Guillain Barre Syndrome-REVISED FINAL Orange2

GUILLAIN- BARRE

SYNDROME

Minnie M. Chavez, M.D.

June 30, 2011

GRAND ROUNDS

Variable Leo Claire Dianne Kervin

Age/Sex 16/ M 14/F 12/F 2/M

Preceding infection

Respiratory

Respiratory

Respiratory

Respiratory

Quadriparesis

Yes Yes Yes Yes

Bulbar weakness

Yes Yes Yes Yes

Cranial neuropath

y

Yes Yes Yes Yes

Variable Leo Claire Dianne

Kervin

Nerve conduction

studies

AMANSevere motor denervation due to severe axonal dysfunction and demyelinating process

AMANDay 30: severe motor denervation RUE/RLE

AMSANDay 7: severe sensorimotor denervation all limbs; motor denervation was due to severe demyelinating and axonal dysfunction

AMANDay 6: severe motor denervation both upper & lower levels tested. SensoryPotential were relatively spared

OBJECTIVES1.To present an atypical

case of post - Rubeola GBS

2.To discuss the approach to diagnosis, differentials, immuno pathogenesis, clinical course and complications in the context of a multi-disciplinary management

GENERAL DATA

16 years oldMaleRight handedFilipinoRoman CatholicCagayan De OroApril 25, 2011

CHIEF COMPLAINT

Difficulty of breathing

HISTORY OF PRESENT ILLNESS

11 days

fever cough rash

pains numbness weakness

dyspnea


fever cough rash

10 days


dyspnea


fever cough rash

7 days


dyspnea


fever cough rash

6 days


dyspnea


fever cough rash

pains

5 days

numbness weakness

dyspnea


fever cough rash

pains numbness

4 days

weakness

dyspnea


fever cough rash

pains numbness

3 days

weakness

dyspnea


fever cough rash


dyspnea

2 days


fever cough rash

pains numbness

Day of Admission

weakness

dyspnea

FAMILY HISTORY

34

5670

192932

BIRTH AND MATERNAL HISTORYΘBorn to a 40 year old, G5P5

(5005)ΘNon-smoker, non-alcoholic

beverage drinker motherΘRegular prenatal check-ups

to a private obstetrician ΘNo maternal illnessΘNo intake of abortifacient

nor exposure to radiationΘFull term ΘNormal spontaneous

delivery ΘHospital in Cagayan De Oro

assisted by an obstetrician ΘNo fetomaternal

complications

NUTRITIONAL HISTORY

Θ Patient was breastfed for few days followed

by milk formulaΘ Regular diet consists of fried

fish, eggs and bread in breakfast, soup, rice and fish at lunch, and rice, fish and meat at dinner

Θ No food preference

IMMUNIZATION HISTORY

Θ BCGΘ DPT-OPV x 3 dosesΘ Hepatitis B x 3 dosesΘ MeaslesΘ MMR at 5 and 10

years oldΘ HiB Θ Varicella vaccines

GROWTH AND DEVELOPMENTAL HISTORY

Recalled developmental milestones were achieved at appropriate ages

HEADSSSΘH Patient is closer to his

mother. At home, he participates in household chores like washing the dishes and preparing meals

ΘE Presently, he is a 2nd year college student taking up Industrial Engineering in De La Salle University- Taft Avenue with three failed grades, however he claimed that his favorite subject is Science

HEADSSSΘA He enjoys playing soccer and other

outdoor physical activities like mountain climbingΘD He has no predilection to drugs nor to

dietingΘS At present, he has no relationship with

the opposite sex but admitted having a relationship in the past that lasted for 2 yearsΘS He has no suicidal ideationΘS He attends mass on Sundays

PAST MEDICAL HISTORY

Θ Diagnosed with Bronchial asthma

Θ No previous head traumaΘ No previous hospitalizationsΘ No allergies to food or drugs

PHYSICAL EXAMINATIONWeak looking, bed-borne, and in respiratory distress Vital Signs: BP 130/70 CR 160 bpm RR 41 bpmT 36.8 CWeight : 62.5 kg Height : 172. 7 cm BMI : 21 kg/m2 HC : 50 cmWarm to touch with generalized brawny desquamation and hyperpigmentation

