Chapter 122
Managing Critically Ill Patients with
AIDP: Relevance of International
Guidelines to Indian Scenario
B Vengamma
ABSTRACT
Guillain-Barré syndrome (GBS) is the most frequent cause of acute flaccid
paralysis globally. It is also an important life-threatening emergencies
requiring critical care in neurology and carries a grave prognosis in a
substantial number of patients. Based on electrophysiological studies,
GBS has been categorized into acute inflammatory demyelinating
polyradiculoneuropathy (AIDP), acute motor axonal neuropathy
(AMAN), and acute motor sensory axonal neuropathy (AMSAN).
From a critical care point of view, 40% of patients may present with
oropharyngeal or respiratory muscle weakness, 25–35% develop
acute respiratory failure requiring assisted mechanical ventilation.
Important complications observed in critically ill patients with AIDP
include unexplained cardiac arrest, perhaps related to dysautonomia,
pneumonia, sepsis, pulmonary embolism, gastrointestinal bleeding,
among others. Neither prednisolone nor methylprednisolone can
significantly accelerate recovery or affect the long-term outcome in
patients with GBS. Plasma exchange is established as effective and
should be offered in severe AIDP/GBS severe enough to impair the
ability to walk independently or to require mechanical ventilation (Class
I studies, Level A). It is probably effective and should be considered
for mild AIDP/GBS in which ambulation is preserved. Intravenous
immunoglobulin (IVIg) is as efficacious as plasma exchange and should
be offered for treating GBS in adults (Level A). It is especially helpful
if initiated within 2 weeks after disease onset. There is no advantage
of combining plasma exchange with IVIg. In the Indian scenario, if
infrastructural facilities exist, plasma exchange is a cheaper option,
but huge initial investment is required to setup plasma exchange, and
procure and periodically renew permissions and licenses for providing
plasma exchange. Though IVIg is more widely available, the cost is
prohibitive.
INTRODUCTION
Guillain-Barré syndrome is the most frequent cause of acute
flaccid paralysis globally.1-3 Currently available evidence supports
autoimmune etiology of GBS.4 In its classic form, the disease is
characterized by acute onset of weakness of the limbs or cranial
nerve innervated muscles, progressive areflexic paralysis, varying
degrees of sensory abnormalities, autonomic dysfunction due
to damage to peripheral nerves and nerve roots, and increased
protein in cerebrospinal fluid (CSF) with no pleocytosis.1-3 It is also
an important life-threatening emergency requiring critical care in
neurology. Contrary to the common misconception that the disease
has a good prognosis, the mortality and severe disability due to GBS
has been documented to be up to 5% and 20% respectively, and
the disease carries a grave prognosis in a substantial number of
patients.1-3
Guillain-Barré syndrome includes a group of peripheral
nerve disorders, each distinguished by the distribution of
weakness in the limbs or cranial nerve innervated muscles and
underlying pathophysiology. Various subtypes of GBS have been
described (Table 1).1-3 Based on electrophysiological studies,
GBS has been categorized into acute inflammatory demyelinating
polyradiculoneuropathy (AIDP), acute motor axonal neuropathy
(AMAN) and acute motor sensory axonal neuropathy (AMSAN).1-3
However, it is difficult to distinguish these subtypes on clinical
features alone.
EPIDEMIOLOGY
In the developed countries, the median incidence of GBS has been
estimated to be 1.11 per 100,000 person-years. After the first decade
of life, there is an escalating increase of 20% with each passing decade
of life. The male and female gender ratio has been observed to be
1.78.1 Nearly two-thirds of cases are preceded by symptoms of upper
respiratory tract infection or diarrhea and rarely vaccination (e.g. A/
New Jersey/1976/H1N1 “swine flu” vaccine). Studies have shown
TABLE 1 │ Various subtypes of Guillain-Barré syndrome
Guillain-Barré syndrome
Acute inflammatory demyelinating polyneuropathy (AIDP)
•  Facial variant: Facial diplegia and paresthesia
Acute motor axonal neuropathy (AMAN)
•  More and less extensive forms
–  Acute motor-sensory axonal neuropathy (AMSAN)
–  Acute motor-conduction-block neuropathy
•  Pharyngeal-cervical-brachial weakness
Acute pandysautonomia
Acute sensory form
Miller-Fisher syndrome
Incomplete forms
•  Acute ophthalmoparesis (without ataxia)
•  Acute ataxic neuropathy (without ophthalmoplegia)
CNS variant: Bickerstaff’s brainstem encephalitis
Source: Yuki N, Hartung HP. Guillain-Barré syndrome. N Engl J Med.
2012;366:2294-304. van Doorn PA, Ruts L, Jacobs BC. Clinical features,
pathogenesis, and treatment of Guillain-Barré syndrome. Lancet Neurol.
2008;7:939-50
 Section 16 Chapter 122  Managing Critically Ill Patients with AIDP

