This document describes a case of Guillain-Barré syndrome (GBS) in a 40-year-old woman. She developed nausea, diarrhea, and muscle aches after her son was diagnosed with rotavirus. Later she experienced numbness and tingling in her legs that progressed to weakness. Testing showed findings consistent with GBS including abnormal electromyography and absent reflexes. She was treated with intravenous immunoglobulin, showed some improvement, and was discharged.

1. Guillain-Barre Syndrome
William Woodfin MD

2. K.F. 40 y.o. r/h woman
3/17 Nausea, diarrhea & severe myalgias
Son dxed c rotavirus 1 wk. Previously
4/21 “Creepy-crawlies” legs>arms
4/25 Weakness legs progressing
4/26 Handwriting looks like “hen scratch”

3. K.F. 40 y.o. woman
4/28 Admitted to outside hospital.
L.P. wnl
EMG positive waves in some leg
muscles
NCVs absent H-reflexes
F responses & motor latencies wnl

4. K.F. 40 y.o. woman
4/29 Transferred to PHD
Hx.: diabetic x 10 yrs.
hypothyroid- treatedx yrs.
no sphincter disrubance
aching pain low back & buttocks
mild postural light headedness
no SOB or palpatations

5. Exam
BP 150/90 P 80 Wt. 250 lbs.
Mild weakness neck flexors
4/5 biceps, grip & interossei- symmetric
2/5 iliopsoas & quadriceps
3/5 hamstrings & adductors
4/5 abductors
4/5 ankles & toes- extensors & flexors

6. Exam
Sensory- intact
DTRs- biceps, BR, knees are trace c
reinforcement. Triceps & ankles
unobtainable
Plantars- flexor
F to N- intact
Gait- not testable

7. Lab
H/H 10.3/33.5 c microcytic indices
A1c Hgb 10.1
TSH 0.97
LDL 182
Serum immunofixation- wnl. No IgA def.
FVCs- consistently 4+ liters

8. MRI
LS spine s & c contrast- no nerve root
enhancement

9. Course in hospital
Treated c IVIG 0.4 gms/kgm daily x 5
Strength fluctuated only mildly
Blood sugars ok in AM, high in afternoons
Repeated NCVs show mild dispersion of F
waves
Transferred back to referring hospital 5/6

10. Telephone FU
Ambulating fairly well c walker. Strength
clearly improving.
Still bothered by “creepy-crawlies”

11. What is the GBS?
• Due to the breadth of clinical presentation it
is of limited help to try to define rigid
diagnostic criteria.
• Thomas Munsat 1965: “…The GBS is easy
to diagnose but difficult to define

12. The typical illness evolves over weeks
usually following an infectious disease
and involves:
• 1. Paresthesiaes
usually hearld the
disease
• 2. Fairly symmetric
weakness in the legs,
later the arms and,
often, respiratory and
facial muscles
• 3. Dimunition and loss
of the DTRs
• 4. Albuminocytologic
dissociation
• 5. Recovery over
weeks to months

13. History
Waldrop 1834
Olliver 1837
Landry 1859
Graves 1884
Ross & Bury 1893
Brussel’s Conf. 1937
Haymaker &
Kernohan 1949
Waksman & Adams
1955
Miller Fisher 1956
Asbury, Aranson &
Adams 1969
Guillain, Barre & Strohl
1916-1920

15. Note sur la paralysie ascendante
aigue 1859
• March 16- a febrile illness
• May 11- mild sensory symptoms in the fingers and
toes
• June 13- knees buckle
• June 16- unable to walk
• Subsequent respiratory failure and death.
• Autopsy unrevealing. Peripheral nerves probably
not examined

16. Late 19th
century
• Westphal 1876- “Landry’s Ascending Paralysis”
• Graves 1884- localized neurologic disease to the
peripheral nerves, “the nervous cords”
• Ross & Bury 1893- 90 cases. A disease of the
peripheral nerves
• Numerous reports emphasizing various aspects of
the disease with most authors crediting Landry

17. Georges Guillain

18. Revue Neurologique 1916

19. Guillain, Barre & Strohl 1916
Revue Neurologique
• Two soldiers in Amiens developing
paralysis and loss of DTRs.
• A new diagnostic feature:
albuminocytologic dissociation in the CSF
• No mention of Landry

20. Foundations
• Quincke- CSF observations 25 years earlier
• Siccard & Foix- “albuminocytologic dissociation”
in Pott’s disease
Late 19th
century: examination of the reflexes had
become a part of the neurologic exam with
appreciated as a sign of neuropathy based on
observations in tabes dorsalis areflexia

21. Haymaker & Kernohan 1949
• Landmark in pathological description c 50 fatal
cases & detailed review of clinical findings
• Emphasized prominent damage to proximal nerves
often at junction of ventral & dorsal roots. Little
study of more distal nerves
• Unified findings of Landry & Guillain, Barre &
Strohl

