神经肌肉紧急情况（ppt55）课件

Neuromuscular Emergencies,July 28, 2010 Sandra Derghazarian,Outline,Approach to rapidly progressing LMN weakness Myasthenic crisis GBS,Intro,Three major tasks: Assess stability, signs of imminent resp failure Generate differential diagnosis Knowledge of localisation Knowledge of major disorders Determine management,Brief Review of Anatomy,Motor unit anatomy Anterior horn cell Its motor axon The synaptic cleft The muscle fibers it innervates Remember sensory and autonomic systems Many disorder with rapidly progressing peripheral neuropathic weakness will have sensory loss and dysautonomia,Classification,Motor neuron Loss of anterior horn cells Motor axon Disruption of myelin sheath Axonal degeneration Neuromuscular junction Pre-synaptic (e.g. Release of Ach) Post-synaptic (e.g. Abnormalities of Ach receptor) Muscle Membrane, contractile elements Genetic or acquired secondary (infex, inflamm, vasc.),Approach to Determining Cause of Weakness,Knowledge of some of the possible disorders Focused history Physical exam Lab studies,Major Disorders,History Key Elements,Pre-existing NM disorder? MG exacerbation 2ary systemic illness, medication ALS accelerated phase, decompensation 2ary pneumonia Pre-existing systemic disorder? Malignancy, CTD, sepsis What drugs is pt taking? Any recent illness? Diet in last 48 hours? Shellfish (saxitoxin, brevetoxin) Home-canned goods (botulinum toxin) Any possible exposure to tick bite, snake bite? Any sensory or autonomic symptoms?,Drugs,Diuretics Hypokalemia Corticosteroids, statins, colchicine, cyclosporine, cocaine, chloroquine, L-tryptophan, penicillamine, zidovudine Myotoxic effect Amiodarone, cytarabine, streptokinase Demyelinating neuropathy Magnesium-containing antacids with pre-existing renal insufficiency Hypermagnesemia,Physical Exam,Vital signs Unstable? Dysautonomia? Respiratory status,Signs of impending NM resp failure,Tachypnea, sinus tachycardia Staccato speech Inability to count to 20 Profound weakness of neck flexion Use of accessory muscles (visible, palpable) Orthopnea Paradoxical breathing pattern Signs of bulbar dysfunction (nasal voice, accumulation of saliva, weak cough) think about aspiration!,Physical Exam,Physical Exam,Vital signs Note any dysautonomia Presence and pattern muscle weakness Proximal (myopathy), distal (peripheral neuropathy) Symmetric, asymmetric Involvement of cranial muscles Reflexes Sensory changes Dysautonomia,Localisation of the Disorders,Clinical picture varies depending on which part of motor unit is involved,Localisation ctnd,Regroup,Is respiratory failure imminent? Should ICU be involved? Where can I localise motor findings? Does it fit with sensory findings? Does it fit with autonomic findings? Does it fit with the history? Can the history help me narrow things down?,Major Disorders,Laboratory Studies,CBC Anemia or leukocytosis - systemic disease Eosinophilia - possibly elevated in vasculitic neuropathy, porphyria Lytes, Cr, BUN, Ca, Mg, PO4, Liver enzymes (consider EtOH myotoxicity) CK (myopathy if very elevated) ESR (infectious or inflammatory disorders) CXR (pneumonia, atelectasis, elevated hemidiaphragm) EKG Changes associated with electrolyte imbalances Arrythmias 2ary to dysautonomia in GBS Axis deviation may be suggestive of cardiomyopathy,Assess Respiratory Status,Tests in ER MIP MEP FVC ABG 20/30/40 rule VC: 20 ml/kg MIP: -30cmH20 MEP: +40cm H20,Myasthenic Crisis,Myasthenia Gravis,Disorder of transmission across NM junction Auto-immune and congenital form Epidemiology (auto-immune form): 200-400 cases per million population Women men (3:2) Bimodal incidence F: 20s, 30s; M: 50s, 60s 5-10% co-association with other auto-immune disorders,Classification,Auto-immune two forms Acquired anti-AChR Abs (85%) Acquired anti-MuSK Abs, a muscle-specific TK 40-50% of anti-AChR seronegative pts Congenital Heterogeneous group (pre or post-synaptic) Of note: do not affect respiratory muscles therefore do not present with myasthenic crisis,Clinical Features,Painless, fatigable weakness of voluntary muscles Repeated activity progressive paresis Rest restoration of strength (at least partial) Usually insidious onset May occur more rapidly after precipitant (stress, infection) Association with thymic abnormalities 10-15% thymoma 50-70% thymic lymphoid hyperplasia,Clinical Features,Presenting symptoms: MuSK-MG Younger women Predominantly facial, bulbar and respiratory weakness Relatively mild limb weakness,Severity Classification,Myasthenic Crisis,Myasthenic weakness leading to respiratory failure and need for ventilatory assistance Severe weakness of respiratory