Acute Treatment of Migraine: Expert Consensus Statements from the United Arab Emirates (UAE).

INTRODUCTION: Migraine, characterized by recurrent headaches and often accompanied by other symptoms like nausea, vomiting, and sensitivity to light and sound, significantly impacts patients' quality of life (QoL) and daily functioning. The global burden of migraines is reflected not only in terms of reduced QoL but also in the form of increased healthcare costs and missed work or school days. While UAE (United Arab Emirates)-specific consensus-based recommendations for the effective use of preventive calcitonin gene-related peptide (CGRP)-based migraine therapies have been published previously, an absence of such regional guidance on the management of acute migraine represents a gap that needs to be urgently addressed. METHODS: A task force of eight neurologists from the UAE with expertise in migraine management conducted a comprehensive literature search and developed a set of expert statements on the management of acute migraine that were specific to the UAE context. To ensure diverse perspectives are considered, a Delphi panel comprising 16 neurologists plus the task force members was set up. Consensus was achieved using a modified Delphi survey method. Consensus was predefined as a median rating of 7 or higher without discordance (if > 25% of the Delphi panelists rate an expert statement as 3 or lower on the Likert scale). Expert statements achieving consensus were adopted. RESULTS: The Modified Delphi method was used successfully to achieve consensus on all nine expert statements drafted by the task force. These consensus statements aim to provide a comprehensive guide for UAE healthcare professionals in treating acute migraine. The statements cover all aspects of acute migraine treatment, including what goals to set, the timing of treatment, treatment strategy to use in case of inadequate response to triptans, safety aspects of combining gepants for acute attacks with preventive CGRP-based therapies, special population (pregnant and pediatric patients) considerations, and the management of the most bothersome symptoms (MBS). CONCLUSIONS: Adopting these consensus statements on the treatment of acute migraine can help enhance patient care, improve outcomes, and standardize treatment practices in the UAE. The collaborative effort of experts with diverse experiences in developing these consensus statements will strengthen the credibility and applicability of these statements to various healthcare settings in the country.

Consensus-Based Recommendations on the Use of CGRP-Based Therapies for Migraine Prevention in the UAE.

INTRODUCTION: Migraine is a common debilitating neurological disorder affecting a large proportion of the general population. Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, plays a key role in the pathophysiology of migraine, and the development of therapies targeting the anti-CGRP pathway has revolutionized the field of migraine treatment. METHODS: An expert task force of neurologists in the United Arab Emirates (UAE) developed and critically assessed recommendations on the use of CGRP-based therapies in migraine treatment and management in the UAE, based on available published literature. A consensus was reached for each statement by means of an open-voting process, based on a predefined agreement level of at least 60%. RESULTS: The consensus recommendations advocate the need for guidelines for the appropriate use of CGRP-based therapies by defining patient cohorts and appropriate monitoring of therapeutic response as well as standardizing the initiation, assessment, and cessation of treatment. The consensus recommendations were primarily formulated on the basis of international studies, because of the limited availability of regional and local data. As such, they may also act as guidelines for global healthcare providers. CONCLUSIONS: These are the first consensus recommendations for the UAE that address the use of CGRP-based therapies in the treatment and management of migraine, integrating both clinical evidence and medical expertise to enhance clinical judgment and decision-making.

Effects of the TENS device, Exopulse Mollii Suit, on pain related to fibromyalgia: An open-label study.

Fibromyalgia is characterized by diffuse and chronic pain, that is often only partially alleviated by the available pharmacological treatments. Therefore, nonpharmacological interventions such as transcutaneous electrical stimulation (TENS) are highly needed to improve the quality of life of this population. However, the classical TENS devices offer a limited number of electrodes and are not adapted to this diffuse painful condition. For these reasons, we aimed to assess the effects of a new TENS device, the Exopulse Mollii Suit, that can stimulate up to 40 muscle groups integrated into pants and jackets and connected to a control unit. We report the data of 50 patients who received one session of active stimulation (pulse intensity 2 mA, and pulse frequency 20 Hz). Pain intensity was evaluated by means of the visual analogue scale (VAS), before (T0) and after the session (T1), and 24 h later (T24). Compared to baseline scores, a significant decrease in VAS was observed after the session (p<0.001), and 24 h later (p<0.001). T1 scores were significantly lower than T24 scores (p<0.001). Therefore, this new system seems to exert analgesic effects whose mechanisms primarily evoke the theory of "gate control". The effects were transient and started to decrease the following day, highlighting the need for additional studies to better evaluate the long-term effects of this intervention on pain, mood, and quality of life.

