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.

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Neuropathic pain (NeP) has been the focus of extensive basic and clinical research over the past 20 years. This has led to an increased understanding of underlying pathophysiological mechanisms and the development of new therapeutic agents, as well as a clearer definition of the role of established medications. To date there are no published treatment guidelines for NeP in the Middle East. A multidisciplinary panel of Middle East and international experts met to review critically and reach a consensus on how best to apply evidence-based guidelines for the treatment of NeP (mainly peripheral NeP) in the Middle East. The expert panel recommended pregabalin, gabapentin and secondary amine tricyclic antidepressants (nortriptyline and desipramine) as first-line treatments for peripheral NeP. Serotonin-norepinephrine reuptake inhibitor antidepressants, tramadol and controlled-release opioid analgesics were recommended as second-line treatments. There is a need to increase diagnostic awareness of NeP, use validated screening questionnaires and undertake more treatment research in the Middle East region.

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

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.