10. Roach A, Boylan K, Horvath S, et al. Characterization of cloned
cDNA representing rat myelin basic protein: absence of expression in brain of shiverer mutant mice. Cell 1983;34:799-806 11. Maniatis T, Frisch EB, Sambrook,J. Molecular cloning: a laboratory manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory, 1982 12. Kamholz J, Spielman R, Gogolin K, et al. The human myelin basic protein gene: chromosomal locahzation and RFLP analysis. Am J Hum Genet 1987;40:365-373 13. Le Beau MM, Ryan D, Pericak-Vance MA. Report of the committee on the genetic constitution of chromosomes 18 and 19. Cytogenet Cell Genet 1989;51:338-357
Recurrent Attacks of Amaurosis Fugax Treated with Calcium Channel Blocker Jacqueline M. S. Winterkorn, PhD, MD, and Allen Jay Teman, MD
Vasospasm may be one of the causes of amaurosis fugax. A patient is reported who daily experienced multiple brief episodes of amaurosis fugax. The absence of physical, laboratory, or radiographic evidence for thromboembolism, hemodynamic compromise, or vasculitis, suggested that the amaurosis might be caused b y vasospasm. This hypothesis was supported by cessation of the attacks of amaurosis when the patient was treated with a calcium channel blocker. Winterkorn JMS, Teman AJ. Recurrent artacks of amaurosis fugax treated with calcium channel blocker. Ann Neurol 1991;30:423-425
Amaurosis fugax can be caused by several mechanisms. Embolism from t h e carotid artery has been accepted as the m o s t c o m m o n cause of amaurosis fugax ever since Fisher El} reported a patient in whom transient monocular blindness associated with hemiplegia was caused b y an embolus from a plaque i n the internal carotid artery. O t h e r suggested causes have included emboli from the heart, retinal vascular insufficiency, vasculitis, hypercoagulable or hyperviscosity syndromes, migraine, and local disk anomalies E2, 31. We have treated a patient who experienced multiple episodes of transient monocular blindness, which ceased
From the Division of Neuro-Ophthalmology, Department of Ophthalmology, and Department of Neurology, North Shore University Hospital-Cornell University Medical College, Manhasset, NY. Received Dec 15, 1990, and in revised form Mar 12, 1991. Accepted for publication Mar 31, 1991. Address correspondenceto Dr Winterkorn, North Shore University Hospital-Cornell University Medical College, Department of Ophthalmology, 300 Community Drive, Manhasset, NY 11030.
immediately when he was administered a calcium channel blocker. We infer that vasospasm w a ~the mechanism underlying arnaurosis fugax in this patient.
Patient Report A 77-year-old man, with mild hypertension controlled on indapamide (Lozol), suddenly began to experience multiple daily episodes of transient monocular blindness in the left eye. No episode ever occurred in the right eye. He had no personal or family history of headaches or migraine diathesis. Onset of an attack was not related to his position or activity. Immediately before each attack of visual loss, he felt an uncomfortable sensation behind his left eye. Then, the vision in the left eye dimmed over a period of 2 to 3 minutes to complete blindness, lasting 2 to 10 minutes. Vision returned to normal over 1 or 2 minutes. For years, he had been taking one aspirin 80 mg per day for cardiac prophylaxis. Although the dosage of aspirin was increased to 325 mg per day, he continued to have 5 to 12 episodes of amaurosis fugax each day. Blood tests were normal, including complete blood count, Westergren erythrocyte sedimentation rate, serum chemistries, anticardiolipin antibody, prothrombin timeipartial thromboplastin time, VDFU (Venereal Disease Research Laboratories) test. Echocardiogram, Holter monitor, and visual-evoked potentials were normal. Carotid duplex scan