PHYSICAL EXAMINATION Anicteric sclerae, hyperemic conjunctivae, no nasal discharge, no tonsillopharyngeal congestion, no cervical lymphadenopathiesSymmetrical chest expansion, decreased breath sounds on the right with subcostal retractions and crackles on bilateral lung fieldsAdynamic precordium, apex beat at 5th left intercostal space mid-clavicular line, tachycardic, no murmursFlat abdomen, normoactive bowel sounds, soft, non-tender, no hepatosplenomegalyTight sphincteric tonePulses full and equal, no cyanosis nor edema

NEUROLOGICAL EXAMINATION

He is oriented to person, place and time .He has intact remote and recent memory. No agraphia, apraxia, dyscalculia, no left to right disorientationCranial Nerves:

I: intactII: Visual acuity 20/20, OU (Jaegers) ; no visual field cuts Fundoscopy: (+) ROR, clear media, AV ratio 2:3,

distinct disc margin, no retinal hemorrhages

II,III: pupils 2-3 mm equally reactive to light and accomodation

III, IV, VI: Extra ocular muscles full and equalV: good temporalis and masseter tone; V1-V3 intactVII: unable to raise eyebrows and wrinkle forehead, unable

to completely close both eyelids, unable to smile, unable to puff air into the cheeks

VIII: gross hearing intactIX, X: weak gag reflex, bilateral; dysphagia with pooling of

saliva (+) hoarse voice with dysphonia

XI: turns head to both sides against resistance; good shoulder shrug

XII: tongue midline on protrusion


Motor Exam: A. Strength

Manual Muscle Testing (MMT)

Right Left

Arm elevation 3/5 3/5

Arm adduction downward

3/5 3/5

Arm adduction across the chest

3/5 3/5

Arm abduction 3/5 3/5

Scapula adduction 3/5 3/5

Elbow flexion 3/5 3/5Elbow extension 3/5 3/5

Wrist Flexion 3/5 3/5Wrist Extension 3/5 3/5

Manual Muscle Testing (MMT)

Right Left

Finger Abduction 3/5 3/5Finger adduction 3/5 3/5Finger extension 3/5 3/5Finger flexion 3/5 3/5Hip flexion 2/5 2/5Thigh abduction 2/5 2/5Thigh adduction 2/5 2/5Hip extension 2/5 2/5Knee extension 2/5 2/5Knee flexion 2/5 2/5Foot dorsiflexion 2/5 2/5Foot inversion 2/5 2/5Foot eversion 2/5 2/5Plantar flexion 2/5 2/5Toe flexion 2/5 2/5Toe extension 2/5 2/5


B. Tone – symmetrically hypotonic in all extremitiesC. Absence of atrophy/BulkD. No muscle tenderness/ pain on palpationE. No involuntary involvementsSensory: intact pain and temperature, position and vibration, light touch, 2-point discriminationCerebellar: Because of the weakness patient was unable to do FTNT, tandem walking and other cerebellar function testsDeep Tendon Reflexes Right Left

Biceps (C5, C6) +1 +1Brachioradialis (C5, C6) +1 +1

Triceps (C6, C7, C8) +1 +1

Patellar (L2, L3, L4) 0 0

Achilles Tendon (S1, L5) 0 0

No extensor toe sign, no clonusMeningeals: no nuchal rigidity

2+

Salient Features

Θ 16 year old male, right handedΘ Preceded by a 10 day history of a systemic

viral illness Θ Low back pains and paresthesias in the

toesΘ Acute ascending symmetric motor

weaknessΘ Normal mental statusΘ Facial diplegia, hoarseness, decreased

muscle strength, hypo/areflexia, no extensor toe sign

2+

2+

Approach to Diagnosis

Is there a disease in the

nervous system?

Yes

2+

Levelize the LesionCerebral cortex

Cerebellum

Brainstem

Spinal Cord

2+

Levelize the Lesion

Motor Neurons• Amyotrophic Lateral Sclerosis

Muscle Fibers• Myotonic Dystrophy

Neuromuscular Junctions• Myasthenia Gravis

Peripheral Nerve• Guillain-Barre Syndrome

2+

LocalizATIONUpper Motor

Neuron

Hyperactive

Absent

Absent

Increased

Positive

Lower Motor

Neuron

Absent

Present

Present

Decreased

Negative

Reflexes

Atrophy

Fasciculations

Tone

Babinski

Patient

Absent

Absent

Absent

Decreased

Negative

THE PERIPHERAL NERVE

Which part of the peripheral nervOUS

SYSTEM?

