APPROACH TO MYOPATHY

MODERATOR- DR.T.P.SINGH DR.A.RAJ

PRESENTED BY-

KESHRI YADAV

DEFINATION

Skeletal muscle diseases or myopathies,are disorders with structural changes or functional

impairment of muscles.Diagnosis of myopathy is based upon clinical

features of patients and investigations.

Muscle weakness – ADULTS

proximal muscle weakness - leading to complaints such as difficulty arising from a chair or low toilet and climbing stairs, a waddling gait or difficulty lifting objects over the head, combing hair or brushing teeth.eg. Muscular dystrophies, DM type 2,

metabolic, PM,DM Distal muscle weakness - Presents with difficulty in turning

keys in holes,grasping things in hands,falls on uneven ground.eg. Distal myopathies, dystrophica myotonica type 1, dysferlin deficiency

Neck muscle weakness – inability to control neck while in a vehicle as it rapidly accelerates and decelerates.

eg. occulopharyngeal dystrophy , inflammatory myopathies

Cranial musculature - facial weakness (inability to close eyes fully,difficulty in drinking with straw) ptosis and extraoccular muscle involvement.

Diplopia is not common, unlike in NM junction disorders and neural disorder. Eg. OP dystrophy, DM1, FSHD

trunk muscles - leads to scoliosis, lumbar lordosis and protuberant abdomen. eg. LGMD, CHILDREN - hypotonia, delayed sitting, standing,

(Delayed milestones)

FATIGUE AND EXERCISE INTOLERANCE Fatigue - an inability to maintain or sustain a force. Asthenia - fatigue caused by excess tiredness or lack of energy. Try to discriminate between physical and mental fatigue.

objective weakness

ABSENT - consider depression, anxiety neurosis.

PRESENT - consider it myopathy.eg. Metabolic,mitchondrial Fatigue elicited after brief exericse – glycogenesis disorder

Fatigue elicited after long exericse – lipid metabolic disorder

MYALGIA MC Cause – orthopedic, rheumatic condition Myopathies less frequent cause Constant proximal myalgia – PM, DM Episodic - metabolic

CRAMPS These are involuntary contractions of muscle that

usually last for several seconds to minutes. Most cramps are benign innature and occur

predominantly in calves. old age, dehydration, use of diuretics,hypothyroid state, and a number of other metabolic disturbances.

In neuromuscular patients, they are most common in motor neuron diseases, especially early amyotrophic lateral sclerosis, and in chronic motor or sensori-motor polyneuropathies.

In myopathies, cramps are only common in metabolic myopathies such as myophosphorylase deficiency(McArdle’s disease), and in hypothyroid myopathy.

CONTRACTURES Joint contractures are uncommon in patients

with muscular sympoms INITIAL PRESENTATION - most cases of

autosomal dominant or recessive and all cases of X-linked recessive Emery-Dreifuss myopathy, and in dystrophies caused by mutations in collagen genes such as Bethlem myopathy.

DURING ILLNESS PRESENTATION - Duchenne and other muscular dystrophies and early in juvenile dermatomyositis.

MYOTONIA Myotonia is characterized by impaired relaxation after

sustained voluntary contraction. This painless phenomenon commonly involves intrinsic hand

muscles and eyelids. It is due to tetanic contraction of the fibers.

Clinical assesment by – tapping the muscle - percussion myotonia voluntary contractions of muscle groups - action

myotonia. With repeated exercise

ALL MYOTONIA - Improves PARAMYOTONIA – Worsens(paradoxical phenomenon)

Cold exposure - makes both worse Causes - sodium or chloride channelopathies , myotonic

dystrophies.

MYOGLBINURIA presence of cola coloured urine.Causes - unaccustomed strenuous exercise,

after drugs or toxin intake and infections, in the wake of prolonged fever or heat stroke, etc.

In case of recurrent myoglobinuria, glycogenoses, lipid storage myopathies or central core disease with malignant hyperthermia have to be excluded.

