Movement Disorders Vol. 15, No. 2, 2000, pp. 335–359 © 2000 Movement Disorder Society Clinical/Scientific Notes Schwab & England scale (for example, composite, on/off, or best/worst). Results were mixed, suggesting there is little uniformity in the way the Schwab & England scale is scored. This may be because various research protocols require different scoring methods, or it may also be the result of training, preference, or scoring norms established at a variety of settings. It is important to determine which method most clearly reflects the patients’ functional status to produce the most accurate results and to maximize the use of the instrument. Results of the survey on the use of the Schwab & England scale indicated that a number of health professionals in some offices reportedly assist with the administration of the Schwab & England scale. With several people participating in this fundamental assessment, there is danger of lack of consistency, which may be a problem for research reliability. To determine the uniformity of measurement among office staff, clinicians might check periodically the reliability of measurement between raters by having all staff look at several patients together. Scores could be compared and understanding clarified about distinction between levels on the scale. Video teaching tapes are another useful tool to ensure standardization and reliability. Schwab & England: Standardization of Administration One of the problems in the assessment of Parkinson’s disease (PD) has been the establishment of reliable and valid measures.1–6 A review of the literature suggests that instruments were sometimes developed for specific situations or purposes and, by default, became widely used over time. This appears to be the case with the Schwab & England scale.7 This instrument has become a standard assessment tool in PD and has been used and cited in hundreds of research studies and publications. However, the original properties of the measure were never established.8 In addition to the need for acceptable psychometric properties, it is also important for scales to be used consistently.3,4 Interrater reliability is especially important in multicenter clinical trials of new treatments. Statistical analyses are often conducted on evaluations performed by several examiners. Thus, it is critical to establish the degree to which the tests are performed uniformly and results are interpreted consistently. If raters are not using the measures in the same way, results of the study may be misleading or erroneous. The purpose of this study was to examine the uniformity with which the Schwab & England scale administered among a number of neurologists. A brief letter and survey consisting of three questions were faxed to 66 neurologists across the United States. This sample was drawn from the total of 137 neurologists participating in the Parkinson Study Group. This group was selected because of their demonstrated involvement in research, probable interest in the study, and familiarity with the scales. Sixty-three (94%) responses were received. This high return rate for the surveys ensures a representative response from this group. Items on the questionnaire sent to neurologists and responses to the items are shown in Table 1. The first question was, “When the Schwab & England is administered in your office, it is done by . . .” Results indicated that a variety of individuals assist in the administration of the Schwab & England scale, which raises the question of uniformity and reliability of measurement. The second question neurologists were asked was, “When the Schwab & England is administered, do you determine the score without looking at the scale, or have the scale in front of you to check the possible responses?” The majority of respondents (n 4 55 [90%]) reported having the scale at hand. Only five physicians reported using a “gestalt” approach. An additional respondent indicated that he or she used both methods and two neurologists did not respond to the question. The final question asked about the scoring method used on the TABLE 1. Questionnaire sent to neurologists examining the uniformity with which the Schwab & England scale is administered Please check your responses to the following questions: 1. When the Schwab & England is administered in your office, it is done by: (check all that apply) No. (%) Physician only 24 (38) Physician and “others” 30 (48) “Others”: Nurse 23 (–) Physician’s assistant 3 (–) Fellow 1 (–) Study coordinator 3 (–) Caregiver/spouse 2 (–) Patient 11 (–) Nurse only 7 (11) Research coordinator only 2 (3) 2. When the Schwab & England is administered, do you (or the person who administers it): No. (%) Determine score without looking at the scale 5 (8) Have the scale in front of you to check the possible responses 55 (90) Both 1 (2) 3. In your office, what score do you use for the Schwab & England? Composite (one overall rating) On/off rating (one score for “on” and one score for “off”) Best/worst rating (one score for “at best” and one score for “at worst”) Combination Received February 24, 1999; revision received September 16, 1999. Accepted January 5, 2000. Address correspondence and reprint requests to Cynthia McRae, PhD, College of Education, University of Denver, Denver, CO 80208, U.S.A. 335 No. (%) 25 (39) 23 (37) 5 (8) 10 (16) 336 CLINICAL/SCIENTIFIC NOTES With a variety of scoring methods used for the Schwab & England scale, it is important to determine if one method depicts patients more accurately than another. The standard administration of the Schwab & England scale for many years was to derive a composite score, or “global” assessment, of the patient’s functioning. Ratings at “on” and “off” times were later included to describe patients who experience fluctuation because of medication effects. To define the outer limits of functioning, the United Parkinson’s Disease Rating Scale9 currently uses the categories of “best” and “worst.” Future research should examine these methods both quantitatively and qualitatively to determine which approach seems to capture the patient’s functioning most accurately. Acknowledgment: Support for completion of this article was provided in part by Grant #R29 NS32009-04 from the National Institute of Neurological Disorders and Stroke to the first author. Drs. O’Brien and Seeberger received support from the National Parkinson Foundation as participants in a Center of Excellence. Cynthia McRae, PhD Gretchen Diem, MA Alexander Vo, MA University of Denver Denver, Colorado, U.S.A. Christopher O’Brien, MD Lauren Seeberger, MD Colorado Neurological Institute Denver, Colorado, U.S.A. References 1. Diamond SG, Markham CH. Evaluating the evaluations, or how to weigh the scales of parkinsonian disability. Neurology 1983;33: 1098–1099. 2. England AC, Schwab RS. Postoperative medical evaluation of 26 selected patients with Parkinson’s disease. J Am Geriatr Soc 1956; 4:1219–1232. 3. Geminiani G, Cesana BM, Tamma F, et al. Interobserver reliability between neurologists in training of Parkinson’s disease rating scales. Mov Disord 1991;6:330–335. 4. Ginanneschi G, Degl’Innocenti F, Magnolfi S, et al. Evaluation of Parkinson’s disease: reliability of three rating scales. Neuroepidemiology 1988;7:38–41. 5. Kennard C, Munro AJ, Park DM. The reliability of clinical assessment of Parkinson’s disease. J Neurol Neurosurg Psychiatry 1984; 47:322–323. 6. Martinez-Martin P, Bermejo-Pareja F. Rating scales in Parkinson’s disease. In: Jankovic J, Tolosa E, eds. Parkinson’s Disease and Movement Disorders. Baltimore, MD: Urban & Schwarzenberg, 1988:235–242. 7. Schwab RS, England AC. Projection technique for evaluating surgery in Parkinson’s disease. In: Gillingham FJ, Donaldson MC, eds. Third Symposium on Parkinson’s Disease. Edinburgh: E & S Livingstone, 1969:152–157. 8. Shindler JS, Brown R, Welburn P, Parkes JD. Measuring the quality of life of patients with Parkinson’s disease. In: Walker SR, Rosser RM, eds. Quality of Life Assessment: Key Issues in the 1990s. Boston, MA: Kluwer, 1993. 9. Fahn S, Elton RL, members of the UPDRS Development Committee. The Unified Parkinson’s Disease Rating Scale. In: Fahn S, Movement Disorders, Vol. 15, No. 2, 2000 Marsden CD, Calne D, Goldstein M, eds. Recent Developments in Parkinson’s Disease, vol 2. Florham Park, NJ: Macmillan Healthcare Information, 1987:153–163,293–304. Idazoxan Is Ineffective for Levodopa-Induced Dyskinesias in Parkinson’s Disease Levodopa-induced dyskinesias (LID) frequently mar the long-term therapeutic response to levodopa. Several new treatment strategies are currently being investigated, including some targeting nondopaminergic pathways.1 Experimental evidence suggests that LID may, in part, be the result of a reduced activity of the indirect pathway and associated increased pallidal inhibition of the subthalamic nucleus (STN).2 Activation of alpha-2 adrenoceptors on the striatal output neurone terminals reduces the gaba release and inhibition of the globus pallidus externa (GPE) in the indirect pathway. Thus, blockade at these sites should upregulate the inhibitory striatopallidal connections and lessen STN inhibition and dyskinesias. Preclinical studies, with selective alpha-2 antagonists such as yohimbime3 and idazoxan,4 have demonstrated marked antidyskinetic effects, and encouraging results have been reported in a small single-dose, pilot study.5 We have conducted a randomized, placebo-controlled 3-week trial of oral idazoxan for the management of LID in Parkinson’s disease. Eight patients (mean age, 57.1 yrs; mean duration PD, 15.9 yrs, mean duration of levodopa, 14.7 yrs; mean daily levodopa dose, 920 mg; mean daily additional antiparkinsonian medication, 2.5 mg pergolide or equivalent) entered the trial. Patients were given 1 week’s idazoxan (20 mg orally three times a day) or placebo for two separate treatment periods, with 1 week’s “washout” between. Video-recorded apomorphine challenges6 (incorporating the motor part [III] of the Unified Parkinson’s Disease Rating Scale [UPDRS]) were conducted at baseline and at the end of each treatment period. These were rated blindly by AJM and HI using the Goetz 5-point rating scale and the mean of the two raters’ scores taken. Patients were also asked to keep on/off and dyskinesia diaries for 3 days at baseline and 3 days at the end of treatment periods 1 and 2. The diaries consisted of hourly self-ratings of on/off state (“on,” “off,” or in-between) and dyskinesia severity (by means of a visual analog scale with a maximum score of 10). UPDRS parts I, II, IV, and V, and the hospital anxiety and depression7 scale, and Mini-Mental State examinations8 were also completed at each visit. All patients were screened at baseline to exclude cardiovascular or other significant concurrent medical condition, including electrocardiography, hematology, and biochemistry profiles performed at baseline and at the end of the trial. Adverse effects were graded on a 3-point scale (1 4 mild, 2 4 moderate, 3 4 severe) and recorded separately. One patient dropped out before entering the treatment period as a result of an inability to complete the diaries. All patients Received October 8, 1999; revision received December 29, 1999. Accepted December 30, 1999. Address correspondence and reprint requests to Andrew J. Lees, MD, The National Hospital for Neurology and Neurosurgery, Queen Square, 3rd Floor, London WC1N 3BG, England. CLINICAL/SCIENTIFIC NOTES experienced side effects during the treatment arm. These were severe in three patients who were forced to withdraw from the trial, two on day 1 and one after 5 days, during which the adverse effects had persisted. Side effects included flushing and sweating (five patients; mean severity: 2.4), headache (four patients, mean severity 4 2.25), nausea (six patients, mean duration 2.3 days), and vomiting (three patients, total events 4 7). No side effects occurred during the placebo phase. (The difference was highly statistically significant.) Some of the patients found the adverse reactions frightening. No significant changes in blood pressure, Mini-Mental State, or depression scores were noted. Only four patients completed the trial for the final analysis. Statistical analysis of data was performed using Wilcoxon’s test for paired samples on the mean results of placebo versus idazoxan and the mean differences from baseline of placebo versus idazoxan scores. Diary dyskinesia scores were slightly (9%) lower (4.7 versus 5.3) and video rating scores slightly (6%) higher (10.9 versus 9.4) on idazoxan compared with placebo, although neither result reached statistical significance (p 4 0.6). Interrater reliability was good (Pearson’s p 4 9.6, mean rater deviation from the mean 4 2%, standard deviation <10%). No significant difference in antiparkinsonian effect or “on” time, as measured by UPDRS ratings, was noted between the two treatments. We were not able to confirm an antidyskinetic effect of idazoxan in patients with Parkinson’s disease and LID. Lack of efficacy may have resulted from the use of a relatively lower dose (mean, <0.35 mg/kg three times a day) compared with the effective dose in animal studies (up to 10 mg/kg), and the use of apomorphine rather than levodopa for the acute challenge.9 Rascol et al. demonstrated a paradoxic increase in dyskinesia at higher single (40 mg) idazoxan doses. Although we chose the same 20-mg dose found to be effective in their single dose study,5 and the half-life of idaxoxan is only 4 hours,10 the three-times-a-day dosing could conceivably have led to relatively higher plasma levels. The high drop-out rate and small final numbers involved in the final analysis may have resulted in missing a possible beneficial effect. Although the number of patients completing the trial was too small to reach statistically significant conclusions regarding efficacy, the adverse event profile was unacceptable. This may, in part, be the result of nonselective effects involving the cardiovascular system, including elevation of blood pressure.5 Similar adverse events were found in earlier parallel group design studies of singledose idaxoxan5 and with a similar drop-out rate during the 3-week course of efaroxan (three of eight patients).11 We conclude that idazoxan is not useful for treating LID and has a high incidence of adverse events which may limit further trials at higher or equivalent doses. 337 References 1. Brotchie JM. Adjuncts to dopamine replacement: a pragmatic approach to reducing the problem of dyskinesia in Parkinson’s disease. Mov Disord 1998;13:871–876. 2. Crossman AR. A hypothesis on the pathophysiological mechanisms that underlie levodopa- or dopamine agonist-induced dyskinesia in Parkinson’s disease: implications for future strategies in treatment. Mov Disord 1990;5:100–108. 3. Gomez-Mancilla B, Bedard PJ. Effect of nondopaminergic drugs on L-dopa-induced dyskinesias in MPTP-treated monkeys. Clin Neuropharmacol 1993;16:418–427. 4. Henry B, Fox SH, Peggs D, Crossman AR, Brotchie JM. The alpha2-adrenergic receptor antagonist idazoxan reduces dyskinesia and enhances anti-parkinsonian actions of L-dopa in the MPTPlesioned primate model of Parkinson’s disease. Mov Disord 1999; 14:744–753. 5. Rascol O, Arnulf I, Agid Y, et al. L-Dopa-Induced dyskinesias improvement by an alpha-2 antagonist, idazoxan in patients with Parkinson’s disease. Mov Disord 1997;12(suppl 1):111. 6. Hughes AJ, Lees AJ, Stern GM. Apomorphine test to predict dopaminergic responsiveness in parkinsonian syndromes [see comments]. Lancet 1990;336:32–34. 7. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361–370. 8. Folstein MF, Folstein SE, McHugh PR. ‘Mini-Mental State.’ A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198. 