Vascular pseudoparkinsonism Chang CM, Yu YL, Ng HK, Leung SY, Fong KY. Vascular pseudoparkinsonism. Acta Neurol Scand 1992: 86: 588-592. 0 Munksgaard 1992. Vascular pseudoparkinsonism may be confused with idiopathic Parkinson’s disease. Patients may be unnecessarily treated with anti-parkinsonian drugs while their underlying vascular disease is ignored. We investigated 250 parkinsonian patients seen in our Movement Disorders Clinic for a possible vascular etiology. After excluding those with a known secondary cause such as drug-induced parkinsonism, progressive supranuclear palsy, multiple system atrophy and hyperparathyroidism, brain computed tomography and/or magnetic resonance imaging were performed on those who showed poor or no response to levodopa. In those with an ischemic lesion demonstrated on neuroimaging, anti-parkinsonian drugs were stopped and the patients were reassessed. Eleven patients (4.4%) had ischemic brain lesions accounting for their parkinsonism. All were initially diagnosed as Parkinson’s disease because of the prominence of bradykinesia and rigidity. Gait disturbance was also common, but resting tremor was distinctly absent. Three anatomical patterns with different prognosis were identified. Three patients with basal ganglia lacunar infarct recovered spontaneously, three with frontal lobe infarcts remained static and five with periventricular and deep subcortical white matter lesions had progressive deterioration. Autopsy in one patient confirmed bilateral frontal lobe watershed infarcts and the absence of brain stem Lewy bodies. Parkinsonian patients with poor or no response to levodopa therapy should be investigated for a vascular etiology. Cerebral arteriosclerosis has long been considered a possible cause of parkinsonism (1). Critchley distinguished arteriosclerotic parkinsonism from Parkinson’s disease (PD) by its absence of tremor and cogwheel rigidity and the presence of catatonia, muscle firmness, pseudobulbar features, dementia, incontinence, focal cerebral symptoms, evidence of cerebral or peripheral blood vessel disease, hypertension and mode of onset (2). He suggested that lesions in the globus pallidus and substantia nigra were vascular in origin. His view was not widely accepted because of the lack of specific character or distribution of the vascular pathology. In addition, other causes of parkinsonism such as multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, which were not recognised at that time, may have been included. Moreover, epidemiological and autopsy studies of PD failed to show an increased incidence of clinical arteriosclerosis (3,4) or basal ganglia vascular pathology (5). Parkes et al. questioned the term arteriosclerotic parkinsonism, but described 12 akinetic-rigid patients with cerebral arteriosclerosis (6). Their patients were similar to Critchley’s, but with additional findings of gegenhalten, normal cerebrospinal fluid homovanillic acid levels, excessive slow waves on 588 C. M. Chan I,Y. L. Yu’, H. K. Ng’, S. Y. Leung , K. Y. Fong 9 ’ Departments of Medicine, Pathology, University of Hong Kong, Queen Mary Hospital, Hong Kong Key words: vascular pseudoparkinsonism; clinical features; CT; MRI C.M. Chang, University Department of Medicine, Queen Mary Hospital, Hong Kong Accepted for publication June 1, 1992 electroencephalography and poor therapeutic response to levodopa. Accepting these features as different from PD, Critchley conceded that arteriosclerotic pseudoparkinsonism was the more appropriate term (7). In the last decade, however, the concept of a vascular cause for parkinsonism was strengthened with the computed tomography (CT) demonstration of basal ganglia infarcts (8-10) and deep white matter lesions (11) in some parkinsonian patients. Magnetic resonance imaging (MRI) provided further evidence (12). Moreover, in a few autopsied cases brain stem Lewy bodies were absent; instead the pathological substrates were status cribrosus of substantia nigra (13), basal ganglia infarcts (14, 15) or multiinfarct, white matter ischaemia and lacunes ( 5 ) . We report herein 11 patients and correlate their clinical features with CT or MRI abnormalities. Material and methods All 250 parkinsonian patients in our Movement Disorders Clinic were reviewed as part of a systematic study. Seven patients with drug induced parkinsonism, four with progressive supranuclear palsy, four with multiple system atrophy and one with hy- Vascular pseudoparkinsonism poparathyroidism were first identified. In the remaining 234 patients, 13 who all along showed poor (questionable or very little response) or no response to optimal dosages of levodopa (Sinemet or Madopar) were investigated for a possible vascular etiology. History of hypertension, heart disease, diabetes mellitus and other risk factors for cerebrovascular disease (CVD) were sought. General and