1/13. Neuropsychological and neuroimaging correlates in corticobasal degeneration.The aim of this study was to correlate neuropsychological and neuroimaging findings in corticobasal degeneration (CBD). Three patients with clinical criteria for CBD were examined by means of neuropsychological tests, brain magnetic resonance imaging (MRI), and flow and metabolism neuroimaging techniques. Neuropsychological assessment revealed impairment in executive functions, manual dexterity and motor programming with significant asymmetry between upper limbs. Ideomotor and oral apraxia were also detected, and memory deficits were observed in one patient. MRI revealed cortical dilation of the frontal and peri-rolandic regions, symmetrical in one case and asymmetrical in the other two cases. An increased T2 signal intensity in the posterolateral putamen and substantia nigra ipsilateral to the cortical atrophy was observed in one patient. Asymmetries of both frontal and parietal cortices and basal ganglia were detected in all three patients by 18-fluorodeoxyglucose positron emission tomography; temporal region hypometabolism was associated in one patient. These cortical and subcortical asymmetries were observed in two patients by single photon emission tomography with the tracer technetium Tc 99m hexamethyl propylenamine oxime; cortical asymmetry was observed in only one patient. The results showed that functional neuroimaging findings correlated well with neuropsychological aspects in CBD. Neuroimaging and neuropsychological correlations may contribute toward understanding anatomical and functional abnormalities associated with this neurodegenerative disorder.- - - - - - - - - - ranking = 1keywords = nigra (Clic here for more details about this article) |
2/13. Neurodegeneration with brain iron accumulation, type 1 is characterized by alpha-, beta-, and gamma-synuclein neuropathology.Neurodegeneration with brain iron accumulation, type 1 (NBIA 1), or Hallervorden-Spatz syndrome, is a rare neurodegenerative disorder characterized clinically by Parkinsonism, cognitive impairment, pseudobulbar features, as well as cerebellar ataxia, and neuropathologically by neuronal loss, gliosis, and iron deposition in the globus pallidus, red nucleus, and substantia nigra. The hallmark pathological lesions of NBIA 1 are axonal spheroids, but Lewy body (LB)-like intraneuronal inclusions, glial inclusions, and rare neurofibrillary tangles also occur. Here we show that there is an accumulation of alpha-synuclein (alphaS) in LB-like inclusions, glial inclusions, and spheroids in the brains of three NBIA 1 patients. Further, beta-synuclein (betaS) and gamma-synuclein (gammaS) immunoreactivity was detected in spheroids but not in LB-like or glial inclusions. Western blot analysis demonstrated high-molecular weight alphaS aggregates in the high-salt-soluble and Triton X-100-insoluble/sodium dodecyl sulfate-soluble fraction of the NBIA 1 brain. Significantly, the levels of alphaS were markedly reduced in the Triton X-100-soluble fractions compared to control brain, and unlike other synucleinopathies, insoluble alphaS did not accumulate in the formic acid-soluble fraction. These findings expand the concept of neurodegenerative synucleinopathies by implicating alphaS, betaS, and gammaS in the pathogenesis of NBIA 1.- - - - - - - - - - ranking = 1keywords = nigra (Clic here for more details about this article) |
3/13. Pallido-Luysio-Nigral atrophy revealed by rapidly progressive hemidystonia: a clinical, radiologic, functional, and neuropathologic study.Pallido-luysio-nigral atrophy (PLNA) is a rare neurodegenerative disease in which the clinical and radiologic correlates have not yet been clearly established. A 62-year-old man insidiously developed dystonic postures, choreoathetoid movements, slowness, and stiffness, which initially affected the right hand and foot and progressively spread to the entire right side. T2-weighted magnetic resonance imaging showed increased signal intensity in both left and right medial pallida and in the left substantia nigra. Tests using HMPAO-SPECT and FDG-PET demonstrated left cortical hyperperfusion and hypermetabolism, whereas the left lenticular nucleus was slightly hypometabolic. At age 65, abnormal movements and postures involved all four limbs and the axis causing major gait disturbances, and facial and bulbar muscles atrophied resulting in dysarthria, dysphagia, and impaired breathing. Diffuse amyotrophy and fasciculations also appeared. death occurred at age 66, 4 years after onset. At autopsy, severe bilateral neuronal loss and gliosis restricted to the pallidum, the subthalamic nucleus, the substantia nigra, and the hypoglossal nucleus were noted, accounting for the diagnosis of PLNA with lower motor neuron involvement. Progressive hemidystonia with adult onset represents an unusual clinical presentation for this disorder. Moreover, this observation indicates that a diagnosis of PLNA should be considered for specific magnetic resonance imaging, SPECT, and/or PET data, and suggests that in PLNA, pallidal dysfunction might play a key role in the dystonic presentation.- - - - - - - - - - ranking = 3keywords = nigra (Clic here for more details about this article) |