Important History family historyDrug history – ART,statins,steroids, diureticsPersonal history – alcohol intake,drug abuse, heroin,cocaine,amphetaminSleep,appetite,weight gain,weight lossSeizure, trauma bowel bladder involvementSensory symptoms eg. Tingling ,numbnessAsymmetrical weakness (except in IBM)

NERVOUS SYSTEM EXAMINATION In motor unit points in favour of myopathy : Muscle appearance – wasting ,atrophy ABSENT fasciculations Tenderness on palpation Tone –normal ,decreased in advanced cases. Distribution of weakness –proximal,distal (distal

myopathies) Tendon reflexes – normal /hypoactive Babinski sign -absent SENSORY system is normal. GAIT – lordosis on stance,increased on toe walking

Waddling gait – b/l pelvic girdle weakness

Creatinine kinase single most useful initial laboratory study in a suspected myopathy pt. CK is elevated in most patients with structural muscle disease. Normal CK in myopathies - mild or slowly progressive disease1. in end stage myopathy with extreme muscle atrophy,2. steroid-treated inflammatory myopathies and rare cases of untreated

dermatomyositis 3. atypical inflammatory myopathies associated with a collagen vascular

disease4. Alcohol/steroid-related or endocrine myopathies (except hypothyroid) CKMM elevation is typical of myopathies, but CKMB is also increased in most

of these subjects and can not be used as evidence of an associated cardiomyopathy.

Consider myopathy if CK is elevated more than 3 times normal value with myalgia, muscle weakness,

Other causes of CK elevation - muscle trauma (after EMG study, injections), viral infections,seizures or strenuous exercise may all be accompanied by transient but severe CK elevation.Drugs - lipid lowering drugs, chloroquine, cyclosporine A,AZT, etc.

Electromyography Use of EMG –

(1)To confirm a suspected myopathy and to exclude other disorders that may mimic myopathy. (2)May provide clues to the etiology of a suspected myopathy.(3) Assists in the selection of the biopsy site or in assessment of the treatment response.

Normal EMG found in - corticosteroidmyopathy, many congenital myopathies and some metabolic and endocrine myopathies .

Repetitive Nerve stimulation(RNS)Nerve conduction studies

Normal in myopathy.Used to exclude NM diseases. Low compound muscle action potential (CMAP)amplitudes may

occur in a number of distal myopathies. More than 50% direct loss of muscle fibers is needed to

significantly reduce the CMAP amplitude.

NEEDLE EMG Reveal irritability on needle placement s/o,dystrophies,toxic

inflammatory,myotonic myopathies, The combined findings in the muscle at rest, i.e. Spontaneous activity and

abnormal insertion activity, and during voluntary contraction, i.e. early recruitment of small, short duration low amplitude motor unit potentials (MUPs), reflect the underlying pathology affecting the muscle fibers.

Abnormal insertional activity-Complex repetitive discharges (CRD) Myotonic discharges CRD - vacuolar myopathies, e.g. acid maltase deficiency and in the

inflammatory myopathies Myotonic discharges are repetitively occurring single fiber action

potentials that are waxing and waning in amplitude and firing rate, producing the characteristic

“dive bomber” sound. They are quite specific for the myotonic dystrophies and disorders of

sodium or chloride channel dysfunction.

CLASSIFICATIONAcquired myopathies Inflammatory myopathies Endocrine myopathies Toxic or drug-induced myopathiesHereditary myopathies Muscular dystrophies Congenital myopathies Myotonias and channelopathies Metabolic myopathies Mitochondrial myopathies

INFLAMMATORY MYOPATIHES Largest group of acquired and potentially treatable

causes of skeletal muscle weakness . POLYMYOSITIS (PM) DERMATOMYOSITIS (DM) INCLUSION BODY MYOSITIS (IBM) 1 :1,00,000 PM – as alone is a rare disease affecting ADULTS. DM – affects both children,adults W>M IBM – M:F –3:1 ,caucasians,>50yrs.

