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Channelopathies CHANNELOPATHIES José Longatto Specialist Neuromuscular Physiotherapist Learning objectives: • Clinic overview • What Skeletal Muscle Channelopathies are • Main groups • Symptoms and triggers • Treatments • Physiotherapy NMCHAN • Once monthly - plans to increase • Consultants: Pinki Munoti (GOSH) Emma Matthews (UCLH) • Physiotherapist: José Longatto • CNS: Sian Craig TOTAL 39 3 3 SCM 5 1 PMC 2 14 MC ATS 10 Hypper PP Hypo PP Undiagnosed/waiting Inherited Ion Channelophaties in Humans Imbrici et al, Frontiers in pharmacology, 2016 Skeletal Muscle Channelopathies: • Hypper PP first discovery 1990 (B Fontaine) • Rare (1 per 100.000) • Inherited – mostly dominant • Paroxysmal neurological dysfunction • Abnormal Muscle excitability Increased Excitability Myotonia - Stiffness • Environmental triggers • Onset Reduced excitability Weakness - paralysis What is a skeletal Muscle Channelopathy? - Muscle and nerves communicate by electrical signals - Electrical signals are made by the movement of positively and negatively charged ions in and out of cells; - The ions can only move through dedicated ion channels - If the channel doesn’t work properly, you have a “Channelopathy” Main groups Symptoms • Fists / hands clenched in cold • Eyelids stuck when crying • Intermittent squint / Double vision intermittently • Gasping or choking when exposed to cold • Leg cramps • Falling over • Limited exercise tolerance • Sodium Channel diseases- Respiratory/Bulbar complications especially in the first years of life • Warm Up phenomenon • Pain Symptoms Investigations • Genetic testing • CK may be normal or elevated • EMG may be myopathic • Exercises and temperature testing • Biopsies may show vacuolation or tubular aggregates • Muscular MRI – fatty infiltration / oedema in STIR in calves • ECG Non – Dystrophic Myotonia Characteristics Triggers Gene Inheritance Myotonia Most Rest Choride- AD/AR Congenita common, Warm Up Channel Gene Stiffness which phenomenon (CLCN1) improves with exercises Paramyotonia Muscle Cold – Sodium- AD Congenita stiffness dramatic Channel gene exacerbated Warm up (SCN4A) paradox Exertion Sodium- No episodes of Overlaps with SCN4A AD/AR Channel weakness. PC but very Myotonias Mild mutation mild causing symptoms if isolated eyelid any myotonia Examining for Myotonia • Grip myotonia • Eyelid Myotonia • Percussion Myotonia • Warms up phenomenon • Transient weakness Periodic Paralysis Recurrent episodes of weakness • Weakness can be focal or generalized • Minor attacks – gait difficulties • Severe attacks – complete paralysis • Some time myotonia • Lasting mins-hours-days • Triggers: rest, carbs, K rich food, exercise, stress • May develop permanent fixed myopathy overtime Periodic Paralysis Periodic Paralyses Characteristics Triggers Gene Inheritance HyperPP Generalized or focal attacks Rest after exercise SCN4A AD May develop fixed proximal Potassium loading weakness HypoPP Generalized or focal attacks Carbohydrate load CACNA1S/SCN4A AD sparing facial and respective muscles Rest after exercise Fixed proximal weakness ATS Generalized or focal attacks Rest after exercise KCNJ2 AD May develop fixed proximal Periods of inactivity weakness May or may not affect facial muscles Dysmorphic features Fainting goat Treatment • Drugs for Myotonia (Non dystrophic): Sodium Channel blockers (mexilitine, carbamazepine, lamotrigine) • Periodic Paralysis: acute attacks (potassium tablets, Acetazolamide, Dichlorphenamide, Bumetanide, Amiloreide, Thiazides for Hyper PP, Spiranolactose for hypokalemic PP. General anaesthetic risks Considerations for exercise • Hypo PP (Ca) - episodes lasting hrs/days • –Precipitated after strenuous exercise, carb heavy meal (am paralysis) Consider: Low carb meals help • Hyper PP (Na) – shorter episodes • –Precipitated by cold, fasting +/- rest after exercise, potassium ingestion Consider: Mild ex/continuing with exercise after start of attack can reduce/stops muscle weakness Low potassium meals help Physiotherapy Advise: Avoid Triggers: (including: Diet life style modification) Mild exercise at onset Warm down Pacing Liaison: Acute episodes of paralysis Educational support and school attendance Not Forgetting: Pain Stretches Education – Exercise avoidance Outcome Measures • TUG • Timed rise • 10 metres • Grip Myometry Physiotherapy Please no pics or videos of this slide https://apcp.csp.org.uk/system/files/guidance_for_paediatric_physiotherapis ts_managing_neuromuscular_disorders_-_2017_0.pdf QUESTIONS? THANK YOU, JOSÉ LONGATTO [email protected].
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