9. Fox SH HM, Crossman AR, Brotchie JM. The neural mechanisms underlying dyskinesia induced by levodopa and apomorphine in parkinsonism are distinct [Abstract]. J Neurol Neurosurg Psychiatry. In press. 10. Muir NC, Lloyd-Jones JG, Nichols JD, Clifford JM. The pharmacokinetics after intravenous and oral administration in man of the alpha 2-adrenoreceptor antagonist idazoxan (RX781094). Eur J Clin Pharmacol 1986;29:743–745. 11. Brefel-Courbon C, Rascol O. Alpha-2-adrenoceptor antagonists: a new approach to Parkinson’s disease. CNS Drugs 1998;11:189– 207. Visuomotor Ataxia in Corticobasal Degeneration Acknowledgments: The authors thank Pierre Fabre (Castres) and Dr. Helene Peyro-St. Paul for supplying idaxoxan and matching placebo. Corticobasal degeneration, or cortical-basal ganglionic degeneration (CBD), is an asymmetric neurodegenerative disorder involving the cerebral cortex and basal ganglia.1,2 In addition to akinetic-rigid syndrome, patients with CBD present frequently with higher brain dysfunctions, including limb apraxia, alien limb, cortical sensory disturbance, and cognitive decline.1–6 We describe a patient with clinically probable CBD with asymmetric visuospatial disorientation, namely visuomotor ataxia. As far as we know, visuomotor ataxia has never been reported in CBD. Alice J. Manson, MBBS Elena Iakovidou, MBBS Andrew J. Lees, MD The Reta Lila Weston Institute of Neurological Studies University College London Windeyer Institute of Medical Science London, U.K. A videotape accompanies this article. Received March 15, 1999; revision received July 21, 1999. Accepted November 22, 1999. Address correspondence and reprint requests to Bungo Okuda, MD, Fifth Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan. Movement Disorders, Vol. 15, No. 2, 2000 338 CLINICAL/SCIENTIFIC NOTES Case Report A 64-year-old, right-handed man with negative familial and medical history was admitted to our department in March 1998 because of progressive gait disturbance. The patient had begun to notice difficulty in writing and buttoning 2 years before admission. He subsequently developed clumsiness of the right upper and lower limbs. His gait disturbance gradually progressed, resulting in frequent falls. On admission, he was mildly demented (WAIS IQ 71) with bradylalia. Visual acuity and field were intact. Visual neglect was absent on visual double stimulation. Vertical pursuit movements were severely limited, especially in the downward direction, whereas horizontal pursuit movements were full and saccadic. Saccades were hypometric and slow in both vertical and horizontal planes. The oculocephalic reflex was fully evoked, but optokinetic stimulation induced only the slow phase in all directions. The patient exhibited bradykinesia, predominantly on the right side. Muscle tone was rigid in the neck and right upper limb, and paratonic in the other limbs. Dystonic posture was present in the right upper and lower limbs. Muscle strength was preserved, and the deep tendon reflexes were generally brisk with flexor plantar reflexes and frontal releasing signs. When walking, he moved the right lower limb in an awkward fashion. Stooping posture was absent but retropulsion was positive. There were no cerebellar signs. The patient’s right upper limb was mildly apraxic, as manifested by clumsiness of complex finger movements, symbolic gestures, and object manipulation. Praxis with the left upper limb was intact. Disorders of visuomotor coordination were more pronounced than limb apraxia. When fixating straight ahead, the patient had difficulty in grasping the object presented in the right peripheral hemifield using the right hand. When searching for the target, he approached it in a wrong orientation, irrespective of the distance at which the object was placed. The visuomotor deficits were independent of the size and color of targets. In contrast, his right hand oriented correctly toward the target placed in the left peripheral hemifield. He was able to promptly and accurately reach targets in the right and left hemifields using his left hand (Fig. 1). When looking at an object, he could easily grasp it with either hand. His preserved visual field was confirmed with a Goldmann’s perimeter. Brain magnetic resonance imaging showed a few periventricular lacunar infarctions, sparing the parieto-occipital regions, and mild atrophy of the midbrain. Single-photon emission computed tomography (SPECT) with N-isopropyl-p[I123]-iodoamphetamine revealed asymmetric cortical hypoperfusion, mainly in the frontal region and, to a lesser degree, in the posterior parietal region, predominating on the left side (Fig. 2). Levodopa–carbidopa was administered up to 400 mg but no beneficial effects were obtained. Discussion Our patient exhibited asymmetric progression of parkinsonism, dystonia, and limb apraxia. His clinical features fit well with the diagnostic criteria for CBD designed by Lang et al.,6,7 and neuroimaging findings were also compatible with FIG. 1. Visuomotor incoordination. When fixating a central point, the patient can accurately grasp a target placed in the right peripheral hemifield with the left hand but not with the right hand. Each hand reaches straight for the target in the left peripheral hemifield. Movement Disorders, Vol. 15, No. 2, 2000 CLINICAL/SCIENTIFIC NOTES 339 FIG. 2. Single-photon emission computed tomography shows an asymmetric decrease in cerebral blood flow in the frontoparietal regions, predominantly on the left side (left/right reversed). CBD.8–10 Although the patient presented with axial rigidity and supranuclear gaze palsy characteristic of progressive supranuclear palsy (PSP),11 these clinical signs are associated with CBD as well.3 Furthermore, asymmetric limb apraxia in agreement with contralateral cortical hypoperfusion on SPECT favors a diagnosis of CBD rather than PSP.8,9 However, our patient showed unusual movement disorders, that is, inability to reach targets under visual control. Right-sided limb apraxia could not account for the deficits, because his right hand was correctly oriented in the left hemifield but incorrectly oriented in the right hemifield. His visual field was preserved and visual neglect was absent. Thus, the deficits were attributable to visuomotor incoordination, which has rarely been reported in neurodegenerative disorders. Visuospatial disorientation involving visually guided movements has been referred to as optic ataxia and is often noted in Balint’s syndrome from stroke or brain tumor.12,13 In addition to optic ataxia, however, patients with Balint’s syndrome develop psychic paralysis of fixation and visual inattention, which were undetectable in our patient. In the literature, visuospatial deficits in optic ataxia varied from case to case, in which unilateral or bilateral incoordination occurred on the ipsilateral or contralateral side to the lesion or both.13,14 Usually, optic ataxia is pronounced in the central visual field, irrespective of which visual hemifield is involved. In our case, however, visuomotor coordination with the right hand was defective only in the right peripheral hemifield, remaining intact in the central visual field. Therefore, the term visuomotor ataxia is more appropriate than optic ataxia in the present case.14 Because parietooccipital lesions cause lateralized visuomotor ataxia,12–14 the left poste- rior parietal hypoperfusion on SPECT in our patient may have been responsible for the asymmetric visuospatial disorientation. It is suggested that lateralized visuomotor ataxia may be a new sign of higher brain dysfunctions in CBD. Legend to the Videotape On the finger–nose test, the patient pointed accurately to the target in the central visual field using either hand. When fixating a central point, the right hand could not accurately approach the target placed in the right peripheral hemifield. Because of failure to catch the target, he occasionally shifted his gaze from the fixation point to the target. The right hand accurately reached the target placed in the left peripheral hemifield. The left hand went straight to the target placed in either hemifield. Bungo Okuda, MD Norihiko Kodama, MD Hisao Tachibana, MD Minoru Sugita, MD Division of Neurology Fifth Department of Internal Medicine Harumi Tanaka Rehabilitation Center Hyogo College of Medicine Nishinomiya, Japan Movement Disorders, Vol. 15, No. 2, 2000 340 CLINICAL/SCIENTIFIC NOTES References 1. Gibb WRG, Luthert PJ, Marsden CD. Corticobasal degeneration. Brain 1989;112:1171–1192. 2. Riley DE, Lang AE, Lewis A, et al. Cortical-basal ganglionic degeneration. Neurology 1990;40:1203–1212. 3. Rinne JO, Lee MS, Thompson PD, Marsden CD. Corticobasal degeneration: a clinical study of 36 cases. Brain 1994;117:1183– 1196. 4. Okuda B, Tachibana H, Kawabata K, Takeda M, Sugita M. Slowly progressive limb-kinetic apraxia with a decrease in unilateral cerebral blood flow. Acta Neurol Scand 1992;86:76–81. 5. Pillon B, Blin J, Vidailhet M, et al. The neuropsychological pattern of corticobasal degeneration: comparison with progressive supranuclear palsy and Alzheimer’s disease. Neurology 1995;45:1477– 1483. 6. Litvan I, Cummings JL, Mega M. Neuropsychiatric features of corticobasal degeneration. J Neurol Neurosurg Psychiatry 1998; 65:717–721. 7. Lang AE, Bergeron C, Pollanen MS, Ashby P. Parietal Pick’s disease mimicking cortical-basal ganglionic degeneration. Neurology 1994;44:1436–1440. 8. Sawle GV, Brooks DJ, Marsden CD, Frackowiak RSJ. Corticobasal degeneration: a unique pattern of regional cortical oxygen hypometabolism and striatal fluorodopa uptake demonstrated by positron emission tomography. Brain 1991;114:541–556. 9. Okuda B, Tachibana H, Takeda M, Kawabata K, Sugita M, Fukuchi M. Focal cortical hypoperfusion in corticobasal degeneration demonstrated by three-dimensional surface display with 123I-IMP: a possible cause of apraxia. Neuroradiology 1995;37:642–644. 10. Markus HS, Lees AJ, Lennox G, Marsden CD, Costa DC. Patterns of regional cerebral blood flow in corticobasal degeneration studied using HMPAO SPECT; comparison with Parkinson’s disease and normal controls. Mov Disord 1995;10:179–187. 11. Daniel SE, de Bruin VMS, Lees AJ. The clinical and pathological spectrum of Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy): a reappraisal. Brain 1995;118:759–770. 12. Damasio AR, Benton AL. Impairment of hand movements under visual guidance. Neurology 1979;29:170–178. 13. Pierrot-Deseilligny C, Gray F, Brunet P. Infarcts of both inferior parietal lobules with impairment of visually guided eye movements, peripheral visual inattention and optic ataxia. Brain 1986; 109:81–97. 14. Rondot P, Recondo J DE, Ribadeau Dumas JL. Visuomotor ataxia. Brain 1977;100:355–376. Levodopa-Induced Dyskinesias in Autopsy-Proven Cortical-Basal Ganglionic Degeneration To our knowledge, levodopa-induced dyskinesias have not been previously reported in cortical-basal ganglionic degeneration (CBGD). We report a patient with asymmetric parkinsonism who experienced levodopa-induced dyskinesias. Fluorode- A videotape accompanies this article. Received June 2, 1999; revisions received August 27 and October 29, 1999. Accepted October 30, 1999. Address correspondence and reprint requests to Steven Frucht, MD, The Neurological Institute, 710 W. 168th St., New York, NY 10032, U.S.A. Movement Disorders, Vol. 15, No. 2, 2000 oxyglucose PET scan supported the clinical impression of CBGD, which was ultimately confirmed at autopsy. Case Report A 74-year-old woman presented to our movement disorders center with a 3-year history of difficulty using her left hand. Pain and paresthesias accompanied loss of dexterity and stiffness in her left arm. She also had an action tremor of the left arm and slight instability when walking. There was no history of cognitive decline, alien limb phenomena, or autonomic complaints. Treatment with 600 mg levodopa before referral had not improved her symptoms. Her family history was notable for her sister and her son, both diagnosed with levodopa-responsive Parkinson’s disease. On initial examination, speech and comprehension were normal. There was no ideomotor apraxia. Extraocular movements were full without square wave jerks. As demonstrated in the first videotape segment, her examination was notable for markedly asymmetric parkinsonism with severe rigidity of the left arm and mild bradykinesia on the right as well. Fine minimyoclonic movements of the left arm were present on posture and action. Stimulus sensitivity was not assessed. There was no rest tremor, sensory examination was normal, and there were no higher cortical sensory deficits. She walked holding her left arm next to her body, flexed in a dystonic posture. An 18-fluorodeoxyglucose (FDG) PET scan was obtained using 4.5 mCi of FDG. Thirty-five PET slices were acquired in three-dimension parallel to the orbitomeatal line with arterial input. As seen in Figure 1, FDG uptake was qualitatively reduced in temporal and parietotemporal areas, marginally more pronounced on the right. Basal ganglia, thalamic and cerebellar FDG uptake were relatively preserved. Over the next year, her left arm became increasingly stiff and useless. She developed mild parkinsonism on the right side and had increasing difficulty walking. She thought she derived benefit from levodopa, although improvement on the motor section of the Unified Parkinson’s Disease Rating Scale was not observed. As demonstrated in the second videotape segment, examination 18 months after her initial visit (on 800 mg levodopa per day) revealed mild to moderate dyskinesias. They were chiefly activated by voluntary movement and consisted of dystonic blinking, neck and torso wiggling, and mild choreic movements of the right arm and both legs. They were not patterned, that is, not simply mirror movements. Reduction of levodopa to 600 mg provided relief from dyskinesias but she experienced worsening of her parkinsonism. She died 2 years after her initial visit from aspiration pneumonia and a large left middle cerebral artery stroke. On examination of the brain (demonstrated in Figure 2), Gallyas silver stain revealed argyrophilic threads and astrocytic plaques within the gray and white matter of the precentral gyrus and in the pencil fibers of Wilson. No typical glial cytoplasmic inclusions or tufted astrocytes were seen. Immunohistochemical staining for phosphorylated neurofilament protein confirmed the presence of ballooned neurons within the precentral, middle frontal, and cingulate gyri. Moderate to marked gliosis was present in the caudate and putamen accompanied by moderately severe loss of pigmented nigral neurons within the midbrain with rare corticobasal inclusions present. Tau protein electrophoresis and mutation analyses were not performed. CLINICAL/SCIENTIFIC NOTES 341 FIG. 1. An axial quantitative 18fluorodeoxyglucose (FDG) PET scan at the level of the basal ganglia demonstrates metabolic reduction in parietotemporal areas, more pronounced on the right. Basal ganglia and thalamic uptake are relatively preserved. Discussion Several features of our patient’s clinical profile suggested the diagnosis of CBGD, particularly the asymmetry of her examination, the presence of action myoclonus, and the dystonic posture and marked rigidity of the left arm. Although levodopainduced blepharospasm may be seen in CBGD, to our knowledge, levodopa-induced dyskinesias of the trunk and extremities have not been previously reported. Their appearance was similar to dyskinesias occurring in patients with advanced Parkinson’s disease. The diagnosis of CBGD was supported by the asymmetric parietotemporal hypometabolism on FDG PET scan, a pattern of asymmetric cortical metabolism that has been reported by several investigators.1–3 Although cortical sensory findings and apraxia were not present, these are not universally