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AJNR. American Journal of Neuroradiology Aug 1995To report the MR and CT findings in a hereditary disease, infantile-onset spinocerebellar ataxia (IOSCA).
PURPOSE
To report the MR and CT findings in a hereditary disease, infantile-onset spinocerebellar ataxia (IOSCA).
METHODS
We studied the brains of 17 patients with infantile-onset spinocerebellar ataxia with CT and/or MR to determine the presence of cerebellar and brain stem atrophy and parenchymal lesions.
RESULTS
Cerebellar cortical atrophy was seen in 13 patients. The degree of atrophy correlated with increasing age and clinical deterioration. Brain stem atrophy was seen in 8 patients. It was never severe, and the basis pontis was not flattened even in the most severe cases. Hyperintense lesions were noted within the white matter of cerebellum, in the dentate nuclei, and in the middle cerebellar peduncles in 3 patients. The upper cervical cord was seen in 9 patients and showed mild to moderate atrophy in 4. The basal ganglia and cerebral hemispheres were normal, except in 2 patients transient cortical and subcortical lesions developed during episodes of status epilepticus; mild cortical brain atrophy subsequently developed.
CONCLUSION
The brain MR and CT findings of patients with infantile-onset spinocerebellar ataxia correspond to the neuropathologic entities of cerebellar cortical atrophy, olivopontocerebellar atrophy, and spinocerebellar atrophy. The appearance of the findings followed a uniform time sequence from cerebellar cortical atrophy in the early stage of the disease to olivopontocerebellar atrophy and spinocerebellar atrophy in the later stage. The severity of atrophy correlated with clinical deterioration.
Topics: Adolescent; Adult; Atrophy; Brain; Brain Stem; Cerebellar Cortex; Cerebellar Nuclei; Cerebral Cortex; Child; Child, Preschool; Dominance, Cerebral; Female; Follow-Up Studies; Humans; Infant; Magnetic Resonance Imaging; Male; Spinal Cord; Spinocerebellar Degenerations; Tomography, X-Ray Computed
PubMed: 7484627
DOI: No ID Found -
Annals of Neurology Dec 1996We used [11C]dihydrotetrabenazine, a new ligand for the type 2 vesicular monoamine transporter (VMAT2), with positron emission tomography to study striatal monoaminergic...
We used [11C]dihydrotetrabenazine, a new ligand for the type 2 vesicular monoamine transporter (VMAT2), with positron emission tomography to study striatal monoaminergic presynaptic terminals in 4 patients with multiple system atrophy, 8 with sporadic olivopontocerebellar atrophy, and 9 normal control subjects. Specific binding in the striatum was significantly reduced in the multiple system atrophy patients as compared with the normal control group, with average reductions of 61% in the caudate nucleus (p = 0.002) and 58% in the putamen (p = 0.009). Smaller reductions were found in the sporadic olivopontocerebellar atrophy group, averaging 26% in the caudate nucleus (p = 0.05) and 24% in the putamen (p = 0.11). Mean blood-to-brain [11C]dihydrotetrabenazine transport (K1) was significantly different between groups only in the cerebellum, with values for the sporadic olivopontocerebellar atrophy group diminished compared with the normal control group. Cerebellar K1 was not significantly decreased in the multiple system atrophy group. The finding of reduced striatal VMAT2 in sporadic olivopontocerebellar atrophy patients suggests nigrostriatal pathology, indicating that some may later develop symptomatic extrapyramidal disease.
Topics: Adult; Aged; Autonomic Nervous System Diseases; Basal Ganglia Diseases; Biological Transport; Cerebellar Diseases; Corpus Striatum; Female; Humans; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Neuropeptides; Olivopontocerebellar Atrophies; Presynaptic Terminals; Tetrabenazine; Tomography, Emission-Computed; Vesicular Biogenic Amine Transport Proteins; Vesicular Monoamine Transport Proteins
PubMed: 9007093
DOI: 10.1002/ana.410400610 -
Journal of Neurology, Neurosurgery, and... May 1997To determine whether Parkinson's disease and multiple system atrophy each has a distinct pattern of micturition abnormalities and whether a urodynamic evaluation could... (Comparative Study)
Comparative Study
AIMS
To determine whether Parkinson's disease and multiple system atrophy each has a distinct pattern of micturition abnormalities and whether a urodynamic evaluation could be useful in the differential diagnosis between the two diseases.