revealed 35% narrowing of the left internal carotid artery at its origin and no ulcerated plaque. After 6 weeks of daily episodes of amaurosis fugax, cerebral angiography was performed. Bilateral carotid and arch angiography confirmed the absence of significant stenosis at the origin of either internal carotid artery. A nonulcerated plaque, however, caused 25% narrowing of the cavernous portion of the left internal carotid artery. In addition, the left ophthalmic artery appeared severely stenotic, narrowed to less than 50% of the diameter of the right ophthalmic artery (Fig). After multiple episodes had occurred daily for 2 months, the patient sought neuro-ophthalmic consultation. As that examination began, the patient experienced an episode of visual loss in his left eye. He reported fading of vision to no light perception over a few minutes. A left afferent pupillary defect was noted, with the left pupil completely unreactive to direct light stimulation. Ophthalmoscopy revealed no perfusion of the central retinal artery, narrowing of the retinal vasculature, and retinal pallor. Recovery followed 12 minutes of nonperfusion. The arteries filled with blood and the veins dilated. Vision gradually cleared to 20/25 - 3 in the left eye, with a brisk pupillary response and no afferent pupillary defect. Visual field testing demonstrated an inferior arcuate scotoma in the left eye, which corresponded to a cotton-wool spot visualized along the superior arcade. No emboli were seen in the blood vessels of either eye. In the absence of embolic fragments, an embolic cause of amaurosis fugax seemed less likely than vasospasm superimposed on a stenotic ophthalmic artery. To control vasospasm, a calcium channel blocker was prescribed. As soon as therapy was initiated with 30 mg of the long-acting form of nifedipine, the attacks ceased completely. After a week of therapy, the patient reported three episodes of premonitory retrobulbar sensation occurring a few hours before his nightly dose of
Copyright 0 1991 by the American Neurological Association
423
nifedipine. The timing and dosage were adjusted, and no further attacks have occurred for 10 months.
A
B Carotid angiography revealed normal filling of the right ophthalmic artery (open arrow) (B), and absence of filling of the left ophthalmic avtevy (closed arrow) (A)The interpretation of the complete angiogram was that the ,!eft ophthalmic artery was narrowed to less than JO% of the diameter of the right ophthalmic artery. (Orientation of A has been inverted t o facilitate campariron with B.)
Discussion Vasospasm is a possible cause of amaurosis fugax. Although calcium channel blockers inhibit vascular spasm, their efficacy in treating amaurosis fugax has not been studied. Vasospasm also has been implicated in patients with migraine, Raynaud's phenomenon, SC hemoglobinopathy, and systemic lupus erythematosus (SLE) [4-61. Miller and Santoro [ 7 ) describe a 26year-old woman with SLE who had recurrent episodes of monocular visual loss, which ceased when she was treated with nifedipine to prevent vasospasm. Amaurosis fugax in elderly patients usually has been attributed to thromboembolism or hemodynamic compromise [33. However, of patients younger than 50 years of age, without a history of migraine and without evidence of atherosclerotic disease, 11% have no identifiable cause for their transient monocular visual loss [Z}. The successful treatment of our patient with a calcium channel blocker suggests that vasospasm may be a mechanism underlying amaurosis fugax in these patients. The hypothesis that vasospasm caused the amaurosis fugax in our patient was suggested by our personal observation of vasospasm during an attack of amaurosis fugax, and was supported by the absence of emboli in the retina, the