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FIG. 1. Photomicrograph from the putamen showing marked spongiosis and gliosis (haematoxylin and eosin; magnification X20).
Acknowledgment: We thank Dr. J. Mike1 for providing the photomicrograph.
C. E. Clarke J . M. Bamford Department of Neurology S t . James’s University Hospital Leeds, U . K .
A . House Department of Liaison Psychiatry The General Infrmaty Leeds, U . K .
References 1. Will RG. Prion disease. Lancer 1990;ii:369. 2. Will RG, Matthews WB. A retrospective study of Creutzfeldt-Jakob disease in England and Wales 197S79. I. Clinical features. J Neurol Neurosurg Psychiat 1984;47: 134-140. 3. Brown P, Cathala F, Sadowsky D , Gajdusek DC. Creutzfeldt-Jakob disease in France: 11. Clinical characteristics of 124 consecutive verified cases during the decade 1968- 1977. Ann Neurol 1979;6:43&437. 4. Sethi KD, Hess DC. Creutzfeldt-Jakob disease presenting
with ataxia and a movement disorder. Movement Disorders 1991;6:157-162.
5 . Fann WE, Sullivan JL, Richman BW. Dyskinesias associated with tricyclic antidepressants. Brit J Psychiut 1976;128: 490-493.
6 . Lane RJM, Routledge PA. Drug-induced neurological disorders. Drugs 1983;26:124147. 7. Garvey MJ, Tollefson GD. Occurrence of myoclonus in patients treated with cyclic antidepressants. Arch Gen Psychiat 1987;44:269-272.
Chorea and Tuberous Sclerosis To the Editor: Tuberous sclerosis is a neurocutaneous disease with autosomal-dominant inheritance classically presenting with a clinical triad of epilepsy, mental retardation, and characteristic skin lesions. The occurrence of choreic movements in tuberous sclerosis is extremely rare with only one previous patient reported (1). We report a second patient with tuberous sclerosis and chorea. A 67-year-old woman, a member of a large pedigree with well-documented tuberous sclerosis (Fig. l), had had a gradual onset of choreic movements during her late 50s. No other members of the pedigree have involuntary movements and there is no family history of Huntington’s disease. Her parents died in their 80s and had normal higher functions. She had not been taking medications or been exposed to toxins known to cause chorea. There was no history of excessive alcohol intake, nor of rheumatic chorea, and she had not suffered from seizures.
Movement Disorders, VoI. 7, Nu. 1 , 1992
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111
FIG. 1. Family tree. IV
V
On examination, she had irregular, jerky, unsustained, involuntary movements of a choreic nature involving her face, head, trunk, and all limbs. Irregular episodic respiratory and speech patterns were present, as well as frequent involuntary protrusions of her tongue when she was attempting to eat or drink. N o abnormal movements of the palate were observed. All involuntary movements disappeared during sleep. She had a positive glabella tap but no other primitive reflexes. Her retinae were normal with no hamartomas. Extraocular voluntary, saccadic, and smooth pursuit movements were normal, as were the remainder of the cranial nerves. Examination of the limbs showed normal tone, power, reflexes, plantar responses, and sensation. Cerebellar function was normal apart from a slight impairment of her ability to perform rapid alternating movements. Her gait was impaired due to choreic movements of her lower limbs but there was no additional ataxia. Shagreen patches were visible on her trunk under ultraviolet light, but she had no facial angiofibromas or periungual fibromas. Neuropsychometric testing showed significant impairment of short- and long-term memory, with impaired ability to learn new information. The WAIS-R verbal IQ was 89. Performance subsets were not administered due to difticulties with fine motor coordination that would have made these timed tests uninterpretable. A computed tomographic (CT) scan of the head showed periventricular calcification bilaterally consistent with calcified subependymal nodules, including a calcified nodule in the left caudate nucleus (Fig. 2). There was atrophy of both caudate nuclei, mild generalized cortical atrophy, and dilation of the lateral ventricles. Investigations included normal liver function tests, electrolytes, calcium, magnesium, glucose, creatine phosphokinase, thyroid function tests, vitamin BI2levels, copper, ceruloplasmin, cortisol, porphyrin screen, and syphilis serology. No acanthocytes were seen on multiple fresh blood screens examined by experienced observers. Her chorea was improved significantly by tetrabenazine, 25 mg q.i.d.