22. Waksman & Adams 1955
• Experimental Allergic Neuritis
• First animal model of a noninfectious
inflammatory neuritis
• Rabbit nerve and Freund’s adjuvant injected
intradermally
• Target of activated T cells uncertain

23. Asbury, Aranson & Adams 1969
• 19 pts. All with well developed
mononuclear infiltrates in spinal roots and
nerves within days of clinical onset
• Pathological hallmark: perivascular
mononuclear inflammatory infiltrates to
adjacent to the areas of demyelination

24. Overview of Adaptive Immunity
• Lymphocytes: “command & control,”
identify antigen components, respond
specifically, mobilize other elements and
direct the attack c memory for each
antigenic assault
• Antibodies: specialized immunoglobulin
molecules directly neutralize and remove
antigen

25. T lymphocytes
• CD8- recognize epitopes paired c MHC-I
• CD4- activate and control the immune response
• Scavenger cells break down antigen into small
peptide fragments (T cell epitopes), MHC-II
epitope complexes are expressed on the surface &
the scavenger become an APC which docks on a
CD4 c a compatible TCR. CD4 proliferates
releasing cytokines.

26. Antibodies
• Cytokines activate other lymphocytes including B
cells that differentiate into plasma cells and serve
as immunoglobulin factories.
• Abs are Ig molecules that recognize, bind,
neutralize and opsonize Ag for phagocytosis. They
activate complement(membrane attack complex)
& induce target cells to activate the inflammatory
response

27. Cellular & Humoral Immune
Mechanisms

28. Self-tolerance
• The process of self recognition
• T & B cells learn self tolerance during
maturation
• Autoimmunity occurs when the
mechanisms of self protection are defective

29. Mechanisms of Autoimmunity
• Molecular mimicry- microbe cell surface Ag
resembles self protein. Damage results from
“friendly fire” The inciting Ag is usually
unidentified & may not exist as a single stimulus.
• Excessive cytokine release due to profound
immune stimulus may awaken self tolerant T cells
or may cause expression of MHC complexes.
• Self Ags bound to drugs may lose tolerated status

30. Antecedent Events: Infectious
• Viral: Influenza, Coxsackie, EBV, Herpes,
HIV, Hepatitis, CMV, WNV
Bacterial: Campylobacter jejuni,
Mycoplasma, E. coli
Parasitic: Malaria, Toxoplasmosis

31. Antecedent Events: Systemic
disease
• Hodgkins
• CLL
• Hyperthyroidism
• Sarcoidosis
• Collagen Vascular d.
• Renal d.

32. Other antecedent events
• Surgery
• Immunization
• Pregnancy
• Envenomization
• Bone marrow transplantation
• Drug ingestion

33. Features of AIDP
• 2/3s have identifiable preceding event
• 50% begin with paresthesias followed by
weakness in legs; 10% begin with arm
weakness; rarely begins in face
• Ophthalmoplegia: partial 15%, total 5%
• Autonomic dysfunction in 65%,
arrhythmias, hypotension,urinary retention
in 10-15%, pupillary inequality

34. AIDP
• Progresses for days to 4 weeks
• 15% with severe disability
• Mortality 3-5%
• CSF: protein may be normal early, elevated
in 90% by clinical nadir, cells< 10 in 95%,
>50 suggests HIV
• EDX: prolonged F & distal motor latencies,
conduction block 30-40% in routine studies

35. AIDP
• Pathology: immune attack directed at
schwann cell plasmalemma esp. at nerve
roots with IgG & complement deposits
preceding demyelination

37. CIDP
• Evolves over months
• Fluctuates
• Respiratory failure, dysautonomia, facial
weakness, ophthalmoplegia- all are rare
• CSF protein often highly elevated
• Marked slowing of motor nerve conduction
• Steroid responsive

38. Features of AMSAN
• Commonly preceded by diarrhea esp. c.
jejuni
• Abrupt onset of weakness c rapid
progression to quadriplegia & respiratory
insufficiency
• Other features as c AIDP
• Longer recovery, more residual & mortality
10-15%

39. AMSAN
• CSF as in AIDP
• EDX: no response in some motor nerves,
decreased amplitude of the CMAPs,
fibrillations on needle study, absent SNAPs
• Immune attack directed at axon
plasmalemma at nodes of Ranvier.
Wallerian degeneration

40. Features of AMAN
• Often preceded by diarrhea affecting
younger population in China. Sporadic in
USA
• Prognosis similair to AIDP
• Mortality <5%
• EDX: reduced CMAPs c normal F & distal
motor latencies and sensory studies.
Fibrillations in 2-3 weeks

41. AMAN
• Pathology: again axonal plasmalemma at
nodes of Ranvier sometimes limited to
physiologic dysfunction c nodal
lengthening. May go on to extension
through axonal basal lamina. Most axons
recover s Wallerian degeneration

