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Acute Immune Polyneuropathies

"Classic" Guillain-Barré
  Associated disorders
  Childhood GBS
  Clinical features
  Electrodiagnostic features
  Epidemiology
  Laboratory features
  Morbidity
  Pathology
  Prognosis
  Prodrome
  Therapy

Acute Immune Neuropathies
  Autonomic
  Motor (AMAN)
  Sensory
  Cranial nerve variants
    Ataxia & Ophthalmoplegia
    Bickerstaff
    Facial diplegia
    Miller Fisher Syndrome
    Pharyngo-Cervico-Brachial
  IgM vs GalNAc-GD1a
  Pathology

General topics
  Acute immune neuropathies
    Antibodies
    Classification
    Differential diagnosis
    General Principles
  GBS-like syndromes: Treatment

Georges Guillain



Ross & Bury 1893

Classification of Acute Immune Neuropathies

Acute immune neuropathies: General principles

Acute immune neuropathies have several features in common as well as those that vary and are distinctive for particular syndromes.
Some features suggest a different diagnosis among the causes of acute motor dysfunction.
Principles regarding which treatment to use are somewhat subjective.
  • Epidemiology
    • Incidence
      • Europe & North America: 0򊞻9 (median 11) cases/100,000 people per year
      • Age association
        • Childhood: 0.6/100,000 people per year
        • Elderly: 2.7/100,000 people per year
    • Males slightly > Females
  • Common features
    • Prodromal illness
      • 50% of patients in 2 weeks prior to disease onset
        • Respiratory or GI
        • Strongest association: C. jejuni
      • GBS syndrome peak frequencies 28
        • Correlate with hospitalizations for Pneumonia & influenza
        • No significant association with vaccinations
    • Progression
      • Average: 5 to 10 days
      • Spectrum: 2 to 28 days
    • Course
      • Usually monophasic
      • Rare relapses
    • Prognosis
      • Recovery in most
    • Cerebrospinal Fluid (CSF)
      • High protein (> 0.55g/L)
      • Few or no cells
  • Variable features
    • Motor, Sensory, or Autonomic involvement
    • Tendon reflexes: More frequently preserved or increased with motor predominant syndromes
    • Demyelinating vs. Axonal Pathology
    • Degree of CNS involvement
    • Humoral vs. Cellular immunity
  • Features suggesting another diagnosis
  • Differential diagnosis of acute motor dysfunction
  • Treatment of GBS-like syndromes: Plasma exchange vs IV Ig
    • Overall: No difference in efficacy
    • Indications for rapid treatment: 1st 2 weeks of disease
      • Bulbar disorders
      • Respiratory dysfunction
      • Inability to walk without assistance
    • Probably indicated: Milder weakness; Early in disease course
    • IV Ig: ? Primary therapy; 2 gm/kg total over 2 to 5 days
      • Slightly lower cost
      • Slightly fewer side effects
      • Easier to administer
      • Use in
        • Children
        • Rural settings with no access to plasma exchange
        • Syndromes with anti-glycolipid antibodies
          • Pure motor syndrome (IgG vs GM1)
          • Miller-Fisher syndrome (IgG vs GQ1b)
        • Patients with
          • Diarrhea prodrome
          • Infectious disorders (HIV)
          • Autonomic instability
          • Poor venous access
          • Relapses of weakness
    • Plasma Exchange: 4 or 5 treatments over 7 to 10 days
      • ? Fewer late relapses
      • No allergic reactions
      • Efficacy somewhat better documented
      • Use in
        • 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


"Classic" Guillain-Barré Syndrome

Autoantibodies
Clinical features
Electrodiagnostic
Laboratory
Morbidity
Other features
Pathology
Prodrome
Prognosis
Therapy