high frequency of amaurotic attacks without other associated neurological deficits, the gradual onset and resolution of visual loss in each attack, and the dramatic response to a calcium channel blocker. This 77-year-old man also probably has atherosclerotic cerebrovascular disease, which Williams and colleagues [S} have proposed predisposes to vasospasm by increasing the sensitivity of the vasculature to vasoconstrictor substances such as serotonin. Complete resolution of symptoms with nifedipine treatment in this patient, after 2 months of multiple daily episodes of amaurosis fugax, is strongly indicative of the efficacy of the treatment. A controlled study to determine the effectiveness of calcium channel blockers in a group of patients with idiopathic amaurosis fugax might be valuable. References 1. Fisher CN. Transient monocular blindness associated with hemiplegia Arch Ophthalmol 1952;47:167-203 2. The Amaurosis Fugax Study Group. Current management of amaurosis fugax. Stroke 1990;21:201-208 3. Wray SH. Visual aspects of extracranial internal carotid artery disease. In: Bernstein E, ed. Amaurosis fugax. New York Springer-Verlag, 1988 4. TippinJ, CorbettJJ, Kerber RE,et al. Amaurosis fugax and ocular infarction in adolescents and young adults. Ann Neurol 1989; 26~69-77 5. Carpenter WM, Carpenter EW. Raynaud's disease and intermittent spasm of the retinal artery and veins. Arch Ophthalmol 1938;19:111
424 Annals of Neurology Vol 30 No 3 September 1991
Shaw HE, Osher RH, Smith JL. Amaurosis fugax associated with SC hemoglobinopathy and lupus erythematosus. Am J Ophthalmol 1979;87:281-285 Miller W ,Santoro TJ. Nifedipine in the treatment of migraine headache and amaurosis fugax in patients with systemic lupus erythematosis. N Engl J Med 1981;311:921 Williams JK, Baumbach GL, Armstrong ML, et al. Hypothesis: vasoconstriction contributes to amaurosis fugax. J Cereb Blood Flow Metab 1989;9:111-116
Presvnamic Parhnsonism in Ok6pontocerebellar Atrophy: Clinical, Pathologcal, and Neurochemical Evidence Julio Pascual, MD,’t Angel Pazos, MD,” Elena del Olmo, MD,” Javier Figols, MD,$ Carlos Leno, MD,t and Jose Berciano, M D t
The substrate for olivopontocerebellar atrophy parkinsonism is obscure due to the lack of clinical and pathological reports and the absence of studies on dopamine receptors in this entity. We describe apatient with olivopontocerebellar atrophy whose clinical presentation was levodopa-responsive parkinsonism in whom pathological examination disclosed pronounced nigral cell loss with no striatal damage. Autoradiographic labeling with 3H-spiperone showed normal densities of D, dopamine striatal receptors. These data show that indistinguishable nigral, presynaptic parkinsonism occurs in patients with idiopathic Parkinson’s disease and in patients with olivopontocerebellar atrophy, and also how a favorable response to levodopa is neither synonymous with idiopathic Parkinson’s disease, nor does it exclude multiple-system, atrophy-related parkinsonism. Pascual J, Pazos A, del Olmo E, Figols J, Len0 C , Berciano J. Presynaptic parkinsonism in olivopontocerebellar atrophy: clinical, pathological, and neurochemical evidence. Ann Neurol 1991;30:425-428
Leaving aside idiopathic Parkinson’s disease (IPD), parkinsonism may be the outstanding clinical feature in
From the *Department of Physiology and Pharmacology, Unit of Pharmacology;tDepartrnent of Medicine, Service of Neurology; and $Section of Neuropathology, Universitary Hospital “MarquCs de
Valdecilla” and Faculty of Medicine, Santander, Spain. Received Oct 22, 1990, and in revised form Feb 5 and Mar 25, 1991. Accepted for publication Mar 30, 1991. Address correspondence to Dr Pascual, Service of Neurology, Universitary Hospital “Marqds de Valdecilla,”39008 Santander, Spain.
