This document provides an overview of the approach to diagnosing and classifying muscle disorders. It discusses taking a clinical history and performing a physical exam to identify symptoms and patterns of weakness. Key investigations include blood tests of enzymes like CK, electromyography and muscle biopsy. Major classifications of myopathies covered are immune-mediated myopathies like dermatomyositis and polymyositis, necrotizing myopathies, inclusion body myositis, and others. Treatment typically involves immunosuppressants like corticosteroids and newer targeted immunotherapies depending on antibody status and subtype.

1. Approach to muscle
disorders
By/ Lobna Ahmed

2. Clinical history:
Identify the
symptoms
Temporal
pattern
Distribution of
weakness
Triggering
events
Family history
Associated
manifestations
6

3. Symptoms
Negative Positive

4. The muscle patterns
10

6. Family
history
• classify disorders as X-linked, AD,
AR or maternally transmitted.
Associated
systemic
symptoms
and signs
• Dermatological.
• Cardiac.
• Pulmonary.
• Connective tissue disease.
• Skeletal deformities or contracture.
• Dysmorphic features.
• GIT.
• Neuropathy.

7. Clinical examination

9. In most myopathies,
muscle tone is
usually normal or
sometimes
decreased.
Tone In the early phases,
reflexes are usually
present.
Specific myopathies
may have
predilection for
certain muscles (ex;
reduced knee jerk in
IBM, preserved ankle
jerk in Duchenne
MD).
Reflexes
Muscle wasting
Myotonia and
paramyotonia
Muscle
tenderness
Sensation

10. Wide based-
gait
Foot drop
High steppage
Trendelenburg
sign
Toe and heel
walking

11. winging of scapula

12. Investigations

13. Electrolytes • Potassium, calcium.
others • Thyroid, ESR, ANA.
CK
• Most useful blood test.
• Doesn’t correlate to degree of weakness
• Not seen in all myopathies
Other
enzymes
• AST, ALT, LDH (in both muscle and liver
diseases)
• DD by CK (Muscle) vs GGT (Liver).
Laboratory

15. Electrodiagnosis
NCS
• Can be normal or may show
low amplitude in patients with
disorders of muscle or NMJ.
• Repetitive stimulation studies
are useful in distinguishing
neuromuscular junction
disorders (ie, botulism, LEMS,
and MG) from myopathies.
EMG
• Assessment for abnormal
insertional and spontaneous
activity.
• Motor unit action potential
(MUAP) duration, amplitude,
morphology, and recruitment.

16. Spontaneous
activity
There is no spontaneous activity in normal muscle, except if the
needle is positioned near a neuromuscular (end plate noise).
• Associated with denervation but
can be present in myopathies
thought to be due to segmental
necrosis and inflammation of the
muscle fibers.
• They can be seen in chronic
neuropathic and myopathic
conditions.
Fibrillation potentials and positive
sharp waves
Complex repetitive discharges
Myotonic discharge

17. MUAP
configuration
and recruitment
• Small duration and amplitude.
• Polyphasic appearance(asynchronous firing of affected fibers).
• Early or rapid recruitment pattern (to generate force with
minimal volitional contraction, many motor units are getting
activated earlier than expected).

18. Histological examination and genetic
testing
• Many patients with a myopathy will
require a muscle biopsy,
particularly for acquired diseases.
• Two types of muscle biopsies can
be conducted: open and needle.
• In chronic myopathies, a mildly
weak muscle (grade 4) should be
selected for biopsy.
• Peripheral blood testing and saliva
DNA analysis have been useful to
identify mutations that are
associated with hereditary muscle
diseases.

19. Classification of
myopathies

21. Dermatomyositis
Immune mediated necrotizing
myopathies
Inclusion body myositis
Anti-synthetase syndrome
Overlap myositis
Polymyositis
Immune-
mediated
myopathies

22. Symmetrical
proximal
weakness
Distal weakness occurs late;
except in IBM (EARLY with
characteristic involvement
of finger flexors).
• Ocular muscles usually spared.
• Facial muscles weakness usually mild.
• Neck flexor weakness more than
extensors.
Diffuse myalgia
or muscle
tenderness

23. Dermatomyositis

24. Proximal muscle weakness that is accompanied or
preceded by a distinct skin rash
The rash generally occurs
in photosensitive areas and
is erythematous, edematous,
and occasionally pruritic.
1- heliotrope rash (upper
eyelids).
2- shawl sign (back-shoulder)
3- V sign (anterior chest)
4- gottron’s sign (MCP, PIP, DIP)
5- mechanic’s hand.
6- peri ungular abnormalities.
Occlusion
of small
BVs

25. Clinical
picture
Weakness
Rash
Systemic
affection
Heart Lung
GIT
Malignancy
Joints
Adenocarcinoma

26. Variants
Amyopathic DM
Hypo
myopathic DM
DM sine
dermatitis
Skin without muscle
“dermatomyositis siné myositis”.
Skin with minimal muscle (abnormal Ix,
no Clinical)
Muscle without skin

27. Evaluation
• CK levels are often increased; however, they may range from normal to
up to thousands.
• In NCS, sensory and motor nerve conduction studies are typically normal;
however, low-amplitude motor nerve responses can be seen when
weakness in myositis is severe and diffuse.
• EMG shows myopathic patterns.
• Perifascicular muscle fiber atrophy is a specific and pathologic hallmark
feature of dermatomyositis in the biopsy.

