10/15/2019 Neuromuscular Diseases Primer K. H. VINCENT LAU, MD ASSISTANT PROFESSOR IN NEUROLOGY BOSTON MEDICAL CENTER 40TH ANNUAL NEUROREHABILITATION CONFERENCE ON TRAUMATIC BRAIN INJURY, STROKE AND OTHER NEUROLOGICAL DISORDERS Disclosures No conflict of interest to disclose Objectives By the end of the session, participants should be able to: ▪ Describe the neuro-axis and name a representative disorder in each level of the axis ▪ Describe the diagnosis, management and expected course of five neuromuscular disease 1 10/15/2019 Neuro-axis ▪ Brain and brainstem (stroke) ▪ Spinal cord (cord compression) ▪ Anterior horn cells (amyotrophy lateral sclerosis) ▪ Nerve roots (Guillain-Barre syndrome - GBS) ▪ Plexus (lumbosacral plexopathy) ▪ Peripheral nerve (GBS, critical illness neuropathy) ▪ Neuromuscular junction (myasthenia gravis) ▪ Muscle (myositis, critical illness myopathy) Neuromuscular Diseases 1. Guillain Barre syndrome 2. Critical illness neuropathy and myopathy 3. Inflammatory myopathies 4. Amytrophic lateral sclerosis 5. Myasthenia gravis Guillain-Barre syndrome: Introduction ▪ Most common cause of acute or subacute flaccid weakness ▪ Monophasic (occurs once in lifetime and rarely recurs) ▪ “Ascending” weakness, usually with numbness and tingling ▪ Symptoms generally nadir within 4 weeks ▪ Risk of respiratory compromise during course of illness ▪ Treat with intravenous immunoglobulin (IVIg) or plasmapheresis ▪ May have prolonged disability 2 10/15/2019 Guillain-Barre syndrome: Epidemiology ▪ After eradication of polio, is now the most common cause of acute or subacute flaccid weakness worldwide ▪ 0.5-2 per 100,000 (lifetime risk 1/1000!) ▪ Men > women Guillain-Barre syndrome: Clinical features ▪ Weakness and numbness in lower extremities, “ascending” ▪ 90% reach peak weakness by 4 weeks ▪ Neuropathic pain usually at lower back or thighs (66%) ▪ Cranial nerves weakness (50%) incl ophthalmoparesis (20%) ▪ Respiratory failure (30%) ▪ Autonomic involvement: tachycardia/bradycardia, hypertension/hypotension, urinary retention, gastric hypomotility ▪ Often with preceding illness (70% have respiratory illness or gastroenteritis within 10-14 days, most often Campylobacter) ▪ Neurological examination: extremities weakness, mild sensory changes, decreased reflexes (possible facial weakness) Guillain-Barre syndrome: Variants ▪ Demyelinating types: ▪ Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) ▪ Most common type of GBS (85-90% of all cases) ▪ Miller Fisher syndrome – clinical triad of: ▪ Ophthalmoparesis/ophthalmoplegia ▪ Areflexia ▪ Ataxia ▪ Axonal variants: ▪ Acute motor axonal neuropathy (AMAN) – more in children ▪ Acute motor and sensory axonal neuropathy (AMSAN) – poor prognosis 3 10/15/2019 Guillain-Barre syndrome: Diagnosis ▪ Clinical presentation ▪ Lumbar puncture: cerebrospinal fluid (CSF) shows “albuminocytologic dissociation” ▪ MRI lumbar spine with and without contrast may show nerve root enhancement; helpful to exclude alternative diagnoses ▪ Electromyography and nerve conduction studies (EMG/NCS) – may show demyelination ▪ Differential diagnoses: ▪ Critical illness neuropathy and myopathy (based on history) ▪ Tick paralysis (more predominantly motor, normal CSF) ▪ Acute intermittent porphyria (usually with psych sxs, prior attacks) ▪ HIV infection (CSF with white blood cells) Guillain-Barre syndrome: Management ▪ Intravenous immunoglobulin (IVIg) or plasmapheresis ▪ Monitor for respiratory failure, cardiac arrhythmias, autonomic dysfunction ▪ Frequent forced vital capacity and negative inspiratory force ▪ Neuropathic pain medication (e.g. gabapentin, pregabalin, tricyclic) ▪ Early physical therapy and occupational therapy Guillain-Barre syndrome: Prognosis ▪ Mortality 3-7% (respiratory, autonomic failure, infection) ▪ Full recovery or minor deficits in 87% ▪ Residual bilateral foot drop (ankle-foot orthoses) ▪ Most recovery occurs over first year, but may occur up to >3 years ▪ May have residual numbness and pain, persistent fatigue ▪ Poor prognostic factors: ▪ Late age ▪ Preceding diarrhea or C. jejuni infection ▪ Need for intubation and ventilator support 4 10/15/2019 Guillain-Barre syndrome: Rehabilitation ▪ “Early rehabilitation intervention ensures medical stability, appropriate treatment and preventive measures to minimise long term complications. Specific problems include deep venous thrombosis prevention, complications of immobility, dysautonomia, de-afferent pain syndromes, muscle pain and fatigue. Longer-term issues include psychosocial adjustment, return to work and driving, and resumption of the role within the family and community. Effective communication between the GP and rehabilitation physicians is imperative for improved functional outcomes and successful social reintegration.” Khan F. Rehabilitation in Guillian Barre syndrome. Aust Fam Physician. 