Myopathies

Presenter: Dr Edom G/medhin (IMR3)

Moderator: Dr Teklil Hagos (Consultant Neurologist)

July 23rd /2021

Outlines of presentation
• Hereditary myopathies

• Inflammatory myopathies

• Drug induced or toxic myopathies

• Infectious myopathies

• Endocrine myopathies
Hereditary myopathies
Muscular dystrophies
• Muscular dystrophy refers to a group of hereditary progressive
diseases each with unique phenotypic and genetic features.

• Different dystrophies occur due to distinct molecular abnormalities

mostly those involving structural proteins*
• sarcolemmal proteins, sarcomeric proteins, and enzymes

• Patients have a slow progressive weakness with variable course and

severity.
Duchenne and Becker Muscular Dystrophy (DMD
and BMD)
• X-linked recessive muscular dystrophies caused by mutations in the dystrophin gene.

• ~65%–75% are associated with a deletion or duplication of one or more exons in the gene.

• The remainder of cases are due to point mutations, smaller deletions, or small insertions or duplications.

• DMD is the most common mutational disease affecting boys with an incidence of 1/3,000
male births.

• The incidence of BMD is ~5 per 100,000

DMD and BMD cont’d
• absence of dystrophin impaired integrity of the sarcolemmal
membrane increased susceptibility to mechanical damage.

• DMD – absence of dystrophin

• BMD – deficiency of dystrophin

• Less severe
• Older age of onset and slower progression of weakness
DMD and BMD cont’d
• Progressive leg weakness, proximal greater than distal, develops through
early childhood.

• Toe walking, waddling gait, inability to jump and Gower sign are seen in
affected toddlers with DMD followed by calf muscle hypertrophy.

• Difficulty in climbing stairs and frequent falls start to occur by age 5-7yrs.

• Loss of ability to walk occurs at about age 9yrs

DMD cont’d

Laboratory workup Treatment options

• markedly elevated serum CK concentration • Physical therapy
(levels >10,000 mU/mL)

• EMG shows myopathic changes • Bracing

• Genetic testing • Reconstructive surgery

• Muscle biopsy with immunohistochemistry

and immunostaining methods • Prednisone 0.75 mg/kg/daily
Limb Girdle Muscular dystrophies
• The LGMDs are a genetically heterogeneous group of dystrophies.

• males and females are affected equally,

• typically manifest with progressive weakness of pelvic and shoulder girdle

musculature.

• onset ranges from late in the first decade to the fourth decade.

• Classified as autosomal dominant (LGMD1) vs autosomal recessive (LGMD2).

Summary of muscular dystrophies
Metabolic myopathies
• Any disturbance in the biochemical pathways that support ATP levels in the muscle
inevitably results in exercise intolerance.

• Other symptoms include muscle pain and sometimes muscle cramps during exercise.

• These group of diseases can be divided into three major categories:

• disorders of carbohydrate metabolism
• disorders of lipid metabolism, and
• disorders of mitochondrial function
Channelopathies
• Cause defects in membrane excitability.

• These disorders usually present with episodic muscle weakness

(periodic paralysis) and sometimes myotonia or paramyotonia.

• Can result from abnormalities involving calcium, sodium, potassium

and chloride ion channels.
Inflammatory myopathies
Inflammatory myopathies
• Characterized by inflammatory infiltrates on muscle biopsy that
primary results from an abnormality of the immune system itself.

• Inflammatory myositis can occur:

• in isolation,
• as a paraneoplastic manifestation of malignancy, or
• in association with other CTDs (overlap syndromes).
Inflammatory myopathy cont’d
• Patients usually present with an insidious or subacute dev’t of the muscle
weakness, with gradual worsening over a period of several months.

• Extramusclular manifestations might be present in some groups of IIM:

• Skin rash, ILD, inflammatory arthritis, malignancy risk etc.

• Laboratory abnormalities:
• Markers of muscle inflammation such as elevated muscle derived enzymes (non specific)
• Presence of myositis specific autoantibodies (only in a few proportion of patients) OR
myositis associated autoantibodies
EULAR/ACR criteria 2017

http://www.imm.ki.se/biostatistics/calculators/iim
Dermatomyositis and polymyositis
• are immune-mediated myopathies, characterized by the shared features
of proximal skeletal muscle weakness and evidence of muscle
inflammation

• DM is associated with a characteristic skin rash and an increased risk of

malignancy.
• can present at any age from childhood through late adult life.

•F>M
Laboratory findings
• Elevated levels of muscle enzymes
• CK (>10x ULN), aldolase
• Autoantibodies
• ANA (up to 80 % of patients)
• myositis-specific autoantibodies (in at least 30 to 40% of patients)
• Antisynthetase antibodies, anit-MDA5, anti-Mi-2, and anti SRP antibodies
• myositis-associated autoantibodies, especially in patients with overlap syndromes.
• anti-Ro, anti-La, anti-Sm, or anti-ribonucleoprotein (RNP) autoantibodies

• ESR - often normal or is only mildly elevated

DM and PM
• EMG

• Muscle biopsy
Antisynthetase syndrome
• The presence of myositis, non-erosive arthritis, ILD, Raynaud
phenomenon, mechanic hands, and fever associated with antibodies
against aminoacyl-tRNA synthetase constitute the ASS.

