Muscle Disease and Myasthenia Gravis Flashcards
Myopathy
(Disease of Voluntary Muscle),
Myositis
(Inflammatory),
Muscular Dystrophy
(Inherited Disorders of Muscle),
Myasthenia
(Fatigable Weakness in NMJ Disease),
Myotonia
(Sustained Contraction/Slow Relaxation)
Polymyositis
Acute Inflammation and Fibre Necrosis
DMD
Genetically-determined Metabolic
Failure
Sarcoidosis
Infiltration by Inflammatory Tissue
Diagnostic Features of Muscle Disease: Serum CK
• Serum CK – Marker of Muscle Fibre Damage; Elevated in Dystrophies and Inflammation
Diagnostic Features of Muscle Disease: Neurogenetic
• Neurogenetic Tests – For Muscle Dystrophies and Mitochondrial Disease
Diagnostic Features of Muscle Disease: EMG
• EMG Studies – Myopathy-Pattern (Short, Spiky Polyphasic Muscle AP; Spontaneous
Fibrillation occasionally recorded), Myotonic Discharges (High-frequency Whine), Decrement
(Following repetitive Motor Stimulation in MG) or Increment (In LEMS); In Denervation,
Diagnostic Features of Muscle Disease: Muscle Biopsy
• Muscle Biopsy with Immunohistochemistry techniques reveal Denervation, Inflammation and Dystrophic changes; Identify Abnormal muscle protein for precision diagnosis
Diagnostic Features of Muscle Disease: MRI
• MRI identifies Signal Changes within Muscle as well as Fatty Replacement in Chronically
damaged muscle
Polymyositis
Rare, Unknown cause; Inflammation of Striated Muscle causing Proximal
Weakness; Skin Involvement =Dermatomyositis; 2-10 per million; All ethnicities and ages
o Viruses and HLA-B8/DR3 Implicated in Pathogenesis
Adult Polymyositis
– 3F:M; Insidious onset of General Malaise, Weight Loss, Fever during
Acute phase; Proximal Muscle Weakness is cardinal sign
o Shoulder and Pelvic Girdle Wasting without
Tenderness
o Involvement of Airway and Respiratory Muscles
lead to Dysphonia and Respiratory Failure
Adult Dermatomyositis
– >F:M; Weakness plus Myalgia,
Polyarthritis and Raynaud’s; Characteristic Rash,
Periorbital Oedema, Vasculitic Patches (Over Knuckles
=Gottron’s Papules) in 70%
o Ulcerative Vasculitis and Calcinosis in 25% of
patients; Fibrosis and Muscle Contracture in the
Long Term
Childhood Dermatomyositis
4-10yrs; Rash plus Muscle Weakness; Muscle Atrophy,
Subcutaneous Calcification and Contractures; Ulcerative Skin Vasculitis and Recurrent
Abdominal Pain due to Vasculitis
Treatment of Myositis
Treatment with Steroids, Bed Rest and Exercise Programme; Steroid Sparing agents
o IVIg in Recalcitrant Cases; Biologics under investigation
Inclusion Body Myositis
Inclusion Body Myositis – Idiopathic Inflammatory Myopathy usually in Men >50yrs;
Weakness of Pharyngeal Muscles leading to Difficulty Swallowing in 50%
o Slow, Progressive Weakness of mainly Distal Muscles with slightly raised CK; (C/f PM/DM); Muscle Biopsy for Diagnosis
o Trial of steroids, but typically poor response
What is myasthenia gravis
Acquired Weakness and Fatigability of Proximal Limb, Bulbar and Ocular Muscles; Heart is not affected; Prevalence of 4 in 100,000; 2F:M, Peak 30yrs
o Respiratory Difficulties can be prominent; Clinical Picture of Fluctuating, Fatigable
weakness is usually Diagnostic; Myalgia is Absent
Pathophysiology of Myasthenia Gravis
Antibodies to Acetylcholine Receptor Protein; Immune Complexes of Anti-AChR IgG and Compliment at Post-Synaptic Membrane, causing Interference and Destruction of AChR