• Anterior horn cell x

• Neuromuscular junction x

• Muscle x

Roots

Nerve

PERIPHERAL NERvous system

2+

What is the etiology?

Infectious

Toxic Vascular

Traumatic

Neoplastic

Metabolic Genetic

Post-infectious

AUTOIMMUNE

Peripheral nerve disorders

Polyneuropathy

Mononeuropath

y

Mono neuritis complex

CLASSIFICATION OF POLYNEUROPATHIES

TYPES OF FIBERS

INVOLVED

PATHOLOGY

TEMPO

DIFFERENT DISEASES WITH polyneuropathies

ΘFatigue

ΘDelayed DTRs

ΘSlow movement and speech

ΘCold intolerance

ΘConstipation and weight gain

HYPOTHYROIDISM

ΘDistal to proximal involvement

ΘSlowly progressive (over months) abnormalities in sensory, motor, autonomic, and gait function

Θ No history of chronic alcohol use with nutritional deficits

ALCOHOLIC NEUROPATHY

TOXIC NEUROPATHY

ΘDrug abuse and exposure to chemicals

ΘDistal > proximal

ΘPains

METAL NEUROPATHY

2+

immunopathology

Spinal nerve roots

Distal nerve segments

Around potential nerve entrapment sites

Lymphocyte attach to the endoneural

vessels

Lymphocyte migration and breakdown of

myelin

Interruption of the axon, polymorphonuclear

leukocytes

Denervation atrophy of muscle

IMMUNOPATHOGENESIS

TRIGGERS

50% 32%

Upper Respiratory Tract InfectionCytomegalovirusEpstein-Barr VirusGastro-intestinal Tract InfectionCampylobacter jejuni

Vaccination, Malignancies, Bone marrow transplantation, surgeries

2+

ImmunoPathogen

• A process wherein exogenous antigens have structural appearance to self-antigens

• The host generates an immune response to the inciting factor (usually an infectious organism) that shares epitopes with host’s affected tissue

MOLECULAR MIMICRY

CELLULAR AND HUMORAL IMMUNITY

COMPLEMENT SYSTEM

2+

Working Impression

Acute post- Rubeola poly radiculoneuropathy (Guillain-Barre Syndrome) with impending respiratory failure

HISTORICAL BACKGROUND

Θ Landry's ascending paralysis, French

polio, acute idiopathic polyneuritis, or acute idiopathic polyradiculoneuritis

Θ French physician Jean Landry had

described the condition in 1859

Θ Named for Georges Guillain and Jean Alexandre Barre: increased level of protein with normal cell count in cerebrospinal fluid (1916)

DEFINITION

An acute, immune-mediated disorder of peripheral nerves, spinal roots, and cranial nerves, commonly presenting as a rapidly progressive, areflexive, relatively symmetric ascending weakness of the limb, truncal, respiratory, pharyngeal, and facial musculature, with variable sensory and autonomic dysfunction

What’s new in Guillain-Barré syndrome? J Pritchard; Dr Jane Pritchard, Neurology Specialist Registrar, The National Hospital for Neurology and Neurosurgery, Queen Square, London; WC1N 3BG, UK; [email protected]

DIAGNOSTIC CRITERIAFeatures required for diagnosis

Progressive weakness in both arms and legsAreflexia

Features strongly supporting diagnosisProgression of symptoms over days, up to four weeksRelative symmetry of symptomsMild sensory symptoms or signsCranial nerve involvement, especially bilateral weakness of facial musclesRecovery beginning two to four weeks after progression ceasesAutonomic dysfunctionAbsence of fever at onsetHigh concentration of protein in cerebrospinal fluid, with fewer than 10 cells per cubic millimeterTypical electrodiagnostic features

Features excluding diagnosisDiagnosis of botulism, myasthenia, poliomyelitis, or toxic neuropathyAbnormal porphyrin metabolismRecent diphtheriaPurely sensory syndrome, without weakness

Annual incidence globally is 0.5 - 1.5 cases per 100,000 population per year < 18 years old. Youngest recorded patient: 2 years old,male predominance. Axonal type in Asians.