English translation: By Bassam Malo MD
  • Epidemiology
    • Incidence: 1 to 2/100,000/year
    • Male: Female = 1.25: 1
    • Peak ages: Bimodal
      • Children & Young adults
      • > 55 years
    • Zika infection: Colombia
    • Winter month peak: United States, Australia & Asia
    • Genetic risk factor : FcγRIIa-H131 allele homozygosity (vs R131) 4
      • More common than in healthy controls
      • Higher risk for severe disease than other genotypes
      • Same allele protective against lupus nephritis
  • GBS Prodrome
    • Upper respiratory: + CMV titers = 18%
      • Younger patients
      • More sensory loss & cranial nerve involvement
      • More severe disease
        • Respiratory insufficiency more common (65%)
        • Longer median time until independent locomotion
      • Antibodies
    • Gastrointestinal: + Campylobacter jejuni titers = 28%
      • Motor predominant
      • More severe outcome
      • + Campylobacter titers in US GBS patients overestimate prevalence of infection
    • Mycoplasma pneumonia
      • Associated with antibodies to galactocerebroside (GalC)
      • Frequency: 5% of GBS patients in Japan
      • ? Associated with younger patients
      • Other associated disorders
    • Other infections
    • Vaccinations
      • Tetanus toxoid; Influenza; ± Polio (oral)
      • Rabies
        • Vaccines: Myelin-containing (Semple); Suckling mouse brain
        • Usually > 10 years old
        • Some cases associated with sensitization to myelin basic protein
        • Occurs in clusters
    • Post-partum: 1st 2 weeks with higher risk
    • Surgery
    • ? Graft vs Host disease
    • Drugs: Zimeldine
  • Clinical features
    • Onset
      • Weakness: Most often symptomatic in legs
      • Pain: Low back & legs
      • Paresthesias: Distal
    • Weakness
      • Distribution: Proximal + Distal; Symmetric
      • Severity: Quadriplegia in 30%; Bedbound another 30%
      • Respiratory failure
        • Vital capacity < 1 liter: Observation in ICU necessary
        • ~33% of GBS require intubation
        • Indications for intubation
          • Vital capacity < 12 to 15 ml/kg: Especially with rapid decline
          • 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
        • Usually 2° to muscle weakness
        • Occasionallly related to aspiration
      • Cranial Nerves (70%)
        • VII
          • Symmetric: Occurs early in parallel with weakness
          • Asymmetric
            • Occurs later in disease course
            • Other weakness may be stable or improving
        • Extra-ocular: Overlap with Miller-Fisher
        • Tongue: Symmetric; Common (50%)
    • Sensory
      • Paraesthesias: Initial symptom in 50%; Eventually occur in 70% to 90%
      • Pain 23
        • Prominent in 70%
        • Location: Extremities > Trunk
        • Timing: May occur with prodrome (35%), disease (65%) or sequelae (40%)
        • Associations
          • Neuropathy: In back, hips & legs at onset; Myalgias; Occasional radicular
          • Immobility: Myalgias
          • More severe disease
          • More prominent sensory involvement
          • Recovery phase: Distal; Legs > Hands; Dysesthesias
      • Loss
        • Distal; Symmetric
        • All modalities involved
    • Tendon reflex loss
      • Early in most (70%) but not all patients
      • Progressive reduction during 1st week
      • Distribution: Ankles most frequently lost; Biceps most frequently spared
      • Associations: Sensory loss; Weakest limbs; Distal
      • Spared reflexes all during disease course suggests another diagnosis
    • Autonomic dysfunction
      • Frequency: 60%
        • More common in more severe syndromes
      • Blood pressure
        • Transient hypertension or, less often, hypotension
        • Increased sensitivity to anti-hypertensive medications
      • Cardiac arrhythmias: Sinus tachycardia; Bradycardia
      • Bladder: Urinary retention; Sphincter symptoms in 10% to 15%
      • GI: Ileus
      • Test: Bilateral ocular pressure x 25 sec; Produces bradycardia (< 40 bpm)
      • Course
        • Usually improves in parallel with motor & sensory function
        • Rarely any long-term autonomic dysfunction
    • Progression
      • Nadir: Mean at 9 days
      • General definition: Progression for < 4 weeks
      • Treatment related fluctuations: More common with
        • Severe disease
        • Prominent sensory abnormalities
      • 1% to 20% have acute onset of CIDP vs GBS: May need repeat treatment; ? Steroid responsive
      • Causes of morbidity
        • Weakness
          • Respiratory failure
          • Pneumonia or sepsis
          • Dysphagia
          • Thromboembolism
          • Corneal exposure
        • Sensory
          • Pain: 2° neuropathy or immobility
        • Autonomic
          • Cardiac Arhythmias
          • Labile blood pressure
          • Hypersensitivity to cardiovascular medications
      • Prognostic factors
        • Mechanical ventilation needed 8
          • Rapid disease progression
          • Bulbar dysfunction
          • Facial weakness: Bilateral
          • Dysautonomia
          • Pulmonary function testing
            • Vital capacity < 20 ml/kg
            • Decrease from baseline > 30%: Vital capacity or Respiratory pressure
        • Residual disability greater
          • Clinical prognostic factors for residual disability
            • Increasing age (especially > 40 to 60)
            • Weakness
              • Severe at nadir
              • Need for ventilatory support
              • Rapid development
            • Complete areflexia in the acute stage
            • Diarrhea prodrome: Especially with Plasma exchange treatment
            • Lack of treatment with plasma exchange or IV Ig
            • Longer time to improvement
              • Initial improvement > 21 days
              • Disability present at 12 to 18 months
          • Laboratory prognostic factors for residual disability
            • Axon loss
              • Low compound motor action potential (CMAP) amplitudes
                  < 20% of normal
              • ? Lack of demyelinating features
            • Serology
              • ? Serum IgG vs GM1 ganglioside
              • ? Preceding Campylobacter jejuni infection (past 4 weeks) or diarrhea
              • Recent CMV infection
            • Serum Albumin: Low 31
              • Respiratory weakness: More
              • Severe weakness at 1 and 6 months: More
              • Inability to walk: More
              • Albumin levels may be reduced after IVIg treatment
    • Death
      • Frequency: 3% to 10%
      • Causes: Pneumonia; Iatrogenic hypotension
      • Associations: Mechanical ventilation; ? Autonomic dysfunction
    • Associated Systemic Disorders
      • Infections: Prodromes
      • Lymphoma
      • Sarcoid
      • Porphyria
      • Hyponatremia
        • Mildly reduced Na+ in 7% to 26%
        • Severely reduced Na+ (SIADH) (105 to 120 mEq/L) may occur
        • No relation to degree of severity of GBS
      • Renal
        • Common: Mild transient proteinuria
        • Rare: Glomerulonephritis
      • Cardiac
        • Arhythmias: 10% to 75%
        • EKG changes: > 50%
      • Serum CK: High in 33%; Up to 4x normal
    • Treatment
      • Immunomodulation
        • Plasma Exchange or IV IgG definitely indicated
        • Probably indicated: Milder weakness; Early in disease course
        • Plasma Exchange and IV IgG
          • Often provide similar degrees of benefit
          • Exception
            • Associated IgG vs GM1, GM1b, or GalNAc-GD1a gangliosides: IVIg more effective
        • Not Corticosteroids
      • Ventilatory support
      • Avoid anti-hypertensive medications
      • ? Sub-cutaneous heparin
        • No evidence of benefit with moderate or mild weakness
        • ? Lower Risk of thromboembolic events in intensive care with severe weakness
  • Childhood GBS
    • Ages: Neonatal to Teens
    • Onset
      • Lower extremity ® Generalized weakness
      • Pain & Paresthesias (60%): Lower limbs or Back
    • Miller-Fisher syndrome: 1% of childhood AIDP
    • CNS signs: More frequent; At onset
      • Bladder dysfunction
      • Mental status changes & headache
      • Pain & meningismus (30%)
      • Ataxia: Gait
      • Occasional: Papilledema (< 5%)
      • Recovery
        • Often more rapid than adults
        • Disability at 1 year: Rarely full recovery
        • Residual disability (~30)%: Foot drop, Pes cavus, Tremor
  • Nerve conduction studies in GBS: Demyelination ± Axonal loss

