The majority of patients continue to have recurrent vertigo in the long-term evolution of VM, and the impact of vertigo may remain severe. Whereas interictal ocular motor abnormalities may show some variation over time, vestibulo-cochlear dysfunction progresses slowly in some patients with VM. Interictal central-type PN may help distinguish VM from peripheral vestibular disorders such as Ménière disease.

Immunological mechanisms and therapy approaches in psychotic syndromes were recently supported by the discovery of autoantibody-associated limbic and non-limbic encephalitis. However, how clinical diagnostic procedures in psychiatry should be adapted to these new insights is still unclear. In this study, we analyzed the cerebrospinal fluid (CSF) and neuroimmunological alterations and their association with cerebral MRI (cMRI) and electroencephalographic (EEG) findings. From 2006 to 2013, we acquired 180 CSF samples from psychotic patients. Between 2006 and 2009, CSF examinations were only performed in cases in which organic brain disease was suspected. Since then, this procedure has been integrated into our routine diagnostic workup. CSF basic diagnostics were supplemented by measuring antineuronal antibodies against intracellular synaptic antigens, antibodies against intracellular onconeural antigens, antibodies against neuronal cell surface antigens and thyroid antibodies. In addition, cMRIs and EEGs were conducted. We found white cell counts elevated in 3.4% of the cases, albumin quotient elevated in 21.8%, and protein concentration elevated in 42.2%. Evidence of intrathecal immunoglobulin synthesis was found in 7.2% of the cases. Antibodies measured against neuronal cell surface antigens were positive in 3.2%. Reactivity on antibodies against intracellular onconeural antigens were detected in 3.5%. Serum thyroid antibodies were elevated in 24.7%. Abnormalities were found in 39.5% of cMRIs and in 34.3% of EEGs. The main finding of our study was the high prevalence of CSF and autoantibody abnormalities in 54.4% of psychotic patients. In combination with cMRIs and EEGs, 75.6% showed abnormal findings. Our results are discussed with regard to the concept of immunological encephalopathy. Future studies should analyze the efficacy of immunomodulatory therapies.

Although VM diagnosis lacks a gold standard for evaluation of diagnostic criteria, repeated comprehensive neurotological evaluation after a long follow-up period indicates not only high reliability but also high validity of presented clinical criteria (positive predictive value 85%). Half of patients with pVM evolve to meet criteria for dVM. However, in a subgroup of VM patients with hearing loss, criteria for dVM and MD are not sufficiently discriminative.

Background: In progressive multiple sclerosis (MS), glial activation is thought to be a relevant mechanism of disability progression. Therefore, in vivo assessment of the glial cell activity is, in the emerging treatment era of primary progressive MS (PPMS), more important than ever. Objectives: To test the association of cerebrospinal fluid (CSF) and serum markers of glial activation in PPMS patients; including glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (CHI3L1), soluble variant of triggering receptor expressed on myeloid cells 2 (sTREM2), and marker of neuroaxonal damage (Neurofilament light chain, NfL) as well as clinical severity. Methods: CSF and serum samples from PPMS patients were collected in the MS-centers at Universities of Freiburg ( n = 49), Ulm ( n = 27), Muenster ( n = 11), and Rostock ( n = 6). sTREM2 and CHI3L1 levels were measured using the previously reported ELISA assays, while NfL and GFAP were measured using SIMOA assays. Clinical data included age, gender, disease duration, treatment status, and Expanded Disability Status Scale (EDSS). Results: 93 CSF samples and 71 matching serum samples were analyzed. The median age of patients was 49 years and disease duration 4.5 years. GFAP serum correlated with EDSS after correction for age (β = 0.3, p = 0.001). Furthermore, EDSS was higher in patients with a GFAP serum level ≥ 151.7 pg/ml compared to patients with GFAP serum below this cut-off (5.5 vs. 4.0, p = 0.009). Other markers did not correlate with the clinical severity. Moreover, we found a correlation between NfL CSF and GFAP CSF , sTREM2 and CHI3L1 (ρ = 0.4 for GFAP CSF and sTREM2, ρ = 0.3 for CHI3L1, p < 0.01 for sTREM2 and CHI3L1 and <0.001 for GFAP CSF ). CHI3L1 did not correlate with GFAP CSF but with sTREM2 (ρ = 0.4, p < 0.01). Discussion: The correlation between the glial activation markers in CSF with the markers of neuroaxonal demise supports the notion of the glial involvement in PPMS. The positive correlation between GFAP CSF with disease duration and GFAP serum with the clinical severity of the disease may highlight a particular role of the astrocytes in PPMS and mark the potential of GFAP serum as a disease severity marker.

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