Obsessive-compulsive disorder associated with brain lesions:

Obsessive-compulsive disorder associated with brain lesions: Clinical phenomenology, cognitive function, and anatomic correlates Marcelo L. Berthier, ...
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Obsessive-compulsive disorder associated with brain lesions: Clinical phenomenology, cognitive function, and anatomic correlates Marcelo L. Berthier, MD; Jaime Kulisevsky, MD; Alex Gironell, MD; and Jos6 A. Heras, MD

Article abstract-We studied the behavioral, cognitive, and neuroimaging characteristics of obsessive-compulsive disorder (OCD) in 13 patients with focal brain lesions (acquired OCD) and compared their clinical features and the severity of obsessive and compulsive (OC) symptoms with patients with idiopathic OCD. Both OCD groups were further compared with matched normal controls on a series of neuropsychological tests. Patients with acquired OCD had a negative familial history and later age a t onset of OCD symptoms than patients with idiopathic OCD. The two OCD groups showed relatively similar clinical phenomenology, severity of OC symptoms, and profile of neuropsychological deficits. Compared with normal control subjects, both OCD groups showed cognitive deficits affecting attention, intellectual function, memory, word retrieval, and motor and executive functions. Eight of the 13 patients with acquired OCD had abnormal neurologic examinations, whereas only 3 of the 13 patients with idiopathic OCD had abnormal neurologic examinations. Neuroimaging in the acquired OCD group disclosed a variety of lesions involving exclusively the cerebral cortex (frontal, temporal, or cingulate regions), the basal ganglia, or both. These results suggest that acquired and idiopathic OCDs may share a common pathophysiologic mechanism, and that structural damage to specific frontal-limbic-subcortical circuits plays an important role in the pathogenesis of acquired OCD. NEUROLOGY 1996;47:353-361

Obsessive-compulsive disorder (OCD) is a relatively frequent anxiety disorder characterized by the presence of intrusive and senseless ideas, thoughts, urges, and images (obsessions), as well as by repetitive cognitive and physical activities that are performed in a ritualistic way (compulsions), usually in an attempt to neutralize anxiety caused by an obsession.' Current neurobiological models of OCD, based on in vivo functional and structural brain imaging studies, and neuropsychological deficits implicate dysfunction of the frontal-basal-ganglia-thalamocortical (FBGTC) circuits in the pathophysiology of idiopathic OCD (I-OCD).2-4PET and single-photon emission computed tomography (SPECT) studies in selected groups of nontreated patients with IOCD documented aberrant hyperactivity within circuits involving the orbitofrontal gyrus, caudate nucleus, and anterior cingulate cortex in both left and right cerebral hemispheres (see references 5 and 6 for review). Moreover, there is abnormal hyperactivity within the FBGTC during experimental symptom provocation, and abnormal activity within these segregated neuronal circuits usually decreases after successful behavioral therapy or pharmacologic t r e a t r n e n t ~ .By ~ . ~contrast, struc-

tural MRI studies, even those performed using quantitative volumetric evaluations, reported either subtle morphologic changes (reduced or increased basal ganglia volumes) or no evidence of macroscopic brain pathology among patients with I-OCD."6 The assessment of I-OCD from a neuropsychological perspective has, in general, supported the hypothesis of frontal lobe or caudate dysf~nction.~ However, there is also other cognitive impairment affecting visuospatial and visuoconstructive functions, attention and memory, and recent nonverbal memory suggesting that other structures (i.e., temporal lobe) besides the fronto-caudate region are involved, and also that OCD may be a heterogenous condition.x Accumulating evidence also indicates that structural damage to the FBGTC circuits is implicated in the pathogenesis of acquired OCD (A-OCD) (i.e., OCD associated with neurologic disorders) (see references 5 , 9, and 10 for review). In fact, there are reports of A-OCD in association with a variety of diseases affecting the basal ganglia, such as von Economo's encephalitis, Parkinson's disease, Tourette's syndrome, Huntington's disease, Sydenham's chorea, idiopathic basal ganglia calcification,

From the Neurology Service (Drs. Berthier and Heras), Virgen de l a Victoria University Hospital, Malaga; and the Department of Neurology (Drs. Kulisevsky and Gironell), Sant Pau Hospital, University of Barcelona, Barcelona, Spain. Presented in part a t the 46th annual meeting of the American Academy of Neurology, Washington, DC, May 1994. Received October 12, 1995. Accepted in final form January 19, 1996. Address correspondence and reprint requests to Dr. Marcelo L. Berthier, Servicio de Neurologia, Hospital Universitario Virgen de la Victoria, Campus Universitario Teatinos-Apartado 3091 (29010), Malaga, Espana. Copyright 0 1996 by the American Academy of Neurology


