Skeletal muscle channelopathies: a guide to diagnosis and management

Abstract

Skeletal muscle channelopathies are a group of rare episodic genetic disorders comprising the periodic paralyses and the non-dystrophic myotonias. They may cause significant morbidity, limit vocational opportunities, be socially embarrassing, and sometimes are associated with sudden cardiac death. The diagnosis is often hampered by symptoms that patients may find difficult to describe, a normal examination in the absence of symptoms, and the need to interpret numerous tests that may be normal or abnormal. However, the symptoms respond very well to holistic management and pharmacological treatment, with great benefit to quality of life. Here, we review when to suspect a muscle channelopathy, how to investigate a possible case and the options for therapy once a diagnosis is made.

Bioisosteric Modification of To042: Synthesis and Evaluation of Promising Use‐Dependent Inhibitors of Voltage‐Gated Sodium Channels

“…Myotonic syndromes are a heterogeneous group of skeletal muscle inherited disorders characterized by enhanced excitability of the muscle fiber that impairs muscle relaxation after activation. The slow relaxation of the muscles causes disabling symptoms such as stiffness and, sometimes, periodic attacks of weakness and pain [2–4] . Tocainide and mexiletine (Figure 1) are well‐known VGSC blockers belonging to the local anesthetic (LA)‐like drug class, which have long been used off‐label for non‐dystrophic myotonias.…”

“…The slow relaxation of the muscles causes disabling symptoms such as stiffness and, sometimes, periodic attacks of weakness and pain. [ 2 , 3 , 4 ] Tocainide and mexiletine (Figure 1 ) are well‐known VGSC blockers belonging to the local anesthetic (LA)‐like drug class, which have long been used off‐label for non‐dystrophic myotonias. However, tocainide was withdrawn from the market in many countries due to harmful agranulocytosis and anemia.…”

Persistent hypokalaemia and intermittent muscle weakness

“…The blood pressure is important as both hypertension and hypotension may accompany secondary causes of hypokalaemia, for example, a high blood pressure in Conn’s syndrome but a low blood pressure in familial hypokalaemia–hypomagnesemia. Besides examining for weakness, we would also look for dysmorphic features and short stature, which may indicate Andersen-Tawil syndrome 5. Investigations should necessarily include acid–base balance, potassium excretion rate and thyroid function.…”

Miotonías no distróficas: aspectos clínicos y terapéuticos

“…Junto a esta miotonía clínica o de acción, distinguimos la denominada miotonía eléctrica, detectable mediante electromiografía con aguja (EMG) y la denominada miotonía mecánica. En esta última, el fenómeno miotónico puede desencadenarse por percusión directa sobre el músculo, por ejemplo, al golpear con el martillo de reflejos la eminencia tenar y provocar una contracción rápida con oposición del pulgar durante unos segundos antes de que aparezca una relajación gradual 2 .…”

“…Las MND son canalopatías del músculo esquelético causadas por mutaciones en los genes que codifican para los canales iónicos de cloro y sodio dependientes del voltaje de la membrana sarcolémica. En conjunto son enfermedades raras, con una prevalencia menor a 1:100.000 habitantes, pero con una importante morbilidad y repercusión en la calidad de vida de los pacientes 2,3 .…”