Publications by authors named "Samar S. Ayache"

78 Publications

Editorial: Corticospinal Excitability in Patients With Multiple Sclerosis.

Front Neurol 2020 12;11:635612. Epub 2021 Jan 12.

EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France.

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http://dx.doi.org/10.3389/fneur.2020.635612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835205PMC
January 2021

Effects of Transcranial Direct Current Stimulation on Information Processing Speed, Working Memory, Attention, and Social Cognition in Multiple Sclerosis.

Front Neurol 2020 15;11:545377. Epub 2020 Oct 15.

Department of Psychiatry and Psychotherapy, Klinikum der Universität München, Munich, Germany.

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Cognitive impairment occurs in 40-65% of patients and could drastically affect their quality of life. Deficits could involve general cognition (e.g., attention and working memory) as well as social cognition. Transcranial direct current stimulation (tDCS), is a novel brain stimulation technique that has been assessed in the context of several neuropsychiatric symptoms, including those described in the context of MS. However, very rare trials have assessed tDCS effects on general cognition in MS, and none has tackled social cognition. The aim of this work was to assess tDCS effects on general and social cognition in MS. Eleven right-handed patients with MS received two blocks (bifrontal tDCS and sham, 2 mA, 20 min, anode/cathode over left/right prefrontal cortex) of 5 daily stimulations separated by a 3-week washout interval. Working memory and attention were, respectively, measured using N-Back Test (0-Back, 1-Back, and 2-Back) and Symbol Digit Modalities Test (SDMT) at the first and fifth day of each block and 1 week later. Social cognition was evaluated using Faux Pas Test and Eyes Test at baseline and 1 week after each block. Interestingly, accuracy of 1-Back test improved following sham but not active bifrontal tDCS. Therefore, active bifrontal tDCS could have impaired working memory via cathodal stimulation of the right prefrontal cortex. No significant tDCS effects were observed on social cognitive measures and SDMT. Admitting the small sample size and the learning (practice) effect that might arise from the repetitive administration of each task, the current results should be considered as preliminary and further investigations in larger patient samples are needed to gain a closer understanding of tDCS effects on cognition in MS.
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http://dx.doi.org/10.3389/fneur.2020.545377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593675PMC
October 2020

Tremor in Multiple Sclerosis-An Overview and Future Perspectives.

Brain Sci 2020 Oct 12;10(10). Epub 2020 Oct 12.

Service de Physiologie-Explorations Fonctionnelles, Henri Mondor Hospital, AP-HP, 94010 Créteil, France.

Tremor is an important and common symptom in patients with multiple sclerosis (MS). It constituted one of the three core features of MS triad described by Charcot in the last century. Tremor could have a drastic impact on patients' quality of life. This paper provides an overview of tremor in MS and future perspectives with a particular emphasis on its epidemiology (prevalence: 25-58%), clinical characteristics (i.e., large amplitude 2.5-7 Hz predominantly postural or intention tremor vs. exaggerated physiological tremor vs. pseudo-rhythmic activity arising from cerebellar dysfunction vs. psychogenic tremor), pathophysiological mechanisms (potential implication of cerebellum, cerebello-thalamo-cortical pathways, basal ganglia, and brainstem), assessment modalities (e.g., tremor rating scales, Stewart-Holmes maneuver, visual tracking, digitized spirography and accelerometric techniques, accelerometry-electromyography coupling), and therapeutic options (i.e., including pharmacological agents, botulinum toxin A injections; deep brain stimulation or thalamotomy reserved for severe, disabling, or pharmaco-resistant tremors). Some suggestions are provided to help overcome the unmet needs and guide future therapeutic and diagnostic studies in this complex disorder.
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http://dx.doi.org/10.3390/brainsci10100722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601003PMC
October 2020

Paroxysmal Symptoms in Multiple Sclerosis-A Review of the Literature.

J Clin Med 2020 Sep 25;9(10). Epub 2020 Sep 25.

Gilbert and Rose Mary Chagoury School of Medicine, Lebanese American University, Byblos 4504, Lebanon.

Paroxysmal symptoms are well-recognized manifestations of multiple sclerosis (MS). These are characterized by multiple, brief, sudden onset, and stereotyped episodes. They manifest as motor, sensory, visual, brainstem, and autonomic symptoms. When occurring in the setting of an established MS, the diagnosis is relatively straightforward. Conversely, the diagnosis is significantly more challenging when they occur as the initial manifestation of MS. The aim of this review is to summarize the various forms of paroxysmal symptoms reported in MS, with emphasis on the clinical features, radiological findings and treatment options.
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http://dx.doi.org/10.3390/jcm9103100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600828PMC
September 2020

Gaze holding abnormalities as an inaugural event in multiple sclerosis - A case report.