seen in this condition, particularly early in the illness.4 The occurrence of three individuals in the same family with parkinsonism is intriguing, suggesting an inherited predisposition to a neurodegenerative process. There is no indication that our patient’s relatives will develop CBGD, because their clinical profiles are consistent with idiopathic Parkinson’s disease. However, the possibility of familial CBGD must be kept in mind, because this would not be without precedent.5,6 Levodopa-induced dyskinesias are often seen in patients with striatonigral degeneration, and rarely also occur in patients with progressive supranuclear palsy. In these disorders and in CBGD, gliosis and degenerative changes typically involve multiple subcortical systems. How then can we explain the rarity of dyskinesias in CBGD? One possibility is that they stem from the combination of dopaminergic nigrostriatal denervation in the presence of a relatively intact striatum. In their original description of the disorder, Reibez et al.7 noted widespread nigral cell loss in three patients, with relative preservation of the striatum. This pattern was also seen in other pathologic reports8,9 and has also been reported on PET scans of patients with CBGD, particularly early in their illness. For example, in six cases of CBGD, striatal FDG uptake was preserved while caudate and putaminal fluorodopa uptake were depressed.3 The presence of mild parkinsonism on our patient’s right side and the severity of pathologic nigral cell loss supports a defect in her nigrostriatal pathway. However, her striatum was not spared at postmortem, evidence against this mechanism. Another possibility is that the cortical hypometabolism present in CBGD may prevent these patients from developing involuntary movements. This cortical deficit is a defining feature of this disorder, separating it from its closely related cousins. However, PET scanning and postmortem examination revealed that her cortex was involved, like in virtually all cases of CBGD. We are thus left without a clear pathologic explanation for the development of dyskinesias in this patient. It is surprising that no other patients similar to ours have been reported. In a review of 147 cases of clinically diagnosed CBGD, 87% were treated with levodopa at a median dose of 300 mg per day. Only 26% perceived any improvement, and no patient developed dyskinesias despite the fact that some patients received high doses of levodopa.10 It is possible that patients with CBGD who do not obtain a good response from levodopa may not continue it long enough for dyskinesias to be recognized by the patient or the physician. Movement Disorders, Vol. 15, No. 2, 2000 342 CLINICAL/SCIENTIFIC NOTES FIG. 2. (A) A section of the precentral gyrus (Gallyas silver stain counterstained with cresyl violet) exhibited frequent “astrocytic plaques” (black arrows) in the upper cortical layers, scattered neurofibrillary tangles within neurons (white arrowheads), and numerous argyrophilic threads in the lower cortical layers (bottom of field). Scale bar 4 100 mm. (B) A section of putamen exhibited numerous argyrophilic, interfascicular threads running within the pencil fibers of Wilson (white matter tract running diagonally from upper left to lower right between the opposing arrows). Scattered argyrophilic threads are also seen within the surrounding neuropil (Gallyas silver stain counterstained with cresyl violet). Scale bar 4 50 mm. Legend to the Videotape Segment 1, recorded at initial presentation to our center, demonstrates asymmetric left-sided parkinsonism with breakdown of rapid succession movements in the arm and leg. Mild slowing of fine hand movements is also present on the right. Fine myoclonic jerks are present in the left hand, activated by Movement Disorders, Vol. 15, No. 2, 2000 movement. Her left arm is held in a dystonic flexed posture when she walks, and she is able to recover on pull test. Segment 2, 1.5 years later and 3 months before her death, shows marked worsening of her parkinsonism with a rigid and functionally useless left arm. Mild parkinsonism is also present on the right, and her postural stability is poor. Dyskinesias are present at rest and markedly activated by movement, consisting CLINICAL/SCIENTIFIC NOTES of blepharospasm, pursing of the lips, truncal wiggling, and bilateral lower extremity choreiform movements. Steven Frucht, MD Stanley Fahn, MD Steven Chin, MD, PhD Columbia-Presbyterian Medical Center New York, NY, U.S.A. Vijay Dhawan, PhD Northshore University Medical Center Manhasset, New York, U.S.A. David Eidelberg, MD Cornell Medical Center New York, NY, U.S.A. References 1. Eidelberg D, Dhawan V, Moeller JR, et al. The metabolic landscape of cortico-basal ganglionic degeneration: regional asymmetries studied with positron emission tomography. J Neurol Neurosurg Psychiatry 1991;54:856–862. 2. Sawle GV, Brooks DJ, Marsden CD, Frackowiak RSJ. Corticobasal degeneration: a unique pattern of regional cortical oxygen hypometabolism and striatal fluorodopa uptake demonstrated by positron emission tomography. Brain 1991;114:541–556. 3. Nagasawa H, Tanji H, Nomura H, et al. PET study of cerebral glucose metabolism and fluorodopa uptake in patients with corticobasal degeneration. J Neurol Sci 1996;139:210–217. 4. Watts RL, Brewer RP. Cortical-basal ganglionic degeneration: classical clinical features and natural history. Mov Disord 1996; 11:346. 5. Brown J, Lantos PL, Roques P, Fidani L, Rossor MN. Familial dementia with swollen achromatic neurons and corticobasal inclusion bodies: a clinical and pathological study. J Neurol Sci 1996; 135:21–30. 6. Caselli RJ, Reiman EM, Timmann D, et al. Progressive apraxia in clinically discordant monozygotic twins. Arch Neurol 1995;52: 1004–1010. 7. Rebeiz JJ, Kolodny EH, Richardson EP. Corticodentatonigral degeneration with neuronal achromasia. Arch Neurol 1968;18:20–33. 8. Scully RE, Mark EJ, McNeely BU. Case 38-1985. N Engl J Med 1985;313:739–748. 9. Gibb WRG, Luthert PJ, Marsden CD. Corticobasal degeneration. Brain 1989;112:1171–1192. 10. Kompoliti K, Goetz CG, Boeve BF, et al. Clinical presentation and pharmacological therapy in corticobasal degeneration. Arch Neurol 1998;55:957–961. Acquired and Persistent Stuttering as the Main Symptom of Striatal Infarction Stuttering is defined as “frequent repetitions or prolongations of sounds or syllables that markedly impair the fluency of speech.”1 Developmental stuttering almost always begins in Received December 2, 1998; revision received June 24, 1999. Accepted November 18, 1999. Address correspondence and reprint requests to Pr. Gilles-Louis Defer, Service de Neurologie Déjerine, CHU de la Côte de Nacre, Caen, France. 343 childhood or early adolescence and is more common in males than females.2 Distinct from developmental stuttering, acquired stuttering is more rare. Acquired stuttering of gradual onset is mainly associated with neurodegenerative diseases such as Parkinson’s disease (PD), progressive supranuclear palsy (PSP), or Alzheimer’s disease.3–5 A sudden onset is typically observed after brain lesions such as head trauma5,6 or stroke,6–10 but in many cases of stroke, acquired stuttering has not been considered as a primary symptom of brain damage, because it was often associated with aphasia.6 However, there were some poststroke cases of acquired stuttering without other language deficits, attesting that acquired stuttering may be accepted as a clinical entity.5,7,9–11 A direct or indirect involvement of the extrapyramidal system in the pathophysiology of stuttering can be hypothesized. This is supported by rare cases of stuttering related to focal lesions of the extrapyramidal system,10,12–14 by pharmacologic data suggesting the participation of the dopaminergic system in stuttering,15 and by the association of stuttering with abnormal involuntary movements.16 These findings raise the question of the role of subcortical structures, such as the basal ganglia or thalamus, in stuttering production and then in speech processing. We describe a patient with detailed clinical and neuroimagering studies who had acquired and persistent stuttering associated with parkinsonian syndrome following an unilateral striatal infarction. Case Report A 58-year-old, right-handed man was initially admitted elsewhere for right hemiparesis with aphasia. His medical history included diabetes and hypertension. He had no history of stuttering or extrapyramidal symptoms. Clinical examination showed in the first days a rest tremor with slight hypertonia of the right side. His speaking difficulty was characterized by incapability of naming his children’s first names and was transient. Computed tomography scan showed a limited lowdensity area in the left basal ganglia. During the first poststroke week, he recovered a normal language. At that time, speech assessment showed normal oral and writing comprehension. Naming and repetitions were normal. Stuttering began to occur during the following weeks. Two months later, he was seen for the first time in the neurologic department. He had right rest tremor, diminished right arm swing on walking, moderate hypertonia, slight amimia, and exaggerated nasopalpebral reflex. No sensory or motor disturbances were observed and there were no pyramidal signs. Ocular motility was normal. The patient had excessive salivation. Principally a stuttering was present. Analysis of dysfluency showed that speech was characterized by clonic blockades and by phonemic and syllable repetitions. Stuttering was present during conversational speech, reading, description of pictures, and naming. Adaptation (decreased dysfluency on successive oral readings of the same material) was present on repetitive effort. During reading, an improvement of stuttering was also observed. No abnormal movement or associated synkinesis were observed. A first magnetic resonance image, 2 months after the stroke, disclosed a lesion located principally in the left putamen but reaching the left caudate, anterior and posterior internal capsule, and adjacent white matter. The lesion appeared on T1, T2-weighted image and on Epi-Flair in high signal intensity which attests the presence of blood, suggesting an embolic mechanism. There was also a slight cortical atrophy in the left superior temporal Movement Disorders, Vol. 15, No. 2, 2000 344 CLINICAL/SCIENTIFIC NOTES gyrus (data not shown). Four weeks after the stroke, he received a dopaminergic agonist (150 mg piribedil) during 1 month which had no effect on stuttering and the parkinsonian syndrome. Twelve months after the stroke, the parkinsonian symptoms were spontaneously and significantly improved. The patient had only an intermittent right rest tremor and slight hypertonia of the right leg. Stuttering was still present with the same characteristics as before. The patient did not notice improvement of stuttering and considered it as a disabling social symptom. At that time a second magnetic resonance image showed a well-delineated lesion involving the left putamen, the left caudate, slightly the anterior and posterior internal capsule, FIG. 2. Two consecutive coronal slices going through the lesion in the axial plane (sequences TR:4000/TE:102). and possibly a small area of the external pallidum. The lesion was best visualized on T2-weighted image (Figs. 1 and 2). There was a slight dilatation of ventricular system toward the lesion and small bilateral lesions of high signal intensity in the white matter. So 1 year after the stroke, the patient presented a severe stuttering which was the main symptom and a slight right parkinsonian syndrome. Discussion FIG. 1. Magnetic resonance image 12 months after stroke showing a left circumscribed striatal lesion. Two consecutive axial T2-weighted images (sequences TR:4000/TE:60). Movement Disorders, Vol. 15, No. 2, 2000 We report a patient who developed a persistent stuttering related to a left striatal infarction. Parkinsonian symptoms were initially observed but were transient. After 1 year of follow up only intermittent rest tremor and minor right hypertonia were observed. Cases of acquired stuttering with lesions limited to basal ganglia are likely rare.10,12–14 Most reported cases have CLINICAL/SCIENTIFIC NOTES been due to vascular disease and typically multiple lesions have been found.5,6–10,17,18 Analysis of published cases with acquired stuttering, whatever the lesion size or location, showed that there is no effect of laterality, acquired stuttering occurring equally with right or left hemispheric lesions.6–10,12–14,17,18 In our patient, the sequel of aphasia and the role of corticalassociated lesion in stuttering may be discussed because he had language disturbances and slight left temporal atrophy on magnetic resonance imaging. In fact, initial language disturbances were transient, and he had no aphasia on speech assessment when stuttering occurred. Therefore, stuttering may not be considered as a sequel of aphasia but more as an independent symptom. Cortical temporal atrophy on magnetic resonance imaging did not change at 1 year and seems not to be related to a previous stroke. If we cannot exclude a temporal cortical dysfunction in the genesis of stuttering in our patient, we suggest it is unlikely, especially because the patient had not stuttered before. The clinical picture that we describe is infrequent because both vascular parkinsonian syndrome and acquired stuttering are two rare clinical entities.6,19,20 We have found only one similar case in the literature.12 Tolosa’s report12 and our case demonstrate that a highly circumscribed and single lesion of basal ganglia can produce stuttering and support the hypothesis of a functional involvement of extrapyramidal system in this speech disorder. This relationship is reinforced by the report of Koller who published four cases of PD and one case of PSP with stuttering demonstrating the interest of looking for a parkinsonian syndrome in patients with acquired stuttering.3 Pharmacologic data led to postulate a dopaminergic mechanism underlying stuttering.15 Neuroleptics have been used with success in the treatment of stuttering and conversely, stuttering can be a side effect of neuroleptic treatment.21–23 Verapamil, a calcium channel blocker known to induce or aggravate parkinsonism and other extrapyramidal symptoms,24 has also been tried for stuttering.25 Finally, developmental stuttering is commonly associated with secondary behaviors, such as head turning, blinking, or upper lip raising.26,27 These movements were considered by some authors as involuntary movements seen in dystonic syndrome suggesting that stuttering could be a form of segmental dystonia.16 Moreover, a family history of stuttering in patients with idiopathic torsion dystonia has been reported.28 Thus, there is the argument suggesting that extrapyramidal system dysfunction can produce stuttering. These observations raise the question of participation of subcortical structures in speech production. Other speech defects close to stuttering have been described after subcortical lesions. Palilalia, a speech defect frequently observed in PD, is commonly related to bilateral lesions of the basal ganglia. Stuttering and palilalia are similar as far as the involuntary repetitions, but stutterers repeat mainly initial syllables whereas patients with palilalia repeat entire words or phrases.29 For Boller, the most distinctive sign is “the painful effort of stutterers as they attempt to speak and the fluent output of the palilalic patient who appears as if he cannot stop speaking.”29 However, in some cases, distinction between stuttering and palilalia can be difficult.17 Palilalia may represent the speech equivalent of motor phenomena such as freezing episode in patients with PD.29 