and striatal necrosis. Moreover, A-OCD may also occur after restricted cortical damage associated with neoplastic and traumatic lesions, as well as degenerative dementing illness affecting predominantly the lateral orbitofrontal and anterior cingulate circ ~ i t s . ~Finally, ~ ~ J ~ ’OCD may occur in association with complex partial seizures originating in the tempora]ll-13 and frontal14 cortices or in the anterior cingulate gyrus.15 Almost all studies that have examined the clinical profile and neuropsychological function of patients with OCD and brain lesions have been in individual patients o r in small series lacking control groups. Moreover, there are no studies comparing the frequency and clinical features of obsessive and compulsive (OC) symptoms of patients with brain lesions with those of patients without a known neurologic disease. In the present study, we examined the clinical phenomenology, cognitive function, and anatomic correlates of OCD in a consecutive series of patients with focal brain lesions. Methods. Patient selection. A-OCD group. The sample consisted of 13 patients who were consecutively referred to the Neurology Service of the Virgen de la Victoria University Hospital (Malaga, Spain) and the Department of Neurology of the Sant Pau Hospital (Barcelona, Spain) during the period between July 1991 and July 1994 with a diagnosis of OCD and a brain lesion. The lack of a known temporal relationship of brain lesion to OCD onset was not considered a n exclusionary criterion. Controls. For the present study two control groups were recruited. (1)I-OCD group. This group consisted of a consecutive series of 25 outpatients with a diagnosis of I-OCD. Patients were considered to have a n I-OCD when they showed a normal MRI of the head and lacked major medical or neurologic disorders. The presence of Axis I comorbid DSM-IV diagnoses (i.e., depression, non-OCD anxiety) was not considered an exclusionary criterion. The whole I-OCD group participated in the phenomenologic comparison of OC symptoms, whereas only 13 patients could be adequately matched with appropriate patients of the AOCD group to compare the results of OC symptom severity, comorbid psychopathology, and neuropsychological testing. (2) Normal control group. This group consisted of 13 healthy individuals recruited from hospital staff according to recent proposed criteria for normal volunteers.16 Once we excluded the presence of psychopathology or major medical illness, the group of normal control (NC) subjects underwent neuropsychological testing. The NC group and patients of both A-OCD and I-OCD groups were matched on the basis of age, sex, and education. Neurologic evaluation. All patients received a complete neurologic examination carried out by a neurologist who was unaware if the patient had either A-OCD or IOCD. Motor performance was assessed with the Finger Tapping Test.I7 Psychiatric evaluation. Psychiatric diagnoses were established by using the Structured Clinical Interview for DSM-111-R: Patient Version (SCID-P).IRAccording to 354

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DSM-IV criteria,’ OCD was defined by the presence of obsessions and compulsions that had caused marked distress or had interfered with the patient’s normal routine for at least a 2-year period. The clinical characteristics and severity of OC symptoms were further assessed by using the following rating- scales: - psychiatric _Yale-Brown Obsessive-Compulsive Scale (YBOCS).19,2nThe Y-BOCS is a clinician-rated scale that contains two components: (a) a symptom checklist designed to elicit past and current obsessions (n = 40) and compulsions (n = 29) organized in 15 categories according to their thematic content (i.e., aggressive obsessions, counting compulsions) and (b) a severity scale composed of 5 items for obsessions and 5 items for compulsions. Each item is rated from 0 (no symptoms) to 4 (extreme symptoms). In the present study, the severity of OCD was measured with the Y-BOCS. A total score >16 indicates clinically significant OCD. Leyton Obsessional Inventory (LOI).21 The LO1 is a self-rated scale that quantifies the range of obsessional thoughts and compulsive behaviors. It contains 69 “yes/no” questions dealing with the subjective assessment of obsessional symptoms (questions 1 to 46) and traits (questions 47 to 69) as well as the degree of “resistence” to symptoms and “interference” with the patient’s life. Since the resistence and interference scales are time-consuming, these measurements were not administered, and the severity of OC symptoms was assessed only with the Y-BOCS. Slowness Questionnaire (SQ).22 The SQ is a self-rated scale that contains a list of 20 common activities of daily living (i.e., dressing). Patients are asked to rate the speed of their own performance on each of these activities in comparison with a healthy person. The maximum possible score is 60, and scores >30 indicate a clinically significant slowness. Phenomenologic comparison of obsessive and compulsiur. symptoms. A phenomenologic comparison of OC symptoms between patients with A-OCD (n = 13) and those with I-OCD (n = 25) was also performed. The subheadings of obsession and compulsion checklists of the Y-BOCS”’ were used to organize seven categories of obsessions (aggressive, contamination, sexual, hoarding, religious/moral, symmetry, and somatic) and six of compulsions (cleaning/ washing, checking, repeating, counting, arranging, and hoarding). The categories of miscellaneous obsessions (i.e., intrusive images) and miscellaneous compulsions (i.e., ritualized eating behaviors) were not analyzed since they contain some symptoms not strictly classified under the diagnosis of OCD. Associated psychopathology. The severity of depressive symptoms was assessed using the 17-item Hamilton Depression Rating Scale.z3The 10-item Tyrer’s Brief Scale for Anxietyz4was used to measure anxiety symptoms. Neuropsychological evaluation. The two patient groups (A-OCD and I-OCD) and the NC group were examined with a battery of neuropsychological tests especially selected to cover a wide range of cognitive deficits previously reported among patients with OCD (see reference 7 for review). This neuropsychological battery included tests of general intelligence (Wechsler Adult Intelligence Scale [WAISl),25attention span (WAIS digit-span),l” verbal and nonverbal memory (Wechsler Memory Scale [WMS J ),Lfi word retrieval (Boston Naming Test [BNT]),27verbal flu-

