| We report a rare familial case of dementia with lewy bodies (DLB). The patient was a man who died at the age of 51. His parents were first cousins. Among three siblings, two were diagnosed as probable cases of DLB, and one was a possible case, according to the clinical diagnostic criteria of the consortium on DLB. Following the patient's autopsy, he was found to have had DLB without neurofibrillary tangles or senile plaques (pure form of diffuse lewy body disease). His other siblings have been followed for more than ten years. Although these patients with familial DLB displayed clinical variability, all three siblings showed progressive dementia of early onset and progressive language disorder with paraphasia and difficulty in finding words. Psychotic features were also seen in the three siblings. The patient's sister showed compulsive behavior, and the other two siblings showed symptoms of parkinsonism. Neuropathologically, in addition to the usual neuropathology of DLB, the autopsy findings showed numerous small spheroids in the stratum pyramidale from the subiculum to CA1 of the hippocampus. Significant neuronal loss in CA2-3 of the hippocampus was detected. Axonal flow disturbance may be involved in the hippocampal formations of this incidence of familial DLB. ( info) |
2/74. Diffuse lewy body disease: clinical, pathological, and neuropsychological review. The pathophysiological etiologies and clinical presentations of neurodegenerative dementias have been found to be complex and heterogeneous. Recently, Lewy body inclusions have been identified as an etiological factor in 20-34% of autopsied dementia cases. The term diffuse lewy body disease (DLBD) is generally accepted as the diagnostic term representative of this currently under-reported and under-recognized disease. This article reviews the literature on the clinical, pathological, and neuropsychological features of this disorder. Differential diagnostic issues are discussed as well as current pharmacological treatment. Nine confirmed cases of DLBD are presented to demonstrate the various features of this disorder. The diagnostic implications of neuropsychological examination results are discussed in relation to other common dementing neurologic diseases. ( info) |
3/74. Electrophysiological observations in hereditary parkinsonism-dementia with Lewy body pathology. We studied the only two living affected individuals who are part of a previously reported kindred that expresses a hereditary parkinsonism-dementia syndrome with Lewy body pathology. The electrophysiological characteristics of the hyperkinetic movement disorders in these patients were examined to provide physiological insights into the clinical phenotype of this syndrome. Evaluation of both patients showed 7-9 Hz electromyographic discharges in upper extremity muscles during postural activation, and one patient showed a 4-5 Hz discharge pattern correlating to a rest tremor. Brief (<50 ms) myoclonic electromyographic discharges were seen in both patients, and a time-locked relationship to a focal cortical premovement electroencephalographic potential was elicited in one patient. Somatosensory evoked potentials were not enlarged and long latency reflexes were not enhanced. electroencephalography was normal in one patient but showed pathologic slow frequencies in the other. The electrophysiological findings show evolution which correlates with an apparent characteristic evolution of hyperkinetic movement disorders that accompanies the severe progression of parkinsonism-dementia in this kindred. These results have implications for the future study of this and similar syndromes. ( info) |
4/74. Donepezil for behavioural disorders associated with lewy bodies: a case series. dementia with lewy bodies (DLB) has been associated with important behavioural disturbances, such as psychotic symptoms. Unfortunately, neuroleptic sensitivity in these patients limits effective pharmacological management of these symptoms. Seven patients, five male and two female (mean age 75.3 /-4.7 years, range 68-81), diagnosed with DLB were treated with the acetylcholinesterase inhibitor donepezil (5-10 mg once daily) to determine its effect on treating behavioural disorders. Although the intended length of treatment was a minimum of 8 weeks, only three patients completed 8 weeks of therapy, one patient completed 6 weeks, two patients completed 4 weeks and one patient was discontinued after 5 days. The primary outcome (behavioural disturbances) was measured prospectively by the Neuropsychiatric Inventory (NPI), while other outcomes included cognition (Mini-Mental State Examination (MMSE)) and Clinical Global Impression. Three of the seven subjects showed marked improvement in behaviour, with NPI scores dropping significantly over time. Donepezil therapy was discontinued prematurely in three of the cases due to insufficient response and/or adverse events. overall, five of the seven patients were rated at least minimally improved in behavioural symptoms. Our experience with donepezil in this group of patients shows promise. Given the limited experience with this agent in treating behavioural disorders associated with DLB, further studies are warranted. ( info) |