several neurodegenerative disorders such as progressive supranuclear palsy (PSPj and multiple-system atrophies (MSA), that is, Shy-Drager syndrome, striatonigral degeneration (SND), and olivopontocerebellar atrophy (OPCA) [l}. In patients with IPD, clinical manifestations are due to degeneration of nigral neurons projecting to striatum. Thus, in patients with IPD, parkinsonian clinical features are presynaptic, there being no significant alteration in D, dopamine receptors at the striatum [a-41. By contrast, parkinsonism in patients with PSP and SND appears to be secondary to both nigral and striatal degeneration, patients responding poorly or not at all to levodopa or dopaminergic agonists [11. Although progressive cerebellar disturbance is considered OPCA’s most outstanding clinical feature, parkinsonian symptomatology occurs in at least 50% of patients 15-71. Furthermore, parkinsonism is the presenting symptom in about 10% of patients with OPCA 15, 63. In contrast to IPD, PSP, and SND, the underlying substrate for OPCA parkinsonism is still debatable due to (1) scarce and conflicting clinical and neuropathological data regarding the relative involvement of nigral or striatal degeneration and (2) the absence of dopamine receptor studies in patients with OPCA. Here, we report a patient with OPCA in whom the clinical presentation was parkinsonism and in whom postmortem autoradiographic labeling of D, dopamine receptors was performed. Patient Report This 73-year-old man had a 12-year history of akinesia, rigidity, and slight right-hand resting tremor. From the beginning, his parkinsonism had been responsive to levodopa, and he thus received a diagnosis of IPD elsewhere. Four years before death, progressive walking difficulties, pseudobulbar features, and urinary incontinence appeared. Seven days before death, the man was admitted to our hospital because of aspirative pneumonia. At that time, neurological examination disclosed no orthostatic hypotension, but did show slaw thinking without significant dementia, difficulties in the saccadic ocular movements, pseudobulbar dysarthria and dysphagia, generalized hyperreflexia, moderate truncal ataxia, and a parkinsonian syndrome (akinesia, rigidity and slight resting manual tremor) that still responded well to 125 to 250 mg of levodopa and 2 mg of trihexyphenidyl three times daily. End-off-dose deterioration, wearing-off phenomenon, and peak-dose dyskinesias were observed in relation to levodopa administration. Computed tomographic scan was not performed. Presumptive antemortem diagnosis was sporadic OPCA (Dejerine-Thomas type).
Methods At autopsy, the brain was promptly removed, one hemibrain being fixed in 10% formalin for neuropathological examination. The other hemibrain was cut into blocks, quickly frozen, and stored at - 70°C until used in binding assays. Autoradiographic labeling of D, dopamine receptors was performed in the caudate-putamen of the patient with OPCA
Copyright @ 1991 by the American Neurological Association
425
cDNA representing rat myelin basic protein: absence of expression in brain of shiverer mutant mice. Cell 1983;34:799-806 11. Maniatis T, Frisch EB, Sambrook,J. Molecular cloning: a laboratory manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory, 1982 12. Kamholz J, Spielman R, Gogolin K, et al. The human myelin basic protein gene: chromosomal locahzation and RFLP analysis. Am J Hum Genet 1987;40:365-373 13. Le Beau MM, Ryan D, Pericak-Vance MA. Report of the committee on the genetic constitution of chromosomes 18 and 19. Cytogenet Cell Genet 1989;51:338-357
Recurrent Attacks of Amaurosis Fugax Treated with Calcium Channel Blocker Jacqueline M. S. Winterkorn, PhD, MD, and Allen Jay Teman, MD
Vasospasm may be one of the causes of amaurosis fugax. A patient is reported who daily experienced multiple brief episodes of amaurosis fugax. The absence of physical, laboratory, or radiographic evidence for thromboembolism, hemodynamic compromise, or vasculitis, suggested that the amaurosis might be caused b y vasospasm. This hypothesis was supported by cessation of the attacks of amaurosis when the patient was treated with a calcium channel blocker. Winterkorn JMS, Teman AJ. Recurrent artacks of amaurosis fugax treated with calcium channel blocker. Ann Neurol 1991;30:423-425
Amaurosis fugax can be caused by several mechanisms. Embolism from t h e carotid artery has been accepted as the m o s t c o m m o n cause of amaurosis fugax ever since Fisher El} reported a patient in whom transient monocular blindness associated with hemiplegia was caused b y an embolus from a plaque i n the internal carotid artery. O t h e r suggested causes have included emboli from the heart, retinal vascular insufficiency, vasculitis, hypercoagulable or hyperviscosity syndromes, migraine, and local disk anomalies E2, 31. We have treated a patient who experienced multiple episodes of transient monocular blindness, which ceased
From the Division of Neuro-Ophthalmology, Department of Ophthalmology, and Department of Neurology, North Shore University Hospital-Cornell University Medical College, Manhasset, NY. Received Dec 15, 1990, and in revised form Mar 12, 1991. Accepted for publication Mar 31, 1991. Address correspondenceto Dr Winterkorn, North Shore University Hospital-Cornell University Medical College, Department of Ophthalmology, 300 Community Drive, Manhasset, NY 11030.
immediately when he was administered a calcium channel blocker. We infer that vasospasm w a ~the mechanism underlying arnaurosis fugax in this patient.
