Bohdan Rozdilsky

Accuracy of clinical diagnosis in Parkinsonism―A prospective study

Clinical diagnosis of Parkinsons syndrome (PS) is reasonably easy in most cases but the distinction between different variants of PS may be difficult in early cases. The correct diagnosis is not only important for counselling and management of patients but also in conducting pharmacological and epidemiological studies. There is very little critical literature on the pathological verification of the clinical diagnosis in PS. We report our 22 years experience to address that issue. Between 1968 and 1990, 65 PS patients came to autopsy. Complete data are available in 59 (M-50, F-19) cases. The initial diagnosis made by a qualified neurologist was idiopathic Parkinsons disease (IPD) in 43 cases. Of those 28 (65%) had Lewy body pathology. After a mean duration of 12 years the final diagnosis was IPD in 41 cases which was confirmed in 31 (76%). The IPD could not be clinically distinguished from cases with severe substantia nigra neuronal loss without inclusions or from those with neurofibrillary tangle inclusions and neuronal loss at the anatomical sites typically involved in IPD. All progressive supra-nuclear palsy, olivopontocerebellar atrophy, Jakob-Creutzfeldts disease and the majority of the multiple system atrophy cases were diagnosed correctly during life. The correct clinical diagnosis in most non-IPD variants of PS was possible within 5 years of onset (range: 2 months to 18 years). We recommend that studies aimed at including only the IPD cases restrict the enrollment to those cases that have had PS motor manifestations for five years or longer duration.

Progressive supranuclear palsy diagnosis and confounding features: Report on 16 autopsied cases†

We evaluated 16 (15 men, 1 woman) autopsy‐verified progressive supranuclear palsy (PSP) cases during 31 years (1969–2000) for clinical diagnosis and the course of the disease. The onset was gait difficulty or postural instability in 9 (56.3%), general motor slowing in 3 (18.8%), and tremor in 2. One case had onset with cognitive decline and 1 as hemidystonia. Four cases had supranuclear ophthalmoplegia (SNO) at the first assessment and were diagnosed as PSP. By last assessment, PSP diagnosis was made in 4 additional cases, but in 8 (50%) who never manifested ophthalmoplegia (mean 9.8 years after onset), PSP diagnosis was not made. Other manifestations included bulbar symptoms in 13 (81.3%), and cognitive impairment in 10 (62.5%) during the course of illness. Fifteen cases received levodopa, amantadine, anticholinergics, dopamine agonists, and selegiline in different combinations with symptomatic benefit in 9 of 15 (60%). Five had some improvement on levodopa alone and 3 showed more improvement when a dopamine agonist was added to levodopa. In general, the benefit was minimal and occurred only early in the course of illness. The mean age at onset was 63.7 (range, 53–85) years. Mean duration at PSP diagnosis was 4.8 (range, 2–11) years. Mean survival was 8.6 (range, 3–24) years and mean age at death was 72.3 (range, 60–89) years. When the different diagnostic criteria recommended in the literature were used, the accuracy of clinical diagnosis did not improve substantially.

Clinicopathologic observations in essential tremor: report of six cases.

Essential tremor (ET) is the most common pathologic tremor, but only eight cases have been studied pathologically. We report detailed clinical and neuropathologic studies of six additional patients. We did not find any neuropathologic lesions that might be specific for ET. Moreover, there were no abnormalities of the substantia nigra consistent with Parkinsons disease. The neuropathologic substrate of ET remains unknown.

Regional metal concentrations in Parkinson's disease, other chronic neurological diseases, and control brains.

Metal deficiency or toxicity states have been recognized as a cause of several neurological disorders and are suspected in others. We analyzed four brain regions (frontal cortex, caudate nucleus, substantia nigra, and cerebellum) in 36 human brains for concentrations of 24 metals (Ag, Al, As, B, Be, Ca, Cd, Co, Cr, Cu, Fe, K, Pb, Mg, Mn, Mo, Na, Ni, P, Se, Ti, V, W, Zn). Regional metal concentrations, measured using atomic absorption and atomic emission spectroscopy, were compared between 9 Parkinsons disease (PD) brains, 15 brains from patients with other chronic neurological diseases, and 12 control brains. No significant metal concentration differences were noted between brains from PD and other chronic neurologic disease. However, parkinsonian brains (PD and parkinsonism secondary to neurofibrillary tangle disease) showed lower concentrations of magnesium in the caudate nucleus and copper in the substantia nigra than control brains. These findings may represent an etiologically important clue to parkinsonism.

Significance of Parkinsonian manifestations in essential tremor

Parkinsonian features, notably resting tremor may be seen in some essential tremor patients but the significance of those is unknown. The reported risk of parkinsonism in essential tremor patients varies from being unchanged to 35 times higher than expected. We studied 9 patients with essential tremor who had autopsies. In 6 of the 9 (66%) resting tremor was noted and in 3 (33%) cases fully developed parkinsonism was noted. The parkinsonism was consequent to neuroleptic usage in 2 and to basal ganglia status lacunaris and cribrosus in one case but no consistent abnormalities were noted in 3 essential tremor only and 3 essential tremor plus resting tremor cases. We conclude that resting tremor is an age-related natural evolution in some essential tremor patients. We recommend that the additional diagnosis of parkinsonism in the essential tremor be made only when resting tremor, bradykinesia and rigidity are all evident. The risk of ideopathic Parkinsons disease in essential tremor cases is similar to the general population.