28. Specific
antibodies
• Five known dermatomyositis-specific autoantibodies (including Mi-
2,TIF-1γ, NXP-2, MDA-5, and SAE).
• Anti–Mi-2 antibody was the first reported myositis-specific
autoantibody associated with rash.
• Anti-Mi 2 positive patients have more classical cutaneous features of
dermatomyositis, confer a good prognosis with a favorable response
to steroids, and have a relatively low malignancy risk.

30. Anti-synthetase syndrome

31. Inflammatory myopathy, Interstitial lung disease, Arthritis, Raynaud syndrome,
Fever, and Mechanic’s hands +/- Skin rashes
similar to dermatomyositis.
Serum autoantibodies to
the aminoacyl transfer
RNA synthetases.
Of the anti-synthetase
antibodies, anti–Jo-1 (the
first to be discovered and
most frequent anti-synthetase
autoantibody) is associated
with the greatest risk of
developing a myositis.

32. Immune-mediated necrotizing
myopathies

33. Severe proximal muscle weakness (acute or subacute)
with rare extra-muscular involvement.
Biopsy shows necrosis and no inflammatory infiltrate.
CK
Serum CK levels typically markedly
elevated, up to several thousands,
with the median peak reported at
4700 U/L.
CK elevation before
clinical weakness
Detect exacerbation
while Rx tapering

34. Specific
antibodies
• The two main antibodies associated with immune-mediated
necrotizing myopathy are the SRP and the anti–3-hydroxy-3-
methylglutaryl coenzyme A (HMG-CoA) reductase
antibodies.
• Anti-HMG-CoA antibody was first described in patients with a
history of statin exposure with weakness that continued to
progress despite stopping use of the statin.
Risk of
malignancy
Double -ve
high
Anti-HMG-
CoA
low
Anti-SRP
No
association

35. Overlap myositis

36. Autoimmune-myopathy may be associated with other well-defined autoimmune
connective tissue disorders, known as overlap syndromes and include SLE ,
Sjögren syndrome, rheumatoid arthritis, and systemic
sclerosis.
The most common myositis-
associated antibodies are anti-Ro52
antibodies, which are nonspecific
and have been detected in
approximately 25% of patients with
all types of myositis.
Anti-Ro52

37. Polymyositis

38. Subacute onset of proximal muscle weakness, CK elevation,
myopathic EMG, and endomysial inflammation with CD8+ T cell
infiltrates seen on muscle biopsy.
The diagnosis
of polymyositis
is seen now as
a diagnosis of
exclusion.

39. Inclusion body myositis

40. Sporadic IBM is the most common acquired muscle disease in patients older than 50 years of age
Slowly
progressive
Late in
life
Distal Arm
Proximal Leg
Asymmetric Quadriceps weakness.
Attempting to make a fist and cannot
bury the fingernails completely or fully
close the hand.
Asymmetric
Peripheral neuropathy is
present in up to 30% of
patients.

41. IBM should be suspected in older patients with suspected
polymyositis that is refractory to treatment, especially those
with asymmetric or distal weakness.
The disease generally has a chronic progressive course and is
considered unresponsive to prednisone and other immune
suppressive (e.g., methotrexate) and immunomodulating (e.g.,
IVIG) therapies.
Modestly elevated creatine kinase levels (≤1500 U/L) and
electrodiagnostic studies that may be challenging to interpret
because they suggest a mixed myopathic/ neuropathic
process.
Concurrent sensory axonal
polyneuropathy
reduced or absent sural sensory nerve
action potentials (SNAPs), is common in
older patients with sporadic IBM

42. Treatment

43. Recent evidence has
suggested that particular
subtypes of autoimmune
myopathies (based on
autoantibodies) may have a
robust response to
particular immunotherapies.
Immunosuppressive therapy is widely accepted as the mainstay of
treatment.
Corticosteroids,
commonly prednisone, are
the first-line therapy in the
treatment of inflammatory
myopathies, typically
prescribed at a dose of
0.5 mg/kg/d to 1 mg/kg/d,
with a maximum dose of
60 mg/d to 80 mg/d.

44. IVIG
• Refractory dermatomyositis and is effective in immune-
mediated necrotizing myopathy (especially in anti–
HMG-CoA reductase antibodies positive patients).
Rituximab
• Anti-synthetase syndrome, primarily anti–Jo-1, and also
in anti–Mi-2 autoantibody–positive patients.
• Anti-SRP antibody immune-mediated necrotizing
myopathy who were refractory to conventional
immunotherapies.

46. Thank you