Since coronavirus disease-2019 (COVID-19) outbreak in January 2020, several pieces of evidence suggested an association between the spectrum of Guillain-Barré syndrome (GBS) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Most findings were reported in the form of case reports or case series, whereas a comprehensive overview is still lacking. We conducted a systematic review and searched for all published cases until July 20th 2020. We included 73 patients reported in 52 publications. A broad age range was affected (mean 55, min 11-max 94 years) with male predominance (68.5%). Most patients showed respiratory and/or systemic symptoms, and developed GBS manifestations after COVID-19. However, asymptomatic cases for COVID-19 were also described. The distributions of clinical variants and electrophysiological subtypes resemble those of classic GBS, with a higher prevalence of the classic sensorimotor form and the acute inflammatory demyelinating polyneuropathy, although rare variants like Miller Fisher syndrome were also reported. Cerebrospinal fluid (CSF) albuminocytological dissociation was present in around 71% cases, and CSF SARS-CoV-2 RNA was absent in all tested cases. More than 70% of patients showed a good prognosis, mostly after treatment with intravenous immunoglobulin. Patients with less favorable outcome were associated with a significantly older age in accordance with previous findings regarding both classic GBS and COVID-19. COVID-19-associated GBS seems to share most features of classic post-infectious GBS and possibly the same immune-mediated pathogenetic mechanisms. Nevertheless, more extensive epidemiological studies are needed to clarify these issues.

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In 2018, the FDA authorized the use of a blood test for glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in mild traumatic brain injury (mTBI), crowning a long success story of CNS-driven blood biomarker development [1][2][3] . Initial efforts to identify fluid biomarkers for neurological diseases focused on the cerebrospinal fluid (CSF) as, compared with blood, CSF is closer to the brain extracellular space and contains higher concentrations of CNS-derived proteins 4 . The establishment of fourth-generation immune assays in the last decade 3,5 brought the possibility of quickly obtaining rapid and robust protein biomarker measurements from blood samples, opening up new perspectives in the field of CNS-derived markers. For example, levels of classic CSF biomarkers of neuroaxonal damage, such as neurofilament light chain (NfL) 5 , phosphorylated tau 217 (ref. 6), and UCH-L1 (ref. 7 ) can now be readily quantified in blood, indicating that these markers hold potential for use in diagnosis and monitoring of disease activity, and as surrogate end points for treatment trials. The literature on the utility of blood GFAP as a biomarker is also growing, reinforcing the large body of published data on CSF GFAP 3,[8][9][10][11][12][13][14] . The evaluation of blood levels of GFAP has the potential to enable the in vivo longitudinal evaluation of different aspects of the astrocytic response in several neurological disorders. Here, we provide an up-to-date review of the analytical aspects, current evidence, perspectives, and limitations of blood GFAP as a biomarker, with the purpose of outlining how to refine its application in the diagnosis and monitoring of neurological diseases. GFAP biology and analysisAstrocytes represent around 30-40% of the cells in the CNS 15 , form an integral part of the blood-brain barrier (BBB) and establish numerous interactions with other cells in the nervous system, including neurons.

The differential diagnosis of Creutzfeldt-Jakob disease (CJD) from other, sometimes treatable, neurological disorders is challenging, owing to the wide phenotypic heterogeneity of the disease. Real-time quaking-induced prion conversion (RT-QuIC) is a novel ultrasensitive in vitro assay, which, at variance with surrogate neurodegenerative biomarker assays, specifically targets the pathological prion protein (PrPSc). In the studies conducted to date in CJD, cerebrospinal fluid (CSF) RT-QuIC showed good diagnostic sensitivity (82–96%) and virtually full specificity. In the present study, we investigated the diagnostic value of both prion RT-QuIC and surrogate protein markers in a large patient population with suspected CJD and then evaluated the influence on CSF findings of the CJD type, and the associated amyloid-β (Aβ) and tau neuropathology. RT-QuIC showed an overall diagnostic sensitivity of 82.1% and a specificity of 99.4%. However, sensitivity was lower in CJD types linked to abnormal prion protein (PrPSc) type 2 (VV2, MV2K and MM2C) than in typical CJD (MM1). Among surrogate proteins markers (14-3-3, total (t)-tau, and t-tau/phosphorylated (p)-tau ratio) t-tau performed best in terms of both specificity and sensitivity for all sCJD types. Sporadic CJD VV2 and MV2K types demonstrated higher CSF levels of p-tau when compared to other sCJD types and this positively correlated with the amount of tiny tau deposits in brain areas showing spongiform change. CJD patients showed moderately reduced median Aβ42 CSF levels, with 38% of cases having significantly decreased protein levels in the absence of Aβ brain deposits. Our results: (1) support the use of both RT-QuIC and t-tau assays as first line laboratory investigations for the clinical diagnosis of CJD; (2) demonstrate a secondary tauopathy in CJD subtypes VV2 and MV2K, correlating with increased p-tau levels in the CSF and (3) provide novel insight into the issue of the accuracy of CSF p-tau and Aβ42 as markers of brain tauopathy and β-amyloidosis.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-017-1683-0) contains supplementary material, which is available to authorized users.