Movement Disorders Vol. 7, No. 4, 1992, pp. 38&386. 0 1992 Movement Disorder Society
Communications matter, the pons, and the left cerebellar white matter. Conspicuous hyperintense lesions were seen in both posterior limbs of the internal capsule outstretching in the adjacent lateral thalamus and globus pallidus bilaterally, but more pronounced on the left (Fig. 1). Treatment by intravenous high-dose 500-mg methylprednisolone during 5 days led to a nearly complete resolution of the extrapyramidal signs. On discharge, mild dysarthria and the right-sided hemiparesis were noted. Up to April 1991 there was no further relapse.
Parkinsonism in Multiple Sclerosis To the Editor: Recent reports in Movement Disorders have pointed to the occurrence of dystonia (1,2), choreoathetosis (3), or ballism (4) during the course of multiple sclerosis (MS). We present two MS cases with parkinsonian features.
Case 1 A 55-year-old clerk with an otherwise unremarkable history had blurred vision, dysarthria, urinary incontinence, and a severe right hemiparesis at age 24 years. Symptoms had remitted spontaneously at that time and the patient had had a total of five similar relapses. At the sixth relapse, at age 52 years, he was first admitted to our hospital. On examination, there was temporal pallor of the optic discs bilaterally. There was a moderate rightsided spastic hemiparesis. Deep tendon reflexes (DTR) were more markedly elicited on the right, plantar response was extensor, and there were bilateral ankle cloni, whereas abdominal reflexes were absent. Finger-to-nose and heel-to-chin tests were normal on the left, whereas on the right they could not be tested due to paresis. Speech was slightly slurred. Gait was hemiparetic. The remainder of the neurological examination showed normal results. The patient showed some indifferent euphoria, and reduced attention, concentration, and short-term memory. Visual evoked potentials (VEP) were normal. Brainstem evoked acoustic potentials were normal on the right, whereas waves IV and V were absent on the left. Routine blood chemistry including thyroid and copper metabolism was normal. Cerebrospinal fluid (CSF) was normal for cells and proteins. Blood-brain barrier function was normal (5). There was oligoclonal IgG banding, but no CSF synthesis of IgG or paraproteins. The Link-Tibbling index was 0.62 (6). Treatment was by intravenous prednisolone (starting dose 100 mg) with tapering down during 5 weeks. A spastic right-sided hemiparesis with slight gait disturbance was noted on discharge. Fourteen months later, the patient was readmitted because of a left facial palsy and a deterioration of his rightsided paresis. Most obvious, however, were seborrhea, masked face, generalized hypokinesia, and a hoarse dysarthria with slurring of syllables and consonants. There was no cogwheel rigidity and no resting tremor. Hand dexterity, rapid hand-arm movements, and diadochokinesia on the left were impaired to a moderate degree, whereas these could not be judged on the right due to paresis. Posture was slightly stooped with some retropulsion, but there was recovery on pull test. Gait showed reduced step length on the left, reduced arm swing, and en bloc turning. The patient had 10 points on the Webster rating scale and was rated stage I1 in the Hoehn and Yahr classification. Proton- and T2- weighed magnetic resonance (MR) imaging showed multiple hyperintense lesions in the peri- and supraventricular cerebral white
Case 2 A 60-year-old housewife had severe obesity and a seronegative, chronic rheumatoid arthritis since 1979 and diabetes mellitus since 1985. Since 1980 a slowly progressive reduction of spontaneous movements and lack of initiative were noted. In the 2 years before the first admission in 1986, head tremor and progressive gait difficulty had developed with repeated falls. On examination, there was a Homer’s syndrome on the right with ptosis and miosis. There was horizontal gazeevoked nystagmus bilaterally. DTR were raised and elevated on the right. There was a right plantar extensor response. Abdominal reflexes were absent. Residual bladder volume was 50 ml. There was coarse “No”tremor of the head, and a voice tremor, but no tremor on the extremities. The patient had seborrhea, masked face, and moderate cogwheel rigidity of the left arm, a bilateral bradydiadochokinesia, a broad-based, short-stepped gait, and a moderately stooped posture with pulsion phenomena in all directions. The remainder of the neurological examination results were normal. Webster rating gave 22 points, and the patient had stage IV according to the Hoehn and Yahr classification. Mental status examination showed reduced impulse, initiative, and spontaneity. She was severely apathetic and hypokinetic. VEP were prolonged on both eyes: right 117 ms, left 119 ms. Routine