extrapyramidal movement disorders is very rare. Bielschowsky and Freund (2) in 1918 reported that athetotic movements may occur if nodules affect the basal ganglia. Gomez (3) noted that athetosis had been observed in only one patient followed at the Mayo Clinic. In 1932, Critchley and Earl (4) described a patient with “motor restlessness,” consisting of “bizarre hyperkinetic movements of the hands and fingers.” Evans and Jankovic (1) have reported the only previous case of definite choreic movements in tuberous sclerosis. Their patient had calcified subependymal nodules present in the region of the basal ganglia bilaterally and the authors postulated that these lesions could have been responsible for the produc-
Discussion Although the basal ganglia region is frequently involved pathologically in tuberous sclerosis, clinical evidence of
Movement Disorders, Vol. 7, N o . 1, 1992
FIG. 2. CT head scan showing caudate atrophy and a calcified nodule in the left caudate nucleus.
COMMUNICATIONS tion of the patient’s chorea, although noting that many patients with tuberous sclerosis have nodules in this region, and do not have movement disorders. The specific location of the nodules in the basal ganglia rather than the degree of abnormality may be important with respect to the production of chorea. Evans and Jankovic’s (1) patient had considerable diffuse bilateral calcification in the caudate nuclei compared to the present patient who, on three CT scans obtained over a 4-year period, had evidence of only o n e small calcified subependymal nodule in the basal ganglia, in the region of the left caudate nucleus. Up to 50% of lesions in this region may be uncalcified (5), although such subependyma1 nodules are usually still visible on CT (6). There was no evidence of uncalcified nodules or other structural lesions such as tumor or hamartoma in the basal ganglia in this patient; it thus seems unlikely that basal ganglia masses were the cause of her movement disorder. The present patient also had dilatation of the lateral ventricles but, as this may be seen in up to 30%of tuberous sclerosis patients ( 2 ) , it is probably unrelated to her chorea. This patient’s significant bilateral caudate nucleus atrophy may have been of more pathophysiological significance; we were unable to find specific reference to atrophy of the caudate nucleus in previous neuroradiological and pathological studies of tuberous sclerosis.
Legend to Videotape The patient exhibits choreiform movements of the head and limbs. Cerebellar function in the arms is normal apart from a slight impairment of rapid alternating movements. Note the lower facial movements and irregular respiratory pattern. The patient’s ability to eat and drink is impaired by choreiform movements and frequent involuntary protrusions of the tongue. Choreiform movements are more marked on the left side. The patient’s gait is impaired by choreiform movements but there is no additional ataxia.
R. A. Wright M. Pollock Division of Neurology Department of Medicine University of Otago Medical School Dunedin, New Zealand
I. MacG. Donaldson Christchurch School of Medicine University of Otago Medical School Christchurch, New Zealand
References 1. Evans BK, Jankovic J. Tuberous sclerosis and chorea. Ann Neurol 1983;13:106-107. 2. Bielschowsky M, Freund CS. Veranderung des Striatums bei tuberoser Sklerose und deren Beziehungen zu den Befunden bei anderen Erkrankungen dieses Hirnteils. J Psychol Neurol 1918;24:2047. 3. Gomez MR, ed. Tuberous sclerosis, 2nd edition. New York: Raven Press, 1988. 4. Critchley M, Earl CJC. Tuberous sclerosis and allied conditions. Brain 1932;55:311-346. 5. Donegani G, Grattarola FR, Wildi E. Tuberous sclerosis. In:
89
Vinken PJ, Bruyn GW, eds. Handbook of clinical neurolo g y , Vol. 14, Chap. 1 1 . Amsterdam: North Holland Publishing Company, 1972:340-389. 6. Altman NR, Purser RK, Post MJD. Tuberous sclerosis: characteristics at CT and MR imaging. Radiology 1988; 167(2):527-532.