4/13. Neuronal intranuclear inclusion disease and juvenile parkinsonism.Juvenile parkinsonism (onset age <20 yrs) is uncommon and few cases with neuropathologic confirmation have been reported. We present the case of a 17-year-old boy who presented with asymmetric arm tremor and bulbar symptoms. His paternal great aunt had parkinsonism with onset at age 22 years. Examination revealed parkinsonism in the absence of additional neurologic signs except for delayed pupillary responses to light. He responded well to levodopa but developed motor fluctuations and disabling dyskinesias after 3 years of treatment. Following attempted withdrawal of levodopa at age 24 years, he developed severe aspiration pneumonia complicated by cardiorepiratory arrests and he died 6 months later. At autopsy, the dominant histologic feature was wide-spread neuronal hyaline intranuclear inclusions. Neuronal depletion was observed in the substantia nigra, locus ceruleus, and, to a lesser extent, in the frontal cortex, and inclusions were particularly prominent in these areas. Inclusions were immunoreactive for ubiquitin and were typical of those seen in neuronal intranuclear inclusion disease (NIID), a rare, multisytem neurodegenerative disease. NIID should be considered in the differential diagnosis of juvenile parkinsonism. A link between NIID and hereditary neurodegenerative disorders characterized by expanded polyglutamine tracts is supported by the similar appearance of intranuclear inclusions in both conditions and by a family history in some cases of NIID.- - - - - - - - - - ranking = 1keywords = nigra (Clic here for more details about this article) |
5/13. Corticobasal degeneration and frontotemporal dementia presentations in a kindred with nonspecific histopathology.We report the clinical, neuropsychological, electroencephalographic and radiologic findings in a kindred with varying clinical presentations of a neurodegenerative disorder. Postmortem examination of one member with clinically suspected corticobasal degeneration (CBD) revealed nonspecific histopathology maximally involving the frontoparietal cortex with negligible degenerative changes in the basal ganglia and substantia nigra. The findings in this and other kindreds demonstrate that (1) similar findings on ancillary testing can occur in relatives presumably suffering from the same pathophysiologic process despite dissimilar clinical presentations, (2) the 'CBD syndrome' is not specific for CBD, (3) extrapyramidal dysfunction can exist in the absence of appreciable basal ganglia and nigral degeneration, (4) nonspecific histopathology can underlie familial focal/asymmetric cortical degeneration syndromes and (5) many of the findings in CBD are comparable to those reported in frontotemporal dementia.- - - - - - - - - - ranking = 2keywords = nigra (Clic here for more details about this article) |
6/13. A case of clinically and neuropathologically atypical corticobasal degeneration with widespread iron deposition.A 65-year-old woman was admitted to our hospital for forgetfulness, depression and eccentric behavior that had been first noticed 2 years prior to admission. She showed memory impairment, perseveration and repeated violent actions, but no limb-kinetic apraxia. She died 12 years after the onset of symptoms. At autopsy, the unfixed brain weighed 820 g. Atrophy was circumscribed in the frontal lobe on both sides. The globus pallidus and the caudate nucleus were markedly atrophic and gold yellow in color, and the substantia nigra was strikingly pale. The cortical area showed neuronal loss and status spongiosus of the second and third cortical layers with ballooned neurons. Marked neuronal loss was observed in the dorsomedial nucleus of the thalamus, Meynert basal nucleus and substantia nigra. With Holzer stain, fibrillary gliosis was found to be severe in the frontal lobe, globus pallidus, subthalamic nucleus, hippocampus, dorsomedial nucleus of thalamus, substantia nigra, pontine tegmentum and inferior olivary nucleus. With Bielschowsky-Hirano stain, neurofibrillary tangles were observed in the cortex, hippocampus, substantia nigra, dentate nucleus, subthalamic nucleus, pontine nucleus, the inferior olivary nucleus, dorsomedial nucleus of the thalamus and, to a lesser extent, the neostriatum. Strikingly numerous argyrophilic and tau-positive threads were present in the cerebral white matter. These neuropathological findings corresponded to corticobasal degeneration, but lesions characteristic of progressive supranuclear palsy were also found. Moreover, widespread iron deposition throughout the central nervous system was the most striking finding of the present case. To our knowledge, such a case has not been reported in the literature to date.- - - - - - - - - - ranking = 4keywords = nigra (Clic here for more details about this article) |
