Transcript AIDP and reflexes - Instituto de Neurologia de Curitiba

Acute Inflammatory Demyelinating
Polyradiculoneuropathy
Dr. Walter Oleschko Arruda
Instituto de Neurologia de Curitiba
Hospital Ecoville
55-41-3028-8552
[email protected]
Immune-mediated inflammatory neuropathies
Acute
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Guillain Barré syndrome
Chronic
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CIDP
Multifocal Motor Neuropathy(MMN)
Anti-MAG Syndrome
GALOP Syndrome
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Gait disorder
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Autoantibody (IgM vs Central Myelin Antigen)
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Late-age
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Onset
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Polyneuropathy
Anti-Sulfatide Antibody Syndrome
Jean Baptiste Octave Landry
de Thézillat (1826-1865)
“...The onset of the paralysis
can be preceded by a general
feeling of weakness, pins and
needles and even slight
cramps. ... the weakness
spreads rapidly from the
lower to the upper parts of
the body with a universal
tendency to become
generalised.
'The first symptoms always
affect the extremities of the
limbs and the lower limbs
particularly. When the
paralysis reaches its
maximum intensity the
danger of asphyxia is always
imminent ...”
1859 – Report based on five
Cases + 5 cases from literature
Georges Charles GuillainJean-Alexandre Barré
1916
André Strohl
AIDP - Epidemiology
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Incidence: 1 to 2/100,000/year
Male: Female = 1.25: 1
Peak ages: Young adults & > 55 years
Genetic risk factor: FcgRIIa-H131
allele homozygosity (vs R131)
More common than in healthy controls
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Higher risk for severe disease than other
genotypes
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Same allele protective against lupus nephritis
AIDP - Clinical features
Onset
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Weakness: Most often symptomatic in legs
Pain: Low back & legs
Paresthesias: Distal
Weakness
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Distribution: Proximal + Distal; Symmetric
Severity: Quadriplegia in 30%; Bedbound
another 30%
Respiratory failure
AIDP - Clinical features
Respiratory failure
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Indications for intubation
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Vital capacity < 1 liter: Observation in ICU
necessary
~33% of GBS require intubation
Vital capacity < 12 to 15 ml/kg
Negative inspiratory force (NIF) < 25 cm H2O
Hypoxemia: PaO2 < 80 mm Hg
Difficulty with secretions
Time of onset: 7 days
Time on respirator: 50% < 3 weeks
AIDP – Clinical features
Cranial Nerves (70%)
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Asymmetric
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VII cranial nerve (bilateral)
Symmetric: Occurs early in parallel with
weakness
Occurs later in disease course
Other weakness may be stable or improving
Extra-ocular: overlap with MillerFisher
Tongue: Symmetric; Common (50%)
Sensory
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Paraesthesias: Initial symptom in 50%;
Eventually occur in 70% to 90%
Pain
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Prominent in 70%
Associations
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Neuropathy: In back, hips & legs at onset;
Myalgias; Occasional radicular
Immobility: Myalgias
Recovery phase: Distal; Legs > Hands;
Dysesthesias
Loss
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Distal; Symmetric; all modalities involved
AIDP – Clinical features
Tendon reflex loss
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Distribution:
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Ankles most frequently lost;
Biceps most frequently spared
Associations:
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Early in most (70%) but not all patients
Progressive reduction during 1st week
Sensory loss; Weakest limbs; Distal
Spared reflexes all during disease
course suggests another diagnosis !!!
AIDP and reflexes
54 patients with GBS
Mean age: 40.1 years (3 to 78 years)
First examination (3-14 days after
onset)
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52 of the 54 patients had areflexia (n=44) or
hyporeflexia (n=8). 2 patients: one had normal
reflexes, and the other, hyperreflexia.
During weeks 3 to 4
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7 patients (13%) developed hyperreflexia
Hoffmann's sign were present in 4 patients, but
none had Babinski's sign.