PATHOGENESIS Autoimmune etiology - assosciation with other autoimmune

CTD ,various Auto Ab, MHC ,T CELL myotoxicity,complement, response to immunotherapy.

AUTOANTIBODIES AND IMMUNOGENETICS: 20% cases – ANA,anti cytoplasmic antigens Anticytoplasmic – anti RNP(anti synthetase), Anti jo 1 – 75% cases -80% assosciation with ILD. Anti Jo 1 –ILD ,RP,non erosive arthritis,MHCDR3,DRw52. DRB1 *0301,DQB1*0201 --- 75% PM,IBM DQA1*0501 –juvenile DM

Association with viral infections Coxsackie,influenza,paramyxoviruses,mumps,CMV,EBV. Autoimmune myositis in coxsackie virus Molecular mimicry of Anti RNAsynthetase and genomic

RNA . Best evidence of viral connection in PM,IBM –retroviruses. HIV,HTLV 1 – PM,IBM May be the initial manifestation or later of viral infection. Retroviral antigens –endomyosial macrophages ,but not in

muscle fibres. AZT induced myopathy –mitochondrial – ragged red fibres. AZT inhibits gamma DNA polymerase.

Clinical featuresIn general : PROGRESSIVE AND SYMMETRIC MUSCLE weakness (IBM –

asymmetric). Increasing difficulty with tasks – getting up from chair,climbing

steps,lifting objects,combing hair. Occular muscles are spared –even in advanced ,untreated

cases –if involved ? Diagnosis Head drop sign - weakness of neck flexors dysphagia – weakness of esophageal muscles Respiratory muscles involved in advanced cases. Muscle wasting in untreated cases . Sensation always normal . DTR preserved.

POLYMYOSITIS Subacute inflammatory myopathy affecting adults,rarely

children. Diagnosis by exclusion. As an isolated entity it is rare. Commonly occurs in assosc.

With systemic autoimmune disease ,viral,bacterial infection. Drugs –AZT,D penicillamine, lipid

lowering drugs

Who DONOT Have 1.Rash2. EOM,facial muscles3.Family H/O NMD4.h/o myotoxic drugs,toxins5.endocrinopathy6.Neurogenic disease7.Muscular dystrophy8.Bicohemical disorder9.IBM

DERMATOMYOSITIS

Characteristic rash accompanying/preceding muscle weakness heliotrope rash - Blue purple discoloration on the upper eyelids

with edema. gottron’s sign - Erythema of the knuckles with a raised violaceous

scaly eruption. V sign Erythematous rash on anterior chest –. shawl sign - Back and shoulders . Mechanic’s hands –irregular dirty horizontal lnies on the palmar

surface of fingers. Dermatomyositis sine myositis – muscle strength normal Photosensitivity present. Erythemaous rash on face and upper chest. Dilated capillary loops at the base of the finger nails. Muscle tenderness,myalgia –connective tissue disease. Perivascular perimysial inflammation

INCLUSION BODY MYOSITIS >50 yrs of age, most common inflammatory myopathy. Often misdiagnosed as PM Suspected when does not respond to therapy. Weakness and atrophy of distal muscles,foot extensors,deep

finger flexors –all cases –clue to early diagnosis. mild facial muscle weakness is common in patientswith IBM. Fine motor movements –affected early Falling is common – quadriceps –buckling of knees. DTR –depressed in presence of atrophy . Dysphagia -60% cases Slow and steady progression (over years) Assisted devices required

Familial IBM 20 % CASES -systemic autoimmune or connective tissue

disease. Familial IBM Hereditary IBM - heterogenous group of recessive,dominant

inherited syndromes,non inflammatory May spare the quadriceps –iranian JEWS Chromosome 9p1 Mutations in the UDP – N acetylglucosamine 2- epimerase n –

acetylmannosamine kinase GNE gene.