From the Philippine Pediatric Society Registry: 168 GBS patients have been reported from a total of 992, 341 cases

From the Philippine Children’s Medical Center: 120 patients have been seen from 1995 to June 2011

Source: Pediatric Guillain-Barre Syndrome Author: Sameer Chhibber, MD, FRCPC; Chief Editor: Amy Kao, MD

www.pps.org/ Registry.

Philippine Children’s Medical Center – Medical Records Section

GLOBAL AND LOCAL Incidence

2+

Clinical Manifestations

WeaknessReduced or absent reflexesSensory disturbancePainCranial nerve involvementRespiratory dysfunctionsDysautonomia

TWO Pathologic classificationS

Demyelinating

Axonal

AIDP

MFS BBE

PCB

Sensory

AMSAN

AMANAutonomic

FD

SPECTRUM OF GBS 2010

JB Winter/ Journal of Immunology 231 (2011)

variantsAcute Motor and Sensory

Axonal Neuropathy

Acute Motor Axonal Neuropathy

Miller Fischer Variant

Pure Motor Variants

Pure Sensory Variants

Pure Dysautonomia Variant

Pharyngeal-Cervical-Brachial Variant

Paraparetic Variant

Less Common variants

ELECTROPHYSIOLOGICAL CRITERIA

Atleast one of the following in each of atleast 2 nerves, or atleast two of the following in one nerve if all others

inexcitable and dCMAP > 10% LLN: Motor conduction velocity < 90% LLN (85% if dCMAP < 50% LLN); Distal motor latency >

110% ULN (> 120% if dCMAP < 100% LLN) pCMAP/dCMAP ratio < 0.5 and dCMAP > 20% LLN, F response latency > 120% ULN

None of the features of AIDP except one demyelinating feature allowed in one nerve

if dCMAP < 10% LLN, sensory action potentials amplitudes < LLN

None of the features of AIDP except one demyelinating feature allowed in one nerve if dCMAP < 10% LLN, sensory action potentials

amplitudes normal

AIDP

AMSAN

AMAN

Classification of GBS syndrome and related disorders

Typical antiganglioside antibodies by pathology

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)

Unknown

Acute motor and sensory axonal neuropathy (AMSAN)

GM1,GM1b,GD1a

Acute motor axonal neuropathy (AMAN) GM1,GM1b,GD1a, GaINac-GD1a

Acute sensory axonal neuropathy GD1b

Acute pandysautonomia Regional variants Fisher’s syndrome Oropharyngeal

GQ1b,GT1aGT1a

Overlap Fisher’s syndrome/ GBS overlap syndrome

GQ1b,GMi, Gmib, GD1a, GaINac-GD1a

Θ Multifocal mononuclear cells infiltration throughout the peripheral nervous system in which the distribution of inflammation corresponds to the clinical deficit

Θ Macrophages invade the myelin sheaths and denude the axons

AIDPAcute Inflammatory Demyelinating

Polyneuropathy

ΘActivation of anti-GQ1b and anti-GT1a antibodies that target oculomotor and bulbar nerves

ΘThe presynaptic nerve terminal axons and perisynaptic Schwann cells are damaged

FISHER’S SYNDROME

ΘThe pathology resembles that in AMAN, with the same pattern of macrophage invasion of the perinodal space

ΘThe dorsal, as well as the ventral, roots are affected

ΘThere is the same paucity of lymphocytic inflammation consistent with an antibody-mediated pathogenesis

AmSanAcute Motor Sensory Axonal Neuropathy

Θ Macrophages invade the nodes of Ranvier, where they insert between the axon and the surrounding Schwann cell axolemma, leaving the myelin sheath intact

Θ Severe: axons are damaged in the ventral root, which may cause severe degeneration of the whole axon