blood chemistry showed elevated serum glucose levels over repeated daytime profiles (between 220 and 270 mg/ dl). Protein content, electrophoresis, and quantitative determination of immunoglobulins were normal. Search for paraproteins, antibodies against cell nuclei, mitochondria, smooth-muscle tissue and DNA, for Rheuma factor, antistreptolysine titer, and Lupus-erythema-todes factor was negative. C-reactive protein was 1:37. Thyroid, parathyroid, and copper metabolism was normal. CSF contained five cells per cubic millimeter. Protein content was 60 mg/dl. Albumin was 25.7 mgldl, and IgG was 8.27 mg/ dl. Blood-brain barrier analysis revealed an increased intrathecal IgG synthesis rate. The CSF showed oligoclonal IgG banding. The Link-Tibbling index was 1.18. There was local synthesis of antibodies against measles, herpes simplex, and zoster in the CSF (7). TI-weighted MR imaging showed several confluant, hyperintense lesions in the peri- and supraventricular cerebral white matter, more pronounced at the tips of the ventricles. Within the
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FIG. 1. Case 1. Magnetic resonance scan of the brain, spin echo technique. Hyperintense lesions of posterior limb of internal capsule and adjacent regions of thalamus and globus pallidus bilaterally; TE 30 ms, TR 2,800 ms.
anterior and posterior limbs of the internal capsule, but also outstretching into the adjacent lateral thalamus and the lentiform nucleus, there were hyperintense areas bilaterally (Fig. 2 ) . There were no lesions in the brainstem and the cervical spinal cord. Treatment by 400 mg L-Dopa (plus 87.5 mg benserazide) given for 10 days did not ameliorate the parkinsonian features. Therefore, intravenous prednisolone with a starting dose of 100 mg was added and tapered down during the next 4 weeks. With this therapy, hypokinesia, pulsion phenomena, and gait improved so that the patient was able to again wash and dress herself. The tremor remained unchanged. During the following months, intermittent pneumonia and urosepsis had made the patient continuously bedridden. On examination in 1988, she had left optic disc pallor and internuclear ophthalmoplegia on the same side. Nuchal rigidity, bilateral cogwheel rigidity of the arms, more markedly on the left, and a fine resting tremor of the left arm were noted as additional signs. There were marked bilateral bradydiadochokinesia, general hypokinesia, and a severe postural instability. With assistance she did some short steps, but had freezing phenomena. Steroid treatment or L-Dopa preparations were not given at this time. The patient was transferred to an institution for the elderly.
Comment Both patients had no prior intake of drugs known to cause parkinsonism. The family history was unremark-
381
able. We therefore think that secondary causes of parkinsonism other than MS have consistently been ruled out in our patients. Both reported cases had definite MS (8): case 1 had clinically definite MS, whereas case 2 had MS with laboratory support. Both developed parkinsonian features during the course of MS. Case 1 had mainly bradykinesia and impaired balance, although he did not present with the classic triad of Parkinson’s disease. Case 2 had the classic triad of Parkinsons’s disease at an advanced stage of disease course. One of the first signs of extrapyramidal involvement had been head tremor. This is thought only rarely, if ever, to appear in idiopathic Parkinson’s disease (9), thus pointing to a secondary etiology such as MS in the present case. Case 2 had a history of chronic rheumatoid arthritis with some deformities of finger joints, but a repeatedly negative rheumatoid factor in serology (similar to a case reported in ref. 3). Because in our case an active rheumatoid disease during the whole observation period could not be evaluated to occur simultaneously with the chronic progressive neurological deterioration, the condition of this case is regarded as MS and not CNS arteritis in rheumatoid arthritis (3). Neither oligoclonal banding, nor increased intrathecal IgG synthesis rate, nor white matter lesions in MR imaging such as in case 2 are specific for MS. However, we consider optic neuritis with delayed VEP, internuclear ophthalmoplegia, and intrathecal synthesis of viral antibodies (7) important pointers toward a diagnosis of MS in this case. The time interval between the first bout of MS and the emergence of parkinsonian symptoms was longer in our cases than in those in the literature (3). This and the obvious rarity of the reported association may indicate a
FIG. 2. Case 2. Magnetic resonance scan of the brain, spin echo technique. Hyperintense lesions adjacent to posterior limbs of internal capsule bilaterally (i.e., thalamus and globus pallidus), more marked on the right; TE 35 rns, TR 3,000 ms.
