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Is it MG Crisis?. Dr Chan Yan Fat Alfred Caritas Medical Center 20/01/2009. Background history. 82-year-old woman, ex-smoker Mother of 6 children Resident in Canada and being FU at there Post-radioactive-iodine hypothyroidism Asthma with nil attack for years Essential hypertension

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Is it mg crisis

Is it MG Crisis?

Dr Chan Yan Fat Alfred

Caritas Medical Center


Background history
Background history

  • 82-year-old woman, ex-smoker

  • Mother of 6 children

  • Resident in Canada and being FU at there

  • Post-radioactive-iodine hypothyroidism

  • Asthma with nil attack for years

  • Essential hypertension

  • Ocular myasthenia gravis (MG) since 2002

Long term medication
Long term medication

  • L-thyroxine 75 microgram daily

  • Candesartan 8mg daily

  • Ventolin 2 puffs Qid PRN

  • Becotide 2 puffs BD

  • Pyridostigmine (Mestinon) 60mg BD

History of present illness
History of present illness

  • Visit Hong Kong since one week ago

  • Upper respiratory infection since arrival

  • Fever and sputum for 3 days, and put on oral Levofloxacin 100mg BD + Romilar

  • Subjective double vision for one day, with bilateral upper limb weakness + numbness, but still able to walk

  • While at Precious blood Hospital, developed choking and SOB

To cmc aed 9 3 08 at 1900
To CMC AED 9/3/08 at 1900

  • BP 202/89, pulse 72, SaO2 88% room air

  • GCS 15/15, Fever 38.0 degree

  • Speak full sentence, SaO2 96% at 2L O2

  • “muscle weakness” at 4/5

  • Chest clear; PFR 170  170  150

  • Impression: mild MG

  • Decision: consult ICU

Direct icu admission
Direct ICU admission

  • Failed bedside swallowing test

  • Impaired abduction of eyes at both side

  • No facial weakness or fatigability

  • Power: bilateral upper limb 4-/5

    bilateral LL 4/5 proximal; 5/5 distal

  • Bilateral down-going plantar

  • Normal deep tendon reflex

Differential diagnosis
Differential diagnosis

  • Generalized myasthenia gravis (MG) with ocular and bulbar involvement

  • Thyroid ophthalmopathy + myopathy

  • Brainstem pathology

  • Motor cranial nerve pathology

  • Pharyngeal-cervical-brachial variant of Gullain-Barre Syndrome

Impression at icu
Impression at ICU

Generalized MG with bulbar involvement

Precipitated by……

Famous mg precipitating causes
Famous MG precipitating causes

  • Antibiotics:aminoglycosides; macrolides; fluoroquinolone; tetracyclines

  • Anesthetic: lidocaine; procaine; NMB

  • Cardiac: betablocker; CCB; procainamide

  • Steroids

  • Anticonvulsant: phenytoin; gabapentin

  • Others: Opiods; thyroxine; diuretics; anti-cholinergics; iodinated contrasts; URI

Management by on call mo
Management by on-call MO

  • Keep NPO for possible intubation later

  • Increase Mestinon 60mg tds

  • Insert RT for medication


  • Blood, sputum and urine for culture

  • Serum viral titre

  • Urgent plain CT brain

Blood test
Blood test

  • WCC 15.4 (Neutrophil 85.4%)

  • Hemoglobin 13.5 with MCV 89.9

  • ESR 87

  • CK 145; albumin 37, globulin 42

  • RFT and LFT normal

  • TSH 1.79 (0.50-4.70)

  • pH 7.41, CO2 42.6, O2 176, HCO3 26

Progress on 10 3 08 at icu d2
Progress on 10/3/08 at ICU D2

  • Subjective deterioration and require frequent suction of oral secretion/ sputum

  • Examination in AM around:

    • Hoarseness and weak cough

    • Drooling of saliva

    • Poor AE over both chest

  • Impression: MG crisis

  • Bronchoscopy

    • Very poor cough effort

    • Continuous aspiration of saliva and upper airway secretion into lower tract

    • BAL done at right lower lobe for virus study and bacterial culture

    Management at icu day 2
    Management at ICU day 2

    • Endotracheal intubation

    • Start IV Augmentin for chest infection

    • Start iv Intragram (IVIG) 21g (BW 53kg), plan daily dose for 5 days

    • Trace old record from Canada family doctor about the diagnosis and previous workup of myasthenia gravis

    Progress at icu day 4
    Progress at ICU day 4

    • All ocular movement is full, no ptosis

    • Hand-grip 3/5; right wrist flexion 2/5; rest of upper limb power 0/5 !

