This document discusses Myasthenia Gravis, an autoimmune disorder where antibodies are produced against acetylcholine receptors at the neuromuscular junction. This leads to loss of functional acetylcholine receptors and weakness of muscles. Symptoms include fatigue of muscles that worsens with use and improves with rest. Early symptoms often involve the eyes, face, and throat. Later the limbs may be involved. Treatment focuses on increasing acetylcholine activity and decreasing the immune attack on motor end plates using anticholinesterase medications, immunosuppressants, plasmapheresis, and sometimes thymectomy. Classification is based on symptoms and presence of crisis requiring ventilation.

1. CHAIRPERSON- DR B.L. BHARDWAJ
SPEAKER-DR YOGESH GUPTA

3.  It is an autoimmune disorder
where antibodies are produced
against Ach receptors located
at motor end plates in
myoneural junctions
 These autoantibodies lead to
loss of functional Ach R at N-M
junction
 It may be a/w
thymoma,hyperthyroidism , RA
& DLE

4.  Thymus is abnormal in approx 75% of patients
with myasthenia gravis
65%- hyperplastic
10%-thymoma

5.  Age of onset is 15-50 yrs
 Females>males
 Insidious onset
 The exacerbation occur in pregnancy or before
menses
 The cardinal symptom is abnormal fatigue of
muscle & intensification of symptom towards end
of the day or following vigorous exercise
 Remission & relapses are seen during early
course of illness
 EOM r m/c affected----ptosis & diplopia
 Intrinsic muscle of eye, smooth muscle& cardiac
muscles r not involved

6. Involvement of bulbar muscle results in
 DYSARTHRIA
 DYSPHAGIA
 NASAL REGURGITATION OF FLUIDS
Limb muscle involved is if proximal group resulting in
1. Difficulty in raising arm above shoulder
2. Problems in getting up from sitting / squatting position
Involvement of respiratory muscle results in myasthenic
crisis & can cause death

7. CLASS 1 ocular only
CLASS 2 Ocular& generalised
symptoms
CLASS 3 Generalised symptoms
& myasthenic crisis
CLASS 4 Acute myasthenic crisis

8.  Is defined as need for assisted ventilation because
of myasthenia induced weakness of muscle of
respiration like diaphragmatic & intercostal muscle
 CAUSE
1. Infection (M/C)
2. Extreme of temperature
3. Exertion
4. Occur in pts with M.G who r either not on any Tx or
r being undertreated

9.  Occur d/t overdose of Anticholinestrase drug
 Pt present with muscuranic feature
1. Increased salivation
2. Increased lacrimation
3. Increased bronchial secretion
4. Miosis
5. Diarrhoea
6. Urinary incontinence

10.  TENSILON TEST(EDROPHONIUM TEST)
 95% Sensitive for generalised M.G & 85%
sensitive for ocular M.G
 It is more specific than electrophysiological test
 ANTI ACH R ANTIBODY TEST
 Most specific test
 80% sensitive for Gen. M.G & 60% sensitive for
ocular M.G
 If test is positive----definitive diagnosis
 Negative result-----does not exclude M.G

11.  ELECTROPHYSIOLOGICAL STUDY
 REPETITIVE NERVE STIMULATION shows
detrimental response
 SINGLE FIBRE EMG shows increased variability
of interpotential interval
 CXR & CT CHEST Thymus enlargement
 TFT 10% may have associated hyperthyroidism
 ICE TEST ptosis improves by >2mm.When ice
is applied to affected eye lid for >2min
 This test is simple,sensitive,specific & non-
invasive

12.  PRINCIPLES OF Tx
 To maximise the activity of Ach at remaining
receptor in N.M junction
 To decrease the immunological attack on motor
end plate

13.  ANTICHOLINESTERASE
1. Neostigmine
2. Pyridostigmine- (more preferred drug)
 These control only relatively mild disease
 Neostigmine 15mg 1-2 tablets 3-6 times per day
 Pyridostigmine 60-120mg 3-6 times per day
 S/E – cholinergic symptoms s/e like abdominal
cramps & increased salivation
 These s/e are managed with propenthilene 2-3
times per day