The impact of forced displacement: trauma, increased levels of inflammation and early presentation of diabetes in women Syrian refugees.

BACKGROUND: Forced displacement and war trauma cause high rates of post-traumatic stress, anxiety disorders and depression in refugee populations. We investigated the impact of forced displacement on mental health status, gender, presentation of type 2 diabetes (T2D) and associated inflammatory markers among Syrian refugees in Lebanon. METHODS: Mental health status was assessed using the Harvard Trauma Questionnaire (HTQ) and the Hopkins Symptom Checklist-25 (HSCL-25). Additional metabolic and inflammatory markers were analyzed. RESULTS: Although symptomatic stress scores were observed in both men and women, women consistently displayed higher symptomatic anxiety/depression scores with the HSCL-25 (2.13 ± 0.58 versus 1.95 ± 0.63). With the HTQ, however, only women aged 35-55 years displayed symptomatic post-traumatic stress disorder (PTSD) scores (2.18 ± 0.43). Furthermore, a significantly higher prevalence of obesity, prediabetes and undiagnosed T2D were observed in women participants (23.43, 14.91 and 15.18%, respectively). Significantly high levels of the inflammatory marker serum amyloid A were observed in women (11.90 ± 11.27 versus 9.28 ± 6.93, P = 0.036). CONCLUSIONS: Symptomatic PTSD, anxiety/depression coupled with higher levels of inflammatory marker and T2D were found in refugee women aged between 35 and 55 years favoring the strong need for psychosocial therapeutic interventions in moderating stress-related immune dysfunction and development of diabetes in this subset of female Syrian refugees.

Autoimmune Brainstem Encephalitis: An Illustrative Case and a Review of the Literature.

Autoimmune brainstem encephalitis (BSE) is a rare neurological condition with a wide range of underlying etiologies. It can be subdivided into two broad groups: a primary inflammatory disease of the central nervous system (CNS) or a brainstem disorder secondary to systemic diseases where the CNS is only one of many affected organs. Symptoms range from mild to life-threatening manifestations. Most cases respond well to immunotherapy. Therefore, broad and in-depth knowledge of the various inflammatory disorders that target the brainstem is essential for guiding the diagnostic approach and assisting in early initiation of appropriate therapy. We herein report on a case of BSE and provide an overview of the various causes of autoimmune BSE with an emphasis on the clinical manifestations and diagnostic approach.

Randomised, controlled trial of erenumab for the prevention of episodic migraine in patients from Asia, the Middle East, and Latin America: The EMPOwER study.

OBJECTIVE: EMPOwER, a double-blind, randomised, phase 3 study, evaluated the efficacy and safety of erenumab in adults with episodic migraine from Asia, the Middle East, and Latin America. METHODS: Randomised patients (N = 900) received monthly subcutaneous injections of placebo, erenumab 70 mg, or 140 mg (3:3:2) for 3 months. Primary endpoint was change from baseline in monthly migraine days at Month 3. Other endpoints included achievement of ≥50%, ≥75%, and 100% reduction in monthly migraine days, change in monthly acute migraine-specific medication treatment days, patient-reported outcomes, and safety assessment. RESULTS: At baseline, mean (standard deviation) age was 37.5 (9.9) years, 81.9% were women, and monthly migraine days was 8.2 (2.8). At Month 3, change from baseline in monthly migraine days (primary endpoint) was -3.1, -4.2, and -4.8 days for placebo, erenumab 70 mg, and erenumab 140 mg, respectively, with a statistically significant difference for erenumab versus placebo (P = 0.002 [70 mg], P < 0.001 [140 mg]). Both erenumab doses were also significantly superior to placebo on all secondary endpoints, including the proportion of patients achieving ≥50% reduction from baseline in monthly migraine days, change from baseline in monthly acute migraine-specific medication treatment days and change from baseline in the Headache Impact Test-6™ scores. The safety profile of erenumab was comparable with placebo; no new safety signals were observed. CONCLUSIONS: This study of erenumab in patients with episodic migraine from Asia, the Middle East, and Latin America met all primary and secondary endpoints. A consistent numerical benefit was observed with erenumab 140 mg versus erenumab 70 mg across all efficacy endpoints. These findings extend evidence of erenumab's efficacy and safety to patients under-represented in previous trials.ClinicalTrials.gov identifier: NCT03333109.