Parkinsonian Syndrome After Long-term Treatment with Clebopride To the Editor: Clebopride, a derivative of the orthopramide group, has been shown to be effective and is currently available in Italy for the treatment of dyspepsia and vomiting (1,2). The compound has central antidopaminergic activity, with affinity for dopamine D2 receptors (3-5). Two patients undergoing long-term treatment with clebopride for gastrointestinal complaints, developed a progressive parkinsonianlike syndrome that reverted after drug withdrawal. A 61-year-old woman had had a right mammectomy 5 years earlier because of adenocarcinoma, without further complications on repeated follow-ups. In the 2 months preceding her presentation to us, she had been prescribed 1.5 mg/d clebopride (Motilex) because of dyspepsia. After about 1 month, she noticed progressive tremor of the upper and especially lower limbs, worse on the right and evident during both rest and especially when sitting with crossed legs. Examination showed a resting and postural tremor of the arms and legs, with a frequency of about 4 Hz and moderate loss of arm swing during walking. Electroencephalogram (EEG) and brain computed tomography (CT) results were normal. The patient was examined again 2 months after clebopride withdrawal, and neurological examination was completely normal. A previously healthy 60-year-old man had been prescribed 1 mgld clebopride (Motilex) because of abdominal pains attributable to gastric ulcer. Over the next 3 months he developed a state of apathy and disconcern, with drowsiness, lack of initiative, and slowing of thought and movements. He became unable to attend to his usual business. Examination showed amimia, bradykinesia with diffuse rigidity, and a slow and shuffling gait. Tremor was absent. EEG and brain CT results were normal. Two weeks after discontinuation of clebopride, symptoms and signs had much decreased, and completely disappeared 3 months later. The absence of other drugs or conditions liable to cause Parkinsonian effects, and the complete reversal upon drug withdrawal, suggest that clebopride was responsible for the complaints reported by our patients. These developed progressively, at normal daily dosages, with the patients seeking medical care after assumption of a total of -90 mg. Acute reactions-dyskinesia, hypertonus, oculogync crises-have been reported after clebopride use in children (6). However, other studies have reported no (7) or “low” (8) side effects on acute administration. Menstrual disorders, galactorrhea, and increased prolactinemia have been associated with long-term administration (9).
Movement Disorders, Vol. 7, No. 1 , 1992
87
FIG. 1. Photomicrograph from the putamen showing marked spongiosis and gliosis (haematoxylin and eosin; magnification X20).
Acknowledgment: We thank Dr. J. Mike1 for providing the photomicrograph.
C. E. Clarke J . M. Bamford Department of Neurology S t . James’s University Hospital Leeds, U . K .
A . House Department of Liaison Psychiatry The General Infrmaty Leeds, U . K .
References 1. Will RG. Prion disease. Lancer 1990;ii:369. 2. Will RG, Matthews WB. A retrospective study of Creutzfeldt-Jakob disease in England and Wales 197S79. I. Clinical features. J Neurol Neurosurg Psychiat 1984;47: 134-140. 3. Brown P, Cathala F, Sadowsky D , Gajdusek DC. Creutzfeldt-Jakob disease in France: 11. Clinical characteristics of 124 consecutive verified cases during the decade 1968- 1977. Ann Neurol 1979;6:43&437. 4. Sethi KD, Hess DC. Creutzfeldt-Jakob disease presenting
with ataxia and a movement disorder. Movement Disorders 1991;6:157-162.
5 . Fann WE, Sullivan JL, Richman BW. Dyskinesias associated with tricyclic antidepressants. Brit J Psychiut 1976;128: 490-493.
6 . Lane RJM, Routledge PA. Drug-induced neurological disorders. Drugs 1983;26:124147. 7. Garvey MJ, Tollefson GD. Occurrence of myoclonus in patients treated with cyclic antidepressants. Arch Gen Psychiat 1987;44:269-272.
Chorea and Tuberous Sclerosis To the Editor: Tuberous sclerosis is a neurocutaneous disease with autosomal-dominant inheritance classically presenting with a clinical triad of epilepsy, mental retardation, and characteristic skin lesions. The occurrence of choreic movements in tuberous sclerosis is extremely rare with only one previous patient reported (1). We report a second patient with tuberous sclerosis and chorea. A 67-year-old woman, a member of a large pedigree with well-documented tuberous sclerosis (Fig. l), had had a gradual onset of choreic movements during her late 50s. No other members of the pedigree have involuntary movements and there is no family history of Huntington’s disease. Her parents died in their 80s and had normal higher functions. She had not been taking medications or been exposed to toxins known to cause chorea. There was no history of excessive alcohol intake, nor of rheumatic chorea, and she had not suffered from seizures.
