NNC CMUThe Northern Neuroscience Centre
Chiang Mai University
4 simple stepsApproach Myopathy
10 March 2016
Neu
rom
uscu
lar p
robl
em
CNS
Sensory with/without
motor
Nerve
Motor
Muscle
Constant weakness
Proximalarms and legs
Most of Myopathies
Distal armprox legs
H. Myotonic dystA. Inclusion body
myositis
Prox armsDistal legs
H. FSHD
Distal arms,legs H. Nonaka,Miyoshi
StiffnessH. Myopathy w
MyotoniaA. Hypothyroid
Episodic weakness
Exercise triggered
H. Metabolic MitochondrialMyopathy
Unrelated or delayed
H.HypoKPP
Oculobulbar
Ptosis with Ophalmoplegia
H. OPMDCPEO
Ptosis without H. Myotonic dyst
bulbar firstH. OPMD
LGMD 1A
Infant onset H. Congenital
NMJ
Nerve
Motor neuron
NNC CMUThe Northern Neuroscience Centre Chiang Mai University
Overview• Step 1 : Symptom definition
• Step2 : Conceptual classification
• Step 3 : Pattern recognition
• Step4 : Investigation
NNC CMUThe Northern Neuroscience Centre Chiang Mai University
Step 1: Symptom definition
Negative symptom
• Weakness• Proximal• Distal• Bulbar
• Exercise intolerant/fatigue• Muscle atrophy
NNC CMUThe Northern Neuroscience Centre Chiang Mai University
Positive symptom:
• Myalgia• Muscle pain without contraction
• Cramp • Episodic involuntary muscle contraction
usually painful
• Myotonia• Impaired relaxation after contraction• Repeated -> improve (warm up phenomenon)
NNC CMUThe Northern Neuroscience Centre Chiang Mai University
Myopathy with myalgia• Note : Not specific with inflammatory
• Infalmatory myopathies Dermatomyositis,Polymyositis
• Infectious myositis
• Mitochondrial myopathies
• Myeoadenylate deaminaase deficienccy
• Eosinophili-myalgia syndrome
• Tubular aggregate myopathy
• Becker dystrophy varient
Myotonia in simple physiology
Muscle membrane hyperexcitability(repetitive repolarization cause delayed depolarization) 1. Na channel gain function2. Cl channel loss function
Berchtold MW et al.Physiol Rev 2000(80) 1215–1265
NNC CMUThe Northern Neuroscience Centre Chiang Mai University
Step 2: Conceptual classification
Myopathy
Hereditary Acquire
1. Structure2. Channel
3.Metabolism
NNC CMUThe Northern Neuroscience Centre Chiang Mai University
Characters of hereditary myopathy
1. Slow progression (onset might be in adult)
2. Myotonia
3. Family history
Her
edita
ry m
yopa
thy
Muscular dystrophy
Congenital myopathy
Channelopathies
Metabolic myopathies
Mitochondrial myopathy
Myopathy with myotonia
• Glucose• Lipid
• Myotonic dystrophy ( Cl channel)• Duchene and Becker• Emery-Drefuss• Facioscapulo-humeral• Limb-girdle • Oculopaharyngeal
• myotonia congenital (Cl channel)• Paramyotonia congenital (Na channel)• HyperKPP (Na channel)• HypoKPP (Ca channel)• Anderson Tawil (K channel)
NNC CMUThe Northern Neuroscience Centre Chiang Mai University
Step 3 : Pattern recognition 1. Proximal arms and legs = Limb Girdle
2. Proximal arms and distal legs = Scapuloperoneal
3. Distal arms and proximal legs
4. Ptosis with or without ophthalmoparesis
5. Bulbar
6. Stiffness
7, 8, 9, 10
Carlyane E et al. Continuum 2013;19(6) 1674-97
• Ptosis with Ophtalmoplegia
• OPMD : oculopharyngeal muscular dystrophy
• OPDM : coulopharyngodistal myopathy
