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Page 1: Myotonic muscle disorders



Page 2: Myotonic muscle disorders

Myotonia is a phenomena of delayed relaxation

after forceful voluntary contraction

Is due to repetitive depolarization of the muscle


Myotonia is due to increased excitability of the

muscle membrane often caused by dysfunction of

muscle ion channels.

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As a clinical sign, myotonia is often best appreciated in the hand and fingers.

To elicit grip myotonia, the patient is instructed to grip the examiner's fingers firmly and then to let go rapidly; in the presence of myotonia, the relaxation of the fingers is delayed.

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To demonstrate percussion myotonia, the examiner firmly percusses the thenar eminence (specifically the abductor pollicis brevis); in the presence of myotonia, the thumb will abduct and then relax slowly.

Alternately, the examiner percusses the extensor digitorum; in the presence of myotonia, the third digit will extend and then relax slowly. Percussion myotonia can be elicited in other muscles as well.

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Electrical myotonia appears as repetitive muscle fiber potential discharges (eg, positive waves or fibrillation potentials) with waxing and waning frequency and amplitude with a firing rate between 20 and 80 Hz.

When played over the audio, myotonic discharges have a characteristic sound of a dive bomber, or an accelerating and decelerating motorcycle engine.

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Muscular dystrophies: Myotonic dystrophy type 1 and 2 Myofibrillar myopathies Chondrodystrophic myotonia(Schwartz Jampel


Muscle channelopathies: Nondystrophic myotonia (myotonia congenita,

paramyotonia congenita, sodium channel myotonia)

Hyperkalemic periodic paralysis

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Metabolic myopathies Acid maltase deficiency, Debrancher deficiency, McArdle disease (myophosphorylase deficiency)

Toxic myopathies Chloroquine/hydroxychloroquine myopathy Statin myopathy Colchicine myopathy

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Inflammatory myopathies Polymyositis Dermatomyositis

Congenital myotubular/centronuclear

Electrical myotonia without clinical myotonia

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The most common;

Age at onset late teens

Inheritance autosomal dominant

Gene defect expansion of a CTG trinucleotide

repeat in the 3'-untranslated region of the

dystrophia myotonica protein kinase gene (DMPK

gene) on chromosome 19q 13.3

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The myotonia mainly distal demonstrated with

grip and percussion myotonia can be elicited most

easily over the thenar muscles and long finger


Mild weakness & wasting distal & bifacial, neck

flexor muscles the distal › proximal,

Muscle stiffness that improves with repeated


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There is a characteristic fascial appearance

Hatchet face Frontal balding, a narrow, elongated face and

horizontal smile Ptosis Atrophy of sternocleidomastoid

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Extra muscular Extra muscular involvement involvement

Cataracts, Slitlamp examination reveals posterior capsular cataracts, which early on have a characteristic multicolored pattern.

Cardiac Conduction defect as arythmia Pulmonary Defects excessive daytime sleepiness

due to weakness of the diaphragm and intercostal ms

Endocrine Dysfunction, insulin resistance Testicular Atrophy, Gynecologic Problems, In Some Patients, Mild To Moderate Cognitive


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Approximately 10%, characterized by severe weakness and hypotonia

at birth mental retardation. Upper lip forms inverted V or shark mouth maternally inherited. In many cases, the mother

may be so minimally affected that her diagnosis is not made until the infant is born with severe hypotonia and a myopathic facies.

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Creatine kinase (CK) levels may be mildly to moderately elevated.

Electrodiagnostic Testing -Widespread electrical myotonia on needle EMG and tends to be“waxing and waning”

Resembles the sound of diving propeller airplane called as dive bomber or motorcycle potentials.

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Muscle biopsy- variation in fiber size,rounded atrophic fibers, increased central nuclei, increased connective tissue,and fatty replacement of muscle. DM1patients show preferential atrophy of type1 fibers.

DNA Analysis- definative diagnostic test.

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Age at onset: Age at onset: Teens to early adult

InheritanceInheritance it is an autosomal dominant

Gene defect: Gene defect: Zinc finger protein-9,

chromosome 3q21, this mutation are expanded

CCTG repeats in intron 1.

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myotonia in the setting of grip and percussion


Bifacial weakness, ptosis, progressive

weakness, predominantly proximal (PROMM)

although proximal and distal weakness is seen,

And some patients may have muscle


Frontal balding

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Posterior capsular cataracts,

Testicular atrophy, and

Cardiac conduction defects.

Many patients have an intermittent pain

syndrome in the thighs, arms, or back.

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Drugs for myotonia- Quinine, phenytoin, procainamide, mexiletine,and acetazolamide.

Modafinil improves hypersomnolance

Genetic screening of family members

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Two major forms- Autosomal dominant and recessive.

Both associated with abnormalities in chloride channel, CLCN1 on chromosome 7q35.

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Myotonia CongenitaMyotonia CongenitaThomsen disease

Myotonia Myotonia CongenitaCongenita Becker

Age of onset infant early childhood

inheritance dominant recessive.

Gene chloride channel chromosome 7q

Myotonia generalized painless myotonia non progressive

Weakness lack of weakness weakness and wasting of distal


Muscle hypertrophy the proximal arms, thighs, and


CK levels Muscle biopsy

may be slightly elevated may show a lack of type IIB fibers

moderately elevated


no no

Provocative cold cold

Alleviating exercise exercise

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Associated with mutations in the SCNA4A gene that encodes the alpha subunit of sodium channel.

Hyperkalemic periodic paralysis Paramyotonia congenita Potassium aggraveted myotonia

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characterized by skeletal deformities, muscle stiffness, and myotonia.

distal weakness and atrophy, with proximal upper and lower extremity muscle hypertrophy.