AmanAcute Motor Axonal Neuropathy

Course in the ICU

ADMISSION

CBC

Hgb 156

Hct 0.46

WBC 17.7

Seg 0.92

Lym 0.02

Mono 0.06

Platelet 494

ABG

pH 7.4

pC02 39

p02 70

HC03 24.2

02 sat

BE -0.5

Θ Is the most common serious complication of Guillain-Barre syndrome

Θ Acute Respiratory Failure:1. Alveolar-arterial oxygen gradient of

300mm Hg with an inspired oxygen fraction of 1.0

2. Arterial PC02 above 45mm Hg3. Static inspiratory pressures below 30

cm H20

Mechanical failure of the thoracic bellows is the problem

Θ Intubation criteria 1. Mechanical ventilator failure with

reduced expiratory VC of 12-15 ml/kg2. P02 below 70 mm Hg with inspired room

air3. Severe oropharyngeal paresis with

difficulty clearing secretions or repeated coughing and aspiration after swallowing

Θ Mortality rate was 3% for all patients who could not walk and zero for those who required mechanical ventilation directly as a result of GBS

Θ Complications of tracheostomy in GBS: 7-55%

2+

investigations

LUMBAR PUNCTURE AND CSF ANALYSIS

Θ Before treatment because IVIG can cause aseptic meningitis

Θ WBC < 10 x 10 cells/ L

Θ Raised protein but normal in the first weekWhat’s new in Guillain-Barré syndrome? J Pritchard; Dr Jane Pritchard, Neurology

Specialist Registrar, The National Hospital for Neurology and Neurosurgery, Queen Square, London; WC1N 3BG, UK; [email protected]

IMMUNO THERAPY

The main modalities of therapy: Θ Intravenous immune

globulinΘ Plasmapheresis

Plasma Exchange

IVIg Combined

Treatments

Corticosteroid

s

Strong evidence supports

PE recommended in nonambulant patients within 4 weeks of onset of neuropathic symptoms(Level A*, Class II**)

IVIG recommended in non ambulant patients within 2 weeks of onset of neuropathic symptoms(Level A, Class II)

Sequential treatment with PE followed by IVIG does not have a greater effect than either treatment given alone (Level A, Class I)

Steroids not recommended in the treatment of GBS (Level A, Class I)

EVIDENCE FOR IMMUNOTHERAPY

2003 Practice Parameter Quality Standards Subcommittee of the American Academy of Neurology

2+

PLASMAPHERESIS

2+

PLASMAPHERESIS

Course in the ICU

2nd – 5th Hospital Day

WEANING

Villaure, Wilson. Guillain-Barré syndrome: Treatment and Prognosis Version 7. Knol. 2009 Feb 8. Available from: http://knol.google.com/k/wilson-villaure/guillain-barré-syndrome/1bbsle13m97c0/127.

Θ Improvement in strength

Θ Serial Pulmonary function tests

Θ Tracheostomy

Θ The autonomic neuropathy involves both the sympathetic and parasympathetic systems

Θ Manifestations: alternating hypotension with hypertension, urinary retention, sweating abnormalities, and sinus tachycardia

Villaure, Wilson. Guillain-Barré syndrome: Treatment and Prognosis Version 7. Knol. 2009 Feb 8. Available from: http://knol.google.com/k/wilson-villaure/guillain-barré-syndrome/1bbsle13m97c0/127.

ACUTE PHASE REHABILITATION

Orsini, M., de Freitas M., Presto, M. Guidelines for Neuromuscular Rehabilitation In Guillain-Barre Syndrome: What can we do ? Rev Neuroscience 2010; 18: 4: 572-580

Course in the ICU

6th - 7th Hospital Day

Thyroid function tests

Free T3 < 0.05 (1.4-4.2)

Free T4 2.135 (0.8-2 ng/dl)

TSH 0.208 uIU/ml(0.4-7

uIU/ml)

Peeters RP, van der Geyten S, Wouters PJ, Darras et al Tissue thyroid hormone levels in critical illness. Journal of Clinical Endocrinology and Metabolism. 90: 6498-6507. 2005

TSH T4 T3 Interpretation

High Normal Normal Mild (subclinical) hypothyroidism

High Low Low or normal Hypothyroidism

Low Normal Normal Mild (subclinical) hyperthyroidism

Low High or normal

High or normal

Hyperthyroidism

Low Low or normal

Low or normal Nonthyroidal illness; rare pituitary (secondary) hypothyroidism

NON THYROIDAL ILLNESS SYNDROME

Peeters RP, van der Geyten S, Wouters PJ, Darras et al Tissue thyroid hormone levels in critical illness. Journal of Clinical Endocrinology and Metabolism. 90: 6498-6507. 2005