Associated clinical findings EXTRAMUSCULAR MANIFESTATIONS: Systemic symptoms --- fever,malaise -- CTD. Joint contractures –DM in children Dysphagia ,GI abn – DM ,IBM Cardiac disturbances –arryhthmias,DCMP,CCF Pulmonary dysfunction – ILD,drug induced – t RNA ab – 10% Subcutaneous calcifications –DM Arthralgias,deforming arthropathy – anti jo1 abMALIGNANCIES – DM(dermomyositis) Nasopharyngeal in india Ovarian,breast,melanoma ,colon,NHLOVERLAP SYNDROMES – DM – SSc,PM – RA ,sjogren’s,SLE Anti PM/Scl - overlap syndrome of DM.

TREATMENT GOAL : improve muscle strength,ameliorate

extramuscular manifestations. Discontinue the drugs if after trial no improvement of

muscle strength. 1.GLUCOCORTICOIDS :oral prednisolone –high doses –

1mg/kg/day – 3-4 weeks,taper later 10 weeks – 1mg/kg every other day.

Lowest possible dose to be used. Efficacy by third month PM > DM better in response. Steroid myopathy – increased weakness –2- 8 weeks.

Treatment cont… 2.IMMUNOSUPPRESSIVE THERAPY : 75% patients ultimately require. A.AZATHIOPRINE : 3mg/kg/day B.MTX : 7.5 mg weekly for the first 3 weeks then add-2.5mg/wk-

max. 25 mg/wk --- MTX pneumonitis. C.mycophenolate MOFETIL – 2.5 mg/d D.rituximab - IN DM E.CYCLOSPORINE – inconsistent benefit F.TACROLIMUS - PM difficult cases. 3.IMMUNOMODULATION: IVIg in refractory DM -short term benefit 2g/kg over 2-5 days /course. PLASMAPHERESIS,LEUKOPHERESIS - NOT EFFECTIVE IN PM,DM

NO RESPONSE TO TREATMENT IBM or metabolic myopathy,muscular dystrophy,

endocrinopathy. Repeat muscle biopsy Calcinosis of DM –difficult to treat IBM –resistant to immunosupressive therapy Drugs not to be withdrawn(subjective weakness) IVIg and prednisolone – not effective PROGNOSIS -5 yr surivival – 95%,10 yr -85% Best prognosis – DM, worst prognosis - IBM Death –pulmonary,cardiac Worse prognosis – older,severe mainfestations at

prsentation

ENDOCRINE MYOPATHIESCauses

1. Thyroid disorders ( hypo, hyper)2. Adrenal disorders ( cusshing syn. Conn’s syndrome)3. Parathyroid disorders ( hypo, hyper)4. Pitutary disorder ( acromegaly)5. Diabetes mallitus6. Vitamin D deficiencyCardinal features Muscle fatigue is more common than true weakness. Serum CK,EMG and muscle histology Normal.

except – hypothyroidism (CK elevated) All respond to treatment

THYROID DISORDERS:HYPOTHYROIDISM

proximal muscle weakness-1/3 Slow muscle contraction and relaxation -

25% cases. Relaxation phase prolonged –ankle,biceps

reflex-hung up reflex RX – thyroxin 1.6 ug/kg

HYPERTHYROIDISM: Proximal muscle weakness,atrophy of

muscles. DTRs enhanced response. Bulbar,esophageal,respiratory muscles

affected. Fasciculations+DTRs –ALS misdiagnosis Acquired hypokalemic periodic

paralysis,MG,graves ophthalmopathy

THYROID MYOPATHY

1.CHRONIC THYROTOXIC MYOPATHY2.GRAVES OPHTHALMOPATHY

3.THYROTOXIC HYPOKALEMIC PERIODIC PARALYSIS

4.MYASTHENIA GRAVIS ASS WITH HYT.