14.  IMMUNOSUPRESENTS
1. Corticosteroids are useful
 In pts with MG with moderate to severe
generalised weakness who is not responding to
anticholinesterase drugs
 In pts with ocular myasthenia
 In pts>50yrs with generalised disease
 Pts without anti Ach R antibodies
2. Other immunosuppressive drugs are
 Azathiopurine
 Cyclosporine
 Cyclophosphamide
 Mycophenolate

15.  PLASMAPHERESIS-indicated in
1. Severe MG that is refractory to Tx with
anticholinesterase drugs & prednisolone
2. During acute worsening
 Role of thymectomy in pts with MG
PREFERRED IN
 Pts with thymoma
 All pts with generalised MG b/w 15-55yrs of age

16. NOT USUALLY DONE
 Children before puberty
 Elderly>55yrs
 Pt with Musk ab positive(antimuscle specific
protein kinase)
 MG limited to EOM(b/c medical therapy control
the disease limited to EOM well)

17. MYASTHENIA GRAVIS
EATEN LAMBERT
SYNDROME
 Post synaptic defect(auto
ab directed against Ach
R)
 Decrease in no: of Ach R
at postsynaptic muscle
membrane
 Ocular muscle is m/c
involved
 Ocular muscle>proximal
muscle
• Presynaptic
defect(Autoantibodies
direct against voltage
sensitive Ca channel)
• Decrease in presynaptic
release of Ach
• Proximal muscle of LL are
m/c involved
• Proximal muscle>ocular
muscle

18. MYASTHENIA GRAVIS
EATEN LAMBERT
SYNDROME
 DTR intact
 No autonomic changes
 Diagnosis
Detrimental response to
repeated nerve
stimulation
 Antibody against Ach R
 DTR decrease/ absent
 Slow autonomic changes
such as dry mouth &
constipation
 Incremental response
 Ab against Ca channel

19. Most effective drug is 3-4 diaminopyrimidine
It blocks K channel in distal motor tunnel which
increase the release of Ach containing vesicle

21. INHERITED
MUSCULAR DYSTROPHIES CONGENITAL MYOPATHIES
MITOCHONDRIAL MYOPATHY SYNDROMES CHANELLOPATHIES
INHERITED DISORDERS OF METABOLISM
ACQUIRED
INFLAMMATORY
PM, DM, IBM
ENDOCRINE ^METABOLIC
HYPOTHYRIODISM
HYERTHYRIODISM
ACROMEGALLY
CUSHING’S SYNDROME
(INCLUDING IATROGENIC)
ADDISONS DISEASE
CONN’S DISEASE
OSTEOMALACIA
HYPERCALCEMIA
HYPOKALEMIA
TOXIC
ALCOHOL (CHRONIC,
ACUTE SYNDROME)
VIT. E
ORGANOPHOSPHATS
SNAKE VENOMES
INFECTIONS
Trichinosis
Cysticercosis
Toxoplasmosis
HIV
Coxackie - A& B
Influenza
Lyme disease
Staph. aureus
/pyomyositis/
DRUGS
STEROIDS
STATINS
B-BLOCKERS
ZIDOVUDINE
AMIODARONE
CHLOROQUINE
CLOFIBRATE
VINCRISTINE
CYCLOSPORINE
OPIATES
E-AMINOCPROIC ACIDS
COLCHICINE
D-PENICILLAMINE

22.  Group of inherited disorders characterized by progressive
degeneration of groups of muscles, sometimes with
involvement of the heart muscle or conducting tissue, and other
parts of the nervous system.
 Classified based on the age at onset, distribution of affected
muscles & pattern of inheritance.

23.  Inheritance- X- linked recessive disorder
 Defective gene- Dystrophin
 Onset- usually b/n 3-5yrs age
 C/F –Males are victims & females carry disease
 Proximal muscles of UL & LL are predominantly
affected( pelvic muscle> shoulder muscle)
 Later neck muscle & EOM , diaphragm are
involved
 Facial muscle & small muscles of hand are
usually spared
 Pseudo hypertrophy in few muscles & atrophy in
some

24.  Waddling gait
 Gower’s maneuver positive
 Smooth muscles are spared but heart is affected
 OTHER FEATURES macroglossia, absence of incisor
tooth, low IQ
 Death is usually result of pulmonary infections & respiratory
failure
GOWER’S SIGN

25.  Serum CK : elevated 20-100x normal
 EMG : myopathic features
 Muscle biopsy: muscle fibers of varying size as well as small groups
of necrotic and regenerating fibers.
: deficiency of dystrophin seen on western blot analysis
 DNA analysis : mutation of gene that encodes dystrophin
Treatment :
prednisolone 0.75mg/kg/day increases muscle strength & slows
the progression of disease for up to 3 yrs.