Patient Report A 77-year-old man, with mild hypertension controlled on indapamide (Lozol), suddenly began to experience multiple daily episodes of transient monocular blindness in the left eye. No episode ever occurred in the right eye. He had no personal or family history of headaches or migraine diathesis. Onset of an attack was not related to his position or activity. Immediately before each attack of visual loss, he felt an uncomfortable sensation behind his left eye. Then, the vision in the left eye dimmed over a period of 2 to 3 minutes to complete blindness, lasting 2 to 10 minutes. Vision returned to normal over 1 or 2 minutes. For years, he had been taking one aspirin 80 mg per day for cardiac prophylaxis. Although the dosage of aspirin was increased to 325 mg per day, he continued to have 5 to 12 episodes of amaurosis fugax each day. Blood tests were normal, including complete blood count, Westergren erythrocyte sedimentation rate, serum chemistries, anticardiolipin antibody, prothrombin timeipartial thromboplastin time, VDFU (Venereal Disease Research Laboratories) test. Echocardiogram, Holter monitor, and visual-evoked potentials were normal. Carotid duplex scan revealed 35% narrowing of the left internal carotid artery at its origin and no ulcerated plaque. After 6 weeks of daily episodes of amaurosis fugax, cerebral angiography was performed. Bilateral carotid and arch angiography confirmed the absence of significant stenosis at the origin of either internal carotid artery. A nonulcerated plaque, however, caused 25% narrowing of the cavernous portion of the left internal carotid artery. In addition, the left ophthalmic artery appeared severely stenotic, narrowed to less than 50% of the diameter of the right ophthalmic artery (Fig). After multiple episodes had occurred daily for 2 months, the patient sought neuro-ophthalmic consultation. As that examination began, the patient experienced an episode of visual loss in his left eye. He reported fading of vision to no light perception over a few minutes. A left afferent pupillary defect was noted, with the left pupil completely unreactive to direct light stimulation. Ophthalmoscopy revealed no perfusion of the central retinal artery, narrowing of the retinal vasculature, and retinal pallor. Recovery followed 12 minutes of nonperfusion. The arteries filled with blood and the veins dilated. Vision gradually cleared to 20/25 - 3 in the left eye, with a brisk pupillary response and no afferent pupillary defect. Visual field testing demonstrated an inferior arcuate scotoma in the left eye, which corresponded to a cotton-wool spot visualized along the superior arcade. No emboli were seen in the blood vessels of either eye. In the absence of embolic fragments, an embolic cause of amaurosis fugax seemed less likely than vasospasm superimposed on a stenotic ophthalmic artery. To control vasospasm, a calcium channel blocker was prescribed. As soon as therapy was initiated with 30 mg of the long-acting form of nifedipine, the attacks ceased completely. After a week of therapy, the patient reported three episodes of premonitory retrobulbar sensation occurring a few hours before his nightly dose of
Copyright 0 1991 by the American Neurological Association
423
nifedipine. The timing and dosage were adjusted, and no further attacks have occurred for 10 months.
A
B Carotid angiography revealed normal filling of the right ophthalmic artery (open arrow) (B), and absence of filling of the left ophthalmic avtevy (closed arrow) (A)The interpretation of the complete angiogram was that the ,!eft ophthalmic artery was narrowed to less than JO% of the diameter of the right ophthalmic artery. (Orientation of A has been inverted t o facilitate campariron with B.)
