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Is it MG Crisis? Dr Chan Yan Fat Alfred Caritas Medical

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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 ... – PowerPoint PPT presentation

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Title: Is it MG Crisis? Dr Chan Yan Fat Alfred Caritas Medical


1
Is it MG Crisis?
  • Dr Chan Yan Fat Alfred
  • Caritas Medical Center
  • 20/01/2009

2
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

3
Long term medication
  • L-thyroxine 75 microgram daily
  • Candesartan 8mg daily
  • Ventolin 2 puffs Qid PRN
  • Becotide 2 puffs BD
  • Pyridostigmine (Mestinon) 60mg BD

4
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

5
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

6
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7
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

8
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

9
Impression at ICU
  • Generalized MG with bulbar involvement
  • Precipitated by

10
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

11
Management by on-call MO
  • Keep NPO for possible intubation later
  • Increase Mestinon 60mg tds
  • Insert RT for medication
  • Check CBP/RFT/LFT/INR/ABG/ESR
  • Blood, sputum and urine for culture
  • Serum viral titre
  • Urgent plain CT brain

12
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

13
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14
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

15
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

16
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

17
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

18
  • Atypical presentation of MG!
  • Deterioration with iv Ig
  • Other pathology?

19
Can it be due to MG crisis
  • Pros
  • Symmetrical proximal muscle weakness
  • Previous ocular MG
  • Bulbar symptom
  • Precipitating factors of crisis seen
  • Cons
  • Different symptom and sign from past
  • Severity of physical sign not fluctuating
  • Global areflexia
  • Sensory symptoms

20
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

21
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22
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23
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

24
Can it be spinal cord insult?!
  • Pros
  • Tetraparesis
  • Areflexia
  • Hypotension
  • Normal cognitive function all along
  • MRI showed vascular lesion around cord
  • Cons
  • Proximal affected preferentially
  • No sensory level
  • Bulbar symptoms
  • Ophthalmoplegia, though improved
  • Normal cord signal

25
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 gt400ml. Failed
    extubation because of aspiration problem

26
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

27
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 (lt0.45, ELIZA method)

28
Every sign must have explanation
29
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

30
  • Retrospectively, look at the graph of vital
    signs.

31
Temp 40 39 38 37
BP/P 240 220 200 180 160 140 120 100 80 60
Off sedation
On sedation
Off sedation
SBP
Temp
Pulse
ICU intubation
8P 9/3
8A 10/3
8P 10/3
8A 11/3
8P 11/3
32
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

33
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

34
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

35
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

36
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

37
Our decision
38
Further progress
  • Off RT and oral diet tolerated since day 11
  • Discharge to general ward on day 15
  • Anti-Ganglioside Q1b 105 (lt20)
  • ANF 1 80 Anti-ds DNA 13 (lt35)
  • C-ANCA weak ve PR3-ANCA 6 (lt20)
  • Cold agglutinin 8 (lt32)
  • Lupus anticoagulant not detected
  • Anti-cardiolipin IgG 9.5 (weak ve)

39
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

40
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

41
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42
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

43
Presenting symptoms
  • Ocular gt50. Among ocular presentation, gt50
    progress to generalized in 2 years
  • Bulbar 15. Dysarthria/ dysphagia and fatigable
    chewing
  • Proximal limb lt5 as presenting symptom
  • Rare isolated neck isolated resp isolated
    distal limb weakness

44
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

45
Ice test
2 min ice
Ophthalmology 1999 1061282
46
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 gt10 within 4-5 stimuli
  • Post-activation exhaustion
  • Post-tetanus potentiation
  • Sensitivity 50 if ocular
  • Sensitivity 75 if generalized

47
MG
Normal
30 seconds post-ex
Post-activation exhaustion
48
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

49
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 2431

50
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51
  • Our patients had all three AchR antibodies
    positive, with titre high or very high at OPD

52
Evaluation of 550 patients with MG Saunders 2001
53
History of Guillain Barre Syndrome
  • Landrys 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

54
  • 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...

55
Guillain
Barre
Strohl
56
Essential features of GBS
  • 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

57
Other features of GBS
  • Facial weakness gt50
  • 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

58
Temp 40 39 38 37
BP/P 240 220 200 180 160 140 120 100 80 60
Off sedation
On sedation
Off sedation
SBP
Temp
Pulse
ICU intubation
8P 9/3
8A 10/3
8P 10/3
8A 11/3
8P 11/3
59
Atypical GBS features
  • 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

60
GBS Pathogenesis
  • 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

61
Possible antecedent infections
  • 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

62
Diagnostic criteria (NINDS)
  • Required features
  • Progressive weakness gt1 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

63
Diagnostic criteria (NINDS)
  • 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

64
Nerve conduction test
  • 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 (gt 3-4 weeks)
  • Slowing of conduction velocity

65
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66
GBS variant
  • Acute motor axonal neuropathy (AMAN)
  • Acute motor and sensory axonal (AMSAN)
  • Pharyngeal-cervical-brachial
  • Paraparesis only
  • Acute pandysautonomia
  • Miller-Fisher syndrome
  • Bickerstaff encephalitis

67
Differential diagnosis for GBS
  • Acute polyneuropathies
  • Vasculitis
  • Spinal cord compression myelitis
  • Neuromuscular junction MG Eaton-Lambert
    botulism
  • Muscle polymyositis CIM

68
Miller Fisher syndrome
  • 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

69
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70
Differential diagnosis for MFS
  • 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

71
Treatment of MFS
  • 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

72
Plasma exchange
  • 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

73
IV IG
  • 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

74
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75
Prognosis
  • 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 lt20 of normal
    axonal degeneration

76
In summary, our patient
  • 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

77
Wish you happy lunar new year
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