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fortuitous coincidence: Population prevalence rates (per 100,000) of MS [110 cases; (lo)] and idiopathic Parkinson’s disease [164 cases; ( I l ) ] would in the Northern hemisphere render -1 individual per 500,000 likely to carry both conditions. Arguments against a mere coincidence and in favor of possible pathophysiological links between the two conditions may be as follows. (a) In case 1, the remission of parkinsonian features occurred in a time-locked fashion together with the remission of MS signs and symptoms subsequent to MS-directed drug therapy. (b) In both cases, MR imaging showed involvement of thalami and basal ganglia adjacent to the internal capsule. Overall, basal ganglia affection in MR imaging has been noted in 25% of MS patients (12). Size, distribution, and dynamics of plaque formation within a strategic area such as the internal capsule may contribute to different clinical expression, when the neighboring basal ganglia and thalamic structures are attached. (c) Because ventral and central parts of the thalamus are functionally involved in the basal ganglia-thalamo-cortical pathways, structural lesions such as demyelinating plaques affecting these circuitries at the thalamic or basal ganglia level may result clinically in hypokinetic (case 1) or full-blown parkinsonian states (case 2) (13). Longitudinal monitoring of MS cases with basal ganglia involvement on MR imaging may help to establish in-vivo the exact meaning of a clinicoradiological correlation between movement disorders and MS. P. Vieregge W. Klostermann Klinik fur Neurologie H. Briickmann Institut fiir Radiologie Medizinische Universitat zu Liibeck Liibeck, Germany
References 1 . Coleman RJ, Quinn NP, Marsden CD. Multiple sclerosis presenting as adult onset dystonia. Mov Disord 1988;3:329332. 2. Plant GT, Kermode AG, du Bouley EP, McDonald WI. Spasmodic torticollis due to a midbrain lesion in a case of multiple sclerosis. Mov Disord 1989;4:359-362. 3. Mao CC, Gancher ST, Herndon RM. Movement disorders in multiple sclerosis. Mov Disord 1988;3:109-1 16. 4. Riley D, Lang AE. Hemiballism in multiple sclerosis. Mov Disord 1988;3:88-94. 5. Reiber HO, Felgenhauer K. Protein transfer at the bloodCSF barrier and the quantitation of the humoral immune response within the central nervous system. Clin Chem Acta 1987;163:319-328. 6. Tibbling G, Link H, Ohman S . Principles of albumin and IgG analysis in neurological disorders. I. Establishment of reference values. Scand J Clin Lab Invest 1977;37:385-390. 7. Schadlich H-J, Karbe H, Felgenhauer K. The prevalence of locally-synthesized virus antibodies in various forms of multiple sclerosis. J Neurol Sci 1987;80:343-349. 8. Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983;13:227-231. 9. Barbeau A. Parkinson’s disease: clinical features and etiopathology. In: Vinken PJ, Bruyn GW, Klawans H, eds. Ex-
Movement Disorders, Vol. 7, No. 4, 1992
10. 11.
12.
13.
trapyramidal disorders. Amsterdam: Elsevier Science, 1986:87-152. [Handbook of clinical neurology; vol5 (49)l. Beer S , Kesselring J. Die Multiple Sklerose im Kanton Bern (CH). Fortschr Neurol Psychiatr 1988;56:390-397. Mutch WJ, Dingwall-Fordyce I, Downie AW, Paterson JG, Roy SK. Parkinson’s disease in a Scottish city. Br Med J 1986;292:534-536. Kesselring J, Ormerod IEC, Miller DH, du Bouley EPGH, McDonald WI. Magnetic resonance imaging in multiple sclerosis. Stuttgart and New York: Georg Thieme Verlag, 1989. Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. TINS 1990;13:266271.
