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Guillain-Barre Syndrome
‫סיפור מקרה‬
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‫בת שנתיים ושלושה חודשים‪ ,‬בריאה‬
‫מיילדות תקינה‪ ,‬אחת מתאומות‪ ,‬התפתחות תקינה‬
‫‪ 5‬ימים כאבים ברגל שמאל המעירים משינה בבכי‬
‫ביממה אחרונה מתנדנדת וצולעת בהליכה‪ ,‬משחקת‬
‫בישיבה‪ ,‬בלילה טרם קבלתה התעוררה כל שעה בבכי‬
‫בגלל כאב‬
‫שוללים טראומה‪ ,‬מחלות במשפחה‬
‫חודש טרם קבלתה מחלת שלשולים‬
‫חוסנה נגד שפעת חודש טרם קבלתה‪ ,‬קיבלה ‪OPV‬‬
‫אביה חלה ב‪ CMV -‬כארבעה חודשים לפני כן‬
‫נבדקה יום טרם קבלתה במיון ושוחררה‬
‫סיפור מקרה‬
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‫סימנים‪ :‬חום ‪ ,36.9‬דופק ‪ ,135‬סטורציה ‪98%‬‬
‫ערנית וחיונית‪ ,‬ללא מצוקה נשימתית‬
‫אישונים שוים ומגיבים לאור‬
‫ללא קשיון עורף או סימני גירוי מנינגיאלי‬
‫אא"ג‪ ,‬ריאות‪ ,‬לב ‪ ,‬בטן – ב‪.‬מ‪.‬פ‬
‫עור ללא פריחה או כתמים‬
‫שלד‪ -‬ללא נפיחות או אודם במפרקים‪ ,‬טווחי תנועה‬
‫שמורים‪ ,‬ללא רגישות גרמית‬
‫נוירולוגית‪ :‬רושם לטונוס תקין‪ ,‬הופקו רפלקסים‬
‫גידיים‪ ,‬הליכה אטקטית‪ /‬מתנדנדת‬
‫סיפור מקרה‬
‫מעבדה‪:‬‬
‫• ספירת דם תקינה‪:‬‬
‫‪WBC 13.4, HGB 13.8, PLT 375‬‬
‫• ‪CRP 0.5, ESR 10‬‬
‫• ‪GLU 65, UREA 23.5, CREAT 0.21, NA 140, K 4.8,‬‬
‫‪CPK 44.3, LDH 448, GOT 32.6‬‬
‫הדמיה‪:‬‬
‫• ‪ US‬פרקי ירכיים וברכיים‪ :‬ללא נוזל וללא הרמת רצועה‬
‫אילאופמורלית‪ ,‬ללא ממצא חריג אחר‬
‫• צילום ברכיים וירכיים תקין‬
‫סיפור מקרה‬
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‫יום לאחר אשפוזה החמרה‪ -‬יושבת ומסרבת ללכת‪ ,‬ללא‬
‫חום‪ ,‬אוכלת ומתנהגת כרגיל‪ ,‬שאר הסקירה המערכתית‬
‫תקינה‬
‫ניסיון הליכה‪ -‬הולכת ‪ 2‬צעדים ונופלת‪ ,‬ניסיון לקום ‪-‬‬
‫‪GOWER‬‬
‫מניעה גפיים בחופשיות ובסימטריות בישיבה‬
‫כוח גס בשתי הגפיים ‪4-3 / 5‬‬
‫החזרי פיקה – חלש בשמאל‪ ,‬לא הופק בימין‬
‫רושם שהתחושה שמורה‬
‫עצבים קרניאלים תקינים‪ ,‬פונדוסים תקינים‬
‫ללא רגישות על פני עמוד השדרה‪ ,‬מפרקים חופשיים‬
‫סיפור מקרה‬
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‫‪ CT‬מוח ועמוד שידרה‪ :‬תקין‬
‫ניקור מתני‪ :‬חלבון מוגבר (‪ ,)120‬גלוקוז ‪,56.8‬‬
‫ללא תאים‬
‫באבחנת גיאן ברה הוחל טיפול ב‪ 2 , IVIG-‬גרם‬
‫לק"ג מחולק ליומיים‪.‬‬
‫ניטור דופק‪ ,‬ל"ד‪ ,‬סטורציה‪ ,‬מתן שתן‬
‫סיפור מקרה‬
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‫החמרה במהלך האישפוז עם חולשה בידיים‪ ,‬לא‬
‫קמה משכיבה לישיבה‪ ,‬ישיבה לא יציבה‪.‬‬
‫ללא מעורבות בולברית‪ ,‬ללא מעורבות‬
‫אוטונומית‪ ,‬יציבה נשימתית‬
‫‪ 4‬ימים לאחר סיום הטיפול הלכה ללא עזרה‪,‬‬
‫אכלה ללא עזרה‪ ,‬עדיין לא הופקו רפלקסים‬
‫גידיים‪.‬‬
‫שוחררה למעקב מרפאתי‬
‫סיפור מקרה‬
‫בירור נוסף‪:‬‬
‫• ‪ 2‬דגימות צואה לפוליו‪ -‬שליליות‬
‫• תרבית צואה שלילית‬
‫• ‪ CMV‬חיובי בשתן‪ ,‬שלילי בנוזל שדרה‪.‬‬
‫• סרולוגיה ל‪ IGG :CMV -‬חיובי‪ IGM ,‬שלילי‬
Guillain-Barre Syndrome
