Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP)

Guillain-Barre syndrome (GBS) or AIDP is an autoimmune disorder that affects peripheral nerves myelin or axons.

Introduction

  • Classified under the eponym Guillain-Barre syndrome (GBS)
  • Other variants of GBS include Acute Motor Axonal Neuropathy (AMAN), Acute Motor and Sensory Axonal Neuropathy (ASMAN), and the Miller Fisher syndrome (MFS).
  • AIDP is acute monophasic immune-mediated polyradiculoneuropathy provoked by a preceding infection

Epidemiology

  • Mean age of onset of 40 years affecting slightly more males than females of all ages, races and nationalities
  • Worldwide incidence of GBS ranges from 0.6 to 4.0/100,000 people

Etiology

  • AIDP is most common form of GBS in North America, Europe and most of the developed world representing about 85% to 90% of cases
  • ⅔ patients give history of antecedent respiratory tract or GI tract infection
  • Campylobacter jejuni infection is most commonly observed in 25-50% of the adult patients, with higher frequency in Asian countries.
  • Campylobacter associated GBS has worse prognosis, manifests slow recovery and with greater residual neurologic disability.
  • Other precipitants include EBV, CMV, mycoplasma, pneumonia, and influenza-like illnesses
  • Also has an association with HIV infection; predominantly in those who are not profoundly immunocompromised

Pathogenesis

  • Molecular Mimicry: auto-antibodies cross-react with peripheral nerve components because of sharing of cross-reactive epitopes
  • Immune response can be directed towards myelin or axon of peripheral nerve
  • Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP): When directed against epitopes in myelin or Schwann cell membrane; cellular + humoral immune responses are involved
  • Progression of disease for about two to four weeks
  • In a study pop. of 494 adult patients, disease nadir was reached in 2 week in 80% and within 4 weeks in 97%
  • If disease progression is more than 8 weeks, it is classified as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
  • Subacute inflammatory demyelinating polyneuropathy (SIDP) is considered if nadir is reached between 4 and 8 weeks

Box 1: Clinical Features of AIDP

 
💡
Box 1: Clinical Features of AIDP
Reaching nadir within 3-4 weeks
  • Dysautonomia (~70%)
  • Facial nerve Palsies (>50%)
  • Oculomotor weakness (15%)
  • Oropharyngeal weakness (50%)
  • SIADH (5%; more in hospitalized patients)
  • Paresthesias accompanying weakness (>80%)
  • Weakness begins in arms and facial muscles (10%)
  • Decreased or absent reflexes in affected arms or legs (90%)
  • Severe respiratory muscle weakness requiring ventilatory support (10%-30%)
  • Progressive, ascending & fairly symmetrical weakness starts in the legs (90%)
  • Pain due to nerve root inflammation, typically in the back and extremities (66%)

Rare features

  • Unusual clinical features of AIDP include: papilledema, facial myokymia, hearing loss, meningeal signs, vocal cord paralysis, and mental status changes.
  • Posterior reversible encephalopathy syndrome, also called reversible posterior leukoencephalopathy syndrome has been associated with GBS in children and adults likely related to acute hypertension from dysautonomia

Investigations

  • CSF Analysis
    • Cytoalbuminologic dissociation: normal cell count and increased protein level
    • In few cases (about 15%), mild increase in CSF cell count was seen
  • Electrodiagnostic findings
    • Absent H reflexes
    • Decreased motor nerve conduction velocity
    • Sural sparing pattern (early stages)
    • Prolonged distal motor latency
    • Increased F wave latency
    • Conduction blocks
    • Temporal dispersion
    • Serial NCS over weeks are sometimes needed to reliably distinguish between AMAN and ADIP
  • MRI
    • Thickening and enhancement of the intrathecal spinal nerve roots and cauda equina
    • Involvement of anterior spinal roots may be present, or both anterior and posterior roots

