Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP)

Authors:

Umair Hamid MD,

Saud Khan MD

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

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

• Progressive motor weakness of more than one limb.

• Areflexia

• 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

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

• Online prognosis model: https://gbstools.erasmusmc.nl/prognosis-tool

Further reading

Bibliography

• Willison, H. J. et. al (2016). Guillain-Barré syndrome. The Lancet. 388:10045(717-727). https://doi.org/10.1016/S0140-6736(16)00339-1

• Walgaard, C. et. al (2011). Early recognition of poor prognosis in Guillain-Barre syndrome. Neurology. 76(11): 968-975. doi: 10.1212/WNL.0b013e3182104407

• Fokke, C. et. al (2014). Diagnosis of Guillain-Barre syndrome and validation of Brighton criteria. Brain. 10.1093/brain/awt285. Epub 2013 Oct 26.

• Rees, J. H. et. al (1995). Campylobacter jejuni infection and Guillain–Barré syndrome. New England Journal of Medicine, 333(21), 1374-1379.

• Visser, L. H. et. al (1995). Guillain-Barré syndrome without sensory loss (acute motor neuropathy) A subgroup with specific clinical, electrodiagnostic and laboratory features. Brain, 118(4), 841-847.

• Jacobs B.C. et. al (1998). The spectrum of antecedent infections in Guillain-Barre syndrome: A case-control study. Neurology. 51(4):1110-1115.

• Dimachkie, M. M., & Barohn, R. J. (2013). Guillain-Barré syndrome and variants. Neurologic clinics, 31(2), 491-510.