Clin Neurol Neurosurg 2020 Nov 9;198:106136. Epub 2020 Aug 9.

EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, 94010, Créteil, France; Service de Physiologie-Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, 94010, Créteil, France. Electronic address:

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http://dx.doi.org/10.1016/j.clineuro.2020.106136DOI Listing
November 2020

Phosphorus magnetic resonance spectroscopy and fatigue in multiple sclerosis.

J Neural Transm (Vienna) 2020 08 28;127(8):1177-1183. Epub 2020 Jun 28.

Service de Neuroradiologie, Hôpital Henri-Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94010, Créteil Cedex, France.

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 (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. 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.
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http://dx.doi.org/10.1007/s00702-020-02221-yDOI Listing
August 2020

Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis.

JAMA Neurol 2020 09;77(9):1079-1088

Service de Neurologie, Clinical Investigation Center Institut National de la Santé et de la Recherche Médicale 1434, Centre Hospitalier Universitaire de Strasbourg, Strasbourg, France.

Importance: Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities.

Objective: To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity.

Design, Setting, And Participants: The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020.

Exposures: COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms.

Main Outcomes And Measures: The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes.

Results: A total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS ≥6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01).

Conclusions And Relevance: In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.
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http://dx.doi.org/10.1001/jamaneurol.2020.2581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320356PMC
September 2020

A Scope of the Social Brain in Multiple Sclerosis: Insights From Neuroimaging Studies.

Cogn Behav Neurol 2020 06;33(2):90-102

Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France.

Multiple sclerosis (MS) is the most common inflammatory neurologic disease in young adults. Its pathological mechanisms include demyelination, neurodegeneration, and synaptopathy. Cognitive deficits occur in up to 65% of individuals with MS and affect both nonsocial (eg, information processing speed, memory, and executive functions) and social (ie, emotion recognition, theory of mind, and empathy) cognitive domains. In the last 3 decades, there has been a growing interest in social cognition and its relationship with neuropsychological, sociodemographic, and disease characteristics in individuals with MS. Uncovering the neuropathological correlates of social cognitive deficits is now a crucial aim that would also help us better understand the underlying mechanisms of social cognition. We reviewed 11 neuroimaging studies to investigate social cognition in MS. These studies focused mainly on facial emotion recognition and theory of mind, with the findings suggesting that a disrupted cortico-subcortical network forms the basis of social deficits involving both domains. We then interpreted these results in the context of multiple disconnection syndrome, which occurs as a result of axonal demyelination and degeneration within the connexome of several neural hubs devoted to social cognition. Heterogeneity in social cognitive performance, observed among our study participants, is discussed with reference to the cognitive reserve and brain reserve hypotheses. These reserves may explain why individuals with comparable clinical characteristics of MS may exhibit different cognitive profiles. Further research is required to generalize these findings to the MS population and to inform the development of effective interventions to improve psychosocial functioning in individuals with MS.
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http://dx.doi.org/10.1097/WNN.0000000000000227DOI Listing
June 2020

Transcranial Direct Current Stimulation and Migraine-The Beginning of a Long Journey.

J Clin Med 2020 Apr 22;9(4). Epub 2020 Apr 22.

EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, 94010 Créteil, France.

Migraine, a benign yet disturbing condition, is one of the frequent neurological disorders, affecting up to 15-20% of the worldwide population [...].
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http://dx.doi.org/10.3390/jcm9041194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230683PMC
April 2020

Transcranial Direct Current Stimulation of the Occipital Cortex in Medication Overuse Headache: A Pilot Randomized Controlled Cross-Over Study.

J Clin Med 2020 Apr 10;9(4). Epub 2020 Apr 10.

Gilbert and Rose Mary Chagoury School of Medicine School of Medicine, Lebanese American University, Byblos 4504, Lebanon.

Background: Medication overuse headache (MOH) is a chronic pain syndrome that arises from the frequent use of acute antimigraine drugs. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique with a possible therapeutic effect in this particular context.

Methods: This was a randomized, sham-controlled, cross-over study. Eighteen patients with MOH (17 women, age range: 20-38 years) received three sets of three consecutive daily sessions of tDCS: anodal tDCS over the prefrontal cortex, cathodal tDCS over the occipital cortex ipsilateral to the dominant side of migraine pain, and sham. The order in which the tDCS blocks were delivered was randomly defined based on a 1:1:1 ratio. Patients filled in a migraine diary that allowed recording of the pain intensity (visual analogue scale) and the daily consumption of analgesic pills from one week before to two weeks after each condition.