Diagnostic Criteria

In 1990, Asbury and Cornblath expanded the diagnostic criteria
Features required:
  • Progressive motor weakness of more than one limb.
  • Areflexia
Features strongly supportive of the diagnosis:
  • Progression of symptoms and signs
  • Relative symmetry
  • Mild sensory symptoms or signs
  • Cranial nerve involvement
  • Recovery
  • Autonomic dysfunction
  • Pain
  • No fever at the onset
  • Elevated protein in CSF with cell count ≤50cells/mm3
  • Electrodiagnostic abnormalities consistent with GBS

Features that make diagnosis of GBS doubtful:

  • Sensory level
  • Marked, persistent asymmetry of weakness
  • Bowel and bladder dysfunction at onset
  • Severe and persistent bowel and bladder dysfunction
  • Severe pulmonary dysfunction with little or no limb weakness at onset
  • Fever at onset
  • CSF pleocytosis
 

Table 2: Differential Diagnosis of AIDP

 
Table 2: Differential Diagnosis of AIDP
Disease
Pattern of Paralysis
Investigation
Autonomic Dysfunction
Cranial Nerve Involvement
Sensory Involvement
Ascending
Cytoalbumin dissociation
+
+
-
Descending
Toxic Detection
+
+
-
Generalized
Serum Electrolytes
-
-
+
Proximal
Repetitive Nerve Stimulation
+
+
-
Proximal
AChR Ab
-
+
-
 

Management

  • Triage and Initial Management algorithm:
    • Urgent intubation if clinical signs of respiratory distress, oxygen desaturation, or hypercapnia are present
    • Admit to ICU and consider elective intubation if
      • Moderate to severe or rapidly progressive appendicular weakness with bulbar dysfunction
      • Symptoms of respiratory insufficiency
      • Abnormal spirometry
        • FVC < 20mL/Kg
        • MIP > (-neg) 30 mmH2O
        • MEP < 40 mmH2O
        • or > 30% decrease from baseline value
      • Evidence of aspiration
      • Pronounced dysautonomia
    • Monitor on the ward if none of the above four mentioned points
  • Dysautonomia:
    • Manifestations:
      • Tachycardia
      • Urinary retention
      • Hypertension alternating with hypotension
      • Orthostatic hypotension
      • Bradycardia
      • Arrhythmias
      • Ileus
      • Loss of sweating
      • So the management must include:
    • Management:
      • Monitoring:
        • Cardiac rhythm
        • Close blood pressure monitoring
        • Fluid status
        • Intra-arterial monitoring if significant blood pressure fluctuations are present
        • Daily abdominal auscultation to monitor for bowel silence and for adynamic ileus
      • Treatment:
        • Low-dose phenylepinephrine if fluids are not effective for hypotension (Only low doses of carefully titrated short-acting vasoactive agents should be used to avoid possible effects of denervation hypersensitivity)
        • Labetalol, esmolol, or nitroprusside for MAP>125 mmHg
        • Intervention with administration of atropine and cardiac pacing might be required in life-threatening arrhythmias like AV block and asystole
        • Erythromycin or neostigmine may be effective for ileus
        • Gabapentin or carbamazepine for ICU pain control in acute phase
        • TCAs, gabapentin, carbamazepine, or pregabalin can be used for long-term pain management
  • Main modalities of treating GBS:
    • Plasmapheresis and IVIg are the mainstay of treatment for AIDP or for other variants of GBS
    • Oral steroids and methylprednisolone have not shown any benefits in this disorder
    • Combination of IVIg and plasma exchange is not significantly better than either alone
    • Plasma exchange:
      • Four to six rounds of plasmapheresis over 8-10 days.
      • Evidence based conclusion:
        • Median time to recover with plasma exchange was shorter than control group
        • Time of onset of motor recovery in mild GBS was significantly shorter than control group
        • More effective when started within 7 days of onset
        • 4 rounds of treatment were superior to 2 in moderate severe GBS
      • Adverse effects:
        • Hypotension
        • Sepsis
        • Problems related to central venous catheter:
          • Local hematoma
          • Pneumothorax
          • Line-related infection
        • Mild coagulopathy
        • Hypocalcemia
        • Transfusion reaction (including transfusion related acute lung injury)
      • Intravenous immune globulin (IVIg):
        • 0.4 gram/kg per day for 5 days
        • Evidence based results:
          • Studies compared IVIg with plasmapheresis
          • IVIg is as effective as plasma exchange for GBS
          • Patients assigned to IVIg are significantly less likely to discontinue treatment than those on plasmapheresis
        • Adverse effects:
          • Aseptic meningitis
          • Chest pain
          • Infusion reaction:
            • Headache
            • Shivering
            • Myalgia
          • Anaphylaxis (if IgA deficient)
          • Acute renal failure
          • Hyperviscosity leading to stroke (rare)
    • No evidence shows a second course of IVIg to be effective in patients of GBS that continue to deteriorate