Real-world retrospective study of effectiveness and safety of FINgOlimod in relapsing remitting multiple sclerosis in the Middle East and North Africa (FINOMENA).

OBJECTIVES: Evidence on the effectiveness and safety of fingolimod in real-world clinical practice in the Middle East and North African (MENA) region is limited. This study aimed to evaluate the effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) in real-world setting in the MENA region. PATIENTS AND METHODS: RRMS patients who had been treated with fingolimod for at least 12 months were retrospectively identified from the databases of 34 centers across the MENA region. Study outcomes included the annualized relapse rate (ARR), relapse-free rate (RFR), time to first and second relapses, mean change in Expanded Disability Status Scale (EDSS), proportion of patients with Magnetic Resonance Imaging (MRI) activity and no evidence of disease activity (NEDA)-3, retention of patients on treatment, as well as all safety measures. RESULTS: A total of 806 patients were included: 66.34 % female; mean age 32.97 ± 9.62 years; mean disease duration 4.92 ± 4.66 years; mean fingolimod use 37.2 ± 16.7 months. Most patients had received previous disease-modifying therapy (79.65 %). Compared to the year preceding fingolimod initiation, RFR improved (33.00%-86.35%; p < 0.001), ARR decreased (0.84 ± 0.73 to 0.16 ± 0.45; p = 0.005), EDSS decreased (2.69 ± 1.74-2.01 ± 1.66; p < 0.001), and the proportion of patients with Gadolinium-enhancing T1 lesions decreased (57.84 % to 12.93 %; p < 0.001), after 12 months of fingolimod treatment. NEDA-3 was achieved in 41.3 % of patients. Median time to first and second relapses was not reached since 86.35 % and 98.39 % of patients had not experienced relapses for the first time and second time, respectively. Eight-hundred one (99.38 %) patients continued fingolimod treatment beyond 12 months. One-hundred thirty patients (16.13 %) experienced adverse events, mainly lymphopenia (5.46 %) and leukopenia (2.11 %), while 13 patients (1.61 %) experienced serious adverse events. CONCLUSION: This study confirms the effectiveness and safety profile of fingolimod in real-world setting in the Middle East and North African (MENA) region.

The value of sensory nerve conduction studies in the diagnosis of Guillain-Barré syndrome.

Electrophysiology plays a determinant role in Guillain-Barré syndrome (GBS) diagnosis, classification, and prognostication. However, traditional electrodiagnostic (EDX) criteria for GBS rely on motor nerve conduction studies (NCS) and are suboptimal early in the course of the disease or in the setting of GBS variants. Sensory nerve conduction studies, including the sural-sparing pattern and the sensory ratio are not yet included in EDX criteria despite their well-established role in GBS diagnosis. The aim of this review is to discuss the diagnostic value of sensory NCS in GBS, their role in establishing the diagnosis and predicting the outcome according to the various subtypes of the disease.

Tremor in Multiple Sclerosis-An Overview and Future Perspectives.

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.

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

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.

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

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.

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

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.

Vitamin K2 Status and Arterial Stiffness Among Untreated Migraine Patients: A Case-Control Study.

OBJECTIVE: We aimed to examine arterial stiffness and vitamin K2 status in migraine subjects by comparison to controls. BACKGROUND: Migraine is a primary headache disorder that has been associated with an increased risk of cardiovascular events. Mechanisms underlying this increased risk, however, remain unclear. Vitamin K2 deficiency emerged as a cardiovascular risk factor, but vitamin K2 status has never been explored in migraine subjects. DESIGN AND METHODS: This is a case-control, single-center, observational study that includes a cohort of subjects with migraine and their age- and sex-matched controls. Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Dephosphorylated-uncarboxylated matrix-Gla-protein (dp-ucMGP) was used as a marker for vitamin K2 status. A propensity-matched scoring method was used. RESULTS: A total of 146 patients (73 matched pairs) were included in this study, of whom 89% were women with a mean age of 31.9 ± 8.4 years. Compared with controls, migraine patients had statistically significantly higher mean cfPWV (7.2 ± 1.1 vs 6.4 ± 0.8 m/s, 95% confidence interval (CI) of mean difference [0.45, 1.08], P < .001), as well as higher dp-ucMGP (454.3 ± 116.7 pmol/L vs 379.8 ± 126.6 pmol/L, 95% CI of mean difference [34.63, 114.31], P < .001). Higher cfPWV was associated with higher dp-ucMGP concentrations only in the migraine with aura (MWA) group. Moreover, migraine subjects had a higher frequency of vitamin K2 deficiency (dp-ucMGP ≥ 500 pmol/L) compared to controls, but this association was not statistically significant (23/73 [31.5%] vs 16/73 [21.9%], P = .193). CONCLUSIONS: Individuals with migraine have worse indices of arterial stiffness as compared with their age- and sex-matched control subjects. This increase in arterial stiffness is associated with an increase in markers of vitamin K2 deficiency in the MWA group.

