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Acute Immune Polyneuropathies

"Classic" Guillain-Barré Syndrome   Associated disorders   Childhood GBS   Clinical features   Electrodiagnostic features   Epidemiology   Laboratory features   Morbidity   Prognosis   Prodrome   Therapy Other Acute Immune Neuropathies   Autonomic   Motor   Sensory   Cranial nerve variants     Ataxia & Ophthalmoplegia     Bickerstaff     Facial diplegia     Miller Fisher Syndrome     Pharyngo-Cervico-Brachial   IgM vs GalNAc-GD1a General topics   Classification: Acute immune neuropathies   Differential diagnosis: Acute neuromuscular disorders   General Principles: Acute immune neuropathies   Treatment of GBS-like syndromes   Antibodies

Guillain Also see: GBS history

Classification of Acute Immune Neuropathies

• Demyelinating (± 2° axonal loss)
  • Motor + Sensory
    • Classic Guillain-Barré
    • CIDP with acute onset: More prominent demyelination on NCV
  • Motor
• Axonal
  • Motor + Sensory (AMSAN)
    • GBS-like syndrome
    • Vasculitis
  • Motor: Associated with
    • Prodromal infection: Campylobacter jejuni; Haemophilus influenzae
    • Serum antibodies: IgG vs GM1, GM1b, GD1a or GalNAc-GD1a ganglioside
  • Sensory
  • Autonomic
• Cranial Nerve Syndromes: Associated with
  • Campylobacter jejuni prodrome
  • Serum IgG vs GQ1b ganglioside
  • Miller-Fisher
  • Facial diplegia
  • Bickerstaff's Brainstem encephalitis
  • Pharyngo-cervico-brachial
    
• Other GBS variants with autoantibodies
  • IgM vs GM2 gangliosides
  • IgM vs GalNAc-GD1a ganglioside

Acute immune neuropathies: General principles

• Common features
  • Prodrome
    • 50% of patients in 2 weeks prior to disease onset
  • 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
  • Sensory level: Spinal cord syndrome
  • Severe bladder or bowel dysfunction: Spinal cord syndrome
  • Marked asymmetry: Vasculitis
  • > 50 WBC/mm3
    • Infectious disorders: HIV; Lyme; Polio
  • Very slow nerve conduction velocities (< 32 M/s): CIDP
    • Relapses, or a chronic course, may be more likely
• 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 Prodrome Prognosis Therapy

• Epidemiology
  • Incidence: 1 to 2/100,000/year
  • Male: Female = 1.25: 1
  • Peak ages: Young adults & > 55 years
  • 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
• 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: Pa_O2 < 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%
    • Pain²³
      • 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
  • Death
    • Frequency: 3% to 10%
    • Causes: Pneumonia; Iatrogenic hypotension
    • Associations: Mechanical ventilation; ? Autonomic dysfunction
• 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
      • Higher Frequency of serum IgM vs GM2 ganglioside
      • Also see IgM vs GalNAc-GD1a ganglioside
  • 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: Epstein-Barr virus; HIV; ? Hepatitis A
  • 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: 1^st 2 weeks with higher risk
  • Surgery
  • ? Graft vs Host disease
  • Drugs: Zimeldine
• 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) features⁹
    • 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
• GBS: Humoral Immunity
  • IgM or IgG vs Tubulin: 10%
  • 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
• 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%), unless associated disorder present
    • 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 patients¹⁴
    • 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: DQβRLD^55–57/ED^70–71 & DRβE⁹V¹¹H¹³
    • Protection: DQβRPD^55–57 epitope
• 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
      
• Associated Systemic Disorders
  • Infections: Prodromes
    • Viral
      • Cytomegalovirus (CMV)
      • Epstein-Barr virus (EBV) ± Hemophagocytic syndrome
      • Human immunodeficiency
      • Influenza
    • Bacterial
      • Campylobacter jejuni
      • Mycoplasma pneumoniae
  • 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
• Prognostic factors
  • Mechanical ventilation needed⁸
    • 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
        • 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
      • Axonal 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
        • Recent CMV infection
• Treatment
  • Immunomodulation
    • Plasma Exchange or IV IgG definitely indicated
      • Patients with inability to walk
      • 1st 2 weeks of disease
      • Decision between IV IgG & PE: Depends on individual features of patient & disease
    • 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 with immobility: Lower Risk of thromboembolic events
• Other: Books by GBS patients or relatives (PDF file)