Other data emphasize the role of the basal ganglia in stuttering and, more generally, in speech processing.30–32 A repetitive 345 speech disorder following lesions in the paramedian thalami and midbrain has been reported.30 During electrical stimulation of the thalamus, repetitions of syllables, words, and phrases have been observed by Schaltenbrand who preferred to use the term “compulsory speech,” which regrouped stuttering, palilalia, and other speech defects because their presentations were very different.31 Like Boller for palilalia, many authors expressed the idea that stuttering could be the result of a motor control disorder affecting the speech rate.3,11,13 The association of stuttering and dystonia4,16,28 and some motor control disorders, such as the difficulty to reproduce and to sustain alternating sequential motor tasks described during stuttering,3,6,13,33 support this hypothesis. Moreover, study by positron emission tomography showed that stuttering was characterized by hyperactivity of the motor system and principally of the supplementary motor area and the superior lateral premotor cortex.34 Probably, acquired as well as developmental stuttering do not have a simple pathophysiological explanation. Moreover, individual differences in brain organization of speech could explain that stuttering was not systematically observed for a defined topographic lesion. Although striatum compared with thalamus seems to be more frequently involved in stuttering,10,12,14 this does not allow us to evoke striatum as a specific neuroanatomic site for stuttering, but it draws attention toward the basal ganglia circuitry for its participation in the occurrence of stuttering. It is suggested that stuttering could be the result of a motor control disorder affecting speech. New studies using functional imagery might bring further explanations to the understanding of this speech disorder. Acknowledgment: The authors thank Dr. Christopher G. Goetz (Chicago, IL, USA) for his critical comments of the manuscript. Laurence Carluer, MD Rose-Marie Marié, MD, PhD Jany Lambert Gilles-Louis Defer, MD Service de Neurologie Dejerine Oz Coskun, MD Service de Neuroradiologie Yvette Rossa, MD Service d’Oto-Rhino-Laryngologie CHU de la Côte de Nacre Caen, France References 1. Diagnostic and Statistical Manual of Mental Disorders, 4th ed (DSM-IV). Washington, DC: American Psychiatric Association, 1994. 2. Speech dysfluency [Editorial]. Lancet 1989;1:530–532. 3. Koller WC. Dysfluency (stuttering) in extrapyramidal disease. Arch Neurol 1983;40:175–177. 4. Abdorasool J. Case report: progressive supranuclear palsy, report of a case with torticollis, blepharospasm and dysfluency. Am J Med Sci 1986;292:391–392. 5. Quinn PT, Andrews G. Neurological stuttering: a clinical entity. J Neurol Neurosurg Psychiatry 1977;40:699–701. 6. Helm NA, Butler RB, Benson DF. Acquired stuttering. Neurology 1978;28:1159–1165. Movement Disorders, Vol. 15, No. 2, 2000 346 CLINICAL/SCIENTIFIC NOTES 7. Rosenfield DB. Stuttering and cerebral ischemia [Letter]. N Engl J Med 1972;287:991. 8. Donnan GA. Stuttering as a manifestation of stroke. Med J Aust 1979;27:44–45. 9. Fleet WS, Heilman KM. Acquired stuttering from a right hemisphere lesion in a right-hander. Neurology 1985;35:1343–1346. 10. Soroker N, Bar-Israel Y, Schechter I, Solzi P. Stuttering as a manifestation of right-hemispheric subcortical stroke. Eur Neurol 1990; 30:268–270. 11. Rosenbek J, Messert B, Collins M, Wertz RT. Stuttering following brain damage. Brain Lung 1978;6:82–96. 12. Tolosa ES, Santamaria J. Parkinsonism and basal ganglia infarcts. Neurology 1984;34:1516–1518. 13. Ludlow CL, Rosenberg J, Salazar A, Grafman J, Smutok M. Site of penetrating brain lesions causing chronic acquired stuttering. Ann Neurol 1987;22:60–66. 14. Nass R, Schreter B, Heier L. Acquired stuttering after a second stroke in a two-year-old. Dev Med Child Neurol 1994;36:70–83. 15. Brady JP. The pharmacology of stuttering: a critical review. Am J Psychiatry 1991;148:1309–1316. 16. Kiziltan G, Akalin MA. Stuttering may be a type of action dystonia. Mov Disord 1996;11:278–282. 17. Horner J, Massey EW. Progressive dysfluency associated with right hemisphere disease. Brain Lang 1983;18:71–85. 18. Ardila A, Lopez MV. Severe stuttering associated with right hemisphere lesion. Brain Lang 1986;27:239–246. 19. Fenelon G, Houeto JL. Les syndromes parkinsoniens vasculaires: un concept controversé. Rev Neurol 1998;154:291–302. 20. Bathia KP, Marsden CD. The behavioural and motor consequences of focal lesions of the basal ganglia in man. Brain 1994;117:859– 876. 21. Prins D, Mandelkorn T, Cerf FA. Principal and differential effects of haloperidol and placebo treatments upon speech dysfluencies in stutterers. J Speech Lang Hear Res 1980;23:614–629. 22. Nurnberg G, Greewald B. Stuttering: an unusual effect of phenothiazines. Am J Psychiatry 1981;138:386–387. 23. Thomas P, Lalaux N, Vaiva G, Goudemand M. Dose dependent stuttering and dystonia in a patient taking clozapine [Letter]. Am J Psychiatry 1994;151:1096. 24. Garcia-Ruiz PJ, Garcia de Yebenes J, Jimenez-Jimenez FJ, Vazquez A, Garcia Urra D, Morales B. Parkinsonism associated with calcium channel blockers: a prospective follow up study. Clin Neuropharmacol 1992;15:19–26. 25. Brady JP, Price TRP, McAllister TW, Dietrich K. A trial of verapamil in the treatment of stuttering in adults. Biol Psychiatry 1989; 25:630–633. 26. Conture EG, Kelly EM. Young stutterers’ nonspeech behaviors during stuttering. J Speech Lang Hear Res 1991;34:1041–1056. 27. Abwender DA, Trinidad KS, Jones KR, Como PG, Hymes E, Kurlan R. Features resembling Tourette’s syndrome in developmental stutterers. Brain Lang 1998;62:455–464. 28. Fletcher NA, Harding AE, Marsden CD. A case control study of idiopathic torsion dystonia. Mov Disord 1991;6:304–309. 29. Boller F, Albert M, Denes F. Palilalia. Br J Disord Com 1975;10: 92–97. 30. Abe K, Yokohama R, Yorifuji S. Repetitive speech disorder resulting from infarcts in the paramedian thalami and midbrain. J Neurol Neurosurg Psychiatry 1993;56:1024–1026. 31. Schaltenbrand G. The effects of speech and language of stereotactical stimulation in thalamus and corpus callosum. Brain Lang 1975;2:70–77. 32. Andy OJ, Bhatnagar SC. Thalamic induced stuttering. J Speech Lang Hear Res 1991;34:786–800. 33. Webster WG. Evidence in bimanual finger taping of an attentional component to stuttering. Behav Brain Res 1990;37:93–100. 34. Fox PT, Ingham RJ, Ingham JC, et al. A PET study of the neural systems of stuttering. Nature 1996;382:158–162. Movement Disorders, Vol. 15, No. 2, 2000 Unilateral Arm Tremor as the Sole Feature of Ischemic Stroke: A 5-Year Follow Up It is uncommon for a stroke to cause movement disorders. In a study of 2500 patients with first-ever stroke in Lausanne, Switzerland, only 29 had acute or delayed movement disorders in which dystonia, chorea, and ballism were the most frequent.1 Tremor is even more rare as a manifestation of stroke, with only one patient reported to have tremor in the above study. We describe a patient with ischemic stroke-related tremor in the absence of other neurologic signs. Case Report A 45-year-old, right-handed woman was referred to the neurology clinic with sudden onset of tremor while walking in the street. This was initially fluctuating in the left thumb but then spread to all digits of her left hand and became persistent. The tremor worsened with stress and excitement. There was no family history of tremor or use of tremor-inducing drugs. Medical history only consisted of hysterectomy. She smoked 15 cigarettes per day and drank less than 2 units of alcohol per week. Initial assessment revealed a coarse, mainly postural tremor affecting the left hand with no evidence of bradykinesia or rigidity. Limb reflexes were abnormally brisk in the left arm and leg, otherwise the neurologic examination was unremarkable. T2-weighted magnetic resonance imaging (MRI) revealed a small focal lesion in the anterolateral aspect of the right putamen and adjacent white matter considered most likely to be an ischemic lesion (Fig. 1). Her tremor failed to respond to propranolol, theophylline, and benzhexol. A year later she was treated with levodopa with no benefit. Two years later, with no improvement in her tremor, the MRI scan was repeated and showed no change in the lesion size. Further investigations, including cerebrospinal fluid analysis and visual evoked potentials, were normal, making demyelination improbable. Routine laboratory tests, coagulation screen, thrombophilia screen, autoantibody screen, syphilis serology, thyroid function test, serum and 24-hour urinary copper were unremarkable. At that time, she reported that two units of alcohol were helpful in controlling her tremor. Five years after the onset there was no change in her tremor, which continues to be unilateral involving the left side. Although mild at rest, it worsens with changes in posture and now requires 4–5 units of alcohol to control it. On one occasion, smoking cannabis produced a similar relieving effect as alcohol. Electrophysiological studies of her tremor were carried out by obtaining surface electromyography (EMG) recording revealing a 5–6-Hz tremor which did not vary in frequency with posture. Frequency analysis of filtered rec- A videotape accompanies this article. Received January 19, 1999; revision received June 24, 1999. Accepted November 17, 1999. Address correspondence and reprint requests to Hani T. S. Benamer, MRCP, Department of Neurology, Institute of Neurological Sciences, Southern General Hospital NHS Trust, 1345 Govan Road, Glasgow G51 4TF, Scotland. CLINICAL/SCIENTIFIC NOTES 347 rest, had a sudden onset, has not become bilateral after 5 years, and thus fails established diagnostic criteria for ET. Ondansetron, a 5-HT3 antagonist, has been shown (when given intravenously at a dose of 20 mg) to control cerebellar tremor in 20 patients with multiple sclerosis, cerebellar degeneration, or drug toxicity.10 As part of a pilot study of this treatment, in which the videotape was reviewed by a clinician blinded to clinical data, a positive response was found to a single oral dose of ondansetron. The role of ondansetron in the treatment of different types of tremor therefore merits further evaluation. Although it is difficult to be certain about the nature of the MRI lesion and its relation to the clinical presentation, the clinical and electrophysiological features of the tremor are supportive of a possible causal relationship between the ischemic lesion and the tremor. Legends to the Videotape Segment 1: Mild resting left hand tremor, worsening with posture, unable to hold a cup of water. Segment 2: Improvement in tremor after four units of alcohol, now able to hold cup of water without difficulty. Segment 3: Improvement in tremor and the ability to hold a cup of water after 8 mg ondansetron. Hani T. S. Benamer, MRCP(UK) Department of Neurology FIG. 1. T2-weighted MRI, 6 months after acute onset of left arm tremor, shows an ischemic lesion in the anterolateral aspect of the right putamen. Aline J. C. Russell, MRCP(UK) Department of Neurophysiology Donald M. Hadley, PhD, FRCR Department of Neuroradiology tified EMG also confirmed a dominant frequency of 5–6 Hz with additional harmonic activity seen at 11 Hz. She did not tolerate primidone; however, her tremor improved dramatically with a single oral dose of 8 mg ondansetron. Donald G. Grosset, MD, FRCP Department of Neurology Institute of Neurological Sciences Glasgow, Scotland Discussion References Tremor as a result of stroke usually accompanies other neurologic features.2–7 Our patient developed tremor as a possible manifestation of ischemic stroke. This rare presentation has been reported, to our knowledge, only twice before. Lee et al.8 reported a patient with a sudden onset of right-hand, levodoparesponsive resting tremor without other features of parkinsonism. MRI revealed a lacunar infarct at the border between the left thalamus and the internal capsule. The authors concluded that the thalamic lesion was likely to be the cause of the tremor, but the possibility of early Parkinson’s disease (PD) could not be excluded. Recently, McAuley et al.9 reported a patient with sudden onset of right hand and arm tremor present at rest, posture, and movement, and there was no change in severity after 2 years. The tremor was initially labeled psychogenic. However, electrophysiological studies revealed 7–8-Hz polyphasic bursts, and MRI showed a small ischemic lesion in the left lentiform nucleus. Our patient has some clinical similarity to this case but is different from the first case in the poor response to levodopa. In addition, absence of rigidity and bradykinesia after 5 years follow up make PD unlikely. The tremor in our patient has the same frequency as essential tremor (ET) and shows a definite response to alcohol but is also present at 1. Ghika-Schmid F, Regli F, Bogousslavsky J. Hyperkinetic movement disorders during and after acute stroke: the Lausanne stroke registry. J Neurol Sci 1997;146:109–116. 2. Ferbert A, Gerwig M. Tremor due to stroke. Mov Disord 1993;8: 179–182. 3. Kim JS. Delayed onset hand tremor caused by cerebral infarction. Stroke 1992;23:292–294. 4. Dethy S, Luxen A, Bidaut LM, Goldman S. Hemibody tremor related to stroke. Stroke 1993;24:2094–2096. 5. Kim JS, Lee MC. Writing tremor after discrete cortical infarction. Stroke 1994;25:2280–2282. 6. Qureshi F, Morales A, Elble RJ. Tremor due to infarction in the ventrolateral thalamus. Mov Disord 1996;11:440–444. 7. Schulze-Bonhage A, Ferbert A. Cortical action tremor and focal motor seizures after parietal infarction. Mov Disord 1998;13:356– 358. 8. Lee MS, Lee SA, Heo JH, Choi IS. A patient with a resting tremor and a lacunar infarction at the border between the thalamus and the internal capsule. Mov Disord 1993;8:244–246. 9. McAuley JH, Rothwell JC, Marsden CD, Findley LJ. Electrophysiological aids in distinguishing organic from psychogenic tremor. Neurology 1998;50:1882–1884. 