Table 1 Demographic characteristics and scores on psychiatric rating scales of groups with acquired and idiopathic obsessiuecompulsive disorder and normal control subjects Item

Acquired OCD (N = 13)

Idiopathic OCD (N = 13)

Normal controls ( N = 13)

Sex (WF)( % males)

914 (63)

518 (38)

518 (38)

35.9 2 10.7

34.5 t 8.4


10.6 t 3.0

11.3 ir 2.8

12.2 2 2.9

Age (mean 2 SD) Education (years) (mean



Family history of OCD (% positive) Age a t onset of OCD (mean t SD; years)

7.65 25




61 9.7$

15.2 f 8.9

Y-BOCS (mean 5 SD) Obsessions

10.7 f 3.6

11.3 2 2.9


11.3 2 2.8

12.5 2 2.4


22.1 ir 5.2

23.5 2 4.7


26.1 t 9.1

30.3 ? 8.3


12.3 ? 4.4

14.3 2 6.6

LO1 (mean ir SD)

SQ (mean


11.2 f 17.3

7.1 2 6.6

HDRS (mean z SD)

9.7 2 4.4

14.5 rt 3.9t

TBSA (mean t SD)

16.0 -C 5.0

19.7 rt 5.5“



< 0.05 (Mann-Whitney U test, two-tailed).

i p < 0.01 (Mann-Whitney U test, two-tailed). $ p < 0.001 (Mann-Whitney U test, two-tailed). S p < 0.005 (Fisher’s exact test). Y-BOCS = Yale-Brown Obsessive-Compulsive Scale; LO1 = Leyton Obsessional Inventory; SQ Hamilton Depression Rating Scale; TBSA = Tyrer’s Brief Scale for Anxiety.

ency (Controlled Oral Word Association Task [COWAT]),28 visuospatial function (WAIS: block design)25and cognitive set-shifting abilities (Trail Making Test, Parts A & B [TMT-A, TMT-B1),17 the Money’s Road Map Test (MRMT),29and the Wisconsin Card Sorting Test (WCST).30 MRIprocedure. After giving informed consent, an MRI was obtained in every patient. Among the A-OCD group, seven MRIs were performed at 0.5 tesla and six a t 1.5tesla (Signa scanner, General Electric Medical Systems, Milwaukee, WI). The same MRI units were used to scan patients of the I-OCD group. All studies were carried out using the same protocol. A midsagittal pilot cut was made to position the axial slices, and on the basis of this midsagittal image, a line extending from the anterior commissure to the posterior commissure was traced as the axial reference plane. Sagittal TI-weighted images (5-mm thick, 2-mm gap; 400-700/13-22 [TWTE]), axial proton density and T,-weighted images (5-mm thick, 2-mm gap; 2,0003,000/100-95 [TR/TE]), and TI-weighted coronal images (400/13) were obtained. In patients with presumed neoplastic lesions or vascular malformations, gadolinium (GdDTPA) contrast enhancement was used. All MRIs were evaluated by one investigator, who was unaware of the clinical assessments, for the presence of focal structural abnormalities, ventricular size, and extracerebral space. MRIs were not performed in the NC group. Statistical analysis. Statistical data are expressed as means ? standard deviations. Categorical data were analyzed by x2 or tables of contingency (Fisher’s exact test). Between-group comparisons (A-OCD versus I-OCD) of scores on psychiatric rating scales were tested with the


Slowness Questionnaire; HDRS


Mann-Whitney U test. Group-specific differences on neuropsychological measures were tested using a one-way analysis of variance (ANOVA), and post hoc Newman-Keuls analyses were performed for differences between the three groups. Probability values reported are two-tailed with significance stipulated as p < 0.05.