Results: Both prefrontal and occipital tDCS lowered the total number of migraine days and the number of severe migraine days per week at week 1, but only the effects of occipital tDCS on these two outcomes lasted until week 2. Only occipital tDCS decreased the daily analgesic pills consumption, at weeks 1 and 2.

Conclusion: Three consecutive days of cathodal occipital tDCS appear to improve the clinical outcomes in patients with MOH.
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http://dx.doi.org/10.3390/jcm9041075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230777PMC
April 2020

Effects of Transcranial Direct Current Stimulation on Hand Dexterity in Multiple Sclerosis: A Design for a Randomized Controlled Trial.

Brain Sci 2020 Mar 23;10(3). Epub 2020 Mar 23.

EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, 94010 Créteil, France.

Background: Cerebellar and motor tracts are frequently impaired in multiple sclerosis (MS). Altered hand dexterity constitutes a challenge in clinical practice, since medical treatment shows very limited benefits in this domain. Cerebellar control is made via several cerebellocortical pathways, of which the most studied one links the cerebellum to the contralateral motor cortex via the contralateral ventro-intermediate nucleus of the thalamus influencing the corticospinal outputs. Modulating the activity of the cerebellum or of the motor cortex could be of help.

Method: The main interest here is to evaluate the efficacy of transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique, in treating altered dexterity in MS. Forty-eight patients will be recruited in a randomized, double-blind, sham-controlled, and crossover study. They will randomly undergo one of the three interventions: anodal tDCS over the primary motor area, cathodal tDCS over the cerebellum, or sham. Each block consists of five consecutive daily sessions with direct current (2 mA), lasting 20 min each. The primary outcome will be the improvement in manual dexterity according to the change in the time required to complete the nine-hole pegboard task. Secondary outcomes will include fatigue, pain, spasticity, and mood. Patients' safety and satisfaction will be rated.

Discussion: Due to its cost-effective, safe, and easy-to-use profile, motor or cerebellar tDCS may constitute a potential tool that might improve dexterity in MS patients and therefore ameliorate their quality of life.
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http://dx.doi.org/10.3390/brainsci10030185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139332PMC
March 2020

Corticospinal inhibition and alexithymia in multiple sclerosis patients-An exploratory study.

Mult Scler Relat Disord 2020 Jun 3;41:102039. Epub 2020 Mar 3.

EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France; Service de Physiologie - Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris, Créteil, France. Electronic address:

Objectives: Alexithymia is a multicomponent personality construct that could occur in up to 53% of patients with multiple sclerosis (MS), with recent works proposing higher rates of alexithymia in progressive MS. Among the available models of alexithymia, some propose a deficient interhemispheric communication and an aberrant GABAergic transmission at its origin. However, no single study has addressed the underlying physiological mechanisms of alexithymia in MS. The aim of this work was to assess the relationship between GABAergic neurotransmission and alexithymia in progressive MS by means of transcranial magnetic stimulation (TMS).

Methods: Twelve patients with high alexithymia and fifteen patients with low alexithymia were included based on Toronto Alexithymia Scale (TAS). Sociodemographic, clinical and neuropsychological data were recorded. The following corticospinal excitability measures were obtained: resting motor threshold, cortical silent period (CSP which reflects cortical GABAergic function), and interhemispheric inhibition (i.e., GABAergic function mediated by interhemispheric fibers).

Results: No significant group differences were observed regarding sociodemographic, clinical or neuropsychological variables. Patients with high alexithymia scores exhibited shorter CSP than those with low alexithymia scores (81.87 ± 45.72 ms vs. 145.27 ± 77.26 ms, respectively, p < 0.05). A significant inverse correlation was also found between TAS scores and CSP duration (r = -0.59, p < 0.05).

Conclusion: This study offers insights into the neurophysiological mechanisms of alexithymia in MS. Reduced GABAergic transmission, as reflected by short CSP, seems to be associated with alexithymia in this population. Future studies would benefit from a more comprehensive evaluation of cortical and interhemispheric mechanisms in MS patients with alexithymia.
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http://dx.doi.org/10.1016/j.msard.2020.102039DOI Listing
June 2020

Bifrontal transcranial direct current stimulation modulates fatigue in multiple sclerosis: a randomized sham-controlled study.

J Neural Transm (Vienna) 2020 06 11;127(6):953-961. Epub 2020 Mar 11.

EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France.