• CPEO & Mitochondrial myopathy group
• Ptosis without
• Myotonic dystrophy
• Congential myopathy
• myofibrillar myopathy
Ptosis with and without opthalmoplegia
Neu
rom
uscu
lar p
robl
em
CNS
Sensory with/without
motor
Nerve
Motor
Muscle
Constant weakness
Proximalarms and legs
Most of Myopathies
Distal armprox legs
H. Myotonic dystA. Inclusion body
myositis
Prox armsDistal legs
H. FSHD
Distal arms,legs H. Nonaka,Miyoshi
StiffnessH. Myopathy w
MyotoniaA. Hypothyroid
Episodic weakness
Exercise triggered
H. Metabolic MitochondrialMyopathy
Unrelated or delayed
H.HypoKPP
Oculobulbar
Ptosis with Ophalmoplegia
H. OPMDCPEO
Ptosis without H. Myotonic dyst
bulbar firstH. OPMD
LGMD 1A
Infant onset H. Congenital
NMJ
Nerve
Motor neuron
Distribution of weakness
10’s 30’s 50’sAge at the onset of symptom
DDx• Hereditary
• Congenital myopathy
• Channelopathies
• Myopathy with myotonia
• Metabolic myopathy
• Mitochondrial myopathy
• Muscular dystrophy
• Duchene
• OPMD
• LGMD
NNC CMUThe Northern Neuroscience Centre Chiang Mai University
DDx• Acquired
• Inflammatory
• Infection
• Drug/toxin
• Endocrine/nutrition
• Overused trauma
NNC CMUThe Northern Neuroscience Centre Chiang Mai University
Step 4: Investigation• Total CK
• EMG
• Muscle biopsy
• Genetic testing
NNC CMUThe Northern Neuroscience Centre
Chiang Mai University
Muscle biopsy
• Rhabdomyolysis
• Alcohol :acute
• Cholesterol lowering drugs
• Toluene
• Drug abuse : amphetamine, heroine, cocain
• Inflammatory
• Levodopa
• Cimetidine
• D-penicilamine
• Procainamide
Drugs induce myopathies
that raise CK
• Myosin loss
• Steroid ( involve type II muscle-> EMG also normal)
• Alcohol :chronic
• Nondepolarizing neuromuscular blocking
ie. Tubercularin
Drugs induce myopathies
that NOT raise CK
NNC CMUThe Northern Neuroscience Centre Chiang Mai University
Alcoholic myopathy• Acute
–Most common cause of nontraumaticrhabdomyolysis
–Patho: muscle fiber necrosis–Days after bing drinking –Precipitate by hypoPO4 ie
refeeding syndrome–Recovery days to wks after
cessation of alc intake
• Chronic –Corelate with alcoholic
cardiomyopathy–Patho: muscle fiber type II
atrophy –Relate to high cumulative
lifetime dose–Recovery 3-18 mos after
cessation of alc intake
NNC CMUThe Northern Neuroscience Centre Chiang Mai University
Limb girdle muscular dystrophy : LGMD• Definiton: genetic muscle disease with postnatal onset
of progressive weakness affecting proximal upper and lower extremities
• Defect of gene required for muscle function
• AD form : 1A, 1B…1H
• AR form : 2A, 2B…2W
NNC CMUThe Northern Neuroscience Centre Chiang Mai University
NNC CMUThe Northern Neuroscience Centre Chiang Mai University
Take home messageStep 1 : Negative and positive symptoms
Step 2 : Conceptual classificationHereditary vs Acquired
Step 3 : Pattern recognition approachDistribution Proximal, distal, oculobulbarPogression : Episodic, acute, chronic, nonprogress
Step 4 : InvestigationSerum CK , EMG, Muscle biopsy
NNC CMUThe Northern Neuroscience Centre Chiang Mai University
Reference• ตําราประสาทวทิยาคลนิิก . สมาคมประสาท
วทิยาแห่งประเทศไทย 2557
• Carlyane E et al. Continuum 2013;19(6) 1674-97