Diagnosis of coexistent neurodegenerative dementias in multiple sclerosis.

Among people with multiple sclerosis, cognitive impairment occurs commonly and is a potent predictor of disability. Some multiple sclerosis patients present with severe cognitive impairment, and distinguishing multiple sclerosis-related cognitive impairment from co-existent progressive neurodegenerative diseases such as Alzheimer disease poses a diagnostic challenge. The use of biomarkers such as PET and CSF proteins may facilitate this distinction. The study was a retrospective, descriptive study on convenience samples of separate cohorts, one of cognitively impaired multiple sclerosis patients evaluated on autopsy to demonstrate coincidence of both multiple sclerosis and neurodegenerative cognitive diseases. The second cohort were cognitively impaired multiple sclerosis patients evaluated by biomarker to investigate possible additional neurodegenerative cognitive disorders contributing to the cognitive impairment. We investigated selected biomarkers among 31 severely impaired patients (biomarker cohort) and 12 severely impaired patients assessed at autopsy and selected 24 (23 biomarker cohort, 1 autopsy cohort) had comprehensive neurocognitive testing. Biomarker cohort investigations included 18F-Fluorodeoxyglucose PET and/or CSF amyloid Aß1-42, phospho-tau and total tau levels. The autopsy cohort was evaluated with comprehensive neuropathological assessment for aetiology of cognitive impairment. The cohorts shared similar sex, age at multiple sclerosis onset and multiple sclerosis clinical course. The autopsy-cohort patients were older at diagnosis (69.5 versus 57 years, P = 0.006), had longer disease duration [median (range) 20 years (3-59) versus 9 (1-32), P = 0.001] and had more impaired bedside mental status scores at last follow-up [Kokmen median (range) 23 (1-38) versus 31 (9-34) P = 0.01]. Autopsy-cohort patients confirmed, or excluded, coexistent neurogenerative disease by neuropathology gold standard. Most biomarker-cohort patients had informative results evaluating coexistent neurogenerative disease. Biomarkers may be useful in indicating a coexistent neurodegenerative disease earlier, and in life, in patients with multiple sclerosis and significant cognitive impairment.

In situ detection of antigenic glycoproteins in Taenia solium metacestodes.

Taenia solium has a complex life cycle. Its cysticercus can lodge in the brain, causing neurocysticercosis (NCC), and the adult tapeworm's survival in the intestine results in taeniasis. In this study, the in situ detection of previously described glycoprotein antigens used for serological diagnosis of NCC and the detection of other glycoconjugates was explored in cysticerci and the surrounding porcine tissue to understand their potential role in pathogenesis. Immunohistochemistry with an antiserum specific for glycoprotein antigens rich in N-linked carbohydrates and in situ histochemistry with a battery of lectins that have affinity to a variety of glycoconjugates were performed. The glycoconjugates rich in N-linked carbohydrates were detected in the vesicular fluid and tegument of the vesicular membrane and scolex, where the parasite has direct contact with the host tissues during cysticercosis and taeniasis, respectively. Additionally, as the inflammatory response progressed, the parasite's antigenic glycoproteins were also detected in the cytoplasm of inflammatory cells in the surrounding granuloma. In contrast, the spiral canal tegument, which will be exposed to intestinal enzymes in taeniasis, had N-acetyl-galactosamine-rich mucins. Thus, the differential saccharidic composition in T. solium metacestode structures may be important for the survival of the parasite in different host sites.

The inflammatory cell infiltrates in porcine cysticercosis: immunohistochemical analysis during various stages of infection.

Taenia solium metacestodes cause cysticercosis in both humans and pigs. In the former host species, the central nervous system involvement (neurocysticercosis (NCC)) may range from asymptomatic to life-threatening, but little is known about the corresponding variation in tissue response due to the difficulty in obtaining parasite-infected brain biopsies. The use of pigs as animal models for cysticercosis is ideal because the histological description of the animal's response around the parasites resembles the one recorded in human specimens. In this study the histological features of the immune response in swine were complemented by immunohistochemical analysis to determine the phenotype of the inflammatory cells. The presence of mononuclear cells and eosinophils, and the co-localization of MHC-II with B lymphocytes and monocytes/macrophages within the granulomas surrounding the parasites, were features that closely resembled the descriptions made in prior studies with human specimens. In addition, there were novel findings such as the upregulation of the adhesin CD44 in cells resembling monocytes/macrophages, eosinophils and in astrocytes from the central nervous system. The upregulation of CD44 may be important for the recruitment of inflammatory cells to the site of the lesion. Finally, the presence of null-gamma delta-T cells since stage I of the immune response was similar to the early detection of these cells in mouse models for cysticercosis.