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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
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 or GalNAc-GD1a ganglioside
- Sensory
- Autonomic
Cranial Nerve Syndromes: Associated with
- Campylobacter jejuni prodrome
- Serum IgG vs GQ1b ganglioside
- Miller-Fisher
- 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

Acute immune neuropathies have several features in common as well as those that vary and are distinctive for a particular syndrome. Some features suggest a different diagnosis among the causes of acute motor dysfunction. Principles regarding which treatment to use are somewhat subjective.

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
- 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%
  - Pain
    - Prominent in 70%
    - Associations
      - Neuropathy: In back, hips & legs at onset; Myalgias; Occasional radicular
      - Immobility: Myalgias
      - 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
  - 1% 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
- 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
  - 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 Neuropathy

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 = Famale
- 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 infection⁵
    - 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
- Weakness
  - Distal > Proximal
  - ± Symmetric
  - Cranial Nerves (25%)
  - ? Less respiratory failure vs classic GBS
- Sensory
  - Normal by clinical & electrodiagnostic testing
  - No paraesthesias
- Reflexes
  - Reduced in proportion to strength
  - Hyperreflexia may occur
- Progression¹⁷
  - Mean nadir at 6 to 12 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
- Serum Antibodies
  - 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
  - IgM vs GM1 ganglioside (30%)
  - ? IgG vs GD1a ganglioside (18% to 60%)
    - May be 2° to IgG binding to GalNAc-GD1a contaminant in GD1a
    - Not present more frequently in any GBS subgroup
  - 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
  - More common with prodromal infections: Campylobacter jejuni; Haemophilus influenzae
  - Time course: Highest titers at disease onset; Fall over weeks¹⁵
  - Also see: IgM vs GalNAc-GD1a ganglioside
- Pathology
  - ? Anti-GM1 & other antibodies block nerve conduction
  - 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 Neuropathy

Clinical
- Onset
  - Over Days to Weeks
  - Paresthesias & Pain
- Pansensory loss
  - Proximal + Distal
- 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
- Prognosis: Often incomplete recovery
- Idiopathic: ? GBS-like syndrome
Differential Diagnosis
- Paracarcinomatous (anti-Hu antibodies)
- Sjögren's (SSA or SSB antibodies)
- GD1b antibodies: Acute or Relapsing
- Toxic: Cis-platinum; Pyridoxine intoxication
Laboratory
- Nerve conduction studies
  - Sensory potential amplitudes: Usually absent; May be reduced or normal
  - Conduction velocities: Relatively normal
- Nerve biopsy: Axonal loss; Mild inflammation
- 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

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12/4/2007