cross-reactivity between infectious and neural epitopes especially
for Campylobacter jejuni and certain forms, for e.g. motor axonal
forms of GBS.1,2,4 Among the electrophysiological subtypes, AIDP is
considered to be the most common in western countries; whereas,
axonal types are more common in Asian countries.1-3 However,
studies from India5-8 have yielded varying results with AIDP being
more commonly described in some of the studies (Table 2).
CLINICAL MANIFESTATIONS
Patients with AIDP present with numbness, paresthesias, weakness,
pain in the limbs, or some combination of these symptoms. AIDP
typically manifests as an ascending paralysis that usually begins in
the feet; at presentation, nearly 60% of patients manifest symmetrical
weakness in all four limbs. Generalized hyporeflexia or areflexia is
common. Mild degrees of asymmetry is not uncommon, especially
early in the course of the disease, and in the arms, the weakness may
be worse proximally than distally. However, variants that differ from
the classic AIDP are frequently encountered. About half the patients
may present with facial weakness, and 5% may manifest varying
degrees of ophthalmoplegia. AIDP encompasses the Miller-Fisher
syndrome characterized by ophthalmoplegia, ataxia and areflexia; its
incomplete forms are manifested by acute ophthalmoparesis without
ataxia and acute ataxic neuropathy without ophthalmoplegia, and
the more extensive form, Bickerstaff’s brainstem encephalitis.
About two-thirds of patients have one or more autonomic
abnormalities. Sustained sinus tachycardia is the most common
dysfunction. Postural hypotension leading to presyncope or syncope
can occur. Pure pandysautonomia with minimal weakness, areflexia
and autonomic failure has also been described. Diagnostic criteria
for GBS have been listed in Table 3.9 Differential diagnosis of AIDP
has been listed in Table 4. Presence of certain clinical features is
considered inconsistent with a diagnosis of AIDP. These include
weakness that remains markedly asymmetric, a sharp sensory level,
and severe bladder or bowel dysfunction at the onset.
CRITICAL CARE CONCERNS
The disease progresses for up to 1–3 weeks after the onset
of symptoms and nearly 40% of patients may present with
oropharyngeal or respiratory muscle weakness. About 25–35%
develop acute respiratory failure requiring assisted mechanical
ventilation.1,2,10-12 Important complications observed in critically
ill patients with AIDP include unexplained cardiac arrest, perhaps

TABLE 2 │ Prevalence of various subtypes of Guillain-Barré syndrome* in some recent studies from India
Variable Kalita et al. (2008)5 Gupta et al. Alexander et al. (2011)7 Vengamma (2011)8
(2008)6
Place of study Lucknow Thiruvananthapuram Vellore Tirupati
No. of subjects studied 51 142 115 59
AIDP 86.3% 85.2% 38.2% 76.2%
Axonal variants AMAN in 7.8% and AMAN in 10.6% 51 (44.3%) AMAN in 3.4%, AMSAN in 12%
AMSAN in 5.9% [AMAN in 35 (30.4%) and
AMSAN in 16 (13.6%)]
Unclassifiable - 4.2% 17.4% 3.4%
* Miller-Fisher syndrome was also observed in 5%
Abbreviations: AIDP, Acute inflammatory demyelinating polyneuropathy; AMAN, Acute motor axonal neuropathy; AMSAN, Acute motor-sensory axonal neuropathy