10. Rice GPA, Lesaux J, Vandervoort P, Macewan L, Ebers GC. Ondansetron, a 5-HT3 antagonist, improves cerebellar tremor. J Neurol Neurosurg Psychiatry 1997;62:282–284. Movement Disorders, Vol. 15, No. 2, 2000 348 CLINICAL/SCIENTIFIC NOTES Focal Task-Specific Dystonia Induced by Peripheral Trauma First described by Gowers over a century ago,1 examples of focal task-specific dystonias (FTSDs) include telegrapher’s cramp, writer’s cramp, golfer’s cramp (“the yips”), and musician’s cramps.2 By definition, FTSD affects one part of the body exclusively during the performance of a specific task. FTSD may be the first sign of a generalized dystonia, before spread to other tasks or other parts of the body. However, in the overwhelming majority of patients with FTSD, dystonia remains confined to the body part and the specific task in which it started. There is considerable debate regarding the role of peripheral trauma in triggering dystonia. Cervical dystonia,3 shoulder dystonia,4 and dystonia of the arm and leg5 have been reported following local trauma. Recent work in primates and humans supports the idea that FTSDs may result from alterations in normal cortical topography.6 Although the etiology of these disorders is unknown, the idea has been proposed that in a susceptible population, FTSD may be triggered by peripheral trauma.7 We report two unusual patients, both musicians, who developed FTSD after peripheral trauma. In both instances, dystonia was temporally and anatomically linked to the peripheral injury. Although the trauma was not severe, dystonia was professionally debilitating, and in one case continued to progress long after the trauma had healed. Case Reports Case 1 A 17-year-old trumpet player presented to our movement disorders center with a history of a marked decline in performance on her instrument. She began her formal studies at the age of 9 and was anticipating a career as a performer. There was no family history of dystonia, no history of neuroleptic exposure, and no significant medical history. Ten months prior to evaluation, she was playing in her marching band when the bell of her trumpet was impaled by the slide of an oncoming trombonist. Her mouthpiece was forced against her lips and teeth with tremendous pressure, causing marked swelling of both lips that was made worse by a coincident second-degree sunburn. After a week of rest, signs of peripheral trauma subsided and she returned to playing. However, her embouchure, the muscles of the lower face and jaw used to approach the mouthpiece, felt awkward and she never felt that her playing returned to its usual proficient level. Over the ensuing 6 months, her playing A videotape accompanies this article. Received September 13, 1999; revisions received November 17 and December 7, 1999. Accepted December 7, 1999. Address correspondence and reprint requests to Steven Frucht, MD, The Neurological Institute, 710 W. 168th St., New York, NY 10032, U.S.A. Movement Disorders, Vol. 15, No. 2, 2000 deteriorated rapidly to the point that she could no longer play at all. Prior evaluations by an oral surgeon, a dermatologist, and three neurologists did not result in a diagnosis. She reported that when she attempted to blow into the mouthpiece of her trumpet, marked tremor of both lips occurred immediately, destroying her air seal. Although the upper register of the instrument (which requires more air pressure) was affected first, difficulty soon spread to involve all notes. There was no impairment in any task except playing the trumpet, and her condition was completely painless. There was also no history of prior oral trauma or significant dental manipulation, and she had not altered her technique prior to the onset of her problem. Rest and retraining approaches were unsuccessful. Neurologic examination was completely normal aside from FTSD. As demonstrated on the videotape, when playing with the mouthpiece or on the trumpet, a fast fine irregular tremor of the orbicularis oris was obvious from the moment she began to play, worse in the upper registers. Flaring of the nostrils and mild puckering of the lips was also evident. The tremor could be heard easily, and she was unable to maintain an air seal on the mouthpiece. Given her young age and the uncertain prospects for her career as a performer, treatment was deferred and she decided instead to pursue an alternate career path. Case 2 A 48-year-old professional bagpipe player was referred for evaluation of difficulty using his left hand when playing the pipes. A world-class professional player, he began his formal studies as a teenager. There was no family history of dystonia and he had not received neuroleptics. Approximately 3 years prior to evaluation, he embarked on a vigorous exercise program including at least 100 push-ups at a time five to six times per day. He also began to participate in karate, including breaking boards with both arms. Soon thereafter, he experienced severe pain in the left axilla radiating down the medial aspect of the left arm to his fourth and fifth fingers. At approximately the same time, he noted the insidious onset of difficulty with his left hand when playing the bagpipe. There was no change in his technique or amount of his playing. The fourth and fifth fingers of his left hand would involuntarily curl while playing, pulling the fourth finger off the keyhole and causing him to make uncharacteristic errors. In retrospect, this difficulty was first noted by judges who evaluated him at international bagpipe competitions. Involuntary flexion increased to the point that he could no longer play professionally. He noted a similar feeling in his fourth and fifth fingers when using a calculator, but otherwise did not have difficulties with any other tasks. He was unaware of weakness of the left hand. Evaluation at another center included imaging studies of the neck revealing mild cervical spondylosis. A nerve conduction study of the arms performed 5 months prior to our evaluation was unrevealing. Aside from slight Dupytren’s contractures, general physical examination at our center was unremarkable. The fourth and fifth fingers of the left hand were slightly flexed when the hand was at rest. There was also evidence of a left ulnar neuropathy at the elbow, with a positive Tinel sign, mild atrophy and weakness (MRC 5-/5) in the flexor carpi ulnaris, abductor digiti minimi, and flexor digitorum profundus (V), and decreased sensation in the volar aspect of the fifth finger. CLINICAL/SCIENTIFIC NOTES As shown in the videotape, when playing the bagpipe his left fourth and fifth fingers involuntarily curled, pulling the fourth finger off the keyhole. A fine tremor of the left arm was also noted. Nerve conduction studies were repeated, revealing marked conduction slowing across the elbow on the left and occasional fasciculations in the first dorsal interosseous. A diagnosis of an ulnar neuropathy at the elbow was made, and he underwent a surgical release of the left ulnar nerve. Discomfort and pain in the medial aspect of the left arm resolved soon after surgery. The degree of atrophy and weakness were too small to appreciate a significant improvement on follow-up evaluation 5 months later. However, his dystonia has remained essentially unchanged. Discussion We report two patients who developed FTSD following peripheral trauma. In the first case, dystonia of the embouchure began immediately after trauma to the lips and teeth. Although evidence of injury disappeared in 1 week, her FTSD progressed to the point that she was forced to give up performing. Her abnormal movements consisted primarily of tremor, and so her movement disorder might also be classified as a task-specific tremor. We chose to call it a FTSD because we have observed similar patterns of tremor in other patients with embouchure dystonia.8 In the second patient, symptoms of FTSD began concurrently with a traumatic ulnar neuropathy. In both cases, symptoms exclusively affected the part of the body that had been injured. The nature of the traumatic insult was different in these two patients: soft tissue injury in the first and compressive neuropathy in the second. Although the extent of local injury was mild in both cases, disappearing in 1 week in the first patient and causing only mild weakness in the second, FTSD was progressive and disabling in both instances. Many patients have been reported with focal dystonia following peripheral trauma. The best known examples of these occur in the setting of reflex sympathetic dystrophy. Abnormal movements are relatively common in reflex sympathetic dystrophy, occurring in over 20% of affected patients.9 Focal dystonias following peripheral trauma may also affect the neck, shoulder, and lower face. Patients with acute posttraumatic cervical dystonia manifest sustained postures of the shoulder and neck, typically with marked shoulder elevation or neck tilt. Sensory tricks are absent, dystonia does not vary with activating maneuvers, and the response to treatment with medications and botulinum toxin is poor.3 Similar clinical syndromes affecting the shoulder4 and the jaw10 have been described. Our report of FTSD triggered by peripheral trauma is not without precedent. Charness reported 24 patients similar to our second patient with task-specific dystonic flexion of the fourth and fifth finger associated with an ipsilateral ulnar neuropathy.11 In some patients, ulnar neuropathy could be demonstrated only on near-nerve conduction studies. Patients with dystonia are predisposed to peripheral nerve injury, and it is possible that both resulted independently from a common antecedent trauma. It was not possible to date the onset of ulnar neuropathy or dystonia in Charness’ series. However, dystonia improved with treatment of the ulnar neuropathy, and in several patients it worsened after the nerve was reinjured. This suggests that at the very least, peripheral nerve injury can worsen dystonia that is already present, and perhaps can trigger its onset. The argument could be advanced that our second patient’s movement disorder might represent a compensatory maneuver 349 to compensate for ulnar weakness. We think this is unlikely for the following reason. The left fourth finger normally lightly covers the keyhole by flexion at the metacarpophalangeal (MCP) joint (through ulnar-innervated lumbricals), and the left fifth finger normally remains in repose. To compensate for weakness of MCP flexion of the fourth finger, one might expect the patient to cover the keyhole by selectively flexing the middle and distal joints of the fourth digit. However, as seen in the videotape, involuntary flexion of both the proximal and distal portions of the fourth and fifth digits were triggered as soon as he started to play. These movements were not compensatory, because they could not be voluntarily suppressed and did not improve his playing but actually hindered it. Charness described the same pattern of abnormal muscle recruitment in his series of musicians with ulnar neuropathy and dystonic flexion of the fourth and fifth digits. His patients often initially recruited median superficial flexors to compensate for ulnar lumbrical weakness (that is, hitting a key by flexing the distal portion of the finger rather than by flexing the MCP joint). Over time, voluntary compensatory flexion of the distal digit transformed into involuntary forced flexion of the fingers. How might peripheral trauma trigger an FTSD? Byl and colleagues have developed a primate model of focal dystonia that may help answer this question. Owl monkeys trained to maintain an attended grasp on a handgrip or close a handpiece against force developed a task-specific movement disorder of the hand after 20 weeks of repetitions. The primary somatosensory cortical receptive fields of the hand were markedly abnormal. Cortical representations of the skin were dedifferentiated, with a 10-fold increase in the size of receptive fields. There was also a breakdown in the normal separation of the representation of digits, and their topography was disordered.7 Despite the intensity and number of repetitions, the nerves and flexor tendons in these animals did not reveal evidence of inflammation. However, in one animal that developed a movement disorder after only 5 weeks of training (as compared with the usual 20–25 weeks required), an unexpected anatomic restriction of the flexor profundus tendon was found. This raises the possibility that peripheral mechanical factors were responsible for the rapid development of the movement disorder in this animal.7 We propose that the nature of the trauma is less critical to the development of dystonia than the location of the insult. This is supported by the clinical observation of focal dystonia following a variety of insults, including mechanical compression, surgery, or even electrocution.12 The nature of the traumatic insult differed in our two patients. However, given the temporal and anatomic link of trauma and the development of dystonia, it seems unlikely that their movement disorders were coincidental. These cases demonstrate that local, anatomically restricted peripheral trauma may trigger the development of an FTSD in patients who are predisposed to the condition by their repetitive and intense daily practice routines. Legends to the Videotape Segment 1: The first patient is shown whistling and protruding her tongue without difficulty. Playing with the mouthpiece alone and with the trumpet, involuntary tremor of the upper and lower lips is visible and audible at the onset of playing. The lateral corners of her mouth cannot maintain contact with the mouthpiece, destroying her air seal. Nasal flairing is also Movement Disorders, Vol. 15, No. 2, 2000 350 CLINICAL/SCIENTIFIC NOTES present. Her difficulty is worse in the upper registers of the instrument. Segment 2: Mild weakness of the abductor digiti minimi is demonstrated in the second patient’s left hand. He is shown playing the bagpipe chanter. Involuntary flexion of the left fourth and fifth fingers occurs as soon as he plays. This pulls the fourth finger off the keyhole, producing audible errors in performance. A fine tremor of the left arm is also present. Steven Frucht, MD Stanley Fahn, MD Blair Ford, MD Columbia-Presbyterian Medical Center New York, NY, U.S.A. References 1. Gowers WR. A Manual of Diseases of the Nervous System. London: Churchill, 1888:656. 2. Tolosa ES, Marti MJ. Adult-onset idiopathic torsion dystonias. In: Watts RL, Koller WC. Movement Disorders; Neurologic Principles and Practice. New York, NY: McGraw-Hill, 1997:433. 3. Tarsy D. Comparison of acute- and delayed-onset posttraumatic cervical dystonia. Mov Disord 1998;13:481–485. 4. Thyagarajan D, Kompoliti K, Ford B. Post-traumatic shoulder ‘dystonia’: persistent abnormal postures of the shoulder after minor trauma. Neurology 1998;51:1205–1207. 5. Jankovic J, Van Der Linden C. Dystonia and tremor induced by peripheral trauma: predisposing factors. J Neurol Neurosurg Psychiatry 1988;51:1512–1519. 6. Byl NN, Merzenich MM, Cheung S, Bedenbaugh P, Nagarajan SS, Jenkins WM. A primate mode for studying focal dystonia and repetitive strain injury: effects on the primary somatosensory cortex. Phys Ther 1997;77:269–284. 7. Topp KS, Byl NN. Movement dysfunction following repetitive hand opening and closing: anatomical analysis in owl monkeys. Mov Disord 1999;14:295–306. 8. Frucht S, Fahn S, Ford B. French horn embouchure dystonia. Mov Disord 1999;14:171–173. 9. Schwartzman RJ, Kerrigan J. The movement disorder of reflex sympathetic dystrophy. Neurology 1990;40:57–61. 10. Schrag A, Bhatia KP, Quinn NP, Marsden CD. Atypical and typical cranial dystonia following dental procedures. Mov Disord 1999;14:492–496. 11. Charness ME, Ross MH, Shefner JM. Ulnar neuropathy and dystonic flexion of the fourth and fifth digits: clinical correlation in musicians. Muscle Nerve 1996;19:431–437. 