Clinical and paraclinical features distinguish fatigue from depression-predominant phenotypes in multiple sclerosis.

In clinical routine, it might be difficult to distinguish between fatigue and depression in Multiple sclerosis (MS). We investigated in two independent observational cohort studies which clinical and paraclinical features distinguish patients reporting fatigue but no depressive symptoms from those suffering from depressive symptoms but having no relevant fatigue. In Study 1, n = 156 MS patients underwent fatigue, depression, cognitive screening and flow cytometry measurements.

Exploring the Link Between Renal Function Fluctuations Within the Physiological Range and Serum/CSF Levels of NfL, GFAP, tTAU, and UCHL1.

Impaired renal function can influence biomarker levels through mechanisms involving blood-brain barrier integrity and clearance pathways; however, the impact of variations within normal renal function remains unclear. The main aim of this study was to determine whether adjustment for the specific level of renal function is necessary when renal function remains within physiological levels. We studied n = 183 patients (NID n = 122; other neurological diseases n = 39; somatoform controls n = 22) who underwent lumbar puncture at University Hospital Frankfurt.

BDNF levels in serum and CSF are associated with clinicoradiological characteristics of aggressive disease in MS patients.

Background: BDNF has increasingly gained attention as a key molecule controlling remyelination with a prominent role in neuroplasticity and neuroprotection. Still, it remains unclear how BDNF relates to clinicoradiological characteristics particularly at the early stage of the disease where precise prognosis for the further MS course is crucial.

Methods: BDNF, NfL and GFAP concentrations in serum and CSF were assessed in 106 treatment naïve patients with MS (pwMS) as well as 73 patients with other inflammatory/non-inflammatory neurological or somatoform disorders using a single molecule array HD-1 analyser.

The relevance of BDNF for neuroprotection and neuroplasticity in multiple sclerosis.

Background: Neuroplasticity as a mechanism to overcome central nervous system injury resulting from different neurological diseases has gained increasing attention in recent years. However, deficiency of these repair mechanisms leads to the accumulation of neuronal damage and therefore long-term disability. To date, the mechanisms by which remyelination occurs and why the extent of remyelination differs interindividually between multiple sclerosis patients regardless of the disease course are unclear.

Evaluating the utility of serum NfL, GFAP, UCHL1 and tTAU as estimates of CSF levels and diagnostic instrument in neuroinflammation and multiple sclerosis.

Background: This study aimed to evaluate the utility of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCHL1) and total tau (tTAU) serum concentrations as approximation for cerebrospinal fluid (CSF) concentrations of the respective biomarkers in the context of neuroinflammation and multiple sclerosis (MS).

Methods: NfL, GFAP, UCHL1 and tTAU concentrations in serum and CSF were measured in 183 patients (122 with neuroinflammatory disease and 61 neurological or somatoform disease controls) using the single molecule array HD-1 analyzer (Quanterix, Boston, MA). Spearman's rank correlations were computed between serum and CSF concentrations.

Matching proposed clinical and MRI criteria of aggressive multiple sclerosis to serum and cerebrospinal fluid markers of neuroaxonal and glial injury.

Background: Definitions of aggressive MS employ clinical and MR imaging criteria to identify highly active, rapidly progressing disease courses. However, the degree of overlap between clinical and radiological parameters and biochemical markers of CNS injury is not fully understood. Aim of this cross-sectional study was to match clinical and MR imaging hallmarks of aggressive MS to serum/CSF markers of neuroaxonal and astroglial injury (neurofilament light chain (sNfL, cNfL), and glial fibrillary acidic protein (sGFAP, cGFAP)).

Focal epilepsy without overt epileptogenic lesions: no evidence of microstructural brain tissue damage in multi-parametric quantitative MRI.

Background And Purpose: In patients with epilepsies of structural origin, brain atrophy and pathological alterations of the tissue microstructure extending beyond the putative epileptogenic lesion have been reported. However, in patients without any evidence of epileptogenic lesions on diagnostic magnetic resonance imaging (MRI), impairment of the brain microstructure has been scarcely elucidated. Using multiparametric quantitative (q) magnetic resonance imaging MRI, we aimed to investigate diffuse impairment of the microstructural tissue integrity in MRI-negative focal epilepsy patients.

Multiparametric quantitative MRI reveals progressive cortical damage over time in clinically stable relapsing-remitting MS.

Background: In relapsing-remitting multiple sclerosis (RRMS), cortical grey matter pathology relevantly contributes to long-term disability. Still, diffuse cortical inflammation cannot be detected with conventional MRI.

Objective: We aimed to assess microstructural damage of cortical grey matter over time and the relation to clinical disability as well as relapse activity in patients with RRMS using multiparametric quantitative (q)MRI techniques.