Results. Demographic findings. Demographic information on all three groups and scores of psychiatric rating scales for both OCD groups are shown in table 1. There were no statistically significant differences in sex ( x 2 3.2, df = 2, p = NS), age (F = 0.11, df = 2, p = NS) or years of education (F = 0.88, df = 2, p = NS). Patients in the A-OCD group had a significantly less frequent positive familial history and later onset of OC symptoms than those of the I-OCD group. OC symptom severity. Eleven of the 13 patients in the A-OCD group had scores on the Y-BOCS that reached the cutoff score of 16 points or higher for clinically significant OCD.19.2n Two patients (patients 1 and 2) had total scores on the Y-BOCS below 16, but high scores in the LO1 (patient l: symptoms score = 24; patient 2: symptoms score = 24). According to recent research on OCD, both patients could be classified as having an “ego-syntonic” variant of OCD.1,31On the Y-BOCS there were no significant differences between the A-OCD and I-OCD groups in symptom severity, and both groups showed similar mean scores on symptoms and traits subscales of the LO1 as well as on the degree of obsessional slowness (SQ)(see table 1). However, patients with I-OCD had significantly higher scores on August 1996 NEUROLOGY 47 355

Table 2 Phenomenologic comparison of symptom categories in patients with acquired and idiopathic obsessive-compulsive

disorder Acquired

Idiopathic OCD (N = 25)

OCD (N = 13) ~

Symptom categories






”/o ~



Obsessions Aggressive





Con tamination





Sexual Hoardinghaving Religious (scrupulosity) Symmetry/exactness Somatic































Repeating Counting



















15 ~


p < 0.05 (Mann-Whitney U test). :‘p < 0.01 (Mann-WhitneyU test). $ p < 0.0005 (Mann-WhitneyU test). :+

rating scales of depression and anxiety than patients of the A-OCD POUP. Clinical features of OCD. In the two OCD groups, all patients had mixed obsessions and compulsions. Of the seven types of obsessions, the I-OCD group had a significantly higher mean number of obsessions than the A-OCD group (4.2 i 1.3 versus 3.0 i 1.4,p < 0.05, Mann-Whitney U test). Of the six types of compulsions, the I-OCD group had a mean number of compulsive behaviors similar to the A-OCD group (3.6 +- 1.3 versus 3.0 2 1.4; p < NS, MannWhitney U test). The frequency of OC symptoms according to categories derived from the Y-BOCS is shown in table 2. There were no significant between-group differences in most symptom categories. The I-OCD group, however, had more frequent hoarding and somatic obsessions, as well as ordering1 arranging and hoardinghaving compulsions compared with the A-OCD group. Neurologic findings, etiology, and neuroimaging correlates. Five of the 13 patients (38%) (nos. 3, 5, 6, 7, and 8) with A-OCD had motor or phonic tics, or both. Four of them (patients 3, 6, 7, and 8 ) had multiple motor and phonic tics that waxed and waned in severity, were suppressible under voluntary control, and began during late adolescence or early adulthood. Two of these patients (nos. 6 and 7 ) had neurologic “soft” signs of the right hand. Of the four patients with motor and phonic tics, three had developmental lesions: patient 3 had a pericallosum lipoma compressing the posterior cingulate gyrus and moderate lateral ventricular dilation bilaterally and patients 6 and 7 had arachnoid cysts involving both temporal lobes 5.56 NEUROLOGY 47

August 1996

(patient 6) or only the left anterior temporal lobe (patient 7). The remaining patient (patient 8 ) with motor and phonic tics had post-encephalitic hydrocephalus and small left frontal subcortical lesions. The patient with simple motor tics (patient 5 ) had a small gliotic focus involving the left caudate nucleus and its adjacent periventricular white matter. Four patients (31%) had traumatic brain injuries (TBIs). Two of these patients (nos. 9 and 10) had chronic cranial nerve palsies (patient 10 additionally had stereotyped right hand movements) that resulted from cerebral contusions involving the orbitofrontal cortices bilaterally (patient 9) or the left orbitofrontal and mesial temporal cortices and the white matter anterolateral to the head of the left caudate nucleus (patient 10). The remaining two patients with TBIs had normal neurologic examinations. In one of these patients (no. 111, the MRI showed a small contusion in the left anterior cingulate gyrus associated with bilateral frontotemporal and left caudate atrophy, whereas in the other patient (no. 12), the MRI disclosed laminar bifrontal hygromas and left caudate atrophy. Three patients (23%) had epilepsy. Two patients had temporal lobe epilepsy. One of these two patients (no. 2 ) had impaired tactile form recognition for the right hand in association with a small cavernous angioma that involved the left hippocampus and amygdala, whereas the other patient (no. 1)with a hamartoma of the right mesial temporal lobe (amygdala, hippocampus, and parahippocampal gyrus) had a normal neurologic examination. The remaining patient (no. 4) with tuberous sclerosis and frontalcingulate epilepsy secondary to a calcified tuber in the right anterior cingulate gyrus had normal neurologic examination. Finally, one patient (8%)(patient 13) with a small ischemic infarction involving the right posterior putamen had a normal neurologic examination. In summary, although 8 of the 13 patients (61%) with A-OCD had abnormal neurologic examinations, in the I-OCD group abnormal neurologic examinations were found only in 3 of the 13 patients (23%) ( p < 0.04, Fisher’s exact test). Of these three patients, two had left-sided neurologic soft signs, and the remaining patient had simple motor tics. (Additional details on clinical, etiologic, and neuroimaging data are filed with NAPS as table 3. See NAPS note at end of text.) Neuropsychological findings. On neuropsychological testing there were no statistically significant differences between the A-OCD and I-OCD groups in most measures of cognitive performance. In fact, patients with A-OCD had significantly lower scores than patients of the I-OCD group only in finger tapping for the right hand. Newman-Keuls post hoc comparisons showed significant differences between both the A-OCD and I-OCD groups compared with the NC group in verbal and performance I& scores, memory quotient, logical memory, and digit-span (forward) subtests of the WMS, COWAT, and MRMT. Patients with A-OCD also did worse than the NC subjects on digit-span (backward) and visual reproduction subtests of the WMS, BNT, WCST, and TMT-A and TMT-B. (Means and standard deviations of these three groups on neuropsychological testing are filed with NAPS as table 4. See NAPS note a t end of text.) However, since the NC group’s average level of intellectual functioning may be inflated relative to both the OCD groups due to the inclusion of some subjects