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 strains¹⁸
        • 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)
          • 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%
  • ? 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: Distal motor, rapidly progressive syndromes
        • Treatment response: IVIg, not plasma exchange
      • IgG subclass: Associated with prodrome & speed of recovery phase¹⁶
        • 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 antibodies¹⁹
        • 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 weeks¹⁵
      • 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: Anecdotal evidence
  • IV Ig
  • Plasma Exchange
  • Not Corticosteroids

Guillain-Barré-like syndrome with serum IgM binding to GalNAc-GD1a ganglioside²

• Epidemiology
  • Japanese patients
  • Younger onset: Mean 3rd decade
  • ? Female > Male
• Clinical
  • Prodrome
    • GI: Campylobacter jejuni (75%)
    • Respiratory: Cytomegalovirus
  • Weakness: Mild; Proximal + Distal
  • Sensory: Paresthesias ± Loss (75%); More common with CMV prodrome
  • Cranial nerves: Facial weakness (27% to 80%); More common with CMV prodrome
  • Recovery: Good at 1 month; Better than with IgG or no antibodies
• Electrodiagnostic
  • Demyelination in many (38% to 64%)
  • Axonal loss uncommon
• Serum antibody
  • IgM vs GalNAc-GD1a ganglioside
  • Cross reactive with GM2 ganglioside: 100% with CMV prodrome; 50% with GI prodrome
  • Patients with GI prodrome commonly have other IgM antibodies as well: anti-GM1 & GD1b
  • Also see
    • Chronic demyelinating neuropathy with IgM binding to GalNAc-GD1a & GM2
    • Chronic motor neuropathy with IgG binding to GalNAc-GD1a

Miller Fisher Syndrome⁶

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 serology¹¹
• 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
  • GBS overlap: Ophthalmoplegia; Weakness; ± Ataxia
  • Internal ophthalmoplegia: Dilated pupils; Light-near dissociation
  • Acute external ophthalmoplegia: Complete or partial
  • Acute ataxia: May progress to Weakness & GBS
  • Visual impairment⁷
  • Rule out: Neurosyphilis
  • Chronic ophthalmoplegia with serum IgG binding to GQ1b ganglioside³
    • May be associated with vestibulopathy or demyelinating neuropathy
  • Acute neuropathies with bulbar dysfunction: Pharyngo-cervical-brachial variants
  • Bickerstaff brainstem encephalitis: Brainstem signs¹³
• Laboratory
  • CSF
    • Protein: 20 to 60 mg/dl
    • Cells: Few or None; 0 to 5/mm³
  • Nerve conduction studies
    • Sensory
      • Axonal loss
      • SNAPs: Reduced amplitude
    • Motor
      • Peripheral nerve: Normal CMAPs
      • Facial: Reduced CMAP amplitude
    • F-waves: Prolonged; Dispersed; Absent
    • H reflexes: Absent from soleus
  • Serum antibodies
    • IgG vs GQ1b (80%)
    • IgG staining of cerebellar molecular layer
  • MRI
    • Cranial nerve enhancement (gadolinium) may occur¹²
    • Brainstem or Cerebellar lesions: Some patients
• Treatment: ? IVIg; ? Plasma exchange

(Sub)Acute Sensory Neuropathies ²⁴

• 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 patients¹

Bickerstaff brainstem encephalitis¹³

• 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 Variant²¹

• Prodromal associations: Within 4 weeks of illness
  • Diarrhea
  • Campylobacter jejuni infection
• Clinical
  • Bulbar palsy
  • Weakness: Neck & proximal arms; Legs relatively preserved
  • Sensation: Normal
  • Tendon reflexes: Reduced, especially in arms
  • Progression: 1 to 3 weeks
• Laboratory
  • CSF protein: High
  • NCV: Abnormal motor conduction or late responses
  • Antibody: IgG binding to GT1a or GM1b gangliosides without binding to GQ1b

Acute neuropathies: Facial Diplegia Variant²²

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