26.  Inheritance – X- linked recessive disorder
 Defective gene – dystrophin
 Onset- experience difficulty b/n 5- 15yrs of age
 C/F – proximal muscles especially of lower extremities are prominently
involved.
- hypertrophy of muscles , particularly the calves, is an early &
prominent finding.
- cardiomyopathy may occur , MR is less common
 Lab. – CK : elevated
- EMG : myopathic
- muscle biopsy : similar to DMD
 Treatment – supportive
 Prognosis- the longevity is better than DMD

27.  Inheritance : Autosomal dominant/ recessive
 Defective gene : several genes
 M:F – 1:1
 Onset – late 1st
to 4th
decade
 In most AR cases, weakness occur early & lead to significant disability in
childhood whereas in AD cases weakness may not be apparent until early or
late in adult life
 C/F – Pelvic & shoulder girdle muscles are predominantly affected
-EOM, Facial muscle & distal muscle are completely spared
- diaphragmatic weakness & cardiomyopathy may also occur
- intellectual function is intact
 Treatment - supportive

28.  Inheritance: AD
 Onset : childhood or young adulthood
 Defective gene: deletion, distal 4q
 C/F- facial weakness: initial manifestation
- weakness of shoulder girdle muscles : weak arm elevation
: scapular winging
- foot drop : weakness of anterior compartment muscles of the legs
- weakness of the pelvic girdle muscles : 20%
- other organ ( rarely) : labile HTN, nerve deafness
 Lab. – CK : N or elevated
- EMG: myopathic pattern
- biopsy: non-specific features of myopathy
 Treatment – no specific treatment is available
- ankle foot orthoses may help for foot drops
- scapular stabilization procedures may improve scapular winging

29.  Inheritance- X-linked recessive/ Autosomal dominant
 Defective gene : Emerin/ Lamins A/C
 Onset – early childhood & teenage years
 C/F – prominent and early contractures ( elbows, neck) often preceding
muscle weakness.
- muscle weakness is in a limb- girdle distribution
- dilated cardiomyopathy may occur and may result in sudden death,
arrhythmia, & conduction defects.
▪ Lab. - CK : 2-10x ed
- EMG : Myopathic
- Biopsy : non-specific dystrophic features
 Treatment - supportive : Ambulatory aid
: manage cardiomyopathy & arrhythmia

30.  Inheritance: AD
 Defective gene: poly-A-RNA binding protein
 Onset – usually late onset ( 4th
– 5th
decade )
 C/F – progressive external ophthalmoplegia ( slowly progressive ptosis,
limitation of eye movements with sparing of pupillary rxns.
- dysphagia : can be life threatening
: may result in repeated episodes of aspiration
- mild weakness of the neck and extremities
 Lab. – EMG: myopathic features
- CK : 2-3x N
- biopsy : distinct features – presence of tubular filaments in muscle
cell nuclei.
 Treatment- Dysphagia : cricopharyngeal myotomy may improve swallowing
- Ptosis : eyelid crutches may improve vision

31.  Three types :
1. Welander DM : AD
Onset 4th
-5th
decade
Predominantly hand is involved
2. Nonanka DM: AR
Onset <30 yrs
Predominantly anterior tibial & distal UL weakness
3. Miyoshi myopathy : AD
- early onset in childhood to adulthood
-Predominantly posterior tibial involvement
 Lab. – CK : only slightly elevated except in Miyoshi myopathy
- Biopsy : non- specific dystrophic changes
- EMG : myopathic
 Treatment – occupational therapy for loss of hand function
- Ankle - foot orthoses to support distal lower limbs