7/13. Severe generalized dystonia due to primary putaminal degeneration: case report and review of the literature.Putaminal lesions of a variety of etiologies may cause secondary dystonia. We report on a case of primary putaminal degeneration as a cause of severe childhood-onset generalized dystonia and review the literature of the pathology of dystonia. A 44-year-old patient with severe generalized childhood-onset dystonia and macrocephaly underwent neurological evaluation and neuropathological examination. Neurological examination was normal apart from dystonia and signs referable to prior cryothalamotomy. Workup for metabolic and genetic causes of dystonia was negative. Neuroimaging showed severe bilateral putaminal degeneration, which subsequently correlated with the neuropathological findings of gliosis, spongiform degeneration, and cavitation. The substantia nigra pars compacta contained a normal number of neurons but decreased tyrosine hydroxylase immunoreactivity. There were no histopathological markers of other metabolic or degenerative diseases.- - - - - - - - - - ranking = 1keywords = nigra (Clic here for more details about this article) |
8/13. Extending the clinicopathological spectrum of neurofilament inclusion disease.We describe features of a patient that broadens the clinical and pathological spectrum of neurofilament inclusion disease (NFID). The patient was a 52-year-old man with a 5--6 year history of progressive, asymmetrical spastic weakness of the upper and lower extremities; L-DOPA-unresponsive parkinsonism; and SPECT evidence of asymmetrical frontoparietal and basal ganglia hypoperfusion. The brain had marked frontoparietal parasagittal cortical atrophy, including the motor cortex, with histopathological evidence of neurofilament- and alpha-internexin-immunoreactive neuronal inclusions. The corticospinal tract had degeneration, but there was minimal lower motor neuron pathology. There was also severe neuronal loss and gliosis in the posterolateral putamen and the substantia nigra, mimicking multiple system atrophy; however, glial cytoplasmic inclusions were not detected with alpha-synuclein immunohistochemistry. This case extends the clinical and pathological spectrum of NFID to include cases with predominant parkinsonian and pyramidal features.- - - - - - - - - - ranking = 1keywords = nigra (Clic here for more details about this article) |
9/13. Tau-predominant-associated pathology in a sporadic late-onset Hallervorden-Spatz syndrome.Hallervorden-Spatz syndrome (HSS) is a heterogeneous clinicopathological disorder currently included within the broader title of neurodegeneration with brain iron accumulation (NBIA). The classic histological hallmarks of HSS are axonal spheroids and excessive iron-containing granules accompanied by neuronal loss and gliosis in the globus pallidus and substantia nigra reticulata. In the modern literature, attention has been drawn to the co-occurrence of two other histological markers: lewy bodies mainly composed of abnormal alpha-synuclein, and neurofibrillary tangles due to hyperphosphorilated tau aggregation. Discrepancies exist regarding the importance of these molecular changes and its relevance for the nosology of HSS. Most authors have emphasized the importance of the Lewy body-like pathology, favoring the inclusion of HSS within the alpha-synucleinopathies. We report on a case of late-onset HSS, with the typical histological findings restricted to the basal ganglia and cerebellum in which tau pathology was exceedingly more abundant than alpha-synuclein pathology. This case contributes to the increasing evidence about the heterogeneity of HSS. We favor the view that the molecular changes and the protein misfolding underlying the Lewy body and tangle formation in HSS/NBIA are secondary to the main pathological process and should not be taken as the basis for its nosological classification.- - - - - - - - - - ranking = 1keywords = nigra (Clic here for more details about this article) |
10/13. autopsy case of pure akinesia showing pallidonigro-luysian atrophy.A 60-year-old man developed levodopa-resistant pure akinesia. The patient gradually became more akinetic without accompanying gaze palsies, nuchal dystonia, or other parkinsonian features such as rigidity or tremor. At the age of 71, he died of bronchopneumonia. Neuropathologically, bilateral marked neuronal loss and gliosis were restrictedly observed in the globus pallidus, substantia nigra and corpus luysii, whereas mild gliosis without neuronal loss was found in the brain stem. With Gallyas-Braak silver stain, numerous argyrophilic fibrous structures partly surrounding glial nuclei were observed in the three major affected regions. With Bodian stain, however, they were rarely recognized. The structures were partly positive for tau protein. Rare neurofibrillary tangles were found in the three areas and brain stem. They were relatively more numerous but still sparse in the hippocampus and the parahippocampus. The present case was diagnosed as having pallidonigro-luysian atrophy based on two characteristic findings: (i) the distribution of lesions showing neuronal loss with gliosis; and (ii) significant presence of tau-positive argyrophilic fibrous structures related to glia but with the absence of neurofibrillary tangles in the major affected regions and the brain stem. As our present case uniquely showed pure akinesia for the whole clinical course, it is noteworthy to report it here with a full neuropathological evaluation. In addition, a moderate number of diffuse plaques positive for beta-amyloid were distributed in the thalamus.- - - - - - - - - - ranking = 1keywords = nigra (Clic here for more details about this article) |
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