Journal of neuropathology and experimental neurology
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J. Neuropathol. Exp. Neurol. · Mar 2020
ReviewUltrastructural Lesions of Nodo-Paranodopathies in Peripheral Neuropathies.
Whatever the cause of myelin damage of the peripheral nervous system, the initial attack on myelin by a dysimmune process may begin either at the internodal area or in the paranodal and nodal regions. The term "nodo-paranodopathy" was first applied to some "axonal Guillain-Barré syndrome" subtypes, then extended to cases classified as chronic inflammatory demyelinating polyradiculoneuropathy bearing IgG4 antibodies against paranodal axoglial proteins. In these cases, paranodal dissection develops in the absence of macrophage-induced demyelination. ⋯ However, it should be borne in mind that identical ultrastructural aspects are seen in other types of polyneuropathies: Genetic, experimental, and in a few polyneuropathies for which there is no obvious etiology. Ultrastructural nerve studies confirm the initial involvement of nodes/paranodes in various types of acquired and genetic neuropathies. For some of them, the antibodies or the proteins involved by mutations are clearly identified such as Caspr-1, Contactin-1, NFasc155, and NFasc186; other unidentified proteins are likely to be involved as well.
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J. Neuropathol. Exp. Neurol. · Mar 2019
Review Case ReportsA Review of Neuropathological Features of Familial and Adult Hemophagocytic Lymphohistiocytosis.
Hemophagocytic lymphohistiocytosis (HLH) is a hematological disorder that can be due to genetic (primary HLH) causes or excessive activation of the immune system in association with infection, malignancy, rheumatologic disorders, or immune suppression (secondary HLH). Hemophagocytic lymphohistiocytosis remains an under-recognized condition among neuropathologists, especially the secondary forms, where it may be diagnosed only at brain biopsy or autopsy due to confounding comorbidities. The CNS is frequently affected, but neuropathological features are underappreciated. ⋯ Children had predominantly secondary HLH: 5/12 co-associated with Epstein Barr (or dual) viral infections, 3/12 with malignancy. One biopsy showed florid lymphohistiocytic infiltrates and hemophagocytosis and served as first diagnosis; 2/5 CNS autopsies had originally been reported as negative for HLH, but on re-review had subtle lymphohistiocytic infiltrates with hemophagocytosis confined to leptomeninges. In conclusion, the neuropathological features are highly variable in HLH; features such as focal erythrophagocytosis may be histologically subtle in early phases, but should be sought.
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J. Neuropathol. Exp. Neurol. · Jul 2012
Review Case ReportsUpdate on PML and PML-IRIS occurring in multiple sclerosis patients treated with natalizumab.
The use of natalizumab to treat multiple sclerosis (MS) has been associated with the development of progressive multifocal leukoencephalopathy (PML), with 242 PML cases reported as of May 3, 2012. Fortunately, rapid withdrawal of the drug and administration of plasma exchange has allowed survival in many of these patients, but a new problem, immune reconstitution inflammatory syndrome (IRIS), has emerged after drug withdrawal. This report provides an update on PML in natalizumab-treated patients and reviews what is currently known about PML-IRIS in this setting; autopsy findings from a well-studied patient are illustrated. ⋯ Immune reconstitution inflammatory syndrome was diagnosed, comfort care was instituted, but demise did not occur until 9 months later. Autopsy showed ongoing severe PML-IRIS, with massive cavitary brain lesions containing abundant perivascular and parenchymal CD8-positive T-cell infiltrates. Bone marrow and spleen, but not brain, contained monoclonal T-cell populations by polymerase chain reaction-based gene rearrangement studies, indicating overstimulation of peripheral T cells; T-cell lymphoma was not identified by morphological or immunohistochemical criteria.
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Since its introduction to the United States in 1999, West Nile virus (WNV) has become endemic in North America and has emerged as the most common cause of epidemic meningoencephalitis in North America and the leading cause of arboviral encephalitis in the United States. West Nile virus is maintained in nature by cycling between mosquito vectors and bird hosts; humans are incidental hosts. Transmission to humans occurs predominantly after a bite from an infected mosquito but has also occurred via transfusion of blood products, via organ transplantation from infected donors, transplacentally, and percutaneously through occupational exposure. ⋯ Reverse transcription polymerase chain reaction tests are useful to screen blood products and for surveillance of birds and mosquitoes. The pathological findings are typical of a viral meningoencephalitis and include microglial nodules, perivascular chronic inflammation, and variable neuronal loss with necrosis or neuronophagia. Treatment is largely supportive, and control of the mosquito vectors may reduce the incidence of human infections.
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J. Neuropathol. Exp. Neurol. · Jul 2009
Review Case ReportsChronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury.
Since the 1920s, it has been known that the repetitive brain trauma associated with boxing may produce a progressive neurological deterioration, originally termed dementia pugilistica, and more recently, chronic traumatic encephalopathy (CTE). We review 48 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 profession althletes, 1 football player and 2 boxers. Clinically, CTE is associated with memory disturbances, behavioral and personality changes, parkinsonism, and speech and gait abnormalities. ⋯ The neurofibrillary degeneration of CTE is distinguished from other tauopathies by preferential involvement of the superficial cortical layers, irregular patchy distribution in the frontal and temporal cortices, propensity for sulcal depths, prominent perivascular, periventricular, and subpial distribution, and marked accumulation of tau-immunoreactive astrocytes. Deposition of beta-amyloid, most commonly as diffuse plaques, occurs in fewer than half the cases. Chronic traumatic encephalopathy is a neuropathologically distinct slowly progressive tauopathy with a clear environmental etiology.