Approach to myopathy

1. Approach to myopathy
DR VINOD SINGH JATAV
SR NEUROLOGY
GMC KOTA

2. Type of muscle fiber

3. Introduction
MYOPATHY means primary skeletal muscle dysfunction.

4. History
Which negative and/or positive
symptoms and signs does the
patient demonstrate?
What is the distribution of
weakness?
Family history What is the temporal
evolution?
Are there precipitating
factors that trigger episodic
weakness or myotonia?
Are associated systemic
symptoms or signs present?

5. Etiology
Acquired
Endocrine
Drug induced
Toxic
Inflammatory/immune
Associated with systemic illness
Critical illness myopathy
Hereditary
Channelopathies
Congenital
Mitochondrial
Metabolic
Muscular dystrophy
Myotonia

6. Symptoms associated with myopathies
Negative symptoms
Fatigue
Exercise intolerance
Weakness
Atrophy
Positive symptoms
Cramp
Contracture
Hypertrophy
Myalgia
Stiffness

7. Myalgia
• Toxin and drug induced myopathy
• Eosinophilia myalgia syndrome
• Hypothyroid myopathy
• Inflammatory myopathies
• Myotonic disorder
• Mitochondrial myopathy
• Muscular dystrophy
(X linked myalgia and cramps/ becker dystrophy variant)
Fatigue
• NMJ
• Glycolysis
• Lipid abnormality
• Mitochondrial myopathy
• Chronic myopathy

8. Stiffness: decrease ability to relax
Improve with exercise
Myotonia: Na or Ca channelopathy
Worsen with exercise/ cold
Paramyotonia
Brody disease
With fixed weakness
Myotonic dystrophy
Becker disease (AR Cl channelopathy
Other
Malignant hyperthermia
Neuromyotonia
Stiffperson syndrome

10. Other symptoms
pseudohypertrophy
Duchenne’s muscular dystrophy,
Becker’s muscular dystrophy,
LGMD (2C-F, 2G, 2I)
Scapular wining
•FSHD.
•LGMD1B (laminopathy), LGMD2A
(calpainopathy), LGMD2C–2F
(sarcoglycanopathies).
Metabolic myopathies - Pompe’s disease and debrancher
deficiency (Cori-Forbes disease)
Myotonia congenita,
Hypothyroidism,
Amyloid and sarcoid myopathies,
Parasitic myositis,
SMA
Muscle hypertrophy

11. Temporal evolution: onset age
Myopathies Presenting at Birth
• Congenital myotonic dystrophy
• Centronuclear (myotubular) myopathy
• Congenital fiber-type disproportion
• Central core disease
• Nemaline (rod) myopathy
• Congenital muscular dystrophy
• Lipid storage diseases (carnitine deficiency)
• Glycogen storage diseases (acid maltase and phosphorylase
deficiencies)

12. Myopathies Presenting in Childhood
•Muscular dystrophies
–Duchenne
–Becker
–Emery-Dreifuss
–Facioscapulohumeral
–Limb-girdle
–Congenital
•Inflammatory myopathies
–Dermatomyositis
–Polymyositis (rarely)
•Congenital myopathies
–Nemaline
–Centronuclear
–Central core
•Lipid storage disease (carnitine deficiency)
•Glycogen storage disease (acid maltase
deficiency)
•Mitochondrial myopathies
•Endocrine-metabolic disorders
–Hypokalemia
–Hypocalcemia
–Hypercalcemia

13. Myopathies Presenting in Adulthood
• Muscular dystrophies
– Limb-girdle
– Facioscapulohumeral
– Becker
– Emery-Dreifuss
• Inflammatory myopathies
– Polymyositis
– Dermatomyositis
– Inclusion body myositis
– Viral [HIV]
• Metabolic myopathies
– Acid maltase deficiency
– Lipid storage diseases
– Debrancher deficiency
– Phosphorylase b kinase deficiency
– Mitochondrial myopathies
• Endocrine myopathies
– Thyroid
– Parathyroid
– Adrenal
– Pituitary disorders
• Toxic myopathies
– Alcohol
– Corticosteroids
– Local injections of narcotics
– Colchicine
– Chloroquine
– Statins
• Myotonic dystrophy
• Distal myopathies
• Nemaline myopathy, Centronuclear
myopathy

14. Temporal evolution: episodic or constant weakness?
Causes of episodic weakness:-
Hypo and hyper kalemic periodic paralysis
Anderson- tawil syndrome
Secondary PP
Metabolic myopathy (glycolytic enzyme defect)

15. Constant weakness
• acute or subacute progression
– inflammatory myopathies (dermatomyositis and polymyositis);
• chronic slow progression over years
– most muscular dystrophies
– IBM
• nonprogressive weakness with little change over decades
– congenital myopathies