    M. Al-Lozi
    • Common early (< 1 week from onset) features 9
      • Reduced H reflex (97%)
      • SNAPs: Upper extremity (61%); Sural may be preserved
      • Reduced F-waves (84%)
    • Other electrodiagnostic features: Demyelination
      • Overall
        • Features less common in 1st 5 to 7 days of disease
        • Increased frequency when multiple nerves studied
      • Features of demyelination for more specific diagnosis
        • One abnormality in 2 different nerves
        • Nerves: Median & Ulnar or Peroneal
        • Specific features
          • Distal motor latency: > 150% upper limit of normal
          • Motor NCV: < 70% lower limit of normal (? CIDP)
          • F-wave latency: > 150% upper limit of normal
          • CMAP amplitude decay: > 10% to 30%
          • CMAP temporal dispersion
              > 300% upper limit of normal (Distal)
          • CMAP temporal dispersion
            • > 150% upper limit of normal
            • Distal: Proximal
    • Motor conduction block probably causes acute weakness
      • Locations
        • Proximal nerve roots
        • Along course of nerve
        • Distal near motor nerve terminals
    • Compound motor action potentials (CMAPs):
      • Often become progressively small
      • Small CMAPs may indicate
        • Axonal loss or distal conduction block
        • Poor prognostic sign
    • EMG: Fibrillations & Positive sharp waves
      • Onset: 2 to 4 weeks
      • Peak: 2 to 3 months
  • Acute immune neuropathies: Humoral Immunity
    • IgM or IgG vs Tubulin: 7%
    • IgG vs GM1, GM1b or GalNAc-GD1a: Motor syndromes
      • United States: < 2%
      • Japan, China, Australia & ? Europe: 10% to 20%
    • IgM or IgG vs Heparan sulfate: 35%
    • IgG vs other glycolipids: 10% to 30%
    • IgM or IgG vs PMP-22: Probably testing artefact; Not specific for GBS
    • Tumor necrosis factor-α: High serum level correlates with demyelination
    • IgG or IgM vs molecules at nodes of Ranvier or paranodes (30%) 27
      • Target molecules
        • Gliomedin (GLDN) : Demyelinating GBS
        • Neurofascin-186 : Axonal acute immune neuropathies
  • GBS: Laboratory
    • CSF: Albumino-cytological dissociation
      • Protein
        • Early (1st 2 days): Usually (85%) normal
        • Later
          • High; 66% in 1st week; 82% in 2nd week
          • Highest with most slowing of NCV
      • Cells: Normal (~90%)
      • Oligoclonal bands: 10% to 30%
    • 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
    • HLA types: Class II associations with AIDP in northern Chinese patients 14
      • General
        • Regions important in peptide binding and T cell recognition
        • Associated with other diseases with pathoimmunological basis
        • No class II associations found for AMAN
      • Susceptibility: DQβRLD5557/ED7071 & DRβE9V11H13
      • Protection: DQβRPD5557 epitope
  • Other: Books by GBS patients or relatives (PDF file)


