•Alexithymia is a frequent manifestation in patients with multiple sclerosis.•The study included clinical, neuropsychological and radiological evaluations.•Alexithymia is associated with low empathy ...scores, and high fatigue and depression ratings.•Alexithymia is associated with low pallidal and thalamic volumes.•Alexithymia is associated with low deep white matter and corpus callosum volumes.
Alexithymia is a personality construct that could occur in up to 53 % of patients with multiple sclerosis (MS). It entails difficulties in identifying and describing one’s feelings and an externally oriented thinking. The current work aims to assess the neural underpinnings of alexithymia in this population.
Forty-five patients with MS filled in the Toronto Alexithymia Scale (n = 17 with high alexithymia and n = 28 with low alexithymia). Brain magnetic resonance imaging was obtained for each patient and a morphometry algorithm (MorphoBox) was applied to calculate regional brain volumes. All patients underwent a clinical and neuropsychological evaluation which included measures for anxiety, depression, fatigue, daytime sleepiness, and basic and social cognition.
Compared to patients with low alexithymia, patients with high alexithymia had significantly higher fatigue and depression ratings, and lower empathy scores. In addition, they had lower volumes of corpus callosum, deep white matter, pallidum bilaterally, and left thalamus. In the whole cohort, alexithymia scores were inversely correlated with gray matter (thalamus and pallidum bilaterally) and white matter volumes (corpus callosum and bilateral deep white matter) after controlling for covariates (ps<0.05).
This study offers insights on the neuropsychological and neural substrates of alexithymia in MS. The current findings are consistent with alexithymia reports in other clinical populations, and suggest an association between alexithymia and atrophy of thalami, pallidum, corpus callosum and deep white matter in MS. Further research is needed to enhance the understanding of alexithymia mechanisms in this clinical context.
Objectives
To evaluate compliance with the available recommendations, we assessed the current clinical practice of imaging in the evaluation of multiple sclerosis (MS).
Methods
An online ...questionnaire was emailed to all members and affiliates. Information was gathered on applied MR imaging protocols, gadolinium-based contrast agents (GBCA) use and image analysis. We compared the survey results with the Magnetic Resonance Imaging in MS (MAGNIMS) recommendations considered as the reference standard.
Results
A total of 428 entries were received from 44 countries. Of these, 82% of responders were neuroradiologists. 55% performed more than ten scans per week for MS imaging. The systematic use of 3 T is rare (18%). Over 90% follow specific protocol recommendations with 3D FLAIR, T2-weighted and DWI being the most frequently used sequences. Over 50% use SWI at initial diagnosis and 3D gradient-echo T1-weighted imaging is the most used MRI sequence for pre- and post-contrast imaging. Mismatches with recommendations were identified including the use of only one sagittal T2-weighted sequence for spinal cord imaging, the systematic use of GBCA at follow-up (over 30% of institutions), a delay time shorter than 5 min after GBCA administration (25%) and an inadequate follow-up duration in pediatric acute disseminated encephalomyelitis (80%). There is scarce use of automated software to compare images or to assess atrophy (13% and 7%). The proportions do not differ significantly between academic and non-academic institutions.
Conclusions
While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that recommendations are only partially followed.
Clinical relevance statement
Hurdles were identified, mainly in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies. This work will help radiologists to identify the mismatches between their own practices and the recommendations and act upon them.
Key Points
• While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that available recommendations are only partially followed.
• Several hurdles have been identified through the survey that mainly lies in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, characterized by the accumulation of demyelinating lesions and axonal loss over its course. This study aimed ...to increase current knowledge of motor preparation in this condition, by assessing the two components of the Bereitschaftspotential (BP1 and BP2), also known as the readiness potential.
Twelve patients with MS and ten age- and gender-matched healthy controls (HC) were included. Patients’ demographic and clinical data were collected. Participants were asked to perform two different tasks, a simple index extension and a Luria sequence. BP1 and BP2 values were obtained from 18 central electroencephalography electrodes and were compared between the two groups.
Compared to HC, patients with MS showed earlier BP1 onset (i.e., longer latency) in almost all the analyzed scalp regions during index extension. This was also observed during the Luria sequence, but only in the centro-parietal regions. As for BP2 latency, no significant difference was noted between groups during either task. With regard to amplitudes, patients with MS had larger BP1 amplitudes in the right fronto-central area during index extension and greater BP1 and BP2 amplitudes in bilateral centro-parietal and left central regions during the Luria task. BP1 latency was also found to be significantly correlated with disease duration and performance on executive function tests (Trail Making Test).
