Limbic encephalitis due to GABAB and AMPA receptor antibodies: a case series.

BACKGROUND: Two novel antibodies (abs) directed to γ-aminobutyric acid B receptor (GABA(B)R) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in patients with limbic encephalitis (LE) were first described by the Philadelphia/Barcelona groups and confirmed by the Mayo group. We present a novel series for further clinical and paraclinical refinement. METHODS: Serum and cerebrospinal fluid samples from a diagnostic laboratory were selected if found to be positive for GABA(B)R or AMPAR abs within a broad antineuronal ab panel. Data were retrospectively compiled. RESULTS: In 10 patients, we detected abs to GABA(B)R. Median age was 70 years. Five of them were diagnosed with small cell lung cancer (SCLC). Intrathecal GABA(B)R ab synthesis was found in all six patients with sufficient data available (median ab-index: 76.8). On MRI, we found bilateral mediotemporal and in two cases cortical abnormalities. EEG revealed encephalopathy, partly with epileptiform discharges. Five patients received immunotherapy, two patients tumour treatment and three both therapies. Three patients died, in five patients cognitive functions declined, one patient improved slightly and one patient fully recovered. AMPAR abs were detected in three patients with mnestic disturbances. Median age was 60.7 years. The only female patient was diagnosed with ovarian cancer. None of the patients had intrathecal ab synthesis. MRI findings showed bilateral mediotemporal abnormalities. EEG was normal in all patients. Two of the three immunologically treated patients improved, one patient stabilised on a low level. DISCUSSION: GABA(B)R and AMPAR abs are well associated with LE. GABA(B)R abs lead to severe clinical, neuroradiological and EEG abnormalities with poorer outcome.

CSF analysis in patients with sporadic CJD and other transmissible spongiform encephalopathies.

Patients with suspected Creutzfeldt-Jakob disease (CJD) often have routine cerebrospinal fluid (CSF) analysis performed to exclude treatable inflammatory conditions; however, little information is available about the range of results obtained for CSF tests in patients with sporadic CJD and other transmissible spongiform encephalopathies (TSE). Data from 450 patients with sporadic CJD and 47 patients with other TSEs were collected as part of an EC-supported multinational study. Raised white cell counts of >5 cells/microl were found in three of 298 patients with sporadic CJD, with two cell counts of 7 cells/microl and one of 20 cells/microl. Total protein concentrations of >0.9 g/l were found in five of 438 patients with sporadic CJD, although none had a concentration of >1 g/l. CSF oligoclonal IgG was detected in eight of 182 sporadic CJD patients. Of the patients with other TSEs, six had elevated cell counts ranging from 6 to 14 cells/microl but none had total protein concentrations of >0.9 g/l and one patient had detectable oligoclonal IgG. None of the patients with sporadic CJD or other TSEs had abnormalities in all three tests.

CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease.

OBJECTIVES: To analyze the diagnostic sensitivity and specificity of various brain-derived proteins (14-3-3, Tau, neuron specific enolase [NSE], and S100b) in the CSF of patients with Creutzfeldt-Jakob disease (CJD) and to analyze biologic factors that modify these parameters. METHODS: CSF was tested for 14-3-3, Tau, NSE, and S100b in 1,859 patients with sporadic, genetic, iatrogenic, and variant CJD, and in 1,117 controls. RESULTS: The highest sensitivity was achieved for 14-3-3 and Tau in sporadic CJD (85% and 86%), and a combined determination of 14-3-3 and Tau, S100b, or NSE increased the sensitivity to over 93%. A multivariate analysis showed that the sensitivity of all tests was highest in patients with the shortest disease duration, age at onset >40 years, and homozygosity at codon 129 of the prion protein gene. In a group of patients with repeated lumbar punctures, a second test also increased the diagnostic sensitivity. CONCLUSIONS: The detection of elevated levels of brain-derived proteins in the CSF in patients with suspected Creutzfeldt-Jakob disease is a valuable diagnostic test. A second lumbar puncture may be of value in patients with atypical clinical course in whom the first test was negative.