Search

Amyloid-β precursor protein (APP) immunohistochemistry has been used to detect axonal injury in forensic neuropathology. However, axonal injury caused by cerebral ischemia has not been investigated by APP immunohistochemistry in detail. In particular, it is unknown if there is a correlation between the prognosis of cerebral ischemia and the distribution of axonal injury detected by APP immunohistochemistry. To address this issue, we compared the distribution of APP-immunoreactive axons in autopsy brains including lesions of acute phase of cerebral infarction in the territory of the middle cerebral artery (MCA) or internal carotid artery (ICA) with the degree of severity. The presence or absence of a midline shift was used as an indicator of the severity of cerebral ischemia. We identified a difference in the distribution of APP-immunoreactive axons between cases with and without a midline shift. In both the groups, APP-immunoreactive axons were detected at the margin of the ischemic lesions; however, only in cases with a midline shift, intense APP-immunoreactive axons were also found in areas other than the MCA and ICA territories, including the white matter of the cerebral hemispheres ipsilateral and contralateral to the ischemic lesions. This distribution was different from that of acute global cerebral ischemia cases reported previously. Our results indicate that the distribution of APP-immunoreactive axons differs according to the severity and type of cerebral ischemia, suggesting that the distribution of APP-immunoreactive axons is associated with the prognosis of cerebral ischemia.

Astroblastoma is a rare glial neoplasm that occurs mostly in the cerebral hemisphere of children, adolescents and young adults. Although astroblastic perivascular pseudorosettes are unique histopathology of this neoplasm, diagnosis is usually challenging. Recently, it was discovered that the meningioma 1 gene (MN1)-altered pediatric central nervous system high-grade neuroepithelial tumors are actually astroblastomas. This case report presents a rare brainstem astroblastoma, with an unusual immunoprofile: negative for glial fibrillary acidic protein and oligodendrocyte transcription factor 2, but with a robust expression of pancytokeratin and epithelial membrane antigen. The diagnosis was confirmed based on the detection of MN1 rearrangement in a fluorescence in situ hybridization study, in addition to typical histopathology. Here we discuss the diagnostic pitfalls and unclear grading system along with a literature review.

Herein, we present a rare case of gliosarcoma arising from oligodendroglioma, isocitrate dehydrogenase (IDH) mutant and 1p/19q codeleted. A 36-year-old man presented with a non-enhanced calcified abnormal lesion on the right frontal lobe. The patient underwent subtotal surgical resection, PAV chemotherapy (procarbazine, nimustine (ACNU) and vincristine), and fractionated radiotherapy with 50 Gy. The pathological diagnosis was oligodendroglioma, IDH mutant and 1p/19q codeleted, World Health Organization 2016 grade II. Six years later, a new enhanced lesion appeared, and the recurrent tumor was surgically removed. Although the histopathological findings indicated gliosarcoma, the recurrent tumor still demonstrated the IDH mutation and 1p/19q codeleted. Thus, the recurrent tumor was considered to originate from oligodendroglioma, rather than being newly generated after chemoradiotherapy. Interestingly, the second recurrent tumor responded well to temozolomide chemotherapy. Based on the findings of this case, oligodendrogliomas have the potential for mesenchymal transformation on progression, while keeping their genotype.

Oligodendroglia are cells responsible for creating myelin sheaths for axons in the CNS. However, pathologies of oligodendroglia other than demyelination are not well understood due to the lack of adequate methods of characterizing pathological conditions affecting oligodendroglia in human tissue. This review discusses three major topics with the aim of clarifying some of the controversies in the study of oligodendroglia. The oligodendroglioma, a relatively indolent form of diffuse gliomas thought to originate in oligodendrocytes, has never demonstrated myelin formation on electron microscopy nor shown a constant expression of myelin-related proteins. Oligodendrogliomas instead share an immune phenotype with oligodendrocyte progenitor cells (OPCs). Another type of cell that resembles OPCs are oligodendroglia-like cells (OLCs), which occur in many types of low-grade tumors and focal cortical dysplasia. In neurodegenerative disorders, oligodendroglia can be a target of abnormal aggregations of proteins such as tau. Tau-positive oligodendroglial inclusions in progressive supranuclear palsy and corticobasal generation differ from each other morphologically, ultrastructurally and biochemically, suggesting disparate underlying pathological processes despite significant overlapping of the clinical manifestations. To promote the study of oligodendroglia, novel methods for detecting OLCs in situ are urgently required.