Discussion Vasospasm is a possible cause of amaurosis fugax. Although calcium channel blockers inhibit vascular spasm, their efficacy in treating amaurosis fugax has not been studied. Vasospasm also has been implicated in patients with migraine, Raynaud's phenomenon, SC hemoglobinopathy, and systemic lupus erythematosus (SLE) [4-61. Miller and Santoro [ 7 ) describe a 26year-old woman with SLE who had recurrent episodes of monocular visual loss, which ceased when she was treated with nifedipine to prevent vasospasm. Amaurosis fugax in elderly patients usually has been attributed to thromboembolism or hemodynamic compromise [33. However, of patients younger than 50 years of age, without a history of migraine and without evidence of atherosclerotic disease, 11% have no identifiable cause for their transient monocular visual loss [Z}. The successful treatment of our patient with a calcium channel blocker suggests that vasospasm may be a mechanism underlying amaurosis fugax in these patients. The hypothesis that vasospasm caused the amaurosis fugax in our patient was suggested by our personal observation of vasospasm during an attack of amaurosis fugax, and was supported by the absence of emboli in the retina, the high frequency of amaurotic attacks without other associated neurological deficits, the gradual onset and resolution of visual loss in each attack, and the dramatic response to a calcium channel blocker. This 77-year-old man also probably has atherosclerotic cerebrovascular disease, which Williams and colleagues [S} have proposed predisposes to vasospasm by increasing the sensitivity of the vasculature to vasoconstrictor substances such as serotonin. Complete resolution of symptoms with nifedipine treatment in this patient, after 2 months of multiple daily episodes of amaurosis fugax, is strongly indicative of the efficacy of the treatment. A controlled study to determine the effectiveness of calcium channel blockers in a group of patients with idiopathic amaurosis fugax might be valuable. References 1. Fisher CN. Transient monocular blindness associated with hemiplegia Arch Ophthalmol 1952;47:167-203 2. The Amaurosis Fugax Study Group. Current management of amaurosis fugax. Stroke 1990;21:201-208 3. Wray SH. Visual aspects of extracranial internal carotid artery disease. In: Bernstein E, ed. Amaurosis fugax. New York Springer-Verlag, 1988 4. TippinJ, CorbettJJ, Kerber RE,et al. Amaurosis fugax and ocular infarction in adolescents and young adults. Ann Neurol 1989; 26~69-77 5. Carpenter WM, Carpenter EW. Raynaud's disease and intermittent spasm of the retinal artery and veins. Arch Ophthalmol 1938;19:111
424 Annals of Neurology Vol 30 No 3 September 1991
Shaw HE, Osher RH, Smith JL. Amaurosis fugax associated with SC hemoglobinopathy and lupus erythematosus. Am J Ophthalmol 1979;87:281-285 Miller W ,Santoro TJ. Nifedipine in the treatment of migraine headache and amaurosis fugax in patients with systemic lupus erythematosis. N Engl J Med 1981;311:921 Williams JK, Baumbach GL, Armstrong ML, et al. Hypothesis: vasoconstriction contributes to amaurosis fugax. J Cereb Blood Flow Metab 1989;9:111-116
Presvnamic Parhnsonism in Ok6pontocerebellar Atrophy: Clinical, Pathologcal, and Neurochemical Evidence Julio Pascual, MD,’t Angel Pazos, MD,” Elena del Olmo, MD,” Javier Figols, MD,$ Carlos Leno, MD,t and Jose Berciano, M D t
The substrate for olivopontocerebellar atrophy parkinsonism is obscure due to the lack of clinical and pathological reports and the absence of studies on dopamine receptors in this entity. We describe apatient with olivopontocerebellar atrophy whose clinical presentation was levodopa-responsive parkinsonism in whom pathological examination disclosed pronounced nigral cell loss with no striatal damage. Autoradiographic labeling with 3H-spiperone showed normal densities of D, dopamine striatal receptors. These data show that indistinguishable nigral, presynaptic parkinsonism occurs in patients with idiopathic Parkinson’s disease and in patients with olivopontocerebellar atrophy, and also how a favorable response to levodopa is neither synonymous with idiopathic Parkinson’s disease, nor does it exclude multiple-system, atrophy-related parkinsonism. Pascual J, Pazos A, del Olmo E, Figols J, Len0 C , Berciano J. Presynaptic parkinsonism in olivopontocerebellar atrophy: clinical, pathological, and neurochemical evidence. Ann Neurol 1991;30:425-428
Leaving aside idiopathic Parkinson’s disease (IPD), parkinsonism may be the outstanding clinical feature in
From the *Department of Physiology and Pharmacology, Unit of Pharmacology;tDepartrnent of Medicine, Service of Neurology; and $Section of Neuropathology, Universitary Hospital “MarquCs de
Valdecilla” and Faculty of Medicine, Santander, Spain. Received Oct 22, 1990, and in revised form Feb 5 and Mar 25, 1991. Accepted for publication Mar 30, 1991. Address correspondence to Dr Pascual, Service of Neurology, Universitary Hospital “Marqds de Valdecilla,”39008 Santander, Spain.