Table 3: Complications of AIDP

Prognosis

  • Respiratory Failure:
    • 15-30% of AIDP patients need ventilatory support
    • Predictors of respiratory failure:
      • Evidence based conclusion: mechanical ventilation was required in >85% patients with four out of the following six predictors
        • Time of onset to admission <7 days
        • Inability to cough
        • Inability to stand
        • Inability to lift the elbows
        • Inability to lift the head
        • Increase in LFTs
  • Disability:
    • 20% of patients are unable to walk after 6 months
    • Most patients have residual pain and fatigue due to persistent axonal loss
  • Mortality rate
    • 3-10%
    • Death can occur in acute progressive state most probably due to ventilatory insufficiency or pulmonary complications, or from dysautonomia like arrhythmia
    • Death can also occur in later stage
  • Treatment Related Fluctuations (TRF)
    • 10% patients will deteriorate within the first 8 weeks after the start of IVIg which is called TRF
    • Repeated treatment with IVIg has been shown to be beneficial in these patients
  • CIDP with acute onset (A-CIDP)
    • 5% of patients initially diagnosed with AIDP were eventually found to have acute onset CIDP
    • Diagnosis should be considered in patients :
      • Initially diagnosed with AIDP who have 3 or more periods with clinical deterioration
      • Or when there is new deterioration after 8 weeks from onset of weakness
  • TRF vs A-CIDP:
    • The difference is significant management wise.
    • There might be improvement with retreatment in TRF whereas patients with A-CIDP need chronic maintenance treatment with IVIg or a switch to corticosteroid treatment
  • GBS Disability Score:
    • It uses level of disability be documented using a scale from 0 to 6.
  • EGOS:
    • The Erasmus GBS Outcome Score (EGOS) is a prognostic model based on age, diarrhea, and GBS disability at 2 weeks after hospital admission
    • It accurately predicts the chance of being able to walk independently at 6 months
  • mEGOS:
    • Modified EGOS was developed to apply at hospital admission and at day 7 of hospital stay as compared to original EGOS model which applied on 14th day of stay
    • It requires Medical Research Council (MRC) Scale for Muscle Strength score instead of disability
    • According to this study, poor outcome is associated with:
      • Older age
      • Rapid disease progression
      • Severe disease indicated by GBS disability score or MRC sumscore
      • C. jejuni or CMV positive serology
      • Preceding respiratory tract infection
  • NCS might also have prognostic value; patients with features of demyelination are more prone to need mechanical ventilation
  • Low compound action potentials (CMAPs) are the most consistent findings predictive of poor outcome

Further reading

Comprehensive review article: Willison, H. J., Jacobs, B.C.. van Doorn, P. A. (2016). Guillain-Barré syndrome. The Lancet. 388:10045(717-727). https://doi.org/10.1016/S0140-6736(16)00339-1

Bibliography

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