32.  Inheritance : AD
 Transmission- mutation in trinucleotide repeat
sequence in a gene at 19q133
 myotonia : usually appears by age 5 yrs
 C/F 5 most striking features of this disease are
 Special tonography of muscle involvement
• Muscle of hand & extensor muscle of forearm
• LPS & facial muscle
• Sternocleidomastoid swan neck appearance
• Hatchet- faced appearance: temporalis , masseter ,
facial muscle atrophy & weakness
• foot drop : pretibial muscle weakness

33.  Cardiac abnormality- extreme bradycardia & high degree AV
block
 Myotonia- relaxation of muscle is impaired after strong
contraction
 Autoimmune feature
- dysarthritic speech,
- nasal voice,
- swallowing problems
- respiratory insufficiency : diaphragm & intercostal muscle
involvement
 Dystrophic changes
1. Lenticular opacity( cataract) M/C
2. Mild- moderate MR
3. Gonadal atrophy
4. Progressive frontal alopecia

34. Hatchet-faced
appearance

35.  Lab. – Dx ; usually based on clinical findings
- CK : N or mildly elevated
- EMG : evidence of myotonia
- Biopsy : atrophy which selectively involves type – 1 fibers in 50%
 Treatment – treat myotonia : membrane stabilizing agents
: phenytoin is preferred
- pacemaker for advanced conduction block
- molded ankle foot - orthoses help prevent foot drop

36.  Rare disorders distinguished from muscular dystrophies by the presence of
specific histochemical & structural abnormalities in muscle fibers.
 Onset : infancy or childhood
 Three types:
-central core disease : AD
- Nemaline (rod ) myopathy: AD
- Myotubular( centronuclear ) myopathy : AD , XR
 C/F - progressive muscle weakness ( proximal> distal, legs> arms)
- skeletal deformities (kyphoscoliosis, club foot, hip dislocation)
 Lab. - CK: usually N or slightly elevated
- EMG : myopathic
- Biopsy : features specific to each type
 Treatment – no specific treatment

37.  C/F- weakness is episodic
-proximal muscles more than distal, mostly sparing ocular
, bulbar and respiratory muscles.
 Inheritance – AD
Recognized by their
1. clinical characteristics
2: provocation by exercise, eating , cold exposure
3. serum potassium concentration during an attack

38. TABLE 368-5 Clinical Features of Periodic Paralysis and Nondystrophic Myotonias
Calcium
Channel Sodium Channel
Potassium
Channel
Feature
Hypokalemic
PP Hyperkalemic PP
Paramyotonia
Congenita
Anderson's
Syndromeb
Mode of
inheritance
AD AD AD AD
Age of onset Adolescence Early childhood Early childhood Early
childhood
Myotoniaa
No Yes Yes No
Episodic weakness Yes Yes Yes Yes
Frequency of
attacks of
weakness
Daily to
yearly
May be 2–3/d With cold, usually
rare
Daily to
yearly
Duration of attacks
of weakness
2–12 h From 1–2 h to >1
day
2–24 h 2–24 h
Serum K+
level
during attacks of
weakness
Decreased Increased or normalUsually normal Variable
Effect of K+
loading
No change Increased
myotonia, then
weakness
Increased myotonia No change
Effect of muscle
cooling
No change Increased myotonia Increased
myotonia, then
weakness
No change
Fixed weakness Yes Yes Yes Yes
a
May be paradoxical in paramyotonia congenita.
b
Dysmorphic features and cardiac arrhythmias are distinguishing features (see text).
Abbreviations: AD, autosomal dominant; AR, autosomal recessive; PP, periodic
paralysis.

39.  HypoKPP
 Attacks may stay for as long as 24hrs
 Precipitated by rest following exercise,
meals high in CHO, Na+
 Biopsy shows single or multiple
centrally placed vacuoles
 Rx of acute paralysis
- K+
supplementation (oral or IV )
 Prevention of recurrent attacks
-low CHO, Na+
diet
-avoid intense exercise
-K+
-sparing diuretics
-Acetazolamide 125-1000mg/day
 HyperKPP
 Attacks are brief and mild (30’- 4hrs)
 Precipitated by rest following exercise,
fasting and K+
administration
 Biopsy shows vacuoles that are
smaller, less numerous & more
peripheral compared to HypoKPP
 Rx of acute paralysis
- not important
 Prevention of recurrent attacks
-increase CHO in diet
-K+
- losing diuretics
-Acetazolamide 125 – 1000mg/day