5.HYPOTHYROID MYOPATHY

Adrenal Disorders Steroid myopathy - Most commonly diagnosed

endocrine muscle disease. Proximal muscle weakness present. Muscle wasting accompanies cushingoid appearance. Type 2b fibres atrophy on histology, so EMG is Normal.

Primary hyperaldosteronism(CONN’S syndrome )- proximal muscle weakness.

Muscle weakness due to K+ depletion not due to direct effect of aldosterone on muscles.

Serum CK LEVELS ELEVATED,vacuoles on biopsy.

DRUG INDUCED MYOPATHY LIPID LOWERING AGENTS – fibrates ,statins& niacin GLUCOCORTICOIDS – acute quadriplegic paralysis(high dose iv

steroid) chronic proximal myopathy(>30mg/d prednisone use) Mainly flourinated-dexa,beta,triacinolone. ART – Zidovudine 17% (mitochondrial myopathy with ragged red

fibres) >1200mg/day for 6months. with no inflamation DRUGS OF ABUSE AND RELATED MYOPATHY-

Alcohol,Amphetamines,Cocaine,Heroin, Phencyclidine, Meperidine(rhabdomyolysis , myoglobinuria)

NON DEPOLARIZING NM BLOCKING AGENTS (acute quadriplegic paralysis)

DRUG INDUCED AUTOIMMUNE MYOPATHIES – D penicillamine(polymyositis, myasthenia gravis)

OTHERS - amiodarone, chloroquine, hydroxychloroquine, colchicine(proximal muscle weakness)

CRITICAL ILLNESS MYOPATHY Acute quadriplegic myopathy/acute steroid myopathy In cases of severe asthma ,sepsis and shock. Neuromuscular blocking agents in 80% cases. High doses of corticosteroids 1mg/kg ,pancuronium -500-4,000 mg Difficulty in weaning from the ventilator Tendon relfexes are normal- diminished –polyneuropathy Serum CK levels elevated. EMG –MYOPATHY with type 2 fibers vacuolation. Striking loss of myosin filaments Severe cases– myoglobinuria,renal failure. Denervation of muscles –increase in glucocorticoid receptors Recovery over 6- 12 weeks

Neuromuscular

blocking agents

Muscle denervati

on -

Increase in the

glucocorticoid

receptors

Myosin filaments loss

Muscular dystrophiesX linked muscular dystrophies

Duchenne muscular dystrophyBecker muscular dystrophyEmery-driefuss muscular dystrophyScapuloperoneal

Autosomal dominant Facioscapulohumoral muscular dystrophyOcculopharyngeal muscular dystrophyLimb girdle muscular dystrophy (1A-1E)Emery-driefuss muscular dystrophy

Autsomal recessive Limb girdle muscular dystrophy(2A-2M)Congenital muscular dystrophy

MUSCULAR DYSTROPHIES

Group of inherited myopathies characterised by progressive muscle weakness and wasting.

Subdivided on the basis of mode of inheritence,age at onset,distribution ,rate of progression and prognosis.

DUCHENE MUSCULAR DYSTROPHY

MC muscular dystrophy.Gene mutation - dystrophin. X recessive Incidence – 30/100000 births

Calf and deltoid hypertrophy

Gower’s maneuver on rising from floor.

Mental retardation.Duchenne's dystrophy is present → at birth

but becomes apparent → b/w 3 and 5 years.

by age 6 years → toe walking with a lordotic posture. Contractures of the achillis and iliotibial bands.

Between ages 8 and 10 years → walking may require the use of braces; joint contractures and limitation of movments.

By age 12 years, → most patients are wheelchair dependent.

By age 16–18 years → patients are predisposed to serious, sometimes fatal pulmonary infections. Other causes of death include aspiration of food and acute gastric dilation.

By age 20 years → patient dies.

