Joseph R. Zunt

Autoimmunity due to molecular mimicry as a cause of neurological disease

One hypothesis that couples infection with autoimmune disease is molecular mimicry. Molecular mimicry is characterized by an immune response to an environmental agent that cross-reacts with a host antigen, resulting in disease. This hypothesis has been implicated in the pathogenesis of diabetes, lupus and multiple sclerosis (MS). There is limited direct evidence linking causative agents with pathogenic immune reactions in these diseases. Our study establishes a clear link between viral infection, autoimmunity and neurological disease in humans. As a model for molecular mimicry, we studied patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs. 5,6,7). HAM/TSP patients develop antibodies to neurons. We hypothesized these antibodies would identify a central nervous system (CNS) autoantigen. Immunoglobulin G isolated from HAM/TSP patients identified heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1) as the autoantigen. Antibodies to hnRNP-A1 cross-reacted with HTLV-1-tax, the immune response to which is associated with HAM/TSP (refs. 5,9). Immunoglobulin G specifically stained human Betz cells, whose axons are preferentially damaged. Infusion of autoantibodies in brain sections inhibited neuronal firing, indicative of their pathogenic nature. These data demonstrate the importance of molecular mimicry between an infecting agent and hnRNP-A1 in autoimmune disease of the CNS.

Parasitic Central Nervous System Infections in Immunocompromised Hosts

Immunosuppression due to therapy after transplantation or associated with HIV infection increases susceptibility to various central nervous system (CNS) infections. This article discusses how immunosuppression modifies the presentation, diagnosis, and treatment of selected parasitic CNS infections, with a focus on toxoplasmosis, Chagas disease, neurocysticercosis, schistosomiasis, and strongyloidiasis.

Changes in CSF and plasma HIV-1 RNA and cognition after starting potent antiretroviral therapy.

The authors assessed CSF and plasma HIV-1 RNA and neuropsychological test performance (composite neuropsychological test Z score [NPZ-4]) in 25 HIV-1–infected subjects 4 and 8 weeks after beginning potent antiretroviral therapy that included a protease inhibitor. In the 14 subjects who entered the study on no antiretroviral treatment, NPZ-4 improvement was associated with decline in CSF HIV-1 RNA at both visits (p = 0.001 and p = 0.02), and those treated with zidovudine or indinavir had greater improvement in NPZ-4 at both visits compared to those treated with other drugs (p = 0.003 and p = 0.01).

Neurocysticercosis: Neglected but Not Forgotten

Neurocysticercosis (NCC) is an infection of the central nervous system caused by the larval form of the tapeworm Taenia solium. Infections occur following the accidental ingestion of tapeworm ova found in human feces. NCC is a major cause of epilepsy and disability in many of the worlds poorer countries where families raise free-roaming pigs that are able to ingest human feces. It is frequently diagnosed in immigrant populations in the United States and Canada, reflecting the high endemicity of the infection in their countries of origin [1]. Although parenchymal cysts are the most common location in the brain and cause seizures, cysts may also be present in the ventricles, meninges, spinal cord, eye, and subarachnoid spaces. Involvement in these other sites may result in aberrant growth (racemose cysts) and complicated disease that is difficult to treat and may cause increased morbidity and mortality.

Evidence-based guideline: Treatment of parenchymal neurocysticercosis Report of the Guideline Development Subcommittee of the American Academy of Neurology

Objective: To review the evidence base for different treatment strategies in intraparenchymal neurocysticercosis in adults and children. Method: A literature search of Medline, EMBASE, LILACS, and the Cochrane Database from 1980 to 2008, updated in 2012, resulted in the identification of 10 Class I or Class II trials of cysticidal drugs administered with or without corticosteroids in the treatment of neurocysticercosis. Results: The available data demonstrate that albendazole therapy, administered with or without corticosteroids, is probably effective in decreasing both long-term seizure frequency and the number of cysts demonstrable radiologically in adults and children with neurocysticercosis, and is well-tolerated. There is insufficient information to assess the efficacy of praziquantel. Recommendations: Albendazole plus either dexamethasone or prednisolone should be considered for adults and children with neurocysticercosis, both to decrease the number of active lesions on brain imaging studies (Level B) and to reduce long-term seizure frequency (Level B). The evidence is insufficient to support or refute the use of steroid treatment alone in patients with intraparenchymal neurocysticercosis (Level U).