12. Tarsy D, Sudarsky L, Charness ME. Limb dystonia following electrical injury. Mov Disord 1994;9:230–232. Paraneoplastic Choreic Syndrome During Non-Hodgkin’s Lymphoma Both Hodgkin’s and non-Hodgkin’s systemic lymphomas can affect the central nervous system (CNS),1–3 as a result of a direct spread from primary nodal or extranodal sites. OccasionA videotape accompanies this article. Received May 5, 1998; revision received April 9, 1999. Accepted July 12, 1999. Address correspondence and reprint requests to Ubaldo Bonuccelli, MD, Department of Neuroscience, University of Pisa, Via Roma, 67 I-56126 Pisa, Italy. Movement Disorders, Vol. 15, No. 2, 2000 ally, it is also possible to observe primary cerebral lymphomas.4 CNS involvement during lymphoma may also occur as a result of radiotherapy or chemotherapy, opportunistic infections of the CNS resulting from bacteria, fungi, or virus, or hemorrhage resulting from thrombocytopenia. In other cases, neurologic involvement is the result of a paraneoplastic syndrome such as encephalomyelopathy and cerebellar cortical degeneration.4 So far only one case of primary CNS lymphoma has been reported in which the first neurologic manifestation consisted of focal choreic involuntary movements.5 We report the case of a patient with non-Hodgkin’s systemic lymphoma and choreic syndrome, presumably paraneoplastic in nature. Case Report A 70-year-old man was observed for the appearance of involuntary movements, slight memory impairment, and transient temporal and spatial disorientation. Family and personal history were negative for neuropsychiatric disorders. No neuropsychoactive drugs had been used by the patient before the appearance of neurologic symptoms. Anamnestic investigation revealed that for a few months the patient had been presenting polyuria, nicturia, anorexia, loss of weight, and occasionally slight fever. Examination showed brief, random, sudden, involuntary movements characterized by bilateral rotation of the head, facial grimaces, raising of the shoulders, abduction of the arms, and intra- or extra-rotation of the feet; deep tendon reflexes were brisk but symmetric. During his hospital stay, he underwent routine blood test, which was normal except for alpha-1acid-glycoprotein 204.1 mg/dL (normal values (n.v.) 55–140), C-reactive protein 10.2 mg/dL (n.v. <0.5), LDH 580 U/l (n.v. <450), white blood count 2600/mm3 (n.v. 7000 ± 3000), red blood count 3,590,000/mm3 (n.v. 5,400,000 ± 900,000), hemoglobin 9.6 g/dL (n.v. 16.0 ± 2.0), hematocrit 30.1% (n.v. 45 ± 7), and platelets 104,000/mm3 (n.v. 130,000–400,000); other laboratory investigations were normal: thyroid hormones, serum copper and ceruloplasmin, serum lactate and pyruvate, search for achantocytes, rheumatoid factor, LE phenomenon, lupus anticoagulant, anticardiolipine antibodies, anti-Borrelia burgdorferi antibodies, and urine tests for copper and aminoacid levels. The genetic test for Huntington’s disease was negative. Cerebral spinal fluid (CSF) examination was normal, in particular, there was no pleiocytosis or abnormal cytology and CSF cultures were sterile. Immunocytochemical studies of CSF, including isoelectrofocusing for oligoclonal bands and anti-Hu and anti-Yo antibodies, were negative. Both human T-cell lymphoma virus (HTLV-I) and human immunodeficiency virus (HIV) antibodies in serum and CSF were negative as well as syphilis serology. Electroencephalogram, cranial computed tomography (CT) with and without contrast medium, cranial magnetic resonance imaging (MRI; 1.5 Tesla) with gadolinium infusion, and spinal cord MRI were negative. Neuropsychological tests showed compromission of language with dysarthria and dysgraphia, short- and long-term memory dysfunctions, and constructional apraxia. The Mini Mental State6 score was 17/30. Abdominal echography, thoracic and abdominal CT, bone marrow biopsy, and right axillary lymphonode biopsy allowed a diagnosis of immunoblastic non-Hodgkin’s T-cell lymphoma, IV (B) stage, according to the NonHodgkin’s Lymphoma Classification Project,7 with thoracic and abdominal nodal lesions. CLINICAL/SCIENTIFIC NOTES The patient was treated with eight weekly infusions with an alternating chemotherapy regimen including adriamycin, etoposide, cyclophosphamide, vincristine, bleomycin, and prednisolone (P-VABEC8). During chemotherapy a clear-cut reduction of choreic movements was observed. The score of the abnormal involuntary movements scale (AIMS9) dropped from 21/42 (basal value) to 6/42 (final value after chemotherapy cycles). General symptomatology and hematologic parameters concomitantly improved with resolution of nodal lesions in thoracic and abdominal sites. Seven months after the end of chemotherapy, the subject had paranoid ideation with the reappearance of choreic movements (AIMS 4 18/42). A new restaging showed nodal abdominal and thoracic lesions again. After a new P-VABEC cycle8 of chemotherapy, a reduction of choreic movements (AIMS 4 4/42) and the disappearance of focal thoracic and abdominal sites were observed. The improvement of choreic movements has persisted to date, 10 months after the end of the last PVABEC cycle.8 Discussion Both B- and T-cell lymphomas of systemic origin may spread to the CNS with fairly high frequency.10 Clinical involvement of the CNS usually occurs late in the course of such disorders and in the setting of advanced and known progressive diseases.10–12 In our case instead, neurologic symptomatology antedated the diagnosis of systemic non-Hodgkin’s lymphoma and constituted the first important clinical sign, supporting the admission to the hospital and the final diagnosis. So far, no cases of non-Hodgkin’s systemic lymphoma in which a choreic symptomatology represented the first appearance have been reported. On the other hand, also in primary cerebral lymphomas with basal ganglia involvement, the presence of movement disorders, such as chorea and segmental dystonia, has rarely been reported.5,13,14 In our patient, we can hypothesize that an etiologic correlation between the appearance of involuntary movements and of aspecific systemic symptomatology, often the initial sign of lymphoproliferative systemic disorders, was present. Moreover, a cycle of chemotherapy resulted in a dramatic reduction in choreic movements with marked simultaneous improvement of hematologic parameters and general condition. Finally, other causes of chorea were excluded. Extensive clinical, laboratory, and instrumental evaluations allowed us to exclude, in our patient, both a lymphomatous infiltration of meningeal structures and direct invasion of the nervous tissue. Also, an opportunistic infection was ruled out. We suggest that the choreic movements appeared on a paraneoplastic basis. By definition, the pathogenesis of the paraneoplastic syndrome is unknown; the best current hypothesis is that most, if not all, paraneoplastic syndromes are immunemediated.15 In our patient, no specific autoimmune serologic or CSF markers for a paraneoplastic syndrome were observed. However, paraneoplastic antibodies are not very sensitive, in that many patients with paraneoplastic syndromes do not harbor identifiable antibodies.16 The fact that a specific chemotherapy regimen induced a dramatic improvement of choreic movements, presumably by immunosuppression, might support the role of immunemediated mechanisms in the genesis of choreic symptomatol- 351 ogy in our case. Furthermore, immunologic abnormalities have been reported in different choreatic conditions such as Sydenham’s chorea17 and Huntington’s disease.18 Choreic dyskinesias also can be observed in patients with immunologic diseases such as systemic lupus erythematosus and primary antiphospholipid antibody syndrome.19 Finally, steroid drugs have been reported to improve choreatic movements in Huntington’s disease and tardive dyskinesias.20,21 In conclusion, although the pathogenetic mechanism in our case is speculative, this report suggests that the remote effects of a cancer should be considered in the differential diagnosis of chorea of unknown origin. Legends to the Videotape Segment 1 illustrates the patient’s choreic movements in the orofacial area, neck, trunk, and limbs, as observed at the time of the first neurologic consultation. Segment 2 shows the clear-cut reduction of the chorea after the chemotherapy. Note the disappearance of choreic movements in the limbs and the marked improvement in axial chorea. Angelo Nuti, MD Roberto Ceravolo, MD Stefania Salvetti, MD Gianna Gambaccini, MD Ubaldo Bonuccelli, MD Department of Neuroscience Section of Neurology University of Pisa Pisa, Italy Enrico Capochiani, MD Department of Internal Medicine Hematology Unit University of Pisa Pisa, Italy References 1. Herman TS, Hammond N, Jones SE. Involvement of central nervous system by non-Hodgkin’s lymphoma. The Southwest Oncology Group experience. Cancer 1979;43:390–397. 2. Levitt LJ, Dawson DM, Rosenthal DS, Moloney WC. CNS involvement in the non-Hodgkin’s lymphomas. Cancer 1980;45: 545–552. 3. Herman MD, Gordon LI, Kaul K, Varakojis D, Bauer K, Levy RM. Systemic T-cell lymphoma presenting with isolated neurological dysfunction and intraparenchymal brain lesions. J Neurosurg 1993;78:997–1001. 4. Davies-Jones GAB. Neurological manifestations of hematological disorders. In: Aminoff MJ, ed. Neurology and General Medicine. New York, NY: Churchill-Livingstone, 1995:219–246. 5. Poewe WH, Kleedorfer B, Willeit J, Gerstenbrand F. Primary CNS lymphoma presenting as a choreic movement disorder followed by segmental dystonia. Mov Disord 1988;3:320–325. 6. Folstein MF, Folstein SE, McHugh PR. Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198. 7. Non-Hodgkin’s Lymphoma Classification Project. National Cancer Institute sponsored study of classifications of non-Hodgkin’s lymphoma: summary and description of working formulation for clinical usage. Cancer 1982;49:2112–2135. 8. Caracciolo F, Petrini M, Capochiani E, Papineschi F, Carulli G, Grassi B. Alternating chemotherapy regimen (P-VABEC) for intermediate and high-grade non-Hodgkin’s lymphoma of the middle aged and elderly. Hematol Oncol 1994;12:185–192. Movement Disorders, Vol. 15, No. 2, 2000 352 CLINICAL/SCIENTIFIC NOTES 9. Guy W. Abnormal involuntary movement scale. In: ECDEU Assessment Manual for Psychopharmacology. Washington, DC: US Dept of Health, Education and Welfare, 1976:534–537. 10. Morgello S, Maiese K, Petito CK. T-cell lymphoma in the CNS: clinical and pathological features. Neurology 1989;39:1190–1196. 11. Pinkus GS, Said JW, Hargreaves H. Malignant lymphoma, T-cell type: a distinct morphologic variant with large multilobate nuclei, with a report of four cases. Am J Clin Pathol 1979;72:540–550. 12. Brisbane JU, Berman LD, Neiman RS. Peripheral T-cell lymphoma: a clinicopathological study of nine cases. Am J Clin Pathol 1983;79:285–293. 13. Letendre L, Banks PM, Reese DF, Miller RH, Scanlon PW, Kiely JM. Primary lymphoma of the central nervous system. Cancer 1982;49:939–943. 14. Helle TL, Britt RH, Colby TV. Primary lymphoma of the central nervous system. J Neurosurg 1984;60:94–103. 15. Voltz RD, Posner JB, Dalmau J, Graus F. Paraneoplatic encephalomyelitis: an update of the effects of the anti-Hu immune response on nervous system and tumor. J Neurol Neurosurg Psychiatry 1997;63:133–136. 16. Posner JB. Paraneoplastic syndromes. Curr Opin Neurol 1997;6: 471–476. 17. Husby G, van de Rijn I, Zabriskie JB. Antibodies reacting with cytoplasm of subthalamic and caudate nuclei neurons in chorea and acute rheumatic fever. J Exp Med 1976;144:1094–1110. 18. Husby G, Li L, Davis LE, Wedege E, Kokmen E, Williams RC Jr. Antibodies to human caudate nucleus neurons in Huntington’s chorea. J Clin Invest 1977;59:922–932. 19. Mark M. Other choreatic disorders. In: Watts RL, Koller WC, eds. Movements Disorders. Neurologic Principles and Practice. New York, NY: McGraw-Hill, 1996:527–540. 20. Bonuccelli U, Nuti A, Maremmani C, Ceravolo R, Muratorio A. Steroid therapy in Huntington’s disease. In: Biggio G, Concas A, Costa E, eds. Gabaergic Synaptic Transmission. New York, NY: Raven Press, 1992:149–154. 21. Benecke R, Conrad B, Klingenhofer J. Successful treatment of tardive and spontaneous dyskinesias with corticosteroids. Eur Neurol 1988;28:146–149. Botulinum Toxin for the Treatment of Oro-Facial-Lingual-Masticatory Tardive Dyskinesia Botulinum toxin A (BTX-A) has been found to be effective in the treatment of focal dystonias, blepharospasm, and hemifacial spasm1,2; more recently, its use has been expanded to spasticity, tics, tremors, spastic dysphonia, torticollis, and sphincter dysinergia.1 The mechanism of action of the drug is related to chemical denervation at the motor end terminal of the alpha motor neuron, resulting in focal muscle paralysis.3 Local adverse effects include pain, equimosis, exposure keratitis, facial distortions, paresis, bruising, and infections, but they are usually mild and transient.3,4 Dysarthria, dysphagia, flu- Received May 5, 1998; revision received February 3, 1999. Accepted May 24, 1999. We declare that no other financial support was received from Speywood and that the authors do not have any connections to their commercial or financial activities. Dysport is now marketed by Ipsen Pharmaceuticals, Ltd, Maidenhead, Berkshire, UK. Address correspondence and reprint requests to Abraham Rapaport, MD, The Department of Neurology, Wolfson Medical Center, PO Box 5, Holon 58100, Israel. Movement Disorders, Vol. 15, No. 2, 2000 like symptoms, and production of antibodies have also been reported.3,5 Tardive dyskinesias occur in approximately 30% of patients receiving dopamine-blocking agents.6 The most prevalent is the oro-facial-lingual-masticatory (OLFM) type, which accounts for 80% of cases.6 In patients with mild to moderate disease, therapeutic efforts are directed primarily at minimizing exposure to neuroleptic agents or changing to atypical antipsychotics7; however, for severe tardive dyskinesia, no single treatment strategy has as yet emerged.7 Dopamine-depleting drugs and gamma-aminobutyric acid agonists are frequently beneficial but they produce a variety of adverse effects.6 Medications with relatively few side effects that have demonstrated efficacy for some patients include calcium channel blockers, adrenergic antagonists, and vitamin E.7 To date, only a few case reports have evaluated the efficacy of BTX-A in the treatment of neuroleptic-induced tardive dystonia and tardive dyskinesia.4,5 Improvement was noted after several injections and was sustained, in some cases, for several months following treatment.4,5 The aim of this study was to assess the efficacy of BTX-A in the treatment of OLFM tardive dyskinesia. Methods Patients The study followed an open-label design. The study population consisted of 12 psychiatric inpatients, eight women and four men with a mean age 73.5 ± 11.9 years. Their demographic and clinical characteristics are summarized in Table 1. Ten patients had schizophrenia and two had bipolar affective disorder; all diagnoses were based on DSM-IV criteria.8 The duration of disease was 26–45 years, and the number of hospitalizations was three to 24. The patients were receiving longterm treatment with phenothiazines or butyrophenones. All had been exhibiting abnormal OLFM movements for at least 3 consecutive months, and all had failed to respond to at least one previous attempt to treat the dyskinesia. Patients with a history of a movement disorder before neuroleptic treatment, seventh nerve disease, or dental pathology (infections, surgery, trauma, or prosthesis) were excluded from the study. The study was approved by the Helsinki Ethics Committee of Abarbanel Mental Health Center, Bat Yam, Israel. All participants and their families gave informed consent. Assessment Prior to and at the end of the study, the patients underwent a complete physical and neurologic examination and the following laboratory tests: erythrocyte sedimentation rate, complete blood cell count, kidney, liver, and thyroid function, and an electrocardiogram. The patients continued to receive their regular neuroleptic medication throughout the trial period and no other medications were allowed. OLFM tardive dyskinesia was determined by the Abnormal Involuntary Movement Scale (AIMS),9 and the severity of the abnormal movements was rated with the Tardive Dyskinesia Rating Scale (TDRS).9 To be included in the study, the severity score on the TDRS had to be at least within the moderate range. Patients were evaluated before receiving the local injections of BTX-A and thereafter at 1, 5, and 8 weeks. Adverse effects were assessed at these times. All evaluations were performed independently by two raters well experienced in these scales CLINICAL/SCIENTIFIC NOTES 353 TABLE 1. Demographic and clinical data Psychiatric diagnosis Duration of illness (yrs) Patient Gender Age (yrs) 1 M 53 2 F 71 3 F 78 Schizoaffective disorder 27 4 M 63 26 5 F 83 Schizophrenia residual Schizophrenia paranoid 6 F 79 Schizophrenia disorganized 35 7 F 71 Schizoaffective disorder 30 8 M 68 Schizophrenia disorganized 45 9 F 71 Schizophrenia residual 41 10 M 77 Schizophrenia paranoid 37 11 F 82 Bipolar disorder 28 12 F 78 Bipolar disorder 38 Schizophrenia paranoid Schizophrenia simple 31 34 36 Abnormal movements Choreoathetoid, T risorius hyperfunction Pouting, LL puckering, L sucking, grimacing, dysarthria choreoathetoid, T