Fatigue is a frequent and debilitating symptom in patients with central nervous system diseases. Up to 90% of patients with multiple sclerosis (MS) suffer from fatigue that drastically affects the quality of life. MS patients also complain of anxiety and depressive symptoms and these three manifestations tend to cluster together in this clinical population. The objective of this work was to assess the effects of transcranial direct stimulation (tDCS), a noninvasive brain stimulation technique, on fatigue as well as anxiety and depressive symptoms. Eleven fatigued MS patients randomly received two blocks (active and sham tDCS) of five consecutive daily sessions of bifrontal tDCS (anode/cathode over the left/right prefrontal cortices, respectively) in a crossover manner, separated by a 3-week washout interval. Evaluation took place at day 1, day 5 (right after each block) and 1 week later. Active but not sham tDCS resulted in a significant improvement of fatigue at day 5 (p < 0.05), an effect that seems to last at least 1 week following the stimulation (p = 0.05). Active tDCS also significantly improved anxiety symptoms, but the effect emerged 1 week later (p < 0.05). No significant effects were obtained regarding depression (p > 0.05). Bifrontal tDCS seems to modulate fatigue in PwMS. The observed anxiolytic effects could constitute delayed after effects of tDCS or might be mediated by fatigue improvement. These findings merit to be addressed in large-scale controlled trials.
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http://dx.doi.org/10.1007/s00702-020-02166-2DOI Listing
June 2020

Deciphering the neural underpinnings of alexithymia in multiple sclerosis.

Neurosci Lett 2020 04 5;725:134894. Epub 2020 Mar 5.

EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France; Service de Physiologie - Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris, Créteil, France. Electronic address:

Objectives: 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.

Methods: 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.

Results: 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).

Conclusion: 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.
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http://dx.doi.org/10.1016/j.neulet.2020.134894DOI Listing
April 2020

Could Transcranial Direct Current Stimulation Join the Therapeutic Armamentarium in Obsessive-Compulsive Disorder?

Brain Sci 2020 Feb 23;10(2). Epub 2020 Feb 23.

Service de Physiologie, Explorations Fonctionnelles, Hôpital Henri-Mondor, AP-HP, 94010 Créteil, France.

Obsessive-compulsive disorder (OCD) is a mental disorder that can affect around 1-3% of individuals [...].
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http://dx.doi.org/10.3390/brainsci10020125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071454PMC
February 2020

Cathodal Transcranial Direct Current Stimulation of the Occipital cortex in Episodic Migraine: A Randomized Sham-Controlled Crossover Study.

J Clin Med 2019 Dec 26;9(1). Epub 2019 Dec 26.

Division of Neurology, Lebanese American University Medical Center Rizk Hospital, Beirut 113288, Lebanon.

Three consecutive daily sessions of cathodal transcranial direct current stimulation (tDCS) was sufficient to show a significant decrease in headache duration and intensity as well as tablets consumption, in patients suffering from episodic migraine.

Background: Migraine prophylaxis is recommended in patients with frequent and/or intense headaches, but poor tolerability and lack of efficacy of preventive drugs are common in clinical practice. Hence, new prophylactic strategies are needed.

Objective: The aim of this study was to evaluate the efficacy of tDCS in terms of migraine prophylaxis.

Methods: This was a double blind and sham-controlled trial. Forty-two migraine patients were randomly assigned in a crossover design to receive three consecutive daily sessions of both sham and cathodal tDCS stimulation (2.0 mA, 20 min) over the occipital cortex of the dominant side of the migraine pain (O1/O2). Migraine duration and intensity, number of analgesic tablets, and number of headache-free days (where no headache abortive medications are taken) were recorded one week before and two weeks after treatment. A washout period of one week was allowed before crossing to the other treatment arm.

Results: Relative to sham, cathodal stimulation was associated with a significant reduction in the number of headache days, tablets consumption, and pain intensity; and a significant increase in the number of headache-free days. These beneficial effects were sustained over two weeks. No serious side effects were observed, and the procedure was well tolerated.

Conclusion: Based on these findings, cathodal tDCS applied to the occipital cortex seems to be an effective and well tolerated alternative to pharmacotherapy in patients with episodic migraine.
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http://dx.doi.org/10.3390/jcm9010060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019486PMC
December 2019

Fatigue and Affective Manifestations in Multiple Sclerosis-A Cluster Approach.

Brain Sci 2019 Dec 22;10(1). Epub 2019 Dec 22.

Service de Physiologie, Explorations Fonctionnelles, Hôpital Henri-Mondor, AP-HP, 94010 Créteil, France.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, characterized by a high prevalence in young people, a drastic impact on the quality of life, and an important economic cost to society [...].
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http://dx.doi.org/10.3390/brainsci10010010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017318PMC
December 2019

Precise finger somatotopy revealed by focal motor cortex injury.

Neurophysiol Clin 2020 Feb 9;50(1):27-31. Epub 2019 Dec 9.