5/74. Distinctive neuropathology revealed by alpha-synuclein antibodies in hereditary parkinsonism and dementia linked to chromosome 4p. The identification of the alpha-synuclein gene on chromosome 4q as a locus for familial Lewy-body parkinsonism and of alpha-synuclein as a component of lewy bodies has heralded a new era in the study of Parkinson's disease. We have identified a large family with Lewy body parkinsonism linked to a novel locus on chromosome 4p15 that does not have a mutation in the alpha-synuclein gene. Here we report the clinical and neuropathological findings in an individual from this family and describe unusual high molecular weight alpha-synuclein-immunoreactive proteins in brain homogenates from brain regions with the most marked neuropathology. Distinctive histopathology was revealed with alpha-synuclein immunostaining, including pleomorphic lewy bodies, synuclein-positive glial inclusions and widespread, severe neuritic dystrophy. We also discuss the relationship of this familial disorder to a lewy body disease clinical spectrum, ranging from Parkinson's disease to dementia with psychosis. ( info) |
6/74. Brainstem-type lewy body disease presenting with progressive autonomic failure and lethargy. The authors report an autopsy case characterized by progressive lethargy and autonomic failure with a distinctive pattern of occurrence of lewy bodies. Autonomic dysfunction such as sleep apnea, orthostatic hypotension, dysuria, and hypohidrosis predominated with lethargy, whereas parkinsonism was not apparent. Numerous lewy bodies were widely evident microscopically in brainstem nuclei and the intermediolateral cell columns of the spinal cord, as well as in the sympathetic ganglia, but were rare or absent in the cerebral cortex and other supratentorial structures. Marked neuronal loss was seen in the locus ceruleus, raphe nuclei, dorsal vagal nuclei, and intermediolateral cell columns, but neurons in the substantia nigra, other brain regions, and sympathetic ganglia appeared undiminished. This case represents a specific clinicopathologic form of lewy body disease occurring predominantly in the brainstem, spinal cord, and sympathetic ganglia. ( info) |
| 1. Conflicting reports are available regarding the sensitivity of patients with dementia with lewy bodies (DLB) to risperidone. 2. The authors studied a rare familial case of probable DLB, who developed a documented episode of neuroleptic malignant syndrome (NMS) following the exposure to risperidone. Previously, the patient had had an episode of NMS on trifluoperazine. 3. The discontinuance of risperidone, in combination with a mild increase of dopaminergic therapy, led to a complete recovery in few days. 4. In patients with DLB, a continued vigilance for extrapyramidal side effects, including NMS, would be advisable during the use of risperidone. ( info) |
| A pure case of autopsy-confirmed dementia with lewy bodies (DLB) is described. The patient presented with distinctive verbal fluency deficits in the context of mild language impairment, intact recognition memory, and impaired paragraph recall. neuroimaging (CT and SPECT) showed progressive medial temporal lobe atrophy. Neuropathology revealed lewy bodies, degeneration in the substantia nigra, nucleus basalis of Meynert (Nakano & Hirano, 1984), and locus ceruleus, but no pathology characteristic of Alzheimer's disease. It is in this sense that the case is "pure" DLB. Early neuropsychological diagnosis of DLB is essential (salmon et al., 1996) given the potentially fatal hazard of neuroleptics (McKeith et al., 1992) and the difficulties associated with clinical neurological diagnoses (Litvan et al., 1998). ( info) |
| A patient with rem sleep behavior disorder who subsequently developed probable Lewy body dementia is now reported to have a definite pathologic diagnosis of Lewy body dementia. Examination of brain revealed lewy bodies as well as marked neuronal loss in brainstem monoaminergic nuclei-particularly locus coeruleus and substantia nigra-that inhibit cholinergic neurons in the pedunculopontine nucleus mediating atonia during REM sleep. ( info) |
10/74. FDG positron emission tomography in diffuse lewy body disease: a case report. lewy body disease is a clinicopathologic condition that includes Parkinson's disease at one end and diffuse lewy body disease at the other hand. The latter is often associated with progressive cognitive deterioration, levodopa-responsive parkinsonism, fluctuations of cognitive and motor functions, and visual and auditory hallucinations. In addition, it can be a familial disease. Clinical and positron emission tomographic findings are described in a patient with atypical dementia and movement disorder and a pathologically proved diagnosis of diffuse lewy body disease. ( info) |