4. historyhistory
Onset ageOnset age
distributiondistribution
CourseCourse
MyalgiaMyalgia
CrampCramp
ContractureContracture
Dark urineDark urine
Myotonia ,Stiffness /warming up phenomenaMyotonia ,Stiffness /warming up phenomena
Aggravating: exercise /diet/temperature/drugAggravating: exercise /diet/temperature/drug
5. examexam
Limb girdleLimb girdle
ScapuloperonealScapuloperoneal
DistalDistal
Ocular or pharyngealOcular or pharyngeal
Neck extensorNeck extensor
Atrophy or hypertrophyAtrophy or hypertrophy
Myotonia or paramyotoniaMyotonia or paramyotonia
6. Ptosis usually without opthalmoplegiaPtosis usually without opthalmoplegia
Myotonic dystrophyMyotonic dystrophy
Congenital myopathyCongenital myopathy
Ptosis with opthalmoplegiaPtosis with opthalmoplegia
Oculopharyngeal muscular dystrophyOculopharyngeal muscular dystrophy
Mitochondrial myopathyMitochondrial myopathy
14. muscular dystrophymuscular dystrophy
are inherited myopathy characterized byare inherited myopathy characterized by
progressive muscles weaknessprogressive muscles weakness
°eneration &subsequent replacement°eneration &subsequent replacement
by fibrous & fatty connective tissueby fibrous & fatty connective tissue
Historically were categorized by their:Historically were categorized by their:
Age onset /distribution of weakness&Age onset /distribution of weakness&
pattern of inheritancepattern of inheritance
The genetic mutation &abnormal geneThe genetic mutation &abnormal gene
product were defined for many of themproduct were defined for many of them
16. Duchenne MDDuchenne MD
Incidence: 1/3500 male birthIncidence: 1/3500 male birth
1/3 new mutation1/3 new mutation
c/p:as early as 2-3y with delayc/p:as early as 2-3y with delay
milestonesmilestones
Progressive limb girdle patternProgressive limb girdle pattern
Fall 5-6y/difficult climb stair 8y,Fall 5-6y/difficult climb stair 8y,
confined to wheelchair 12yconfined to wheelchair 12y
17. Joint constructers 6-10yJoint constructers 6-10y
Calf hypertrophy is earlyCalf hypertrophy is early
Muscles atrophy lateMuscles atrophy late
Progressive kyphscliosis due to ParaspinalProgressive kyphscliosis due to Paraspinal
muscles weaknessmuscles weakness
Reflex: biceps/knee/lost by age 10yReflex: biceps/knee/lost by age 10y
ankle preserved late in diseaseankle preserved late in disease
Respiratory s/s after age 10Respiratory s/s after age 10
18. Cardiac: generally asymptomaticCardiac: generally asymptomatic
CHF, arrhythmia lateCHF, arrhythmia late
90% abnormal ECG :tall rt R90% abnormal ECG :tall rt R
wave,deep left Q wavewave,deep left Q wave
Echo: hypokinesia ,dilatation ofEcho: hypokinesia ,dilatation of
ventricular wallventricular wall
GI: intestinal pseudo obstructionGI: intestinal pseudo obstruction
IQ: one SD below NIQ: one SD below N
19. lablab
A dystrophin gene deletion can be detected by:A dystrophin gene deletion can be detected by:
DNA analyses from leukocytes by PCR in 2/3DNA analyses from leukocytes by PCR in 2/3
patient or DNA musclespatient or DNA muscles
The other 1/3 DX by… muscles biopsy( dystrophinThe other 1/3 DX by… muscles biopsy( dystrophin
def by stain &WB ,typical features of MD)def by stain &WB ,typical features of MD)
CK:20-100 XN ,decline laterCK:20-100 XN ,decline later
EMG:myopathic &fibrillationEMG:myopathic &fibrillation
Note :if DNA study +ve no need for EMGNote :if DNA study +ve no need for EMG
&muscles biopsy&muscles biopsy
20. Beckers MDBeckers MD
Is milder formIs milder form
5/100,0005/100,000
Age :5-15yAge :5-15y
Wheelchair at 30yWheelchair at 30y
Cardiac similar to duchenneCardiac similar to duchenne
Death by age 40Death by age 40
Dx: DNA, muscle biopsy decrease inDx: DNA, muscle biopsy decrease in
dystrophindystrophin
CK:moderatly elevatedCK:moderatly elevated
21. treatmenttreatment
No treatment prevent theNo treatment prevent the
progressionprogression
corticosteroid :controlled trial withcorticosteroid :controlled trial with
predinsone 0,75mg/kg demonstratepredinsone 0,75mg/kg demonstrate
moderate improvement in strengthmoderate improvement in strength
