychiatric disease, cognitive impairment, swallowing difficulty or possible incompliance with the required close follow-up for programming and maintenance of the device after the surgery are contraindications. Psychiatric side effects may limit the success of the surgery [36••, 37••]. Patients with poor performance in neuropsychological testing, especially in frontal lobe and memory domains, may not be suitable candidates and may be at risk for worsening with DBS [36••].

Complications

Intraoperative hemorrhage or ischemia, perioperative infection, displacement or fracture of the extension cable, are uncommon complications [36••, 37••].

Cost/cost-effectiveness

The cost benefit for DBS has not been systematically analyzed in focal forms of dystonias. In dystonia overall, a gain of 0.94 quality-adjusted life-years (QALY) with a cost of £33,980 per QALY was observed [38]. The cost may be justifiable only in the focal dystonia cases that are medically refractory with severe disability.

Treatment with selective peripheral denervation &

Prior to the widespread use of DBS in dystonia, selective peripheral denervation (SPD) was tried in patients who did not respond to medical treatment. There are no class I studies in this regard. Two of the largest patient series on SPD in CD included 260 [39, Class IV] and 207 cases [40, Class IV] refractory to medical treatment and found “very good to excellent” results in 88% (228/260 and 182/207).

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SPD was found to be an effective treatment for patients with secondary, but probably not for those with primary, BoNT failure in another large study [41, Class IV]. There were National Institute of Clinical Excellence (NICE) guidelines published in 2004 [42]. The evidence from the several case series was considered adequate to support the use in cases refractory to best medical treatment. This procedure is rarely used since the introduction of DBS.

Treatment with oral medication Trihexyphenidyl Mechanism of action

Trihexyphenidyl is an anticholinergic drug that is useful in generalized and focal dystonia.

Evidence for use

There is evidence from a randomized control trial [43] that has been the only one included in Cochrane review [9] that suggests that BoNT A injections provide more objective and subjective benefit than trihexyphenidyl to patients with CD. The evidence is insufficient and no recommendations can be made to guide prescribing in focal dystonia [6••].

Standard dose

Start with 1 mg daily and increase by 1 mg every 4–7 days to reach 1 mg three times daily. Then increase by 1 mg every 4–7 days to reach 2–4 mg three times daily. In case of side effects, dose titration must be stopped and reattempted after 1 to 2 weeks. Maximum dose is 50–100 mg/day [24].

Side effects

Dry mouth, dry eyes, nausea, confusion, memory complaints, hallucination, constipation, urinary retention [3].

Contraindications

Closed angle glaucoma, urinary retention [24].

Tetrabenazine Mechanism of action Evidence for use

Standard dose

Side effects Contraindications

This is a dopamine-depleting drug, an inhibitor of vesicular monoamine transporter 2 [3]. Benefit was observed with tetrabenazine in a study of dystonia due to several causes including CD [44, Class IV]. No other studies have systematically assessed the benefit with tetrabenazine in CD against placebo or BoNT. At present there is insufficient evidence to support the use of tetrabenazine for CD. Start with 12.5 mg once daily and increase 12.5 mg every week to reach 12.5 mg three times a day. Average dose 25–50 mg three times a day. Maximum dose 200 mg per day [24]. Depression and parkinsonism. Hypotension, depression, and parkinsonism.

Clonazepam Mechanism of action Evidence for use Standard dose

This is a benzodiazepine that acts as a muscle relaxant [3]. Though commonly used for its benefit in generalized dystonia, there are no randomized controlled studies of clonazepam in focal dystonia. Starting dose 250 μg once daily increased by 250 μg every week to reach 500 μg to 1 mg two three times daily. Maximum dose 4–6 mg/day [24].

Treatment of Focal Dystonia

Main side effects Contraindications

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Sedation, fatigue. Machine operation and driving may be at risk and professions involving these activities are relative contraindications.

Other oral drugs Amantadine

There are studies suggesting mild to moderate benefit with amantadine [45, 46, Class IV] against placebo in randomized control trials.

Levodopa

Has been evaluated in several randomized control studies against placebo in the past [47, 48]. Some cases reported worsening and there was no benefit compared to placebo [45].

Amphetamine Haloperidol Others

Has been evaluated in a randomized study and shown to have significant benefit [49, Class II]. Has been evaluated in combination with amantadine but no evidence of benefit was found [45]. Other drugs that have been tried in focal dystonia include risperidone, tiapride, and clozapine but they were not found to be useful [6••]. Bromocriptine and lisuride have been evaluated in CD with transient, subjective, or mild benefit in randomized controlled studies [50, Class II]. There is no current evidence to support use of any of these oral medications for cervical or other focal dystonias.

