Dysphagia Affecting Quality of Life in Cerebellar Ataxia-a Large Survey.

Dysphagia is a common symptom in neurodegenerative disorders and is generally associated with increased mortality. In the clinical care setting of ataxia patients, no systematical and standardized assessment of dysphagia is employed. Its impact on patients' health-related quality of life is not well understood. To assess the impact of dysphagia in ataxia patients on diet, body weight, and health-related quality of life. We conducted a large survey using self-reported questionnaires for swallowing-related quality of life (Swal-QOL) and a food frequency list in combination with retrospective clinical data of 119 patients with cerebellar ataxia treated in the neurological outpatient clinic of a large German university hospital. Seventeen percent of ataxia patients suffered from dysphagia based on the Swal-QOL score. Less than 1% of all patients reported dysphagia as one of their most disabling symptoms. Dysphagia was associated with unintentional weight loss (p = 0.02) and reduced health-related quality of life (p = 0.01) but did not affect individual nutritional habits (p > 0.05; Chi-squared test). Dysphagia is a relevant symptom in cerebellar ataxia. A systematic screening for dysphagia in patients with cerebellar ataxia would be desirable to enable early diagnosis and treatment.

Considerations for Mean Upper Cervical Cord Area Implementation in a Longitudinal MRI Setting: Methods, Interrater Reliability, and MRI Quality Control.

BACKGROUND AND PURPOSE: Spinal cord atrophy is commonly measured from cerebral MRIs, including the upper cervical cord. However, rescan intraparticipant measures have not been investigated in healthy cohorts. This study investigated technical and rescan variability in the mean upper cervical cord area calculated from T1-weighted cerebral MRIs. MATERIALS AND METHODS: In this retrospective study, 8 healthy participants were scanned and rescanned with non-distortion- and distortion-corrected MPRAGE sequences (11-50 sessions in 6-8 months), and 50 participants were scanned once with distortion-corrected MPRAGE sequences in the Day2day daily variability study. From another real-world observational cohort, we collected non-distortion-corrected MPRAGE scans from 27 healthy participants (annually for 2-4 years) and cross-sectionally from 77 participants. Statistical analyses included coefficient of variation, smallest real difference, intraclass correlation coefficient, Bland-Altman limits of agreement, and paired t tests. RESULTS: Distortion- versus non-distortion-corrected MPRAGE-derived mean upper cervical cord areas were similar; however, a paired t test showed incomparability (t = 11.0, P = <.001). Higher variability was found in the mean upper cervical cord areas calculated from an automatic segmentation method. Interrater analysis yielded incomparable measures in the same participant scans (t = 4.5, P = <.001). Non-distortion-corrected mean upper cervical cord area measures were shown to be robust in real-world data (t = -1.04, P = .31). The main sources of variability were found to be artifacts from movement, head/neck positioning, and/or metal implants. CONCLUSIONS: Technical variability in cord measures decreased using non-distortion-corrected MRIs, a semiautomatic segmentation approach, and 1 rater. Rescan variability was within ±4.4% for group mean upper cervical cord area when MR imaging quality criteria were met.

MRI-Based Methods for Spinal Cord Atrophy Evaluation: A Comparison of Cervical Cord Cross-Sectional Area, Cervical Cord Volume, and Full Spinal Cord Volume in Patients with Aquaporin-4 Antibody Seropositive Neuromyelitis Optica Spectrum Disorders.