Movement Disorders, VoI. 7, Nu. 1 , 1992
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88
111
FIG. 1. Family tree. IV
V
On examination, she had irregular, jerky, unsustained, involuntary movements of a choreic nature involving her face, head, trunk, and all limbs. Irregular episodic respiratory and speech patterns were present, as well as frequent involuntary protrusions of her tongue when she was attempting to eat or drink. N o abnormal movements of the palate were observed. All involuntary movements disappeared during sleep. She had a positive glabella tap but no other primitive reflexes. Her retinae were normal with no hamartomas. Extraocular voluntary, saccadic, and smooth pursuit movements were normal, as were the remainder of the cranial nerves. Examination of the limbs showed normal tone, power, reflexes, plantar responses, and sensation. Cerebellar function was normal apart from a slight impairment of her ability to perform rapid alternating movements. Her gait was impaired due to choreic movements of her lower limbs but there was no additional ataxia. Shagreen patches were visible on her trunk under ultraviolet light, but she had no facial angiofibromas or periungual fibromas. Neuropsychometric testing showed significant impairment of short- and long-term memory, with impaired ability to learn new information. The WAIS-R verbal IQ was 89. Performance subsets were not administered due to difticulties with fine motor coordination that would have made these timed tests uninterpretable. A computed tomographic (CT) scan of the head showed periventricular calcification bilaterally consistent with calcified subependymal nodules, including a calcified nodule in the left caudate nucleus (Fig. 2). There was atrophy of both caudate nuclei, mild generalized cortical atrophy, and dilation of the lateral ventricles. Investigations included normal liver function tests, electrolytes, calcium, magnesium, glucose, creatine phosphokinase, thyroid function tests, vitamin BI2levels, copper, ceruloplasmin, cortisol, porphyrin screen, and syphilis serology. No acanthocytes were seen on multiple fresh blood screens examined by experienced observers. Her chorea was improved significantly by tetrabenazine, 25 mg q.i.d.
extrapyramidal movement disorders is very rare. Bielschowsky and Freund (2) in 1918 reported that athetotic movements may occur if nodules affect the basal ganglia. Gomez (3) noted that athetosis had been observed in only one patient followed at the Mayo Clinic. In 1932, Critchley and Earl (4) described a patient with “motor restlessness,” consisting of “bizarre hyperkinetic movements of the hands and fingers.” Evans and Jankovic (1) have reported the only previous case of definite choreic movements in tuberous sclerosis. Their patient had calcified subependymal nodules present in the region of the basal ganglia bilaterally and the authors postulated that these lesions could have been responsible for the produc-
Discussion Although the basal ganglia region is frequently involved pathologically in tuberous sclerosis, clinical evidence of
Movement Disorders, Vol. 7, N o . 1, 1992
FIG. 2. CT head scan showing caudate atrophy and a calcified nodule in the left caudate nucleus.
COMMUNICATIONS tion of the patient’s chorea, although noting that many patients with tuberous sclerosis have nodules in this region, and do not have movement disorders. The specific location of the nodules in the basal ganglia rather than the degree of abnormality may be important with respect to the production of chorea. Evans and Jankovic’s (1) patient had considerable diffuse bilateral calcification in the caudate nuclei compared to the present patient who, on three CT scans obtained over a 4-year period, had evidence of only o n e small calcified subependymal nodule in the basal ganglia, in the region of the left caudate nucleus. Up to 50% of lesions in this region may be uncalcified (5), although such subependyma1 nodules are usually still visible on CT (6). There was no evidence of uncalcified nodules or other structural lesions such as tumor or hamartoma in the basal ganglia in this patient; it thus seems unlikely that basal ganglia masses were the cause of her movement disorder. The present patient also had dilatation of the lateral ventricles but, as this may be seen in up to 30%of tuberous sclerosis patients ( 2 ) , it is probably unrelated to her chorea. This patient’s significant bilateral caudate nucleus atrophy may have been of more pathophysiological significance; we were unable to find specific reference to atrophy of the caudate nucleus in previous neuroradiological and pathological studies of tuberous sclerosis.