Blepharospasm & &

The involuntary, intermittent or persistent, usually bilateral eye closure produced by contractions of the orbicularis oculi is termed blepharospasm. The main treatment option available for blepharospasm is BoNT. The use of BoNT in blepharospasm is based mainly on the openlabel observations that showed efficacy but there have been only a few attempts to perform properly controlled clinical trials [5].

Treatment with BoNT &

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A Cochrane review published in 2005 could not find any suitable study to include in the systematic review. The US Food and Drug Administration (FDA) approval and later American Academy of Neurology (AAN) recommendations (Level B) [5] were based on two class II studies (Table 2). More recently, two placebo-controlled studies with Xeomin® [51, Class I], and Dysport® [52••, Class I] forms of BoNT A became available. These studies found significant benefit with use of BoNT in blepharospasm (Table 2). Several studies have compared various preparations of BoNT A in blepharospasm [51, 57] (Table 2), and evidence suggests that neither preparation is better than the other [53•• Class I].

BoNT Standard injection procedure

For the majority of the patients, injection above and lateral and one below and lateral on orbicularis oculi is used [24]. In cases with levator inhibition

11

Double blind, prospective, 212 cross-over design; comparison

Jankovic 1987 Blinded, prospective, [54] cross-over design

Sampaio 1997 Single-blind, randomized 42 [56] parallel comparison study of Botox and Dysport Roggenkamper Double-blind, randomized, 300 2006 [57] prospective, parallel design; comparison of Botox and Xeomin

II

BoNT A (Oculinum)

Wabbles 2010 Double-blind, randomized, 65 [53••] parallel-group pilot study: comparison of Botox and Xeomin

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BoNT A/Botox: III BoNT A/Dysport: BoNT A/Botox: I BoNT A NT201 (Xeomin)

I

A/Botox: A/Xeomin:

Jankovic 2011 Randomized, placebo[52••] controlled, double-blind trial

Randomized, double-blind, 120 placebo-controlled, multi-dose

Nussgens 1997 [55]

I

Xeomin

Truong 2008 [51]

Significant adverse events reported

Eyelid ptosis (25% in 120U/eye group), blurred vision, lagophthalmos, diplopia, increased lacrimation, and aggravated dry eyes Jankovic Rating 1.0 point on severity and Dry eye, dysphagia, Scale 0.5 on functional ability epiglottitis, and muscular weakness in 4/74 patients treated with Xeomin BSDI: 7.9 (Botox) 8.3 No difference in Blepharospasm (Xeomin) periorbital hematoma Disability Index JRS: 2.3 on OS 2.2 on and headache in the (total BSDI) OD (Botox), 1.5 two groups Jankovic rating (Xeomin) scale(JRS) Fahn scale and 71.6% on a clinical rating Blurred vision, tearing, patient subjective score, 38.9% by videoptosis, ecchymosis scale rating; Only duration and There was no significant Botox: 17% side effects difference in the Dysport: 24.1% Ptosis duration (less with Botox), tearing, blurred vision, diplopia, hematoma,foreign body sensation Only duration and There was no significant Botox: 47%, Dysport: side effects difference in the 50%; ptosis most common duration 2.90 for the NT 201 group Ptosis, 6.08% for Jankovic Rating and 2.67 for the Botox Xeomin and 4.52% scale BSDI, group for Botox Patient Global, Investigator Global

Benefit on scores

BDS, SRS, FIM, At 4 weeks 2 points on Global impairment FIM scale in all dose (VAS) groups. 1 point on SRS with 40 and 80 U doses per eyes and 2 points with 120 U per eye

Score used No. of patients (treatment group)

BoNT A/Botox: II BoNT A/Dysport:

I

Dysport

Intervention Class of First author Trial design evidence

Table 2. Evidence for use of botulinum toxin in blepharospasm

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due to the dystonia of pretarsal portion of orbicularis oculi, injections are given only to the pretarsal portion of orbicularis oculi. The smaller needle size of 30- and 32-gauge [58•] and greater dilution of toxin 10 U/mL versus 100 U/mL [59•] have been studied for comparing pain during injection Although there was no benefit was with smaller needle [58•], higher dilution reduced the pain measured by pain scores (1.94 vs 4.59, PG0.001) [59•].

