Explore the vast range of titles available.

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.

Tear fluid is receiving growing attention as a source for novel diagnostic biomarkers. Multiple techniques are available for its collection and impact the composition of acquired samples. We sought to provide a direct comparison of two collection methods with regard to implementation, acceptance, and impact on sample composition. Tear fluid was collected from fifteen healthy volunteers with capillary tubes and Schirmer strips and analyzed for total protein and IgG concentrations. Sampling parameters and perception by test persons were compared. The use of capillary tubes was more convenient for the participants while causing more effort for the collector. Tear flow rates as well as the relative and absolute amount of IgG were higher when Schirmer strips were used. Consecutive collections with Schirmer strips significantly influenced tear flow rates, IgG, and protein concentrations. A moderate correlation was observed between tear flow rates and IgG concentrations for both methods. Samples collected with both methods can be analyzed by isoelectric focusing, a potential diagnostic application in the field of neurology. The specific advantages and limitations of tear fluid sampling with either capillary tubes or Schirmer strips demonstrate the need for a thorough investigation of collection methods with regard to the application of interest.

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, and Switzerland).

ObjectiveTo determine the diagnostic and prognostic performance of serum neurofilament light chain (NFL) in amyotrophic lateral sclerosis (ALS).MethodsThis single-centre, prospective, longitudinal study included the following patients: 124 patients with ALS; 50 patients without neurodegenerative diseases; 44 patients with conditions included in the differential diagnosis of ALS (disease controls); 65 patients with other neurodegenerative diseases (20 with frontotemporal dementia, 20 with Alzheimer’s disease, 19 with Parkinson’s disease, 6 with Creutzfeldt-Jakob disease (CJD)). Serum NFL levels were measured using the ultrasensitive single molecule array (Simoa) technology.ResultsSerum NFL levels were higher in ALS in comparison to all other categories except for CJD. A cut-off level of 62 pg/mL discriminated between ALS and all other conditions with 85.5% sensitivity (95% CI 78% to 91.2%) and 81.8% specificity (95% CI 74.9% to 87.4%). Among patients with ALS, serum NFL correlated positively with disease progression rate (rs=0.336, 95% CI 0.14 to 0.506, p=0.0008), and higher levels were associated with shorter survival (p=0.0054). Serum NFL did not differ among patients in different ALS pathological stages as evaluated by diffusion-tensor imaging, and in single patients NFL levels were stable over time.ConclusionsSerum NFL is increased in ALS in comparison to other conditions and can serve as diagnostic and prognostic biomarker. We established a cut-off level for the diagnosis of ALS.

Background The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. Objective To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. Methods Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). Results Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. Conclusion This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.

The description of every possible adverse effect or event related to vaccines is mandatory during the ongoing worldwide COVID-19 vaccination program. Although cases of cutaneous varicella zoster virus (VZV) reactivation after COVID-19 vaccination have been increasingly reported in literature and database sets, a description of VZV-induced neurological disease (VZV-ND) is still lacking. In the present study, we retrospectively evaluated patients admitted to our clinic and diagnosed with VZV-ND during the COVID-19 vaccination campaign (January–April 2021) and in the same months in the previous two years. We identified three patients with VZV-ND after COVID-19 vaccination and 19 unvaccinated VZV-ND cases as controls. In the case–control analysis, the two groups showed no difference in clinical features, results of diagnostic investigations, and outcome. Thus, VZV reactivation with neurological involvement might be a possible event triggered by COVID-19 vaccination, but the benefit following COVID-19 vaccination overcomes significantly the potential risk associated with a VZV reactivation.

Oligoclonal Ig bands (OCBs) of the cerebrospinal fluid are a hallmark of multiple sclerosis (MS), a disabling inflammatory disease of the central nervous system (CNS). OCBs are locally produced by clonally expanded antigen-experienced B cells and therefore are believed to hold an important clue to the pathogenesis. However, their target antigens have remained unknown, mainly because it was thus far not possible to isolate distinct OCBs against a background of polyclonal antibodies. To overcome this obstacle, we copurified disulfide-linked Ig heavy and light chains from distinct OCBs for concurrent analysis by mass spectrometry and aligned patient-specific peptides to corresponding transcriptome databases. This method revealed the full-length sequences of matching chains from distinct OCBs, allowing for antigen searches using recombinant OCB antibodies. As validation, we demonstrate that an OCB antibody from a patient with an infectious CNS disorder, neuroborreliosis, recognized a Borrelia protein. Next, we produced six recombinant antibodies from four MS patients and identified three different autoantigens. All of them are conformational epitopes of ubiquitous intracellular proteins not specific to brain tissue. Our findings indicate that the B-cell response in MS is heterogeneous and partly directed against intracellular autoantigens released during tissue destruction. In addition to helping elucidate the role of B cells in MS, our approach allows the identification of target antigens of OCB antibodies in other neuroinflammatory diseases and the production of therapeutic antibodies in infectious CNS diseases.