J Neurol Neurosurg Psychiatry 1999;67:180-184
AIDP and reflexes
1 in 17
J Neurol Neurosurg Psychiatry 1999;67:180-184
AIDP and reflexes
GBS showed obvious hyperreflexia
when:
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They had the AMAN pattern (33% had hyperreflexia)
Presence of anti-GM1 antibody
Milder muscle weakness
The incidence of hyperreflexia in AMAN was 33%
Hyperreflexia was significantly more
frequent in patients with anti-GM1
antibodies
C jejuni infection had no relevant
association with hyperreflexia.
J Neurol Neurosurg Psychiatry 1999;67:180-184
AIDP – Clinical features
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Autonomic dysfunction (60%)
Blood pressure
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Transient hypertension or, less often, hypotension
 Increased sensitivity to anti-hypertensive
medications
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Cardiac arrhythmias:
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Sinus tachycardia; bradycardia
Bladder:
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Urinary retention; sphincter symptoms in 10% to
15%
AIDP – Clinical features
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Gastrointestinal: Ileus
Test:
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Bilateral ocular pressure x 25 sec; Produces
bradycardia (< 40 bpm)
Course
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Usually improves in parallel with motor &
sensory function
 Rarely any long-term autonomic dysfunction
AIDP – Clinical course
Progression
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Nadir: Mean at 9 days
General definition: Progression for < 4 weeks
1% have acute onset of CIDP vs GBS:
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May need repeated treatment;
? Steroid responsive
Death
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Frequency: 3% to 10%
Causes: Pneumonia; Iatrogenic hypotension
Associations: Mechanical ventilation; ?
Autonomic dysfunction
AIDP - Prodrome
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Upper respiratory: + CMV titers = 18%
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Higher frequency of serum IgM vs GM2
ganglioside
Gastrointestinal: + Campylobacter jejuni
titers = 28%
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Motor predominant
 More severe outcome
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Mycoplasma pneumonia
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Associated with antibodies to galactocerebroside
(GalC)
AIDP and infection
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229 patients with GBS
Campylobacter jejuni: 53 (23%)
Cytomegalovirus: 19 (8%)
Epstein–Barr virus: 4 (2%)
Patients with C. jejuni infection were
more likely to have a worse outcome
Most patients had no identified infection
Preceding infections, immune factors, and outcome in Guillain–Barré syndrome
Neurology 2001;56:758-765
AIDP and infection
Pour outcome
35
40
%
20
15
11
0
Infection
Neurology 2001;56:758-765
No infection
C. jejuni
CMV
EBV
All
AIDP - Prodome
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Other infections:
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Vaccinations
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Epstein-Barr virus; HIV; ? Hepatitis A; Rabies
Tetanus toxoid; Influenza; ±polio (oral)
Post-partum: 1st 2 weeks with higher
risk
Surgery
? Graft vs Host disease
Drugs: Zimeldine
AIDP in children
Onset
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Lower extremity  Generalized weakness
Pain & Paresthesias (60%): Lower limbs or back
Miller-Fisher syndrome:
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1% of childhood AIDP
CNS signs: More frequent
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Bladder dysfunction
Mental status changes & headache
Pain & meningismus (30%)
Gait ataxia
Occasional: Papilledema (< 5%)
Miller-Fisher syndrome
Onset: Mean 40 years (13 to 78 years)
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Myalgia & Paresthesias
Eye
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Diplopia (Asymmetric) (80%)
External ophthalmoplegia (100%)
Pupillary dysfunction (42%): Mydriasis
Ptosis (58%)
Ataxia (100%):
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Vertigo; Dysmetria; Gait ataxia; Arms & Legs
Miller-Fisher syndrome
Areflexia (100%): By 1 week of disease
Sensory
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Distal & Facial paresthesias & dysesthesias (24%)
Sensory loss: Minimal; Definite in 20%
Weakness: 20%
Autonomic: Bladder dysfunction (16%)
Other Cranial nerve disorders
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Oropharyngeal weakness (26%)
Facial weakness (32%)
Miller-Fisher syndrome
CSF
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Serum antibodies
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IgG vs GQ1b (80%)
IgG staining of cerebellar molecular layer
MRI
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Protein: 20 to 60 mg/dl
Cells: Few or None; 0 to 5/mm3
Cranial nerve enhancement (gadolinium) may
occur
Brainstem or Cerebellar lesions: Some patients
Treatment: ? IVIg; ? Plasma exchange
AIDP in children