Treatment with DBS & &

There are no studies assessing usefulness of DBS in blepharospasm. DBS has been shown to benefit blepharospasm when tried for Meige’s syndrome. Mean improvement of 25% (P=0.006) in 3 to 6 months and 38% (PG0.001) at 12 to 78 months of follow-up have been noted on the blepharospasm movement scale [60•].

&

There is no evidence from any large studies with oral medication in blepharospasm [6••, 24]. Some authors recommend use of clonazepam [3].

&

Oromandibular dystonia (OMD) mainly involves the masticatory muscles. In addition it may involve lower facial and tongue muscles [2]. The jaw dystonia can be classified as jaw-closing, jaw opening, or jaw-deviation dystonia [2]. BoNT remains the treatment of choice for OMD.

Treatment with oral medication

Oromandibular dystonia

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Treatment with BoNT &

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Standard injection procedure

The evidence for the use of BoNT in OMD is derived from several open-label studies [61–67, 68•, 69] and a double-blind study with BoNT in craniocervical dystonia where some of the patients included had OMD [65]. A large follow-up study of 162 injected patients found the mean global effect of BoNT was 3.1±1.0 (range, 0 to 4, where 4 equals the complete abolition of the dystonia) [66]. Jaw opening involves lateral pterygoids. In the initial opening the submentalis complexes—mylohyoid, digastric, and geniohyoid play a part [68•]. Most studies suggest injections of the lateral pterygoid in jawopening dystonia [61–64]. The jaw closure dystonia and jaw deviation types respond better than jaw opening type [67].The jaw closure is mediated by masseter, temporalis, and medial pterygoids. The usual starting dose for the jaw closure dystonia are 100 units of Dysport® or equivalent doses of Botox® in masseter and temporalis and 30 units in medial pterygoid [67, 68•]. In jaw-deviation OMD protrusion is often combined. The contralateral external pterygoid muscle is preferably injected. When jaw protrusion is dominating, both external pterygoid muscles are often injected [24, 68•].

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Treatment with DBS & &

There is no evidence for use of DBS in isolated OMD. Oromandibular movements have however responded to DBS when tried in 12 patients with Meige’s syndrome [60•].

&

The results of previous drug trials in OMD have been largely disappointing [69, 70]. The efficacy of tetrabenazine, clonazepam, or other oral drugs has not been assessed in a systematic way in any large studies. Some authors find oral baclofen to be useful for OMD [3].

Treatment with oral medication

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Spasmodic dysphonia & &

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Spasmodic dysphonia (laryngeal dystonia) is characterized by change in voice due to dystonia of laryngeal muscles [2, 71•]. This may mainly be adductor type spasmodic dysphonia (ADSD) or abductor type (ABSD). ADSD is characterized by “strain-strangled” quality of voice, whereas ABSD leads to breathy breaks or whispering quality of voice [71•]. The evidence favors the use of BoNT for treatment [72].

Treatment with BoNT &

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&

Two systematic reviews [72, 73] and two meta-analyses [74, 75] that have considered the effectiveness of BoNT for spasmodic dysphonia have been published in the literature. A Cochrane review has analyzed use of BoNT in spasmodic dysphonia [73] and found insufficient evidence to support the use. A Class I, double-blind, randomized controlled study [76] assessed 13 patients with ADSD who had improved voice quality (P=0.01) on 4th day of injection. The adverse events reported were excessive breathiness (2/13), mild bleeding (1/13), and vocal fold edema (1/13) [76]. The benefit and safety has been documented in other studies [77–79, Class III] on ADSD.

BoNT Standard injection procedure

Common side effects

BoNT is injected into the thyro-arytenoid muscles, bilaterally (0.9 unit/ 0.1 mL per vocal fold). This is done through laryngoscopy. The average dose used in most studies is 2.5 to 3 units [67, 77–79]. The common adverse events reported are hypophonia, breathiness, coughing, choking, and swallowing problems [77–79].

Treatment with DBS and oral medication &

There is no evidence of benefit with DBS or oral medication in spasmodic dysphonia [6••].

Treatment of Focal Dystonia

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Focal hand dystonia &

&

Focal hand dystonia encompasses writer’s cramp, other occupational hand dystonia, and non-task-specific hand dystonia. When taskspecific dystonia gets worse the task specificity is often lost. The task specificity may be only apparent to the patient and careful assessment can reveal a mild motor control disorder [2]. BoNT remains the mainstay of treatment in focal hand dystonia.