Figure 1. (Patient 1) Postenhancement (Gd-DTPA) T I weighted views (TRITE 630f20) sagittal and coronal MRI views showing a tumor (surgically confirmed hamartoma) involving the right parahippocampal gyrus.

with greatly discrepant mean values, statistical comparisons were reanalyzed excluding three subjects. After removing these cases, statistical differences between the AOCD and NC groups remained highly significant in all but one (TMT-A) cognitive test. On the other hand, statistical differences between the I-OCD and the NC groups remained highly significant only for verbal I& score ( p < 0.051, logical memory subtest of the WMS ( p < 0.051, and MRMT ( p < 0.01). In addition, since group data may mask important individual differences, analyses of individual test scores were performed. Performance was considered abnormal when an individual score fell below the normal range established in normative data.32 In the A-OCD group, four patients (39%)had decreased verbal I& scores, and two (15%)had decreased performance I& scores. Eleven patients (85%) had WMS quotient scores below the normal range. Eight patients (61%)had impaired word retrieval on the BNT and four patients on the COWAT. Ten patients (77%) did poorly in the TMT-B and six patients (46%)in the TMT-A. Eight patients (61%)had poor performance on the WCST, seven patients (54%)on the MRMT. In the I-OCD group, four patients (30%) had decreased verbal I& scores, whereas all patients had performance I& scores ranging from average to superior. On the WMS, five patients (38%) had decreased quotient scores. Three patients had reduced word retrieval on the BNT and two patients (15%)on the COWAT. Five patients (38%) did poorly on the WCST, seven patients (54%)on the TMT-B, eight patients (61%) on the TMT-A, and five patients (38%)on the MRMT. In the NC group, all subjects obtained normal IQs, with scores ranging from average to superior, and only one subject had a WMS quotient score below average. All subjects obtained normal scores on the MRMT and BNT, and 12 subjects (92%)on the WCST and COWAT. Three subjects (23%)had a below-average performance on the TMT-A and two subjects (15%)on the TMT-B. MRI findings. Five of the 13 patients (38%)had spaceoccupying lesions (tumors, arachnoid cysts) (figures 1 and 2), 4 patients (31%)had traumatic lesions (figure 31, and another 4 patients (31%)had other etiologies (encephalitis, gliosis, infarct, and vascular malformation). Six patients (46%)had bilateral lesions (with greater left- than righthemisphere involvement), five patients (38%)had unilateral left-hemisphere lesions, and the remaining two patients (15%) had unilateral right-hemisphere lesions. Seven patients (54%)had single lesions, whereas multiple

lesions were documented in six patients (46%).The anterior or mesial temporal lobe (temporopolar, hippocampus, amygdala, and parahippocampal gyrus) was involved in five patients (nos. 1, 2, 6, 7, and 8), the dorsolateral prefrontal cortex region (including its immediate subcortical white matter) was involved in three patients (nos. 4, 8, and ll), the anterior cingulate cortex region was involved in two patients (nos. 4 and 111, whereas the posterior cingulate cortex was involved in another patient (no. 31, the lateral orbital cortex region was involved in two patients (nos. 9 and lo), the caudate nucleus was involved in three patients (nos. 5, 11, and 121, and the putamen in one patient (no. 13). Four patients (nos. 3, 8, 11, and 12) had radiologic evidence of lateral ventricular enlargement.