Putnam 1909

Acute Motor (Axonal) Neuropathy (AMAN)

  • Epidemiology
    • Geography
      • More common: Japan, China, Mexico & 3rd world countries
      • Rare: Most parts of United States
      • Occasional: Europe
    • Onset age: More common in children
    • Male = Female
    • Seasonal peaks
      • Mexico & China: July to September (Rainy season)
      • Japan: March for C jejuni + patients
  • Prodrome
    • Gastrointestinal: Diarrhea
      • + Campylobacter jejuni titers in 67%
      • Campylobacter jejuni in GBS
        • Serotype associations
          • O-19 (HS:19) type
            • > 50% when Campylobacter culture positive
            • Risk of acute neuropathy: 1 in 158
            • 6x greater than after other Campylobacter infections
            • Common in China & Japan
            • Different isolates clonally related
              • Commonly bind cholera toxin
          • O-41 (HS:41): Over represented in South Africa & Mexico
          • Carbohydrate epitope associations: GD1a but not clearly GM1
        • Higher frequency of TNF-α polymorphism
        • Campylobacter jejuni cst-II polymorphisms: Neuropathic strains 18
          • cst-II: Gene encoding sialyltransferase
          • cst-II (Thr51)
            • More common than enteritic strains
            • Express GM1 (92%) & GD1a (91%) epitopes
            • Associated with related antibodies & Limb weakness
          • cst-II (Asn51)
            AMAN: After recovery