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Recovery
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Often more rapid than adults
Disability at 1 year: Rarely full recovery
Residual disability (~30)%:
 Foot drop, Pes cavus, Tremor
AIDP - Neurophysiology
Nerve conduction studies:
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Demyelination ± Axonal loss
Common early (< 1 week from onset)
features
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Reduced H reflex (97%)
SNAPs: Upper extremity (61%); Sural may be
preserved
Reduced F-waves (84%)
AIDP - Neurophysiology
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Motor conduction block
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probably causes acute weakness
AIDP - Neurophysiology
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Compound motor action potentials
(CMAPs):
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Often become progressively small
Small CMAPs may indicate
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Axonal loss or distal conduction block
 Poor prognostic sign
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EMG: Fibrillations & Positive sharp
waves
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Onset: 2 to 4 weeks
 Peak: 2 to 3 months
AIDP - CSF
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Protein
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Early (1st 2 days): Usually (85%) normal
 Later
 High; 66% in 1st week; 82% in 2nd week
 Highest with most slowing of NCV
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Cells: Normal (~90%), unless
associated disorder present
Oligoclonal bands: 10% to 30%
AIDP – Laboratory tests
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Hematology: Only abnormal with
associated infection or other disorder
Serum CK: Higher in patients with pain
ESR: Usually < 50 mm/hr
Mild proteinuria: 25%
Liver function test: Abnormal in 10%
WBC: Most commonly normal; >
20,000 only with associated infections
AIDP - Morbidity
Weakness
Respiratory failure
Pneumonia or sepsis
Dysphagia
Thromboembolism
Corneal exposure
Sensory
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Pain: 2° neuropathy or immobility
Autonomic
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Cardiac Arhythmias
Labile blood pressure
Hypersensitivity to cardiovascular medications
AIDP – prognosis
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Increasing age (especially > 40 to 60)
Weakness
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Severe
Need for ventilatory support
Rapid development
Complete areflexia in the acute stage
Diarrhea prodrome
No treatment with plasma exchange or IV Ig
Longer time to improvement
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Initial improvement > 21 days
Disability present at 12 to 18 months
AIDP – prognosis
Axonal loss
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? Lack of demyelinating features
Serology
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Low compound motor action potential (CMAP)
amplitudes
< 20% of normal
? Serum IgG vs GM1 ganglioside
? Preceding Campylobacter jejuni infection
Recent CMV infection
AIDP - Treatment
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Plasma Exchange or IV IgG definitely
indicated
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Patients with inability to walk
 1st 2 weeks of disease
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Decision between IV IgG & PE:
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Depends on individual features of patient & disease
IVIG: 2 g/Kg total over 2 to 5 days
AIDP - Treatment
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Plasma Exchange and IV IgG
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Exception
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Often provide similar degrees of benefit
Associated IgG vs GM1, GM1b, or GalNAc-GD1a
gangliosides: IVIg more effective
Not Corticosteroids !!!!!
Ventilatory support
Avoid anti-hypertensive medications
? Sub-cutaneous heparin with
immobility: lower risk of
thromboembolic events
AIDP - Treatment
Plasma Exchange: 4 or 5 treatments
over 7 to 10 days
Use in
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Adults with good venous access
Very recent onset of symptoms (1 to 3 days)
History of side effects with IV Ig
Pregnancy
Congestive heart failure
Renal insufficiency
IgA deficiency
AIDP - Treatment
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PE is recommended for nonambulant
adult patients with GBS within 4 weeks
of the onset of neuropathic symptoms.
PE should also be considered for
ambulant patients within 2 weeks of the
onset of neuropathic symptoms.
IVIg is recommended for nonambulant
adult patients with GBS within 2 or 4
weeks of the onset of neuropathic
symptoms.
Neurology 2003;61:736-740
AIDP - Treatment
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The effects of PE and IVIg are
equivalent
Corticosteroids are not recommended
for the management of GBS
Sequential treatment with PE followed
by IVIg, or immunoabsorption followed
by IVIg is not recommended for
patients with GBS
PE and IVIg are treatment options for
children with severe GBS.
Neurology 2003;61:736-740