16. Precipitating factors
• illegal drug or prescription medication use that might produce a myopathy.
• weakness, pain, and/or myoglobinuria provoked by exercise
– a glycolytic pathway defect.
• Episodes of weakness with a fever
– carnitine palmityl transferase deficiency.
• Periodic paralysis -provoked by exercise or ingestion of a carbohydrate meal followed
by a period of rest.
• paramyotonia congenita -cold exposure

17. Pattern of weakness:- proximal
Most dystrophies(dystrophinopathies, limb girdle, myotonic dystrophy 2, rare
FSHD)
Congenital myopathies( nemaline, central core)
Metabolic myopathies(glycogen and lipid storage)
Mitochondroal myopathy
PM, DM
Toxic myopathy
Endocrine myopathy

18. Myopathies Characterized by Predominantly Distal Weakness
• Distal Myopathies
– Late adult-onset distalmyopathy type 1
(Welander)
– Late adult-onset distal myopathy type 2
(Markesbery/Udd)
– Early adult-onset distal myopathy type 1 (Nonaka)
– Early adult-onset distal myopathy type 2 (Miyoshi)
– Early adult-onset distal myopathy type 3 (Laing)
– Desmin myopathy
– Childhood-onset distal myopathy"
• Myotonic Dystrophy
• FSHD*"
• Scapuloperoneal Myopathy*"
• OPMD
• Emery-Dreifuss Humeroperoneal Dystrophy*"
• Inflammatory Myopathies (IBM)
• Metabolic Myopathies
– Debrancher deficiency
– Acid-maltase deficiency*"
• Congenital Myopathies
– Nemaline myopathy*
– Central core myopathy*
– Centronuclear myopathy
*" Scapuloperoneal pattern can occur

19. Proximal arm and distal leg:-
Facioscapulohumeral dystrophy
Scapuloperoneal dystrophy
Emery dreifuss humeroperoneal dystrophy
LGMD 2A( calpain), 2C-F(sarcoglycan)
2I(FKRP)
Nemaline and central core myopathy
Acid maltase deficiency
Distal arm and proximal leg:-
 IBM
 Myotonic dystrophy

20. Pattern of weakness:- axial
 Cervico brachial myositis
 hIBM
 FSHD
 MD 2
 Hyperparathyroidism/vit d deficiency
 Metabolic ( late onset pompe and mc'ardle)

21. Pattern of weakness:- Ptosis
Ptosis without opthalmoparesis
Myotonic dystrophy
Nemaline myopathy
Central core myopathy
Myofibrillar myopathy
Ptosis with opthalmoparesis
OPMD
Mitochondrial myopathy
Centronuclear myopathy
NMJ disorder

22. Myopathies With Prominent Neck Extensor Weakness
• Isolated neck extensor myopathy"
• Polymyositis "
• Dermatomyositis "
• Inclusion body myositis "
• Carnitine deficiency "
• Facioscapulohumeral dystrophy "
• Myotonic dystrophy "
• Congenital myopathy "
• Hyperparathyroidism

24. FamilyHistory
• X-Linked
– Duchenne
– Becker
– Emery-Dreifuss
• Autosomal Dominant
– Facioscapulohumeral
– Limb-girdle
– Oculopharyngeal muscular dystrophy
– Myotonic dystrophy
– Periodic paralysis
– Paramyotonia congenita
– Thomsen disease
– Central core myopathy"
• Autosomal Recessive
– Limb-girdle
– Metabolic myopathies
– Becker myotonia
• Maternal Transmission
– Mitochondrial myopathies

25. Are associated systemic symptoms or signs present?
Cardiac disease
• Arrhythmias
– Kearns-Sayre syndrome
– Andersen’s syndrome
– Polymyositis
– Muscular dystrophies
• Myotonic
• Limb-girdle 1B, 2C-2F, 2G
• Emery-Dreifuss
• Congestive Heart Failure
– Muscular dystrophies
• Duchenne
• Becker
• Emery-Dreifuss
• Myotonic
• Limb-girdle 1B, 2C-2F, 2G
– Nemaline myopathy
– Acid maltase deficiency
– Carnitine deficiency
– Polymyositis

26. Respiratory Insufficiency
• Muscular Dystrophies
– Duchenne
– Becker
– Emery-Dreifuss
– Limb-girdle
– Myotonic
– Congenital
• Metabolic Myopathies
– Acid maltase deficiency
– Carnitine deficiency
• Mitochondrial Myopathies
• Congenital Myopathies
– Nemaline
– Centronuclear
• Inflammatory Myopathies
– Polymyositis