BACKGROUND AND PURPOSE: Measures for spinal cord atrophy have become increasingly important as imaging biomarkers in the assessment of neuroinflammatory diseases, especially in neuromyelitis optica spectrum disorders. The most commonly used method, mean upper cervical cord area, is relatively easy to measure and can be performed on brain MRIs that capture cervical myelon. Measures of spinal cord volume (eg, cervical cord volume or total cord volume) require longer scanning and more complex analysis but are potentially better suited as spinal cord atrophy measures. This study investigated spinal cord atrophy measures in a cohort of healthy subjects and patients with aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders and evaluated the discriminatory performance of mean upper cervical cord cross-sectional area compared with cervical cord volume and total cord volume. MATERIALS AND METHODS: Mean upper cervical cord area, cervical cord volume, and total cord volume were measured using 3T MRIs from healthy subjects (n = 19) and patients with neuromyelitis optica spectrum disorders (n = 30). Group comparison and receiver operating characteristic analyses between healthy controls and patients with neuromyelitis optica spectrum disorders were performed. RESULTS: Mean upper cervical cord area, cervical cord volume, and total cord volume measures showed similar and highly significant group differences between healthy control subjects and patients with neuromyelitis optica spectrum disorders (P < .01 for all). All 3 measures showed similar receiver operating characteristic-area under the curve values (mean upper cervical cord area = 0.70, cervical cord volume = 0.75, total cord volume = 0.77) with no significant difference between them. No associations among mean upper cervical cord cross-sectional area, cervical cord volume, or total cord volume with disability measures were found. CONCLUSIONS: All 3 measures showed similar discriminatory power between healthy control and neuromyelitis optica spectrum disorders groups. Mean upper cervical cord area is easier to obtain compared with cervical cord volume and total cord volume and can be regarded as an efficient representative measure of spinal cord atrophy in the neuromyelitis optica spectrum disorders context.

[Optical coherence tomography in neuromyelitis optica spectrum disorders]. / Optische Kohärenztomographie bei Neuromyelitis optica-Spektrum-Erkrankungen.

Neuromyelitis optica spectrum disorders (NMOSD) are mostly relapsing inflammatory conditions of the central nervous system (CNS). In 55% of the cases of NMOSD optic neuritis (ON) is the most frequent first manifestation and can cause severe damage to the afferent visual system and the retina with resultant severe visual impairment. In recent years, investigations of the retina as part of the CNS by optical coherence tomography (OCT) has been shown to be a valid and efficient method for diagnostics and evaluation of the disease course in NMOSD. In addition, OCT not only shows severe damage of the afferent visual system due to multiple bouts of ON but also reveals NMOSD-specific intraretinal pathologies. The latter could be just as important for future differential diagnostics as for the evaluation of potential therapeutic targets. This article briefly reviews the principles of the OCT technique and describes its relevance for the diagnostics and assessment of disease course in NMOSD.

Brain parenchymal damage in neuromyelitis optica spectrum disorder - A multimodal MRI study.

OBJECTIVE: To investigate different brain regions for grey (GM) and white matter (WM) damage in a well-defined cohort of neuromyelitis optica spectrum disorder (NMOSD) patients and compare advanced MRI techniques (VBM, Subcortical and cortical analyses (Freesurfer), and DTI) for their ability to detect damage in NMOSD. METHODS: We analyzed 21 NMOSD patients and 21 age and gender matched control subjects. VBM (GW/WM) and DTI whole brain (TBSS) analyses were performed at different statistical thresholds to reflect different statistical approaches in previous studies. In an automated atlas-based approach, Freesurfer and DTI results were compared between NMOSD and controls. RESULTS: DTI TBSS and DTI atlas based analysis demonstrated microstructural impairment only within the optic radiation or in regions associated with the optic radiation (posterior thalamic radiation p < 0.001, 6.9 % reduction of fractional anisotropy). VBM demonstrated widespread brain GM and WM reduction, but only at exploratory statistical thresholds, with no differences remaining after correction for multiple comparisons. Freesurfer analysis demonstrated no group differences. CONCLUSION: NMOSD specific parenchymal brain damage is predominantly located in the optic radiation, likely due to a secondary degeneration caused by ON. In comparison, DTI appears to be the most reliable and sensitive technique for brain damage detection in NMOSD. KEY POINTS: • The hypothesis of a widespread brain damage in NMOSD is challenged. • The optic radiation (OR) is the most severely affected region. • OR-affection is likely due to secondary degeneration following optic neuritis. • DTI is currently the most sensitive technique for NMOSD-related brain-damage detection. • DTI is currently the most reliable technique for NMOSD-related brain-damage detection.

Altered basal ganglia functional connectivity in multiple sclerosis patients with fatigue.