&delay progression to wheel chair&&delay progression to wheel chair&
respiratory compromiserespiratory compromise
23. CK :normal to or only moderateCK :normal to or only moderate
elevatedelevated
The muscle biopsy :myopathicThe muscle biopsy :myopathic
&fewer dystrophic&fewer dystrophic
DNA:mutation gene in Xq28 code forDNA:mutation gene in Xq28 code for
protien emerinprotien emerin
24. Limb girdle dystrophyLimb girdle dystrophy
AR majorityAR majority
Onset: adolescence or lateOnset: adolescence or late
childhood: sever child recessive muscularchildhood: sever child recessive muscular
dystrophydystrophy
25. AR: defect in sacroglycan component ofAR: defect in sacroglycan component of
the DGC( sacroglycanopathythe DGC( sacroglycanopathy((
Alpha sacrglycan adhelin is account forAlpha sacrglycan adhelin is account for
20%20%
Onset:childhood& variableOnset:childhood& variable
No intellectual impairment or cardiacNo intellectual impairment or cardiac
Muscle biopsy :immune stain absent orMuscle biopsy :immune stain absent or
diminished for sacroglycandiminished for sacroglycan
26. AD: onset: second and third decadesAD: onset: second and third decades
Protein defect:caveolin-3Protein defect:caveolin-3
There are multiple subtypesThere are multiple subtypes
AD type 1:1A,1B …AD type 1:1A,1B …
AR type 2:AR type 2:
27. Congenital muscular dystrophyCongenital muscular dystrophy
ARAR
Perinatal onsetPerinatal onset
c/p:hypotonia &proximalc/p:hypotonia &proximal
weakness,arthrogryposisweakness,arthrogryposis
Two typesTwo types
CNS involvement: severCNS involvement: sever mental retardationmental retardation
,visual, seizure ..cerebrocular dysplasia,,visual, seizure ..cerebrocular dysplasia,
progressive death by age 10-12progressive death by age 10-12
No CNS :classic typeNo CNS :classic type MRI (hypomyelination),MRI (hypomyelination),
benign outcome, non progressivebenign outcome, non progressive
Muscle biopsy :dystrophy…Muscle biopsy :dystrophy…
28. FSHFSH
InheritanceInheritance: AD: AD
Variable expression within the familiesVariable expression within the families
AgeAge: childhood or adult life: childhood or adult life
C/PC/P::
weakness early facial then descending to scapula stabilizerweakness early facial then descending to scapula stabilizer
muscles &muscles of the upper limb& distal weaknessmuscles &muscles of the upper limb& distal weakness
..peroneal ,the rate of progression to forearm &pelvic girdle..peroneal ,the rate of progression to forearm &pelvic girdle
Asymmetrical/Asymmetrical/ deltoid preserved / joint contracture aredeltoid preserved / joint contracture are
uncommonuncommon
Popeye handPopeye hand/ winging scapula// winging scapula/ no muscle hypertrophyno muscle hypertrophy
Early onset worse prognosisEarly onset worse prognosis
20% require wheelchair20% require wheelchair
29. Work upWork up
CK:N or mild elevationCK:N or mild elevation
Muscles biopsy: myopathicMuscles biopsy: myopathic
dystrophicdystrophic& occasionally prominent& occasionally prominent
mononuclear infiltratemononuclear infiltrate
Gene: ch 4q35 gene deletionGene: ch 4q35 gene deletion
30. Myotonic dystrophyMyotonic dystrophy
AD,AD, CTG repeatCTG repeat
Affect :Affect :
skeletal,cardiac, smooth muscles, eye,endocrineskeletal,cardiac, smooth muscles, eye,endocrine
&brain&brain
Onset :at any age ,usually at late 2Onset :at any age ,usually at late 2ndnd
decadedecade
Some individual can be symptoms free theirSome individual can be symptoms free their
entire lifeentire life
Sever form :congenital myotonic dystrophySever form :congenital myotonic dystrophy
32. systemicsystemic
Posterior sub scapular cataractPosterior sub scapular cataract
Testicular atrophy& impotenceTesticular atrophy& impotence
Intellectual impairmentIntellectual impairment
Hypersomnia (central & obstructive)Hypersomnia (central & obstructive)
Respiratory failureRespiratory failure
Elevation of serum glu, rarely frank DMElevation of serum glu, rarely frank DM
GI: dysphagea, pseudo obstructionGI: dysphagea, pseudo obstruction
