Myasthenia Gravis GuillainBarre Syndrome

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Myasthenia GravisGuillain-Barre Syndrome

• ICU teaching
• April 27th

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Myasthenia Gravis

• Autoimmune disorder
• Antibodies directed against acetylcholine
  receptor (AChR)
• Best understood clinical disorder of
  neuroreceptor function.
• Clinically characterised by weakness and
  fatigability on sustained effort
• Intensive care required due to severe involvement
  of bulbar and respiratory muscles

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incidence

• 1 in 20 000
• No racial or geographical prediliction
• Any age although rare in lt2yrs
• Peaks incidence in young females
• Females x2 males
• Gender preference diminishes with increasing age
• Smaller second peak in elderly males

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Pathophysiology

• IgG AB interact with the postsynaptic AChR at the
  nicotinic neuromuscular junction(NMJ).
• This reduces the number of functional receptors
  by blocking Ach attachment, by increasing the
  degradation of receptors and by complement
  induced damage to the NMJ
• MG pts have a reduced AChR density and have 30
  the normal number of AChR
• This reduces the safety margin at the NMJ

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• The reduced AChR density leads to decreased
  amplitude in AP in the post synaptic region
  leading to failure in initiation in muscle fibre
  contraction.
• When it occurs at many NMJs manifests as weakness
  of voluntary muscle-cardinal feature

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Aetiolgy

• Antibody mediated, origin uncertain
• Thymus gland possible generator
• Gland abnormal in 75 of patients with MG(
  hyperplasia and thymoma)
• B and T lymphocytes become sensitised to AChR
  found in myoid cells in the gland
• Reason for breakdown in normal immune tolerance
  uncertain

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Clinical features

• Voluntary muscle weakness cardinal feature, with
  fatigability, relieved with rest
• 15 pts have disease confined to the eyes
• 85 generalised ocular, facial, bulbar, limb
• Respiratory muscles affected mildly however in
  myasthenic crisis resp failure requiring support
  may be required
• Symptoms of diplopia, ptosis, dysarthria,
  regurgitation,dysphagia are all common.

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Diagnosis and Ix

• History and examination
• EMG
• Recording of compound muscle action
  potentials(CMAP)
• Following repetitive stimulation of motor nerve
• In MG this leads to reduction in CMAP (gt10)

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• All EMG abnormalities are not specific for MG
• Detection of anti-AChR antibodies
• In 80-85 cases and are pathognomonic
• The Tensilon test-
• up to 10mg edrophonium is administered IV is
  standard test.
• Mg pts show marked improvement after 30sec and
  lasts 5min

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Management

• Anticholinesterase drugs potentiate the Ach at
  receptor sites, Pyridostigmine most common up to
  60mg QID. Effects diminish over months
• Thymectomy best results and advocated early in
  all patients regardless of severity or presence
  of thymoma. Earlier remission, lower mortality,
  greater delay in recurrences.

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Management continued

• Immunosuppression - corticosteroids mainstay
• effective in 70
• best results when used high dose and reduced
• average of 4months with some indefinitely
• Azothiprine and methotrexate effective adjuncts,
  80 helped, few remission

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Mx continued

• Plasma exchange effective in achieving short term
  remission, for preoperative thymectomy, in
  myasthenic crisis or respiratory failure.
  Reduction in level of antibodies correlates with
  the improvement in muscle power. Improvement seen
  within days and is short lived.five exchanges
  3-4litres each over 2 weeks
• Iv IG similar effects as plasma exchange ,
  400mg/kg/day for 5days. Some pts get long term
  benefit. No effect on ab numbers and mechanism of
  action unknown.

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Complications of all treatments

• Sepsis and infections related to IV catheters and
  immunosuppression
• Renal failure from IgG and Cyclosporin
• All the complications of long term steroid use

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Myasthenic and cholinergic crisis

• Known MG pts may have life threatening acute
  deteriorations
• Following infections, pregnancy and
  administration of some drugs
• Most resolve over several weeks some last months
• Incidence of M.crisis increases with age

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Management of the crisis

• Risk of pulmonary aspiration due to bulbar muscle
  involvement, bacterial pneumonia due to stasis,
  acute resp failure and cardiorespiratory arrest.
• Resusitation as for any patient
• Followed by edrophonium, this will indicate
  whether patient will respond to increasing dose
  of anticholinergic drug.