This study showed, for the first time, changes in the Bereitschaftspotential in patients with MS. These data reflect prolonged movement preparation in this population and may suggest global alteration of the premotor scheme.
Background and purpose
Charcot–Marie–Tooth (CMT) disease, an untreatable hereditary polyneuropathy, may mimic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a treatable neuropathy.
...Methods
In this retrospective study, we analyzed the characteristics of CMT patients misdiagnosed as CIDP at 16 university hospitals in three countries, compared these patients with a reference group of CIDP patients, and estimated the cost of misdiagnosis.
Results
Among 1104 CIDP cases, we identified 35 CMT patients misdiagnosed as CIDP (3.2%). All were initially diagnosed with definite or probable CIDP (European Federation of Neurological Societies/Peripheral Nerve Society criteria), and mutations in PMP22, MPZ, and 10 other CMT genes were found in 34%, 31%, and 35% of cases, respectively. In comparison with a reference group of 35 CIDP patients, CMT patients were younger (median age at disease onset = 39 vs. 56 years) and more frequently had motor weakness at disease onset (80% vs. 29%), hearing loss (14% vs. 0%), normal brachial plexus imaging (70% vs. 40%), lower cerebrospinal fluid protein content (median = 0.5 vs. 0.8 g/L), and lower treatment response (20% vs. 69%). Treatment cost in these 35 misdiagnosed patients was estimated at 4.6 million euros (M€), whereas the cost of CMT genetic analysis in 1104 patients was estimated at 2.7 M€.
Conclusions
In this study, 35 of 1104 (3.2%) patients initially diagnosed with CIDP had CMT. Importantly, the cost of treating these 35 misdiagnosed patients was significantly higher than the cost of performing CMT genetic analysis in 1104 patients (4.6 M€ vs. 2.7 M€), suggesting that CMT genetic investigations should be more widely used before diagnosing CIDP.
Amongst 1,104 CIDP cases, we identified 35 CMT patients misdiagnosed as CIDP (3.2%). In comparison with a reference group of 35 CIDP patients, CMT patients were younger, had more frequently motor weakness at disease onset, hearing loss, lower cerebrospinal fluid protein content, and lower treatment response. The cost of treating these 35 misdiagnosed patients was significantly higher than the cost of performing CMT genetic analysis in 1,104 patients (4.6 M€ vs 2.7 M€).
•Anxiety and depressive symptoms are frequent in multiple sclerosis (MS).•Their neurophysiological correlates in MS have not been previously addressed.•Transcranial magnetic stimulation was employed ...for this purpose.•Anxiety was significantly correlated with transcallosal transfer.
Depression and anxiety stand among the most frequent and debilitating complaints in multiple sclerosis (MS) patients. Understanding their neurophysiological correlates might improve their management. To date, no single study has addressed this issue.
Patients completed the Hospital Anxiety and Depression Scale (HADS). Transcranial magnetic stimulation (TMS) was performed to obtain the following corticospinal excitability measures: resting motor threshold, short-interval intracortical inhibition and facilitation, cortical silent period and interhemispheric inhibition (IHI). Anxiety and depression scores were the primary outcomes in the univariate analysis. When obtaining significant associations between anxiety/depression and TMS measures, a multivariate analysis was performed using stepwise linear regression with anxiety and depression scores employed separately as dependent variables and TMS measures, clinical and sociodemographic data as independent variables. Due to the small sample size and the large number of studied variables, only variables with p values <0.05 in the univariate analysis were included in the multivariate analysis.
Fifty patients completed the study (n = 24 women). Their mean age was 51.82 ± 12.72 years. Mean depression score was 6.08 ± 3.66. Mean anxiety score was 5.82 ± 3.42. A significant association was found between anxiety and IHI (p < 0.05), fatigue (p < 0.05), depression (p < 0.05), and female gender (p < 0.05). Stepwise linear regression analysis was performed and IHI values explained 9.10% of variance in anxiety levels (standardized β: 0.31; p < 0.01) when controlling for remaining variables. As for depression, it did not significantly correlate with any TMS measures.