We describe a Japanese man with familial amyotrophic lateral sclerosis (ALS) associated with a p.Cys146Arg mutation in the copper/zinc superoxide dismutase gene (SOD1). The patient developed bulbar signs followed by rapidly progressive limb muscle weakness. The prominent clinical feature was orthostatic hypotension due to autonomic failure, which occurred after he underwent tracheostomy 1 year and 3 months after the onset. Thereafter, he required mechanical ventilation and progressed to communication stage V (totally locked-in state) 7 years after the onset. Neuropathology showed ALS with posterior column degeneration and multiple system degeneration. Severe neuronal loss in the intermediolateral nucleus was also observed. Two previously reported cases of ALS patients with autonomic failure showed severe neuronal loss in the intermediolateral nucleus in addition to degeneration of the motor neurons. Thus, autonomic failure due to neuronal loss in the intermediolateral nucleus could present in patients with ALS associated with certain mutations in SOD1.

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.

Argyrophilic grain (ArG) is the main pathological feature of argyrophilic grain disease (AGD) and is clinically characterized by cognitive impairment, behavioral abnormalities, personality changes, and emotional imbalances. However, ArG can not only be found in AGD but also in various other neurological disorders, including Parkinson's disease (PD). The association of ArG with psychosis and/or dementia in various neurological disorders remains unknown; in this study, we have investigated this in PD. The distribution and degree of ArG deposition, spongiform change in the transentorhinal cortex (TER SpC), and phosphorylated alpha-synuclein-positive neurites in CA2/3 were assessed, and we used formalin-fixed, paraffin-embedded specimens obtained from the anterior/posterior medial temporal region of 20 autopsy cases diagnosed as PD. These cases were clinically divided into two groups: PD without dementia (PDND) and PD with dementia (PDD). Most PDD cases revealed scattered to numerous ArG or moderate to severe TER SpC, both of which were rarely observed in the PDND group. Furthermore, by the degree of ArG density and TER SpC, the PDD group was further divided into three subtypes: PDD with ArG, with TER SpC and without ArG/TER SpC. Scattered-to-numerous ArG and/or moderate-to-severe TER SpC were observed only in PDD, which suggested that both ArG and TER SpC could be important factors affecting dementia in PD and that their distribution and degree are equally important.

We describe a Japanese patient with familial amyotrophic lateral sclerosis (ALS) and a p.K510M mutation in the fused in sarcoma gene (FUS). The patient's condition was characterized clinically by an early onset and rapid progression. The patient eventually required mechanical ventilation and progressed to the totally locked-in state. Neuropathologically, multiple system degeneration with many FUS-immunoreactive structures was observed. The involvement of the globus pallidus, subthalamic nucleus, substantia nigra, cerebellar efferent system, and both upper and lower motor neurons in the present patient was comparable to that described for ALS patients with different mutations in FUS, all of whom progressed to the totally locked-in state. However, the patient also exhibited degeneration of the cerebellar afferent system and posterior column. Furthermore, the appearance of non-compact FUS-immunoreactive neuronal cytoplasmic inclusions and many FUS-immunoreactive glial cytoplasmic inclusions were unique to the present patient. These features suggest that the morphological characteristics of the FUS-immunoreactive structures and distribution of the lesions vary with the diversity of mutations in FUS.