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• If edrophonium worsens condition patient
  suffering cholinergic crisis which is due to over
  admin of anticholinesterase drugs( cramps,
  brady,salivation,diarrhoea)
• Improvement seen if anticholinesterase drugs
  reduced, withdrawn and restarted

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ICU management

• Frequent estimations of VC and inspiratory force
• Consideration of mechanical ventilation given to
  those with severe bulbar and respiratory muscle
  involvement
• Deterioration of ABGs often late sign
• Good ICU care, maintaining K, Ca Mg levels
  normal. Physio and NG feeding.
• If adjustment of medications not sufficient to
  see improvement need to consider high dose
  steroid and plasma exchange therapy.

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Drugs to avoid

• Polymyxin group of antibiotics
• Aminoglycosides
• B blockers
• Procainamide, lignocaine
• Suxamethonium

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Associated disorders

• Thyroid abnormality
• Rheumatoid disease
• Scleroderma
• Psoriasis
• Polymyositis
• SLE
• Pernicious anaemia

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anaesthesia

• Pre op optimisation
• Airway assessment if RA
• Avoid premedication
• Avoid depolarising mr
• Reduce dose of non-depolarisers if any used at
  all, monitoring at all times
• Continue steroid and give additional on day of
  surgery
• Post op hdu-up to 33 require ventilation
  predicted by long pre-op hx MG, high
  anticholinesterase requirements, VC lt2.9l.

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Guillain Barre Syndrome

• Acute demyelinating polyneuropathy
• Commonest cause of rapid-onset flaccid paralysis
  since polio decline
• Occurs as an autoimmune response following a GI
  or respiratory infection
• Potentially severely debilitating disorder
  affecting 1-3 per 100,000
• 10 die from associated complications
• A further 10 suffer from long term neurological
  sequelae and physical dependence

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• Guillain, Barre and Strohl first described a
  disease affecting French soldiers ( motor
  weakness, areflexia and CSF abnormalities) in
  1916
• Descriptions date back to 1859 when Laundry
  described ascending paralysis

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• Despite well recognized syndrome and potentially
  fatal
• Often misdiagnosed and subtle signs of
  decompensation missed

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Aetiology

• All ages affected with bimodal distribution
  towards young adults and the elderly
• Slight male preponderance
• Children less severely affected
• Most commonly occurs within a month of GI or resp
  upset.
• Commonest organism is campylobacter
• Others inc EBV, CMV, complication of HIV

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• Have been reports of association with vaccines,
  surgery, epidurals, bone marrow and organ
  transplantation, SLE, lymphoma, sarcoidosis
• Pregnancy and OCP confer some protection

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Pathogenesis

• Immunologically mediated nerve injury
• Inflammatory cell infiltrates are seen in
  association with the demyelination, which is
  regarded as the primary pathological process
• Precise mechanism of sensitisation not known
• Peripheral nerves show infiltration of the
  endoneurium by mononuclear cells in a perivenular
  distribution

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• Distributed throughout the nerve length but
  focused at nerve roots, spinal nerves and major
  plexuses
• Macrophages actively strip myelin from bodies of
  schwann cells and axons
• Underlying immune response is complex
• Effectiveness of plasma exchange and IgG is
  thought to be blocking of demyelinating antibodies

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Clinical presentation

• Several distinct clinical pictures described
• Acute inflammatory demyelinating
  polyradiculopathy (AIDP)
• Acute motor axonal neuropathy (AMAN)
• Acute motor sensory axonal neuropathy (AMSAN)
• Miller-Fisher syndrome ( ataxia, areflexia and
  opthalmoplegia which may be accompanied by limb
  weakness, ptosis and facial and bulbar palsy

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• Classical picture is that of ascending limb
  weakness with areflexia, although a purely
  sensory variant has been well documented
• Features of GBS include
• Progressive motor weakness, usually ascending
  from the legs
• Areflexia
• Facial palsy and bulbar weakness
• Opthalmoplegia
• Sensory symptoms