Cardiac conduction defect sudden deathCardiac conduction defect sudden death
Fetal loss in femaleFetal loss in female
33. PROMMPROMM
ADAD
Proximal weakness, no distalProximal weakness, no distal
weaknessweakness
Myotonia &myalgiaMyotonia &myalgia
Less cardiac &other organLess cardiac &other organ
involvement except cataractinvolvement except cataract
34. Work upWork up
CK:N or mild elevationCK:N or mild elevation
EMG: myopathic &EMG: myopathic & myotoniamyotonia
Muscle biopsy: atrophic, non specificMuscle biopsy: atrophic, non specific
Gene :CTG repeat >50 in ch19q13.2Gene :CTG repeat >50 in ch19q13.2
35. tttttt
Myotonia rarely sever to require tt:Myotonia rarely sever to require tt:
phenytoin is the only safe drugphenytoin is the only safe drug
Annual ECG ..pacemaker mayAnnual ECG ..pacemaker may
requiredrequired
Positive pressure ventilation supportPositive pressure ventilation support
High risk in surgery (cardiacHigh risk in surgery (cardiac
&respiratory)&respiratory)
Sedation & opiod use with cautionSedation & opiod use with caution
36. Distal dystrophyDistal dystrophy
TypesTypes
AD:4AD:4thth
&6&6thth
decadedecade
AR:in early adult onset/late secondAR:in early adult onset/late second
or early 3or early 3rdrd
CK :elevated 200xN ARCK :elevated 200xN AR
37. oculopharengealoculopharengeal
ADAD
Onset:5Onset:5thth
&6&6thth
decadedecade
Ptosis &dysphagea later all extra ocularPtosis &dysphagea later all extra ocular
muscles &extremities affected (limb girdle)muscles &extremities affected (limb girdle)
but distal can be significant in somebut distal can be significant in some
variantvariant
Slow progressive ,death from aspirationSlow progressive ,death from aspiration
pneumonia or starvationpneumonia or starvation
Ck:n or mild elevatedCk:n or mild elevated
Muscle biopsy :Muscle biopsy :rim vacuolesrim vacuoles
Genetic GCG repeat in ch14Genetic GCG repeat in ch14
38.
39. Congenital myopathyCongenital myopathy
Are distinguished from dystrophy inAre distinguished from dystrophy in
threethree respect:respect:
Characteristic morphologic alterationCharacteristic morphologic alteration
At birthAt birth
Non progressiveNon progressive
However there are exception to allHowever there are exception to all
these generalizationthese generalization
Inheritance: are variableInheritance: are variable
40. c/p:c/p: hypotonia with subsequent developmental delayhypotonia with subsequent developmental delay
Reduce muscles bulk, slender body build &long narrow faceReduce muscles bulk, slender body build &long narrow face
Skeletal abnormalities: high arched palate ,pectusSkeletal abnormalities: high arched palate ,pectus
exacavitum, kyphscliosis, dislocated hip, pes cavusexacavitum, kyphscliosis, dislocated hip, pes cavus))
Absent or reduced muscle stretch reflexAbsent or reduced muscle stretch reflex
Weakness: limb girdle mostly, butWeakness: limb girdle mostly, but distaldistal weakness existweakness exist
CK &EMG may be normalCK &EMG may be normal
Muscle biopsy: the diagnostic methodMuscle biopsy: the diagnostic method
41. Central core myopathyCentral core myopathy
Characterized by discrete zones ofCharacterized by discrete zones of
myofibrillar disruption in the centermyofibrillar disruption in the center
of muscles fiberof muscles fiber
AD but can be sporadicAD but can be sporadic
Mutation ch 19,similar to malignantMutation ch 19,similar to malignant
hyperthermia patienthyperthermia patient
So anesthesia precaution areSo anesthesia precaution are
necessarynecessary
42. Nemaline myopathyNemaline myopathy
Pathology: thePathology: the presence of rods orpresence of rods or
melamine bodies within muscles fibermelamine bodies within muscles fiber
AD or ARAD or AR
c/p:c/p:
Sever neonatalSever neonatal form which is fatal in theform which is fatal in the
first year of lifefirst year of life
Mild staticMild static
Slowly progressiveSlowly progressive from birth or earlyfrom birth or early
childhoodchildhood
Note :rods can present in HIV relatedNote :rods can present in HIV related
myopathy ,some inflammatorymyopathy ,some inflammatory