Pouting, LL puckering, L sucking, chewing chin dyskinesias Dysarthria bonbon sign Pouting, LL protrusion, T grimacing, dysarthria Choreoathetoid, T rhythmic opening of mouth, grimacing, dysarthria Choreoathetoid, T grimacing, dysarthria pouting, LL protrusion, T Choreoathetoid, T pouting, LL protrusion, T Choreoathetoid, T dysarthria, rabbit syndrome, bonbon sign, puckering, L pouting, LL tremor, UL Choreoathetoid, T chewing, facial tics puckering, L pouting, LL grimacing smacking, L Pouting, LL puckering, L smacking, L grimacing Tremor, T, UL, perioral, rabbit syndrome L, lips; LL, lower lip; UL, upper lip; T, tongue. (AR and DS). Interrater reliability for the severity of OLFM dyskinesia was approximately .85. Technique and Rationale of Injection The patients received a standard subcutaneous dose of 80 units of BTX-A (Dysportt, Berkshire, UK) divided into four anatomic sites (20 units or 0.1 mL per site) as follows: 1 cm lateral to the buccal commissures, midpoint of the upper lip, and the mid-central area of the chin. This dose was chosen as being the standard dose injected into each eyelid in cases of hemifacial spasm given at multiple sites up to a total of 120 units per eyelid.2 All injections in individual patients were performed on the same day with a tuberculin syringe and a 27-g needle. Multiple-site injections were used to achieve a homogeneous effect, because BTX-A tends to diffuse away from the point of injection. In our patients who have complex movement abnormalities involving diffuse innervation of the associated muscles, multiple injections have the potential to increase the saturation of the innervation zones.10 The target muscles were the orbicularis oris, which contains fibers originating from the buccinator, levator, and depressor anguli oris, risorius, zygomaticus major and minor, and the ala nasi. A subcutaneous route was used because these muscles are superficial and attached to the skin. Movement Disorders, Vol. 15, No. 2, 2000 354 CLINICAL/SCIENTIFIC NOTES FIG. 1. Tardive Dyskinesia Rating Scale—total: mean (± SD) scores at evaluation points. Statistical Analysis The TDRS total score was calculated at each evaluation point according to the TDRS scoring system.9 Overall change was analyzed with the Friedman Test for k-related samples. Changes at each follow-up assessment from baseline, for the total TDRS and for individual items, were calculated with the Wilcoxon signed rank test. All p values are for two-sided tests. Results Figure 1 shows the mean (± standard deviation) total TDRS score at each time point. A significant reduction from baseline (43.9 ± 17) was seen after 1 week (to 31.3 ± 5, p 4 0.008), 5 weeks (to 27.0 ± 4, p 4 0.013), and 8 weeks of treatment (27.6 ± 7, p 4 0.013). All patients exhibited two or more abnormal OLFM movements. The movements were mainly choreoathetoid in nature, with the exception of the more stereotyped FIG. 2. Tardive Dyskinesia Rating Scale—individual items: mean (± SD) scores at evaluation points. Movement Disorders, Vol. 15, No. 2, 2000 rabbit syndrome and tongue and perioral tremors. The most frequent individual dyskinesias (Table 1) were pouting of the lower lip (eight patients), choreoathetoid movements of the tongue (seven patients), grimacing (six patients), dysarthria (six patients), puckering of lips (five patients), and tongue protrusion (three patients). As shown in Figure 2, there was a significant response to BTX-A for pouting, grimacing, and dysarthria, and a trend for improvement for puckering and choreoathetoid movements of the tongue. No local adverse effects were noted, and no dysphagia, dysarthria, fever, or flu-like symptoms. All laboratory tests were within normal limits. Discussion Although there are limitations to an open trial performed in only 12 patients, the present study demonstrates the beneficial CLINICAL/SCIENTIFIC NOTES effect of BTX-A in the treatment of OLFM tardive dyskinesia. Grimacing, dysarthric speech, and involuntary movements of the tongue were among the frequent individual abnormal movements that responded best to injections, even though the tongue itself was not injected. Interestingly, in another study of BTXA, Yasufuku-Takano et al.5 also reported an improvement in some dyskinetic movements associated with noninjected muscles. Tongue protrusion dyskinesia was not affected. However, only a few patients demonstrated this abnormal movement, and it was not specifically treated (the tongue was not injected). The submandibular muscles were also not injected to specifically treat masticatory dyskinesias because of the risk of dysphagia.1 Forced-dyskinetic closure of the mouth did not significantly affect our patients so we did not inject the masseter and pterygoid muscles. Adverse effects were less severe in our cohort than in previous series.3–5 This discrepancy may be explained by differences in technique. In earlier studies, each site was injected several times,2 whereas in ours, the patients received only one injection per site with a relatively low dose. In conclusion, our results suggest that BTX-A may be beneficial for the treatment of OLFM tardive dyskinesia secondary to dopamine receptor blockers. These results are particularly encouraging because of the lack of significant adverse effects, and because the patients had failed to respond to at least one previous treatment strategy. Controlled double-blind trials for extended periods are required to verify our findings and to establish the place of BTX-A in the treatment of OLFM tardive dyskinesia. Acknowledgment: The authors thank Speywood Pharmaceuticals, Ltd, Berkshire, UK, for supplying the Dysport vials used in the study. Abraham Rapaport, MD Menachem Sadeh Department of Neurology Wolfson Medical Center Holon, Israel Sackler School of Medicine Tel Aviv University Tel Aviv, Israel Daniel Stein Sheba Medical Center, Tel Hashomer Sackler School of Medicine Tel Aviv University Tel Aviv, Israel Joseph Levine Beer Sheva Mental Health Center Beer Sheva, Israel Pinhas Sirota Tania Mosheva Shaul Stir Avner Elitzur Ilia Reznik Abarbanel Mental Health Center Bat Yam, Israel Sackler School of Medicine Tel Aviv University Tel Aviv, Israel 355 Diklah Geva Department of Biostatistics and Epidemiology Wolfson Medical Center Holon, Israel J. Martin Rabey Sackler School of Medicine Tel Aviv University Tel Aviv, Israel Department of Neurology Assaf Harofe Hospital Tzrifin, Israel References 1. Jankovic J, Brin MF. Therapeutic uses of botulinum toxin. N Engl J Med 1991;324:1186–1194. 2. Mauriello JA Jr, Leone T, Dhilon S, Pakeman B, Mostafavi R, Yepez MC. Treatment choices of 119 patients with hemifacial spasm over 11 years. Clin Neurol Neurosurg 1996;98:213–216. 3. Dutton JJ. Botulinum-A toxin in the treatment of craniocervical muscle spasms: short and long-term local and systemic effects. Surv Ophthalmol 1996;41:51–65. 4. Chatterjee A, Forrest GM, Giladi N, Trosch R. Botulinum toxin in the treatment of tardive dystonia. J Clin Psychopharmacol 1997; 17:497–498. 5. Yasufuku-Takano J, Sakurai M, Kanazawa I, Nagoka M. Successful treatment of intractable tardive dyskinesia with botulinum toxin. J Neurol Neurosurg Psychiatry 1995;58:511–512. 6. Jankovic J. Tardive syndromes and other drug-induced movement disorders. Clin Neuropharmacol 1995;18:197–214. 7. Egan MF, Apud J, Wyatt RJ. Treatment of tardive dyskinesia. Schizophr Bull 1997;23:583–609. 8. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Press, 1994. 9. Abnormal Involuntary Movement Scale (AIMS) and Tardive Dyskinesia Rating Scale (TDRS). Psychopharmacol Bull 1988;24: 781–783. 10. Borodic GE. Hemifacial spasm, evaluation and management with emphasis on botulinum toxin therapy. In: Jankovic J, Hallett M, eds. Therapy with Botulinum Toxin. New York, NY: Marcel Dekker, 1994:331–353. Propriospinal Myoclonus in Ischemic Myelopathy Secondary to a Spinal Dural Arteriovenous Fistula In 1991, Brown et al.1 described propriospinal myoclonus in people, a peculiar type of spinal myoclonus originating in the long propriospinal pathways and involving axial muscles. Since then, several reports on propriospinal myoclonus have appeared, most cases proving to be idiopathic or secondary to mild spinal cord injuries without any significant magnetic resonance image (MRI) abnormalities.2–5 Propriospinal myoclonus A videotape accompanies this article. Received July 28, 1999; revisions received October 21 and November 18, 1999. Accepted November 18, 1999. Address correspondence and reprint requests to Martı́n Nogués, MD, Departamento de Neurologı́a Clı́nica, Instituto de Investigaciones Neurológics Raúl Carrea, Montañeses 2325 (1428) Buenos Aires, Argentina. Movement Disorders, Vol. 15, No. 2, 2000 356 CLINICAL/SCIENTIFIC NOTES has also been documented in association with severe spinal cord injury,6 multiple sclerosis,7 HIV infection,8 Lyme neuroborreliosis,9 and syringomyelia.10 Detailed electrophysiological studies have localized the spinal generator to the thoracic spinal cord in most cases. Here we describe severe extensor axial propriospinal myoclonus in a patient with an ischemic myelopathy secondary to a spinal dural arteriovenous fistula (SDAVF), a condition not previously associated with propriospinal myoclonus. The myoclonus originated at the level of the lumbar segments of the spinal cord. Case Report A 70-year-old woman with a history of mild arterial hypertension, heavy smoking, and surgical resection and radiotherapy for a breast carcinoma in 1980 developed a slowly progressive distal lower limb weakness, urinary incontinence, and burning pain radiating from the lumbar region to both feet in 1994. Cerebrospinal fluid analysis showed 91 mg% protein, normal cell count, 47 mg% glucose, and no malignant cells. Brain MRI disclosed T2-weighted small white matter lesions, and a spinal MRI showed an abnormal T2-hyperintense central cord lesion suggestive of edema or ischemia extending from T8 to the conus medullaris (Fig. 1). Spinal angiographic examination by hypogastric artery injection demonstrated arteriovenous shunting into an enlarged pial vein of the spinal cord indicating the presence of an SDAVF. No abnormalities were present at other levels, apart from severe atheromatosis. Embolization was performed with liquid acrylic injected through a posterolateral branch of the right hypogastric artery leading to complete occlusion of the SDAVF. This was followed by resolution of the urinary incontinence and improvement in lower limb weakness. Two months after the procedure and without any significant change in her neurologic status, she developed involuntary truncal jerks, which thereafter worsened in frequency and severity. Jerks appeared mainly while sitting, to a lesser degree standing or lying supine, and disappeared during sleep. Walking did not induce the jerks. Jerks were particularly severe during meals. On attempting to take a glass or some food to her mouth, she developed severe extensor axial jerks that on occasion threw her from her chair. On examination, cognitive function, cranial nerves, and upper limb motor and sensory examination were normal. She could only walk with assistance. There was moderate (MRC grade 4/5) bilateral weakness of the tibialis anterior and gastrocnemius muscles. Knee and ankle jerks were absent bilaterally, and plantar responses indeterminate. There was sensory loss for pain and temperature sensation in a saddle and sock distribution bilaterally. Deep sensation was normal. There were spontaneous extensor jerks involving mainly the paraspinal muscles while sitting or standing. When severe, the patient’s trunk and head were thrown backward so that it was necessary to protect her from injuries (see the videotape). Jerks could be evoked by a sudden and unexpected noise, by bending over, tapping the involved muscles, and particularly by lifting a glass with her right hand. Meals became distressing and she had to be fed in a wheelchair to avoid falls. She managed to drink and eat by concentrating on performing hand movements slowly and carefully. The response to sudden and unexpected noises habituated. Jerks were not influenced by breath-holding or hyperventilation, and disappeared during sleep. They were typically less frequent in the mornings, increasing in frequency and severity in the evenings. Myoclonus was not observed in the facial muscles and during jerks she was able to speak and breathe. Despite the presence of distal lower limb weakness, the patient was able to walk with support, and she was usually free from involuntary jerks during walking. A second MRI was remarkable for diffuse enlargement of the cord at levels below the midthoracic portion. On T2weighted images, increased signal intensity was present throughout the cord from midthoracic levels to the conus medullaris. Diffuse heterogeneous enhancement of the lower cord was apparent after gadolinium administration. Myoclonus failed to respond to medical treatment with 4.8 g piracetam per day or 1.5 g sodium valproate per day, and showed only modest improvement with 0.5 mg clonazepam per day. The patient was unable to tolerate higher doses of clonazepam. Electrophysiological Investigations FIG. 1. Pre-embolization MRI image: T2-weighted sagittal image demonstrating enhancement of the lower thoracic and lumbar spinal cord, especially of the conus medullaris. There are also large serpentine vessels on the anterior and posterior surface of the cord. Movement Disorders, Vol. 15, No. 2, 2000 Nerve conduction studies were normal except for lowamplitude peroneal nerve compound muscle action potentials. Needle electromyography (EMG) showed fibrillations and positive sharp waves in the gastrocnemius muscles bilaterally. Somatosensory evoked potentials disclosed prolongation of the initial positive cortical SEP after stimulation of the tibial nerve bilaterally at the ankle (44.8 msec on the right and 46.4 msec on the left side). The initial major cortical positive wave had an amplitude of 0.47 mV on the right side and 0.69 mV on the left side, a value within the normal range for our laboratory. EMG recordings of the lumbar, thoracic, and cervical paraspinal, rectus abdominis, orbicularis oculi, sternocleidomastoid, biceps, rectus femoris, tibialis anterior, and gastrocnemius muscles were obtained using surface electrodes placed over the muscle bellies. During EMG recording, the following stimuli CLINICAL/SCIENTIFIC NOTES were used: clapping, tendon taps, voluntary hand movements, and electrical stimulation of the median and tibial nerves. Spontaneous jerks occurred randomly at a frequency ranging from 0.5 to 5 jerks per minute, although at times they recurred in a semirhythmic pattern. EMG bursts were observed spontaneously or evoked by a sudden and unexpected noise or electrical stimulation of a peripheral nerve and showed a characteristic pattern of propagation. The onset of EMG activity was first recorded in the lumbar paraspinal muscles approximately in the region of the L2-L3 lumbar vertebrae, followed by rostral propagation to thoracic and cervical paraspinal muscles (Fig. 2). The approximate cord length between C7 and L2 is 30 cm,11 giving an approximate spinal conduction velocity of 4 m/s up the cord, which is entirely consistent with other reports.1–3,7 Mean latencies and standard deviation obtained from 10 successive jerks evoked by supramaximal median nerve stimulation at the wrist were: (1) lumbar paraspinal: 79.0 ± 10.0 msec; (2) rectus femoris: 95.0 ± 18.6 msec; (3) tibialis anterior: 106.0 ± 12.4 msec; (4) gastrocnemius: 107.0 ± 7.5 msec; (5) cervical paraspinal: 144.0 ± 5.0 msec; and (6) abductor pollicis brevis: 153 ± 5.1 msec. The mean duration of EMG bursts was 616.6 ± 32.5 msec (range, 400–1200 msec). Some delayed EMG activity was occasionally recorded from the orbicularis