Neuromuscular Disease Stacy Rudnicki, MD Department of Neurology Disorders of the Motor Unit • • • • Motor neuron disease Peripheral nerve disorders Neuromuscular junction disease Muscle disease.
Download ReportTranscript Neuromuscular Disease Stacy Rudnicki, MD Department of Neurology Disorders of the Motor Unit • • • • Motor neuron disease Peripheral nerve disorders Neuromuscular junction disease Muscle disease.
Neuromuscular Disease Stacy Rudnicki, MD Department of Neurology Disorders of the Motor Unit • • • • Motor neuron disease Peripheral nerve disorders Neuromuscular junction disease Muscle disease Motor Neuron Disease • Diseases that can involve Betz cells of the motor cortex, the lower CN motor nuclei, the CST, and/or the anterior horn cells – Amyotrophic Lateral Sclerosis (ALS) – Progressive bulbar palsy – Progressive muscular atrophy, spinal muscular atrophy – Primary lateral sclerosis ALS • Loss of motor neurons in the cortex, brainstem and spinal cord • Mix of upper motor neuron and lower motor neuron findings – Weakness, atrophy, fasciculations – Slurred speech, difficulty swallowing, shortness of breath • Can start in any extremity or the bulbar musculature • Relentlessly progressive ALS • 50 % dead in 3 years, 80% dead in 5 years, 510% live more than 10 years • Death usually from respiratory failure • Etiology still only theoretical – Excess glutamate – Oxidative stress – Free radicals – Mitochondrial dysfunction Peripheral Nerve Disorders • Mononeuropathy – Pattern of weakness and sensory loss conforms to the distribution of a single nerve • Carpal tunnel syndrome • Peroneal palsy at the fibular head • Mononeuritis multiplex – Multiple nerves affected in a random pattern • Acute onset, frequently painful • Diabetes mellitus, vasculitis • Polyneuropathy (peripheral neuropathy) – Distal, symmetric Polyneuropathies • Can affect different types of fibers – Autonomic – Motor – Sensory • Large well myelinated • Small poorly myelinated or unmyelinated Symptoms of a Polyneuropathy • Sensory symptoms – Start in feet, move proximally – Hand sxs appear when LE sxs up to knees – Positive • Pins and needles • Tingling • Burning – Negative • Numbness • Deadness • “Like I’m walking with thick socks on” Polyneuropathy Symptoms, cont • Motor – Weakness first in feet • Tripping • Turn ankles – Progress to weakness in hands • Trouble opening jars • Trouble turning key in lock Polyneuropathy: Signs • Distal sensory loss – Large fiber – Small fiber • Distal weakness and atrophy • Decreased or absent reflexes – Ankle jerks lost first Classification of Polyneuropathies • By types of fibers involved – – – – Pure sensory Sensory motor Pure motor Autonomic • By pathology – Demyelinating – Axonal – Mixed • By tempo – Acute – Subacute – Chronic Acute Polyneuropathies • Guillain Barre Syndrome • Porphyria – Neuropathy, psychiatric disorder, unexplained GI complaints • Toxins – Glue sniffing (n-hexane) – Arsenic Guillain Barre Syndrome • Most common cause of rapidly progressive weakness • Demyelinating neuropathy • Ascending weakness which may include cranial neuropathies • Exam reveals symmetric weakness with areflexia and large fiber sensory loss • Bowel and bladder usually preserved Guillain Barre Syndrome, cont • Respiratory failure can be precipitous • Other causes of morbidity and mortality – Autonomic instability – DVT – Infection • Immune mediated, may be post infectious • Treatment – Plasma exchange – Intravenous immunoglobulin Subacute Polyneuropathies • Vasculitis – Can be isolated to peripheral nerves or part of a more systemic process • Paraneoplastic – May be presenting symptom of the cancer • Chronic inflammatory demyelinating polyneuropathy – With or without a gammopathy • Toxins • Drug Chronic Polyneuropathies • Metabolic – Diabetes mellitus – Chronic renal failure – Chronic liver failure – Thyroid disease • Nutritional – B12 deficiency • Infections – HIV – Leprosy • Inherited Evaluation of a Polyneuropathy • Lab work • Nerve conduction study/electromyography – Distinguishes between axonal and demyelinating – Helps ascertain severity • Nerve biopsy – Frequently non-diagnostic – Can establish the dx in certain disorders, such as vasculitis and amyloidosis Disorders of the Neuromuscular Junction NMJ • Pre-synaptic – Lambert Eaton myasthenic syndrome – Botulism • Post-synaptic – Myasthenia Gravis Myasthenia Gravis • Antibody that alters the acetylcholine receptor – Binding – Blocking – Modulating • Antibody detected in – 50% of pts with pure ocular MG – 90-95% of pts with generalized MG Clinical Manifestation of MG • Sxs worsen with exercise, end of day (Fatigue) • Ocular – Droopy eyelids (ptosis) – Double vision (diplopia) • Extremity weakness – Arms > legs • Bulbar – Dysarthria – Dysphagia • Respiratory – Shortness of breath Approach to treating MG • Remove any exacerbating factors – Infections, medication, endocrine disease • Acetylcholinesterase inhibitors • Plasma exchange/ intravenous immunoglobulin • Thymectomy • Immunosuppressants – Prednisone – Imuran (azathioprin) Myopathies Clinical Manifestations of Myopathies • Proximal muscle weakness – Waddling gait – Difficulty climbing stairs – Trouble lifting arms over head • Cramps with the metabolic myopathies • Myalgias with the inflammatory myopathies • Swallowing and breathing difficulties, when present, are usually late Classification of Muscle Disease • Dystrophies – Duchenne’s Muscular Dystrophy – Myotonic Dystrophy • Congenital Myopathies – Glycogenoses – Mitochondrial • Acquired Myopathies – Polymyositis – Dermatomyositis – Inclusion body myositis – Drug related Duchenne’s Muscular Dystrophy • X-linked recessive • Absence of dystrophin protein • Slow to reach motor milestones, sxs by age 5 – All walk, may never run – End up in wheelchair by age 10-12 • Steroids may delay time until wheelchair bound • Muscles replaced by fat may appear hypertrophic • Frequently mildly mentally retarded • Life expectancy < 20 years with death related to respiratory failure or cardiomyopathy Polymyositis • Presents with proximal muscle weakness in 92% • Myalgias in 25% • Associated symptoms may include fever, weight loss • Slightly increased risk of cancer – Bladder, lung, lymphoma • Biopsy of muscle confirms diagnosis • Treatment with immunosuppression – Prednisone – Methotrexate Evaluation of the Patient with Suspected Muscle Disease • Lab – Muscle enzymes (CPK, aldolase) – Erythrocyte sedimentation rate (ESR or sed rate) if suspect inflammatory disease – Genetic test • Duchenne’s • Myotonic dystrophy • EMG/NCS • Muscle biopsy • May provide a definitive diagnosis Extremity Weakness CN Reflexes Sensation ALS Random yes Increased Normal Polyneuropathy Distal> Proximal rare Decreased distally Lost distally > proximally LEMS LE > UE Prox>distal rare Decreased or absent Normal MG UE>LE +/-prox>distal yes Normal or dec Normal Myopathy Prox>distal occ Normal or dec Normal