            Putnam 1909
            • 83% express GQ1b epitope
            • Associated with
              • Anti-GQ1b antibodies
              • Bulbar palsy
              • Ophthalmoparesis
    • Upper respiratory
      • Haemophilus influenzae infection 5
        • Geography: Japan
        • Frequency: 13%
        • Organism type: Non-typable; Contains GM1-like structure
        • Infection preceded disease by 4 to 12 days
        • Serum antibodies: IgG vs GM1 & GD1b ganglioside common (83%)
      • + CMV titers in 0%
    • Zika virus
    • ? Treatment with parenteral ganglioside mixture
      • Acute axonal motor syndromes reported
        • Onset 5 to 15 days after Rx
        • Associated serum IgG anti-GM1 antibodies
  • Clinical 20
    • Weakness
      • Distal: More severe than proximal
        • Finger extensors: May be selectively weak
        • Arms > Legs
      • Proximal: Mild weakness common (85%)
      • Symmetric: Usually
      • Cranial Nerves (6% to 25%)
        • Facial weakness: Occurs but less commonly than in AIDP
      • Respiratory failure
        • Uncommon
        • Less than in classic demyelinating GBS
    • Sensory
      • Normal by clinical & electrodiagnostic testing
      • No paraesthesias
    • Reflexes
      • Usual: Reduced in proportion to strength
      • Occasional: Preserved; Hyperreflexia in some 26: Associated with
        • Milder disease
        • Serum IgG vs GM1, GM1b, GD1a or GalNAc-GD1a
    • Progression 17
      • Nadir: Mean at 6 to 12 days; May be as short as 2 days
      • Shorter course than demyelinating GBS
    • Recovery
      • Significant improvement in strength over 1 to 2 months
      • ? More rapid with Haemophilus influenzae prodrome
  • Laboratory
    • Nerve conduction studies
      • Axonal >> Demyelination
      • May have prolonged distal latencies or conduction block
        • Occurs early: 1st 2 weeks
        • Disappears at later times
        • Less common than in AIDP
    • Serum Antibodies 25
      • IgG vs GM1 ganglioside (40% to 50%)
        • IgG reactivity to both GM1 & GM1b gangliosides
          • More strongly associated syndromes
            • Distal motor
            • Rapidly progressive
          • Treatment response: IVIg, not plasma exchange
        • IgG subclass: Associated with prodrome & speed of recovery phase 16
          • IgG1
            • Preceding gastroenteritis
            • Campylobacter jejuni serology +
            • Slow recovery (> 1 month)
          • IgG3
            • Preceding respiratory infection
            • Rapid recovery within 1 month
        • Epidemiology
          • Common: Japan, China & 3rd world countries
          • Rare: Most GBS-like sydromes (AIDP) in US & Canada
        • Pathophysiology of IgG anti-GM1 antibodies 19
          • May bind to: Nodes of Ranvier & Paranode of axons
          • Induce binding of C3 complement
          • Nodes of Ranvier: Disrupts Na+ channel clusters
          • Paranode
            • Detachment of paranodal myelin terminal loops
            • Caspr: Absent or reduced
          • ? Anti-GM1 & other antibodies block nerve conduction
      • IgG vs GalNAc-GD1a: Similar to syndrome with IgG vs GM1 ganglioside
        • Campylobacter jejuni infection
        • Acute motor neuropathies
        • Distal predominant weakness & Sparing of the cranial nerves
        • Rapidly progressive, severe weakness
        • Poor recovery
      • Other antibodies in AMAN syndromes
        • IgM vs GM1 ganglioside (30%)
        • IgG vs GD1a ganglioside (12% to 60%)
          • May be 2° to IgG binding to GalNAc-GD1a contaminant in GD1a
          • May be associated with AMAN or AIDP
        • IgG vs GM1b (15%)
        • IgM vs GalNAc-GD1a ganglioside
      • Antibody associations: Other
        • More common with prodromal infections: Campylobacter jejuni; Haemophilus influenzae
        • Time course: Highest titers at disease onset; Fall over weeks 15
        • Geography: Uncommon in many areas of US
    • Pathology
      • Motor nerve terminal degeneration
      • Severe weakness: More proximal axonal damage
      • Ventral root: Axon loss
      • Macrophage invasion of motor nodal axolemma: Focal axon damage
      • Sensory nerves normal
  • Treatment
    • IV Ig: Anecdotal evidence
    • Plasma Exchange: No evidence for benefit
    • Not Corticosteroids
  • Variant syndrome: Acute Motor-Sensory Axonal Neuropathy (AMSAN)
    • Nosology: ? Severe form of AMAN
    • Clinical
      • Weakness: Severe; Distal & Proximal
      • Sensory loss
    • Laboratory
      • NCV: Axon loss; Sensory & Motor
      • Serum IgG vs GM1 ganglioside: Some patients
    • Pathology

