The pathogenesis of the fatal neurodegenerative condition amyotrophic lateral sclerosis (ALS) remains to be fully understood. Blood–brain barrier damage (BBBD) has been implicated as an exacerbating factor in several neurodegenerative conditions, including ALS. Therefore, this cross-sectional study used the novel D50 progression model to assess the clinical relevance of BBBD within a cohort of individuals with either ALS (n = 160) or ALS mimicking conditions (n = 31). Routine laboratory parameters in cerebrospinal fluid (CSF) and blood were measured, and the ratio of CSF to serum albumin levels (Qalb) was used as a proxy measure of BBBD. In the univariate analyses, Qalb levels correlated weakly with disease aggressiveness (as indicated by individual D50 values) and physical function (as measured by ALS Functional Rating Scale). However, after adjustment for cofactors in the elastic net regularization, only having limb-onset disease was associated with BBBD. The results reported here emphasize the clinical heterogeneity of ALS and the need for additional longitudinal and multi-modal studies to fully clarify the extent and effect of BBBD in ALS.

BackgroundNeurosarcodosis is one of the most frequent differential diagnoses of multiple sclerosis (MS) and requires central nervous system (CNS) biopsy to establish definite diagnosis according to the latest consensus diagnostic criteria. We here analyzed diagnostic values of basic cerebrospinal fluid (CSF) parameters to distinguish neurosarcoidosis from MS without CNS biopsy.MethodsWe retrospectively assessed clinical, radiological and laboratory data of 27 patients with neurosarcoidosis treated at our center and compared following CSF parameters with those of 138 patients with relapsing-remitting MS: CSF white cell count (WCC), CSF/serum albumin quotient (Qalb), intrathecal production of immunoglobulins including oligoclonal bands (OCB), MRZ reaction, defined as a polyspecific intrathecal production of IgG reactive against ≥2 of 3 the viruses measles (M), rubella (R), and zoster (Z) virus, and CSF lactate levels. Additional inflammatory biomarkers in serum and/or CSF such as neopterin, soluble interleukin-2 receptor (sIL-2R) and C-reactive protein (CRP) were assessed.ResultsThere was no significant difference in the frequency of CSF pleocytosis, but a CSF WCC > 30/μl was more frequent in patients with neurosarcoidosis. Compared to MS, patients with neurosarcoidosis showed more frequently an increased Qalb and CSF lactate levels as well as increased serum and CSF levels of sIL-2R, but a lower frequency of intrathecal IgG synthesis and positive MRZ reaction. Positive likelihood ratio (PLR) of single CSF parameters indicating neurosarcoidosis was highest, if (a) CSF WCC was >30/μl (PLR 7.2), (b) Qalb was >10 × 10−3 (PLR 66.4), (c) CSF-specific OCB were absent (PLR 11.5), (d) CSF lactate was elevated (PLR 23.0) or (e) sIL-2R was elevated (PLR>8.0). The combination of (a) one of three following basic CSF parameters, i.e., (a.1.) CSF WCC >30/ul, or (a.2.) QAlb >10 × 10−3, or (a.3.) absence of CSF-specific OCB, and (b) absence of positive MRZ reaction showed the best diagnostic accuracy (sensitivity and specificity each >92%; PLR 12.8 and NLR 0.08).ConclusionCombined evaluation of basic CSF parameters and MRZ reaction is powerful in differentiating neurosarcoidosis from MS, with moderate to severe pleocytosis and QAlb elevation and absence of intrathecal IgG synthesis as useful rule-in parameters and positive MRZ reaction as a rule-out parameter for neurosarcoidosis.

Zusammenfassung. Die Frühsommer-Meningoenzephalitis (FSME) ist eine akute entzündliche Erkrankung des zentralen Nervensystems, die durch Zecken übertragen und durch das FSME-Virus verursacht wird, das in immer mehr Teilen Europas und Asiens vorkommt. Nur 2–30% der Infektionen verlaufen symptomatisch, dabei ist im Prodromalstadium ein zweigipfliger Fieberverlauf typisch. Klinisch-neurologisch entwickeln 50% der Fälle eine Meningitis, 40% eine Meningoenzephalitis und 10% eine Meningoenzephalomyelitis. Letztere ist häufig mit einer gefürchteten Beteiligung des Hirnstamms vergesellschaftet. Bei der Enzephalitis stehen Bewusstseinsstörungen, Fatigue, emotionale Labilität und neurokognitive Defizite im Vordergrund, bei der Myelitis schlaffe Paresen an Armen oder Beinen. Zur Diagnosesicherung ist der gleichzeitige Nachweis FSME-spezifischer IgM- und IgG-Antikörper im Serum und eines passenden entzündlichen Liquorsyndroms erforderlich. Die Meningitis heilt ohne Folgen aus, 80% der Fälle von Enzephalitis und nur 20% der Fälle von Myelitis erholen sich vollständig. Die Gesamtletalität liegt bei 1%. Bei immungeschwächten, älteren und myelitischen Patienten besteht ein höheres Risiko für einen schweren Krankheitsverlauf und eine höhere Sterblichkeit. Da keine spezifische antivirale Therapie zur Verfügung steht, bleibt die aktive FSME-Impfung für alle Menschen ab 6 Jahren mit Aufenthalt in Risikogebieten die wichtigste Präventivmassnahme.