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Introduction: A beta-related angiitis (ABRA) is a very rare disease entity with combined features of cerebral amyloid angiopathy and primary angiitis of the CNS. However, the pathogenesis has not been conclusively described yet. Interestingly though, a possible paraneoplastic origin has been reported in the past. ABRA leads to severe encephalopathy with a broad spectrum of unspecific neurological symptoms and usually occurs in older patients. Because of the response to immunological treatment, it is important to confirm the diagnosis as fast as possible. Unfortunately, the pathway to a definite diagnosis is often complicated and prolonged. Case Report: Here, we describe a 48-year-old-female patient presenting headache, behavioral changes as well as subacute fatigue and epileptic seizures in the recent past. The initial neuroradiological examination demonstrated extended lesions in the left hemisphere compatible with an inflammatory or neoplastic disease. After extensive investigations, initially without a definite result, we finally validated the diagnosis of ABRA by brain biopsy. Shortly afterwards a routine check-up revealed an invasive mammary carcinoma. Owing to a mandatory mastectomy and chemotherapy, an immunosuppressive therapy was not implemented. Conclusions: The reported case demonstrates our diagnostic approach and the clinical difficulties in validating a rare cause of encephalopathy in a young patient with nonspecific clinical and neuroradiological findings. Because of the possibility of an effective treatment, it is important to consider ABRA in the differential diagnosis especially when blood tests, analysis of cerebrospinal fluid, and angiography show normal results. Since a paraneoplastic genesis is presumed, a search for an underlying tumor disease should be considered.

In neuron-specific ovalbumin-transgenic CKTAC mice, antigen-specific OT-I CD8 T cells home to the enteric nervous system, where they attack and destroy neurons of the myenteric and submucosal plexus. Clinically, experimental autoimmune enteric ganglionitis (EAEG) manifests with gastrointestinal dysmotility and rapidly progresses to lethal ileus. Although interferon-g has been identified as capable of damaging neurons in EAEG, the role of perforin, Fas/FasL, and tumor necrosis factor-alpha (TNF-alpha) in this disease is still a matter of debate. Thus, CKTAC mice were adoptively transferred with either perforin(-/-) or wild-type OT-I CD8 T cells. In addition, CKTAC mice that had received wild-type OT-I CD8 T cells were treated by either anti-TNF-alpha or anti-FasL. Furthermore, wild-type OT-I CD8 T cells were adoptively transferred into CKTAC mice with neuron-specific deletion of Fas. Although neither inactivation of enteric neuronal Fas nor anti-FasL treatment improved the disease, the absence of perforin from OT-I CD8 T cells and anti-TNF-alpha treatment significantly ameliorated EAEG and prevented lethal ileus by rescue of enteric neurons. Thus, these experiments identify perforin and TNF-alpha as important in the pathogenesis of EAEG.