A 19-year-old woman developed memory loss followed by psychosis, coma, convulsion, and central hypoventilation requiring mechanical ventilation. MRI of the brain showed minimal changes, and SPECT imaging revealed a small region of increased uptake in the cortex. Intravenous acyclovir and high-dose corticosteroids were administered without any effect. An extensive work-up revealed an elevated serum alpha-fetoprotein (AFP) concentration and the presence of an ovarian tumor. Following resection of the tumor, an immature teratoma by pathology, the patient had significant recovery of her cognitive function with some psychotic sequela. Serum anti-neuronal antibody (anti-Hu) was negative both by immunohistochemistry and by Western blot analysis. A rare combination of paraneoplastic limbic encephalitis and brainstem encephalitis was the suspected diagnosis. Because the tumor contained a neuronal component, we propose an immunologic cross-reaction as the pathomechanism, but the lack of a specific antibody may suggest cell-mediated rather than globulin-mediated immunity.

Paraneoplastic neuropathy can be characterized into two groups by the presence of sensory ataxia or severe spontaneous pain and severe mechanical hyperalgesia. Preferential small myelinated and unmyelinated fiber loss correlated to the cases of severe pain.

The occurrence and topographic analysis of granulovacuolar degeneration (GVD) in the hippocampal cortex of mentally normal controls (75 cases) and patients with Alzheimer's dementia (AD; 17 cases which included Alzheimer's disease and senile dementia of Alzheimer type), multi-infarct dementia (MID; 16 cases), Pick's disease (PD; 5 cases) and atypical dementia [5 cases; non-Alzheimer, non-Pick dementia with Fahr's syndrome (NANPDF)] were investigated. GVD was rarely found in control cases below the age of 60 years. In elderly normal brains, the statistically most representative ranking order of predilection for GVD (in decreasing severity) was: in the 60 s, CA1 > prosubiculum > CA2 (no GVD was found in the CA3 and CA4); in the 70 s, CA1 > prosubiculum > CA2 > CA3 > CA4; in the 80 s, CA1 > prosubiculum > CA2 > CA3 > CA4; in the 90 s, CA1 > prosubiculum > CA2 > CA3 > CA4. In the brains of demented patients, the rank order for GVD was: for AD, CA1 > CA2 > CA3 > prosubiculum > CA4; for MID, CA1 > prosubiculum > CA2 > CA3 > CA4; for PD, CA1 > CA2 > CA3 > prosubiculum > CA4; and for atypical dementia (NANPDF), CA1 > CA2 > prosubiculum > CA3 > CA4. The similarity of the predilection to ranking order was noted both in normal aged subjects and in MID as well as both in AD and in PD.(ABSTRACT TRUNCATED AT 250 WORDS)

We have recently demonstrated by immunohistochemistry that amyloid beta 2-microglobulin (beta 2m) is modified with advanced glycation end products (AGEs) in dialysis-related amyloidosis (DRA). To further investigate the role of the Maillard reaction in the pathogenesis of DRA, we produced a monoclonal antibody to imidazolone, a novel AGE, and a reaction product of arginine and 3-deoxyglucosone (3-DG) which was accumulated in uremic serum. Then we determined the localization of imidazolone in the amyloid tissues by immunohistochemistry using the antibody. The connective tissues in carpal tunnel and ligamentum flavum were obtained from six patients with carpal tunnel syndrome and two patients with destructive spondyloarthropathy. Imidazolone was localized to all the beta 2m-positive amyloid deposits in these patients. Western blotting using the antibody demonstrated that beta 2m extracted from the synovium amyloid of hemodialysis patients was modified with imidazolone. Further, beta 2m isolated from the blood ultrafiltrate of hemodialyzed patients was also modified with imidazolone. In vitro incubation of beta 2m with 3-DG produced imidazolone-modified beta 2m. In conclusion, amyloid tissue beta2m is modified with imidazolone in patients with DRA. 3-DG accumulating in uremic serum may be involved in the modification of beta 2m with imidazolone.