TABLE 3 │ Diagnostic criteria for typical GBS

Features required for diagnosis
Progressive weakness in both arms and legs (might start with weakness only in the legs)
Areflexia (or decreased tendon reflexes)
Features that strongly support diagnosis
Progression of symptoms over days to 4 weeks
Relative symmetry of symptoms
Mild sensory symptoms or signs
Cranial nerve involvement, especially bilateral weakness of facial muscles
Autonomic dysfunction
Pain (often present)
High concentration of protein in CSF
Typical electrodiagnostic features
Features that should raise doubt about the diagnosis of GBS include presence of the following manifestations at the onset, such as fever, severe pulmonary
dysfunction with limited limb weakness at onset, severe sensory signs with limited weakness, bladder or bowel dysfunction, a sharp sensory level, slow progression
with limited weakness without respiratory involvement (subacute inflammatory demyelinating polyneuropathy or CIDP likely), marked persistent asymmetry of
weakness, persistent bladder or bowel dysfunction, increased number of mononuclear cells in CSF (> 50 × 106/L) and presence of polymorphonuclear cells in
CSF.
Abbreviations: GBS, Guillain-Barré syndrome; CSF, Cerebrospinal fluid; CIDP, Chronic inflammatory demyelinating polyneuropathy
Source: Asbury AK, Cornblath DR. Assessment of current diagnostic criteria for Guillain-Barré syndrome. Ann Neurol. 1990;27 Suppl:S21-4.

557
 Neurology Section 16

TABLE 4 │ AIDP: Differential diagnosis

Muscular abnormalities Neuromuscular Peripheral nerve Spinal nerve Anterior Intracranial/spinal
junction abnormalities root abnormalities horn cell cord abnormalities
abnormalities abnormalities
Critical illness Myasthenia gravis CIDP Compression Poliomyelitis Brainstem encephalitis
Polyneuromyopathy Botulism Drug-induced Inflammation (e.g. West Nile virus Meningitis
Polymyositis Organophosphate neuropathy cytomegalovirus) Carcinomatosis/
Dermatomyositis poisoning Porphyria Leptomeningeal lymphomatosis
Acute rhabdomyolysis Critical illness malignancy Transverse myelitis
Polyneuropathy Cord compression
Vasculitis
Diphtheria
Beri-beri
Heavy metal or drug
intoxication
Tick paralysis
Metabolic disturbances
(hypokalemia,
hypophosphatemia,
hypermagnesemia,
hypoglycemia)
Abbreviations: AIDP, Acute inflammatory demyelinating polyneuropathy; CIDP, Chronic inflammatory demyelinating polyneuropathy
Source: Yuki N, Hartung HP. Guillain-Barré syndrome. N Engl J Med. 2012;366:2294-304. van Doorn PA, Ruts L, Jacobs BC. Clinical features, pathogenesis,
and treatment of Guillain-Barré syndrome. Lancet Neurol. 2008;7:939-50.