• An acquired disease of the peripheral
nervous system
• Major features: weakness and areflexia
• The most common cause of acute flaccid
paralysis in all ages.
• No specific test to confirm the diagnosis
• A syndrome rather than a disease
nced Search
THE ORIGINAL PAPER 1916
Epidemiology
• Annual incidence: 0.4 – 1.7 / 100.000
• Rare before 1 year of age
• M:F - 1.5:1
Guillain-barre Syndrome
Clinical features
• Progressive weakness and diminished
deep tendon reflexes in a symmetric
distribution.
• Ascending progression – most common
• 5 – 10% upper >> lower
• 5-10% proximal >> distal
Guillain-barre Syndrome
Clinical features
• Sensory disturbances: 40% pain or
paresthesias
• Cranial nerves
• Autonomic disturbances – infrequent
but life threatening.
• 15-20% progress to respiratory
failure.
Guillain-barre Syndrome
diagnostic features
Clinical features
Stages:
• Progression phase- days to weeks,
max. 6 weeks. Period of major
complications
• plateau phase - days to weeks
• Recovery – weeks to months
clinical variants
Laboratory findings:
CSF
• normal cell count – up to 10
lymphocytes
• elevated protein – 80-200 mg/dl ,
after 1 week
Laboratory findings
Electrophysiological tests:
• 80% abnormal studies
• Multiple nerves must be studied
• Evidence of multifocal demyelination in
motor and sensory nerves.
• prolonged distal latency
• Reduction of the F WAVE response and HREFLEX.
• H REFLEX – single most sensitive test for
early GBS, absent in 97% of pts in the
first week (Gordon at al. neurol 2001)
Pathology
Depend upon the form of GBS.
AIDP and MILLER-FISHER:
• Inflammation and demyelination
• More severe inflammation at the
junction of dorsal and ventral roots
at the site of the dural attachment.
• Secondary axonal degeneration
Histology
Pathology
Motor and motor-sensory variants:
• Axonal degeneration without an
inflammatory response
• The immune process is directed at
the nodes of Ranvier
• No demyelination
Pathophysiology
• Immune mediated disease
• Possible mechanism: autoAB bind to
glycoproteins on peripheral myelin ,
causing a cascade of events which
eventually destroy the myelin.
Pathophysiology
• 50 – 70% have an antecedent illness
within the previous 4 weeks.
• URTI, gastroenteritis
• C. Jejuni – more severe symptoms
• CMV, EBV
The Lancet; Nov 5-Nov 11, 2005; 366, 9497;
• Campylobacter is the most commonly
identified precipitant of GBS
• Demonstrated in up to 30% of cases
• 27 / 103 pts (26%) with GBS had
evidence of C.jejuni infection
compared with 1% of controls.
• 70% of those infected with C.jejuni
reported diarrheal illness within 12
weeks before the onset of GBS.