LEVODOPA EFFICACY AND PATHOLOGICAL BASIS OF PARKINSON SYNDROME

Levodopa is the most effective drug for symptomatic control of Parkinson syndrome (PS). We report a 22-year clinicopathological study of 59 PS cases. Of the entire group, 37 (63%) had an adequate trial on levodopa. Some improvement was noted on that drug in 24 (65%) cases. Improvement was seen in 94% of idiopathic Parkinsons disease cases as well as in all cases in which the pathology was characterized by neuronal loss in the substantia nigra without Lewy body inclusions. Improvement was also noted in 60% of patients with the dual pathology of idiopathic Parkinsons disease and Alzheimers disease, and in one-third of early multiple system atrophy cases. We conclude that improvement on levodopa is a strong indication that the pathological basis of the parkinsonism is the damage to substantia nigra neurons. A favorable response to levodopa, however, is not an indication of idiopathic (Lewy body) Parkinsons disease.

Noradrenaline, dopamine and serotonin levels and metabolism in the human hypothalamus: observations in Parkinson's disease and normal subjects

In order to determine whether, besides the severe striatal dopamine (DA) loss, other brain neurotransmitter changes may be a constant biochemical feature of idiopathic Parkinsons disease (iPD), we measured the concentration of the three major brain monoamines noradrenaline (NA), DA, and serotonin (5-HT) and their metabolites in five rostro-caudal subdivisions of the hypothalamus of eight control patients and nine patients with morphologically confirmed iPD. In the whole hypothalamus of the iPD patients we found a mild to moderate mean reduction of NA (-52%, P < 0.05), DA (-25%), and 5-HT (-26%). At the subregional level, the most consistently affected area was the intermediate subdivision of the hypothalamus proper where all three monoamines were statistically significantly reduced. Evaluation of individual patient values indicated that, in contrast to the constant and severe DA reduction present in putamen of each of the iPD patients (DA loss ranging from 96% to 99%), several of these patients had whole (and subregional) hypothalamic monoamine values well within the range of controls. We conclude that, although possibly involved in autonomic and/or endocrine disturbances in some patients with iPD, none of the observed monoamine changes in the hypothalamus is an obligatory feature of iPD. Our study demonstrates the need for evaluation of individual patient values rather than mean differences in order to permit valid conclusions to be drawn as to whether an observed neurochemical change can be regarded as specific to a given brain disorder.

Occurrence of resting tremor in Parkinson's disease

Several previous studies have noted that resting tremor (RT) is absent in 10% to 30% of idiopathic Parkinsons disease (IPD) patients. We report our 22-year observations in 47 pathologically verified parkinsonian patients. In all the IPD cases with median follow-up of 3.7 years, RT was noted on at least one evaluation. Among other parkinsonian syndrome variants characterized by widespread subcortical pathology with median follow-up of 2.86 years, RT was seen in 31% of the cases. Our data indicate that the sites typically involved in IPD are sufficient to produce RT.

Supratentorial capillary hemangioblastoma presenting with fatal spontaneous intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage from a supratentorial capillary hemangioblastoma resulting in the death of a 26-year-old woman is reported. We suggest that the presence of glial fibrillary acidic protein containing stromal cells in the tumor tissue may serve as a point distinguishing hemangioblastoma from angioblastic meningioma.

Alzheimer's disease and idiopathic Parkinson's disease coexistence.

Idiopathic Parkinsons disease (IPD) and Alzheimers disease (AD) are common neurologic diseases of old age. Parkinson syndrome is easy to recognize even at an early stage, but identifying early AD is often difficult. Accurate clinical diagnosis is important for assigning the prognosis and for studies aimed at assessing the efforts to slow down progression of these diseases. During 22 years, we identified six patients who had clinical features of parkinsonism and dementia and who at autopsy had both IDP and AD and 20 parkinsonian patients without dementia who at autopsy had only IPD. The clinical profile in these two groups was compared. The onset of Parkinson syndrome in the patients with dual pathology had a bimodal distribution—before or after age 65 years. In the three cases with onset before age 65 years, there was sequential evolution of IPD and AD. In contrast, those older than 65 years at onset manifested the clinical features of both IPD and AD simultaneously. The mode of onset and the dominant parkinsonian features in the three patients with sequential clinical evolution were similar to those seen in the nondemented IPD cases; however, lack of self-confidence and inability to make decisions resulted in considerably greater functional disability than could be accounted for by parkinsonism alone. These characteristics may be helpful in early recognition of dual IPD and AD pathology. Psychiatric side effects of levodopa therapy were more common in those with dual pathology than in those with IPD alone.