The results highlight the relationship between anxiety and callosal transfer as reflected by IHI values. The current findings are consistent with previous works assessing healthy participants and patients with social anxiety disorders. Compared to MS patients with aberrant callosal transfer (suggested by low IHI values), those exhibiting a relatively more efficient one (reflected by high IHI values) seem to have higher anxiety scores, a finding that merits further assessment.
Fatigue stands among the most debilitating multiple sclerosis (MS) manifestations. Several pathophysiological mechanisms have been proposed at its origin. However, unmet needs still exist, and ...further investigations are required to better understand and manage this complaint. A new imaging modality—the phosphorous magnetic resonance spectroscopy (
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P-MRS)—might help studying fatigue by allowing the measurement of energy metabolites of various cerebral regions. Therefore, this work aimed to explore the association between fatigue and brain energy status. Thirty MS patients with progressive disease forms completed the study. Their sociodemographic and clinical data including fatigue and disability scores i.e., Fatigue Severity Scale (FSS) and Expanded Disability Status Scale (EDSS) were collected.
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P-MRS spectra of (1) bilateral frontoparietal area and (2) centrum semiovale normal appearing white matter (NAWM) were obtained. Percentages of phosphocratine and β-adenosine triphosphate (β-ATP) were calculated. FSS scores were found to be directly correlated with the frontoparietal β-ATP % (
p
< 0.05). However, there were no significant correlations between FSS scores and NAWM energy metabolites or clinical data (i.e., age, EDSS scores or disease duration). These findings point toward the existence of a link between fatigue severity and the amount of cerebral ATP metabolites. Such a link might reflect either a high production or low utilization of ATP, both of which were paralleled with increased fatigue perception. While the former would be due to a redistribution of ion channels along demyelinated axons and subsequent changes in mitochondrial activity; the latter could be interpreted in the light of neuronal loss which would lead to a decrease in ATP utilization and accumulation of its metabolites.
•EEG provides signatures of motor preparation and execution.•Motor preparation is altered in MS patients, with a delayed cortical activation (ERD).•Motor execution is also altered, with a delayed and ...reduced post-movement inhibition (ERS).•Preserved clinical performance is associated with preserved deep brain structures.
Motor preparation and execution can be impaired in patients with multiple sclerosis (pwMS). These neural processes can be assessed using electroencephalography (EEG). During a self-paced movement, EEG signal amplitude decreases before movement (event-related desynchronization, ERD) and increases after movement (event-related synchronization, ERS).
To reappraise ERD/ERS changes in pwMS compared to healthy controls (HC).
This single-center study included 13 pwMS and 10 sex/age-matched HC. 60-channel EEG was recorded during two self-paced movements of the right hand: a simple index finger extension task and a more complex finger tapping task. Clinical variables included MS type, sex, age, disease duration, disability, grip strength, fatigue and attentional performance. EEG variables included ERD and ERS onset latency, duration, and amplitude determined using two methods of signal analyses (based on visual or automated determination) in the alpha and beta frequency bands in five cortical regions: right and left frontocentral and centroparietal regions and a midline region. Neuroimaging variables included the volumes of four deep brain structures (thalamus, putamen, pallidum and caudate nucleus) and the relative lesion load.
ERD/ERS changes in pwMS compared to HC were observed only in the beta band. In pwMS, beta-ERD had a delayed onset in the midline and right parietocentral regions and a shortened duration or increased amplitude in the parietocentral region; beta-ERS had a shorter duration, delayed onset, or reduced amplitude in the left parieto/frontocentral region. In addition, pwMS with a more delayed beta-ERD in the midline region had less impaired executive functions but increased caudate nuclei volume, while pwMS with a more delayed beta-ERS in the parietocentral region contralateral to the movement had less fatigue but increased thalami volume.
This study confirms an alteration of movement preparation and execution in pwMS, mainly characterized by a delayed cortical activation (ERD) and a delayed and reduced post-movement inhibition (ERS) in the beta band. Compensatory mechanisms could be involved in these changes, associating more preserved clinical performance and overactivation of deep brain structures.
Fatigue is a multifactorial symptom frequently reported by multiple sclerosis (MS) patients. To date, the pathophysiology of MS fatigue remains poorly understood and little is known about the ...relationship between this symptom and various clinical, neuropsychological, neurophysiological and radiological data. The aim of this work is to understand the underlying mechanisms of MS fatigue by means of a multidimensional evaluation.
