Myopathy Dr. Maitham F. Jalal F.I.B.M.S F.E.B.N

When you suspected myopathay Proximal weakness difficulty in going upstairs difficulty combing hair No parasthesia and numbness

1. The first goal in approaching a patient with a suspected muscle disease is to determine : 1. The the cause of the myopathy. 1. To determine whether a specific treatment is available and if not, to optimally manage the patient’s symptoms, functional abilities and enhance quality of life.

ETIOLOGY / CLASSIFICATION Inherited myopathies ◦ Muscular dystrophies ◦ Congenital myopathies ◦ Inherited metabolic myopathies Acquired myopathies Inflammatory myopathies Acquired metabolic myopathies Toxic myopathies

Myopathies Presenting in Adulthood Inherited 1 Muscular dystrophies ◦ Limb-girdle ◦ Facioscapulohumeral FSHD ◦ Becker, DMD ◦ Myotonia dystrophica 2 Metabolic myopathies ◦ Acid maltase deficiency ◦ Lipid storage diseases ◦ Mitochondrial myopathies 3 Congenital myopathy Nemaline myopathy Acquired 1 Inflammatory myopathies ◦ Polymyositis ◦ Dermatomyositis ◦ Inclusion body myositis 2 Endocrine( metabolic) myopathies ◦ Thyroid 3 Toxic myopathies ◦ Alcohol ◦ Corticosteroids ◦ Statin

What is Muscular Dystrophy? (MD) Muscular Dystrophy: group of genetic disorders that are characterized by progressive loss of muscle integrity, wasting, and weakness. Characterized by degeneration and regeneration of muscle fibers (in contrast with static or structural myopathies) Muscular Dystrophy Association ◦ Multisystem diseases : cardiac, respiratory GIT and cognitive

Dystrophinopathy: disorders involving dystrophin Duchenne MD and Becker MD the two most common and severe dystrophies Dystrophin is a very large gene on the X- chromosome, ubiquitous in the human body

Duchenne Muscular Dystrophy  Presentation: 3-5 y/o with pseudohypertrophy of calf muscles, frequent falls, tip toe walking, slow running, and waddling gait  Other organs affected Heart – cardiomyopathy Respiratory Intellect - 30 % with impairment IQ  Very high CPK

Myotonia Dystrophica Presentation – adult with multiple systems affected ◦ Primarily distal and facial weakness ◦ Facial features: frontal balding in men, ptosis, hatchet face ^ shaped upper lip ◦ Myotonia: difficulty in relaxation after contraction In addition : ◦ Heart: conduction block – evaluate syncope ◦ Brain: learning disabilities ◦ Ophthalmology: cataracts ◦ Endocrine: insulin resistance, hypothyroidism, testicular atrophy

Facioscapulohumeral FSHD normal deltoids biceps, triceps commonly weak, forearm muscles are less involved resulting in a popeye-like appearance Scapular winging may be very asymmetric (misdiagnosed as long thoracic nerve of palsy)

General Diagnostic Testing Creatine kinase : ◦ greatly elevated (50 times normal) ◦ Increased in DMD Genetic analysis nucleotide repeats …..dystrophen Electromyography EMG/NCS ◦ Differentiates neuropathic vs. myopathic ◦ Characteristic myotonic discharges in adults with myotonia – “dive bomber” sound may be seen in MD

Treatment - Medications Steroids ◦ Briefly increase strength, slow progression in dystrophinopathy Creatine and glutamine may help delay progression/improve energy in youngest with DMD Physiotherapy, contracture prevention and surgeory Treat respiratory, cardiac

Idiopathic inflammatory myopathies Polymyositis Dermatomyositis Inclusion body myositis

Clinical features Progressive painful weakness ◦ Difficulty lifting above head/combing hair ◦ Difficulty arising from a low chair or toilet ◦ Nasal regurgitation or choking when eating ◦ Hoarseness, change in voice ◦ *Ocular/facial muscle involvement is very uncommon ◦ Symmetric weakness of limb girdle muscles and anterior neck flexors. Fatigue Fever

Dermatologic features in dermatomyositis including a heliotrope rash with periorbital edema a scaly, erythematous dermatitis over the dorsa of the hands, especially over the MCP and PIP joints (Gottron's sign), mechanical hand apperance involvement of the shoulder shawl sign anterior chest V sign

Dermatologic manifestations

Inclusion body myositis May differ from PM and DM : Occur in elderly focal, distal UL and proximal LL weakness. Dyspagia is a late occurrence. CK only slightly increased and can be normal in up to 25% of patients.

Multisystem disease Cardiac Respiratory involvement fibrosis with anti –JO antibody GIT Autoantibody

Malignancy risk Strong association between malignancy and dermatomyositis, but less clearly with polymyositis. ◦ Ovarian, lung, pancreatic, stomach and colorectal and non-Hodgkin lymphoma The overall risk is greatest in the first 3 years after diagnosis but is still increased through all years of follow-up.

Investigations Muscle Biopsy NCS/EMG Lab ( CK)

Electromyographic (EMG) triad of short, small polyphasic motor units MUP fibrillations, positive waves and bizarre high-frequency discharges.

Corticosteroids is mainstay of treatment in most cases Start 1-2 mg/kg/day Continue until CPK returns to normal, then slow taper. For severe acute disease, consider pulse dose steroids.

Other treatments Steroid sparing ◦ Methotrexate ◦ Imuran Non-responders ◦ Rituxan ◦ IVIG ◦ Cyclosporin ◦ Cyclophosphamide ◦ Plasmapheresis

Corticosteroid- Corticosteroid- Induced Myopathy Steroid myopathy is usually an insidious disease process that causes weakness mainly to the proximal muscles of the upper and lower limbs and to the neck flexors. An excess of either endogenous or exogenous corticosteroids is believed to cause the condition. Excess endogenous corticosteroid production can arise from adrenal tumors. An excess of exogenous corticosteroid can result from steroid treatment for asthma, chronic obstructive pulmonary disease, and inflammatory processes, such as polymyositis, connective tissue disorders, and rheumatoid arthritis

Corticosteroid- Corticosteroid- Induced Myopathy Investigation Serum levels of creatine kinase typically are within the normal range. Electromyography (EMG) and nerve conduction studies (NCSs) 1. Motor and sensory NCS results typically are normal. 2. EMG studies reveal normal insertional without abnormal spontaneous activity (positivesharp waves and fibrillation potentials). Which is the main difference between inflammatory myopathy and myopathy result from steriod use in case of inflammatory myopathy

Corticosteroid- Corticosteroid- Induced Myopathy Treatment The main treatment recommendations for steroid myopathy are a decrease in the dose of steroid to below a threshold level or the discontinuation of the corticosteroid's use. Alternate-day dosing could also be considered. Another recommendation is that the currently administered steroid be exchanged for one that is not fluorinated.

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