Guillain-Barré-like syndrome with serum IgM binding to GalNAc-GD1a ganglioside 2

Miller Fisher Syndrome 6

Serum IgG staining of
cerebellar molecular
layer in MFS
  • Epidemiology in Japan
    • Onset: Mean 40 years; Range 13 to 78 years
    • Seasonal: Higher frequency in Spring (March to May)
    • Clinical prodrome: Respiratory most common
    • Frequency: 25% of GBS in Japan; 1% of GBS in US
    • Associated infections
      • Campylobacter jejuni: Often serotype O-2 or O-10
      • Hemophilus influenzae: 7% of MFS patients with positive serology 11
  • Clinical
    • Onset
      • Diplopia (Asymmetric) (80%)
      • Myalgia & Paresthesias
      • Vertigo & Ataxia
    • Eye
      • External ophthalmoplegia (100%): Symmetric or Asymmetric
      • Pupillary dysfunction (42%): Mydriasis
      • Ptosis (58%)
    • Ataxia (100%): Dysmetria; Gait ataxia; Arms & Legs
    • Areflexia (100%): By 1 week of disease
    • Sensory
      • Distal & Facial paresthesias & dysesthesias (24%)
      • Sensory loss: Minimal; Definite in 20%
    • Weakness: 20%
    • Autonomic: Bladder disorders 16%
    • Other Cranial nerve disorders
      • Oropharyngeal weakness (26%)
      • Facial weakness (32%)
    • Progression
      • Over days to weeks
      • May progress to generalized weakness
      • Recovery
        • Onset: After 2 weeks to 2 months
        • Long term: Many with no residual defects
  • MFS-Cranial nerve variants: Often associated with IgG vs GQ1b or GT1b gangliosides
  • Laboratory
    • CSF
      • Protein: 20 to 60 mg/dl
      • Cells: Few or None; 0 to 5/mm 3
    • Nerve conduction studies
      • Sensory
        • Axonal loss
        • SNAPs: Reduced amplitude
      • Motor
        • Peripheral nerve: Normal or Reduced (35%) CMAP amplitudes
        • Facial: Reduced CMAP amplitude
      • F-waves: Prolonged; Dispersed; Absent
      • H reflexes: Absent from soleus
    • Serum antibodies
      • IgG vs GQ1b (80%)
      • IgG vs GT1a
      • IgG staining of cerebellar molecular layer
    • MRI
      • Cranial nerve enhancement (gadolinium) may occur 12
      • Brainstem or Cerebellar lesions: Some patients
  • Treatment: ? IVIg; ? Plasma exchange

(Sub)Acute Sensory Neuropathies 24

Autonomic
Acute ataxic: GD1b antibodies; Acute or Relapsing
Paracarcinomatous (anti-Hu antibodies)
Sensory Guillain-Barré
Sjögren's (SSA or SSB antibodies)
Small fiber neuropathy/neuronopathy, Acute
Toxic
  Cis-platinum
  Pyridoxine intoxication

Also see: Acute neuropathies


Acute sensory polyneuropathy with some demyelinating features (Sensory Guillain-Barré)
  • Clinical
    • Antecedent illness: Flu or URI in some
    • Onset
      • Over Days to Weeks
      • Paresthesias & Pain
    • Sensory
      • Loss
        • Pansensory
        • Proximal + Distal
      • Paresthesias & Pain
    • Autonomic dysfunction: Mild
    • Motor: Normal; Occasional mild weakness
    • Tendon reflexes
      • Usually absent
      • Rare patients may have preserved tendon reflexes
        • ? Central branch of sensory neuron damaged rather than cell body
        • ? Preserved Ia afferents to motor neurons
    • Course
      • Monophasic
      • Prognosis: Often incomplete recovery
  • Laboratory
    • Nerve conduction studies
      • Sensory potential amplitudes: Usually absent; May be reduced or normal
      • Conduction velocities: Relatively normal
      • Demyelinating features: Prolonged distal latencies in some patients
    • CSF: Protein high; No cells
    • Pathology
      • Nerve biopsy: Axonal loss; Mild inflammation
      • Autopsy: Lymphocytes in nerves & Dorsal roots
    • Epstein-Barr virus titers elevated in some patients 1