Treatment with BoNT & &

& &

The evidence to support BoNT use in writer’s cramp is level B (AAN) [5]. One randomized double-blind trial [80, Class I] of 40 patients with writer’s cramp reported a significant (PG0.01) improvement on writer’s cramp scale with BoNT. There were significant improvements in handwriting (P=0.01) and symptom severity (P=0.02) but not on functional status (P=0.1). The efficacy has been demonstrated in three other studies [81–84, Class II] using different objective and subjective measures of improvement. The focal dystonia affecting lower limb is uncommon. Benefit with BoNT [87, Class II] has been reported in this condition. The evidence is insufficient for recommending use.

BoNT Standard injection procedure

The use of mirror dystonia to identify active muscles is popular and also based on personal experiences of some authors [68•, 84]. The recommended technique is to let the dystonic hand relax and do the writing task with the contralateral hand. Mirror dystonia appears often in the dystonic hand, making it easier to find the muscles requiring injection. Some studies have suggested the benefit of electromyographic (EMG) guidance for identifying the correct muscles for injection [85, Class II]. However, another study reported no difference in weakness observed in the muscles injected with or without EMG guidance [86, Class II]. In case the clinical judgement is difficult or inadequate, EMG may be used for identification and injection of overactive muscles. The use of exercise immediately after injections has been shown to result in decreased grip strength but did not affect subjective benefit in 10 patients evaluated [87, Class II study].

Common side effects

Temporary hand weakness (18/20 injected patients) and pain (1/20 injected patients) at the injection site were the only adverse events reported [84]. The weakness was reported variably as 53% [81, Class II], 80% [83, Class II] to 100% [82, Class II] in the studies.

Treatment with DBS & &

Thalamic DBS and thalamotomy have been tried for writer’s cramp in small nonrandomized studies with some benefit [88, Class IV]. The thalamic stimulation was more effective than GPi DBS in treating writer’s cramp [88, Class IV].

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&

The use of DBS in writer’s cramp cannot be recommended based on limited studies. The use of DBS must be limited to medically refractory cases. Thalamus ventralis oralis/ventralis intermedius (VO/ VIM) appears to be the preferred site for stimulation [88, Class IV].

&

Anticholinergics or baclofen provide modest, if any, benefit for primary limb dystonias [6••, 24, 68•]. The efficacy of oral drugs has not been assessed in a systematic way in any large studies in primary limb dystonia.

Treatment with oral medication

&

Disclosure A. Batla: none. M. Stamelou: none. K.P. Bhatia has received research support from Ipsen and from the Halley Stewart Trust through Dystonia Society UK, and the Wellcome Trust MRC strategic neurodegenerative disease initiative award (Ref. number WT089698), a grant from the Dystonia Coalition, and a grant from Parkinson’s UK (Ref. number G-1009). He has received personal compensation for scientific advisory board for GlaxoSmithKline and Boehringer Ingelheim, and royalties from the publication of Oxford Specialist Handbook of Parkinson’s Disease and Other Movement Disorders (Oxford University Press, 2008). He has also received funding for travel from GlaxoSmithKline, Orion Corporation, Ipsen, and Merz Pharmaceuticals, LLC, and received speaker honoraria from GlaxoSmithKline, Ipsen, Merz Pharmaceuticals, LLC, and Sun Pharmaceutical Industries Ltd.

References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1. 2.

3. 4.

5.

6.••

Fahn S, Bressman S, Marsden CD. Classification of dystonia. Adv Neurol. 1998;78:1–10. Jankovic J. Dystonic disorders. In: Tolosa JJ, editor. Parkinson’s disease and movement disorders. 5th ed. Philadelphia: Williams and Wilkins; 2007. p. 321–47. Jankovic J. Treatment of dystonia. Lancet Neurol. 2006;5:864–72. Montal M. Botulinum neurotoxin: a marvel of protein design. Annu Rev Biochem. 2010;79:591– 617. Simpson DM, Blitzer A, Brashear A, Comella C, et al. Assessment: Botulinum neurotoxin for the treatment of movement disorders (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2008;70(19):1699–706. Albanese A, Asmus F, Bhatia KP, et al. EFNS guidelines on diagnosis and treatment of primary dystonias. Eur J Neurol. 2011;18(1):5–18