muscles and/or Severe weakness of upper airway muscles (bulbar myasthenia),Prevalence and Characteristics,Life-time prevalence: 20-30% Early onset younger pt, median onset w/in 8 mos, fast recovery Late onset older pts, later in dz course, slower recovery White pts respond more poorly than black pts Pregnancy aggravates MG in 30% of women High potential mortality of crisis,Precipitants,Elements to look for in history/chart: Poor control of generalised disease Medical treatment for bulbar myasthenia Steroids and anti-cholinesterases Use of certain drugs (next slide) Systemic infection, esp. of respiratory tract Aspiration Surgery Others (in refractory myasthenia): Emotional stress Hot environment Hyperthyroidism,Drugs,Anticholinesterases can also lead to myasthenic crisis Signs of excessive cholinergic activity Miosis, diarrhea, salivation, abdominal cramps, sweating, weakness,Investigations,CBC, extended lytes, BUN, Cr, liver enzymes CXR, U/A +/- blood cultures Obtain VC, MIP, MEP 20/30/40 rule,Investigations,Repetitive motor nerve stimulation Stimulate motor nerve at 2-3 Hz and measure CMAP of stimulated muscle Positive if er 10% decrement in amplitude of CMAP from the 1st to the 5th potential Positive in about 75% of patients with generalized MG, if Proximal & clinically involved muscles are tested Muscle is warm More than one muscle is tested Single fibre EMG Tensilon test not recommended in pt suspected of being in crisis False postive, false negative Risk of worsening muscle weakness in pts with anticholinesterase overdose Worsening of bulbar and respiratory symptoms in MuSK-MG,Management,Monitoring of respiratory status Recognition of impending resp failure Tachypnea, inability to count to 20, saliva pooling, nasal voice, NF weakness, paradoxical breathing Deciding when to intubate (Code status) 20/30/40 rule If in doubt, intubate ?BiPAP Limited experience. May reduce prolonged intubatn and trach,Management,General Stop any meds that may be contributing Treat any infection Specific PLEX and IVIG comparable efficacy Based on clinical evidence, few RTCs Earlier response seen with PLEX More likely to extubate at 14 days, better 1-month functional outcome (Qureshi, et al. Neurology, 1999).,Management,PLEX Removal of anti AChR and antiMuSK Abs 1 session/day x 5 No superiority of PLEX qd x 5 vs qod x 5 Rapid onset of action (3-10 days) Need central line with associated complications PTX, hemorrhage, line sepsis Caution in pts with sepsis, hypotension; may lead to increased bleeding and cardiac arrhythmias,Management,IVIG 0.4gm/kg/day x 5 days Easily administered and widely available Long duration of action May last as long as 30 days Side effects Anaphylaxis in IgA deficiency Renal failure, pulmonary edema Aseptic meningitis Thrombotic complications and stroke,MG Overall Treatment Summary,1. Mild weakness: cholinesterase inhibitors 2. Moderate-marked localized or generalized weakness Cholinesterase inhibitors, and Thymectomy for patients under age 50-60 yrs 3. Symptoms uncontrolled on cholinesterase inhibitors Prednisone if severe or urgent Azathioprine Prednisone failure Excessive prednisone side-effects 4. Plasma exchange or IV Ig Impending crisis; crisis Pre-operative boost Chronic disease refractory to drug therapy 5. If above fails Search for residual thymus tissue Cyclosporine or mycophenylate mofetil (Sem. Neurol., 2001;21:425-440),Guillain-Barre Syndrome,GBS,Most common cause of acute and subacute generalised paralysis Incidence of 0.4 to 1.7/100 000 per yr Worldwide, all ages, both sexes Preceding mild resp or GI infection in 60% (1-3 wks) Campylobacter jejuni (26%), CMV, EBV, VZV Influenza, cocksackie, hepatitis A and B, HIV May also be preceded by: Surgery Immunisations,Typical Symptoms & Signs,Sensory Paresthesias and slight numbness distally earliest Sx Reduced proprioception and vibration sense (1 wk) Motor Weakness Evolves symmetrically over days to 1-2 weeks Usually LE before UE, proximal + distal +/- trunk, intercostal, neck, cranial muscles Progresses to total motor paralysis and respiratory failure in 5% of cases,Typical Symptoms & Signs,Reflexes Reduced and then absent Autonomic dysregulation Sinus tachycardia/bradycardia, facial flushing, labile BP, excess or loss of sweating, urinary retention Usually do not persist for er 1 wk Other Myalgias (50%) in hips, thighs, back,Variants,Fisher syndrome Ophthalmoplegia, ataxia, areflexia +/- bilateral facial nerve paresis Associated with anti-GQ1b Ab Acute motor sensory axonal neuropathy (5% of GBS cases) Severe and diffuse axonal damage Abrupt and explosive onset Severe