Parkinson’s Disease in a Patient with Mitochondria1 Myopathy: Is There a Causative Relationship? To the Editor: The cause of the progressive nigral degeneration in Parkinson’s disease (PD) is unknown. It was recently suggested that the mitochondrial respiratory enzyme complex-1 (NADH: ubiquinone oxidoreductase) activity is deficient in the CNS and platelets of patients with PD (1-3). Interestingly, 1-methyl-4-phenyl-pyridinium ion (MPP ), the toxic metabolite of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), kills nigral neurons by poisoning their mitochondrial respiration (4). After its entry into dopaminergic neurons, MPP is taken-up and concentrated by the mitochondria where it inhibits the NADH-linked fraction of complex-I activity (5). These observations suggest that nigral neurons may die in PD because of impaired mitochondrial energy metabolism due to hereditary, neurotoxic, or other factors (6,7). The mitochondrial myopathies are a heterogenous group of diseases that share the common features of structural changes in skeletal muscle mitochondria and may cause muscular as well as nervous system dysfunction. We now report a patient with longstanding mitochondrial myopathy who developed PD. The intriguing question is whether the two disorders are causatively related or purely coincidental. A 60-year-old man was under long-term follow-up because of a syndrome consisting of slowly progressive muscle weakness, peripheral neuropathy and external ophthalmoplegia. He was readmitted because during the last year he developed symptoms of PD. There was no family history of myopathy, PD, or other neurological disorders. He was never exposed to neuroleptic drugs. On examination, his older signs included complete external ophthalmoplegia, bilateral facial weakness, reduced proximal muscle strength symmetrically affecting both upper and lower limbs, generally absent tendon jerks, and distal hypoesthesia to pain and touch. Plantar responses were bilaterally flexor. There were no signs of dementia. The new neurological findings included marked reduced facial mimicry with monotonous and slow speech. He was generally bradykinetic and rigid, with slow and shuffling gait. He had coarse resting tremor af-
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+
Communications matter, the pons, and the left cerebellar white matter. Conspicuous hyperintense lesions were seen in both posterior limbs of the internal capsule outstretching in the adjacent lateral thalamus and globus pallidus bilaterally, but more pronounced on the left (Fig. 1). Treatment by intravenous high-dose 500-mg methylprednisolone during 5 days led to a nearly complete resolution of the extrapyramidal signs. On discharge, mild dysarthria and the right-sided hemiparesis were noted. Up to April 1991 there was no further relapse.
Parkinsonism in Multiple Sclerosis To the Editor: Recent reports in Movement Disorders have pointed to the occurrence of dystonia (1,2), choreoathetosis (3), or ballism (4) during the course of multiple sclerosis (MS). We present two MS cases with parkinsonian features.