EA 4391, excitabilité nerveuse et thérapeutique, université Paris-Est-Créteil, Créteil, France; Service de physiologie - Explorations fonctionnelles, hôpital Henri-Mondor, AP-HP, Créteil, France.

Background: Somatotopy is considered the hallmark of the primary motor cortex. While this is fundamentally true for the major body parts (head, upper and lower extremities), evidence supporting the existence of within-limb somatotopy is scarce.

Method: We report a young man presenting recurrent ischemic strokes with selective finger weakness in whom serial motor cortex mapping procedures were performed.

Result: Following the first stroke, which largely spared the motor cortex, motor mapping displayed overlap of the motor representations of the hand muscles. The second focal stroke, affecting the lateral part of the hand knob, resulted in selective loss of the first dorsal interosseous muscle motor evoked potentials while sparing those of the adductor digiti minimi muscle. This observation is in apparent contradiction with the first mapping results that suggested complete overlap of motor representations.

Discussion: Our mapping results provide evidence for the existence of very precise within-limb somatotopy and confirm the proposed homuncular order, whereby lateral fingers are represented laterally and medial fingers medially. The discrepancy between the initial and subsequent mapping results is discussed in light of functional organization of the primary motor cortex.
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http://dx.doi.org/10.1016/j.neucli.2019.11.001DOI Listing
February 2020

Cortical Excitability Measures May Predict Clinical Response to Fampridine in Patients with Multiple Sclerosis and Gait Impairment.

Brain Sci 2019 Dec 5;9(12). Epub 2019 Dec 5.

Lebanese American University Gilbert and Rose Mary Chagoury School of Medicine, Byblos P.O. Box 36, Lebanon.

Most multiple sclerosis (MS) patients will develop walking limitations during the disease. Sustained-release oral fampridine is the only approved drug that will improve gait in a subset of MS patients. (1) Evaluate fampridine cortical excitability effect in MS patients with gait disability. (2) Investigate whether cortical excitability changes can predict the therapeutic response to fampridine. This prospective observational study enrolled 20 adult patients with MS and gait impairment planned to receive fampridine 10 mg twice daily for two consecutive weeks. Exclusion criteria included: Recent relapse (<3 months), modification of disease modifying drugs (<6 months), or Expanded Disability Status Scale (EDSS) score >7. Neurological examination, timed 25-foot walk test (T25wt), EDSS, and cortical excitability studies were performed upon inclusion and 14 days after initiation of fampridine. After treatment, the mean improvement of T25wt (ΔT25wt) was 4.9 s. Significant enhancement of intra-cortical facilitation was observed (139% versus 241%, = 0.01) following treatment. A positive correlation was found between baseline resting motor threshold (rMT) and both EDSS ( = 0.57; < 0.01) and ΔT25wt ( = 0.57, = 0.01). rMT above 52% of the maximal stimulator output was found to be a good predictor of a favorable response to fampridine (accuracy: 75%). Fampridine was found to have a significant modulatory effect on the cerebral cortex, demonstrated by an increase in excitatory intracortical processes as unveiled by paired-pulse transcranial magnetic stimulation. rMT could be useful in selecting patients likely to experience a favorable response to fampridine.
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http://dx.doi.org/10.3390/brainsci9120357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956091PMC
December 2019

Longitudinal Extensive Transverse Myelitis in an Immunocompetent Older Individual-A Rare Complication of Varicella-Zoster Virus Reactivation.

Medicina (Kaunas) 2019 May 23;55(5). Epub 2019 May 23.

EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, 94010 Créteil, France.

Varicella-zoster virus (VZV) is a human neurotropic herpes virus that causes chickenpox in children. After becoming latent in dorsal root ganglia, it can reactivate to cause dermatological manifestations, the most common one being shingles or herpes zoster. Severe neurologic dysfunctions can occur in immunocompromised patients such as encephalitis, meningitis, myelitis and neuropathy. Longitudinal extensive transverse myelitis (LETM) is an unusual neurological complication mainly described in immunocompromised patients, with very few cases described in immunocompetent ones. We hereby report a case of VZV-induced LETM in an immunocompetent older adult-a situation rarely described in the literature. LETM is a rare complication of VZV and its pathogenesis; therapeutic interventions and prognosis are far from being fully clarified. However, a prompt diagnosis is needed to allow a rapid initialization of treatment and ensure a better outcome. Although the therapeutic lines are not clear, immunosuppressive agents may have their place in cases of unsuccessful results and/or relapses following acyclovir coupled with a well conducted methylprednisolone therapy. Further studies are highly needed to improve the current understanding of the disease course and mechanisms, and to optimize therapeutic strategies.
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http://dx.doi.org/10.3390/medicina55050201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572170PMC
May 2019

Noninvasive Brain Stimulation and Psychotherapy in Anxiety and Depressive Disorders: A Viewpoint.