Discussion. There were several important findings in this study of A-OCD. First, all but one of the patients with A-OCD had a negative familial history of OCD, and this group showed a later age of onset of OC symptoms than patients with I-OCD. Second, comparison of different types of obsessions and com-

Figure 2. (Patient 6) Proton density weighted axial MRI (TRITE 2,000f25) showing bilateral temporal arachnoid cysts. August 1996 NEUROLOGY 47 357

Figure 3. (Patient 10) T,-weighted (TRITE 2,000/100) axial MRI views showing multiple left-hemisphere contusions involving the anterior temporal lobe, the orbital frontal cortex, and the head of the caudate nucleus (arrows).

pulsions between the A-OCD and I-OCD groups revealed a considerable phenomenologic overlap. Third, both OCD groups showed a relatively similar pattern of neuropsychological deficits affecting attention, intelligence, memory, language, and executive functions. Fourth, several patients with A-OCD lacked focal “localizing” neurologic signs, but a subgroup had A-OCD associated with chronic motor and phonic tics. Fifth, A-OCD was variously associated with TBI, symptomatic temporal or frontal-cingulate epilepsy (i.e., tumors, congenital malformations, and vascular lesions). Finally, structural abnormalities on MRIs involved exclusively temporal, frontal, and cingulate cortices and basal-ganglia structures. The presence of negative familial history for OCD in the A-OCD group is consistent with previous single case studies of OCD associated with focal brain lesion^,^"^^ and also parallels the low family burden reported in other types of psychopathology acquired after brain injury such as affective disorder^,^^.^^ anxiety,40 and schizophrenia-like p s y ~ h o s i s .Although ~~ our A-OCD group had a later age at onset of symptoms than the I-OCD group, the average age a t onset of OC symptoms of the former was similar to clinical and epidemiologic studies of large groups of patients with I-OCD.31342,43 Moreover, the age a t onset of AOCD may depend upon the etiology of the brain lesion (i.e., early-onset in developmental lesions versus late-onset in cerebrovascular disease and dementia). We were unable to test this hypothesis because of the limited number of patients in our A-OCD group. Although patients with I-OCD were more depressed and anxious than patients with A-OCD, both groups showed the same severity of symptoms in the Y-BOCS and similar scores on other OC rating scales (LO1 and SQ). We found clinical phenomenologic similarities of OC symptoms between the A-OCD and I-OCD groups. Both groups showed a high frequency of aggressive, contamination, and need for symmetry and precision obsessions as well as washinglcleaning, checking, repeating, and ordering rituals-a profile of clinical subtypes and frequency documented in previous studies of idiopathic OCD.”1.42*44” Distinctive features of OC symptoms in these two groups were also documented and included a higher frequency in the I-OCD group of hoarding/ saving and somatic obsessions, and counting and hoarding compulsions relative to the A-OCD group. 368 NEUROLOGY 47 August 1996

However, in the I-OCD group these OC categories were never described as the target symptoms, and some of these OC symptoms (i.e., somatic obsessions) may reflect comorbid psychopathology (i.e., hypochondriasis, body dysmorphic disorder) usually associated with I-OCD,44rather than being integral components of the syndrome. Thus, the clinical features of OC symptoms among our patients with focal brain lesions is similar to the pattern of I-OCD. Nonetheless, given the small number of patients in the AOCD group, this phenomenologic comparison of specific OC behaviors should be viewed as preliminary and requires replication with larger sample sizes. The pattern of neuropsychological deficits in both OCD groups was relatively similar, although patients with A-OCD had a significant reduction in finger dexterity for the right hand as compared with the I-OCD group. However, the presence of significantly higher scores on depression and anxiety rating scales in the I-OCD group relative to the A-OCD group might have worsened the performance on various tasks in the former group, attenuating potential between-group differences. Therefore, future studies comparing the neuropsychological performance between A-OCD and I-OCD populations may examine patients matched for the severity of comorbid depression and anxiety. The two OCD groups differed significantly from the group of NC subjects in IQ scores, memory quotient scores of the WMS, recent verbal memory, verbal attention-span, verbal fluency, spatial shifting, and finger tapping for both hands. In addition, patients with A-OCD did worse than the NC subjects on other frontal lobe tests (WCST, TMT) as well as on word retrieval and recent nonverbal memory. Overall, this pattern of results suggests that our patients with A-OCD and I-OCD had bilateral hemispheric dysfunction. Neuropsychological findings in our A-OCD group are difficult to compare with the few previous studies of A-OCD reported to date because of methodologic differences. Although our AOCD group is heterogenous regarding etiology and lesion location, in other studies of A-OCD, the samples were selected on the basis of well-defined clinical disorders (i.e., Parkinson’s disease)45or similar lesion locations (i.e., anoxic-ischemic pallidal necroS ~ S ) In . ~ spite ~ of these methodologic issues, the findings of our study parallel to some extent the results

