Search

Introduction: Indications for autoantibody testing in patients with rapid-onset cognitive impairment have expanded in step with the growing number of disease-associated autoantibodies and clinical syndromes. Although increased access to autoantibody testing has broadened our understanding of the spectrum of autoimmune encephalitis (AE), it has also produced new challenges associated with deciphering the contributions of disease-associated autoantibodies in patients with atypical clinical features and/or multiple autoantibodies. These challenges are illustrated through presentation of a patient with AE associated with autoantibodies against intracellular and cell-surface neuronal antigens. The implications of detection of multiple autoantibodies are considered in the context of relevant literature, and used to frame a diagnostic and therapeutic approach., Case Report: A previously well 67-year-old man presented with encephalopathy and psychosis, impaired visual fixation, and ataxia, emerging over 3 months. Hu, CRMP-5, and NMDAR autoantibodies were identified in the cerebrospinal fluid. No malignancy was discovered despite extensive investigations. An aggressive course of immunotherapy temporarily stabilized his course; however, the patient succumbed to his illness 10 months after symptom onset. Lack of sustained response to immunotherapy and neuropathologic findings suggested that AE associated with Hu antibodies was primarily responsible for this patient's progressive decline., Conclusions: Multiple autoantibodies may be detected in patients with AE. When antibodies targeting intracellular and cell-surface antigens are detected together, investigation and treatment of syndromes associated with intracellular antibodies should be prioritized, acknowledging the link between these antibodies and irreversible neuronal injury. In paraneoplastic cases, prognosis may be tied to early detection and treatment of the underlying malignancy.

A 22-year-old woman gradually developed depression, dementia, and chorea over an 8-month period. She fulfilled the criteria for the primary antiphospholipid antibody syndrome but not those for systemic lupus erythematosus. Her chorea and neurobehavioral deficits responded favorably to a regimen of prednisone, hydroxychloroquine, and aspirin. This appears to be the first report of a patient with a lupus anticoagulant and reversible dementia. The response to immunosuppressive therapy implies an antibody-mediated condition similar to Sydenham's chorea.

We determined the gene frequencies for the alleles of the HLA-linked complement markers C2, properdin factor B (BF), C4A (Rodgers) and C4B (Chido), and the red cell enzyme glyoxalase-I in 38 unrelated patients with senile dementia of the Alzheimer type, 42 patients with idiopathic Parkinson's disease, and 59 unaffected, aged-matched control blood donors. In senile dementia of the Alzheimer type and in Parkinson's disease, no significant difference was found in the gene frequencies of alleles at either the BF, C2, or GLO-I locus compared with those of age-matched controls. In senile dementia of the Alzheimer type, a striking increase in the frequency of the rare C4B locus allele, C4*B2, was apparent, resulting in the high relative risk of RR = 8.8 (p less than 0.0001) for this disorder.

Antibodies to negatively charged phospholipids including cardiolipin have been recognized in the sera of patients with systemic lupus erythematosus and other disorders. We report 4 patients who experienced cerebral infarctions and dementia in association with anticardiolipin antibodies. These patients did not have the characteristic lupus anticoagulant or systemic lupus erythematosus. The occurrence of anticardiolipin antibodies in patients with multiple cerebral infarctions who do not have evidence of a systemic vasculitis or inflammatory condition suggests that this association may be more common than previously recognized. It may be useful to test for the presence of anticardiolipin antibodies in patients who have unexplained cerebral infarctions.

We compared patients with senile dementia of the Alzheimer's type (SDAT) and age-matched controls with respect to T8+-cell-mediated suppressor function using a pokeweed mitogen (pwm)-induced IgG secretion assay. The responding B cells were allogeneic to the T-regulator cells. T8+-cell-mediated suppression was lower in SDAT patients than the controls when we used either 2 X 10(4) or 5 X 10(4) T8+ cells. Suppressor function was lower in both SDAT and elderly controls than in young adults. SDAT patients and controls did not differ with regard to T4+-cell-mediated helper activity. In SDAT patients, there seems to be an exaggeration of the age-related decline in suppressor-cell function. Whether such changes reflect accelerated changes of intrinsic lymphocyte properties or aberrant neural influences on lymphocytes remains to be resolved.

The frequency of antinuclear antibodies was evaluated in older men and women aged 60 to 100 years with presumptive diagnoses of chronic brain syndrome or dementing illness. Thirteen per cent of the women and none of the men with organic brain syndrome had positive titers, compared to 3% for older men and women aged 60 to 89 years evaluated in a medical clinic population. It would appear to be valuable to evaluate the significance of antinuclear antibodies and other autoantibodies in the pathogenesis of dementing illness in the elderly.