Assessing mNIS+7Ionis and international neurologists' proficiency in a familial amyloidotic polyneuropathy trial

INTRODUCTION: Polyneuropathy signs (Neuropathy Impairment Score, NIS), neurophysiologic tests (m+7Ionis ), disability, and health scores were assessed in baseline evaluations of 100 patients entered into an oligonucleotide familial amyloidotic polyneuropathy (FAP) trial. METHODS: We assessed: (1) Proficiency of grading neurologic signs and correlation with neurophysiologic tests, and (2) clinometric performance of modified NIS+7 neurophysiologic tests (mNIS+7Ionis ) and its subscores and correlation with disability and health scores. RESULTS: The mNIS+7Ionis sensitively detected, characterized, and broadly scaled diverse polyneuropathy impairments. Polyneuropathy signs (NIS and subscores) correlated with neurophysiology tests, disability, and health scores. Smart Somatotopic Quantitative Sensation Testing of heat as pain 5 provided a needed measure of small fiber involvement not adequately assessed by other tests. CONCLUSIONS: Specially trained neurologists accurately assessed neuropathy signs as compared to referenced neurophysiologic tests. The score, mNIS+7Ionis , broadly detected, characterized, and scaled polyneuropathy abnormality in FAP, which correlated with disability and health scores. Muscle Nerve 56: 901-911, 2017

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

Moussa A Chalah,1,2 Samar S Ayache1–3 1EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France; 2Service de Physiologie – Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique – Hôpitaux de Paris, Créteil, France; 3Neurology Division, Lebanese American University Medical Center, Rizk Hospital, Beirut, Lebanon 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, CD3+CD4+ 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. Keywords: pathophysiology, cytokines, interleukins, cerebrospinal fluids, inflammatory marker

Stem Cells Therapy in Multiple Sclerosis - A New Hope for Progressive Forms

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system and represents a major cause of disability in young adults. Nowadays, the dichotomy between demyelination and neurodegeneration has been challenged, and both processes are believed to occur independently early in the disease process. ‘Relapsing-remitting’ MS is the most common subtype which generally shifts to a ‘secondary progressive’ form; MS progression is usually accompanied by a worsening of the motor, cognitive and emotional symptoms, as well as an increase in the disability level. Primary progressive MS represents a third subtype with severe disability scores, poor prognosis, and usually symptomatic management. In this perspective, an ideal therapy should have immunomodulatory, neuroprotective, regenerative and remyelinating potentials. Here, we discuss the promising abilities of stem cells therapies in patients with MS. The available data are tackled aiming to overcome the previously faced limitations and pave the way for larger scale randomized and controlled studies

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS).

A group of European experts was commissioned to establish guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) from evidence published up until March 2014, regarding pain, movement disorders, stroke, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consciousness disorders, tinnitus, depression, anxiety disorders, obsessive-compulsive disorder, schizophrenia, craving/addiction, and conversion. Despite unavoidable inhomogeneities, there is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency (LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke. The effects of rTMS in a number of indications reach level C (possible efficacy), including LF-rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations. It remains to determine how to optimize rTMS protocols and techniques to give them relevance in routine clinical practice. In addition, professionals carrying out rTMS protocols should undergo rigorous training to ensure the quality of the technical realization, guarantee the proper care of patients, and maximize the chances of success. Under these conditions, the therapeutic use of rTMS should be able to develop in the coming years