40.  Types : - Polymyositis ( PM )
- Dermatomyositis ( DM )
- Inclusion body myositis ( IBM
 COMMON FEATURES OF INFLAMMATORY MYOPATHY
o Proximal muscles more commonly involved(LL>UL)
o Distal muscles of limb r rarely involved except in IBM
o Pharyngeal & neck flexor muscles r often involved-—dysphagia & head drop
o No involvement of ocular muscles even in advanced untreated cases
o Facial muscles r not involved except in IBM
 SPECIFIC FEATURES OF PM
o Disease progression is subacute
o F:M=1:1
o Blacks>whites
o Onset age >18yrs………….peak incidence 50-60 yrs

41.  PM is a diagnosis of exclusion i.e. there is
1. No rash
2. No involvement of facial & EOM
3. No exposure to myotoxic drug & toxin
4. No muscular dystrophy
5. No muscle enzyme deficiency
6. No family H/O neuromuscular disorders

42.  SPECIFIC FEATURES OF DM
 Skin manifestations
1. Heliotrope rash
2. Gottron papule
3. Mechanic’s hand
4. Calcinosis cutis
5. Shawl sign
6. V sign
7. DM sine myositis

43.  SPECIFIC FEATURES OF IBM
o onset>50yrs
o Disease progression is chronic
o Whites>black
o M>F
o Pattern of weakness is asymmetrical
o Proximal & distal muscles both r involved
o Mild weakness of facial muscles
o Quadriceps atrophy with repeated falling

44.  Extramuscular manifestations of Inflammatory
myopathy
- skin manifestations –DM
- systemic symptoms: fever, malaise, wt. loss, arthralgia, Raynaud’s Phen.
These r found when inflammatory myopathies r associated with connective
tissue diseases
- joint contractures : mostly in DM
- dysphagia : DM, IBM,PM
- cardiac disturbances : cardiomyopathy, arrhythmias, conduction defects
- subcutaneous calcifications : DM
- pulmonary dysfunction : PM, DM
 ASSOCIATED MALIGNANCY SPECIFIC TO DM
ovarian malignancy
Breast ca, NHL

46.  Dx.
- CK : elevated as much as 50 times in DM & PM
10 times in IBM
- Needle EMG : myopathic potentials
: increased spontaneous activity with fibrillations, complex
repetitive discharges, & positive sharp waves
: mixed potentials - IBM indicating chronic process
- Biopsy : definitive diagnosis
PM- intramyceal inflammation
DM- perimyceal & perivascular inflammation
IBM- vacoulated cell in muscle

47. Treatment
 Goal :
1. improve muscle strength,
2. Decrease the extra muscular manifestations( rash, dysphagia, dyspnea,
fever)
 Step- 1 : high- dose prednisolone
- 1mg/kg/day : taper gradually based on the response until the
lowest possible dose that controls the disease is reached
 Step- 2 : immunosuppressive drugs : if a patient fails to respond adequately
to glucocorticoids after a 3 month trial.
 Azathioprine – 3mg/kg/day
 Methotrexate – 7.5mg weekly with gradual dose escalation
 Cyclophosphamide – 0.5mg-1mg IV. Monthly for 6 months
 rituximab
 Cyclosporine

48.  Step- 3 IVIg : short lived & repeated infusions are required
 Step -4 trial with any of the following drug
------cyclosporine, rituximab,cyclophosphamide
 Prognosis : treatment
- 5yr. Survival : 95% for PM, DM
- 10yr. Survival : 84%
- poor : severe illness, long duration, older age, associated cancer
severe dysphagia or respiratory difficulties
: IBM

49.  Onset : most in childhood or early adulthood
 Lab. - CK : usually N or slightly increased
- Serum lactate : usually increased
- EMG : myopathic
- Biopsy :modified trichrome stain - ‘ragged red
fiber ‘ appearance
 Structures affected: skeletal muscles, CNS, endocrine
glands, heart
 Course : progressive & downhill
 Treatment : supportive - exercise
- pace maker insertion
for heart block
- treat epilepsy
- treat endocrinopathies