neurological examination and brain CT or MRI were performed. A cerebral ischemic lesion was defined as periventricular hypodensity, lacune, cortical, subcortical infarct on CT or intense halo of periventricular hyperdensity of variable thickness with patchy distribution and irregular margin on T2 weighted MRI (16). Anti-parkinsonian drugs were stopped, and the patients reassessed. As part of our on-going systematic study, brain CT scans had also been performed in 100 patients who had responded to levodopa. These were reviewed to determine the frequency of coexistent ischemic lesions. Coexistent ischemic lesions on brain CT were found in 22 of 100 patients (only 5 had previous history of stroke) who had responded to levodopa (cortical infarcts in 3, lacunes in 9, periventricular hypodensities in 17). These patients therefore had both CVD and PD. The clinical characteristics of the 11 patients (4.4%) with vascular pseudoparkinsonism are summarised in the Table. The three patterns of cerebral ischemic lesions are illustrated below: Periventricular and deep subcortical white matter lesion Case 1 . This 69-year-old retired merchant with a history of hypertension complained of insidious onset of weakness of both legs 16 months previously, followed by clumsiness of right hand, poor memory and deterioration in calculation. He was treated by a general practitioner with Madopar 125 mg tds daily for one year without improvement. Examination revealed masked face, monotonous speech, positive glabellar tap, axial and right sided lead-pipe rigidity, slow but wide based shuffling gait, poor arm swing, turning hesitation and an upright posture. There was no festination, freezing, tremor, cogwheel rigidity, pyramidal signs or pseudobulbar features. CT showed bilateral deep white manner hypodensities more prominent on the left side (Fig. 1). MRI revealed intense periventricular and deep subcortical white matter hyperdensities on T2 weighted images Results Vascular pseudoparkinsonism was diagnosed in 11 patients who had ischemic lesions on CT or MRI, and whose parkinsonism did not deteriorate after discontinuation of drugs. Two other patients had normal brain CT and showed obvious deterioration after levodopa was stopped. Table 1. Data on 11 patients with vascular pseudoparkinsonism Case Sex Onset (yr) Age at last follow up (yr) Immediately following stroke Hypertension lschaemic heart disease Diabetes mellitus Akinesia Rigidity Gait disturbance Resting tremor Pyramidal signs Pseudobulbar features Dementia Urinary incontinence CT MRI Course 1 2 3 4 5 6 7 8 9 10 F 61 F 68 M 80 M 76 F 63 M 71 67* 69 80* 78* 66 79 t t - - t t - t t - - t t t t t t t t t t t - t t t t t t t t t t - t t t t t t t - - - - t t - - - - - t - - P nd Pr f nd f nd f f St St St - - P P Pr - - - - - 11 - I nd r Abbreviations: *=age of death, d=deep subcortical white matter lesion, F=female, f=large frontal lobe infarct, kbasal ganglia lacune, M=male, nd=not done, p=periventricular white matter lesion, pr=progressive, r=spontaneous recovery, st=static. 589 Chang et al. convalescence, he was noticed to be akinetic and rigid, with markedly impaired intellect. He was treated as for P D with benzhexol and then Sinemet 125 mg tds for three months with no improvement. CT brain showed bilateral frontal lobe watershed infarcts (Fig. 3) and Sinemet was stopped. Five months later, he died of superior vena cava obstruction and autopsy showed squamous cell carcinoma of the trachea with thrombosis of the superior vena cava, old posterior myocardial infarction, moderate atherosclerosis of the aorta, basilar artery and circle of Willis, and old watershed infarcts between the middle and the anterior cerebral artery territories bilaterally. The substantia nigra and locus ceruleus were well pigmented with adequate number of neurons containing neuromelanin; there were no Lewy body inclusions (Fig. 4). Cerebral metastasis was not found. Lacunar infarct of basal ganglia Fig. I. Case 1. CT brain showing bilateral deep subcortical white matter hypodensities, more prominent in the left hemisphere. (Fig. 2). Madopar was discontinued and there was no neurological deterioration when he was reassessed at six weeks and at subsequent follow-up visits. Frontal lobe infarcts Case 6. This 80-year-old man was admitted with uncomplicated acute myocardial infarction. During Fig. 2 . Case 1. T2 weighted MRI brain showing hyperintense signals in periventricular and deep subcortical white matter. 