related to dysautonomia, pneumonia, sepsis, pulmonary embolism,
gastrointestinal bleeding, among others (Table 5).
UTILITY OF INTERNATIONAL GUIDELINES
ON ­DIAGNOSIS
Till 2009, several case definitions of GBS existed like the Asbury-
Cornblath case definition8 (Table 3), which required ancillary
diagnostic testing including electrophysiological studies.
Subsequently, Brighton criteria (Table 6)13 based on purely clinical
case definition have been introduced for use in resource limited
countries. In a study conducted from India,14 the sensitivity of the
Brighton Working Group case definitions for GBS was evaluated using
a population-based cohort from the National Polio Surveillance Unit
of India (that actively collects all cases of acute flaccid paralysis in
children under 15 years old). During the period 2002–2003, 79 cases
with GBS were selected, in which the diagnosis of GBS was based on
clinical history, neurological examination findings, CSF and nerve
conduction studies (NCS) results. The sensitivity of the Brighton GBS
criteria (Table 6) for level 3 of diagnostic certainty (which requires no
clinical laboratory testing), level 2 (which employs CSF or NCS) and
level 1 (which employs both) was computed. The majority of cases
(86%) fulfilled Brighton level 3 (86%), level 2 (84%), and level 1 (62%)
diagnostic certainty suggesting that these criteria are potentially
useful with a moderate to high sensitivity in resource limited settings
like India.14
TREATMENT
General Measures
Ideally, all patients with AIDP should remain hospitalized until it is
certain that there is no evidence of clinical progression of the disease.
Patients with AIDP should be ideally treated in a neurological
intensive care unit, where adequate resources for continuous
cardiac and respiratory monitoring are available. The key principles
underlying the general care and monitoring of patients with AIDP
have been listed in Table 7 and Flow chart 1. Early assessment
and careful monitoring of swallowing will identify patients at risk
for aspiration, necessitating the placement of a nasogastric tube.
TABLE 5 │ Complications of acute inflammatory demyelinating
polyneuropathy (AIDP)
Respiratory failure
Acute respiratory distress syndrome
Pneumonia
Aspiration
Sepsis
Pulmonary embolism
Deep vein thrombosis
Hypotension or hypertension
Cardiac arrhythmias
Pressure sores
Paralytic ileus
Urinary retention
Psychiatric problems such as depression and anxiety
Careful watch of the breath holding time and single breath counting
time will facilitate early identification of patients requiring assisted
mechanical ventilation.
Patients with AIDP with dysautonomia can manifest serious
and potentially fatal arrhythmias and extreme hypertension or
hypotension, which may be seen in 20% of patients with GBS, and
these need to be monitored carefully. Severe bradycardia may
warrant the use of a temporary cardiac pacemaker.
Mechanical Ventilation
Even in the absence of clinical respiratory distress, mechanical
ventilation may be required in patients with at least one major
criterion or two minor criteria. The major criteria are hypercarbia
(partial pressure of arterial carbon dioxide > 48 mm Hg), hypoxemia
(partial pressure of arterial oxygen while the patient is breathing
ambient air < 56 mm Hg) and a vital capacity less than 15 mL/kg
of body weight. The minor criteria are inefficient cough, impaired
swallowing and atelectasis.1

558
 Section 16 Chapter 122  Managing Critically Ill Patients with AIDP

TABLE 6 │ Brighton Working Group clinical case definitions: GBS

Level 1 of Diagnostic Certainty
Presence of:
1. Acute onset of bilateral and relatively symmetric flaccid weakness/paralysis of the limbs with or without involvement of respiratory or cranial nerve
innervated muscles
2.  Decreased or absent deep tendon reflexes at least in affected limbs
3. Monophasic illness pattern with weakness nadir reached between 12 hours and 28 days, followed by clinical plateau and subsequent
improvement or death
4.  Electrophysiologic findings consistent with GBS
5. Presence of albuminocytologic dissociation (elevation of CSF protein level above laboratory normal value and CSF total white cell count < 50
cells/mm3)
6.  Absence of an alternative diagnosis for weakness
Level 2 of Diagnostic Certainty
Presence of:
1. Acute onset of bilateral and relatively symmetric flaccid weakness/paralysis of the limbs with or without involvement of respiratory or cranial nerve
innervated muscles
2.  Decreased or absent deep tendon reflexes at least in affected limbs
3. Monophasic illness pattern, with weakness nadir reached between 12 hours and 28 days, followed by clinical plateau and subsequent
improvement or death
4. CSF with a total white cell count < 50 cells/mm3 (with or without CSF protein elevation above laboratory normal value) or if CSF not collected or
results not available, and electrodiagnostic studies consistent with GBS
5.  Absence of an alternative diagnosis for weakness
Level 3 of Diagnostic Certainty (clinical case definition)
Presence of:
1. Acute onset of bilateral and relatively symmetric flaccid weakness/paralysis of the limbs with or without involvement of respiratory or cranial nerve
innervated muscles
2.  Decreased or absent deep tendon reflexes at least in affected limbs
3. Monophasic illness pattern, with weakness nadir reached between 12 hours and 28 days, followed by clinical plateau and subsequent
improvement or death
4.  Absence of an alternative diagnosis for weakness
Abbreviations: GBS, Guillain-Barré syndrome; CSF, Cerebrospinal fluid