o Antibodies against Muscle-Specific Tyrosine Kinase (Anti-MuSK) identified in Anti-
AChR negative cases of MG
Causes of MG
• Thymic Hyperplasia in 70% of MG patients <40yrs; In 10%, Thymic tumour can be found
• Transient MG can sometimes be caused by D-Penicillamine treatment (Copper Chelator, also
used in RA and Cystinuria)
MG Investigations
• Serum Anti-AChR (Positive in 80-90%; Less
common in Ocular MG) and Anti-MuSK (Most
common in Bulbar, Facial and Neck Muscles)
• Repetitive Nerve Stimulation – Characteristic
Decrement in Evoked Muscle AP during
repetitive stimulation; EMG otherwise normal
• Tensilon (Edrophonium) Test – Seldom required; Substantial improvement of Weakness
within seconds, and lasts up to 5 minutes; Control test with Saline with Observer
o Edrophonium can cause Bronchospasm and Syncope – Resus on standby
• Imaging – Mediastinal MRI for Thymoma
Management of MG: Course and Monitoring
• Fluctuating in Severity; Protracted, Lifelong course; Respiratory Impairment, Nasal Regurgitation and Dysphagia can occur, requiring Ventilation
o Simple Monitoring tests (E.g. How long an arm can be held outstretched) and Vital
Capacity are useful for monitoring disease
o Exacerbations are usually unpredictable and unprovoked; Can be brought about by Infections and Aminoglycosides, and Mg Enemas
Management of MG: Medication
• Oral Anticholinesterases – Pyridostigmine 60mg tabs, 4 – 16 per day Widely used; 3 – 4hr
Duration of action; Overdose leads to Severe Weakness (Cholinergic Crisis)
o Muscarinic SE, e.g. Colic and Diarrhoea are common; Oral Atropine helps to reduce
• Immunosuppressants – For patients who do not respond to Pyridostigmine, or Relapse on Treatment; Steroids (Improvement in 70%), Azathioprine, MMF etc
Management of MG: Surgery
Thymectomy – Improves Prognosis, more so F>M <50yrs with positive Anti-AChR even without Thymoma; Anti-MuSK positive tends not to benefit
o If Thymoma present, Surgery necessary due to risk of Malignancy
Management of MG: Acute Exacerbations
• IVIg and Plasma Exchange are useful in Acute Exacerbations
Lambert Eaton Myasthenic Myopathic Syndrome
• Proximal Limb Weakness, ± Ocular/Bulbar with Absent Tendon Reflexes
o Weakness tends to improve after few minutes of Contraction, and Absent Reflexes
returns (C/f Myasthenia)
• Classically, Paraneoplastic Manifestation of Small-cell Bronchial Carcinoma – Due to Defective
AChR release at NMJ; Antibodies to P/Q-type VgCC in 90% of cases
• Diagnosis confirmed by EMG and RNS (Increment)
• Amifampridine (=DAP), which blocks Potassium Efflux, prolonging the Presynaptic AP
What is myotonia
• Continued, Involuntary Muscle Contraction after
Cessation of Voluntary Effort (Failure of Muscle
Relaxation); EMG is Characteristic
• NB: Myotonic Patients tolerate General Anaesthetics poorly
Myotonic Dystrophy
Autosomal Dominant Triple-repeat Mutation in DMPK gene, or in Zn
Finger Protein gene; Correlation between Severity, Age of onset and Size of Repeats
o Progressive Distal Muscle Weakness, Ptosis, Facial Wasting and Weakness
o Part of Syndrome – Cataracts, Frontal Baldness, Mild Cognitive Impairment,
Oesophageal Dysfunction, Cardiomyopathy, Small Pituitary Fossa, Glucose
Intolerance etc
Myotonia Congenita
– AD, Mild, becoming evidence in Childhood; CLC1 gene codes for
Muscle Cl Channel; Accentuated by Rest and Cold; Diffuse Muscle Hypertrophy develops