Guillain-barre Syndrome
and Campylobacter
• Campylobacter associated GBS have
a worse prognosis – slower recovery
and greater residual neurological
disability.
• The risk of developing GBS during the 2
months after C.jejuni infection is 100-fold
higher than the risk in the general
population!
(30.4/100,000 compared with
0.3/100,000)
J Infect Dis. 2006 Feb 15;193(4):547-55.
Comprehensive Analysis of Bacterial Risk Factors for
the Development of Guillain-Barre Syndrome after
Campylobacter jejuni Enteritis.
Koga M, Gilbert M, Takahashi M, Li J, Koike S, Hirata K, Yuki N.
• Specific strains (class A, serotype HS:19)
were found more frequently (78% vs 17%)
in patients with GBS than in patients with
enteritis.
• Class A strain carries gangliosid -like
lipo-oligosaccharide
• Increased risk of producing
antiganglioside autoantibodies and
developing GBS.
Pathophysiology
Immunizations:
• “swine flu” vaccine (1976)
• Rabies vaccine
AAP News Vol. 26 No. 11 November 2005, p. 6
© 2005 American Academy of Pediatrics
Guillain-Barré cases among recipients of meningococcal conjugate
vaccine
The Food and Drug Administration (FDA) and the Centers
for Disease Control and Prevention (CDC) are investigating
six cases of Guillain-Barré syndrome that occurred after
receipt of meningococcal conjugate vaccine (MCV4,
Menactra – sanofi pasteur). This number of cases of GuillainBarré syndrome is not greater than would be expected in an
unvaccinated teenage population. However, the onset of
neurologic symptoms within two to five weeks following
vaccination is a reason to gather further information.
The AAP Committee on Infectious Diseases continues to
recommend MCV4 for adolescents
"Anyone who has ever had Guillain-Barré syndrome
should talk with their doctor before getting MCV4."
Differential Diagnosis
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encephalopathy
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• Neuromascular
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junction
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Constipation,
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• muscle
swallow
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Cerebral
Cerebellar
level
Spinal
Anterior horn cell
Peripheral nerve
Hypotonia,
Bilateral strokes
pleocytosis
Acute cerebellar ataxia
Transverse myelitis
Compressive myelopathy
Poliomyelitis (wild/ vaccine)
Toxic neuropathy
Asymmetric,
Diphtheria
pure motor
Porphyria
Tick paralysis
Botulism
Ptosis,
Myasthenia gravis
reflexes
Neuromascular blocking agents
Acute inflammatory myopathies
Metabolic: periodic paralysis
Proximal
weakness
Therapy
• Supportive
• Monitoring: BP, HR, RR, TEMP.
• Frequent physical examinations to
establish a trend.
• Serial lung function testing
• If dysphagia or shoulder weakness:
respiratory assistance may be
necessary.
Therapy
Indications for transfer to ICU:
• Respiratory failure
• Autonomic dysfunction
• Bulbar dysfunction
• Bilateral facial weakness
• aspiration
Therapy
• Anticipate the need for mechanical
ventilation – better to intubate electively!
• Vital capacity < ½ normal for age or <15-20
ml /kg
• Serial measurements of pulmonary
function tests were most helpful in
detecting the risk of respiratory failure
(Arch Neurol 2001)
• Children < 6 years – monitor fatigue: blood
gases, chest x-ray.
Therapy
American Academy of Neurology
recommendations for treatment of GBS:
indications for treatment:
• Rapidly progressing weakness
• Worsening respiratory status or need for
mechanical ventilation
• Significant bulbar weakness
• Inability to walk unaided.
GBS Motor Disability Scale
grade
Motor disability
0
Normal
1
Minor symptoms
2
Able to walk 5 meters unaided
3
Able to walk 5 meters aided
4
Bedridden
5
Respiratory failure
6
death
Therapy
Corticosteroids:
• First immunotherapy for GBS
• “Corticosteroid medications do not seem
to help improve symptoms or lessen
nerve damage from Guillain-Barre
syndrome” - The Cochrane Database of
Systematic Reviews 2000 (6 RCT’s, 195
pts treated with steroids vs 187 pts
with supportive care)
• No indication as monotherapy, evidence of
benefit if added to IVIG.