Legend to Videotape The patient exhibits choreiform movements of the head and limbs. Cerebellar function in the arms is normal apart from a slight impairment of rapid alternating movements. Note the lower facial movements and irregular respiratory pattern. The patient’s ability to eat and drink is impaired by choreiform movements and frequent involuntary protrusions of the tongue. Choreiform movements are more marked on the left side. The patient’s gait is impaired by choreiform movements but there is no additional ataxia.
R. A. Wright M. Pollock Division of Neurology Department of Medicine University of Otago Medical School Dunedin, New Zealand
I. MacG. Donaldson Christchurch School of Medicine University of Otago Medical School Christchurch, New Zealand
References 1. Evans BK, Jankovic J. Tuberous sclerosis and chorea. Ann Neurol 1983;13:106-107. 2. Bielschowsky M, Freund CS. Veranderung des Striatums bei tuberoser Sklerose und deren Beziehungen zu den Befunden bei anderen Erkrankungen dieses Hirnteils. J Psychol Neurol 1918;24:2047. 3. Gomez MR, ed. Tuberous sclerosis, 2nd edition. New York: Raven Press, 1988. 4. Critchley M, Earl CJC. Tuberous sclerosis and allied conditions. Brain 1932;55:311-346. 5. Donegani G, Grattarola FR, Wildi E. Tuberous sclerosis. In:
89
Vinken PJ, Bruyn GW, eds. Handbook of clinical neurolo g y , Vol. 14, Chap. 1 1 . Amsterdam: North Holland Publishing Company, 1972:340-389. 6. Altman NR, Purser RK, Post MJD. Tuberous sclerosis: characteristics at CT and MR imaging. Radiology 1988; 167(2):527-532.
Parkinsonian Syndrome After Long-term Treatment with Clebopride To the Editor: Clebopride, a derivative of the orthopramide group, has been shown to be effective and is currently available in Italy for the treatment of dyspepsia and vomiting (1,2). The compound has central antidopaminergic activity, with affinity for dopamine D2 receptors (3-5). Two patients undergoing long-term treatment with clebopride for gastrointestinal complaints, developed a progressive parkinsonianlike syndrome that reverted after drug withdrawal. A 61-year-old woman had had a right mammectomy 5 years earlier because of adenocarcinoma, without further complications on repeated follow-ups. In the 2 months preceding her presentation to us, she had been prescribed 1.5 mg/d clebopride (Motilex) because of dyspepsia. After about 1 month, she noticed progressive tremor of the upper and especially lower limbs, worse on the right and evident during both rest and especially when sitting with crossed legs. Examination showed a resting and postural tremor of the arms and legs, with a frequency of about 4 Hz and moderate loss of arm swing during walking. Electroencephalogram (EEG) and brain computed tomography (CT) results were normal. The patient was examined again 2 months after clebopride withdrawal, and neurological examination was completely normal. A previously healthy 60-year-old man had been prescribed 1 mgld clebopride (Motilex) because of abdominal pains attributable to gastric ulcer. Over the next 3 months he developed a state of apathy and disconcern, with drowsiness, lack of initiative, and slowing of thought and movements. He became unable to attend to his usual business. Examination showed amimia, bradykinesia with diffuse rigidity, and a slow and shuffling gait. Tremor was absent. EEG and brain CT results were normal. Two weeks after discontinuation of clebopride, symptoms and signs had much decreased, and completely disappeared 3 months later. The absence of other drugs or conditions liable to cause Parkinsonian effects, and the complete reversal upon drug withdrawal, suggest that clebopride was responsible for the complaints reported by our patients. These developed progressively, at normal daily dosages, with the patients seeking medical care after assumption of a total of -90 mg. Acute reactions-dyskinesia, hypertonus, oculogync crises-have been reported after clebopride use in children (6). However, other studies have reported no (7) or “low” (8) side effects on acute administration. Menstrual disorders, galactorrhea, and increased prolactinemia have been associated with long-term administration (9).
Movement Disorders, Vol. 7, No. 1 , 1992