These guidelines provide a comprehensive overview of the treatment options and evidence-based recommendations for generalized and focal dystonia. 7. Albanese A, Barnes MP, Bhatia KP, et al. A systematic review on the diagnosis and treatment of primary (idiopathic) dystonia and dystonia plus syndromes: report of an EFNS/MDS-ES Task Force. Eur J Neurol. 2006;13(5):433–44. 8. Costa J, Espírito-Santo C, Borges A, et al. Botulinum toxin type A therapy for cervical dystonia. Cochrane Database Syst Rev. 2005;1:CD003633. 9. Costa J, Espírito-Santo C, Borges A, et al. Botulinum toxin type A versus anticholinergics for cervical dystonia. Cochrane Database Syst Rev. 2005;1:CD004312. 10. Costa J, Espírito-Santo C, Borges A, et al. Botulinum toxin type B for cervical dystonia. Cochrane Database Syst Rev. 2005;1:CD004315. 11. Costa J, Borges A, Espírito-Santo C, Ferreira J, et al. Botulinum toxin type A versus botulinum toxin type B for cervical dystonia. Cochrane Database Syst Rev. 2005;1:CD004314.

Treatment of Focal Dystonia 12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

Lew MF, Adornato BT, Duane DD, et al. Botulinum toxin type B: a double-blind, placebo-controlled, safety and efficacy study in cervical dystonia. Neurology. 1997;49(3):701–7. Brashear A, Lew MF, Dykstra DD, et al. Safety and efficacy of NeuroBloc (Botulinum toxin type B) in type A-responsive cervical dystonia. Neurology. 1999;53(7):1439–46. Brin MF, Lew MF, Adler CH, et al. Safety and efficacy of NeuroBloc (Botulinum toxin type B) in type A-resistant cervical dystonia. Neurology. 1999;53(7):1431–8. Comella CL, Jankovic J, Shannon KM, Dystonia Study Group, et al. Comparison of botulinum toxin serotypes A and B for the treatment of cervical dystonia. Neurology. 2005;65(9):1423–9. Pappert EJ, Germanson T, Myobloc/Neurobloc European Cervical Dystonia Study Group. Botulinum toxin type B vs. type A in toxin-naïve patients with cervical dystonia: Randomized, double-blind, non inferiority trial. Mov Disord. 2008;23(4):510–7. Poewe W, Schelosky L, Kleedorfer B, et al. Treatment of spasmodic torticollis with local injections of botulinum toxin. One-year follow-up in 37 patients. J Neurol. 1992;239(1):21–5. Truong D, Duane DD, Jankovic J, et al. Efficacy and safety of botulinum type A toxin (Dysport) in cervical dystonia: results of the first US randomized, double-blind, placebo-controlled study. Mov Disord. 2005;20(7):783–91. Benecke R, Jost WH, Kanovsky P, et al. A new botulinum toxin type A free of complexing proteins for treatment of cervical dystonia. Neurology. 2005;64 (11):1949–51. Brans JW, Lindeboom R, Snoek JW, et al. Botulinum toxin versus trihexyphenidyl in cervical dystonia: a prospective, randomized, double-blind controlled trial. Neurology. 1996;46(4):1066–72. Greene P, Kang U, Fahn S, et al. Double-blind, placebo-controlled trial of botulinum toxin injections for the treatment of spasmodic torticollis. Neurology. 1990;40:1213–8. Marchetti A, Magar R, Findley L, et al. Retrospective evaluation of the dose of Dysport and BOTOX in the management of cervical dystonia and blepharospasm: the REAL DOSE study. Mov Disord. 2005;20 (8):937–44. Odergren T, Hjaltason H, Kaakkola S, et al. A double blind, randomised, parallel group study to investigate the dose equivalence of Dysport and Botox in the treatment of cervical dystonia. J Neurol Neurosurg Psychiatry. 1998;64(1):6–12. Edwards M, Quinn N, Bhatia K. Dystonia. In: Edwards M, Quinn N, Bhatia K, editors. Oxford specialist handbook: Parkinson’s disease and other movement disorders. Oxford: Oxford University Press; 2008. p. 202–7.

25.

Batla et al.