Case 1 A 55-year-old clerk with an otherwise unremarkable history had blurred vision, dysarthria, urinary incontinence, and a severe right hemiparesis at age 24 years. Symptoms had remitted spontaneously at that time and the patient had had a total of five similar relapses. At the sixth relapse, at age 52 years, he was first admitted to our hospital. On examination, there was temporal pallor of the optic discs bilaterally. There was a moderate rightsided spastic hemiparesis. Deep tendon reflexes (DTR) were more markedly elicited on the right, plantar response was extensor, and there were bilateral ankle cloni, whereas abdominal reflexes were absent. Finger-to-nose and heel-to-chin tests were normal on the left, whereas on the right they could not be tested due to paresis. Speech was slightly slurred. Gait was hemiparetic. The remainder of the neurological examination showed normal results. The patient showed some indifferent euphoria, and reduced attention, concentration, and short-term memory. Visual evoked potentials (VEP) were normal. Brainstem evoked acoustic potentials were normal on the right, whereas waves IV and V were absent on the left. Routine blood chemistry including thyroid and copper metabolism was normal. Cerebrospinal fluid (CSF) was normal for cells and proteins. Blood-brain barrier function was normal (5). There was oligoclonal IgG banding, but no CSF synthesis of IgG or paraproteins. The Link-Tibbling index was 0.62 (6). Treatment was by intravenous prednisolone (starting dose 100 mg) with tapering down during 5 weeks. A spastic right-sided hemiparesis with slight gait disturbance was noted on discharge. Fourteen months later, the patient was readmitted because of a left facial palsy and a deterioration of his rightsided paresis. Most obvious, however, were seborrhea, masked face, generalized hypokinesia, and a hoarse dysarthria with slurring of syllables and consonants. There was no cogwheel rigidity and no resting tremor. Hand dexterity, rapid hand-arm movements, and diadochokinesia on the left were impaired to a moderate degree, whereas these could not be judged on the right due to paresis. Posture was slightly stooped with some retropulsion, but there was recovery on pull test. Gait showed reduced step length on the left, reduced arm swing, and en bloc turning. The patient had 10 points on the Webster rating scale and was rated stage I1 in the Hoehn and Yahr classification. Proton- and T2- weighed magnetic resonance (MR) imaging showed multiple hyperintense lesions in the peri- and supraventricular cerebral white
Case 2 A 60-year-old housewife had severe obesity and a seronegative, chronic rheumatoid arthritis since 1979 and diabetes mellitus since 1985. Since 1980 a slowly progressive reduction of spontaneous movements and lack of initiative were noted. In the 2 years before the first admission in 1986, head tremor and progressive gait difficulty had developed with repeated falls. On examination, there was a Homer’s syndrome on the right with ptosis and miosis. There was horizontal gazeevoked nystagmus bilaterally. DTR were raised and elevated on the right. There was a right plantar extensor response. Abdominal reflexes were absent. Residual bladder volume was 50 ml. There was coarse “No”tremor of the head, and a voice tremor, but no tremor on the extremities. The patient had seborrhea, masked face, and moderate cogwheel rigidity of the left arm, a bilateral bradydiadochokinesia, a broad-based, short-stepped gait, and a moderately stooped posture with pulsion phenomena in all directions. The remainder of the neurological examination results were normal. Webster rating gave 22 points, and the patient had stage IV according to the Hoehn and Yahr classification. Mental status examination showed reduced impulse, initiative, and spontaneity. She was severely apathetic and hypokinetic. VEP were prolonged on both eyes: right 117 ms, left 119 ms. Routine blood chemistry showed elevated serum glucose levels over repeated daytime profiles (between 220 and 270 mg/ dl). Protein content, electrophoresis, and quantitative determination of immunoglobulins were normal. Search for paraproteins, antibodies against cell nuclei, mitochondria, smooth-muscle tissue and DNA, for Rheuma factor, antistreptolysine titer, and Lupus-erythema-todes factor was negative. C-reactive protein was 1:37. Thyroid, parathyroid, and copper metabolism was normal. CSF contained five cells per cubic millimeter. Protein content was 60 mg/dl. Albumin was 25.7 mgldl, and IgG was 8.27 mg/ dl. Blood-brain barrier analysis revealed an increased intrathecal IgG synthesis rate. The CSF showed oligoclonal IgG banding. The Link-Tibbling index was 1.18. There was local synthesis of antibodies against measles, herpes simplex, and zoster in the CSF (7). TI-weighted MR imaging showed several confluant, hyperintense lesions in the peri- and supraventricular cerebral white matter, more pronounced at the tips of the ventricles. Within the
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FIG. 1. Case 1. Magnetic resonance scan of the brain, spin echo technique. Hyperintense lesions of posterior limb of internal capsule and adjacent regions of thalamus and globus pallidus bilaterally; TE 30 ms, TR 2,800 ms.
