Chronic hepatitis E virus-induced spinal cord atrophy in a patient with chronic lymphatic leukemia: a case report and interdisciplinary management proposal.

Background: The hepatitis E virus (HEV) can cause acute viral hepatitis with or without neurological manifestations, and occasionally progresses to chronic infection in immunocompromised individuals. The management of chronic HEV infection in cancer patients may be challenging due to the complex immunological constellation. Furthermore, the diagnostic workflow and the impact on quality of life of neurological HEV manifestations in immunocompromised patients have not been sufficiently delineated previously.

Multiple Sclerosis and Epsilon Toxin: Is There a Relationship?

Recent research has suggested a link between multiple sclerosis and the gut microbiota. This prospective pilot study aimed to investigate the composition of the gut microbiota in MS patients, the presence of epsilon toxin in the serum of MS patients, and the influence of disease-modifying drugs (DMDs) on epsilon toxin levels and on the microbiota. Epsilon toxin levels in blood were investigated by two methods, a qualitative ELISA and a highly sensitive quantitative ELISA.

Serum neurofilament light chain and glial fibrillary acidic protein for predicting response to apheresis in steroid-refractory multiple sclerosis relapses.

Background And Purpose: The predictive value of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) for apheresis outcome in steroid-refractory multiple sclerosis (MS) relapse has not yet been evaluated.

Methods: We used pre- and postapheresis serum samples from 38 participants of the IAPEMS trial (clinicaltrials.gov: NCT02671682), which investigated the use of immunoadsorption versus plasma exchange for the treatment of steroid-refractory MS attacks.

Primary lateral sclerosis: application and validation of the 2020 consensus diagnostic criteria in an expert opinion-based PLS cohort.

Background: Validation of the 2020 consensus criteria for primary lateral sclerosis (PLS) is essential for their use in clinical practice and future trials.

Methods: In a large cohort of patients diagnosed with PLS by expert opinion prior to the new criteria with detailed clinical baseline evaluation (n=107) and longitudinal follow-up (n=63), we applied the new diagnostic criteria and analysed the clinical phenotype, electromyography (EMG), diagnostic accuracy and prognosis, adding neurofilaments and MRI as potential biomarkers.

Results: The criteria for definite PLS were met by 28% and those for probable PLS by 19%, whereas 53% did not meet the full criteria at baseline, mainly due to the time, EMG and region criteria.

Patient-reported outcome parameters and disability worsening in progressive multiple sclerosis.

Objectives: Detection and prediction of disability progression is a significant unmet need in people with progressive multiple sclerosis (PwPMS). Government and health agencies have deemed the use of patient-reported outcomes measurements (PROMs) in clinical practice and clinical trials a major strategic priority. Nevertheless, data documenting the clinical utility of PROMs in neurological diseases is scarce.

Clinical associations and characteristics of the polyspecific intrathecal immune response in elderly patients with non-multiple sclerosis chronic autoimmune-inflammatory neurological diseases - a retrospective cross-sectional study.

Introduction: The polyspecific intrathecal immune response (PSIIR), aka MRZ reaction ( = measles,  = rubella, = zoster, optionally Herpes simplex virus, HSV) is defined as intrathecal immunoglobulin synthesis (IIS) for two or more unrelated viruses. Although an established cerebrospinal fluid (CSF) biomarker for multiple sclerosis (MS), a chronic autoimmune-inflammatory neurological disease (CAIND) of the central nervous system (CNS) usually starting in young adulthood, the full spectrum of CAINDs with a positive PSIIR remains ill defined.

Methods: In this retrospective, cross-sectional study, patients with CSF-positive oligoclonal bands (OCB) and - to enrich for non-MS diagnoses - aged ≥50 years were enrolled.

Development of an ultrasensitive microfluidic assay for the analysis of Glial fibrillary acidic protein (GFAP) in blood.

A rapid and reliable detection of glial fibrillary acidic protein (GFAP) in biological samples could assist in the diagnostic evaluation of neurodegenerative disorders. Sensitive assays applicable in the routine setting are needed to validate the existing GFAP tests. This study aimed to develop a highly sensitive and clinically applicable microfluidic immunoassay for the measurement of GFAP in blood.

Monocyte chemoattractant protein 1 as a potential biomarker for immune checkpoint inhibitor-associated neurotoxicity.

Background: Oncological patients can benefit substantially from treatment with immune checkpoint inhibitors (ICI). However, there is a growing awareness of immune-related adverse events (irAE). Especially ICI-mediated neurological adverse events (nAE(+)), are tough to diagnose and biomarkers to identify patients at risk are missing.

Association of Serum GFAP with Functional and Neurocognitive Outcome in Sporadic Small Vessel Disease.

Cerebrospinal fluid (CSF) and serum biomarkers are critical for clinical decision making in neurological diseases. In cerebral small vessel disease (CSVD), white matter hyperintensities (WMH) are an important neuroimaging biomarker, but more blood-based biomarkers capturing different aspects of CSVD pathology are needed. In 42 sporadic CSVD patients, we prospectively analysed WMH on magnetic resonance imaging (MRI) and the biomarkers neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), chitinase3-like protein 1 (CHI3L1), Tau and Aβ1-42 in CSF and NfL and GFAP in serum.

Glial fibrillary acidic protein in cerebrospinal fluid of patients with spinal muscular atrophy.