50. 1. progressive external ophthalmoplegia ( CPEO ): > 50%, characterized by
ptosis & extra ocular muscle weakness in the absence of diplopia
KSS, AD- CPEO, ARCO
2. skeletal muscle- CNS syndromes : MERRF, MELAS
3. pure myopathy simulating muscular dystrophy
Kearns sayre syndromeKearns sayre syndrome
( KSS( KSS )
- sporadic, non-inherited disorder, single deletions of mtDNA
-Triads : CPEO
: pigmentary retinopathy
: heart block &/or cerebellar ataxia, &/or CSF protein>100mg/dl
others: short stature ,dementia, MR, sensory neural hearing loss, diabetes,
hypothyroidism, gonadal dysfunction in both sexes.
Course – most die in their 4th
or 5th
decade

51. Myoclonic Epilepsy with Ragged Red Fibers/Myoclonic Epilepsy with Ragged Red Fibers/
MERRFMERRF
 Point mutation of mitochondrial transfer RNA
 C/F - myoclonic epilepsy: integral part & may be the initial symptom
- cerebellar ataxia : progressive, both trunks & the limbs
- progressive muscle weakness : limb- girdle distribution
 others: dementia, optic atrophy, peripheral neuropathy, hearing loss ,
Diabetes
 Rx- supportive with special attention to epilepsy

52. Mitochondrial myopathy,Encephalopathy, LacticMitochondrial myopathy,Encephalopathy, Lactic
acidosis, Stroke-like episodes / MELASacidosis, Stroke-like episodes / MELAS
 Most common encephalomyopathy
 Maternally inherited point mutations of mtRNA gene
 C/F - partial or generalized seizures : could be the 1st
sign
- stroke- like Sxs- hemiparesis, hemianopia, cortical blindness
- serum lactic acid : typically increased
others : dementia, hearing loss, hypothyroidism, diabetes,
hypothalamic- pituitary dysfunction
 Neuroimaging : basal ganglia calcifications in high percentage of
cases
 Treatment – supportive , fatal outcome

53. Pure myopathy syndromePure myopathy syndrome
 C/F – muscle weakness and fatigue which makes it
difficult to differentiate from muscular dystrophies
 Onset - usually neonatal, occasionally at a later age
- weakness, hypotonia, delayed milestones &
death before age 2 yrs
 Treatment – supportive care similar to muscular
dystrophies

54.  Fatigueness is more common than weakness
 Cause : not well defined
 - CK : usually N , except in hypothyroidism
 - muscle histology : atrophy rather than destruction of the
muscle fibers
 Rx- nearly all respond to treatment

55.  Hypothyroidism
-muscle weakness with muscle
cramps, pain & stiffness in 1/3rd
-
prolonged relaxation phase of
muscle stretch reflexes
-Hoffman’s syndrome: muscle
enlargement ( unknown cause),
&weakness with muscle stiffness
-CK- usually >10x ed
-Biopsy : normal
 Hyperthyroidism
-proximal weakness with atrophy
-sometimes bulbar, respiratory &
esophageal muscle involvement
: dysphagia, dysphonia, aspiration
-muscle stretch reflexes are
often brisk
-CK: usually N
-Biopsy : atrophy of fibers
 Others:
- thyrotoxic periodic paralysis
- Grave’s ophthalmopathy
:progressive ophthalmopathy, with
proptosis

56.  Hyperparathyoidism
-proximal muscle weakness, muscle
wasting, brisk stretch reflexes
-CK : usually N
-Biopsy : varying degrees of atrophy
 Hypoparathyoidism
- Hypocalcemia resulting in
sustained tetany & muscle
damage
- Hypo- or areflexia
- CK : may be increased
 Diabetes mellitus
- myopathy is uncommon
- rarely ischemic infarction of the
thigh muscles
- abrupt onset of pain, tenderness,
& edema of one thigh
- hard & indurated area on palpation
Dx- imaging / CT, MRI /
-focal abnormality in muscle
 Vitamin deficiency
- myopathy is rare
- proximal muscle weakness
- CPEO
- Vit. D , Vit. E deficiency

57.  Cushing’s disease
- Steroid excess causes various
degrees of muscle weakness
- proximal limb muscle weakness
- striking muscle atrophy
- Associated cushingoid appearance
- CK: Usually N
-Biopsy : atrophy of fibers
▪ Acromegally
- Mild proximal muscle weakness
without muscle atrophy
 Adrenal insufficiency
- mild weakness with prominent
fatigue
 Conn’s syndrome
- due to persistent hypokalemia
- Persistent muscle weakness
- muscle wasting if long standing
- CK : may be elevated
- Biopsy : degenerating fibers