Course in the ICU


SIADH

Θ 1/3rd of patientsΘ Rarely symptomaticΘ In ventilated patients: 42% versus 19%Θ Average occurrence: 10 days after intubation (range 1-23 days)Θ Resolved after fluid restrictionΘ Downward osmotic resetting and enhanced renal sensitivity to ADH

2+

NeurophysiologyNCVAmplitudes of sensory nerve action potentials (SNAPs) evoked on antidromic stimulation of the left median, left ulnar, left radial, right and left (bilateral) sural nerves were normal. Distal sensory latencies were normal.Sensory nerve conduction velocities(NCVs) were normal.

No compound muscle action potentials (CMAPs) were evoked on proximal stimulation of right peroneal tibial nerve. Amplitude of the CMAPs evoked on stimulation of the left medial, left ulnar and bilateral peroneal nerves were severely reduced. Temporal dispersion was appreciated Motor latencies were generally prolongedMotor NCVs of the left median and left ulnar and right peroneal nerves were normal. Distal and proximal motor NCVs of the left peroneal nerve were normal and mildly slowed, respectively. Motor NCV of the left tibial nerve was mildly slowed

Course in the ICU


Plasma Renin

132.5 pg/ml

Supine: 1.1-20 pg/ml

Upright: 1.8-60 pg/ml.

PLASMA RENIN

ELEVATED LIVER FUNCTION TESTS

ELEVATED LIVER FUNCTION TESTS

Liver function disturbances in Guillain-Barre syndrome. A prospective longitudinal study in 100 patients P. G. Oomes, MD, F.G.A. van der Meche, MD, PhD and R. P. Kleyweg, MD, PhD

Θ 100 patients with Guillain-Barre syndromeΘ On admission, 38% showed an increase SGPT ..10% had

serologic evidence of recent cytomegalovirus infection. The remaining 28 patients were negative for other known causes of liver damage

Θ In the IVIg-treated group, 35% before to 69% shortly after treatment

Θ In the PE-treated group, 41% to 36%

Conclusion: Θ GBS patients had mild liver function disturbances

without obvious cause Θ IVIg was associated with mild transient liver

function disturbances through an unknown mechanism

Course in the ICU

13th -16th Hospital Day

Course in the ICU

17th- 23rd Hospital Day

Course in the ICU

24th – 26th Hospital Day

Course in the ICU

27th- 30th Hospital Day

2+

Treatment SUMMARY

Supportive care

Ventilatory support

Autonomic dysfunction

Nosocomial infections

Venous thrombosis

Nutritional support

Immune therapy

SUPPORTIVE CARE

Prophylaxis for deep vein

thrombosis

Bowel and bladder

care

Physical and

occupational

therapy

Psychosocial

support

2+

prognosis

Mortality rates range from 2 to 13%

Most common causes of death after GBS: respiratory failurecardiovascular and autonomic disturbancesthrombo-embolisms

15% have mild illness, remain ambulatory, and recovery after few weeks5-20% have fulminant course

low mean Compound Muscle Action Potential Amplitude (CMAP) - the most powerful predictor of poor recovery rate

Guideline for Neuromuscular Rehabilitation in Guillain-Barré Syndrome: What can we do? Marco Orsini, Marcos RG de Freitas, Bruno Presto, Rev Neurocienc 2010;18(4):572-580

Θ MonophasicΘ 10% - early

relapse in 1st week or two following treatment

Θ 3% - subsequent years

Θ CIDP

What’s new in Guillain-Barré syndrome? J Pritchard; Dr Jane Pritchard, Neurology Specialist Registrar, The National Hospital for Neurology and Neurosurgery, Queen Square, London; WC1N 3BG, UK; [email protected]

recurrence

2+

Final Diagnosis

Post-Rubeola Guillain-Barre Syndrome with respiratory failure, resolvedSecondary HypertensionSecondary HypothyroidismExposure Keratitis, OU

Follow-up

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Guillain Barre Syndrome-REVISED FINAL Orange2