Objective: Activated astroglia is involved in the pathophysiology of neurodegenerative diseases and has also been described in animal models of spinal muscular atrophy (SMA). Given the urgent need of biomarkers for treatment monitoring of new RNA-modifying and gene replacement therapies in SMA, we examined glial fibrillary acidic protein concentrations in cerebrospinal fluid (cGFAP) as a marker of astrogliosis in SMA.

Methods: 58 adult patients and 21 children with genetically confirmed 5q-associated SMA from four German motor neuron disease specialist care centers and 30 age- and sex-matched controls were prospectively included in this study.

The Sexual Dimorphism in Cerebrospinal Fluid Protein Content Does Not Affect Intrathecal IgG Synthesis in Multiple Sclerosis.

(1) Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) that mainly affects young adults and females more than males. The detection of intrathecal IgG synthesis (IIS) on cerebrospinal fluid (CSF) analysis supports the diagnosis of MS. A sexual dimorphism has recently been described in CSF protein content.

Differential Expression of Serum Extracellular Vesicle miRNAs in Multiple Sclerosis: Disease-Stage Specificity and Relevance to Pathophysiology.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Its first clinical presentation (clinically isolated syndrome, CIS) is often followed by the development of relapsing-remitting MS (RRMS). The periphery-to-CNS transmission of inflammatory molecules is a major pathophysiological pathway in MS.

Blood GFAP as an emerging biomarker in brain and spinal cord disorders.

Blood-derived biomarkers for brain and spinal cord diseases are urgently needed. The introduction of highly sensitive immunoassays led to a rapid increase in the number of potential blood-derived biomarkers for diagnosis and monitoring of neurological disorders. In 2018, the FDA authorized a blood test for clinical use in the evaluation of mild traumatic brain injury (TBI).

Diagnostic biomarkers in tear fluid: from sampling to preanalytical processing.

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.

Beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimer's disease.

Objective: Synaptic loss plays a major role in Alzheimer's disease (AD). However so far no neurochemical marker for synaptic loss has been introduced into clinical routine. By mass spectrometry beta-synuclein was established as a candidate marker.

Cerebrospinal Fluid Biomarkers in Relation to MRZ Reaction Status in Primary Progressive Multiple Sclerosis.

The MRZ reaction (MRZR) comprises the three antibody indices (AIs) against measles, rubella, and varicella zoster virus, reflecting an intrathecal polyspecific B cell response highly specific for multiple sclerosis (MS). Thus, MRZR can be used to confirm a diagnosis of primary progressive MS (PPMS) but its pathophysiological and wider clinical relevance is unclear. This study aimed to investigate whether PPMS patients with a positive MRZR (MRZR+) differ from those with a negative MRZR (MRZR-) according to cerebrospinal fluid (CSF) biomarkers of B cell activity, neuroaxonal damage or glial activity, and clinical features.

Emotional Components of Pain Perception in Borderline Personality Disorder and Major Depression-A Repetitive Peripheral Magnetic Stimulation (rPMS) Study.

Various studies suggested alterations in pain perception in psychiatric disorders, such as borderline personality disorder (BPD) and major depression (MD). We previously investigated affective components of pain perception in BPD compared to healthy controls (HC) by increasing aversive stimulus intensities using repetitive peripheral magnetic stimulation (rPMS) and observed alterations in emotional rather than somatosensory components in BPD. However, conclusions on disorder specific alterations in these components of pain perception are often limited due to comorbid depression and medication in BPD.

Serum neurofilament light chain: No clear relation to cognition and neuropsychiatric symptoms in stable MS.

Objective: To explore the hypothesis that serum neurofilament light chain (sNfL) indicative of neuroaxonal damage may improve precise disease profiling with regard to cognition and neuropsychiatric symptoms, we analyzed potential associations of sNfL levels with cognitive test scores, fatigue, depression, and anxiety.

Methods: Patients with relapsing-remitting and secondary progressive MS (SPMS) underwent an elaborated assessment including MRI, various cognitive tests, and patient-reported outcomes. We determined sNfL levels by single molecule array (Simoa) assay.

Longitudinal Serum Neurofilament Levels of Multiple Sclerosis Patients Before and After Treatment with First-Line Immunomodulatory Therapies.

Serum neurofilament light chain (NfL) has been shown to correlate with neuroaxonal damage in multiple sclerosis (MS) and various other neurological diseases. While serum NfL is now regularly reported in clinical approval studies, there is a lack of longitudinal data from patients treated with established basic immunotherapies outside of study conditions. In total, 34 patients with early relapsing-remitting MS (RRMS) were included.

A Score Based on NfL and Glial Markers May Differentiate Between Relapsing-Remitting and Progressive MS Course.

The diagnostic use of biomarkers in body fluids of multiple sclerosis (MS) patients allows the monitoring of different pathophysiological aspects of the disease. We previously reported elevated cerebrospinal fluid (CSF) and serum levels of glial fibrillary acidic protein (GFAP) but not neurofilament light chain (NfL) in progressive (PMS) compared to relapsing-remitting MS (RRMS) patients. We analyzed the glial marker chitinase-3-like protein 1 (CHI3L1) in the CSF and serum of PMS and RRMS patients.

Explorative study of emerging blood biomarkers in progressive multiple sclerosis (EmBioProMS): Design of a prospective observational multicentre pilot study.

Background: Defining clinical and subclinical progression in multiple sclerosis (MS) is challenging. Patient history, expanded disability status scale (EDSS), and magnetic resonance imaging (MRI) all have shortcomings and may underestimate disease dynamics. Emerging serum biomarkers such as glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) proved useful in many cross-sectional studies.