Transcript Guillain-Barre Syndrome

Guillain-Barre Syndrome
William Woodfin MD
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”
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
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
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
Exam
Sensory- intact
DTRs- biceps, BR, knees are trace c
reinforcement. Triceps & ankles
unobtainable
Plantars- flexor
F to N- intact
Gait- not testable
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
MRI
LS spine s & c contrast- no nerve root
enhancement
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
Telephone FU
Ambulating fairly well c walker. Strength
clearly improving.
Still bothered by “creepy-crawlies”
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
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
History
Waldrop 1834
Olliver 1837
Landry 1859
Graves 1884
Ross & Bury 1893
Guillain, Barre & Strohl
1916-1920
Brussel’s Conf. 1937
Haymaker &
Kernohan 1949
Waksman & Adams
1955
Miller Fisher 1956
Asbury, Aranson &
Adams 1969
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
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
Georges Guillain
Revue Neurologique 1916
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
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
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
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
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
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
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.
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
Cellular & Humoral Immune
Mechanisms
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
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
Antecedent Events: Infectious
• Viral: Influenza, Coxsackie, EBV, Herpes,
HIV, Hepatitis, CMV, WNV
Bacterial: Campylobacter jejuni,
Mycoplasma, E. coli
Parasitic: Malaria, Toxoplasmosis
Antecedent Events: Systemic
disease
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Hodgkins
CLL
Hyperthyroidism
Sarcoidosis
Collagen Vascular d.
Renal d.
Other antecedent events
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Surgery
Immunization
Pregnancy
Envenomization
Bone marrow transplantation
Drug ingestion
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
AIDP
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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
AIDP
• Pathology: immune attack directed at
schwann cell plasmalemma esp. at nerve
roots with IgG & complement deposits
preceding demyelination
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
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%
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
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
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
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
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
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
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.
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.
Differential
• Metabolic: Periodic paralyses,
Hypokalemia, Hypermagnesemia,
Hypophoshatemia c parenteral
hyperailimentation, Thyrotoxicosis, ICU
myoneuropathy (CIP)
• Heavy metal: Lead, Arsenic, Thallium,
Barium c hypokalemia
Differential: Miller Fisher Syn.
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Multiple sclerosis
Encephalitis
Posterior circulation ischemia or infarct
Other: Botulism, MG, Tick
Treatment
Respiratory failure
Autonomic dysfunction
DVT & PE
Pain
Positioning & Skin care
Physical therapy
Nutrition
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
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
Psychological
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Fear
Helplessness
Communication
Pain
Sleep deprivation & hallucinosis
Depression
Visits from other GBS patients
Personal Experience
• Bowes, Denise; The doctor as patient: an
encounter with Guillain-Barre syndrome.
Can Med Assoc J 131:1343-1348
Corticosteroids
• Lancet 1993 242 pts.
IV Methylprednisilone 500 mgm/day x 5.
Ineffective
May cause relapse
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
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
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
IVIG
• Mechanism of action- unknown
? Antiidiotypic antibody action
? Inhibition of cytokines
? “Sponging” of complement
? Binding to Fc receptors so macrophages
can’t bind
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
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
• 1 Week post discharge, elevated titers to
West Nile Virus
• Follow up at 1 month- continued
improvement