TABLE 7 │ General care and monitoring of patients with AIDP Immunotherapy

• Regular monitoring of pulmonary function (vital capacity, respiration
frequency), initially every 2–4 hours; in stable phase, every 6–12
hours
• Regular check for autonomic dysfunction (at initial presentation: blood
pressure, heart rate, pupils, ileus; preferably continuous monitoring
of ECG, pulse and blood pressure; if logistically difficult, check every
2–4 hours; in stable phase, every 6–12 hourly)
• Careful check for swallowing dysfunction
• Recognition and treatment of pain: acute nociceptive pain (preferably
avoid opioids), chronic neuropathic pain (amitriptyline or antiepileptic
drugs)
• Prevention and treatment of infections and pulmonary embolism
• Prevention of corneal ulceration due to facial weakness
• Prevention of decubitus ulcers and contractures
In studies from India, factors independently associated with the
need for mechanical ventilation included elderly age (p = 0.014),
simultaneous motor weakness in both upper and lower limbs as
the initial symptom (p = 0.02), upper limb power less than grade 3/5
(Medical Research Council grade) at nadir (p = 0.013), presence of
bulbar weakness (p < 0.001), autonomic dysfunction (p = 0.002) and
pulmonary complications (p = 0.011).10-12
Plasma Exchange
Plasma exchange eliminates circulating immunoglobulins
and immune complexes directed at components of the central
and peripheral nervous system. This was the first therapeutic
intervention found to be effective in hastening recovery in patients
with GBS, especially if it was started within the first 2 weeks
after disease onset in patients who were unable to walk. Plasma
exchange nonspecifically removes antibodies and complement,
and appears to be associated with reduced nerve damage
and faster clinical improvement as compared with supportive
therapy.15
As per the report of the Therapeutics and Technology Assessment
Subcommittee of the American Academy of Neurology,16 plasma
exchange is established as effective, and should be offered in severe
AIDP/GBS severe enough to impair the ability to walk independently
or to require mechanical ventilation (Class I studies, Level A). It is
probably effective and should be considered for mild AIDP/GBS
in which ambulation is preserved. The usual empirical regimen is
five exchanges over a period of 2 weeks with a total exchange of five
plasma volumes. One trial showed that patients who could walk with
or without aid but could not run benefited from two exchanges of 1.5
plasma volumes, but more severely affected patients required at least
four exchanges.
559
 Neurology
Flow chart 1: Algorithm for the management of critically ill patients with AIDP
Abbreviations: AIDP, Acute inflammatory demyelinating polyneuropathy; CSF, Cerebrospinal fluid; NCS, Nerve conduction studies; BP, Blood pressure; VC, Vital
capacity; IVIg, Intravenous immunoglobulin
Intravenous Immunoglobulin
As per the report of the Therapeutics and Technology Assessment
Subcommittee of the American Academy of Neurology,17 IVIg is as
efficacious as plasma exchange and should be offered for treating
GBS in adults (Level A). It is especially helpful if initiated within 2
weeks after disease onset. In general, IVIg has replaced plasma
exchange as the treatment of choice in many medical centers because
of its greater convenience and availability. According to the standard
treatment regimen, IVIg is given at a total dose of 2 g/kg body weight
over a period of 5 days. The pharmacokinetics of IVIg varies among
patients, and some patients have a smaller rise in serum IgG after
the administration of IVIg. These patients are likely to have a poorer
outcome with fewer patients being able to walk unassisted at 6