METHODS
Sixty two patients (30 with Parkinson's disease and 32 with multiple system atrophy) underwent a complete urodynamic evaluation and neurophysiological testing.
RESULTS
Of the parkinsonian patients 36.6% had normal micturition findings with normal bladder sensitivity; 26.7% had delayed or incomplete pelvic floor relaxation; 26.7% had hyperreflexia with vesicosphincteric synergy; and 10% had hyperreflexia with vesicosphincteric synergy associated with incomplete pelvic floor relaxation. Parkinsonian patients with a normal urodynamic pattern had significantly less severe disease and a shorter duration of disease in years than those who had abnormal patterns. Patients with hyperreflexia had significantly higher severity of disease. All the patients with multiple system atrophy had hyperreflexia with synergy. Two urodynamic patterns were identified: hyperreflexia with vesicosphincteric synergy (90.6% of patients), and hyperreflexia with vesicosphincteric synergy and incomplete pelvic floor relaxation (in 9.4%). Hyperreflexia with synergy correlated neither with the severity nor with the duration of disease. Sphincter EMG analysis showed that all the parkinsonian patients had normal sphincter EMG whereas 24 of the 32 patients with multiple system atrophy had neurogenic signs.
CONCLUSIONS
Urodynamic evaluation and sphincter EMG are both useful tests in the differential diagnosis between Parkinson's disease and multiple system atrophy. Urodynamic findings may be abnormal before patients with multiple system atrophy reach an advanced stage of the disease. Recordings of EMGs from perineal muscles become abnormal as the disease progresses in multiple system atrophy but not in Parkinson's disease.
Topics: Aged; Brain Diseases; Corpus Striatum; Electromyography; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Olivopontocerebellar Atrophies; Parkinson Disease; Perineum; Shy-Drager Syndrome; Substantia Nigra; Tomography, X-Ray Computed; Urodynamics; Urologic Diseases
PubMed: 9153611
DOI: 10.1136/jnnp.62.5.507 -
Brain : a Journal of Neurology Feb 2024The spinocerebellar ataxias (SCAs) are a group of dominantly inherited neurodegenerative diseases, several of which are caused by CAG expansion mutations (SCAs 1, 2, 3,...
The spinocerebellar ataxias (SCAs) are a group of dominantly inherited neurodegenerative diseases, several of which are caused by CAG expansion mutations (SCAs 1, 2, 3, 6, 7 and 12) and more broadly belong to the large family of over 40 microsatellite expansion diseases. While dysregulation of alternative splicing is a well defined driver of disease pathogenesis across several microsatellite diseases, the contribution of alternative splicing in CAG expansion SCAs is poorly understood. Furthermore, despite extensive studies on differential gene expression, there remains a gap in our understanding of presymptomatic transcriptomic drivers of disease. We sought to address these knowledge gaps through a comprehensive study of 29 publicly available RNA-sequencing datasets. We identified that dysregulation of alternative splicing is widespread across CAG expansion mouse models of SCAs 1, 3 and 7. These changes were detected presymptomatically, persisted throughout disease progression, were repeat length-dependent, and were present in brain regions implicated in SCA pathogenesis including the cerebellum, pons and medulla. Across disease progression, changes in alternative splicing occurred in genes that function in pathways and processes known to be impaired in SCAs, such as ion channels, synaptic signalling, transcriptional regulation and the cytoskeleton. We validated several key alternative splicing events with known functional consequences, including Trpc3 exon 9 and Kcnma1 exon 23b, in the Atxn1154Q/2Q mouse model. Finally, we demonstrated that alternative splicing dysregulation is responsive to therapeutic intervention in CAG expansion SCAs with Atxn1 targeting antisense oligonucleotide rescuing key splicing events. Taken together, these data demonstrate that widespread presymptomatic dysregulation of alternative splicing in CAG expansion SCAs may contribute to disease onset, early neuronal dysfunction and may represent novel biomarkers across this devastating group of neurodegenerative disorders.
Topics: Animals; Mice; Alternative Splicing; Spinocerebellar Ataxias; Cerebellum; Mutation; Disease Progression; Trinucleotide Repeat Expansion; Olivopontocerebellar Atrophies
PubMed: 37776516
DOI: 10.1093/brain/awad329 -
Acta Neuropathologica May 2013Corticobasal degeneration (CBD) is a disorder affecting cognition and movement due to a progressive neurodegeneration associated with distinctive neuropathologic...
