Neuromuscular disease with abnormal 11/30/17 movement Cramp • Episodic and involuntary muscle contraction • Associated with pain Neuromuscular disease with abnormal movement • Occur in shorten position and contracting muscle • Motor neuron hyperactivity causing sustained muscle spasm Charungthai Dejthevaporn, MD, PhD, FRCP(T), FRSM • Preceded by fasciculations or muscle twitching du to repetitive Consultant Neurologist, Department of Medicine contractions of motor units Head of Clinical Neurophysiology Unit, EMG Laboratory and • High freQuency discharge (20-150 Hz) on EMG Neuromuscular Clinic Section, Queen Sirikit Medical Center Faculty of Medicine, Ramathibbodi Hospital Mahidol University, Bangkok, Thailand Classification of Cramp Classification of Cramp • Paraphysiological cramp • Idiopathic • occur in healthy person related to specific physiology circumstances • Sporadic • pregnancy or eXercise • Cramp-fasciculation syndrome • hypereXcitability of nerve terminal branches due to continued muscle use • Myokymia-hyperhydrosis syndrome • Inherited • Familial nocturnal cramps Classification of Cramp Classification of Cramp • Symptomatic cramp • Symptomatic cramp • CNS : • Multiple sclerosis, Parkinson’s disease • Hydroelectrolyte disturbances • hypo-Mg++ • PNS : • dehydration • motor neuron disease, neuropathy, radiculopathy, pleXopathy, • Heat cramp, perspiration myopathy • hyper-hypo Na+, K+, Ca++ • Cardiovascular disease • Endocrine-metabolic condition • arterial or venous disease • hypo- hyperthyroid • hypo-hyperparathyroidism • Toxic/medication • uremia and dialysis • statin, fibrate, diuretic • cirrhosis • hypoadrenalism Charungthai Dejthevaporn 1 Neuromuscular disease with abnormal 11/30/17 movement Specific muscle diseases associated with Contracture myalgia and muscle cramps • Myotonic dystrophy • Do not occur at rest • Muscle channelopathies • Develop during eXercise • Chloride channel : MC (Becker, Thomsen) • Related to muscle damage • Sodium channel : PMC, hyperKPP • • Calcium channel : hypoKPP Leading to myoglobinuria and acute tubular necrosis • • Metabolic myopathies Electrically silent on EMG • Glycogen metabolism disorder • Lipid metabolism disorder Disorder of glycolytic or glycogenolytic Contracture enzyme defect • McArdle disease • Painful contracture • myophosphorelase deficiency • Metabolic myopathy – glucose metabolism • Tarui disease • Sodium channelopathy – paramyotonia congenita • phosphofructokinase deficiency • Hypothyroid myopathy • Rippling muscle disease • Exercise intolerance • Painless contracture • Progressive weaKness • Spasticity (damage of descending motor pathway) – muscle stiffness, cramps • Painful contracture and spasms • Prolonged muscle immobilization McArdle’s disease Forearm exercise test • Myalgia and painful muscle cramps • Baseline lactate and ammonia level • develop within minutes only after forceful eXercise • Isometric handgrip contraction • Resolve with rest • • Improve after warm up period of non-exhausting exercise (second wind measure lactate and ammonia level at 1,2,4,6 and 10 minutes phenomenon) • Normal : 3-5 X elevation of lactate and ammonia within 5 min of exercise and return to baseline level within 30 min • Hand cramp posture (similar to focal dystonia or myotonia) • No elevation of lactate in muscle glycogenosis • after forearm eXercise test for lactate production • after performing repetitive gripping movements Charungthai Dejthevaporn 2 Neuromuscular disease with abnormal 11/30/17 movement Hypothyroid myopathy Tetany or capopedal spasm • Myalgia • Continuous tonic spasm of muscle • Muscle cramp • motor unit hyperactivity • Contractures • Paraesthesia • sensory hyperactivity • Muscle stiffness and slow movement • Worsened by cold • Myoedema Rippling muscle disease Caveolinopathy • Painful muscle stiffness, contractures and rippling movement in Caveolin 3 : Component of muscle fibre membrane muscles 4 major phenotypes • Induced with muscle stretching by either voluntary contraction or percussion • LGMD 1C • Myoedema • Distal Myopathy • Electrically silent on EMG • Raised CK • Rippling muscle disease Myotonia Myotonic disorder • Phenomenon of impaired relaXation of the muscle after forceful • Acquired myotonia voluntary contraction • drugs • Repetitive depolarization of muscle membrane • malignancy • Warm up phenomenon • Paramyotonia – worse with cold temperature • Genetic myotonia • Myotonic dystrophy (DM1, 2, 3…) • Spontaneous discharges of muscle fibers on EMG • Non-dystrophic myotonia • waXing and waning of amplitude and freQuency with high firing rate between • Myotonia congenita (chloride channel) 20-150 Hz • Paramyotonia congenita (sodium channel) • hypoKPP (calcium channel) Charungthai Dejthevaporn 3 Neuromuscular disease with abnormal 11/30/17 