It is unclear whether tau-positive granular glial pathology is a characteristic feature of MSA. We aimed to analyse the prevalence and significance of tau-positive granular glial pathology in MSA.
...Fourteen MSA cases were clinicopathologically investigated, focusing on tau-positive granular glial pathology in the frontal and temporal white matter and putamen.
In five MSA cases, the temporal white matter showed AT8-positive granular glial pathology; this pathology was detected in the frontal white matter in three cases. AT8-positive granular glia in the white matter were associated with long disease duration with long-term tube feeding and/or long-term tracheotomy. Alpha-synuclein-positive glial cytoplasmic inclusion intensity was not associated with AT8-positive granular glial pathology. The tau isoform of AT8-positive granular glia in the cerebral white matter exhibited three-repeat, not four-repeat, tau. Ten MSA patients showed tau-positive granular glial pathology in the putamen; the tau isoform was predominantly three-repeat tau and four-repeat tau in cases with disease duration ≥13 years and < 13 years, respectively.
Tau-positive granular glia in the putamen is a characteristic pathological feature of MSA. Tau-positive granular glia appear in the cerebral white matter in MSA patients and are associated with long disease duration with long-term tube feeding and/or long-term tracheotomy.
•Tau-positive granular glial pathology in the putamen is characteristic of MSA.•Tau-positive granular glial pathology is evident in the cerebral white matter.•Long disease duration with long-term tube feeding and/or tracheotomy is a key feature of this pathology.
To investigate somatosensory cortex excitability and its relationship to survival prognosis in patients with amyotrophic lateral sclerosis (ALS).
A total of 145 patients with sporadic ALS and 73 ...healthy control participants were studied. We recorded compound muscle action potential and sensory nerve action potential of the median nerve and the median nerve somatosensory evoked potential (SEP), and we measured parameters, including onset-to-peak amplitude of N13 and N20 and peak-to-peak amplitude between N20 and P25 (N20p-P25p). Clinical prognostic factors, including ALS Functional Rating Scale-Revised, were evaluated. We followed up patients until the endpoints (death or tracheostomy) and analyzed factors associated with survival using multivariate analysis in the Cox proportional hazard model.
Compared to controls, patients with ALS showed a larger amplitude of N20p-P25p in the median nerve SEP. Median survival time after examination was shorter in patients with N20p-P25p ≥8 μV (0.82 years) than in those with N20p-P25p <8 μV (1.68 years,
= 0.0002, log-rank test). Multivariate analysis identified a larger N20p-P25p amplitude as a factor that was independently associated with shorter survival (
= 0.002).
Sensory cortex hyperexcitability predicts short survival in patients with ALS.
Multinodular and vacuolating neuronal tumors (MVNT) have been referred to as distinctive neuronal tumors whose characteristic features include multiple nodules localized in the subcortical white ...matter. MVNT are composed of vacuolating dysplastic neurons reactive to HuC/HuD. A significant overexpression of alpha‐internexin (INA) limited to the stroma of nodules was reported in one tumor. Since genetic analyses have failed to demonstrate any consistent alterations, the nosological position as well as the nature of MVNT, namely, neoplastic or dysplastic, remains unclear. We herein present another example of MVNT involving the amygdala and anterior hippocampus in a 41‐year‐old man. In addition to the nodular lesions described earlier, we found INA‐positive ribbon‐like lesions that replaced neuropil and extended along the hippocampal gray matter. We also identified dysplastic neurons infiltrating into the CA4 hilus of the hippocampus. Intense INA expression was present in the stroma as well as the cytoplasmic membrane of dysplastic neurons and their processes. While the invasiveness suggested a neoplasm, a relatively restrictive, either nodular or ribbon‐like growth pattern with INA‐positive abnormal neuropil suggested a hamartoma. Such quasi‐tumors should be accommodated in the World Health Organization classification of tumors of the central nervous system, as are dysembryoplastic neuroepithelial tumor and Lhermitte‐Duclos disease.
Multiple system atrophy (MSA) is an adult‐onset neurodegenerative disease, which is characterized clinically by parkinsonism, cerebellar ataxia and/or autonomic dysfunction, and pathologically by ...alpha‐synuclein‐related multisystem neurodegeneration, so‐called alpha‐synucleinopathy, which particularly involves the striatonigral and olivopontocerebellar systems, with glial cytoplasmic inclusions and neuronal cytoplasmic/nuclear inclusions (NCIs/NNIs). In the recent consensus criteria for the diagnosis of MSA, dementia is described as one of the features not supporting a diagnosis of MSA. However, MSA with dementia has been reported, although the location of the lesion responsible for the dementia remains unclear. In the present study, we aimed to investigate where this lesion may be found, by analyzing 12 autopsy‐proven MSA cases, with a particular focus on the medial temporal region. Three of 12 cases with MSA had dementia (MSA‐D). Compared with MSA cases without dementia, MSA‐D cases had frequent globular NCIs (G‐NCIs) in the medial temporal region, especially in their subiculum. In addition, MSA‐D cases could be divided into two types; MSA‐D with distinct fronto‐temporal lobar degeneration (FTLD type) and without distinct fronto‐temporal lobar degeneration (non‐FTLD type). There was no association between dementia and Alzheimer pathologies, such as neurofibrillary tangles and senile plaques. We suggest that frequent G‐NCIs in the medial temporal region, and particularly the subiculum, is one of the important pathological findings of MSA‐D, even when a case with MSA‐D reveals no significant cerebral atrophy.