    • Both thigh 3/5, both ankle 4/5

    • Absent deep tendon reflex of lower limb, markedly decreased at upper limb

    • Paraesthesia over 4 limb, nil sensory level

    • BP 100/55, fever down

    Atypical presentation of MG!

    Deterioration with iv Ig

    Other pathology?

    Can it be due to mg crisis


    Symmetrical proximal muscle weakness

    Previous ocular MG

    Bulbar symptom

    Precipitating factors of crisis seen


    Different symptom and sign from past

    Severity of physical sign not fluctuating

    Global areflexia

    Sensory symptoms

    Can it be due to MG crisis

    Management at icu day 4
    Management at ICU day 4

    • Stop Intragram

    • Off Mestinon  plan to have more MG workup first e.g. electrophysiology

    • Urgent MRI cervical spine to upper thoracic spine to look for cord lesion

    • Trace again past medical record from Canada doctor by relative

    Urgent mri report
    Urgent MRI report

    • Serpentine intradural extramedullary flow-related signals and flow voids are demonstrated from C5 to T9 level, but no definite intramedullary involvement.

    • No hemorrhage or abnormal signal in cord

    • No mass effect on cervical/ thoracic cord

    • Impression: spinal vascular malformation, likely spinal dural AV fistula

    Can it be spinal cord insult





    Normal cognitive function all along

    MRI showed vascular lesion around cord


    Proximal affected preferentially

    No sensory level

    Bulbar symptoms

    Ophthalmoplegia, though improved

    Normal cord signal

    Can it be spinal cord insult?!

    Progress at icu day 5
    Progress at ICU day 5

    • Orthopedics  intramedullary lesion better be managed by neurosurgery

    • Neurosurgery  no evidence of acute element for intervention, suggest to transfer patient when nil airway problem

    • ICU  noted good respiratory effort with spontaneous tidal volume >400ml. Failed extubation because of aspiration problem

    Progress at icu day 6 1
    Progress at ICU day 6 (1)

    Medical summary from Canada

    • Patient presents as ptosis and diplopia in June 2002. Nil peripheral/ bulbar or respiratory involvement

    • Nil Tensilon test, nil anti-acetylcholine receptor antibody checked

    • Prompt effect with Mestinon

    • CT thorax showed no thymoma

    Progress at icu day 6 2
    Progress at ICU day 6 (2)

    • Proximal muscle power 2/5, distal 4/5

    • Double-blinded Tensilon test

       no significant change in limb power

    • Bedside EMG: no typical decrement of amplitude with repetitive stimulation

    • Acetylcholine receptor binding antibody

       10.57 (<0.45, ELIZA method)

    Neurologist icu day 7
    Neurologist (ICU Day 7)

    • All along no cognitive impairment

    • No objective sensory deficit

    • Diplopia on presentation, though remitted

    • Bulbar symptom: choking/ hoarseness

    • Both shoulder and hip power 2/5

    • Both ankle/wrist and hand power 4/5

    • Global areflexia + withdrawal plantar

    • Impression: Miller Fisher syndrome






    Off sedation

    On sedation

    Off sedation















    ICU intubation

    8P 9/3

    8A 10/3

    8P 10/3

    8A 11/3

    8P 11/3

    Management at icu day 7 1
    Management at ICU day 7 (1)

    • Contrast CT brain  nil significant lesion

    • Lumbar puncture

       Protein 1.85, glucose 4.0 (serum 9.0)

       unfit for cell count

       PCR for HSV/ VZV not detected

    • Check ANF/ANCA/Anti-cardiolipin/ lupus anticoagulant/ cold agglutinin/ atypical pneumonia titer/ CMV and EBV serology

    Management at icu day 7 2
    Management at ICU day 7 (2)

    • Check Anti-Ganglioside Q1b antibody by private lab

    • Give 3 more days of Intragram 21g daily

    • Plan perform nerve conduction test on working day to detect any features of polyneuropathy, and to differentiate demyelinating/ axonal degeneration if any