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• Severe pain esp girdle
• Resp muscle weakness
• Autonomic dysfunction( over or underactivity of
  the SNS or PSNS)

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Features required for diagnosisdefined by
national institute of neurological and
communicative diseases and strokes

• Progressive muscle weakness of more than one limb
• Areflexia or marked hyporeflexia
• CSF cell counts of no more than 50 monocytes or 2
  polymorphonuclear leucocytes
• Features highly suggestive
• Features required to rule out other diagnosis

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Differential diagnosis

• Rapidly progressive space occupying lesion eg
  epidural abscess
• Critical illness polyneuropathy, associated with
  recovery from multiorgan failure, steroids and
  muscle relaxants
• EMG shows pure axonal degeneration patterns
  compared to demyelination seen in GBS
• CSF protein level normal in CIP

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Monitoring

• Cardiac
• Blood pressure
• Vital capacity measured three times a day
• Bulbar function monitored to prevent aspiration

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Investigations

• In over 90 patients CSF protein is raised (
  gt0.4g/l) within a week of onset of symptoms
• Level does not correlate with clinical findings
• Nerve conduction studies demonstrate reduced
  conduction velocity
• Liver and renal function may be impaired
• Antiganglioside antibody should be searched for

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• SIADH may occur in association with GBS
• Stool cultures for campylobacter
• Ecgs for QT, T and ST abnormalities
• Head CT to exclude raised ICP and other pathology
  prior to LP

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Treatment

• Major challenge
• Outcome excellent if complications treated or
  avoided
• Prevented by meticulous attention to detail

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Specific treatment-disease modifying modalities

• Plasma exchange
• Immunoglobin
• Both should be used when patient non-ambulatory
  or resp decompensation occurs
• Both have been examined in RCT and no difference
  in efficacy demonstrated between them

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Plasma exchange

• 2 RCT showed reduction in ventilation and reduced
  time to motor recovery
• Mortality was not altered
• Most effective within 7 days of onset
• 3-5 exchanges of 1-2 plasma volumes each over 1-2
  weeks
• Ffp more complications than albumin
• CI include CVS instability, sepsis and
  haemostatic problems
• Side effects are hypotension, hypocalcaemia,coagul
  ation abnormalities and sepsis

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IV Immunoglobin

• 0.4mg/kg daily for 5-6 days
• Easier administration
• Fewer side effects
• Commence tx within 2 weeks of onset of symptoms
• CI include IgA deficiency(anaphylaxis)
• Renal function may deteriorate
• Severe congestive cardiac failure major
  contraindication
• RCT has suggested as effective as plasma exchange

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Steroids

• No place in the treatment of GBS
• RCT have shown no advantage

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CSF filtration

• Few case reports
• When plasmapheresis and IgG have failed
• Logistics difficult!

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Supportive care

• Respiratory,
• 25 require ventilated
• Physio and VC monitoring in the spont breathing.
  If less than 15ml/kg or rising pCO2 ventilation
  likely
• Monitoring of bulbar function for prevention of
  aspiration
• Non-invasive ventilation often not useful as does
  not eliminate the problem of not being able to
  clear secretions due to poor cough
• Early tracheostomy should be considered

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Supportive care

• Cardiovascular
• Full invasive monitoring
• Care with induction of anaesthesia as leads to
  hypotension and arrhythmias
• Care with suxamethonium may lead to arrhythmias
• Instability may be worsened by other drugs
• Autonomic instability common

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Supportive care

• Nutrition, fluid and electrolytes
• Paralytic ileus common
• Tpn may be required
• Energy and fluid requirements are reduced in
  these patients
• Physiotherapy
• DVT prophylaxis
• Sepsis survellience
• Psychological care
• analgesia

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Prognosis

• Death in up to 25 of those who require ICU has
  been reported often from autonomic abnormalities
• Approx 16 patients suffer permanent disability
• Those who require ventilation, improve after more
  than 3 weeks, not improved within 1 month have
  greater risk of poorer outcome
• Gradual improvement may occur over 18months
  -2years
• Recurrence n 2-5 cases

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