16 Dec 2021

WARS2 mutations cause dopa-responsive early-onset parkinsonism and progressive myoclonus ataxia

Introduction: Sixteen subjects with biallelic WARS2 variants encoding the tryptophanyl mitochondrial aminoacyl-tRNA synthetase, presenting with a neonatal- or infantile-onset mitochondrial disease, have been reported to date. Here we present six novel cases with WARS2-related diseases and expand the spectrum to later onset phenotypes including dopa-responsive early-onset parkinsonism and progressive myoclonus-ataxia.

Methods: Six individuals from four families underwent whole-exome sequencing within research and diagnostic settings. Following the identification of a genetic defect, in-depth phenotyping and protein expression studies were performed.

Results: A relatively common (gnomAD MAF = 0.0033) pathogenic p.(Trp13Gly) missense variant in WARS2 was detected in trans in all six affected individuals in combination with different pathogenic alleles (exon 2 deletion in family 1;

13 Dec 2021

Shannon entropy: A novel parameter for quantifying pentagon copying performance in non-demented Parkinson's disease patients

Introduction: Impaired copy of intersecting pentagons from the Mini-Mental State Examination (MMSE), has been used to assess dementia in Parkinson's disease (PD). We used a digitizing tablet during the pentagon copying test (PCT) as a potential tool for evaluating early cognitive deficits in PD without major cognitive impairment. We also aimed to uncover the neural correlates of the identified parameters using whole-brain magnetic resonance imaging (MRI).

Methods: We enrolled 27 patients with PD without major cognitive impairment and 25 age-matched healthy controls (HC). We focused on drawing parameters using a digitizing tablet. Parameters with between-group differences were correlated with cognitive outcomes and were used as covariates in the whole-brain voxel-wise analysis using voxel-based morphometry; familywise error (FWE) threshold p < 0.001.

10 Dec 2021

Development and Validation of the 5-SENSE Score to Predict Focality of the Seizure-Onset Zone as Assessed by Stereoelectroencephalography

Importance: Stereoelectroencephalography (SEEG) has become the criterion standard in case of inconclusive noninvasive presurgical epilepsy workup. However, up to 40% of patients are subsequently not offered surgery because the seizure-onset zone is less focal than expected or cannot be identified.

Objective: To predict focality of the seizure-onset zone in SEEG, the 5-point 5-SENSE score was developed and validated.

Design, setting, and participants: This was a monocentric cohort study for score development followed by multicenter validation with patient selection intervals between February 2002 to October 2018 and May 2002 to December 2019. The minimum follow-up period was 1 year. 

7 Dec 2021

Processing of emotionally ambiguous stimuli in eating disorders: an fMRI pilot study

Purpose: People with eating disorders (EDs) have difficulties understanding their own emotions and recognizing the emotions of others, especially in ambiguous settings. We examined the neuronal mechanisms underlying the emotion processing of ambiguous interpersonal stimuli in EDs and healthy controls (HCs).

Methods: The fMRI data were acquired by a blocked experimental design with 28 women (14 EDs) during the visual presentation of a modified Thematic Apperception Test.

Results: EDs showed very strong associations between experienced and inferred emotions evoked by the stimuli; no such relationship was found in HCs. HCs displayed elevated left anterior insula activity during the mentalizing condition; EDs showed increased activity in the right supramarginal gyrus and medial prefrontal cortex.

7 Dec 2021

Infantile status epilepticus disrupts myelin development

Temporal lobe epilepsy (TLE) is the most prevalent type of epilepsy in adults; it often starts in infancy or early childhood. Although TLE is primarily considered to be a grey matter pathology, a growing body of evidence links this disease with white matter abnormalities. In this study, we explore the impact of TLE onset and progression in the immature brain on white matter integrity and development utilising the rat model of Li-pilocarpine-induced TLE at the 12th postnatal day (P). Diffusion tensor imaging (DTI) and Black-Gold II histology uncovered disruptions in major white matter tracks (corpus callosum, internal and external capsules, and deep cerebral white matter) spreading through the whole brain at P28. These abnormalities were mostly not present any longer at three months after TLE induction, with only limited abnormalities detectable in the external capsule and deep cerebral white matter. Relaxation Along a Fictitious Field in the rotating frame of rank 4 indicated that white matter changes observed at both timepoints, P28 and P72, are consistent with decreased myelin content. 

5 Nov 2021

Primary progressive multiple sclerosis overlapping with anti-GAD and anti-Hu antibodies positive neurological syndromes

Although still rare, there have been reports describing autoimmune demyelinating disorders associated with specific antibodies which overlap with multiple sclerosis (MS) and other demyelinating syndromes in clinical, radiological and immunological features. A relationship between anti-myelin-associated glycoprotein (MOG) syndrome, anti-aquaporin-4 (AQ-4) neuromyelitis optica spectrum disorders, and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been described. The opportunity of discovering yet unknown associations is based on the presumption of the co-occurrence of immune mediated diseases [1]. The association of multiple sclerosis with glutamic acid decarboxylase (GAD) neurological syndromes has only been reported in one case [2, 3]. The associated neurological syndromes include stiff-person syndrome (SPS), cerebellar ataxia, epilepsy, and limbic encephalitis. Paraneoplastic origin is rare, and comorbidities include autoimmune thyreoiditis, pernicious anaemia and vitiligo [4].

3 Nov 2021

Diffusion magnetic resonance imaging reveals tract-specific microstructural correlates of electrophysiological impairments in non-myelopathic and myelopathic spinal cord compression

Background and purpose: Non-myelopathic degenerative cervical spinal cord compression (NMDC) frequently occurs throughout aging and may progress to potentially irreversible degenerative cervical myelopathy (DCM). Whereas standard clinical magnetic resonance imaging (MRI) and electrophysiological measures assess compression severity and neurological dysfunction, respectively, underlying microstructural deficits still have to be established in NMDC and DCM patients. The study aims to establish tract-specific diffusion MRI markers of electrophysiological deficits to predict the progression of asymptomatic NMDC to symptomatic DCM.

Methods: High-resolution 3 T diffusion MRI was acquired for 103 NMDC and 21 DCM patients compared to 60 healthy controls to reveal diffusion alterations and relationships between tract-specific diffusion metrics and corresponding electrophysiological measures and compression severity. 

3 Nov 2021

Contribution of the multi-echo approach in accelerated functional magnetic resonance imaging multiband acquisition

We wanted to verify the effect of combining multi-echo (ME) functional magnetic resonance imaging (fMRI) with slice acceleration in simultaneous multi-slice acquisition. The aim was to shed light on the benefits of multiple echoes for various acquisition settings, especially for levels of slice acceleration and flip angle. Whole-brain ME fMRI data were obtained from 26 healthy volunteers (using three echoes; seven runs with slice acceleration 1, 4, 6, and 8; and two different flip angles for each of the first three acceleration factors) and processed as single-echo (SE) data and ME data based on optimal combinations weighted by the contrast-to-noise ratio. Global metrics (temporal signal-to-noise ratio, signal-to-noise separation, number of active voxels, etc.) and local characteristics in regions of interest were used to evaluate SE and ME data. ME results outperformed SE results in all runs; the differences became more apparent for higher acceleration, where a significant decrease in data quality is observed.