Characteristic facial and physical appearance include short stature, short neck, and multiple facial anomalies (micrognathia, low-set ears,pursed lips, prominent eyebrows, upward slanting eyes, blepharophimosis, exotropia, and microcornea)

20% with cognitive impairment.

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1. Needle EMG proximal and distal muscles of one upper and lower extremity, as well as facial and paraspinal muscles.

abnormal spontaneous activity, including myotonic discharges, complex repetitive discharges, fibrillation potentials and positive waves

MUAP low amp, short duration and polyphasic

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A myotonic discharge:A myotonic discharge: On emg the spontaneous discharge of a muscle

fiber Waxes and wanes in both amplitude and

frequency. Myotonic potential may have either a positive

wave or a brief spike morphology. Produce a dive bomber sound .

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2. Muscle cooling2. Muscle cooling : : paramyotonia congenita. A. Wrap the limb in a plastic bag, submerge in ice

water for about 10 to 20 minutes to bring skin temperature to 20·

C. Remove the patient's hand from water. B. Needle EMG of a distal forearm or hand muscle

is performed, noting the presence of abnormal spontaneous activity (fibrillation potentials, myotonic bursts)

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3. Short exercise test3. Short exercise test..

Record at abductor digiti minimi stimulating ulnar nerve at the wrist.

Supra maximal CMAPs are recorded at baseline and then following 10 seconds of sustained contraction of the ADM. Additional CMAPs are recorded 2 seconds after exercise and then every 10 seconds for a total of 60 seconds; this protocol is repeated 3 times.

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The short-exercise protocol has a high sensitivity of 100% (83%–100%) in PC, 83% (53%–100%) in MC, and 60% in SCM.

Three patterns are observed in patients with NDM, Fournier I, II, and III

Patients with MC commonly exhibit Fournier pattern II with an initial postexercise CMAP decrement, which repairs by 60 seconds

subset of MC patients (primarily dominant MC) exhibit Fournier pattern III

Patients with PC exhibit Fournier pattern I

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Fig. 2. Short exercise test. (A) Transient decrease in C M AP am plitude in m yoton ia congenita . (B) Fournier pattern III: in itia l increment in CMAP with return to baseline. No change w ith subsequent tests. (C ) Fournier pattern II: in itia l C M AP decrem ent postexercise with return to baseline on subsequent trials. (D) Fournier pattern I: decrem ent of CMAP am plitude postex- ercise, which worsens on subsequent trials. (M od ified from Fournier E , Arzel M, Sternberg D, et al. E lectrom yography guides tow ard subgroups of m utations in muscle channelopath ies. Ann Neurol 2004;56:650–61; with permission. Copyright with Wiley InterScience.)

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5. Prolonged exercise:5. Prolonged exercise:

a. Have the patient perform maximal voluntary

muscle contraction for 2 to 5 minutes, resting every

15 seconds for 3 to 4 seconds. then relax


c. Record the CMAP immediately, then every 1 to 2

minutes for 40 to 60 minutes afterward or until

there is no further decline observed in the CMAP.

Decrement is calculated as follows: (Highest CMAP

amplitude after exercise - Smallest CMAP amplitude

after exercise)/(Highest CMAP amplitude after

exercise x 100). Any decrement >40% abnormal.

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LET has a sensitivity of 80% to 90% in both hypokalemic PP and hyperkalemic PP

Patients with a sodium channel mutation often exhibit Fournier pattern IV manifest by an increment in CMAP amplitude/area with exercise followed by a decrement in amplitude/area 40% to 80% of baseline; maximal decrement is observed between 30 and 45 minutes postexercise.

Fournier pattern V manifest by a maximal decrement in area/amplitude after 20 to 40 minutes is more typical of calcium channel-related PP;

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Fig. 3. Long exercise test. Example of long exercise test (Fournier patte rn IV) in a patient with hypokalemic PP believed due to S C N 4A m utation. (A) C M AP s evoked (5 m V/d ivis ion) from the ADM during brief pauses (every 1 minute) in a 3-minute exercise with a transient increase in am plitude (17%) and area (81%). (B and C ) After exercise, there is a gradual 70% decrease in CM AP amplitude to 70% of postexercise baseline by 30 minutes. (From Logigian EL, Barbano RL. Applied physiology of muscle. In: Disorders of vo luntary muscle. 7th E dition. 2001. p. 219–51; with permission. C opyright with Cambridge University Press.)

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Bradleys neurology in clinical practice- sixth edition

Harrisons principles of internal medicine18 e Matthews E, Fialho D, Tan SV, et al. The non-

dystrophic myotonias: molecular pathogenesis, diagnosis and treatment. Brain 2010;133:9–22.

Venance SL, Cannon SC, Fialho D, et al. The primary periodic paralyses: diagnosis, pathogenesis, and treatment. Brain 2006;129:8–17.

Saperstein DS. Muscle channelopathies. Semin Neurol 2008;28(2):260–9.

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Logigian EL, Ciafaloni E, Quinn LC, et al. Severity, type, and distribution of myotonic discharges are different in type 1 and type 2 myotonic dystrophy. Muscle Nerve 2007;35:479–85.

Electrodiagnosis of Myotonic Disorders Michael K. Hehir, MDa,*, Eric L. Logigian, MDb

Michel P, Sternberg D, Jeannet PY, et al. Comparative efficacy of repetitive nerve stimulation, exercise, and cold in differentiating myotonic disorders. Muscle Nerve 2007;36:643–50.

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