227

Allergan. BOTOX® Prescribing Information [online]. Available at: http://www.allergan.com/assets/pdf/ botox_pi.pdf 26.• Burbaud P, Ducerf C, Cugy E, et al. Botulinum toxin treatment in neurological practice: how much does it really cost? A prospective cost-effectiveness study. J Neurol. 2011;258(9):1670–5. This study has evaluated cost-effectiveness of botulinum toxins in clinics and provides a review of the financial impact of the use of BoNT in neurology practice. 27. Comella CL. The treatment of cervical dystonia with botulinum toxins. J Neural Transm. 2008;115 (4):579–83. 28. Jankovic J, Leder S, Warner D, et al. Cervical dystonia: clinical findings and associated movement disorders. Neurology. 1991;41(7):1088–91. 29. Jankovic J, Vuong KD, Ahsan J. Comparison of efficacy and immunogenicity of original versus current botulinum toxin in cervical dystonia. Neurology. 2003;60(7):1186–8. 30.•• Lawrence I, Moy R. An evaluation of neutralizing antibody induction during treatment of glabellar lines with a new US formulation of botulinum neurotoxin type A. Aesthet Surg J. 2009;29(6):S66–71. Though tested for a nondystonic condition, this study of neutralizing antibody testing in patients with the current form of toxin provides a better insight into the matter of testing neutralizing antibody. 31.•• Skogseid IM, Ramm-Pettersen J, Volkmann J, et al. Good long-term efficacy of pallidal stimulation in cervical dystonia: a prospective, observer-blinded study. Eur J Neurol. 2011. doi:10.1111/j.1468-1331. 2011.03591.x. This is a recent study assessing long-term efficacy of DBS in CD in a blinded form. 32. Kiss ZH, Doig-Beyaert K, Eliasziw M, et al. The Canadian multicentre study of deep brain stimulation for cervical dystonia. Functional and Stereotactic Section of the Canadian Neurosurgical Society; Canadian Movement Disorders Group. Brain. 2007;130(11):2879–86. 33. Pretto TE, Dalvi A, Kang UJ, et al. A prospective blinded evaluation of deep brain stimulation for the treatment of secondary dystonia and primary torticollis syndromes. J Neurosurg. 2008;109(3):405–9. 34. Hung SW, Hamani C, Lozano AM, et al. Long-term outcome of bilateral pallidal deep brain stimulation for primary cervical dystonia. Neurology. 2007;68 (6):457–9. 35.•• Cacciola F, Farah JO, Eldridge PR, et al. Bilateral deep brain stimulation for cervical dystonia: long-term outcome in a series of 10 patients. Neurosurgery. 2010;67(4):957–63. This is a study of 10 patients of bilateral DBS for CD with long-term follow-up. 36.•• Tagliati M, Krack P, Volkmann J, et al. Long-term management of DBS in dystonia: response to stimulation, adverse events, battery changes, and special considerations. Mov Disord. 2011;26(1):S54–62.

228

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This is a useful review of evidence and technical issues associated with DBS use. 37.•• Jeong SG, Lee MK, Kang JY, et al. Pallidal deep brain stimulation in primary cervical dystonia with phasic type: clinical outcome and postoperative course. J Korean Neurosurg Soc. 2009;46(4):346–50. This is a study on DBS in CD with prospective long-term measurement of response and outcome. 38. Yianni J, Green AL, McIntosh E, et al. The costs and benefits of deep brain stimulation surgery for patients with dystonia: an initial exploration. Neuromodulation. 2005;8(3):155–61. 39. Bertrand CM. Selective peripheral denervation for spasmodic torticollis: surgical technique, results, and observations in 260 cases. Surg Neurol. 1993;40 (2):96–103. 40. Chen X, Ma A, Liang J, et al. Selective denervation and resection of cervical muscles in the treatment of spasmodic torticollis: long-term follow-up results in 207 cases. Stereotact Funct Neurosurg. 2000;75(2– 3):96–102. 41. Münchau A, Palmer JD, Dressler D, et al. Prospective study of selective peripheral denervation for botulinum-toxin resistant patients with cervical dystonia. Brain. 2001;124(4):769–83. 42. National Institute for Clinical Excellence. Interventional Procedure Consultation Document Selective peripheral denervation for cervical dystonia www. nice.org.uk/nicemedia/pdf/ip/IPG080guidance.pdf. 43. Burke RE, Fahn S. Double-blind evaluation of trihexyphenidyl in dystonia. Adv Neurol. 1983;37:189– 92. 44. Jankovic J. Treatment of hyperkinetic movement disorders with tetrabenazine: a double-blind crossover study. Ann Neurol. 1982;11:41–7. 45. Gilbert GJ. The medical treatment of spasmodic torticollis. Arch Neurol. 1972;27:503–6. 46. West HH. Treatment of spasmodic torticollis with amantadine: a double blind study. Neurology. 1977;27:198–9. 47. Shaw KM, Hunter KR, Stren GM. Medical treatment of spasmodic Torticollis. Lancet. 1972;1(7765):1399. 48. Ansari KA, Webster D, Manning N. Spasmodic torticollis and L-Dopa: results of therapeutic trial in six patients. Neurology. 1972;22:672–4. 49. Myerson A, Loman J. Amphetamine sulfate in treatment of spasmodic torticollis. Arch Neurol Psychiatry. 1942;48:823–8. 50. Jantunen J, Kaste M, Iivanainen M, et al. Bromocriptine treatment of spasmodic torticollis: a double blind crossover study. Arch Neurol. 1979;36:449–50. 51. Truong D, Comella C, Fernandez HH, Dysport Benign Essential Blepharospasm Study Group, et al. Efficacy and safety of purified botulinum toxin type A (Dysport) for the treatment of benign essential