Dysembryoplastic neuroepithelial tumor (DNT) is a benign glioneuronal tumor, occurring in children and adolescents, typically associated with drug-resistant partial seizures. Pathologically, DNT is characterized by a specific glioneuronal element that is comprised of oligodendroglia-like cells (OLC) and floating neurons. The definition of DNT is currently controversial and the incidence of DNT varies among institutions. In this study we characterize the morphologic profiles of OLC and floating neurons by performing immunohistochemical and morphometric studies on seven cases of a simple form of DNT. While a majority of OLC was positive for oligodendrocyte transcription factor 2 (Olig2), only floating neurons and a few small cells were positive for neuronal nuclear antigens (NeuN). Double immunofluorescence studies revealed co-localization of Olig2 and galectin 3 in OLC, but no co-localization of Olig2 and NeuN. The distribution pattern of NeuN-positive nuclei within the tumor tissue was not different from that in the adjacent neural tissue. A section cut perpendicular to the cortex stained with NeuN showed a continuous laminar arrangement with the adjacent cortex. Densities of NeuN-positive nuclei from tumors embedded in the white matter were significantly lower than those from tumors in the gray matter. Our results suggest that the NeuN-positive small and large cells observed within the specific glioneuronal element are in fact entrapped granular and pyramidal cells within the cortex and that OLCs are essentially glial and not neuronal in nature. DNT is thus a pure glial tumor rather than a glioneuronal tumor, that is, the equivalent of non-infiltrating oligodendroglioma, grade I.

This report describes cerebral cortical dysplasia in a 20 week fetus, aborted as a result of the prenatal genetic analysis which provided evidence of Fukuyama congenital muscular dystrophy (FCMD). The histological appearance of the brain of this fetus was similar to that of previously described cases. However, cortical dysplasia was less severe in this 20 week fetus, and the interesting finding was the existence of a leptomeningeal lesion probably preceding dysplasia. In this case, abnormal findings were found mainly in the cerebral surface, and maturation of the brain seemed appropriate for the gestational age. Furthermore, periodic acid-methenamine-silver-positive linear structure of the cerebral surface was disrupted irregularly. These findings suggest that defects in the pial-glial barrier of the cerebral surface may play a cardinal role for the genesis of cortical dysplasia. It is suggested that the extracortical abnormal tissue would be detectable morphologically at least in the 12-13th week because cells considered as subpial granular cells were contained in the lesion. This report on the brain of a fetus with FCMD provides information on relatively early central nervous system alterations in this disease, and may be of importance in clarifying their pathogenesis.

We describe the presence of tau protein-positive argyrophilic meshwork structures in the cerebral corticomedullary junctions of three patients with progressive supranuclear palsy (PSP). Meshwork structures are composed of fine, winding fibrils, partly connected to coiled inclusions in oligodendrocytes, and are present on neurofilament protein-positive axons. The novel abnormal structures are numerous in the middle frontal and precentral gyri, and at the ultrastructural level they are present mainly in the outer myelin sheath. Our results suggest that the unusual meshwork structures are formed in processes of oligodendroglia in the cerebral cortex. Further study of well characterized cases is required in order to determine the significance of these structures in cerebral cortical functions in patients with PSP.

We identified 19 cases of dementia characterized by cerebral atrophy with non-specific cortical degeneration, but without pathologic features of Alzheimer's disease or other known neurodegenerative disorders. The cases were selected by a review of 14 000 autopsies and from the clinical records of the Mayo Clinic from 1972 to 1992. Microscopically, four general topographic patterns of atrophy were identified: frontal (n=6), frontotemporal (n=4), temporal (n=3), and mesiotemporal (n=4). The characteristic microscopic findings in the atrophic cortex included neuronal loss with astrocytosis, which predominantly involved the upper cortical layers, and superficial vacuolar changes. A focal or regional accentuation of involvement with different extents and severities of change was common. Neuronal achromasia was present in seven cases. Rare to sparse ubiquitin-positive linear structures were identified in small neurons in the second cortical layer in nine cases. Argentophilic cortical grains, predominantly in the subiculum, were detected in only three cases. Involvement of the cerebral white matter corresponded to the cortical involvement. The striatum, thalamus, or substantia nigra was affected in all cases. Hippocampal involvement was evident only in the mesiotemporal type; the prosubiculum was the most severely affected area. After analyzing similar cases which had previously been reported under diverse diagnostic terms, we propose the term ‘simple cerebral atrophy of non-Alzheimer type’ as a tentative comprehensive category for direct correlation, encompassing a spectrum of non-Alzheimer type dementia.