Difficulty rising (Gower’s sign)

Muscles that are affected

In the early stages, Duchenne MD affect the pectoral muscles , the trunk, hamstrings, calf muscle.

Mental retardation also common.

PSEUDOHYPERTROPHY

ATROPHY

Investigations Muscle enzymes

Creatinine kinase [CK]-20-100 times of Normal. Muscle biopsy-investigation of choice.

Electromyogram-features of myopathy.

Treatment –

Glucocorticoids, administered as prednisone in a dose of 0.75 mg/kg per day, significantly slow progression of Duchenne's dystrophy for up to 3 years.

BECKER MUSCULAR DYSTROPHY

an incidence of about 3 per 100,000 live-born males. Less severe than DMD. Onset between 5 and 15 yrs. Ambulatory beyond age 15 yrs while in DMD typically on

wheelchair at 5 yrs. CMP may occure with CHF BUT mental impairment

uncommon. CPK,EMG,and muscle biopsy closly resemble to DMD. Pateint doesn’t respond to steroid therapy.

MYOTONIC DYSTROPHY

Two types on the basis of overlapping phenotypes and distinct molecular genetic defects: myotonic dystrophy type 1 (DM1) - chromosome 19q,expansion of CTG repeatsmyotonic dystrophy type 2 (DM2/PROMM) chromosme 3q, expansion of CCTG repeats

Clinical features of DM1 Myotonia apears by 5 years.hatchet-faced appearance- temporalis, masseter,

and facial muscle atrophy.Distal weakness - Weakness of wrist

extensors,finger extensors, and intrinsic hand muscles impairs function. Ankle dorsiflexor weakness may cause footdrop.

Other features - Frontal baldness,cataracts,mental impairment CHB, MVP,Insulin resistance and gonadal atrophy are common.

Clinical features of DM2 It has a distinct pattern of muscle weakness

affecting mainly proximal muscles.Cardiac conduction defects occur but are less

common, and the hatchet face and frontal baldness are less consistent features.

Investigations CK – normal to elevated EMG – myotonia present . It sounds similar to reviving of

motorcycle. Muscle biopsy - shows muscle atrophy, which selectively involves

type 1 fibers in 50% of cases, and ringed fibers in DM1 but not in DM2.

Treatment The myotonia in DM1 rarely warrants treatment. Though some patients with DM2 are significantly bothered by

the discomfort related to the associated muscle stiffness. Phenytoin and mexiletine are the preferred agents.

other agents, particularly quinine and procainamide, may worsen cardiac conduction.

FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY

FSHD1 is associated with deletions at 4q35 FSHD2-no deletion of 4q both have

hypomethylation leading to toxic menifestation of DUX4 gene,

initial manifestation → facial weakness Weakness of the shoulder girdles, rather than

the facial muscles, usually brings the patient to medical attention.

Facial weakness →biceps,triceps,shoulder girdle (winging of scapula)→wrist extensor →anterior compartment of leg.

No Cardiac involvement,deltoid is spared.

CPK may be Normal/mildly elevated.No specific treatment required.foot arthoses and

scapular stablization procedures are helpful

OCULOPHARYNGEAL DYSTROPHY Late onset (4th to 6th decade),expansion,polyA RNA binding

protein. Ptosis and dyphagia are common presentation. progressive external ophthalmoplegia

ptosis + limitation of eye movements sparing of pupillary reactions Muscle biopsy - muscle fibers are found to contain rimmed

vacuoles. Treatment - Cricopharyngeal myotomy may improve swallowing, although

it does not prevent aspiration. Eyelid crutches can improve vision when ptosis obstructs

vision

LIMB-GIRDLE MUSCULAR DYSTROPHY

AR/AD,affect pelvic and shoulder girdle muscles,no mental impairment

Defect of sarcoglyconRespiratory insufficiency,cardiac involvement-

CHF/arrythmias; ocasionaly CMPAD-LGMD1A-1EAR-LGMD2A-2O except LGMD2E

Prenatal diagnosis

This is achieved by studying the foetus’s own DNA on

a chorion villus biopsy.