of a previous study of OCD associated with focal might share similar functional mechanisms. Finally, brain lesions. Laplane et al.:34performed neuropsyanother patient developed a severe OCD in associachologic studies in seven patients with OCD assocition with a very small ischemic infarction restricted ated with bilateral necrosis of the globus pallidus to the right putamen. This clinico-radiologic correla(some patients also had decreased orbitofrontal metion was reported in two OCD patients with pretabolism on PET). These authors found reduced atsumed anoxic-ischemic perinatal i n j ~ r i e s . ~ ~ , ~ ~ tention and verbal fluency for letters, impaired perAnother finding in the present study was that in 5 formance on the WCST and visuoconstructive tasks, of the 13 patients of the A-OCD group, OC symptoms and a decline of general intelligence and memory coexisted with a chronic tic disorder (motor or was documented in some cases. A similar profile of phonic) that started during adolescence or early cognitive impairment was present in single case adulthood and were associated with developmental studies of A-OCD.33,95.37,4&47 or early acquired lesions. Three patients (nos. 3, 6, In our study, eight (61%) of the 13 patients with and 7) fulfilled DSM-IV criteria for Tourette's synA-OCD had either normal examinations (5 patients) drome (TS), with the exception of tics associated with or abnormal examinations without localizing neurogross brain damage (Tourettism). One of the remainlogic signs (3 patients). Four of these patients had ing two patients with tics had motor tics, whereas TBIs involving mainly the orbitofrontal, anterior cinthe other patient had both chronic motor and phonic gulate gyrus, anterior temporal cortex, and head of tics that started after the age of 18 years. In only one the caudate nucleus. Although OCD after TBI has of these five cases (patient 8, who had suffered an mainly been reported after minor t r a ~ m a ,Max ~ ~ et , ~ ~ encephalitis during his childhood) was there a positive history for both TS and OCD in first-degree relal.48reported OCD and impulsive aggression in an atives. Among the remaining A-OCD patients with adolescent after extensive contusions that involved tics but negative family history for OCD or TS, lesion the frontotemporal cortex bilaterally and the right location and etiology vaned considerably. Patient 5 anterior cingulate gyrus, but spared the basal ganhad a small focal lesion in the left caudate nucleus glia. MRI findings in our four traumatic cases not that probably induced OCD by interrupting the doronly replicate the finding of cortical damage, but adsolateral prefrontal and lateral orbitofrontal cirditionally suggest that lesions in the basal ganglia c u i t ~ Patient .~ 3 had a pericallosum lipoma com(i.e., caudate nucleus) may be important in the pressing the posterior cingulate cortex. Although the pathogenesis of OCD associated with TBI. posterior cingulate gyrus has not been traditionally Three patients developed OCD several years after implicated in the pathogenesis of OCD, a recent PET the onset of complex partial seizures that originated study reported marked activation of the posterior within either the temporal or frontal lobes. These cingulate cortex during experimental OC symptom clinico-anatomic associations were reported among provocation.6 The remaining two cases (patients 6 epileptic patients with either no obvious brain paand 7) had perisylvian arachnoid cysts. These lesions thology,"J2 hippocampal ~clerosis,'~ or frontal lobe did not involve major components of the lateral ortumors and strokes.14 Our two patients with tempobital and anterior cingulate circuits previously reral lobe epilepsy (patients 1 and 2) and MRI evidence to the pathophysiology of OCD, but afferents to lated of focal lesions involving the hippocampus, amygthese circuits from the temporopolar region, anterior dala, and parahippocampal gyrus may have developed OC symptoms as a result of disrupted connec- insula, and opercular and inferior frontal regions4J1 were clearly damaged in these two cases. In addition, tivity between the amygdala-hippocampus region recent evidence with PET demonstrated that anteand the ventral striatum. However, since both parior perisylvian arachnoid cysts may induce remote tients did poorly on frontal lobe tasks (i.e., WCST) metabolic changes in structurally undamaged frontal besides the expected impaired functioning in temponeocortical paralimbic areas normally involved in ral lobe tests, the mesial temporal epileptic focus emotional processing and executive functions.52 may also have induced long-term changes in pathIn conclusion, our preliminary findings suggest ways linking the hippocampal formation and parasimilarities in clinical phenomenology and a pattern hippocampal cortex with the dorsolateral prefrontal of cognitive impairment between patients with acand orbitofrontal c o r t i c e ~ .The ~ ~ ,patient ~~ with tuberquired or idiopathic OCD. Moreover, our findings ous sclerosis and frontal-cingulate epilepsy (patient also support the notion that single or multiple le4)had palilalia followed by generalized seizures and sions of the FBGTC circuits, whether cortical or subMRI evidence of bilateral prefrontal cortex atrophy cortical, may produce similar behavioral and cogniand a calcified intracortical nodule involving the tive deficit^.^ right anterior cingulate cortex. This patient showed abnormal performance on tests susceptible to frontal Note. Readers can obtain 8 pages of supplementary material from lobe dysfunction such as the TMT-B and MRMT, but the National Auxiliary Publications Service, c/o Microfiche Publialso did poorly on memory tasks (WMS quotient cations, P.O. Box 3513, Grand Central Station, New York, NY 10163-3513. Remit with your order (not under separate cover), in score: 79) dependent upon the integrity of the tempoUS funds only, $7.75 for photocopies or $4.00 for microfiche. Outral lobes. Therefore, these findings raise the possibilside the United States and Canada, add postage of $4.50 for the ity that OCD associated with complex partial seifirst 20 pages and $1.00 for each 10 pages of material thereafter, or $1.75 for the first microfiche and $.50 for each fiche thereafter. zures of either temporal or frontal-cingulate origin August 1996 NEUROLOGY 47 359

