Autopsy Case of Meningoencephalomyelitis Associated With Glial Fibrillary Acidic Protein Antibody.

BACKGROUND AND OBJECTIVES: To describe the autopsy findings and neuropathologic evaluation of autoimmune meningoencephalomyelitis associated with glial fibrillary acidic protein (GFAP) antibody. METHODS: We reviewed the clinical course, imaging, laboratory, and autopsy findings of a patient with autoimmune meningoencephalomyelitis associated with GFAP antibody who had a refractory course to multiple immunosuppressive therapies. RESULTS: The patient was a 70-year-old man who was diagnosed as GFAP antibody-associated autoimmune meningoencephalomyelitis. MRI of the head showed linear perivascular enhancement in the midbrain and the basal ganglia. Despite treatment with high-dose corticosteroids, plasma exchange, IV immunoglobulins, and cyclophosphamide, he died with devastating neurologic complications. Autopsy revealed a coexistent neuroendocrine tumor in the small intestine and diffuse inflammation in the brain parenchyma, perivascular spaces, and leptomeninges, with predominant T-cells, macrophages, and activated microglia. B-cells and plasma cells were absent. There was no astrocyte involvement with change in GFAP immunostaining. DISCUSSION: This case illustrates autoimmune meningoencephalomyelitis associated with GFAP antibody in the CSF and coexistent neuroendocrine tumor. The autopsy findings were nonspecific and did not demonstrate astrocyte involvement. Further accumulation of cases is warranted to delineate the utility and pathogenic significance of the GFAP autoantibody.

Education Research: Multiple sclerosis and neuroimmunology fellowship training status in the United States.

OBJECTIVE: To investigate the current status of postgraduate training in neuroimmunology and multiple sclerosis (NI/MS) in the United States. METHODS: We developed a questionnaire to collect information on fellowship training focus, duration of training, number of fellows, funding application process, rotations, visa sponsorship, and an open-ended question about challenges facing training in NI/MS. We identified target programs and sent the questionnaires electronically to fellowship program directors. RESULTS: We identified and sent the questionnaire to 69 NI/MS fellowship programs. We successfully obtained data from 64 programs. Most programs were small, matriculating 1-2 fellows per year, and incorporated both NI and MS training into the curriculum. Most programs were flexible in their duration, typically lasting 1-2 years, and offered opportunities for research during training. Only 56% reported the ability to sponsor nonimmigrant visas. Most institutions reported having some internal funding, although the availability of these funds varied from year to year. Several program directors identified funding availability and the current absence of national subspecialty certification as major challenges facing NI/MS training. CONCLUSION: Our study is the first to describe the current status of NI/MS training in the United States. We found many similarities across programs. We anticipate that these data will serve as a first step towards developing a standard NI/MS curriculum and help identify areas where shared resources could enhance trainee education despite differences in training environments. We identified funding availability, certification status, and nonimmigrant visa sponsorship as potential barriers to future growth in the field.

Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift.

Traumatic brain injury (TBI) is a leading cause of morbidity and disability, with a considerable socioeconomic burden. Heterogeneity of pathoanatomical subtypes and diversity in the pathogenesis and extent of injury contribute to differences in the course and outcome of TBI. Following the primary injury, extensive and lasting damage is sustained through a complex cascade of events referred to as "secondary injury." Neuroinflammation is proposed as an important manipulable aspect of secondary injury in animal and human studies. Because neuroinflammation can be detrimental or beneficial, before developing immunomodulatory therapies, it is necessary to better understand the timing and complexity of the immune responses that follow TBI. With a rapidly increasing body of literature, there is a need for a clear summary of TBI neuroimmunology. This review presents our current understanding of the immune response to TBI in a chronological and compartment-based manner, highlighting early changes in gene expression and initial signaling pathways that lead to activation of innate and adaptive immunity. Based on recent advances in our understanding of innate immune cell activation, we propose a new paradigm to study innate immune cells following TBI that moves away from the existing M1/M2 classification of activation states toward a stimulus- and disease-specific understanding of polarization state based on transcriptomic and proteomic profiling.

Barraquer-Simons Syndrome.

BACKGROUND: Barraquer-Simons syndrome (BSS) is a rare acquired lipodystrophy characterized by gradually symmetric subcutaneous fat loss in a craniocaudal distribution, associated with hypocomplementemia, diabetes and hypertriglyceridemia. Few investigators have studied body fat distribution with cross-sectional imaging techniques. METHODS: We present 2 cases of BSS with emphasis on phenotypic analysis through cross-sectional imaging. RESULTS: For the first time, we demonstrate bone marrow involvement and deep cervical and axillary fat sparing of Barraquer-Simons using magnetic resonance imaging. CONCLUSION: Phenotypic analysis in lipodystrophies such as Barraquer-Simons is an essential guide for future experiments. Therefore, careful analysis of cross-sectional imaging should be conducted in future studies as areas of involvement or fat sparing may be overlooked. The major contributions of our work are that this is the first time that deep cervical or nuchal and axillary fat sparing and bone marrow involvement has been documented in BSS.

Lyme meningo-radiculitis responsive to oral doxycycline therapy in the USA.

The spirochete strains that cause Lyme disease are different between the USA and Europe. This leads not only to a variation in clinical presentations, but it was also thought to alter responsiveness to antibiotic treatment. Unlike in Europe, in the USA there are no head-to-head trials of oral and intravenous antibiotics in the treatment of neuroborreliosis. Guidelines from the American Academy of Neurology (AAN) state that oral doxycycline is probably safe and effective in treating neuroborrliosis without parenchymal involvement, this was mainly extrapolated from European studies data with no reports from North America. To the best of our knowledge, this is the first reported case of Lyme meningo-radiculitis successfully treated with oral doxycycline alone in the USA. This comes in support of the oral doxycycline as an initial and even monotherapy for non-parenchymal Lyme disease of the nervous system in the USA.