    Progress at icu day 9
    Progress at ICU day 9

    • Shoulder/ elbow power 4-/5; hand 5/5

    • Hip/ knee power 3/5; ankle 4/5

    • Nerve conduction test bedside

      • Absent F wave response in 5 nerves

      • Prolonged distal latency

      • Amplitude and velocity within normal

      • No conduction block; sural nerve spared

      • Axonal degeneration; motor dominant

    Progress at icu day 10
    Progress at ICU day 10

    • Proximal power 4/5, distal power 5/5

    • Right brachioradialis reflex intact, right knee jerk has minimal response

    • Complained of severe headache and low back pain. ?neck stiffness on exam

    • ?Mechanical injury of AVM during LP

    Ct brain c spine l spine
    CT brain + C-spine + L-spine

    • Brain showed nil significant abnormality

    • No abnormal vasculature in cervical cord

    • Small enhancing vessels along surface of thecal sac at level down to L2

    • No evidence of bleeding from vessel

    Further progress
    Further progress

    • Off RT and oral diet tolerated since day 11

    • Discharge to general ward on day 15

    • Anti-Ganglioside Q1b 105 (<20)

    • ANF 1: 80; Anti-ds DNA 13 (<35)

    • C-ANCA weak +ve; PR3-ANCA 6 (<20)

    • Cold agglutinin 8 (<32)

    • Lupus anticoagulant not detected

    • Anti-cardiolipin IgG 9.5 (weak +ve)

    At rehabilitation
    At rehabilitation

    • Repeated NCT on day 19 showed improving polyneuropathy. Yet EMG showed equivocal MG features

    • Repeated Tensilon test on day 25  Still NEGATIVE result

    • Neurology opinion  not to resume Mestinon since MG not the dominant illness

    • Home on day 48

    Neurology fu
    Neurology FU

    • No ocular/ bulbar or peripheral symptom

    • Private MRI brain and brain stem

       bilateral frontal lobe atrophy only

    • Imp: assay for AChR binding antibody in HA is ELIZA, may not be specific enough

    • Decision: check AChR binding antibody (RIA) + AChR modulating antibody + AChR blocking antibody

    Myasthenia gravis overview
    Myasthenia Gravis overview

    • Autoimmune disease

    • Antibodies against post-synaptic acetylcholine receptor (AChR), or receptor associated protein (muscle-specific TK)

    • Fluctuating weakness of muscles in various combination of ocular; bulbar; limb; resp

    • Two clinical form: Ocular vs. Generalized

    Presenting symptoms
    Presenting symptoms

    • Ocular: >50%. Among ocular presentation, >50% progress to generalized in 2 years

    • Bulbar: 15%. Dysarthria/ dysphagia and fatigable chewing

    • Proximal limb: <5% as presenting symptom

    • Rare: isolated neck; isolated resp; isolated distal limb weakness

    Bedside diagnostic test of mg
    Bedside diagnostic test of MG

    • Tensilon test:

      • Sensitivity is 0.92 for ocular;

      • Sensitivity is 0.88 for generalized

      • False +ve: MND; brainstem tumor

  • Ice-pad test:

    • Best use for ocular MG

    • Sensitivity: 0.94 for ocular;

    • Sensitivity: 0.82 for generalized

      Neuromuscular disorders 2006; 16: 459-67

  • Ice test
    Ice test

    2 min ice

    Ophthalmology 1999: 106:1282

    Electrophysiological studies
    Electrophysiological studies

    Repetitive nerve stimulation (RNS)

    • Motor nerve is stimulated 6-10 times under low frequencies (2-3 Hz)

    • Positive result if decrement in compound muscle action potential >10% within 4-5 stimuli

    • Post-activation exhaustion

    • Post-tetanus potentiation

    • Sensitivity: 50% if ocular

    • Sensitivity: 75% if generalized



    30 seconds post-ex

    Post-activation exhaustion

    Acetylcholine receptor antibodies
    Acetylcholine receptor antibodies

    • Binding antibody

      • Most sensitive: 0.93 in severe generalized MG

      • False +ve in Eaton-Lambert; MND; myositis

      • Positive in SLE; PBC; thymoma; relative of MG

  • Blocking

    • Found in 50% of generalized disease

    • May be seen in 1% of MG with negative binding antibody

  • Modulating

    • Increases sensitivity only ~5% to binding antibody

      Neurology 1997; 48 (5): S23-27

  • Other antibodies
    Other antibodies

    • Striational antibody (anti-striated muscle)