several neurodegenerative disorders such as progressive supranuclear palsy (PSPj and multiple-system atrophies (MSA), that is, Shy-Drager syndrome, striatonigral degeneration (SND), and olivopontocerebellar atrophy (OPCA) [l}. In patients with IPD, clinical manifestations are due to degeneration of nigral neurons projecting to striatum. Thus, in patients with IPD, parkinsonian clinical features are presynaptic, there being no significant alteration in D, dopamine receptors at the striatum [a-41. By contrast, parkinsonism in patients with PSP and SND appears to be secondary to both nigral and striatal degeneration, patients responding poorly or not at all to levodopa or dopaminergic agonists [11. Although progressive cerebellar disturbance is considered OPCA’s most outstanding clinical feature, parkinsonian symptomatology occurs in at least 50% of patients 15-71. Furthermore, parkinsonism is the presenting symptom in about 10% of patients with OPCA 15, 63. In contrast to IPD, PSP, and SND, the underlying substrate for OPCA parkinsonism is still debatable due to (1) scarce and conflicting clinical and neuropathological data regarding the relative involvement of nigral or striatal degeneration and (2) the absence of dopamine receptor studies in patients with OPCA. Here, we report a patient with OPCA in whom the clinical presentation was parkinsonism and in whom postmortem autoradiographic labeling of D, dopamine receptors was performed. Patient Report This 73-year-old man had a 12-year history of akinesia, rigidity, and slight right-hand resting tremor. From the beginning, his parkinsonism had been responsive to levodopa, and he thus received a diagnosis of IPD elsewhere. Four years before death, progressive walking difficulties, pseudobulbar features, and urinary incontinence appeared. Seven days before death, the man was admitted to our hospital because of aspirative pneumonia. At that time, neurological examination disclosed no orthostatic hypotension, but did show slaw thinking without significant dementia, difficulties in the saccadic ocular movements, pseudobulbar dysarthria and dysphagia, generalized hyperreflexia, moderate truncal ataxia, and a parkinsonian syndrome (akinesia, rigidity and slight resting manual tremor) that still responded well to 125 to 250 mg of levodopa and 2 mg of trihexyphenidyl three times daily. End-off-dose deterioration, wearing-off phenomenon, and peak-dose dyskinesias were observed in relation to levodopa administration. Computed tomographic scan was not performed. Presumptive antemortem diagnosis was sporadic OPCA (Dejerine-Thomas type).
Methods At autopsy, the brain was promptly removed, one hemibrain being fixed in 10% formalin for neuropathological examination. The other hemibrain was cut into blocks, quickly frozen, and stored at - 70°C until used in binding assays. Autoradiographic labeling of D, dopamine receptors was performed in the caudate-putamen of the patient with OPCA
Copyright @ 1991 by the American Neurological Association
425
