Neuromuscular diseases Definition muscle function disorder caused by

Neuromuscular diseases

Definition • muscle function disorder • caused by defect of muscles and/or nervous control Classification • myopathies (muscle dystrophy) • neural atrophy (primary peripheral nerve damage, secondary muscle athrophia) • basal ganglia atrophy • motor end plate diseases (Myasthenia gravis)

Myasthenia gravis

Definition • Autoimmune disease leading to fluctuating muscle weakness and fatigability caused by circulating antibodies that block acetylcholine receptors in the postsynaptic part of neuromuscular junction • the autoantibodies against nicotinic acetylcholine receptor on the postsynaptic membrane of the motor end plate – inability of acetylcholine to bind to receptor – destruction of receptors Causes: • unknown • genetic predisposition? – HLA (B 8, DR 3, DR 1) • abnormality of the thymus (75% of patients)

Classification (Myasthenia Gravis Foundation of America Clinical Classification) • Class I: Any eye muscle weakness, possible ptosis, no other muscle weakness elsewhere • Class II: Eye muscle weakness of any severity, mild weakness of other muscles – Class IIa: Predominantly limb and axial muscles – Class IIb: Predominantly bulbar and/or respiratory muscles • Class III: Eye muscle weakness of any severity, moderate weakness of other muscles – Class IIIa: Predominantly limb and axial muscles – Class IIIb: Predominantly bulbar and/or respiratory muscles • Class IV: Eye muscle weakness of any severity, severe weakness of other muscles – Class IVa: Predominantly limb and axial muscles – Class IVb: Predominantly bulbar and/or respiratory muscles (feeding tube, without ventilation) • Class V: Intubation needed to maintain airway

Neuromuscular junction

Signs and symptoms • fatigability – muscles become progressively weaker during activity and improve after rest – myashenic reaction • especially facial muscles – muscles that control eye and eyelid movement, facial expression, chewing, talking, swallowing – facies myasthenica – ptosis (dropping of eyelids) – diplopia (double vision) – dysphagia (difficulty in swallowing) – dysarthria ( impaired speech) • also affected muscles control breathing and neck and limb movement – shortness of breath – waddling gait – weakness in arms, hands, fingers, legs, neck • other physical examination – in normal limits

Regional distribution of muscle weakness 95% 60% 30% 10% Ptosis and weakness of smile Improvement after therapy In early stages patient may feel fine in the morning but develops diplopia and speech slurs later in the day Patient with chin on chest cannot resist when physician pushes head back

Blepharoptosis of the left eye Weakness of neck

Lambert-Eaton myasthenic syndrome

Definition • Autoimmune disease lthat affects voltage-gated calcium channels on the presynaptic membrane of the neuromuscular junction, that leads to inhibition of acetylcholine release from the presynaptic terminal Causes: • small-cell lung cancer (50%) • genetic predisposition? Signs and symptoms • progressive weakness (not involve/or rare facial and respiratory muscles) • the symptoms are worse in the morning and improve with excercise (opposite to MG) • predominantly affected proximal parts of legs and arms • autonomic symptoms – dry mouths, impotence • reduced or absent reflexes

Areflexia Difficulty in climbing stairs or arising from chair often early symptom due to weakness of muscles Dryness of mouth due to decreased saliva secretion

Mucular dystrophy

Definition • Group of hereditary muscle diseases characterized by progressive skeletal muscle weakness Causes: • inherited (XR) Signs and symptoms • progressive muscular weakness • poor balance • walking difficulty, frequent falls, inability to walk • calf pain • limited range of movement • dropping eyelids • scoliosis

Duchenne muscular dystrophy

Definition • Inherited muscular dystrophy characterized by rapid progression of muscle degeneration, eventually leading to loss of ambulation and death. Causes: • X recessive inherited mutation of DMD gene (Xp 21) that codes the protein dystrophin – structural component of muscles - no protein production Signs and symptoms • progressive muscle weakness – pelvis, calves, arms, neck (age 5 -6 years) • awkward manner of walking, running (on forefoot) • frequent falls • fatigue • lumbar lordosis, scoliosis • muscle contractures • pseudohypertrophy of tongue and calf muscles • higher risk of learning dificulties (because of muscular fatigue)

Becker´s muscular dystrophy

Definition • Inherited muscular dystrophy characterized by slowly progressive muscle weakness of legs and pelvis Causes: • X recessive inherited mutation of DMD gene (Xp 21) that codes the protein dystrophin - lower concentration of dystrophin Signs and symptoms • slowly progressive muscle weakness (sometimes normal walking into adulthood, variable) • toe-walking • frequent falls • difficulty breathing • skeletal deformities