Corticobasal degeneration (CBD) is a disorder affecting cognition and movement due to a progressive neurodegeneration associated with distinctive neuropathologic features, including abnormal phosphorylated tau protein in neurons and glia in cortex, basal ganglia, diencephalon, and brainstem, as well as ballooned neurons and astrocytic plaques. We identified three cases of CBD with olivopontocerebellar atrophy (CBD-OPCA) that did not have α-synuclein-positive glial cytoplasmic inclusions of multiple system atrophy (MSA). Two patients had clinical features suggestive of progressive supranuclear palsy (PSP), and the third case had cerebellar ataxia thought to be due to idiopathic OPCA. Neuropathologic features of CBD-OPCA are compared to typical CBD, as well as MSA and PSP. CBD-OPCA and MSA had marked neuronal loss in pontine nuclei, inferior olivary nucleus, and Purkinje cell layer. Neuronal loss and grumose degeneration in the cerebellar dentate nucleus were comparable in CBD-OPCA and PSP. Image analysis of tau pathology showed greater infratentorial tau burden, especially in pontine base, in CBD-OPCA compared with typical CBD. In addition, CBD-OPCA had TDP-43 immunoreactive neuronal and glial cytoplasmic inclusions and threads throughout the basal ganglia and in olivopontocerebellar system. CBD-OPCA met neuropathologic research diagnostic criteria for CBD and shared tau biochemical characteristics with typical CBD. These results suggest that CBD-OPCA is a distinct clinicopathologic variant of CBD with olivopontocerebellar TDP-43 pathology.
Topics: Aged; Cerebellar Ataxia; DNA-Binding Proteins; Female; Humans; Male; Nerve Degeneration; Olivopontocerebellar Atrophies; Supranuclear Palsy, Progressive
PubMed: 23371366
DOI: 10.1007/s00401-013-1087-8 -
Proceedings of the Royal Society of... 1910
PubMed: 19974522
DOI: No ID Found -
Archives of Neurology May 2008Autoantibodies against glutamate receptors, first reported in Rasmussen encephalitis, have been observed in other focal epilepsies, central nervous system ischemic... (Review)
Review
Autoantibodies against glutamate receptors, first reported in Rasmussen encephalitis, have been observed in other focal epilepsies, central nervous system ischemic infarcts, transient ischemic attacks, sporadic olivopontocerebellar atrophy, systemic lupus erythematosus, and paraneoplastic encephalopathies. The detection of glutamate receptor autoantibodies is not useful in the evaluation of Rasmussen encephalitis but may be a biomarker for brain ischemia, and it is helpful in diagnosing certain paraneoplastic encephalopathies. Passive transfer of glutamate receptor autoantibodies from patients with systemic lupus erythematosus or paraneoplastic encephalopathy suggests that glutamate receptor autoantibodies can actively contribute to neurologic dysfunction.
Topics: Autoantibodies; Autoimmune Diseases of the Nervous System; Biomarkers; Brain; Brain Diseases; Brain Ischemia; Humans; Lupus Vasculitis, Central Nervous System; Paraneoplastic Syndromes, Nervous System; Receptors, Glutamate
PubMed: 18474732
DOI: 10.1001/archneur.65.5.589 -
Journal of Neurology, Neurosurgery, and... Jun 1989Multiple system atrophy (MSA) is generally considered a rare disease, but may account for up to 10% of patients with Parkinsonism. The profusion of names for this... (Review)
Review
Multiple system atrophy (MSA) is generally considered a rare disease, but may account for up to 10% of patients with Parkinsonism. The profusion of names for this disease, which may present to general physicians, psychiatrists, cardiologists, autonomic specialists, general neurologists and those with a special interest in Parkinsonism (this author's own perspective) or cerebellar disorders, together with ignorance of its protean manifestations, may account for its underrecognition and misdiagnosis. In this article, the history and nosology of the condition are considered, and provisional diagnostic criteria are advanced. The usefulness (or otherwise) of ancillary investigations is addressed, and the shortcomings of current methods of treatment are stressed. As with idiopathic Parkinson's disease, the ultimate goal of eradicating the disease entails better diagnosis in order to establish the cause, and thence to develop a radical treatment capable of preventing or arresting the disease process.