The test is performed on a tiny piece of the

developing placenta usually at the 11th –12th week of

pregnancy.

Congenital muscular dystrophyClassification 1. Merosin deficiency (merosin)gene-laminin alfa2 chain

2. Fukitin-related protein deficiency (fukitin)3. Fukuyama congenital muscular dystrophy (fukitin)4. Muscle-eye-brain disease

(N-acetyl-glucosaminyl transferase/POMGnT1)5. Walker-Warburg syndrome

(O-mannoxyl-transferase-1/POMT1)

Three forms of congenital muscular dystrophy have severe brain impairment- FCMD, MEB disease, WWS.

Worst prognosis – Walker warburg syndrome

Common clinical features 1. Onset at birth, hypotonia2. Generalized muscle weakness3. Joint contractures(arthrogryposis)

Treatment There is no specific treatment for CMD. Proper wheelchair seating is important.

Management of epilepsy and cardiac manifestations is necessary for some patients.

CONGENITAL MYOPATHY

Rare and relatively nonprogressive disorderBegins in infancy/childhood but apparent in

adulthoodProximal weakness,hypotonia,hyporeflexia

and normal CPK.differenciated from dystrophies by specific

structural and histochemical abnormality.

CENTRAL CORE DISEASES

AD,biopsy shows fibers with single/multiple central/ecccentric discrete zones (core)devoid of oxydative enzymes (esp.in type1 fibers)

C/F-have decreased fetal movement and breech presentation,delay in moter milestones(perticularly walking).

NEMALIN MYOPATHY

Muscle biopsy shows clusters of small rods(nemalin bodies-thread like structures),but not exclusive for type 1 fibers.

Clinically hetrogenous. Facial and generalized muscle weakness is common.

CENTRONUCLEAR MYOPATHY

Muscle biopsy shows-rows of central nuclei often surrounded by a halo.

Three distinct variants are known to occur-Neonatal formLate infancy early childhoodLate childhood.

DISTAL MYOPATHIES

Late onset,>40 yrsDominantly

inherited

WELANDER

Markesbery - Griggs

Udd ,tibial muscular

dystrophy

WELANDER MYOPATHY

WRIST ,FINGER EXTENSORS

•DOMINANT,TIBIAL WEAKNESS•CHILDHOOD IN ONSET•RIMMED VACUOLES ON BIOPSY

LAING DISTAL MYOPATHY

•AR inheritance.•NONAKA - -- ANTERIOR TIBIAL WEAKNESS•MIYOSHI – GASTROCNEMIUS.,ELEV.CK,ABSENT DYSFERLIN

NONAKA DISTAL,MIYOSHI

MYOPATHY

•AD/AR,CLINCALLY HETEROGENOUS•MYOTONIC DISCHARGES ON EMG•DENSE INCLUSION ON BIOPSY,DESMIN

MYOFIBRILLAR MYOPATHY

****LIMITED TO SKELETAL MUSCLES

DISORDERS OF MUSCLE MEMBRANE EXCITABILITY• ADOLESCENCE,M>W,HIGH CARB DIET,REST AFTER EXERCISE,CARDIAC

ARRYHTHMIAS• TYPE 1 –AD,CALCIA3 GENE,10% TYPE 2 –SCN4• RX—ORAL KCL -0.2-0.4MMOL/Kg EVERY 30 MIN(,MANNITOL-

vehicle),oral acetazolamide 500 bd reduces attacks in type1• LOW CARB,LOW SODIUM DIET,ACETAZOLAMIDE MAY ABOLISH