590 Case 9. This 65-year-old gardener complained of an subacute onset of right upper limb weakness followed by a dragging sensation of the right leg 3 days later. He was a chronic smoker, but had no history of hypertension, heart disease or diabetes mellitus. Examination revealed cogwheel rigidity of the right upper limb, bradykinesia of right hand and fingers and reduced right arm swing on walking. There was no tremor, pyramidal signs, pseudobulbar features or dementia. Treatment with Sinemet 125 mg tds for one month conferred no benefit and was stopped because of postural dizziness. Amantadine 100 mg bd was also ineffective. CT brain was then performed and showed a lacunar infarct in the body of the left Fig. 3. Case 6 . CT brain showing bilateral frontal lobe watershed infarcts. Vascular pseudoparkinsonism Discussion Fig. 4. Case 6. Normal density of melanin-containing neurons with no Lewy body inclusion bodies in the substantia nigra (H & E, x200). caudate nucleus (Fig. 5). Amantadine was stopped and the patient spontaneously recovered completely one month later. Fig. 5. Case 9. CT brain showing lacunar infarct in the body of the left caudate nucleus. Since CVD is common in the elderly, its presence in a parkinsonian patient does not necessarily implicate it as the cause of parkinsonism. In this series, CT ischemic lesions were found in 22% of patients who had PD and responded to levodopa. Hence, the co-existence of CVD and PD is probably not uncommon. Indeed, lacunar state was found in 32% and old infarcts in 6% of PD patients examined at autopsy (5). However, in 11 patients (4.4%) the cause of the parkinsonism was likely to be vascular. In Case 6, the vascular etiology was confirmed at autopsy, while in the other 10 patients, it was based on CT or MRI findings and the lack of response to levodopa therapy. All 11 patients were initially diagnosed as having PD because of the prominence of akinesia and rigidity, a mask-like face and generalised slowness being the most common akinetic features. The slow shuffling gait, reduced arm swing and turning hesitation were similar to patients with PD but the upright posture, wide based stance and the absence of festination should help in differentiating (1 1). Although cogwheel rigidity was absent in Critchley’s patients (2), our five patients and others (8, 9, 15) exhibited this feature. However, the absence of resting tremor in all our patients and others (2, 6, 12) is a very useful distinguishingfeature. Pyramidal signs, pseudobulbar features, early dementia and early urinary incontinence are not features of PD, and their presence suggests a vascular etiology. Like PD, the onset of vascular pseudoparkinsonism is often insidious. If it is acute and apparently follows a stroke, a vascular etiology should be particularly suspected. Three patterns of ischemia were identified on CT or MRI. Periventricular and deep subcortical white matter ischemia has previously been described (11, 12). In our five cases with this pattern, parkinsonian features were steadily progressive and two patients died six and seven years after onset. The course was therefore more rapid than PD. These patients’ features probably overlap with those of Binswanger’s disease (1 1, 12, 17). The pathology has been shown to be complete or incomplete infarction of the white matter as a result of small artery disease (17). Since small vessel CVD is common in the Chinese (18) and Binswanger disease has also been documented in the local population (19), we believe this form of vascular pseudoparkinsonism will become increasingly recognised. However, our three patients and others (8,9) with basal ganglia lacunar infarcts had a good prognosis, in that the parkinsonian features resolved spontaneously. Frontal lobe infarction leading to vascular pseudoparkinsonism has not hitherto been reported. The parkinsonian features 59 1 Chang et a]. may be the result of disruption of neural connections between the frontal lobes and the striatum within the cortico-strio-pallido-thalamo-corticalloop. The neurologic conditions in our three patients were static, presumably because the cerebral infarction was due to hypotension or cardiogenic emboli which had not been recurrent. Even though vascular pseudoparkinsonism was found in only 4.4% of our parkinsonian patients, we suspect the figure may be much higher in other nonspecialist units. We may also have under-estimated the figure because these patients may occasionally benefit from levodopa, abeit only partially (14, 15). In doubtful cases, a therapeutic trial of levodopa is justified. Patients with vascular pseudoparkinsonism are often labelled as PD and hence unnecessarily treated chranically with anti-parkinsonian drugs while their underlying vascular disease is ignored. Moreover, it is important to exclude these patients from PD research projects. Based on our experience, we recommend full investigation including CT or MRI for a vascular etiology in parkinsonian patients with poor or no response to levodopa treatment. References BRISSAUD E. Lecons sur les maladies nerveuses. Paris: Masson, 1895: 486-501. CRITCHLEY M. Arteriosclerotic parkinsonism. Brain 1929: 52: 23-83. EADIEMJ, SUTHERLAND JM. 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