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Acknowledgments The authors thank Ruth Stoner for review of the manuscript and Salvador Barea for photographic assistance.

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A comparison of subcutaneous sumatriptan and dihydroergotamine nasal spray in the acute treatment of migraine J. Touchon, MD, PhD; L. Bertin, MD; A.J. Pilgrim, BM, DPhil; E. Ashford, BSc; and A. Bes, MD, PhD

Article abstract-We compared the efficacy and safety of subcutaneous (SC) sumatriptan (6 mg) with that of dihydroergotamine (DHE) nasal spray (1 mg plus optional 1 mg) in the acute treatment of migraine. Two hundred sixty-six adult migraineurs (International Headache Society criteria) completed a multicenter, double-blind, double-dummy, cross-over study. Patients took SC sumatriptan for one attack and DHE nasal spray for the other in random order. Data from both treatment periods show that a t all time points from 15 minutes, SC sumatriptan was significantly better than DHE nasal spray at providing both headache relief (moderatehevere headache improving to mildnone) and resolution of headache. Similarly, SC sumatriptan was superior to DHE nasal spray for the other efficacy end points assessed in the study. Patients reported that both treatments were well tolerated. Adverse events were reported by 43% of patients taking SC sumatriptan and 22% of patients taking DHE nasal spray. These were usually mild and transient. We conclude that subcutaneous sumatriptan has a faster onset of action than DHE nasal spray and provides greater relief of acute migraine symptoms. NEUROLOGY 1996;47:361-365

Over five trials of 6 mg SC sumatriptan, 70 to 77% of Dihydroergotamine (DHE) in its intranasal, subcutapatients reported headache relief (placebo response neous (SC), IM, or IV formulations is used as an 22 to 26%) and 37 to 49%were headache-free 1hour acute treatment for migraine and cluster headache after dosing (placebo response 3 to 9%). Symptom in many countries. DHE has a high affinity for the relief continued t o improve up to 2 hours, when 70 to serotonin 5-HT, receptor and also acts as an agonist 90% of patients reported headache relief (placebo reat a variety of other receptors, including 5-HT2, dosponse 21 to 37%) and 59 to 70% were headache-free pamine, and other catecholamine receptors.’ Eight (placebo response 3 to 18%).15 publications report on the efficacy and safety of DHE DHE nasal spray is the formulation of this drug nasal spray in placebo-controlled s t u d i e ~ . ~ These -~ used for the acute treatment of migraine that is most studies used multiple end points and variable methreadily self-administered by patients at home. For this odologies, making the data difficult to evaluate. Most reason, and because of its reported effica~y,”~ this forwere performed before the International Headache mulation of DHE is widely used. There are no good Society (IHS) guidelines for controlled trials of drugs data comparing DHE nasal spray and sumatriptan rein migrainelo and diagnostic criteria for migraine” ported in the literature.16 We present the first rigorwere published. ously designed randomized double-blind trial allowing Sumatriptan, a selective 5-HT, receptor agonist a direct comparison of the efficacy and tolerability of that is effective in the treatment of migraine and SC sumatriptan and DHE nasal spray. cluster headache attacks, has been assessed in clinical trials involving over 12,000 patients with over Methods. Patients. Men and women aged between 18 72,000 migraine and cluster headache a t t a c k ~ . ~ ~ -and l ~ 65 years were included in the study if they had at From the Department of Neurology (Pr. Touchon), HBpital Arnaud de Villeneuve, Montpellier, France; GlaxoWellcome Research and Development Limited (Dr. Pilgrim, Ms. Ashford, Dr. Bertin), Greenford, U K and the Department of Neurology (Pr. Bes), CHU Rangueil, Toulouse, France. Received May 12, 1995. Accepted in final form February 14,1996. Address correspondence and reprint requests to Dr. L. Bertin, Glaxo Wellcome Research and Development Limited, Greenford Road, Greenford, Middlesex UB6 OHE, UK. Copyright 0 1996 by the American Academy of Neurology 361

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