Fatigued (n = 21) and non-fatigued (n = 17) MS patients were enrolled based on the Modified Fatigue Impact Scale. They underwent clinical (disability score and disease duration), neuropsychological (scales of depression, anxiety, alexithymia, sleep, and Symbol Digit Modalities Test), neurophysiological (corticospinal excitability measures using transcranial magnetic stimulation), and radiological (volume-based morphometric magnetic resonance imaging) evaluations. The normality of data distribution was studied by the Kolmogorov-Smirnov test. Group comparison was performed using the Mann-Whitney or Student t test (quantitative data) and the exact Fisher's test (qualitative data). Correlation analysis was done using Pearson and Spearman tests.
Fatigued patients had higher depression (p = 0.02), anxiety (p = 0.02) and alexithymia (p = 0.04) scores compared to non-fatigued patients. On the neurophysiological and radiological evaluations, they also had higher short-interval intracortical inhibition (p = 0.04), larger caudate nuclei (p ≤ 0.01) and smaller left parietal cortex (p = 0.01). These findings were in line with the correlation analyses results.
The neuropsychological findings suggest common underlying mechanisms as well as bi-directional relationships between fatigue and each of anxiety, depression, and alexithymia. The neurophysiological findings may reflect maladaptive neuroplasticity processes and an aberrant GABAergic transmission in the generation of fatigue. The radiological findings could be interpreted in the light of the 'dysfunctional hypertrophy' or 'compensatory hypertrophy' hypotheses.
Pain and cognitive impairment are frequent symptoms in patients with multiple sclerosis (MS). Neglecting experimental pain and paying attention to demanding tasks is reported to decrease the pain ...intensity. Little is known about the interaction between chronic neuropathic pain and attention disorders in MS. Recently, transcranial direct current stimulation (tDCS) was used to modulate various cognitive and motor symptoms in MS. We aimed to study the effects of transcranial random noise stimulation (tRNS), a form of transcranial electric stimulation, over the left dorsolateral prefrontal cortex (DLPFC) on attention and neuropathic pain in MS patients.
16 MS patients were included in a randomized, sham-controlled, cross-over study. Each patient randomly received two tRNS blocks, separated by three weeks of washout interval. Each block consisted of three consecutive daily sessions of either active or sham tRNS. The patients were evaluated for pain, attention and mood and further underwent an electrophysiological evaluation.
Compared to sham, tRNS showed a trend to decrease the N2-P2 amplitudes of pain related evoked potentials and improve pain ratings. Attention performance and mood scales did not change after stimulations.
This study suggests the role of tRNS in pain modulation, which could have been more evident with longer stimulation protocols.
In this retrospective study, we aimed at defining the clinical, paraclinical and outcome features of acute neurological syndromes associated with anti-GQ1b antibodies.
We identified 166 patients with ...neurological symptoms appearing in less than 1 month and anti-GQ1b antibodies in serum between 2012 and 2022. Half were female (51%), mean age was 50 years (4-90), and the most frequent clinical features were areflexia (80% of patients), distal upper and lower limbs sensory symptoms (78%), ophthalmoplegia (68%), sensory ataxia (67%), limb muscle weakness (45%) and bulbar weakness (45%). Fifty-three patients (32%) presented with complete (21%) and incomplete (11%) Miller Fisher syndrome (MFS), thirty-six (22%) with Guillain-Barre syndrome (GBS), one (0.6%) with Bickerstaff encephalitis (BE), and seventy-three (44%) with mixed MFS, GBS & BE clinical features. Nerve conduction studies were normal in 46% of cases, showed demyelination in 28%, and axonal loss in 23%. Anti-GT1a antibodies were found in 56% of cases, increased cerebrospinal fluid protein content in 24%, and Campylobacter jejuni infection in 7%. Most patients (83%) were treated with intravenous immunoglobulins, and neurological recovery was complete in 69% of cases at 1 year follow-up. One patient died, and 15% of patients relapsed. Age > 70 years, initial Intensive Care Unit (ICU) admission, and absent anti-GQ1b IgG antibodies were predictors of incomplete recovery at 12 months. No predictors of relapse were identified.
This study from Western Europe shows acute anti-GQ1b antibody syndrome presents with a large clinical phenotype, a good outcome in 2/3 of cases, and frequent relapses.
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