58.  Direct toxicity : common
: muscle breakdown, rhabdomyolysis & myoglobinuria may occur
Ex.- lipid lowering agents, glucocorticoids - common
 Drug induced autoimmune myopathy
Ex. – D-penicillamine : features similar to polymyositis
 Lipid lowering agents
 all classes
 Sx - proximal weakness
- myalgia, malaise, muscle tenderness
- severe rxns : rhabdomyolysis & myoglobinuria
 Lab.- CK: elevated
- EMG : myopathic
- Biopsy : muscle necrosis
 Rx – cessation of drugs

59.  Glucocorticoid related
 Fluorinated steroids ( triamcinolone, dexamethasone, bethametasone)
 Chronic use of steroids ( prednisolone > 30mg/day )
 Respiratory muscles could be involved
 Presentation
1. Chronic : proximal muscle weakness associated with cushingoid
appearance
: Lab. - CK , EMG are usually N
- Biopsy – preferential atrophy of type – II muscle fibers
: Rx – drug withdrawal
2. Acute : associated with high dose iv. glucocorticoid use ( severe asthma,
COPD)
: acute quadriplegia
: Biopsy – distinctive loss of thin filaments by electron microscopy
: Rx- drug withdrawal, supportive care, rehabilitation
- recovery is slow

60.  Zidovudine / AZT / related myopathy
 Mitochondrial myopathy
 Occurs in 17% of patients treated with doses of 1200mg/day for
6 months.
 Sx.- myalgias, muscle weakness & atrophy affecting the thigh
& calf muscles
 Lab.- CK : elevated
- EMG : myopathic
- Biopsy : ragged red fibers with minimal inflammation
 ( HIV- related myopathy : marked inflammation)
 Rx – reduce dose or withdraw drug

63.  Abnormalities in either glucose or lipid utilization
 Presentation
:acute painful syndromes with rhabdomyolysis & myoglobinuria
:chronic progressive muscle weakness simulating dystrophies

64.  C/F – usually present during infancy
- severe muscle weakness, delayed milestones,, cardiomegally,
hepatomegally, respiratory insufficiency
- death usually occurs by 1 yr of age
 Three types: 1. Debranching enzyme deficiency
2. Branching enzyme deficiency
3. Acid maltase deficiency – commoner, AR inheritance
-can present during adulthood
-Heart & liver not involved
-respiratory failure & diaphragmatic weakness are often
initial manifestations, heralding progressive proximal weakness
Dx- membrane bound & free tissue glycogen on electron microscopy
- definitive diagnosis through enzyme determination in muscle
Rx. – recombinant enzyme replacement may improve muscle weakness
& prolong life.

65.  Effects: failure to support energy production at the initiation of exercise
 Onset : adolescence
 C/F – painful muscle contractures followed by myoglobinuria
- Sxs are precipitated by brief bursts of high intensity exercise such as
running or lifting heavy objects
 5 types : Myophosphorylase deficiency ( McArdle’s disease )
- most common , AR inheritance
 Lab.- CK : >100x elevated
- U/A : myoglobinuria
- Fore arm exercise test : impaired rise in venous lactate
 Definitive diagnosis : muscle biopsy
 Treatment : exercise tolerance can be enhanced by training / warm-up or
brief periods of rest

66.  Most common cause of recurrent myoglobinuria
 Cause : CPT-II deficiency
 Inheritance : AR ; but commoner in men / 5:1 /
 Onset – teenage years or early childhood
 C/F – muscle pain & myoglobinuria : following prolonged exercise, some
times following fasting
: doesn’t occur until the limits of utilization have been exceeded & muscle
breakdown has already begun unlike glycolytic defects
- strength is normal in b/n attacks unlike carnitine deficiency.

67.  Lab.- CK, EMG usually N b/n attacks
-forearm exercise test : normal rise of
venous lactate
- muscle biopsy : usually N
 Dx.- direct measurement of muscle CPT-II
 Rx.- frequent meals /low fat, high CHO/ may prolong
exercise tolerance