paralysis, minor sensory features Slow and poor recovery Pandysautonomia Severe orthostatic hypotension, anhidrosis, dry eyes and mouth, fixed pupils, arrhythmia, bowel/bladder dysfunction Areflexia without somatic motor/sensory involvement Other variants: Initial cervico-brachial-pharyngeal muscle involvement Generalised ataxia without dysarthria or nystagmus Facial and abducens weakness, distal paresthesias, proximal leg weakness,Laboratory Findings,Most important: CSF, EMG CSF Normal pressure Protein Early (1st 2 days): Usually normal (85%) Later: High (66% in 1st week, 82% in 2nd week) Amount not correlated with clinical course or prognosis Acellular or few lymphocytes 10% : 10-50 lymphocytes, decreases over 2-3 days; if not: other Dx Oligoclonal bands (10-30%),Laboratory Findings,EMG Abnormalities seen within first week of sx Reduction in motor amplitude Slowed conduction velocities Conduction block in motor nerves Prolonged distal latencies (distal conduction block) Prolonged/absent F-responses (involvement of proximal parts of nerves and roots),Laboratory Findings,Hematology Abnormal only with infection or other disorder Biochemistry Mild-severe SIADH in 7-26% Liver enzymes Elevated 10% reflecting CMV or EBV infection ESR: Normal unless co-existing process,Diagnostic Criteria,National Institute of Neurological Disorders and Stroke (NINDS) criteria are based on expert consensus. Required features include: Progressive weakness of more than one limb, ranging from minimal weakness of the legs to total paralysis of all four limbs, the trunk, bulbar and facial muscles, and external ophthalmoplegia Areflexia. While universal areflexia is typical, distal areflexia with hyporeflexia at the knees and biceps will suffice if other features are consistent. Supportive features include: Progression of symptoms over days to four weeks Relative symmetry Mild sensory symptoms or signs Cranial nerve involvement, especially bilateral facial nerve weakness Recovery starting two to four weeks after progression halts Autonomic dysfunction No fever at the onset Elevated protein in CSF with a cell count 10 mm3 Electrodiagnostic abnormalities consistent with GBS,Differential Diagnosis,Features suggesting another diagnosis: Sensory level, severe bladder or bowel dysfunction Spinal cord syndrome Marked asymmetry Mononeuritis multiplex/vasculitis CSF pleocytosis Infectious disorders: viral, HIV, lyme, poliomyelitis Very slow nerve conduction velocities, multiple relapses or chronic course - CIDP Persistent abdominal pain and psychiatric signs Acute intermittent porphyria,Management,General: Recommend admission for observation Can deteriorate rapidly in first days of presentation M&M: Respiratory failure, dysautonomia 25% will require mechanical ventilation Respiratory Measure MIP/MEP/FVC Decision to intubate should be based on downward trend Other measures of respiratory status same Counting to 20, strength of NF,Management,Dysautonomia 10% develop hypotension Volume, +/- pressors Hypertension IV labetolol Other complications Adynamic ileus PE Aspiration,Management,PLEX and IVIG No difference in efficacy between the two Indications for prompt initiation Respiratory failure Bulbar involvement Inability to walk without assistance Usually see these signs day 5-10 May occur anywhere from day 1 week 3 Steroids No proven benefit,PLEX,Regimen: 4-6 treatments on alternate days Established usefulness in evolving phase If treated within 2 wks onset Decrease in LOS, ventilation, time to independent ambulation by approx. half Value less clear if started later than 2 wks after initial symptoms Predictors of response Age Preservation of motor CMAP amplitudes pre-PLEX,IVIG,Dose: 0.4 gm/kg/day x 5 consecutive days Cheaper, easier to administer Rare complications Renal failure, proteinuria, pulmonary edema Asceptic meningitis Anaphylaxis in IgA deficiency,Course and Prognosis,Progressive symptoms : 1-4 weeks Plateau: 2-4 weeks Recovery: A few weeks to months Recurrence: 5-10% Mortality 3-5% Cardiac arrest, ARDS, PTX, HemoTX, PE Pronounced disability: 10% Clinical prognostic indicators Greater age Rapid evolution; early and prolonged ventilatory assistance, rapid course Lack of treatment with IVIG or plasma exchange Laboratory EMG: severely reduced CMAP and widespread denervation,Pathogenesis,Most evidence points to cell-mediated immunologic reaction directed at peripheral nerve May be precipitated by antecedent infection Antibodies against myelin components with complement-mediated damage T cells and macrophages become involved in process and lead to destruction of myelin/axon,Thank you,