Topics: Autonomic Nervous System Diseases; Corpus Striatum; Diagnosis, Differential; Humans; Nerve Degeneration; Olivopontocerebellar Atrophies; Parkinson Disease; Parkinson Disease, Secondary; Shy-Drager Syndrome; Spinocerebellar Degenerations; Substantia Nigra
PubMed: 2666581
DOI: 10.1136/jnnp.52.suppl.78 -
Frontiers in Neurology 2020Spinocerebellar ataxia type 3 (SCA) is a cerebellum-dominant degenerative disorder that is characterized primarily by infratentorial damage, although less severe...
Spinocerebellar ataxia type 3 (SCA) is a cerebellum-dominant degenerative disorder that is characterized primarily by infratentorial damage, although less severe supratentorial involvement may contribute to the clinical manifestation. These impairments may result from the efferent loss of the cerebellar cortex and degeneration of the cerebral cortex. We used the three-dimensional fractal dimension (3D-FD) method to quantify the morphological changes in the supratentorial regions and assessed atrophy in the relatively focal regions in patients with SCA3. A total of 48 patients with SCA3 and 50 sex- and age-matched healthy individuals, as the control group, participated in this study. The 3D-FD method was proposed to distinguish 97 automatic anatomical label regions of gray matter (left cerebrum: 45, right cerebrum: 45, cerebellum: 7) between healthy individuals and patients with SCA3. Patients with SCA3 exhibited reduced brain complexity within both the traditional olivopontocerebellar atrophy (OPCA) pattern and specific supratentorial regions. The study results confirmed the extensive involvement of extracerebellar regions in SCA3. The atrophied regions of SCA3 in infratentorial and supratentorial cortex showed a wide range of overlapped areas as in two functional cortexes, namely cerebellum-related cortex and basal ganglia-related cortex. Our results found that the atrophy of the SCA3 are not only limited in the infratentorial regions. Both cerebellar related cortex and basal ganglia related cortex were affected in the disease process of SCA3. Our findings might correlate to the common symptoms of SCA3, such as ataxia, Parkinsonism, dysarthria, and dysmetria. SCA3 should no longer be considered a disease limited to the cerebellum and its connections; rather, it should be considered a pathology affecting the whole brain.
PubMed: 32194495
DOI: 10.3389/fneur.2020.00124 -
Brain Pathology (Zurich, Switzerland) May 2020Multiple system atrophy (MSA) and Parkinson's disease (PD) are synucleinopathies characterized by aggregation of α-synuclein in brain cells. Recent studies have shown...
Multiple system atrophy (MSA) and Parkinson's disease (PD) are synucleinopathies characterized by aggregation of α-synuclein in brain cells. Recent studies have shown that morphological changes in terms of cerebral nerve cell loss and increase in glia cell numbers, the degree of brain atrophy and molecular and epidemiological findings are more severe in MSA than PD. In the present study, we performed a stereological comparison of cerebellar volumes, granule and Purkinje cells in 13 patients diagnosed with MSA [8 MSA-P (striatonigral subtype) and 5 MSA-C (olivopontocerebellar subtype)], 12 PD patients, and 15 age-matched control subjects. Only brains from MSA-C patients showed a reduction in the total number of Purkinje cells (anterior lobe) whereas both MSA-P and MSA-C patients had reduced Purkinje cell volumes (perikaryons and nuclei volume). The cerebellum of both diseases showed a reduction in the white matter volume compared to controls. The number of granule cells was unaffected in both diseases. Analyses of cell type-specific mRNA expression supported our structural data. This study of the cerebellum is in line with previous findings in the cerebrum and demonstrates that the degree of morphological changes is more pronounced in MSA-C than MSA-P and PD. Further, our results support an explicit involvement of cerebellar Purkinje cells and white matter connectivity in MSA-C > MSA-P and points to the potential importance of white matter alterations in PD pathology.
Topics: Aged; Aged, 80 and over; Atrophy; Cerebellum; Female; Humans; Male; Middle Aged; Multiple System Atrophy; Nerve Degeneration; Neurons; Organ Size; Parkinson Disease; Purkinje Cells; White Matter
PubMed: 31769073
DOI: 10.1111/bpa.12806