2004 Dec;33(12):1013-7. Critical illness neuropathy/myopathy: Introduction ▪ Causes of weakness and difficulty with weaning off mechanical ventilation in intensive care settings ▪ Subtypes: ▪ Critical illness neuropathy or polyneuropathy (CIN) ▪ Critical illness myopathy (CIM) ▪ Critical illness polyneuromyopathy (CIPNM) ▪ Early recognition may lead to earlier management and better outcomes Critical illness neuropathy/myopathy: Epidemiology ▪ Prevalence depends on underlying disease and degree of involvement: ▪ E.g. multiorgan dysfunction - perhaps close to 100% ▪ E.g. sepsis/systemic inflammatory response syndrome – >70% ▪ E.g. status asthmaticus – 33% develop CIM 5 10/15/2019 Critical illness neuropathy/myopathy: Clinical feat. ▪ Weakness: ▪ CIM – proximal > distal weakness and atrophy (sensory spared) ▪ CIN - distal > proximal weakness, sensory changes and limited atrophy ▪ CIPNM – combination of proximal > distal weakness, distal sensory loss and variable atrophy ▪ Gradual loss of reflexes ▪ Respiratory failure, inability to wean from ventilator ▪ Secondary to ICU diagnoses, e.g. status asthematicus, sepsis, trauma ▪ Risk factors: systemic inflammatory response syndrome, multiorgan dysfunction, mechanical ventilation, possibly hyperglycemia (unclear if steroid use or neuromuscular blockade truly risk factors) Critical illness neuropathy/myopathy: Pathophys. ▪ CIN – unclear mechanism, hypotheses include microcirculatory injury from systemic inflammation or vascular permeability ▪ CIM – myosin loss and contractile apparatus dysfunction ▪ Neurophysiological findings can be seen within hours of admission to ICU Critical illness neuropathy/myopathy: Diagnosis ▪ Exclude neuromuscular causes e.g. GBS, Lambert Eaton, botulinum toxin, ongoing neuromuscular blockade (usually need EMG/NCS) ▪ Exclude non-neuromuscular causes e.g. primary pulmonary or cardiovascular, central nervous system ▪ Consider muscle biopsy if EMG/NCS difficult to interpret ▪ In CIP would show neurogenic changes ▪ in CIM would show myogenic changes (specifically loss of type 2 greater than type 1 muscle fibers) 6 10/15/2019 Critical illness neuropathy/myopathy: Management ▪ Modify the modifiable risk factors: ▪ Tight glucose control – only intervention with clear benefit ▪ Treat sepsis ▪ Immunotherapy not yet demonstrated to improve outcomes ▪ Early ICU mobility Critical illness neuropathy/myopathy: Prognosis ▪ Results in increased length of stay, more ventilator-dependent days than without diagnosis ▪ May have worsened hospital mortality (conflicting data) ▪ May have ongoing noticeable weakness at time of discharge (20%) ▪ CIM has better prognosis than CIN; in one study: ▪ 11/12 of patients with CIM had complete recovery at 6 months ▪ Only 2/7 of patients with CIN/CIPNM had complete recovery ▪ Note conflicting data with another prior study ▪ Recovery can continue up to 24 months Critical illness neuropathy/myopathy: Rehabilitation ▪ No randomized control trials, but it is thought that early ICU mobility can decrease length of stay ▪ One case series: ▪ Group A: 19 patients received 30 minutes a day x 5 days of PT Group B: 35 patients received intermittent PT ▪ Result: Group A, 32% discharged home; Group B, 11% ▪ Earlier mobility does not appear to change rate of ICU-acquired weakness ▪ Direct muscle stimulation x 30 minutes daily showed decreased loss of cross-sectional area of muscle mass 7 10/15/2019 Critical illness neuropathy/myopathy: Rehabilitation ▪ “There are no published RCTs or quasi-RCTs that examine whether physical rehabilitation interventions improve activities of daily living for people with CIP and CIM. Large RCTs, which are feasible, need to be conducted to explore the role of physical rehabilitation interventions for people with CIP and CIM.” Mehrholz J, Pohl M, Kugler J, Burridge J, Mückel S, Elsner B. Physical rehabilitation for critical illness myopathy and neuropathy: an abridged version of Cochrane Systematic Review. Eur J Phys Rehabil Med. 2015 Oct;51(5):655-61. Epub 2015 Jul 9. Inflammatory Myositis: Introduction ▪ Largest group of potentially treatable myopathies in adults and children ▪ Heterogeneous, with four subtypes: ▪ Dermatomyosits ▪ Polymyositis ▪ Necrotizing autoimmune myositis ▪ Inclusion-body myositis (IBM) ▪ All cause proximal weakness except IBM has special pattern ▪ All treated with immunotherapy except IBM (no treatment) Inflammatory Myositis: Clinical features ▪ Proximal weakness (except IBM) – difficulty getting up from a chair, climbing steps, lifting objects, with eventual atrophy ▪ IBM: weakness in finger flexors, quadriceps and ankles (may also have facial weakness) ▪ May have head drop and dysphagia ▪ May have respiratory