Brain Sci 2019 Apr 14;9(4). Epub 2019 Apr 14.

Service de Physiologie, Explorations Fonctionnelles, Hôpital Henri-Mondor, AP-HP, 94010 Créteil, France.

Among the most prevalent psychiatric conditions stand anxiety and depression. Psychotherapy and medications are considered effective treatments in these clinical settings. However, pharmacotherapy and psychotherapy (i.e., cognitive behavioral therapy (CBT)) administered in monotherapy or in a combined regimen do not result in satisfactory outcomes in all patients. Therefore, finding new treatments would be of great help. In the last three decades, noninvasive brain stimulation (NIBS) has emerged as a safe tool to improve several neuropsychiatric symptoms. The following work revisits the available reports that assessed the add-on value of NIBS techniques when combined to psychotherapy (CBT or related interventions) in mood and anxiety disorders. The available protocols targeted the prefrontal cortex, a region that was previously found to have an enhanced activity or functional connectivity after psychotherapeutic interventions. Promising yet scarce evidence exists on this matter. A discrepancy exists among the available reports regarding the type and duration of interventions, the patients' clinical profiles, and the presence of a sham intervention. NIBS may have acted by enhancing psychotherapy effects on the top-down cognitive control of emotions. Combining both therapies may result in promising effects, but future large-scale trials are needed to judge the utility of this combination in psychiatric populations.
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http://dx.doi.org/10.3390/brainsci9040082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523510PMC
April 2019

Coaching of lifestyle recommendations improves sensory neurophysiological parameters in neuropathies related to glycemic disorder or metabolic syndrome. A pilot study.

Neurophysiol Clin 2019 Feb 4;49(1):59-67. Epub 2019 Jan 4.

EA 4391, Faculté de médecine de Créteil, Université Paris Est Créteil, 94010 Créteil, France; Service de neurologie, Groupe hospitalier Henri-Mondor, Centre hospitalier universitaire Henri-Mondor, Assistance publique-Hôpitaux de Paris, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil, France. Electronic address:

Objectives: Metabolic abnormalities, such as, glycemic disorders and metabolic syndrome (GDMS) are one of the main causes of peripheral neuropathies. The objective of this study was to evaluate the impact of adding specific coaching care (CC) to standard care (SC) of therapeutic education based on lifestyle recommendations for neuropathies associated with GDMS.

Methods: This prospective randomized study included two groups of four patients (SC vs. CC) with examiners blinded to group allocation. The SC group had one day of therapeutic education on lifestyle measures (physical activity and diet recommendations) followed by only one phone call of reinforcement. The CC group received an additional weekly phone call of reinforcement for 3 months. Clinical, biological and neurophysiological variables were compared between the two groups at baseline and for the percentage of change at 3 months.

Results: All patients (4 men and 4 women) had diabetes or pre-diabetes, which was associated with metabolic syndrome in 5 cases. There was no difference on any variable at baseline, but at 3 months, Mann-Whitney test showed a difference (P=0.0008) between the two groups regarding the sensory neurophysiological variable, which deteriorated in the SC group (median: -6.0%) and improved in the CC group (median: +12.4%). No significant difference was observed between the two groups for the other variables at 3 months.

Conclusion: The weekly coaching of recommendations for lifestyle measures over a period of three months allows an improvement of GDMS neuropathies, at least in terms of sensory aspects, as evidenced by neurophysiological assessments.
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http://dx.doi.org/10.1016/j.neucli.2018.12.004DOI Listing
February 2019

Neurophysiological, radiological and neuropsychological evaluation of fatigue in multiple sclerosis.

Mult Scler Relat Disord 2019 Feb 21;28:145-152. Epub 2018 Dec 21.

Service de Physiologie, Explorations Fonctionnelles, Hôpital Henri-Mondor, AP-HP, Créteil, France; EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France; Neurology Division, Lebanese American University Medical Center-Rizk Hospital (LAUMC-RH), Beirut, Lebanon. Electronic address:

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1016/j.msard.2018.12.029DOI Listing
February 2019

Moral Judgment: An Overlooked Deficient Domain in Multiple Sclerosis?

Behav Sci (Basel) 2018 Nov 16;8(11). Epub 2018 Nov 16.