•Small-sized fasciculation potentials detected with EMG may be undetectable with ultrasonography.•Muscle strength between the muscles with and without fasciculations was not different.•Both EMG and ...ultrasonography should be used for diagnosis of amyotrophic lateral sclerosis.
Fasciculation potentials (FP) are an important consideration in the electrophysiological diagnosis of ALS. Muscle ultrasonography (MUS) has a higher sensitivity in detecting fasciculations than electromyography (EMG), while in some cases, it is unable to detect EMG-detected fasciculations. We aimed to investigate the differences of FP between the muscles with and without MUS-detected fasciculations (MUS-fas).
Thirty-one consecutive patients with sporadic ALS were prospectively recruited and in those, both needle EMG and MUS were performed. Analyses of the amplitude, duration, and number of phases of EMG-detected FPs were performed for seven muscles per patient, and results were compared between the muscles with and without MUS-fas in the total cohort.
The mean amplitude and phase number of FP were significantly lower in patients with EMG-detected FP alone (0.39 ± 0.25 mV and 3.21 ± 0.88, respectively) than in those with both FP and MUS-fas (1.22 ± 0.92 mV and 3.74 ± 1.39, respectively; p < 0.0001 and p = 0.017, Welch’s t-test).
Small FP may be undetectable with MUS. MUS cannot replace EMG in the diagnostic approach for ALS.
Clinicians should use a combination of EMG and MUS for the detection and quantitative analysis of fasciculation in ALS.
Based on the hypothesis that autoimmunity plays a role in the pathogenesis of neuralgic amyotrophy (NA), immunotherapy is sometimes administered. Early intervention is recommended for a good ...prognosis. We herein report the case of a 55-year-old man who presented with neuralgia, weakness, and muscle atrophy in his right shoulder girdle and upper arm, which progressed for ten months following a marine sports accident. The patient was diagnosed with NA. His neurological deficits gradually improved after several courses of immunotherapy, suggesting that in addition to being effective for treating early-stage disease, immunotherapy may be effective for treating chronic cases.
The patient was a 74-year-old woman with rheumatoid arthritis who developed ataxia. MRI revealed T2-hyperintense lesions predominantly in the left middle cerebellar peduncle. Punctate or linear Gd ...enhancement was also observed on T1-weighted images. A brain biopsy was conducted and the pathology revealed a mild demyelinated lesion. Polymerase chain reaction (PCR) of biopsied brain tissues revealed the presence of JC virus (JCV) DNA, but JCV-infected oligodendroglia-like cells were not apparent on immunohistochemistry. Sensitive in-situ hybridization, however, detected three JCV-positive cells and the infiltration of CD4+ and CD8+ T cells and plasma cells was also observed. Immunosuppressants were tapered off and mirtazapine and mefloquine administered, resulting in a favorable outcome.
We herein report a case of myoclonic epilepsy with ragged-red fibers (MERRF) harboring a novel variant in mitochondrial cysteine transfer RNA (MT-TC). A 68-year-old woman presented with progressive ...myoclonic epilepsy with optic atrophy and peripheral neuropathy. A skin biopsy revealed p62-positive intranuclear inclusions. No mutations were found in the causative genes for diseases known to be related to intranuclear inclusions; however, a novel variant in MT-TC was found. The association between intranuclear inclusions and this newly identified MERRF-associated variant is unclear; however, the rare complication of intranuclear inclusions in a patient with typical MERRF symptoms should be noted for future studies.
Due to its rarity and the limited literature, the clinicopathological characteristics of peripheral nerve involvement in immunoglobulin G4 (IgG4)-related disease are unknown. We present two cases of ...IgG4-related disease, accompanied by peripheral neuropathy, presenting as unilateral ptosis (case 1) and sclerosing cholangitis (case 2), respectively. In both cases, sural nerve biopsy indicated vasculitis as the underlying pathophysiology; the peripheral neuropathy was refractory to corticosteroid therapy. In contrast to the previously proposed pathomechanism of IgG4-related neuropathy (direct lymphoplasmacytic infiltration), the pathological findings in our cases suggest that vasculitis occurs secondary to systemic autoimmune conditions.
We treated a myelin oligodendrocyte glycoprotein (MOG) antibody disease patient who had been prescribed dimethyl fumarate because she was thought to have been suffering from multiple sclerosis (MS). ...Mild optic neuritis relapsed at one year and four months after the administration of dimethyl fumarate. Therefore, dimethyl fumarate was ineffective for preventing relapse of MOG antibody disease. However, dimethyl fumarate for MOG antibody disease was not harmful compared with when disease-modifying drugs (DMDs) of MS were used for anti-aquaporin-4 antibody-positive neuromyelitis optica. If MS patients repeat relapses even after the start of DMDs, a differential diagnosis including MOG antibody disease should be made.
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