Parasitic Central Nervous System Infections in Immunocompromised Hosts: Malaria, Microsporidiosis, Leishmaniasis, and African Trypanosomiasis

Immunosuppression associated with HIV infection or following transplantation increases susceptibility to central nervous system (CNS) infections. Because of increasing international travel, parasites that were previously limited to tropical regions pose an increasing infectious threat to populations at risk for acquiring opportunistic infection, especially people with HIV infection or individuals who have received a solid organ or bone marrow transplant. Although long-term immunosuppression caused by medications such as prednisone likely also increases the risk for acquiring infection and for developing CNS manifestations, little published information is available to support this hypothesis. In an earlier article published in Clinical Infectious Diseases, we described the neurologic manifestations of some of the more common parasitic CNS infections. This review will discuss the presentation, diagnosis, and treatment of the following additional parasitic CNS infections: malaria, microsporidiosis, leishmaniasis, and African trypanosomiasis.

2017 Infectious Diseases Society of America's Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis.

The Infectious Diseases Society of America (IDSA) Standards and Practice Guidelines Committee collaborated with partner organizations to convene a panel of 10 experts on healthcare-associated ventriculitis and meningitis. The panel represented pediatric and adult specialists in the field of infectious diseases and represented other organizations whose members care for patients with healthcare-associated ventriculitis and meningitis (American Academy of Neurology, American Association of Neurological Surgeons, and Neurocritical Care Society). The panel reviewed articles based on literature reviews, review articles and book chapters, evaluated the evidence and drafted recommendations. Questions were reviewed and approved by panel members. Subcategories were included for some questions based on specific populations of patients who may develop healthcare-associated ventriculitis and meningitis after the following procedures or situations: cerebrospinal fluid shunts, cerebrospinal fluid drains, implantation of intrathecal infusion pumps, implantation of deep brain stimulation hardware, and general neurosurgery and head trauma. Recommendations were followed by the strength of the recommendation and the quality of the evidence supporting the recommendation. Many recommendations, however, were based on expert opinion because rigorous clinical data are not available. These guidelines represent a practical and useful approach to assist practicing clinicians in the management of these challenging infections.

CEREBROSPINAL FLUID TESTING FOR THE DIAGNOSIS OF CENTRAL NERVOUS SYSTEM INFECTION

The central nervous system (CNS) is susceptible to bacterial, viral, and fungal infections, and prion diseases. Examination of the cerebrospinal fluid (CSF) is crucial in diagnosing these infections. Cerebrospinal tests may directly identify an organism and its nucleic acid and surface constituents by culture, polymerase chain reaction (PCR), or antigen detection. Alternatively, antibody to an organism may be identified in CSF by enzyme-linked immunosorbent assay (ELISA), Western blot, or complement fixation assay. This article discusses how these CSF tests are performed and addresses the sensitivity and specificity of such tests for the diagnosis of selected CNS infections.

Tuberculosis of the Central Nervous System in Immunocompromised Patients: HIV Infection and Solid Organ Transplant Recipients

Central nervous system (CNS) tuberculosis (TB) is a devastating infection with high rates of morbidity and mortality worldwide and may manifest as meningitis, tuberculoma, abscess, or other forms of disease. Immunosuppression, due to either human immunodeficiency virus infection or solid organ transplantation, increases susceptibility for acquiring or reactivating TB and complicates the management of underlying immunosuppression and CNS TB infection. This article reviews how immunosuppression alters the clinical presentation, diagnosis, treatment, and outcome of TB infections of the CNS.

High Endemicity of Human T-cell Lymphotropic Virus Type 1 Among Pregnant Women in Peru

Summary: Human T-cell lymphotropic virus type 1(HTLV-1) is associated with adult T-cell leukemia, tropical spastic paraparesis, and other immune-mediated diseases. There are reports of groups with high prevalences of HTLV-1 infection in Peru, but there is limited knowledge of the epidemiology of infection or which routes of infection are most important. We studied 2492 women presenting to a large maternity hospital in Lima for prenatal, delivery, or abortion services. HTLV-1 seropositivity was confirmed in 42 women (1.7%; 95% confidence interval, 1.2-2.2). Seroprevalence increased with age but did not vary by region of birth or recency of migration to Lima. Age greater than 30 years and sexual intercourse before 20 years of age were strongly and independently associated with infection. History of abortion and history of transfusion were of borderline significance. Women whose male partner had a characteristic that might be a marker for risk of sexually transmitted infections were also more likely to be infected. HTLV-1 is common among Peruvians throughout the country and is maintained by a low level of neonatally acquired infection that is amplified by sexual transmission. In addition to screening of the blood supply, instituted in 1997, programs designed to reduce neonatal and sexual transmission should be effective.