      • Present in 30% of MG only, but 80% in those thymoma-assocated MG

      • Useful marker of thymoma at age 20-50

  • Muscle-specific receptor TK (MuSK)

    • Present in 50% of Ach-R Ab negative case

    • ?Different pathogenesis with seropositive

    • Oculobulbar rather than pure ocular

    • Nil thymoma or even ?thymic atrophy

    • Respond less to cholinesterase inhibitor

      Semin Neurol 2004; 24:31

  • Evaluation of 550 patients with MG titre high or very high at OPD

    Saunders 2001

    History of guillain barre syndrome
    History of Guillain Barre Syndrome titre high or very high at OPD

    Landry’s ascending paralysis 1859

    • Landry described 10 cases of weakness which ascended from lower limb to become generalized, and one of died of asphyxia

    • “usually a motor disorder characterized by a gradual diminution of muscular strength with flaccid limbs and without contractures, convulsions or reflex movements”

    • “weakness spreads rapidly from the lower to the upper parts of the body with a universal tendency to become generalised”

    • Landry offered no explanation of disease

    • Guillain and Barre spotted two soldiers in WWI becoming partially paralyzed, but then recovered spontaneously

    • With Strohl, a paper was published in 1916, reporting educed reflexes and CSF finding of raised protein without high WCC

    • In 1927, Guillain Barre syndrome was introduced, but Strohl…...

    Guillain partially paralyzed, but then recovered spontaneously



    Essential features of gbs
    Essential features of GBS partially paralyzed, but then recovered spontaneously

    • Progressive symmetrical muscle weakness associated with depressed deep tendon reflexes, usually begins at proximal legs

    • Severity varies a lot from mild difficulty in walking to complete paralysis and respiratory failure

    • Extremities, facial, bulbar and respiratory muscles are affected in combination

    Other features of gbs
    Other features of GBS partially paralyzed, but then recovered spontaneously

    • Facial weakness >50%

    • Oropharyngeal weakness 50%

    • Oculomotor weakness 15%

    • Respiratory failure  ventilation 30%

    • Begins from face and UL 10%

    • Paresthesias in hand/feet 80% (Yet nil sign)

    • Prominent severe back pain

    • Dysautonomia 70% (e.g. HT alt with shock)

      NEJM 1992; 326: 1130

    Temp partially paralyzed, but then recovered spontaneously





    Off sedation

    On sedation

    Off sedation















    ICU intubation

    8P 9/3

    8A 10/3

    8P 10/3

    8A 11/3

    8P 11/3

    Atypical gbs features
    Atypical GBS features partially paralyzed, but then recovered spontaneously

    • Meningism

    • Papilloedema

    • Vocal cord palsy

    • Hearing loss

    • Mental state change e.g. hallucination, delusion and vivid dream has been reported in a cohort of 139 patients of GBS in ICU

      Brain 2005; 128: 2535

    Gbs pathogenesis
    GBS Pathogenesis partially paralyzed, but then recovered spontaneously

    • Heterogenous syndrome caused by immune-mediated peripheral nerve damage after being evoked by antecedent infection

    • Acute inflammatory demyelinating polyradiculoneuropathy (AIDP): epitopes in Schwann cell surface membrane

    • Acute motor axonal neuropathy (AMAN): epitopes in axonal membrane

    Possible antecedent infections
    Possible antecedent infections partially paralyzed, but then recovered spontaneously

    • Campylobacter jejuni

      • Generate antibody to specific ganglioside GM1

      • 60% of AMAN/ AMSAN

      • Axonal degeneration  worse prognosis

  • CMV/ Epstein-Barr virus/ Mycoplasma

  • HIV

  • ?VZV/ HSV/ H influenzae

  • Diagnostic criteria ninds
    Diagnostic criteria (NINDS) partially paralyzed, but then recovered spontaneously

    • Required features

      • Progressive weakness >1 limb, ranging from minimal LL to complete tetraparesis, bulbar/facial muscles and ophthalmoplegia

      • Areflexia. Typiclly global areflexia, but distal areflexia + hyporeflexia at knee/ biceps will suffice