anterior and posterior limbs of the internal capsule, but also outstretching into the adjacent lateral thalamus and the lentiform nucleus, there were hyperintense areas bilaterally (Fig. 2 ) . There were no lesions in the brainstem and the cervical spinal cord. Treatment by 400 mg L-Dopa (plus 87.5 mg benserazide) given for 10 days did not ameliorate the parkinsonian features. Therefore, intravenous prednisolone with a starting dose of 100 mg was added and tapered down during the next 4 weeks. With this therapy, hypokinesia, pulsion phenomena, and gait improved so that the patient was able to again wash and dress herself. The tremor remained unchanged. During the following months, intermittent pneumonia and urosepsis had made the patient continuously bedridden. On examination in 1988, she had left optic disc pallor and internuclear ophthalmoplegia on the same side. Nuchal rigidity, bilateral cogwheel rigidity of the arms, more markedly on the left, and a fine resting tremor of the left arm were noted as additional signs. There were marked bilateral bradydiadochokinesia, general hypokinesia, and a severe postural instability. With assistance she did some short steps, but had freezing phenomena. Steroid treatment or L-Dopa preparations were not given at this time. The patient was transferred to an institution for the elderly.
Comment Both patients had no prior intake of drugs known to cause parkinsonism. The family history was unremark-
381
able. We therefore think that secondary causes of parkinsonism other than MS have consistently been ruled out in our patients. Both reported cases had definite MS (8): case 1 had clinically definite MS, whereas case 2 had MS with laboratory support. Both developed parkinsonian features during the course of MS. Case 1 had mainly bradykinesia and impaired balance, although he did not present with the classic triad of Parkinson’s disease. Case 2 had the classic triad of Parkinsons’s disease at an advanced stage of disease course. One of the first signs of extrapyramidal involvement had been head tremor. This is thought only rarely, if ever, to appear in idiopathic Parkinson’s disease (9), thus pointing to a secondary etiology such as MS in the present case. Case 2 had a history of chronic rheumatoid arthritis with some deformities of finger joints, but a repeatedly negative rheumatoid factor in serology (similar to a case reported in ref. 3). Because in our case an active rheumatoid disease during the whole observation period could not be evaluated to occur simultaneously with the chronic progressive neurological deterioration, the condition of this case is regarded as MS and not CNS arteritis in rheumatoid arthritis (3). Neither oligoclonal banding, nor increased intrathecal IgG synthesis rate, nor white matter lesions in MR imaging such as in case 2 are specific for MS. However, we consider optic neuritis with delayed VEP, internuclear ophthalmoplegia, and intrathecal synthesis of viral antibodies (7) important pointers toward a diagnosis of MS in this case. The time interval between the first bout of MS and the emergence of parkinsonian symptoms was longer in our cases than in those in the literature (3). This and the obvious rarity of the reported association may indicate a
FIG. 2. Case 2. Magnetic resonance scan of the brain, spin echo technique. Hyperintense lesions adjacent to posterior limbs of internal capsule bilaterally (i.e., thalamus and globus pallidus), more marked on the right; TE 35 rns, TR 3,000 ms.
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fortuitous coincidence: Population prevalence rates (per 100,000) of MS [110 cases; (lo)] and idiopathic Parkinson’s disease [164 cases; ( I l ) ] would in the Northern hemisphere render -1 individual per 500,000 likely to carry both conditions. Arguments against a mere coincidence and in favor of possible pathophysiological links between the two conditions may be as follows. (a) In case 1, the remission of parkinsonian features occurred in a time-locked fashion together with the remission of MS signs and symptoms subsequent to MS-directed drug therapy. (b) In both cases, MR imaging showed involvement of thalami and basal ganglia adjacent to the internal capsule. Overall, basal ganglia affection in MR imaging has been noted in 25% of MS patients (12). Size, distribution, and dynamics of plaque formation within a strategic area such as the internal capsule may contribute to different clinical expression, when the neighboring basal ganglia and thalamic structures are attached. (c) Because ventral and central parts of the thalamus are functionally involved in the basal ganglia-thalamo-cortical pathways, structural lesions such as demyelinating plaques affecting these circuitries at the thalamic or basal ganglia level may result clinically in hypokinetic (case 1) or full-blown parkinsonian states (case 2) (13). Longitudinal monitoring of MS cases with basal ganglia involvement on MR imaging may help to establish in-vivo the exact meaning of a clinicoradiological correlation between movement disorders and MS. P. Vieregge W. Klostermann Klinik fur Neurologie H. Briickmann Institut fiir Radiologie Medizinische Universitat zu Liibeck Liibeck, Germany