ATTACKS(exacerbated IN TYPE2)• thyrotoxic PP resembles but w>M AGE >25

CALCIUM CHANNEL –HYPOKALEMIC

PERIODIC PARALYSIS

• MISNOMER – AD IN INHERITANCE• PROXIMAL MUSCLES ,BULBAR ARE SPARED.• MYOTONIA WITHOUT WEAKNESS –COLD STIFFNESS• LESS VACUOLES,MORE PERIPHERAL• ACETAZOLAMIDE,MEXILITINE

SODIUM CHANNEL –HYPERKALEMIC

PERIODIC PARALYSIS

• MYOTONIA WORSENS WITH MUSCULAR ACTIVITY• SENSORY,MOTOR NERVE CONDUCTION STUDIES ARE NORMAL• MYOTONIC DISCHARGES DISAPPEAR ON COOLING• AD,SODIUM CHANNEL• INCREASED CARBOHYDRATE IN THE DIET,MEXILITENE,THIAZIDE

DIURETICS

SODIUM CHANNEL

PARAMYOTONIA CONGENITA

POTASSIUM CHANNEL DISORDERS: 1.ANDERSEN TAWIL SYNDROME: Episodic weakness,dysmorphic features. cardiac arrythmias are life threatening. autosomal dominant kir 2.1 gene Acetazolamide

CHLORIDE CHANNEL DISORDERS: AD –THOMSEN’S DISEASE AR – BEKER’S DISEASE Myotonia worsened by cold,improved by activity Muscle strength normal in thomson’s Quinine,mexiletine,phenytoin.

METABOLIC MYOPATHIES

Ppted by brief

bursts of high

intensity exercise

Warm up exercise

helpful in mc ardles’s

diseaseHemolytic

anemia seen with

phosphofructokinase deficiency

Phosphoglycerate kniase –mental

retardation,Forear

m exercise

test

• Infantile form most common• Glycogen accumulation occurs in neurons• Childhood form –muscular dystrophy,only heart • Heart and liver not involved in

adult ,resp .failure

Acid maltase deficiency (pompe’s

disease) (AR)

• Slowly progressive• Diagnosed in infancy with hypotonia,hepatomegaly• hypoglycemia

Debranching enzyme deficiency

Type III glycogenosis

• Rare AND FATAL • HEPATOMEGALY• SKELETAL MUSCLE MANIFESTATIONS ARE MINOR

Branching enzyme deficiency

Type IV glycogenosis

MYOPHOSPHORYLASE DEFICIENCY(TYPE V)

PHOSPHOFRUCTOKINASE (TYPE VII)XLR

BETA ENOLASE DEFICIENCY

Lipid abn myopathiesCarnitine

Palmiotyl transferase deficiency

Mc cause of recurrent myoglobinuria

Muscle pain only after the limit exceeded.

A normal rise in venous lactate on forearm exercise test

CPT II deficiency more common in men than womenHigh carb diet

MITOCHONDRIAL MYOPATHIES TERM RAGGED RED FIBRES –ABNORMAL MITOCHONDRIA ON MODIFIED

TRICHROME STAIN . Mitochondria are enlarged,bizarrely shaped,crystalline inclusions Most common is CPEO >50% cases of mitochondrial myopathies.

KEARNS SAYRE SYNDROME

ONSET<20 YRS,CPEO,PIGMENTARY RETINOPATHY PLUS CHB,CSF PROTEIN >1 G/L,CERBELLAR ATAXIA

DEATH DUE TO HEART BLOCK -20%

ENDOCRINE ABN ARE COMMON –DIABETES MELLITUS -13%

MENTAL RETARDATION ,DEMENTIA

SERUM CK LEVLES NORMAL,SERUM LACTATE AND PYRUVATE LEVELS ELEVATED

MELAS

MOST COMMON MITOCHONDRIAL ENCEPHALOMYOPATHY

NO STRICT VASCULAR DISTRIBUTION-STROKE LIKE

STROKE <40 YRS AGE

DEMENTIA,BEDRIDDEN,FATAL STATE

SERUM LACTIC ACID ELEVATED

T RNA MUTATIONS -LETHAL

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