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

Background: 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. Objectives: (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. Method: 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. Results: After treatment, the mean improvement of T25wt (ΔT25wt) was 4.9 s. Significant enhancement of intra-cortical facilitation was observed (139% versus 241%, p = 0.01) following treatment. A positive correlation was found between baseline resting motor threshold (rMT) and both EDSS (r = 0.57; p < 0.01) and ΔT25wt (r = 0.57, p = 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%). Discussion: 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.

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

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.

Hyperacoustic hypoacusis: A new pontine syndrome-Case report.

We herein report a unique case of a lateral pontine demyelinating lesion presenting with unilateral sensorineural hearing loss and paradoxical ipsilateral hyperacusis. The association of unilateral hearing loss and ipsilateral hyperacusis is a rare manifestation of a central nervous system lesion. The paradoxical combination of these symptoms strongly suggests pontine dysfunction and prompts urgent neurological evaluation.

Effects of left DLPFC versus right PPC tDCS on multiple sclerosis fatigue.

BACKGROUND AND OBJECTIVE: Fatigue is a frequent and debilitating symptom in patients with multiple sclerosis (MS). Its classical treatments are still faced with limited benefits and numerous side effects. Hence, we aimed to evaluate the effects of transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique, on such a challenging symptom. Our secondary outcomes included the assessment of tDCS impact on mood and attentional performance. METHODS: Ten fatigued MS patients were enrolled in a double-blind, sham-controlled, and cross-over study. Each patient randomly received three anodal tDCS blocks: active stimulation over the left dorsolateral prefrontal cortex (DLPFC), active stimulation over the right posterior parietal cortex (PPC), and sham stimulation over either cortical site. Both cortical targets are key components in the MS fatigue networks. The blocks consisted of five consecutive daily sessions and were held apart by a washout interval of three weeks. RESULTS: Only active left DLPFC stimulation significantly ameliorated fatigue. Mood improvement was exclusively obtained following active right PPC stimulation. Neither intervention had effects on attention. CONCLUSION: Our study supports the role of anodal tDCS over the left prefrontal in treating MS fatigue. The lack of tDCS effects on attention might be related to the heterogeneity of the studied cohort, the relatively small sample size, the protocol design and duration. Modifying these variables and coupling tDCS with neuroimaging might improve the clinical outcomes and enhance our understanding of the tDCS mechanism of actions.

Fatigue in Multiple Sclerosis: Neural Correlates and the Role of Non-Invasive Brain Stimulation.

Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the central nervous system (CNS) and the major cause of non-traumatic disability in young adults. Fatigue is a frequent symptom reported by the majority of MS patients during their disease course and drastically affects their quality of life. Despite its significant prevalence and impact, the underlying pathophysiological mechanisms are not well elucidated. MS fatigue is still considered the result of multifactorial and complex constellations, and is commonly classified into "primary" fatigue related to the pathological changes of the disease itself, and "secondary" fatigue attributed to mimicking symptoms, comorbid sleep and mood disorders, and medications side effects. Radiological, physiological, and endocrine data have raised hypotheses regarding the origin of this symptom, some of which have succeeded in identifying an association between MS fatigue and structural or functional abnormalities within various brain networks. Hence, the aim of this work is to reappraise the neural correlates of MS fatigue and to discuss the rationale for the emergent use of noninvasive brain stimulation (NIBS) techniques as potential treatments. This will include a presentation of the various NIBS modalities and a suggestion of their potential mechanisms of action in this context. Specific issues related to the value of transcranial direct current stimulation (tDCS) will be addressed.

Permanent reversal of essential tremor following a frontal lobe stroke.

Following a right prerolandic stroke, a 76 year old woman with bilateral upper extremity essential tremor (ET) recovered permanently from the latter contralaterally to the affected hemisphere. The ischemic stroke likely interrupted the cortical component of the ET network. Given the magnitude of neuronal loss, post-stroke cortical reorganization was unable to restore this important component of the ET network, accounting for the permanent nature of ET suppression.