BACKGROUND: Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis, but its pathophysiological mechanisms are poorly understood. It is in particular unclear whether and how fatigue relates to structural and functional brain changes. OBJECTIVE: We aimed to analyse the association of fatigue severity with basal ganglia functional connectivity, basal ganglia volumes, white matter integrity and grey matter density. METHODS: In 44 patients with relapsing-remitting multiple sclerosis and 20 age- and gender-matched healthy controls, resting-state fMRI, diffusion tensor imaging and voxel-based morphometry was performed. RESULTS: In comparison with healthy controls, patients showed alteration of grey matter density, white matter integrity, basal ganglia volumes and basal ganglia functional connectivity. No association of fatigue severity with grey matter density, white matter integrity and basal ganglia volumes was observed within patients. In contrast, fatigue severity was negatively correlated with functional connectivity of basal ganglia nuclei with medial prefrontal cortex, precuneus and posterior cingulate cortex in patients. Furthermore, fatigue severity was positively correlated with functional connectivity between caudate nucleus and motor cortex. CONCLUSION: Fatigue is associated with distinct alterations of basal ganglia functional connectivity independent of overall disability. The pattern of connectivity changes suggests that disruption of motor and non-motor basal ganglia functions, including motivation and reward processing, contributes to fatigue pathophysiology in multiple sclerosis.

Optical coherence tomography does not support optic nerve involvement in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: In recent years a possible non-motor involvement of the nervous system in amyotrophic lateral sclerosis (ALS) has come into the focus of research and has been investigated by numerous techniques. Optical coherence tomography (OCT) - with its potential to reveal neuroaxonal retinal damage - may be an appropriate tool to investigate whether the anterior visual pathway is involved. Our aim was to determine whether OCT-based measures of retinal nerve fiber layer, ganglion cell layer, inner nuclear layer and outer nuclear layer thickness are abnormal in ALS, or correlated with disease severity. METHODS: Seventy-six ALS patients (144 eyes) and 54 healthy controls (108 eyes; HCs) were examined with OCT, including automated intraretinal macular segmentation. ALS disease severity was determined with the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. RESULTS: There was no significant difference between ALS patients and HCs in any of the examined OCT measures. Moreover, OCT parameters showed no correlation with clinical measures of disease severity. CONCLUSIONS: These findings indicate that involvement of the anterior visual pathway is not one of the non-motor manifestations of ALS.

Loss of retinal nerve fibre layer axons indicates white but not grey matter damage in early multiple sclerosis.

BACKGROUND AND PURPOSE: Optical coherence tomography (OCT) has shown thinning of the retinal nerve fibre layer (RNFL) and total macular volume (TMV) in multiple sclerosis (MS) patients. Measures of retinal atrophy are associated with the brain parenchymal fraction (BPF) assessed by magnetic resonance imaging (MRI). However, in MS, data on the relation of OCT measures and grey and white matter volumes are contradictory. We performed a prospective cross-sectional study with a statistically pre-defined endpoint to test our hypothesis that OCT measures of neuro-axonal degeneration are related to global and partial brain atrophy in early forms of MS. METHODS AND RESULTS: Forty-four patients with clinically isolated syndrome (n = 10) or relapsing-remitting MS (n = 34; mean disease duration = 3.2 years, median EDSS = 1.5) were enrolled in the study. Peripapillary- and volumetric OCT scans of the macula were performed using latest spectral-domain OCT technology. BPF as well as white and grey matter fractions (WMF/GMF) were assessed by 1.5 Tesla MRI scans. Generalized estimating equation models adjusted for age and linear regression statistics were used to assess the association between OCT and MRI measures. RNFL thickness, TMV and age were significantly associated with BPF. RNFL thickness and TMV independently predicted WMF (P = 0.003 and P = 0.032) but not GMF (P = 0.717 and P = 0.357) when corrected for age. In contrast, age was strongly associated with GMF (P < 0.001) but not WMF. CONCLUSION: Our study suggests that, in early MS, OCT measures of retinal atrophy are related to volumetric changes in the white but not grey matter compartment as assessed by MRI. It further substantiates the association of retinal thinning and brain tissue loss in MS.