Neuropathology最新文献

Granular cell tumors of the neurohypophysis (GCT) are rare benign neoplasms belonging, along with pituicytoma and spindle cell oncocytoma, to the family of TTF1-positive low-grade neoplasms of the posterior pituitary gland. GCT usually present as a solid sellar mass, slowly growing and causing compressive symptoms over time, occasionally with suprasellar extension. They comprise polygonal monomorphous cells with abundant granular cytoplasm, which is ultrastructurally filled with lysosomes. Here we report the case of a GCT presenting as a third ventricle mass, radiologically mimicking chordoid glioma, with aberrant expression of GFAP and Annexin-A, which lends itself as an example of an integrated diagnostic approach to sellar/suprasellar and third ventricle masses.

Spinal ependymoma with MYCN amplification is a newly recognized type of spinal ependymoma that is known to be associated with poor prognosis. Available studies on this relatively rare tumor type have observed that these tumors tend to disseminate along the spinal cord and behave aggressively with worse overall and progression-free survival compared to the other types of ependymoma. In this study, we describe the clinical and histopathological features of spinal ependymomas in a single institution cohort with emphasis on those with MYCN amplification.

Sevoflurane (SEV) is a commonly used anesthetic in pediatric surgery. Recent studies reported that repeated use of SEV contributes to cognitive impairment. Engeletin has been discovered to exert anti-inflammatory effects in various diseases. However, the detailed roles and mechanisms of engeletin in SEV-induced cognitive dysfunction of neonatal mice remain unclear. In this study, C57BL/6 neonatal mice were randomly divided into Ctrl, SEV, SEV + Engeletin (10 mg /kg), SEV + Engeletin (20 mg/kg), and SEV + Engeletin (40 mg/kg) groups. The Morris water maze (MWM) test suggested that engeletin treatment significantly improved SEV-induced cognitive impairment in neonatal mice. Employing ELISA and Nissl staining analysis, engeletin reduced neuroinflammation and loss of nerve cells caused by SEV, respectively. The treatment of engeletin dramatically suppressed the activation of microglia and apoptosis induced by SEV in the hippocampus of neonatal mice. Furthermore, the inhibition of PPAR-γ obviously reversed the abovementioned effects of engeletin in the hippocampus of newborn mice. In conclusion, this study verified that engeletin notably ameliorated SEV-induced cognitive deficiencies in neonatal mice at least partially by mediating the expression of PPAR-γ.

Genetic Creutzfeldt-Jakob disease (gCJD) with a V180I mutation (V180I gCJD) is the most common type of gCJD in Japan, characterized by an older age at onset, slower progression, and moderate to severe cortical degeneration with spongiform changes and sparing of the brainstem and cerebellum. Degeneration of the inferior olivary nucleus (IO) is rarely observed in patients with CJD but is known to occur in fatal familial insomnia (FFI) and MM2-thalamic-type sporadic CJD (sCJD-MM2T) involving type 2 prion protein (M2T prion). Here we report on an 81-year-old Japanese woman who initially developed depressive symptoms followed by progressive cognitive impairment, myoclonus, and hallucinations and died after a clinical course of 23 months. Insomnia was not evident. Genetic analysis of the prion protein (PrP) identified a V180I mutation with methionine/valine heterozygosity at codon 129. Pathologic analysis demonstrated extensive spongiform degeneration, neuronal loss in the cortices, and weak synaptic-type PrP deposition. Except for IO degeneration, the clinicopathologic features and Western blotting PrP band pattern were compatible with those of previously reported V180I gCJD cases. Quantitative analysis revealed that the neuronal density of the IO, especially in the dorsal area, was considerably reduced to the same extent as that of a patient with sCJD-MM2T but preserved in other patients with V180I gCJD and sCJD-MM1 (this patient, 2.3 ± 0.53/mm² ; a patient with sCJD-MM2T, 4.2 ± 2; a patient with V180I gCJD, 60.5 ± 9.3; and a patient with sCJD-MM1, 84.5 ± 17.9). Use of the protein misfolding cyclic amplification (PMCA) method confirmed the presence of the M2T prion strain, suggesting that the latter might be associated with IO degeneration in V180I gCJD. Autopsy studies are necessary to better understand the nature of CJD, since even if patients present with the common clinical picture, pathologic analysis might provide new insights, as was the case here.

Tuberculosis of the hypothalamo-pituitary axis is extremely uncommon. The presentation of panhypopituitarism in a case of sellar tuberculosis is an even rarer occurrence. We present a case of a 44-year-old man who presented with complaints of headache and right-sided diminution of vision for six months. A hormone profile showed abnormal anterior pituitary assay suggestive of panhypopituitarism. Magnetic Resonance imaging of the brain showed a sellar mass measuring 1.8 × 1.5 × 1.3 cm with suprasellar extension suggestive of a pituitary adenoma. Histopathological examination showed multiple epithelioid cell granulomas along with Langhans giant cells and mixed inflammatory infiltrates against a necrotic background. Zeihl Neelson stain demonstrated the presence of acid-fast bacilli. Thus, a final diagnosis of pituitary tuberculoma was made, and the patient started on antitubercular therapy. It is extremely important to correctly diagnose sellar tuberculosis as the treatment is entirely different, and the patient usually responds well to therapy.