movement Myotonia Congenita Myotonia congenita Features Thomsen’s disease Becker’s disease Clinical features Inheritance Dominant Recessive • Myotonia with warm up phenomenon Onset Infancy or Early First decade (4-12 years) childhood • Muscle hypertrophy Distribution Face, arms > legs Legs > face, arms • Pain/ stiffness Myotonia Warm-up phenomenon Warm-up phenomenon • Transient weakness Precipitants Rest Rest • Dominant Thomson’s Additional symptoms None Transient; progressive • upper > lower limb; early age of onset from 2 years weakness • Recessive Becker’s Routine EMG Myotonic discharge Myotonic discharge Cold immersion No CMAP amplitude No CMAP amplitude • Lower limb > upper limb; transient weakness on initiation of movement; muscle hypertrophy; age of onset from 4 neurophysiology decrement with cooling decrement with cooling years Treatment MeXilitine, phenytoin MeXilitine, phenytoin Channel affected Cl- Channel Ch 7q Cl- Channel Ch 7q Paramyotonia Congenita Features Paramyotonia congenita PMC Inheritance Dominant Onset Birth/infancy • associated with episodes of weakness Distribution Face, tongue, arm • as a result of a persistent inward current causing depolarization of the muscle Myotonia ParadoXical worsening membrane Precipitants Cold and eXertion • overlap with HyperPP Additional symptoms Cold induced weakness • presence of paradoXical eye closure myotonia - specific Some with periodic paralysis Routine EMG Myotonic discharge Cold immersion neurophysiology CMAP amplitude decrease with cooling Treatment MeXilitine, acetazolamide Channel affected Na+ channel SCM (SCN4A myotonia) Peripheral nerve hyperexcitability syndrome • Continuous motor unit and muscle fiber activity • Painful myotonia is more prevalent and severe generated by discharges in motor aXon • prominent eyelid/ facial myotonia • Evident at rest and during sleep • Myokymia • dietary triggers (potassium sensitive myotonias) • Clinically visible undulating, wave like or worm like rippling of muscle • can have neonatal onset • EMG findings of continuous muscle fiber activity with doublet, • Neonatal hypotonia triplet, and multiple motor unit discharges • Neonatal stridor • Fasciculations • Episodic neonatal laryngospasm • Neuromyotonia • repetitive trains of high freQuency discharges • After discharges following voluntary contraction, peripheral nerve stimulation, and gentle percussion of peripheral nerve • Delayed muscle relaXation Charungthai Dejthevaporn 4 Neuromuscular disease with abnormal 11/30/17 movement Causes of peripheral nerve hyperexcitability Causes of peripheral nerve hyperexcitability • Inherited disorders • Nerve injury • Episodic ataXia type 1 with myokymia (Kv1.1; KCNA1) • Radiation toXicity • Benign familial neonatal epilepsy and myokymia • Inherited neuropathies (CMT II) • (KCNQ2) • Hereditary myokymia without central nervous system features • Inflammatory demyelinating neuropathies • Familial cramp syndrome • Multiple sclerosis (facial myokymia) • Toxins • Conduction block neuropathy • Acetylcholinesterase inhibitors • Focal compression neuropathy • Gold • Chronic motor nerve disorders (ALS) • Toluene • Amyloidosis • OXaliplatin (Wilson et al., 2002) • Uremia • Timber rattle snake venom • Black widow spider venom (α--latrotoXin) • Green mamba venom (α-dendrotoXin) Causes of peripheral nerve hyperexcitability Schwartz-Jampel syndrome • Autoimmune disorders • AcQuired neuromyotonia (Isaacs syndrome) • Rare condition presents in childhood with continuous and generalized muscle • Morvan syndrome activity • Cramp-fasciculation syndrome • Neuromyotonia on EMG • Paraneoplastic neuromyotonia • Thymoma (with or without myasthenia gravis) • Skeletal abnormality • Small-cell lung carcinoma • Facial blepharophimosis and dimpling of the chin (caused by continuous • Associated with other autoimmune conditions contraction of facial muscles) • Myasthenia gravis • Guillain–Barre´ syndrome or Chronic Inflammatory • Slow movement due to delay muscle relaXation (ongoing muscle activity and after • Demyelinating Polyneuropathy (CIDP) discharges) • Systemic lupus • Mutation in the gene encoding the basement membrane protein perlecan that • Multiple sclerosis anchors acetylcholinesterase to the synaptic memebrane in NMJ • Penicillamine • • Other disorders Persistent cholinergic activation of NMJ • Benign fasciculation syndrome • Benign focal myokymia Charungthai Dejthevaporn 5 Neuromuscular disease with abnormal 11/30/17 movement Localized peripheral nerve hyperexcitability Hemi-masticatory spasm • Focal myokymia and neuromyotonia from radiation • Involuntary painful spasm of jaw closure due to unilateral contraction • Hemifacial spasm of temporalis and masseter muscles • Hemi-masticatory spasm • Triggered by chewing or talking • Trigeminal