Background Comprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far. Objective To analyze systematically the CSF profile in COVID-19. Methods Retrospective analysis of 150 lumbar punctures in 127 patients with PCR-proven COVID-19 and neurological symptoms seen at 17 European university centers Results The most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.4 [6.72–50.8]), which was present in 58/116 (50%) samples from patients without pre-/coexisting CNS diseases (group I). QAlb remained elevated > 14d (47.6%) and even > 30d (55.6%) after neurological onset. CSF total protein was elevated in 54/118 (45.8%) samples (median 65.35 mg/dl [45.3–240.4]) and strongly correlated with QAlb. The CSF white cell count (WCC) was increased in 14/128 (11%) samples (mostly lympho-monocytic; median 10 cells/µl, > 100 in only 4). An albuminocytological dissociation (ACD) was found in 43/115 (37.4%) samples. CSF l -lactate was increased in 26/109 (24%; median 3.04 mmol/l [2.2–4]). CSF-IgG was elevated in 50/100 (50%), but was of peripheral origin, since QIgG was normal in almost all cases, as were QIgA and QIgM. In 58/103 samples (56%) pattern 4 oligoclonal bands (OCB) compatible with systemic inflammation were present, while CSF-restricted OCB were found in only 2/103 (1.9%). SARS-CoV-2-CSF-PCR was negative in 76/76 samples. Routine CSF findings were normal in 35%. Cytokine levels were frequently elevated in the CSF (often associated with BCB dysfunction) and serum, partly remaining positive at high levels for weeks/months (939 tests). Of note, a positive SARS-CoV-2-IgG-antibody index (AI) was found in 2/19 (10.5%) patients which was associated with unusually high WCC in both of them and a strongly increased interleukin-6 (IL-6) index in one (not tested in the other). Anti-neuronal/anti-glial autoantibodies were mostly absent in the CSF and serum (1509 tests). In samples from patients with pre-/coexisting CNS disorders (group II [ N  = 19]; including multiple sclerosis, JC-virus-associated immune reconstitution inflammatory syndrome, HSV/VZV encephalitis/meningitis, CNS lymphoma, anti-Yo syndrome, subarachnoid hemorrhage), CSF findings were mostly representative of the respective disease. Conclusions The CSF profile in COVID-19 with neurological symptoms is mainly characterized by BCB disruption in the absence of intrathecal inflammation, compatible with cerebrospinal endotheliopathy. Persistent BCB dysfunction and elevated cytokine levels may contribute to both acute symptoms and ‘long COVID’. Direct infection of the CNS with SARS-CoV-2, if occurring at all, seems to be rare. Broad differential diagnostic considerations are recommended to avoid misinterpretation of treatable coexisting neurological disorders as complications of COVID-19.

Encephalitis is a potentially life-threatening condition with long-term neurological sequelae. However, data on early clinical, demographic, and diagnostic predictors of functional outcomes remain limited. We performed a retrospective monocentric study including 98 patients diagnosed with infectious encephalitis of various etiologies treated in the University Hospital Ulm between January 2014 and December 2024. Ordinal logistic regression models were applied to evaluate associations between admission characteristics and functional outcome at discharge, as measured by the modified Rankin Scale. Three multivariate models incorporating clinical, demographic, and MRI/EEG variables explained up to 53% of the variance in mRS at discharge (p < 0.001), outperforming models based solely on CSF parameters. Key predictors of poor functional outcome included ‘altered consciousness’ (OR 7.08, p < 0.001), higher ‘mRS at admission’ (OR 0.03–0.07 across categories, p < 0.001), ‘focal/generalized EEG slowing’ (OR 9.97, p < 0.001), ‘epileptiform EEG activity’ (OR 17.49, p < 0.001), ‘MRI: myelitis’ (OR 16.44, p = 0.004), and ‘intrathecal IgM synthesis’ (OR 8.93, p = 0.018). Conversely, ‘longer hospitalization’ (OR 0.13–0.17 for different intervals, p < 0.006) and ‘intrathecal IgG synthesis’ (OR 0.05, p = 0.03) were associated with more favorable outcomes. Despite the single-center and retrospective aspects of this study, our findings underscore a multifactorial pattern of outcome determinants in infectious encephalitis, highlighting the prognostic relevance of initial neurological status, electrophysiological abnormalities, and neuroimaging features.

ObjectivesBiomarkers for the diagnosis of motoneuron diseases (MND) are urgently needed to improve the diagnostic pathway, patient stratification and monitoring. The aim of this study was to validate candidate markers for MND in cerebrospinal fluid (CSF) and specify cut-offs based on large patient cohorts by especially considering patients who were seen under the initial differential diagnosis (MND mimics).MethodsIn a prospective study, we investigated CSF of 455 patients for neurofilament light chain (NfL), phosphorylated heavy chain (pNfH), tau protein (Tau) and phospho-tau protein (pTau). Analysed cohorts included patients with apparently sporadic and familial amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) (MND, n=253), MND mimics (n=85) and neurological control groups. Cut-off values were specified, and diagnostic performance and correlation with progression were analysed.ResultsNfs were significantly higher in the MND group compared to the control groups, whereas Tau and pTau did not differ. At a cut-off level of 2200 pg/mL for NfL, a 77% diagnostic sensitivity (CI 71% to 82%), 85% specificity (CI 79% to 90%) and 87% positive predictive value (PPV) (CI 81% to 91%) were achieved. For pNfH, we calculated 83% sensitivity (CI 78% to 88%), 77% specificity (CI 71% to 83%) and 82% PPV (CI 77% to 86%) at 560 pg/mL. There were no significant differences between sporadic and genetic ALS or PLS. Nf levels were elevated at early disease stage, and correlated moderately with MND progression and duration.ConclusionsNeurofilaments in CSF have a high relevance for the differential diagnosis of MNDs and should be included in the diagnostic work-up of patients. Their value as prognostic markers should be investigated further.