blepharospasm: a randomized, placebo-controlled, phase II trial. Parkinsonism Relat Disord. 2008;14 (5):407–14. 52.•• Jankovic J, Comella C, Hanschmann A, et al. Efficacy and safety of incobotulinumtoxinA (NT 201, Xeomin) in the treatment of blepharospasm-a randomized trial. Mov Disord. 2011;26(8):1521–8. This is a randomized control trial of Xeomin in treatment of blepharospasm, the first and largest trial of BoNT in blepharospasm. 53.•• Wabbels B, Reichel G, Fulford-Smith A, et al. Doubleblind, randomised, parallel group pilot study comparing two botulinum toxin type A products for the treatment of blepharospasm. J Neural Transm. 2011;118(2):233–9. This study compares Dysport and Botox preparations for use in blepharospasm. 54. Jankovic J, Orman J. Botulinum A toxin for cranial cervical dystonia: a double-blind, placebo-controlled study. Neurology. 1987;37:616–23. 55. Nussgens Z, Roggenkamper P. Comparison of two botulinum-toxin preparations in the treatment of essential blepharospasm. Graefes Arch Clin Exp Ophthalmol. 1997;235:197–9. 56. Sampaio C, Ferreira JJ, Simoes F, et al. DYSBOT: a single-blind, randomized parallel study to determine whether any differences can be detected in the efficacy and tolerability of two formulations of botulinum toxin type A—Dysport and Botox—assuming a ratio of 4:1. Mov Disord. 1997;12:1013–8. 57. Roggenkamper P, Jost WH, Bihari K, et al. Efficacy and safety of a new botulinum toxin type A free of complexing proteins in the treatment of blepharospasm. J Neural Transm. 2006;113:303–12. 58.• Yomtoob DE, Dewan MA, Lee MS, et al. Comparison of pain scores with 30-gauge and 32-gauge needles for periocular botulinum toxin type A injections. Ophthalmic Plast Reconstr Surg. 2009;25(5):376–7. This study assessed the impact of using a smaller needle for BoNT injection in blepharospasm. 59.• Boyle MH, McGwin Jr G, Flanagan CE, et al. High versus low concentration botulinum toxin A for benign essential blepharospasm: does dilution make a difference? Ophthalmic Plast Reconstr Surg. 2009;25 (2):81–4. This study assessed the impact of using lower concentration of toxin for BoNT injection in blepharospasm. 60.• Reese R, Gruber D, Schoenecker T, et al. Long-term clinical outcome in meige syndrome treated with internal pallidum deep brain stimulation. Mov Disord. 2011;26(4):691–8. This is a study of DBS in Meige’s syndrome that includes cases of OMD and blepharospasm. 61. Brin MF. Oromandibular dystonia: treatment of 96 patients with botulinum toxin type A. In: Jankovic J, Hallett M, editors. Therapy with Botulinum Toxin. New York: Marcel Dekker; 1994. p. 429–35.

Treatment of Focal Dystonia 62.

