Barriers to accessing multiple sclerosis disease-modifying therapies in the Middle East and North Africa region: A regional survey-based study.

Background: Multiple sclerosis (MS) management varies markedly between different countries of the Middle East and North Africa (MENA) region based on the availability and accessibility of disease-modifying therapies (DMTs).

Objective: To evaluate the accessibility to DMTs in each MENA country, identify barriers to treatment and make recommendations for improved access to DMTs across the region.

Methods: This is a descriptive, survey-based study whereby we extracted data collected, between October 2019 and April 2020, for countries in the MENA region by the Multiple Sclerosis International Federation (MSIF) through their Atlas of MS survey.

Myotonia in a patient with a mutation in an S4 arginine residue associated with hypokalaemic periodic paralysis and a concomitant synonymous CLCN1 mutation.

The sarcolemmal voltage gated sodium channel Na1.4 conducts the key depolarizing current that drives the upstroke of the skeletal muscle action potential. It contains four voltage-sensing domains (VSDs) that regulate the opening of the pore domain and ensuing permeation of sodium ions.

Spider toxin inhibits gating pore currents underlying periodic paralysis.

Gating pore currents through the voltage-sensing domains (VSDs) of the skeletal muscle voltage-gated sodium channel Na1.4 underlie hypokalemic periodic paralysis (HypoPP) type 2. Gating modifier toxins target ion channels by modifying the function of the VSDs.

Dysfunction of NaV1.4, a skeletal muscle voltage-gated sodium channel, in sudden infant death syndrome: a case-control study.

Background: Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant death in high-income countries. Central respiratory system dysfunction seems to contribute to these deaths. Excitation that drives contraction of skeletal respiratory muscles is controlled by the sodium channel NaV1.

Congenital myopathy with "corona" fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A.

We describe two brothers with lower facial weakness, highly arched palate, scaphocephaly due to synostosis of the sagittal and metopic sutures, axial hypotonia, proximal muscle weakness, and mild scoliosis. The muscle MRI of the younger sibling revealed a selective pattern of atrophy of the gluteus maximus, adductor magnus and soleus muscles. Muscle biopsy of the younger sibling revealed myofibres with internalized nuclei, myofibrillar disarray, and "corona" fibres.

Contrasting roles of Ih and the persistent sodium current at subthreshold voltages during naturalistic stimuli.

The subthreshold activity of hippocampal CA1 pyramidal neurons is regulated by the persistent sodium current (I) and the h-current (I), carried by tetrodotoxin-sensitive sodium channels and hyperpolarization-activated cyclic-nucleotide-gated channels, respectively. Recently, Yamada-Hanff and Bean (J Neurophysiol 114: 2376-2389, 2015) used pharmacological methods to discern the roles of I and I at subthreshold voltages during naturalistic stimuli. We discuss these findings in the context of dorsoventral heterogeneity in the hippocampus and suggest further applications of the method.

Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.

Congenital myopathies are a clinically and genetically heterogeneous group of muscle disorders characterized by congenital or early-onset hypotonia and muscle weakness, and specific pathological features on muscle biopsy. The phenotype ranges from foetal akinesia resulting in in utero or neonatal mortality, to milder disorders that are not life-limiting. Over the past decade, more than 20 new congenital myopathy genes have been identified.