43. Centro nuclear (myotubularCentro nuclear (myotubular((
Pathology: large central nuclei in thePathology: large central nuclei in the
muscle fibermuscle fiber
X linked/AD/ARX linked/AD/AR
sever neonatal/static or slowlysever neonatal/static or slowly
progressiveprogressive
c/p: ptosis & opthalmoparesisc/p: ptosis & opthalmoparesis
Genetic defect: mutation inGenetic defect: mutation in
myotubularin gene Xp28myotubularin gene Xp28
46. Metabolic myopathyMetabolic myopathy
Clues to hereditary metabolicClues to hereditary metabolic
myopathymyopathy
Excersize induce weaknessExcersize induce weakness
&myoglobinuria…glycogen &lipid&myoglobinuria…glycogen &lipid
Part of diffuse neurologicalPart of diffuse neurological
syndrome…mitochondrialsyndrome…mitochondrial
47. Glucose/glycogenGlucose/glycogen
Glucose &its storage is essential for theGlucose &its storage is essential for the
short termshort term anaerobic energy (glycogensis)anaerobic energy (glycogensis)
Two clinical presentation:Two clinical presentation:
1-dynamic:type V/V11/V111/1X//XX11-dynamic:type V/V11/V111/1X//XX1
2-static:fix weakness2-static:fix weakness
1/111/1V1/111/1V
Inheritance:AR except forInheritance:AR except for
phosphoglycerate kinasephosphoglycerate kinase
48. Glycogensis with exerciseGlycogensis with exercise intoleranceintolerance
C/P: exercise intolerance in the childhoodC/P: exercise intolerance in the childhood
followed by excertional induced muscle painfollowed by excertional induced muscle pain
&myoglobinurea in sec or 3&myoglobinurea in sec or 3rdrd
decade..decade..
(Second wind phenomena)(Second wind phenomena)
work up:work up:
CK/EMG normal between the attack in early stageCK/EMG normal between the attack in early stage
but after attack( myopathic &fibrillation)but after attack( myopathic &fibrillation)
Forearm exercise testForearm exercise test
Enzyme assayEnzyme assay
Muscle biopsyMuscle biopsy
Genetic for mutationGenetic for mutation
49. What is 0ther causes ofWhat is 0ther causes of
myoglobinureamyoglobinurea??
50. Glycogensis with fixed weaknessGlycogensis with fixed weakness
Acid maltase deficiency:Acid maltase deficiency:
Enzyme convert glycogen to glucoseEnzyme convert glycogen to glucose
Three clinical variant:Three clinical variant:
Infantile: pompes: progressiveInfantile: pompes: progressive
weakness ,enlargement of heart, tongueweakness ,enlargement of heart, tongue
&liver&liver death by age 2death by age 2
Juvenile type: proximal weakness, mayJuvenile type: proximal weakness, may
calf hypertrophy death by age 20 fromcalf hypertrophy death by age 20 from
respiratory failurerespiratory failure
Adult type:2&7Adult type:2&7thth
progressive limb girdle orprogressive limb girdle or
scapuloperoneal .no liver ,no heartscapuloperoneal .no liver ,no heart
involvementinvolvement
51. Work upWork up
CK :moderately increasedCK :moderately increased
EMG: myopathic changes &EMG: myopathic changes &myotonicmyotonic
discharge in paraspinusdischarge in paraspinus
Enzyme assay:Enzyme assay:
Muscle biopsy: a vacuolar myopathyMuscle biopsy: a vacuolar myopathy
with high glycogen contentwith high glycogen content
Genetic: mutation in ch 17Genetic: mutation in ch 17
52. Fatty acid metabolismFatty acid metabolism
Lipids are essential for aerobicLipids are essential for aerobic
metabolismmetabolism
Dynamic & staticDynamic & static
CPT:carnitine palmitoyl transeferaseCPT:carnitine palmitoyl transeferase
deficiencydeficiency
Carnitine deficiencyCarnitine deficiency
53. CPTCPT
Type 1:infancy &child hood with hepaticType 1:infancy &child hood with hepatic
dysfunctiondysfunction
Type 2:exertional myalgia &myoglobinurea,Type 2:exertional myalgia &myoglobinurea,
it is the most frequently definableit is the most frequently definable
metabolic defect presenting with myoglobinureametabolic defect presenting with myoglobinurea
AR ,gene 1p32AR ,gene 1p32
The attacks occur after prolonged exercise,The attacks occur after prolonged exercise,
fasting, febrile illnessfasting, febrile illness