27. Hepatomegaly
• may be seen in acid maltase, debranching enzyme deficiency
• mitochondrial disorder.

29. DMD sarconoglycanopathy
inheritance X- linked recessive Autosomal recessive
Female sex Less likely May be affected
Calf hypertrophy present May be present
Muscle knee extensors
and hip abductors more
commonly involved than knee
flexors and hip adductors
Deltoid and infraspinatus
preserved
Hamstring>quadriceps
Biceps and deltoid
involved
Triceps preserved
intelligence May be subnormal normal
cardiac involved Less likely
Scapular winging Not usually May be present

30. GNE myopathy-quadriceps sparing myopathy
Distal anoctaminopathy- Asymmetrical calf atrophy, distal upper limbs may remain spared

31. Approach to metabolic myopathy
Darras BT, Friedman NR. Metabolic myopathies: A clinical approach; Part I. Pediatr Neurol 2015;22:87-97.
When to suspect
• Cramps, myalgias and exercise intolerance
• Rhabdomyolysis
How to investigate
• Ischemic exercise test
• Muscle biopsy
• Genetic tests

32. Examination
Muscle appearance – wasting ,atrophy (neurogenic)
ABSENT fasciculations (+Denervation)
 Tenderness on palpation
 Tone –normal ,decreased in advanced cases.
 Distribution of weakness –proximal,distal (distal myopathies)
 Tendon reflexes – normal /hypoactive in adv.cases
 Babinski sign negative
 SENSORYsystem is normal.
 GAIT – lordosis on stance,increased on toe walking
 Waddling gait – b/l pelvic girdle weakness
 Genu recurvatum –quadriceps weakness

33. Creatininekinase
• CK is elevated in the majority of myopathies but may be normal in slowly
progressive myopathies.
• CK level may not be elevated in
 corticosteroid administration,
 collagen diseases,
 Alcoholism
 hyperthyroid
 profound muscle wasting
 Metabolic myopathies

34. Differential Diagnosis of Creatine Kinase Elevation
• Myopathies
– Muscular dystrophies
– Congenital myopathies
– Metabolic myopathies( macrdle disease)
– Inflammatory myopathies
– Drug/toxin-induced
– Carrier state (dystrophinopathies)
• Channelopathies
• Motor Neuron Diseases
– ALS
– SMA
– Postpolio syndrome
• Neuropathies
– GBS
– CIDP
• Viral Illness
• Medications
• Hypothyroidism/ Hypoparathyroidism
• Surgery/Trauma (electromyography studies,
intramuscular or subcutaneous injections)
• Strenuous Exercise
• Increased Muscle Mass
• Race
• Sex
• ‘‘Idiopathic HyperCKemia’’

35. Other laboratory test
Electrolytes including calcium and magnesium
S.myoglobin level
Urinanalysis:- myoglobinuria
ESR
TFT
ANA

36. EMG
Indication:-
To confirm muscle localization and rule outAHC, neuropathy
Guide for muscle biopsy
Common pattern:-
Brief duration small amplitude MUAP with early recruitment

37. Muscle biopsy
Should not be taken from muscle with grade 3 or less power
Avoid biopsy from EMG needle site insertion
Punch biopsy is preferred over open biopsy
Common site:- biceps, deltoid, vastus lateralis
Emergence of genetics has reduce need of biopsy

38. Muscle biopsy
Common pattern:-
Central nuclei, both small and large hypertrophic round fibers, split fibers, and
degenerating and regenerating fibers
 Inflammatory myopathy:-
Presence of mononuclear inflammatory cells in the endomysial and perimysial
connective tissue between fibers and occasionally around blood vessels
Dermatomyositis, atrophy of fibers located on the periphery of a muscle fascicle,
perifascicular atrophy, is a common finding
Chronic myopathies frequently show evidence of increased connective tissue and
fat.

39. Stain used in myopathy

40. Genetic T
esting

41. FSHD
Pradhan S. Poly-hill sign in facioscapulohumeral dystrophy. Muscle Nerve 2002;25:754-5

42. Valley sign :-DMD
Pradhan S. Valley sign in duchenne muscular dystrophy : importance in patients with inconspicuous calves. Neurol
India [serial online] 2002 [cited 2021 Jul 16];50:184
valley sign- simultaneous hypertrophy
of deltoid superolaterally, infraspinatus
inferomedially and wasting of posterior
axillary fold

43. Diamondsign:- dysferlinopathy
Pradhan S. Diamonds on quadriceps sign in dysferlinopathy. Neurology 2008;70:322
Biceps lump in a patient with
dysferlinopathy