Primary neuroendocrine carcinoma (NEC) of the brain is an extremely rare presentation, with only a few previous case reports. We describe a primary NEC arising from the left parieto-occipital lobe. The 55-year-old patient presented with complaints of headache and dizziness for the preceding 7 months. Magnetic resonance imaging revealed a large ill-defined mass in the left parieto-occipital lobe, with possible differential diagnosis of meningioma. A craniotomy was performed, and a firm vascular tumor was removed. Histopathological examination revealed a large cell NEC. Immunohistochemistry was performed to exclude the possibility of an extracranial primary. Based on the immunohistochemical expression and absence of any extracranial tumor on positron emission tomography, the diagnosis of primary NEC of the brain was made. It is important to differentiate between primary and metastatic neuroendocrine tumors because they show a significant difference in prognosis and treatment.

Spinal muscular atrophy (SMA), an autosomal-recessive lower motor neuron disease, causes progressive proximal muscle waste and weakness. It remains unclear whether myopathic changes are involved in pathogenesis. We encountered a patient with adult-onset SMA caused by a homozygous deletion in exon 7 of the survival motor neuron 1 (SMN1) gene who had had four copies of SMN2 exon 7. Muscle biopsy showed neurogenic features of groups of atrophic fibers, fiber-type grouping, and pyknotic nuclear clumps associated with fibers with rimmed vacuoles. Immunohistochemistry revealed sarcoplasmic aggregates of phosphorylated TDP-43 and p62 but not SMN. This study demonstrated myopathic changes with the accumulation of phosphorylated p62 and TDP-43 in the muscles of a patient with SMA, suggesting that abnormal protein aggregation may be involved in myopathic pathology.

Cerebral ischemia starts with cerebral blood flow interruption that causes severely limited oxygen and glucose supply, eliciting a cascade of pathological events, such as excitotoxicity, oxidative stress, calcium dysregulation, and inflammatory response, which could ultimately result in neuronal death. Hirudin has beneficial effects in ischemic stroke and possesses antioxidant and anti-inflammatory properties. Therefore, we investigated the biological functions of hirudin and its related mechanisms in cerebral ischemia. The ischemia-like conditions were induced by transient middle cerebral artery occlusion (MCAO). To investigate hirudin roles, intracerebroventricular injection of 10 U hirudin was given to the rats. Cognitive and motor functions were examined by beam walking and Morris water maze tests. 2,3,5-triphenyl tetrazolium chloride-stained brain sections were used to measure infarct volume. Oxidative stress was determined by assessment of oxidative stress markers. The proliferated cells were labeled by BrdU and Nestin double staining. Western blotting was performed to measure protein levels. Hirudin administration improved cognitive and motor deficits post-ischemia. Hirudin reduced brain infarction and neurological damage in MCAO-subjected rats. Hirudin alleviated oxidative stress and enhanced neurogenesis in ischemic rats. Hirudin facilitated the promotion of phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and serine-threonine kinase. In sum, hirudin alleviates cognitive deficits by attenuating oxidative stress and promoting hippocampal neurogenesis through the regulation of ERK1/2 and serine-threonine kinase in MCAO-subjected rats.

Spinocerebellar ataxia type 8 (SCA8) is a neurodegenerative condition that presents with several neurological symptoms, such as cerebellar ataxia, parkinsonism, and cognitive impairment. It is caused by a CTA/CTG repeat expansion on chromosome 13q21 (ataxin 8 opposite strand [ATXN8OS]). However, the pathological significance of this expansion remains unclear. Moreover, abnormal CTA/CTG repeat expansions in ATXN8OS have also been reported in other neurodegenerative diseases, including progressive supranuclear palsy. In this study, we analyzed all available autopsy cases in Japan to investigate common pathological features and profiles of tau pathology in each case. Severe neuronal loss in the substantia nigra and prominent loss of Purkinje cells, atrophy of the molecular layer, and proliferation of Bergmann glia in the cerebellum were common features. Regarding tauopathy, one case presented with progressive supranuclear palsy-like 4-repeat tauopathy in addition to mild Alzheimer-type 3- and 4-repeat tauopathy. Another case showed 3- and 4-repeat tauopathy accentuated in the brainstem. The other two cases lacked tauopathy after extensive immunohistochemical studies. The present study confirmed common pathological features of SCA8 as degeneration of the substantia nigra in addition to the cerebellum. Our study also confirmed unique tauopathy in two of four cases, indicating the necessity to further collect autopsy cases.