    Diagnostic criteria ninds1
    Diagnostic criteria (NINDS) partially paralyzed, but then recovered spontaneously

    • Supportive features

      • Progression of symptoms over days to 4/52

      • Symmetrical involvement

      • Bilateral facial nerve weakness

      • Autonomic dysfunction

      • Mild sensory symptoms/ signs

      • Raised CSF protein with normal white cell

        Ann Neurol 1978; 3: 565

    Nerve conduction test
    Nerve conduction test partially paralyzed, but then recovered spontaneously

    • Early change (~1 week)

      • Signify nerve root demyelination

      • Absent or prolonged F waves

      • Absent H reflexes

  • Intermediate change (~1-2 weeks)

    • Increased distal latency

    • Temporal dispersion of motor response

  • Late change (> 3-4 weeks)

    • Slowing of conduction velocity

  • Gbs variant
    GBS variant partially paralyzed, but then recovered spontaneously

    • Acute motor axonal neuropathy (AMAN)

    • Acute motor and sensory axonal (AMSAN)

    • Pharyngeal-cervical-brachial

    • Paraparesis only

    • Acute pandysautonomia

    • Miller-Fisher syndrome

    • Bickerstaff encephalitis

    Differential diagnosis for gbs
    Differential diagnosis for GBS partially paralyzed, but then recovered spontaneously

    • Acute polyneuropathies

    • Vasculitis

    • Spinal cord: compression; myelitis

    • Neuromuscular junction: MG; Eaton-Lambert; botulism

    • Muscle: polymyositis; CIM

    Miller fisher syndrome
    Miller Fisher syndrome partially paralyzed, but then recovered spontaneously

    • Triad: ophthalmoplegia, ataxia and areflexia

    • 20% patient may have extremities weakness

    • Anti-Ganglioside q1b antibody present in 85-90% of cases

    • NCT shows absent or diminished sensory response, and may show similar change of AIDP for cases with weakness

    • CSF has similar change with GBS

    Differential diagnosis for mfs
    Differential diagnosis for MFS partially paralyzed, but then recovered spontaneously

    • Brainstem stroke

    • Myasthenia gravis

    • Wernicke encephalopathy

    • Other neuromusclar junction disease e.g. Eaton-Lambert, botulism

    • Bickerstaff encephalitis: ophthalmoplegia + ataxia + hyper-reflexia + anti-G Q1b +ve

    Treatment of mfs
    Treatment of MFS partially paralyzed, but then recovered spontaneously

    • Supportive care including ventilatory support, DVT prophylaxis, pain control

    • Cardiovascualar monitoring and control

    • Cholinesterase inhibitor not useful

    • Immunomodulating therapy: IVIG; plasmapheresis

    • Steroid has not been shown beneficial

    Plasma exchange
    Plasma exchange partially paralyzed, but then recovered spontaneously

    • Maximal benefit when given within 7 days

    • ?Optimal number of exchange. Possibly lying between 4-6 exchanges

    • Dose of volume: 200-250ml/kg weight

    • Shorten median time to recover walking by 40-50% compared to supportive treatment

    • May be a problem in hemodynamics

    Iv ig
    IV IG partially paralyzed, but then recovered spontaneously

    • Five days of IVIG of 0.4g/kg body weight

    • No inferiority compared to plasmapheresis

    • Common minor side-effect: headache

    • Other effects: aseptic meningitis; allergy; skin rash; acute renal failure

    • Life-threatening anaphylaxis reported

      Brain 2007; 130: 2245-2257

    Prognosis partially paralyzed, but then recovered spontaneously

    • Median time to walk unaided 53-85 days

    • 5-10% patients with prolonged ventilator dependency, and incomplete recovery

    • Overall mortality 5%; 20% ventilator cases

    • Poor prognosis indicator: old age; rapid onset; diarrhoea preceded; ventilator need; reduced distal motor response amplitude <20% of normal; axonal degeneration

    In summary our patient
    In summary, our patient partially paralyzed, but then recovered spontaneously

    • Past history of ocular MG

    • Symptom and sign suggest MFS

    • MRI shows bystander vascular malformation around spinal cord

    • NCT showed axonal degeneration

    • Improved rapidly

    • Presence of anti-gangliose Q1b antibody

    • Anti-AchR antibodies signify underlying MG

    Wish you happy lunar new year partially paralyzed, but then recovered spontaneously