• The most common aminoacyl-tRNA synthetase antibody is

anti-Jo-1 (30%).
Inclusion body myositis (IBM)
• IBM is a rare sporadic disorder with a prevalence that is estimated at
five to nine cases per million adults.

•M>F

• The mean age at onset of symptoms is approximately 60 years

• Compared with patients with PM and DM, patients with IBM are more
likely to have asymmetric and distal muscle involvement.
Inclusion body myositis (IBM)
• IBM is a rare sporadic disorder with a prevalence that is estimated at
five to nine cases per million adults.

•M>F

• The mean age at onset of symptoms is approximately 60 years

• Compared with patients with PM and DM, patients with IBM are more
likely to have asymmetric and distal muscle involvement.
Laboratory findings
• Elevated muscle enzymes
• CK (<10x ULN)

• ESR, CRP usually normal

• Myositis-specific autoantibodies are typically absent in patients with IBM.

• Cytosolic 5’- Nuclotidase 1A (upto 2/3 of cases)

• Additional workup: Serum electrolytes, TSH, PITC, HCVab

IBM cont’d
• EMG in IBM typically reveals an "irritable myopathy" with increased
insertional activity, fibrillations, positive waves, and early recruitment
of short-duration, small-amplitude polyphasic MUAPs.

• Muscle biopsy
Immune mediated inflammatory myopathy
(IMNM)
• Symmetric, proximal >distal
weakness
• Dysphagia, dysarthria, or
myalgia may occur.
• May be idiopathic,
paraneoplastic or associated with
other CTD.
• Autoantibodies:
• Anti SRP Ab:
• Associated with severe weakness, ILD,
muscular atrophy and dysphagia
• Not associated with malignancy
• Found in 5% of Pts
• Anti HMGCR (3-hydroxy-3-
methylglutayl-coenzyme reductase)
• 30-60 % has previous Statin exposure
• Associated with malignancy
• In 2/3rd of cases
• Ab negative
Treatment
• Goal:
• Objective increase in muscle strength
• Improvement in daily activities
• Chemical improvement may be ineffective

• Therapy include:
• Immuno suppression
• Physical therapy and Exercise

35
Cont..
• Glucocorticoids:
• Remain 1st line therapy for IIMs (PM&DM)
• High dose 0.75-1.5 mg/kg
• Late or severe onset or rapid worsening
• Methyl prednisolone 1000mg iv daily for 3-5 days ( then switch to oral)
• IVIG :
• Steroid refractory
• Life threatening weakness with dysphagia
• 2 g/kg total dose over 2-5days ( monthly for at least 3 months)

36
Cont..
• Other 2nd lines
• Azathioprine (1.5-2mg/kg)
• Methotrexate (7.5-25mg/week)
• Mycophenolate mofetil (1-1.5
g/day)
• Rituximab, Cyclophosphamide…
• Other General measures
• Exercise
• Aspiration risk
• Osteoporosis prevention
• Infection Prevention
• Immunization
• Pruritus treatment
• Skin disease and Sunlight
protection
• Cancer screening
37
Cont..
• IBM Rx

• Generally resistant to treatment

• Trial of Immunosuppressive therapy in certain scenarios

• Overlap Sx ( Sjogren’s, SLE),
• Atypical presentations ( rapid, high CK, high Inflamm on biopsy…)

• Supportive non pharmacologic treatment

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Prognosis
• DM > PM > IBM in terms of favorable response
•
• Poor prognostic features
• Advanced age
• Severe weakness at onset
• ILD
• Dysphagia
• Cardiac involvement or Malignancy
• Late or inadequate Treatment

39
Drug induced and toxic
myopathies
Drug induced myopathies
• The most common toxic
myopathies are caused by the
cholesterol lowering agents and
glucocorticoids.
Drug induced myopathies cont’d
Statin induced myopathy
• Can cause toxic myopathy and sometimes
IMNM
• myalgia and elevated CKs
are the most common manifestations.
• proximal weakness or myoglobinuria – rare
• EMG demonstrates irritability and myopathic
units and muscle biopsies reveal necrotic
muscle fibers in weak muscles.
Glucocorticoid related myopathy
• occurs with chronic treatment or as “acute
quadriplegic” myopathy secondary to high-
dose IV glucocorticoid use
• In chronic steroid myopathy, the serum CK
is usually normal. Serum potassium may be
low.
• The muscle biopsy in chronic cases shows
preferential type 2 muscle fiber atrophy;
EMG is usually normal.
Infectious myopathies
Trichinosis
• Is a parasitic disease is caused by the nematode
Trichinella spiralis. • Peripheral blood eosinophilia always present
in the peripheral blood (>700 cells/mm3)
• Patients might present with strabismus, diplopia,
dysarthria, difficulty with chewing and swallowing
• ESR – normal
• Any weakness of limb muscles is usually mild and
more severe proximally than distally. • The CK level is moderately elevated.

• Clinically, one should suspect the disease • Biopsy of almost any muscle, regardless of
in a patient who presents with a puffy face and
tender muscles. whether it is painful or tender, is the most
reliable confirmatory test.
Endocrine myopathies
Endocrine myopathies
• Hypothyroidism

• Hyperthyroidism

• Parathyroid disorders
References
• Bradley and Daroff’s Neurology in clinical practice, 8th ed

• Harrison Principles of Internal medicine, 20th ed

• UpToDate 2021
THANK YOU