Neurological Infectious Disease
Viral and immune mediated disorders of the nervous system are among the most challenging neurological disorders. The most common neuroimmune disorder is multiple sclerosis; and HIV is the most common viral infection of the nervous system. Common to both disorders is the progressive loss of neurons, resulting in significant cognitive and motor dysfunction. A major focus of Mayo researchers is to understand the pathophysiology of neuronal injury associated with these disorders to develop new diagnostic markers, therapeutic targets, and new areas of research applicable to other neurodegenerative diseases.
The research of Allen Aksamit M.D., is focused in the following areas:
Dr. Aksamit studied progressive multifocal leukoencephalopathy (PML), a destructive demyelinating infection that attacks oligodendrocytes. It has recently occurred in multiple sclerosis patients treated with natalizumab, a monoclonal antibody that interferes with lymphocyte "trafficking" into the brain. Magnetic resonance imaging (MRI) of the brain gives clues to diagnosis, but is nonspecific in distinguishing multiple sclerosis from PML.
Spinal fluid detection of human neurotropic polyomavirus (JC virus) is specific, but incompletely sensitive. Immunosuppression of cell–mediated type immunity leads to this disease, but it is difficult to defined this immunosuppression on clinical grounds in some patients, and the development of PML may come as a surprise when an immunosuppressed state was not previously suspected. It is apparent that natalizumab is a predisposing factor for developing PML in the six cases of natalizumab–treated patients, and three new cases were recently reported. While there is no reliable presymptomatic way to detect PML or JC virus infection of the brain by virologic or imaging surveillance techniques, one patient with multiple sclerosis and natalizumab treatment has survived, indicating that withdrawal of the antibody, possibly in combination with antiviral therapy, may permit survival. However, immune reconstitution disease is a risk after immune restoration and withdrawal of natalizumab. PML deficits are usually permanent, at least to some degree. The current estimate of PML risk in natalizumab–treated patients is 1 per 1000. The duration of natalizumab treatment may be an independent risk factor for development of PML. The study showed that PML, a usually fatal neurologic infection, should be considered as a risk factor when using natalizumab. The treatment of multiple sclerosis patients with natalizumab is a matter of informed risk, individualized for each patient. The study was published in Neurologist. 2006 Nov;12(6):293–8.
In another study, Dr. Aksamit investigated herpes simplex encephalitis (HSE), a neurologically devastating illness associated with substantial morbidity and mortality in adults and older children. Recognition of HSE, and distinction from other forms of encephalitis, brain abscess or mimicking disorders early in the course of evaluation facilitates early treatment, which can prevent disastrous neurologic complications. The combination of clinical characteristics, magnetic resonance imaging of the head, and polymerase chain reaction (PCR) analysis of cerebrospinal fluid for herpes simplex type 1 DNA is a sensitive and specific way of diagnosing HSE for proper treatment. HSE is treated with acyclovir 10 mg/kg every eight hours intravenously for 21 days, unless the illness is mild, or nephrotoxicity occurs. Whether prolonged therapy with oral antiviral treatment after standard intravenous acyclovir offers any advantage from the standpoint of neurologic morbidity or mortality is unproven. PCR–negative typical cases and PCR–positive atypical cases of HSE can occur and require treatment with acyclovir. The study is published in Current Treat Options Neurology. 2005 Mar;7(2):145–150.
Several Mayo Clinic researchers (Drs. Aksamit, Castillo, Woodruff, Caselli, Vernino, Lucchinetti, Swanson, Noseworthy, Carter, Sirven, Hunder, Fatourechi, Mokri, Drubach, Pittock, Lennon, Boeve) investigated steroid–responsive encephalopathy associated with autoimmune thyroiditis (SREAT), often termed Hashimoto encephalopathy, a poorly understood and often misdiagnosed entity. Their goal was to characterize the clinical, laboratory, and radiologic findings in patients with SREAT to potentially improve recognition of this treatable entity in a retrospective analysis of clinical features and diagnostic test data. These researchers found that the clinical, laboratory, and radiologic findings associated with SREAT are more varied than previously reported, andmisdiagnosis at presentation is common. This treatable syndrome should be considered even if the serum sensitive thyroid–stimulating hormone level and erythrocyte sedimentation rate are normal; the cerebrospinal fluid profile does not suggest an inflammatory process; and neuroimaging results are normal. Until the pathophysiologic mechanism of this and other autoimmune encephalopathies is better characterized, they conclude that descriptive terms that reflect an association rather than causation are most appropriate. The study is published in the Archives of Neurology. 2006 Feb;63(2):197–202.
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