43. Miller Fisher Syndrome
• Ophthalmoplegia, Ataxia, Areflexia
• May be heterogonous: 1. Related to other patterns
of GBS
2. Related to brainstem encephalitis, Bickerstaff
1952
3. CNS demyelination in association with GBS

44. Miller Fisher Syndrome
• 95% have serum IgG Ab to ganglioside GQ1b
• Studies show preferential location of anti-GQ1b to
cerebellar molecular layer & Cranial Nerves 3,4 &
6
• May act at N-M junction depleting acetylcholine
from nerve terminals

45. Acute Panautonomic Neuropathy
• Manifests over 1-2 weeks but may be of
subacute onset
• Frequent preceding infection
• DTRs lost in 1/3, distal sensory changes 1/4
• Albuminocytologic dissociation
• EDX: NCVs usually normal
• Recovery is gradual and incomplete

46. Differential Diagnosis
• Consider the possibility of an upper motor
neuron lesion
• Other considerations are rare. Diphtheritic
neuritis & poliomyelitis belong more to the
history section of this presentation. A new
possibility is West Nile Virus.

47. Differential
• N-M: MG, LES, Antibiotics
• Toxic: Cigutera (ciguatoxin), Pufferfish
(tetrodotoxin), Shellfish (saxitioxin),
Botulism, Tick paralysis (Lone Star tick,
Gulf Coast tick), Glue sniffing, Buckthorn
• Mononeuritis multiplex assoc. c Wegner’s.
PAN, SLE, RA, Sjogren’s,
Cryoglobulinemia etc.

48. Differential
• Metabolic: Periodic paralyses,
Hypokalemia, Hypermagnesemia,
Hypophoshatemia c parenteral
hyperailimentation, Thyrotoxicosis, ICU
myoneuropathy (CIP)
• Heavy metal: Lead, Arsenic, Thallium,
Barium c hypokalemia

49. Differential: Miller Fisher Syn.
• Multiple sclerosis
• Encephalitis
• Posterior circulation ischemia or infarct
• Other: Botulism, MG, Tick

50. Treatment
Respiratory failure
Autonomic dysfunction
DVT & PE
Pain
Positioning & Skin care
Physical therapy
Nutrition

51. Respiratory Failure
• Oropharyngeal weakness in ~25% with
impaired swallowing of secretions &
aspiration
• Mechanical respiratory failure- mainly due
to diaphragmatic weakness (Phrenic
nerves.) Inspiratory c MIF (Max. Inspir.
Force) a good supplement measure to FVC

52. Respiratory Failure
• ~33% require intubation
• Avg. time to intubation is 1 week & these
pts. have substantially longer recovery time
• Need is unlikely if patient does well for 2
wks. post onset of paresthesiaes
• Guidelines: FVC <15 mL/kgm
MIF < 25 cm water

53. Psychological
• Fear
• Helplessness
• Communication
• Pain
• Sleep deprivation & hallucinosis
• Depression
• Visits from other GBS patients

54. Personal Experience
• Bowes, Denise; The doctor as patient: an
encounter with Guillain-Barre syndrome.
Can Med Assoc J 131:1343-1348

55. Corticosteroids
• Lancet 1993 242 pts.
IV Methylprednisilone 500 mgm/day x 5.
Ineffective
May cause relapse

56. Plasma Exchange
• Removal of the blood’s liquid soluble
components including complement,
immunoglobulin, immune complexes,
cytokines and interleukins
• A typical session removes about 60% of the
body mass of plasma proteins which is
replaced c saline, albumin & FFP
• Done qod for 3-5 sessions

57. Plasma Exchange
• Various studies since 1985
• Time on ventilator reduced by ½
• Full strength regained at 1 year: Exchange
71%, Untreated 52%
• Limitations: Limited availability
Avoid with autonomic instability

58. Intravenous Immune Globulin
• Originally used for immune insufficiency
• Use as an immunosuppresant “seems to
defy reason”
• 1981 Rx for ITP
• 5,000-10,000 donors/batch. Diversity of
Abs from large donor pool maximizes effect

59. IVIG
• Mechanism of action- unknown
? Antiidiotypic antibody action
? Inhibition of cytokines
? “Sponging” of complement
? Binding to Fc receptors so macrophages
can’t bind

60. IVIG
• Dosage: 0.4 gms/kgm/day x 5 c each dose
given over 3-4 hours preceded by IV
diphenhydramine &/or po ibuprofen
• Caution c renal insufficiency or IgA
deficiency
• 38 Center trial in 1997
• Equal to plasma exchange

61. J.H.C. 48 yo welder
• June ’02 H.A. followed in 2 wks by Lt.
Facial weakness
• June ’03 Rhinorrhea & cough
• August 6 Pain lt. Hip spreading over a few
days to back 7 legs
• August 15 Legs buckle c lt.facial weakness
1 wk later. LP c protein of 70. NCVs c
prolonged F waves

62. • 1 Week post discharge, elevated titers to
West Nile Virus
• Follow up at 1 month- continued
improvement