Therapy
The Cochrane Database of Systematic Reviews
2002
Plasma exchange for Guillain-Barre syndrome
Raphal JC, Chevret S, Hughes RAC, Annane
"Plasma exchange is the first and only
treatment that has been proven to be
superior to supportive treatment alone
in Guillain-Barre syndrome.
Consequently, plasma exchange should
be regarded as the treatment against
which new treatments, such as
intravenous immunoglobulin, should be
judged."
Therapy
Plasma exchange
• reduce length of stay in the ICU and in
hospital
• Reduce need for and period of ventilation
• Reduce length to unaided walking and
neurological sequele.
• 4 double-volume exchanges on alternate
days over 1 week.
• exchange with albumin 5%
• more beneficial when started within seven
days of the disease onset.
Therapy
• Small children: access problems
(need central line – thrombosis,
bleeding, infections), CVS instability
after exchange
• No EBM regarding plasmapheresis in
children
Therapy
Use of plasma exchange:
• severe disease
• Failure of IVIG treatment
• Previous adverse reaction to IVIG
Therapy
IVIG
• Probably same effects as plasma
exchange or even superior
• More available, less side effects
• 2 g/ Kg over 2-4 days
• Caution: early transient relapse
after IVIG administration
The Cochrane Database of Systematic Reviews 2006
Intravenous immunoglobulin for Guillain-Barre
syndrome
Hughes RAC, Raphael J-C, Swan AV, van Doorn PA
• 6 RCT’s, 536 patients (mostly adults)
• Plasma exchange vs IVIG
• No statistically significant difference in
primary and secondary outcome
• Regimen: no significant difference
between 5 days and 2 days
• 3 studies including 75 children suggested
that IVIG significantly hasten recovery
compared with supportive care.
Immune globulins are effective in severe
pediatric Guillain-Barre syndrome.
Shahar E, Shorer Z, Roifman CM, Levi Y,
Brand N, Ravid S, Murphy EG.
Pediatr Neurol. 1997 Jan;16(1):32-6.
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26 children,Prospective, no control
All bedridden, 2 needed artificial ventilation
All treated with IVIG 2g/kg in 2 days
No adverse effects
25 improved in 1-2 grades in GMDS within 2
weeks
• 18 recovered by 2 weeks
• The rest recovered within 4 months
• Rapid improvement compared with the natural
history of GBS.
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Outcome of severe Guillain-Barre syndrome in
children: comparison between untreated cases
versus gamma-globulin therapy.
Shahar E, Leiderman M.
Clin Neuropharmacol. 2003 Mar-Apr;26(2):84-7
Retrospective, 23 children
15 treated with IVIG
5 supportive care, 3 oral steroids
Improvement by 1 grade in the GMDS
mean 10 days in the IVIG group vs 30
days
Walk unaided: mean 20 days vs 100 days
Eur J Paediatr Neurol. 1997;1(1):7-12.
Intravenous immunoglobulin treatment in
children with Guillain-Barre syndrome.
Kanra G, Ozon A, Vajsar J, Castagna L, Secmeer G,
Topaloglu H
• 47 children treated with IVIG compared
with 28 treated with supportive care
• Retrospective, case-control
• Mean time to improve in 1 grade in GMDS
was 20 days in the IVIG group vs 62 days
in the control
Prognosis
• 3% mortality
• Recovery- 1-6 months
• 80% have complete recovery in 12
months
‫תודה‬
CIDP
Neonatal Guillain-Barre syndrome.
al-Qudah AA, Shahar E, Logan WJ, Murphy EG.
Department of Pediatrics; Hospital for Sick Children, Toronto, Ontario,
Canada.
A term female infant had the clinical manifestations and accompanying
electrophysiologic studies to fulfill the criteria of Guillain-Barre
syndrome. At birth, she presented with generalized hypotonia, paucity of
lower limb movements, and diminished muscle stretch reflexes. At 3
weeks of age, motor nerve conduction studies demonstrated evidence of
demyelination and axonal involvement. Progressive clinical
improvement was observed beginning at the age of 2 weeks with
subsequent normalization of clinical examinations and nerve conduction
studies. To our knowledge, this patient is the youngest reported with
Guillain-Barre syndrome.