Bickerstaff brainstem encephalitis 13

  • Epidemiology: Most reports from Japan
  • Antecedent illness (92%): Most commonly upper respiratory infection
  • Age: 3 to 91 years
  • Onset: Diplopia or gait disorder most common
  • Clinical: Brainstem signs
    • Reduced consciousness (74%): Drowsy, stupor or coma
    • Ataxia: Often trunk & limb
    • Eyes
      • Ophthalmoplegia, external (100%): Relatively symmetric
      • Pupil disorders (34%)
      • Ptosis (29%)
      • Nystagmus (27%)
    • Other cranial nerves
      • Facial diplegia (45%)
      • Bulbar weakness (34%)
    • Weakness: Flaccid tetraparesis (60%); Respiratory failure
    • Pyramidal signs
      • Tendon reflexes: Variable; Hyperreflexia to Absent
      • Plantar responses (40%): Extensor
    • Sensory loss
      • Small fiber (31%)
      • Large fiber (16%)
      • Hemisensory loss
    • Course
      • Monophasic
      • Often good prognosis: Complete remission in 51%; Death 4%
  • Laboratory
    • Serum IgG binding to GQ1b ganglioside (66%)
    • Electrophysiology
      • Motor axon degeneration
      • Central involvement
    • MRI: CNS abnormalities
      • High intensity T2 signal
      • Locations: Brainstem, Thalamus, Cerebellum
    • CSF
      • Cells: Usually normal; Occasionally high WBCs (37%)
      • Protein: High in 59%; Higher in 2nd week than 1st
    • Pathology
      • Perivascular lymphocytic infitration
      • Edema
      • Glial nodules

Acute neuropathies: Pharyngo-Cervical-Brachial Variant 21

  • Prodromal associations: Within 4 weeks of illness
    • Upper respiratory infection (70%)
    • Diarrhea or other GI (30%)
    • Infection: Campylobacter jejuni > Cytomegalovirus
  • Clinical
    • Bulbar palsy
      • Dysphagia
    • Weakness
      • Neck
      • Arms: Proximal; Often initial symptom
      • Legs: Relatively preserved; Hip flexors most involved
      • Face: 50%
    • Sensation: Reduced or Normal
    • Tendon reflexes: Reduced, especially in arms
    • Cranial nerves
      • External ophthalmoplegia (50%)
    • Ataxia (40%)
    • Autonomic(20%): Especially heart rate & bladder dysfunction
    • Progression: 1 to 3 weeks
    • Overlap syndromes
  • Laboratory
    • CSF protein: High in some (42%)
    • NCV: Abnormal motor conduction or late responses
    • Antibody
      • IgG binding to GT1a or GM1b gangliosides without binding to GQ1b (65%)
      • IgG binding to GQ1b: Common with MFS overlap

Acute neuropathies: Bulbar Palsy Variant 29

  • Epidemiology: Asian patients
  • Clinical
    • Onset age: 18 to 54 years
    • Bulbar: Weakness
    • Gait: Ataxia (82%)
    • Face palsy (55%)
    • Ophthalmoplegia (82%): Abducens or Complete
    • Strength: Normal
    • Tendon reflexes: Absent (90%)
    • Paresthesias (55%): Limbs
    • Dizziness (90%)
    • Course: Monophasic over weeks to 3 months
  • Laboratory
    • NCV: Few patients with absent H-reflexes; Often normal
    • CSF protein: Usually normal
    • Antibody
      • IgG binding to GT1a (100%)
      • IgG binding to GQ1b (55%)


Acute Immune Neuropathies: Facial Diplegia Variant (BFP) 22

  • Epidemiology
    • Japanese & North American patients
  • Prodrome
    • Infectious symptoms in previous 4 weeks
      • Frequency: 86%
      • URI or Fever most common
  • Clinical
    • Onset
      • Age: 18 to 65 years
      • Limb numbness
    • Bifacial weakness
      • Progressive: Over weeks
      • Asymmetric: Often
    • Paresthesias
      • Most patients
      • Distal limbs
      • May persist for months
    • Strength: Normal or Mildly reduced
    • Tendon reflexes: Reduced or Absent
    • Other cranial nerves: Often normal
    • Course
      • Monophasic
      • Nadir at 4 weeks
      • Improvement over months
    • Differential diagnosis
  • Laboratory
    • CSF: Albumino-cytologic dissociation
      • Protein: 51 to 256
      • Cells: 1 to 8
    • Nerve conduction studies
      • Demyelination (64%)
        • Evolve with disease course
        • Proximal or Distal
        • Distal latencies & F-waves: Prolonged
        • Recovery toward normal over months
    • CMV antibodies: 35%
    • Other possible infection: B. burgdorferi
    • IgM anti-GM2: 23%; Commonly with anti-cytomegalovirus IgM antibodies
    • No IgG antibodies

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4/21/2018