Unlike mecardle disease the patient can tolerateUnlike mecardle disease the patient can tolerate
brief exercise ,no second wind phenomenabrief exercise ,no second wind phenomena
Muscle strength are normal at restMuscle strength are normal at rest
54. lablab
CK:n at restCK:n at rest
Forearm exercise test :NForearm exercise test :N
EMG: n at rest ,&myopathic during theEMG: n at rest ,&myopathic during the
attackattack
Muscle biopsy: usually N ,except ofMuscle biopsy: usually N ,except of
myopathic changes after rhabdomylsismyopathic changes after rhabdomylsis
Enzyme assayEnzyme assay
ttt &meal frequency: increase CHO intakettt &meal frequency: increase CHO intake
&education about fasting &exercise&education about fasting &exercise
56. channelopathychannelopathy
Non dystrophic myotoniaNon dystrophic myotonia
Periodic paralysisPeriodic paralysis
It due to mutation in differentIt due to mutation in different
channels gene leading to :channels gene leading to :
Hyper excitability :myotoniaHyper excitability :myotonia
In excitability: paralysisIn excitability: paralysis
57. Chloride channelopathyChloride channelopathy
Mutation in CLMutation in CL
channel..hyperexcitability afterchannel..hyperexcitability after
depolarizationdepolarization
Myotonia congenita:Myotonia congenita:
AD..thomsen /AR:beckerAD..thomsen /AR:becker
C/P:C/P:
muscle hypertrophy,muscle hypertrophy,
myotonia/becker type has fluctuatingmyotonia/becker type has fluctuating
limb girdle weaknesslimb girdle weakness
61. Paramytonia congenitaParamytonia congenita
ADAD
Onset :1Onset :1stst
decadedecade
Paradoxical myotonia (Aggravated byParadoxical myotonia (Aggravated by
warm as well cold)warm as well cold)
Face ,neck,forearmFace ,neck,forearm
After several attempt of eye closure theAfter several attempt of eye closure the
patient can not open the eyepatient can not open the eye
ttt: Na channels blocker mexiletinettt: Na channels blocker mexiletine
62. Hyperkalamic periodic paralysisHyperkalamic periodic paralysis
K sensitive periodic paralysisK sensitive periodic paralysis
Onset :1Onset :1stst
decadedecade
Attack last:1-2 hAttack last:1-2 h
During attack: areflexic with no ocular orDuring attack: areflexic with no ocular or
respiratory muscles weaknessrespiratory muscles weakness
Strength is n between the attack, but someStrength is n between the attack, but some
patient has interictal limb girdle weaknesspatient has interictal limb girdle weakness
Some families have myotonia ¶myotoniaSome families have myotonia ¶myotonia
Aggravated: fasting/cold, shortly after exercise, KAggravated: fasting/cold, shortly after exercise, K
load, early AMload, early AM
63. Episodes are rarely serous enough toEpisodes are rarely serous enough to
require acute tttrequire acute ttt
ttt:ttt:
oral CHOoral CHO
Prevention: thiazide,B agonist, lowPrevention: thiazide,B agonist, low
K,high CHOK,high CHO
Avoid fasting, strenuous exercise/Avoid fasting, strenuous exercise/
64. myotoniamyotonia
No weaknessNo weakness
Aggravated by K diet/ excretionAggravated by K diet/ excretion
Can response to acetazolamideCan response to acetazolamide
65. hypokalemiahypokalemia
AD:AD:
It is the most frequent form of periodicIt is the most frequent form of periodic
paralysisparalysis
Common in maleCommon in male
Age: adolescenceAge: adolescence
The attacks 3-24h/vague prodorme ofThe attacks 3-24h/vague prodorme of
stiffness &heaviness& rarely ocular,stiffness &heaviness& rarely ocular,
bulbar, respiratory involvedbulbar, respiratory involved
Early Myotonia of eyelid & late interictalEarly Myotonia of eyelid & late interictal
proximal weaknessproximal weakness
66. AggravatedAggravated: CHO meal, cold,hrs post: CHO meal, cold,hrs post
exercise, sleepexercise, sleep
Work up:K level q 30min /TFT/Work up:K level q 30min /TFT/
R/O 2R/O 2ndnd
causes of hypokalemiacauses of hypokalemia
Tttt:Tttt:
Acute:Acute: oral K Q30min ,if symptoms severoral K Q30min ,if symptoms sever
iv Kiv K
Prevention:Prevention:
Low CHO, low sodium dietLow CHO, low sodium diet
,spirnolactone, trimetrine,spirnolactone, trimetrine