Serum and cerebrospinal fluid BDNF concentrations are associated with neurological and cognitive improvement in multiple sclerosis: A pilot study.

Background: Biomarkers of disease activity have been intensively studied in multiple sclerosis (MS) but knowledge on predictors of disability improvement is limited. The aim of this pilot study was to explore whether increased brain-derived neurotrophic factor concentrations in serum and CSF (sBDNF/cBDNF) precede neurological and cognitive improvement in MS.

Methods: In this pilot, monocentric prospective cohort study we collected serum/CSF samples at baseline together with EDSS (n = 36) and cognitive testing (n = 34) in patients with relapsing-remitting/primary progressive MS or clinically isolated syndrome.

Multiparametric Quantitative MRI in Neurological Diseases.

Magnetic resonance imaging (MRI) is the gold standard imaging technique for diagnosis and monitoring of many neurological diseases. However, the application of conventional MRI in clinical routine is mainly limited to the visual detection of macroscopic tissue pathology since mixed tissue contrasts depending on hardware and protocol parameters hamper its application for the assessment of subtle or diffuse impairment of the structural tissue integrity. Multiparametric quantitative (q)MRI determines tissue parameters quantitatively, enabling the detection of microstructural processes related to tissue remodeling in aging and neurological diseases.

Improved Visualization of Focal Cortical Dysplasia With Surface-Based Multiparametric Quantitative MRI.

Purpose: In the clinical routine, detection of focal cortical dysplasia (FCD) by visual inspection is challenging. Still, information about the presence and location of FCD is highly relevant for prognostication and treatment decisions. Therefore, this study aimed to develop, describe and test a method for the calculation of synthetic anatomies using multiparametric quantitative MRI (qMRI) data and surface-based analysis, which allows for an improved visualization of FCD.

Cortical Changes in Epilepsy Patients With Focal Cortical Dysplasia: New Insights With T Mapping.

Background: In epilepsy patients with focal cortical dysplasia (FCD) as the epileptogenic focus, global cortical signal changes are generally not visible on conventional MRI. However, epileptic seizures or antiepileptic medication might affect normal-appearing cerebral cortex and lead to subtle damage.

Purpose: To investigate cortical properties outside FCD regions with T -relaxometry.

Detection of cortical malformations using enhanced synthetic contrast images derived from quantitative T1 maps.

The detection of cortical malformations in conventional MR images can be challenging. Prominent examples are focal cortical dysplasias (FCD), the most common cause of drug-resistant focal epilepsy. The two main MRI hallmarks of cortical malformations are increased cortical thickness and blurring of the gray (GM) and white matter (WM) junction.

How stable is quantitative MRI? - Assessment of intra- and inter-scanner-model reproducibility using identical acquisition sequences and data analysis programs.

Background: Quantitative MRI (qMRI) techniques allow assessing cerebral tissue properties. However, previous studies on the accuracy of quantitative T1 and T2 mapping reported a scanner model bias of up to 10% for T1 and up to 23% for T2. Such differences would render multi-centre qMRI studies difficult and raise fundamental questions about the general precision of qMRI.

Cortical quantitative MRI parameters are related to the cognitive status in patients with relapsing-remitting multiple sclerosis.

Objectives: We aimed to assess cortical damage in patients with relapsing-remitting multiple sclerosis (RRMS)/clinically isolated syndrome (CIS) with a multiparametric, surface-based quantitative MRI (qMRI) approach and to evaluate the correlation of imaging-derived parameters with cognitive scores, hypothesizing that qMRI parameters are correlated with cognitive abilities.

Methods: Multiparametric qMRI-data (T1, T2 and T2* relaxation times and proton density (PD)) were obtained from 34 patients/24 matched healthy control subjects. Cortical qMRI values were analyzed on the reconstructed cortical surface with Freesurfer.

Multimodal Quantitative MRI Reveals No Evidence for Tissue Pathology in Idiopathic Cervical Dystonia.

While in symptomatic forms of dystonia cerebral pathology is by definition present, it is unclear so far whether disease is associated with microstructural cerebral changes in idiopathic dystonia. Previous quantitative MRI (qMRI) studies assessing cerebral tissue composition in idiopathic dystonia revealed conflicting results. Using multimodal qMRI, the presented study aimed to investigate alterations in different cerebral microstructural compartments associated with idiopathic cervical dystonia .

Improved synthetic T1-weighted images for cerebral tissue segmentation in neurological diseases.

Structural cerebral MRI analysis in patients with neurological diseases usually requires T1-weighted datasets for tissue segmentation. For this purpose, synthetic T1-weighted images which are constructed from quantitative maps of the underlying tissue parameters such as the T1 relaxation time and the proton density (PD) may provide advantages over conventional datasets. However, in some cases synthetic images may suffer from specific artifacts, hampering accurate tissue segmentation.