Blitzer A, Brin MF, Greene PE, et al. Botulinum toxin injection for the treatment of oromandibular dystonia. Ann Otol Rhinol Laryngol. 1989;98:93–7. 63. Hermanowicz N, Truong DD. Treatment of oromandibular dystonia with botulinum toxin. Laryngoscope. 1991;101:1216–8. 64. Van den Bergh P, Francart J, Mourin S, et al. Five-year experience in the treatment of focal movement disorders with low-dose Dysport botulinum toxin. Muscle Nerve. 1995;18:720–9. 65. Jankovic J, Orman J. Botulinum A toxin for cranialcervical dystonia: a double-blind, placebo-controlled study. Neurology. 1987;37:616–23. 66. Tan EK, Jankovic J. Botulinum toxin A in patients with oromandibular dystonia: long-term follow-up. Neurology. 1999;53:2102–7. 67. Bhidayasiri R, Cardoso F, Truong DD. Botulinum toxin in blepharospasm and oromandibular dystonia: comparing different botulinum toxin preparations. Eur J Neurol. 2006;13(1):21–9. 68.• Hallett M, Benecke R, Blitzer A, et al. Treatment of focal dystonias with botulinum neurotoxin. Toxicon. 2009;54(5):628–33. This is an evidence-based review of BoNT use in focal dystonia with personal recommendations from the authors. 69. Greene P, Shale H, Fahn S. Analysis of open-label trials in torsion dystonia using high dosages of anticholinergics and other drugs. Mov Disord. 1988;3:46–60. 70. Klawans HL, Tanner CM. Cholinergic pharmacology of blepharospasm with oromandibular dystonia (Meige’s syndrome). Adv Neurol. 1988;49:443–50. 71.• Ludlow CL. Spasmodic dysphonia: a laryngeal control disorder specific to speech. J Neurosci. 2011;31 (3):793–7. This is a review of clinical features and pathophysiology of spasmodic dysphonia. 72. Watts CC, Whurr R, Nye C. Botulinum toxin injections for the treatment of spasmodic dysphonia. Cochrane Database Syst Rev. 2004:CD004327. 73. Watts CR, Nye C, Whurr R. Botulinum toxin for treating spasmodic dysphonia (laryngeal dystonia): a systematic Cochrane review. Clin Rehabil. 2006;20(2):112–22. 74. Boutsen F, Cannito MP, Taylor M, et al. Botox treatment in adductor spasmodic dysphonia: a meta-analysis. J Speech Lang Hear Res. 2002;45(3):469–81. 75. Whurr R, Nye C, Lorch M. Meta-analysis of botulinum toxin treatment of spasmodic dysphonia: a re-

76.

77.

78.

79.

80.

81.

82.

83.

84.

85.

86.

87.

88.

Batla et al.

229

view of 22 studies. Int J Lang Commun Disord. 1998;33:327–9. Troung DD, Rontal M, Rolnick M, et al. Doubleblind controlled study of botulinum toxin in adductor spasmodic dysphonia. Laryngoscope. 1991;101:630–4. Wong DL, Adams SG, Irish JC, et al. Effect of neuromuscular activity on the response to botulinum toxin injections in spasmodic dysphonia. J Otolaryngol. 1995;24:209–16. Bielamowicz S, Squire S, Bidus K, et al. Assessment of posterior cricoarytenoid botulinum toxin injections in patients with abductor spasmodic dysphonia. Ann Otol Rhinol Laryngol. 2001;110:406–12. Sulica L, Blitzer A, Brin MF, et al. Botulinum toxin management of adductor spasmodic dysphonia after failed recurrent laryngeal nerve section. Ann Otol Rhinol Laryngol. 2003;112(6):499–505. Kruisdijk JJ, Koelman JH, Ongerboer de Visser BW, et al. Botulinum toxin for writer’s cramp: a randomised, placebo-controlled trial and 1-year follow-up. J Neurol Neurosurg Psychiatry. 2007;78:264–70. Yoshimura DM, Aminoff MJ, Olney RK. Botulinum toxin therapy for limb dystonias. Neurology. 1992;42:627–30. Tsui JK, Bhatt M, Calne S, Calne DB. Botulinum toxin in the treatment of writer’s cramp: a double-blind study. Neurology. 1993;43:183–5. Cole R, Hallett M, Cohen LG. Double-blind trial of botulinum toxin for treatment of focal hand dystonia. Mov Disord. 1995;10:466–71. Marion MH, Afors K, Sheehy MP. Problems of treating writer’s cramp with botulinum toxin injections: results from 10 years of experience. Rev Neurol (Paris). 2003;159:923–7. Molloy FM, Shill HA, Kaelin-Lang A, et al. Accuracy of muscle localization without EMG: implications for treatment of limb dystonia. Neurology. 2002;58:805–7. Geenen C, Consky E, Ashby P. Localizing muscles for botulinum toxin treatment of focal hand dystonia. Can J Neurol Sci. 1996;23:194–7. Chen R, Karp BI, Goldstein SR, et al. Effect of muscle activity immediately after botulinum toxin injection for writer’s cramp. Mov Disord. 1999;14:307–12. Fukaya C, Katayama Y, Kano T, et al. Thalamic deep brain stimulation for writer’s cramp. J Neurosurg. 2007;107(5):977–82.

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