EA 4391 Excitabilité Nerveuse et Thérapeutique, Université Paris-Est, 94010 Créteil, France.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system through which patients can suffer from sensory, motor, cerebellar, emotional, and cognitive symptoms. Although cognitive and behavioral dysfunctions are frequently encountered in MS patients, they have previously received little attention. Among the most frequently impaired cognitive domains are attention, information processing speed, and working memory, which have been extensively addressed in this population. However, less emphasis has been placed on other domains like moral judgment. The latter is a complex cognitive sphere that implies the individuals' ability to judge others' actions and relies on numerous affective and cognitive processes. Moral cognition is crucial for healthy and adequate interpersonal relationships, and its alteration might have drastic impacts on patients' quality of life. This work aims to analyze the studies that have addressed moral cognition in MS. Only three works have previously addressed moral judgement in this clinical population compared to healthy controls, and none included neuroimaging or physiological measures. Although scarce, the available data suggest a complex pattern of moral judgments that deviate from normal response. This finding was accompanied by socio-emotional and cognitive deficits. Only preliminary data are available on moral cognition in MS, and its neurobiological foundations are still needing to be explored. Future studies would benefit from combining moral cognitive measures with comprehensive neuropsychological batteries and neuroimaging/neurophysiological modalities (e.g., functional magnetic resonance imaging, tractography, evoked potentials, electroencephalography) aiming to decipher the neural underpinning of moral judgement deficits and subsequently conceive potential interventions in MS patients.
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http://dx.doi.org/10.3390/bs8110105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262463PMC
November 2018

The place of transcranial direct current stimulation in the management of multiple sclerosis-related symptoms.

Neurodegener Dis Manag 2018 12 19;8(6):411-422. Epub 2018 Nov 19.

Service de Physiologie, Explorations Fonctionnelles, Hôpital Henri-Mondor, AP-HP, 94010 Créteil, France.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized by chronic inflammation, demyelination, synaptopathy and neurodegeneration. Patients may exhibit sensory, motor, cognitive, emotional and behavioral symptoms throughout their disease process. Nowadays, the challenge is to find optimal treatment for MS symptoms, especially that available pharmacological interventions are faced by modest therapeutic outcomes and numerous side effects. Thus, finding alternative strategies might be of help in this context. The aim of this report is to visit the effects of transcranial direct current stimulation - a noninvasive brain stimulation technique - in the context of MS symptoms, namely fatigue, cognitive deficits, psychiatric complaints, neuropathic pain and some sensorimotor manifestations.
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http://dx.doi.org/10.2217/nmt-2018-0028DOI Listing
December 2018

Isolated Mammillary Bodies Damage-An Atypical Presentation of Wernicke Syndrome.

Behav Sci (Basel) 2018 Nov 12;8(11). Epub 2018 Nov 12.

EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, 94010 Créteil, France.

We report atypical magnetic resonance imaging (MRI) lesions in a case of Wernicke encephalopathy. The patient presented with isolated anterograde amnesia following a partial colectomy complicated by peritonitis. Fluid-attenuated inversion recovery and T2 MRI sequences were normal. However, bilateral contrast enhancement of mammillary bodies was shown on T1 gadolinium-enhanced sequences. Blood tests revealed thiamine deficiency. The diagnosis of Wernicke encephalopathy was made and thiamine supplementation was given, resulting in complete recovery of the memory functions.
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http://dx.doi.org/10.3390/bs8110104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262580PMC
November 2018

Interhermispheric inhibition predicts anxiety levels in multiple sclerosis: A corticospinal excitability study.

Brain Res 2018 11 30;1699:186-194. Epub 2018 Aug 30.

EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, 94010 Créteil, France; Service de Physiologie - Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris, 94010 Créteil, France; Neurology Division, Lebanese American University Medical Center Rizk Hospital, Beirut, Lebanon. Electronic address:

Background: 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.

Method: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1016/j.brainres.2018.08.029DOI Listing
November 2018

Disentangling the Neural Basis of Cognitive Behavioral Therapy in Psychiatric Disorders: A Focus on Depression.

Brain Sci 2018 Aug 9;8(8). Epub 2018 Aug 9.

EA 4391 Excitabilité Nerveuse et Thérapeutique, Université Paris-Est, 94010 Créteil, France.

