A patient with cerebral Whipple disease with gastric involvement but no gastrointestinal symptoms: a consequence of local protective immunity?

Whipple disease is a granulomatous infectious disease caused by Tropheryma whipplei. The bacteria accumulate within macrophages, preferentially in the intestinal mucosa. Disease manifestation seems to be linked to immunological abnormalities of macrophages. We describe a patient with cerebral Whipple disease who presented with changes in mental status, confusion, inverse sleep-wake cycle, bilateral ptosis and vertical gaze palsy. Endoscopic biopsy sampling revealed Whipple disease in the gastric antrum but not in the duodenum. Whole blood stimulation displayed reactivity to T. whipplei that was at the lower end of healthy controls while reactivity of duodenal lymphocytes was not diminished. We propose that in cases of neurological symptoms suspicious of Whipple disease with normal duodenal and jenunal findings, biopsy sampling should be extended to the gastric mucosa. The robust reactivity of duodenal lymphocytes may have prevented our patient from developing small bowel disease, whereas the impaired reactivity in peripheral blood lymphocytes might yet explain the bacterial spreading to the central nervous system leading to the rare case of predominant neurological symptoms without relevant systemic involvement.

Neuromyelitis optica in a patient with an early onset demyelinating episode: clinical and autoantibody findings.

Recent clinical and laboratory findings have substantially advanced our understanding of neuromyelitis optica (NMO) as a humorally mediated, autoimmune disorder. We report on a patient who suffered a first episode of transverse myelitis at the age of 6 months following diphtheria-pertussis-tetanus (DPT) vaccination which had therefore been considered suggestive of acute disseminated encephalomyelitis (ADEM). Fifteen years later, the further disease course revealed typical NMO meeting all diagnostic criteria. This development points to a broad clinical and temporal heterogeneity of NMO, with ADEM probably occurring in the context of a shared autoimmune diathesis. Despite therapy response following B-cell depletion by rituximab, positive NMO-IgG autoantibody status remained unchanged, whereas direct testing for anti-aquaporin-4 (AQP-4)-antibodies was negative throughout. Our findings challenge the pathogenic relevance of NMO-IgG and indicate a varying diagnostic value of testing for NMO-IgG and AQP-4-autoantibodies.

Elevated Bcl-X(L) levels correlate with T cell survival in multiple sclerosis.

T cell resistance towards apoptotic elimination by activation-induced cell death (AICD) might be a crucial pathogenic feature of multiple sclerosis (MS). Since the Bcl-2 family is critically involved in the regulation of apoptosis, we investigated the protein expression of Bcl-2, Bcl-X(L), and Bax in peripheral blood mononuclear cells (PBMC) of 23 MS patients and 29 control subjects. An in vitro model of AICD, which exemplifies the elimination of antigen-reactive T cells in vivo, was used as an indication of T cell susceptibility or resistance towards apoptosis. Increased expression of the survival factor Bcl-X(L), which directly correlated with a resistance towards AICD, was observed in peripheral immune cells of MS patients. In contrast to Bcl-X(L), no differences were found in the protein expression of Bcl-2 and Bax between patients and controls. Our data indicate that the anti-apoptotic factor Bcl-X(L), responsible for T cell resistance towards apoptosis, might be an important factor in the MS pathogenesis and a potential target for therapeutic intervention.

Improvement of paraneoplastic limbic encephalitis after systemic treatment with rituximab in a patient with B-cell chronic lymphocytic leukemia.

Limbic encephalitis is an inflammatory disease of the central nervous system characterized by diverse neurologic symptoms including mnestic disturbances, hallucinations, and seizures as well as behavioral symptoms like depression, personality changes, and acute confusional states resembling dementia. Several antibodies have been described in the pathogenesis of limbic encephalitis. It is often a paraneoplastic syndrome associated with small cell lung cancer, breast cancer, or Hodgkin's lymphoma among others. Here, we report a patient with B-cell chronic lymphocytic leukemia (B-CLL), presenting with otherwise unexplained neurologic symptoms consistent with limbic encephalitis. Despite intensive diagnostic procedures, no causing agent could be identified. Pleocytosis consisting of T cells was detected in the cerebrospinal fluid (CSF). We initiated anti-B-cell therapy with Rituximab for B-CLL with quick and durable resolution of symptoms. We speculate that disruption of interaction between autoreactive T and malignant B cells is responsible for the therapeutic effect of Rituximab.

Granulomatous tissue response in germinoma, a diagnostic pitfall in endoscopic biopsy.

We report a case of a 24-year-old man with a right thalamic germinoma that initially mimicked a granulomatous inflammation, compatible with neurosarcoidosis based on clinical symptoms, imaging results and histology of an endoscopically navigated biopsy. A second biopsy, prompted by clinical course, and performed openly from parieto-lateral revealed the underlying germinoma, obscured in the first biopsy by a granulomatous tissue response, particularly at the tumor edge. The present case highlights granulomatous inflammatory tissue response on the tumor edge of germinoma as a tumor-immanent diagnostic challenge. This diagnostic problem is aggravated by stereotactic and endoscopic approaches. We conclude that granulomatous inflammation in a specimen obtained by biopsy of a midline lesion should always be considered for the differential diagnosis of germinoma. Stereotactic and endoscopic surgery should sample several different target points within the lesion. Because of tumor heterogeneity of germinoma, the open biopsy approach is advantageous compared to endoscopic or stereotactic techniques for germinoma and should be considered if a germinoma is in the differential diagnosis and if allowed by the clinical situation.

A novel subtype of Creutzfeldt-Jakob disease characterized by a small 6 kDa PrP fragment.

We report on a novel subtype of Creutzfeldt-Jakob disease with a single proteinase K-resistant prion protein fragment of about 6 kDa in Western blots of brain homogenates. Clinically this patient showed a progressive spastic disorder and dementia over 3 years. No mutation of the prion protein gene was found. Since this patient had received a blood transfusion, an iatrogenic cause, albeit unlikely, cannot be ruled out. Future studies will have to be attentive to small prion protein fragments, which may cause or be associated with unusual clinical disease that might possibly only be diagnosed by immunoblotting of brain homogenates.

Pilocytic astrocytoma presenting as primary diffuse leptomeningeal gliomatosis: report of a unique case and review of the literature.

We describe a 25-year-old male patient with primary diffuse leptomeningeal gliomatosis (PDLG) presenting with gait ataxia, positive Lhermitte's sign, double vision, and right abducens nerve palsy. Spinal magnetic resonance imaging showed extended intradural, extramedullary, contrast-enhancing masses with compression of the myelon. Spinal leptomeningeal biopsy revealed a pilocytic astrocytoma WHO grade I. Despite chemotherapy with vincristin and carboplatin, the patient died 2 months after admission. A thorough autopsy showed no evidence for primary neoplasms in brain, spine and optic nerve. Sequence analysis of tumor protein 53 gene (TP53) revealed a missense mutation in exon 5, and expression of phosphatase and tensin homolog (mutated in multiple advanced cancers 1) (PTEN) protein was not detected, which may have contributed to astrocytoma development. To our knowledge, this is the first definitive case of pilocytic astrocytoma presenting as PDLG.