44. Calf head sign:- Miyoshi myopathy
Calf heads on a trophy sign: Miyoshi myopathy M. Mundayadan Shyma, P. Sreedharan Roopchand, K. Mohan Ram, C. Velayudhan Shaji J Neurosci
Rural Pract. 2015 Jul-Sep; 6(3): 428–430. doi: 10.4103/0976-3147.158798

45. Fish mouth:- Cong. Myotonic dystrophy

46. Which myopathy?
Myotonic
dystrophy

47. Dermatomyositis
Gottron papules
Shawl sign
V sign
Heliotrope rash
Mechanics hand

48. Clinical features frequently observed in patients with LGMD: Gower’s manoeuvre in LGMD2A (a), atrophy of gastrocnemius
muscle in distal Miyoshi myopathy (b), Achilles tendon retraction in LGMD2A (c), scapular winging and atrophy of scapular
girdle muscles in LGMD2A (d), scoliosis in LGMD1F (e), severe hip and knee contractures in LGMD2C (f), tongue muscle
hypertrophy or macroglossia in LGMD2E (g).

49. Calpainopathy. (a) Scapular winging. (b) Abdominal hernia
due to weakness of external oblique muscle
GNE myopathy. (a) Wasting of tibialis anterior muscle
resulting in prominence of shin of tibia. (b) Wasting of first
dorsal interosseous muscle (distal myopathy) quadriceps
sparing myopathy.

50. Swan neck in myotonic dystrophy.
The hip abduction sign- LGMD (sarcoglycanopa
Khadilkar SV, Singh RK. Hip abduction sign: A new clinical sign in sarcoglycanopathies. J Clin Neuromusc Dis
2001;3:13-5
Mild ptosis, hatchet face and
thin neck in a patient with DM1

51. Rigid spine syndrome
Emery–Dreifuss muscular dystrophy
Nemaline myopathy,
multiminicore disease,
Bethlem myopathy,
and rigid spine muscular dystrophy
Contractures of the spine: As this patient tries to
bend forward, the lower and mid spine remain in the
extended
position.
Herculean appearance in two brothers with MC
a) Asymmetrical left > right foot drop and (b) asymmetrical calf atrophy (left >
right) in brothers with anoctaminopathy

52. Pradhan S. Shank sign in myotonic dystrophy type-I (DM-I): Utility in differentiation from DM-II and
some other common muscular dystrophies. J Clin Neurosci 2007;14:27-32

56. References
• Jackson et al A Pattern Recognition Approach to Myopathy Continuum (Minneap
Minn) 2013;19(6):1674–1697
• Khadilkar SV, Singh RK. Limb girdle muscular dystrophies in India. Neurol India
[serial online] 2008 [cited 2021 Jul 16];56:281-8
• Bradely’s Neurology In Clinical Practise, 8th Edition
• Pradhan S. Clinical and magnetic resonance imaging features of 'diamond on
quadriceps' sign in dysferlinopathy. Neurol India 2009;57:172-5
• Pradhan S. Shank sign in myotonic dystrophy type-I (DM-I): Utility in
differentiation from DM-II and some other common muscular dystrophies. J Clin
Neurosci 2007;14:27-32
• Up to date.com

57. Case
• A 55-year-old man noticed gradually progressive weakness of both lower limbs since age of 25 years. Initially, he noticed
weakness of the left calf and soon within months the right calf weakened. In the ensuing 3 years, he developed bilateral
progressive foot drop. Over the next few years, he developed wasting of calves and then anterior leg muscles, which was
much more prominent on the left calf. Since 10–11 years, he noticed gradually progressive weakness of both lower limbs
and had developed difficulty in getting up from chair. Since 5–6 years, he has noticed mild weakness of arms associated
with wasting, more noticeable on the left side. On examination, there was evidence of asymmetric (left > right), bilateral
distal > proximal lower limb weakness affecting plantar flexors > dorsiflexors, quadriceps, hamstrings and hip adductors.
Deep tendon reflexes were present. Sensory examination was normal. His brother was also affected with similar
phenotype. Investigations revealed CK value of 3430 U/L. NEE showed myopathic potentials
• Summary: Familial, slowly progressive, asymmetric distal (calves > anterior leg muscles) > proximal lower limb weakness
followed by wasting, mild affection of upper limb proximal muscles and much elevation of serum CK.
• Discussion: Since calves were affected at the onset of illness, possibilities of dysferlinopathy and anoctaminopathy were
considered. The asymmetry of weakness, very gradual course of the illness and involvement of upper limbs starting after
almost 30 years of illness favoured anoctaminopathy. On genetic testing, no mutation was detected in dysferlin gene.
There was homozygous mutation in ANO5 gene which suggested diagnosis of anoctaminopathy.

58. Thank you