Major depressive disorder (MDD) stands among the most frequent psychiatric disorders. Cognitive behavioral therapy (CBT) has been shown to be effective for treating depression, yet its neural mechanisms of action are not well elucidated. The objective of this work is to assess the available neuroimaging studies exploring CBT's effects in adult patients with MDD. Computerized databases were consulted till April 2018 and a research was conducted according to PRISMA guidelines in order to identify original research articles published at any time in English and French languages on this topic. Seventeen studies were identified. Only one study was randomized comparing CBT to pharmacological interventions, and none included an effective control. Following CBT, changes occurred in cerebral areas that are part of the fronto-limbic system, namely the cingulate cortex, prefrontal cortex and amygdala-hippocampal complex. However, the pattern of activation and connectivity in these areas varied across the studies. A considerable heterogeneity exists with regard to study design, adapted CBT type and intensity, and employed neuroimaging paradigms, all of which may partly explain the difference in studies' outcomes. The lack of randomization and effective controls in most of them makes it difficult to draw formal conclusion whether the observed effects are CBT mediated or due to spontaneous recovery. Despite the observed inconsistencies and dearth of data, CBT appears to exert its anti-depressant effects mainly by modulating the function of affective and cognitive networks devoted to emotions generation and control, respectively. This concept remains to be validated in large scale randomized controlled trials.
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http://dx.doi.org/10.3390/brainsci8080150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120051PMC
August 2018

The ulnar ratio as a sensitive and specific marker of acute inflammatory demyelinating polyneuropathy.

Clin Neurophysiol 2018 08 11;129(8):1699-1703. Epub 2018 Jun 11.

Division of Neurology, Lebanese American University Medical Center, Beirut, Lebanon; EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France; Service de Physiologie - Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris, 51 avenue de Lattre de Tassigny, 94010, Créteil, France. Electronic address:

Objectives: To explore the value of a novel sensory criterion, the ulnar ratio - defined as the SNAP amplitude of the palmar cutaneous (pUN) over that of the dorsal branch (dUN) of the ulnar nerve - as a predictor of Acute Inflammatory Demyelinating Polyneuropathy (AIDP).

Methods: We prospectively included 22 patients with AIDP, 20 patients with diabetic peripheral neuropathy (DPN), and 18 controls. Eligible subjects underwent nerve conduction studies including, among others, the dUN, pUN, and sural nerve.

Results: A sural sparing pattern was found in 72% of AIDP cases. The ulnar ratio was significantly lower in patients with AIDP compared to those with DPN or controls. The ROC curve area to discriminate AIDP (versus controls and diabetics together) was higher with the ulnar ratio and pUN compared to dUN. An ulnar ratio ≥ 0.78 seems to be the best threshold to rule out the diagnosis of AIDP, with a specificity of 100% and a sensitivity of 87%. The ulnar ratio was equally reliable in the subgroup of patients presenting within a week of symptoms onset.

Conclusion: The ulnar ratio is a highly sensitive and specific marker of AIDP and can help confirm the diagnosis when direct signs of demyelination are lacking.

Significance: Incorporating specific sensory abnormalities, such as the ulnar ratio, in the electrodiagnostic criteria of AIDP could enhance their reliability.
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http://dx.doi.org/10.1016/j.clinph.2018.05.017DOI Listing
August 2018

Is there a link between inflammation and fatigue in multiple sclerosis?

J Inflamm Res 2018 7;11:253-264. Epub 2018 Jun 7.

EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France.

Purpose: Among autoimmune diseases of the central nervous system stands multiple sclerosis (MS), which is characterized by demyelination, synaptopathy, and neurodegeneration. MS fatigue can affect up to 90% of patients and be very disabling, with a drastic impact on their quality of life. To date, the evaluation of MS fatigue has relied mainly on subjective scales, and actual therapeutic interventions are challenged by modest efficacy and numerous undesirable effects. Therefore, finding biomarkers of MS fatigue might help in optimizing evaluation and treatment strategies. The main objective here was to assess the relationship between MS fatigue and inflammatory or other immunomediated markers.

Methods: Research was conducted according to PRISMA guidelines. Computerized databases (ie, PubMed/Medline and Scopus) were consulted till February 2018 aiming to identify articles that addressed inflammation and MS fatigue. Studies in English and French published at any time were considered.

Results: A total of 27 studies matched the research criteria. Inconsistency existed regarding the relationship between fatigue and the orexin A system, hypothalamus-pituitary-adrenal axis, and cerebrospinal fluid inflammatory markers. As for peripheral markers, although there was scarcity in the available data, serum proinflammatory cytokines (ie, IL6, TNFα, and IFNγ) seem to be associated with MS fatigue. Finally, no link was found between MS fatigue and T-cell populations (ie, CD3CD4 T lymphocytes, regulatory T cells) or other peripheral markers of inflammation (ie, CRP, erythrocyte-sedimentation rate, soluble ICAM1).

Conclusion: Future large-scale studies would benefit from comparing the relationship between fatigue and immune measures in patients with different disease phenotypes with and without disease-modifying drugs. With the subjective nature of fatigue scales, finding objective biomarkers for fatigue would be of great help.
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http://dx.doi.org/10.2147/JIR.S167199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995280PMC
June 2018