References 1 . Coleman RJ, Quinn NP, Marsden CD. Multiple sclerosis presenting as adult onset dystonia. Mov Disord 1988;3:329332. 2. Plant GT, Kermode AG, du Bouley EP, McDonald WI. Spasmodic torticollis due to a midbrain lesion in a case of multiple sclerosis. Mov Disord 1989;4:359-362. 3. Mao CC, Gancher ST, Herndon RM. Movement disorders in multiple sclerosis. Mov Disord 1988;3:109-1 16. 4. Riley D, Lang AE. Hemiballism in multiple sclerosis. Mov Disord 1988;3:88-94. 5. Reiber HO, Felgenhauer K. Protein transfer at the bloodCSF barrier and the quantitation of the humoral immune response within the central nervous system. Clin Chem Acta 1987;163:319-328. 6. Tibbling G, Link H, Ohman S . Principles of albumin and IgG analysis in neurological disorders. I. Establishment of reference values. Scand J Clin Lab Invest 1977;37:385-390. 7. Schadlich H-J, Karbe H, Felgenhauer K. The prevalence of locally-synthesized virus antibodies in various forms of multiple sclerosis. J Neurol Sci 1987;80:343-349. 8. Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983;13:227-231. 9. Barbeau A. Parkinson’s disease: clinical features and etiopathology. In: Vinken PJ, Bruyn GW, Klawans H, eds. Ex-
Movement Disorders, Vol. 7, No. 4, 1992
10. 11.
12.
13.
trapyramidal disorders. Amsterdam: Elsevier Science, 1986:87-152. [Handbook of clinical neurology; vol5 (49)l. Beer S , Kesselring J. Die Multiple Sklerose im Kanton Bern (CH). Fortschr Neurol Psychiatr 1988;56:390-397. Mutch WJ, Dingwall-Fordyce I, Downie AW, Paterson JG, Roy SK. Parkinson’s disease in a Scottish city. Br Med J 1986;292:534-536. Kesselring J, Ormerod IEC, Miller DH, du Bouley EPGH, McDonald WI. Magnetic resonance imaging in multiple sclerosis. Stuttgart and New York: Georg Thieme Verlag, 1989. Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. TINS 1990;13:266271.
Parkinson’s Disease in a Patient with Mitochondria1 Myopathy: Is There a Causative Relationship? To the Editor: The cause of the progressive nigral degeneration in Parkinson’s disease (PD) is unknown. It was recently suggested that the mitochondrial respiratory enzyme complex-1 (NADH: ubiquinone oxidoreductase) activity is deficient in the CNS and platelets of patients with PD (1-3). Interestingly, 1-methyl-4-phenyl-pyridinium ion (MPP ), the toxic metabolite of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), kills nigral neurons by poisoning their mitochondrial respiration (4). After its entry into dopaminergic neurons, MPP is taken-up and concentrated by the mitochondria where it inhibits the NADH-linked fraction of complex-I activity (5). These observations suggest that nigral neurons may die in PD because of impaired mitochondrial energy metabolism due to hereditary, neurotoxic, or other factors (6,7). The mitochondrial myopathies are a heterogenous group of diseases that share the common features of structural changes in skeletal muscle mitochondria and may cause muscular as well as nervous system dysfunction. We now report a patient with longstanding mitochondrial myopathy who developed PD. The intriguing question is whether the two disorders are causatively related or purely coincidental. A 60-year-old man was under long-term follow-up because of a syndrome consisting of slowly progressive muscle weakness, peripheral neuropathy and external ophthalmoplegia. He was readmitted because during the last year he developed symptoms of PD. There was no family history of myopathy, PD, or other neurological disorders. He was never exposed to neuroleptic drugs. On examination, his older signs included complete external ophthalmoplegia, bilateral facial weakness, reduced proximal muscle strength symmetrically affecting both upper and lower limbs, generally absent tendon jerks, and distal hypoesthesia to pain and touch. Plantar responses were bilaterally flexor. There were no signs of dementia. The new neurological findings included marked reduced facial mimicry with monotonous and slow speech. He was generally bradykinetic and rigid, with slow and shuffling gait. He had coarse resting tremor af-
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+