oculi and sternocleidomastoid muscles in the most violent jerks, perhaps as part of a startle response evoked by the involuntary jerk itself (or by hand claps, when these were used to elicit jerks). Discussion The main findings in this case report are: (1) the association of ischemic myelopathy with SDAVF, a further cause of propriospinal myoclonus; (2) the extreme severity of the jerks, particularly with actions such as eating, which became the most FIG. 2. Rectified EMG record of a single spontaneous jerk recorded from surface electrodes on paraspinal muscles along the spinal processes. Numbers in milliseconds indicate individual latencies of jerks in relation to sweep onset. The interval between onset of bursts at C7 and L2-L3 is 76 msec. The distance between L2 and C7 is approximately 30 cm,11 giving an approximate conduction velocity of 4 m/s. 357 disabling manifestation of the patient’s myelopathy; (3) the lack of response to medical treatment; and (4) the finding that audiogenic stimuli occasionally triggered the jerks. The exacerbation of spinal myoclonus by voluntary action and sound has also been reported in some cases with segmental myoclonus.12 The extension of the legs during the jerks seemed to be compensatory for the trunk displacement. A psychogenic origin for the jerks seemed unlikely given the presence of an underlying lesion and the order of recruitment of muscles, which was different from that observed in psychogenic myoclonus.13 From the electrophysiological point of view, a slow ascending conduction from the lumbar to the cervical spinal cord was recorded during spontaneous jerks, and also during jerks induced by clapping and electrical nerve stimulation with conduction velocities along the spinal cord in the range previously described in propriospinal myoclonus.1–4 Furthermore, electrical stimulation of peripheral nerves elicited motor responses in limb muscles at long latency, like frequently found in stimulus-sensitive reflex propriospinal myoclonus.12 Other focal spinal cord lesions may lead to segmental spinal myoclonus, including experimental encephalomyelitis resulting from Newcastle disease virus,14 ischemic infarction of the spinal cord,15 intramedullary tumors,16 and syringomyelia.10 Levy et al.17 described myoclonus affecting the thorax and abdomen in a 57-year-old man with a spinal arteriovenous malformation brought on consistently by Valsalva maneuver or forced exhalation, which responded to clonazepam therapy. Aminoff and Logue18 found spinal myoclonus in one of 60 patients with spinal arteriovenous malformations. It is thought that damage to inhibitory interneurons located in the central region of the spinal cord gray matter may lead to spinal cord disinhibition and myoclonus.16 Inhibitory interneurons are placed in the commissural spinal gray matter.16 In SDAVF, there is a tendency for ischemic lesions to extend ventrally from the posterior funiculus into the commissural gray matter.19,20 Neurologic findings in the present case and the presence of denervation in EMG are suggestive of predominant involvement of the central spinal cord, including the gray matter. A mechanism similar to the one proposed for generation of segmental spinal myoclonus, but leading to activation of propriospinal rather than segmental pathways, may be responsible for the appearance of propriospinal myoclonus. The actual role of embolization in the generation of propriospinal myoclonus is unclear, because there was a 2-month delay between the procedure and the appearance of involuntary movements. Embolization may lead to further ischemic damage but this was unlikely in our case, because the patient’s neurologic deficit improved after the procedure. SDAVF produces its damage by long-standing and progressively increased venous hypertension within the pial veins of the spinal cord,19 which may be reversed by embolization.21 Perhaps propriospinal myoclonus only appeared as long as propriospinal tracts recovered. Further study will be helpful in determining the actual incidence of spinal myoclonus in ischemic myelopathy and the therapeutic effect of intrathecal baclofen in severe propriospinal myoclonus resulting from this etiology. Legend to the Videotape Extensor axial muscle contractions together with lower limb extension occurring spontaneously on attempting to lift a glass Movement Disorders, Vol. 15, No. 2, 2000 358 CLINICAL/SCIENTIFIC NOTES or to write. There appears to be some habituation on repeated attempts. Knee extension movements are probably compensatory. The order of recruitment was different from that observed in psychogenic jumps.13 The patient is partially treated at the time of the video. Acknowledgments: The authors thank Professor Salomón Muchnik for referring the patient, Dr. Ana Pardal for her technical advice, and Mrs. Sonia Lepore for diligently typing the manuscript. Martı́n Nogués, MD Angel Cammarota, MD Claudia Solá Department of Clinical Neurophysiology Raúl Carrea Institute for Neurological Research (FLENI) Buenos Aires, Argentina Peter Brown, MD MRC Human Movement and Balance Unit Institute of Neurology Queen Square London, U.K. 15. Tarlov IM. Rigidity in man due to spinal interneuron loss. Arch Neurol 1967;16:536–543. 16. Rushworth G, Lishman WA, Hughes JT, Oppenheimer DR. Intense rigidity of the arms due to isolation of motoneurons by a spinal tumour. J Neurol Neurosurg Psychiatry 1961;24:132–142. 17. Levy R, Plassche W, Riggs J, Shoulson I. Spinal myoclonus related to an arteriovenous malformation. Response to clonazepam therapy. Arch Neurol 1983;40:254–255. 18. Aminoff M, Logue V. The prognosis of patients with spinal vascular malformations. Brain 1974;97:211–218. 19. Hurst R, Kenyon L, Lavi E, Raps E, Marcotte P. Spinal dural arteriovenous fistula: the pathology of venous hypertensive myelopathy. Neurology 1995;45:1309–1313. 20. Kim R, Smith H, Henbest M, Choi B. Nonhemorraghic venous infarction of the spinal cord. Ann Neurol 1994;15:379–385. 21. Criscuolo G, Oldfield E, Doppman J. Reversible acute and subacute myelopathy in patients with dural arteriovenous fistulas. J Neurosurg 1989;70:354–359. Marked Improvement in a Stiff-Limb Patient Treated With Intravenous Immunoglobulin References 1. Brown P, Thompson PD, Rothwell JC, Day BL, Marsden CD. Axial myoclonus of propriospinal origin. Brain 1991;114:197– 214. 2. Chokroverty S, Walters A, Zimmerman T, Picone M. Propriospinal myoclonus: a neurophysiologic analysis. Neurology 1992;42: 1591–1595. 3. Brown P, Rothwell JC, Thompson PD, Marsden CD. Propriospinal myoclonus: evidence for spinal ‘pattern’ generators in humans. Mov Disord 1994;9:571–576. 4. Shulze-Bonhage A, Knott H, Ferbert A. Pure stimulus-sensitive truncal myoclonus of propriospinal origin. Mov Disord 1996;11: 87–90. 5. Montagna P, Provini F, Plazzi G, Liguori R, Lugaresi E. Propriospinal myoclonus upon relaxation and drowsiness: a cause of severe insomnia. Mov Disord 1997;12:66–72. 6. Fouillet N, Wiart L, Arne P, Alaoui P, Petit H, Barat M. Propriospinal myoclonus in tetraplegic patients: clinical, electrophysiological and therapeutic aspects. Paraplegia 1995;33:678–681. 7. Kappor R, Brown P, Thompson PD, Miller DH. Propriospinal myoclonus in multiple sclerosis. J Neurol Neurosurg Psychiatry 1992;55:1086–1088. 8. Lubetzki C, Vidailhet M, Jedynak CP, et al. Propriospinal myoclonus in a patient seropositive for human immunodeficiency virus. Rev Neurol (Paris) 1994;150:70–72. 9. De la Sayette V, Schaeffer S, Queruel C, et al. Lyme neuroborreliosis presenting with propriospinal myoclonus [Letter]. J Neurol Neurosurg Psychiatry 1996;61:420. 10. Nogués MA, Leiguarda R, Rivero A, Salvat F, Manes F. Involuntary movements and abnormal spontaneous EMG activity in syringomyelia and syringobulbia. Neurology 1999;52:823–834. 11. Donaldson HH, Davis DJ. A description of charts showing the areas of the cross section of the human spinal cord at the level of each spinal nerve. J Comp Neurol 1903;13:19–40. 12. Brown P. Spinal myoclonus. In: Marsden CD, Fahn S, eds. Movement Disorders 3. Boston, MA: Butterworth Heinmann, 1994:467. 13. Thompson PD, Colebatch JG, Rothwell JC, et al. Voluntary stimulus-sensitive jerks and jumps mimicking myoclonus or pathological startle syndromes. Mov Disord 1992;7:257–262. 14. Luttrell CN, Bang FB. Newcastle disease encephalomyelitis in cats. I: clinical and pathological features. Arch Neurol Psychiatry 1958;79:647–657. Movement Disorders, Vol. 15, No. 2, 2000 Stiff-limb syndrome is a rare neurologic condition, recently described by Brown et al.1 and Barker et al.,2 characterized by the association of stiffness and painful spasms restricted to one or more limbs (usually the legs) and the presence of continuous motor unit activity. This syndrome was delineated in opposition to the stiff-trunk (or true stiff-man) syndrome which is also characterized by the association of stiffness, painful spasms, and continuous motor unit activity, but the distribution of the signs always involves the axial musculature. Apart from this difference, stiff-trunk (man) syndrome is usually associated with the presence of serum anti-GAD antibodies and responds well to treatment with a combination of baclofen and diazepam.3 On the contrary, stiff-limb syndrome is usually antiGAD-negative and does not respond well to these treatments. It was recently reported that patients with stiff-trunk syndrome responded to intravenous immunoglobulin, and this treatment, to our knowledge, has been tried specifically in one patient with stiff-limb syndrome by Saiz et al.4 The purpose of the present report is to describe the response of a patient with stiff-limb syndrome treated with intravenous immunoglobulin. Case Report A 60-year-old Brazilian woman had been well until 4 years ago when she noticed difficulty in walking and had sustained frequent falls related to startle reactions. One year later she began to have episodes of painful spasms in the left leg associated with intense sweating. These episodes became frequent and for 2 years she had persistent rigidity in the left leg and was A videotape accompanies this article. Received April 19, 1999; revisions received August 12 and December 17, 1999. Accepted December 17, 1999. Address correspondence and reprint requests to Henrique Ballalai Ferraz, MD, PhD, Alameda Casa Branca, 799 apto 72, São Paulo, SP-Brazil 01408-001. CLINICAL/SCIENTIFIC NOTES restricted to a wheelchair. She had no significant medical history. On examination she showed severe rigidity in the left lower limb which prevented its passive and active flexion. The left leg had a fixed posture of extension and the foot was plantar-flexed and internally rotated. Her deep tendon reflexes were brisk and the plantar responses were flexor. The rest of the neurologic examination was unremarkable. Magnetic resonance imaging studies of the brain and of the lumbosacral, thoracic, and cervical spinal cord were normal. Cerebrospinal fluid with protein electrophoresis was also normal. She was submitted to an extensive work-up seeking neoplasm, which was normal. She had no diabetes mellitus. Sensory and motor conduction were normal in the lower limbs. Concentric needle electromyography showed signs suggestive of chronic and recent denervation in the tibialis anterior, medial gastrocnemius, and extensor digitorum brevis muscles of the right leg. On the left leg, homologous muscles showed continuous motor unit activity at rest and abnormally segmented electromyographic activity during spasms. Lumbar paraspinal muscles showed continuous bilateral motor unit activity despite all attempts at relaxation. Serum anti-GAD antibodies were present (161.0 U/mL, with normal values below 1.0 U/mL). No other auto-antibodies were tested. She was treated with 400 mg/kg intravenous human immunoglobulin per day for 5 consecutive days. Three days after the end of the medication she began to feel less rigidity in her left leg and, within 1 week, she was able to walk and her left leg exhibited full flexion. Two months after the treatment, she felt a progressive return of the rigidity and was submitted to another session of intravenous human immunoglobulin. The second treatment was also successful and she remains well at 6-month follow up. Discussion Our patient has the clinical and the electromyographic findings of stiff-limb syndrome.4,5 The absence of spasm in paravertebral muscles and abnormally segmented electromyographic activity during spasms in the left leg muscles were the differences between true stiff-man syndrome (or stiff-trunk syndrome), although these muscles showed continuous motor unit activity. Barker et al.,2 in an extensive review, pointed out that stifflimb is distinguished from true stiff-man syndrome by the typical absence of anti-GAD antibodies and lack of association with autoimmune disease. Furthermore, true stiff-man syndrome usually responds well to immune therapy, but this has not been studied to any extent in stiff-limb syndrome.5–10 Recently, Saiz et al.4 documented a similar good response with intravenous immunoglobulin in their first patient. The dramatic response to immunoglobulin in our patient suggests that stiff-limb syndrome, as well as true stiff-man syndrome, can respond to immunotherapy, although Barker et al.2 359 noted that many patients have a “relapsing and remitting course.” It may be speculated that the presence of anti-GAD antibodies is determinant for a good response to immunoglobulin in stiff-limb patients. Legends to the Videotape Segment 1: Severe stiffness in the left leg before treatment. The leg had a fixed posture of extension and the foot was flexed and internally rotated. She is restricted to a wheelchair. Segment 2: Dramatic improvement of the stiffness after 1 month of treatment with intravenous immunoglobulin. The patient is able to make a full flexion of the left leg and walk with no assistance. Segment 3: Persistent improvement of walking after 9 months. Carlos Frederico L. Souza-Lima, MD Henrique Ballalai Ferraz, MD, PhD Claudia Aparecida Braz, MD Angela Maysa Araüjo, MD Gilberto Mastrocola Manzano, MD, PhD Department of Neurology Federal University of São Paulo São Paulo, Brazil References 1. Brown P, Rothwell JC, Marsden CD. The stiff leg syndrome. J Neurol Neurosurg Psychiatry 1997;62:31–37. 2. Barker RA, Revesz T, Thom M, Marsden CD, Brown P. Review of 23 patients affected by the stiff man syndrome: clinical subdivision into stiff trunk (man) syndrome, stiff limb syndrome, and progressive encephalomyelitis with rigidity. J Neurol Neurosurg Psychiatry 1998;65:633–640. 3. Gorin F, Baldwin B, Tait R, Pathak R, Seyal M, Mugnaini E. Stiff-man syndrome: a GABAergic autoimmune disorder with autoantigenic heterogeneity. Ann Neurol 1990;28:711–714. 4. Saiz A, Graus F, Valldeoriola F, Valls-Solé J, Tolosa E. Stiff-leg syndrome: a focal form of stiff-man syndrome. Ann Neurol 1998; 43:400–403. 5. Thaler C, Kiechl S, Kofler M, Willeit J, Wissel J, Poewe W. Stiff leg syndrome—a focal form of stiff man syndrome? Mov Disord 1998;13(suppl 2):308. 6. Karlson EW, Sudarsky L, Ruderman E, Pierson S, Scot M, Helfgott SM. Treatment of stiff-man syndrome with intravenous immunoglobulin. Arthritis Rheum 1994;37:915–918. 7. Amato AA, Cornman EW, Kissel JT. Treatment of stiff-man syndrome with intravenous immunoglobulin. Neurology 1994;44: 1652–1654. 8. Vicari AM, Folli F, Pozza G, et al. Plasmapheresis in the treatment of stiff-man syndrome. N Engl J Med 1989;320:1499. 9. Harding AE, Thompson PD, Kocen RS, Batchelor JR, Davey N, Marsden CD. Plasma exchange and immunosupression in the stiff man syndrome. Lancet 1989;2:915. 10. Barker RA, Marsden CD. Successful treatment of stiff man syndrome with intravenous immunoglobulin. J Neurol Neurosurg Psychiatry 1997;62:426–427. Movement Disorders, Vol. 15, No. 2, 2000