months. A second course of IVIg in severely unresponsive patients
has also been reported to be beneficial.17,18
Combination of Plasma Exchange Followed by a Course of
Intravenous Immunoglobulin
Recent guidelines suggest that IVIg combined with plasma exchange
should not be considered for treating GBS (Level  B) and there is no
advantage of combining these two therapies.15-18
Methylprednisolone
Neither prednisolone nor methylprednisolone have been shown to
significantly accelerate recovery or affect the long-term outcome in
patients with GBS.15-18
Plasma Exchange, IVIg: Implications of the Guidelines for
Indian Scenario
As per the current guidelines, IVIg appears as efficacious as plasma
exchange for treating GBS in adults (Level A). In the Indian scenario,
560
Section 16
if infrastructural facilities exist, plasma exchange is a cheaper
option. However, huge initial investment is required to setup
plasma exchange. Furthermore, there is need for procuring, and
periodically renewing permissions and licenses from regulatory
authorities for providing plasma exchange. Although IVIg is more
widely available, the cost is prohibitive. These factors influence
the utilization of these treatment options in patients with AIDP in
hospitals across India.
REFERENCES
1. Yuki N, Hartung HP. Guillain-Barré syndrome. N Engl J Med.
2012;366:2294-304.
2. van Doorn PA, Ruts L, Jacobs BC. Clinical features, pathogenesis, and
treatment of Guillain-Barré syndrome. Lancet Neurol. 2008;7:939-50.
3. Talukder RK, Sutradhar SR, Rahman KM, et al. Guillian-Barre
syndrome. Mymensingh Med J. 2011;20:748-56.
4. Hardy TA, Blum S, McCombe PA, et al. Guillain-barré syndrome:
modern theories of etiology. Curr Allergy Asthma Rep. 2011;11:197-204.
5. Kalita J, Misra UK, Das M. Neurophysiological criteria in the diagnosis of
different clinical types of Guillain-Barré syndrome. J Neurol Neurosurg
Psychiatry. 2008;79:289-93.
6. Gupta D, Nair M, Baheti NN, et al. Electrodiagnostic and clinical
aspects of Guillain Barré syndrome: an analysis of 142 cases. J Clin
Neuromuscular Dis. 2008;10:42-51.
7. Alexander M, Prabhakar AT, Aaron S, et al. Utility of neurophysiological
criteria in Guillain Barré syndrome: subtype spectrum from a tertiary
referral hospital in India. Neurol India. 2011;59:722-6.
8. Vengamma B. Guillain-Barré syndrome: an overview. 7th CME on Recent
Advances organized by Association of Physicians of India, Mumbai
branch INHS Asvini Hospital Auditorium, Mumbai, 22-01-2011.
9. Asbury AK, Cornblath DR. Assessment of current diagnostic criteria for
Guillain-Barré syndrome. Ann Neurol. 1990;27 Suppl:S21-4.
10. Paul BS, Bhatia R, Prasad K, et al. Clinical predictors of mechanical
ventilation in Guillain-Barré syndrome. Neurol India. 2012;60:150-3.
 Section 16 Chapter 122  Managing Critically Ill Patients with AIDP
11. Netto AB, Taly AB, Kulkarni GB, et al. Mortality in mechanically
ventilated patients of Guillain Barré Syndrome. Ann Indian Acad
Neurol. 2011;14:262-6.
12. Netto AB, Taly AB, Kulkarni GB, et al. Prognosis of patients with
Guillain-Barré syndrome requiring mechanical ventilation. Neurol
India. 2011;59:707-11.
13. Sejvar JJ, Kohl KS, Gidudu J, et al. Brighton Collaboration GBS
Working Group. Guillain-Barré syndrome and Fisher syndrome: case
definitions and guidelines for collection, analysis, and presentation of
immunization safety data. Vaccine. 2011;29:599-612. Epub 2010 Jun 18.
14. Mateen FJ, Cornblath DR, Jafari H, et al. Guillain-Barré syndrome in
India: population-based validation of the Brighton criteria. Vaccine.
2011;29:9697-701. Epub 2011 Oct 11.
15. McDaneld LM, Fields JD, Bourdette DN, et al. Immuno­modulatory
therapies in neurologic critical care. Neurocrit Care. 2010;12:132-43.
Epub 2009 Sep 23.
16 Cortese I, Chaudhry V, So YT, et al. Evidence-based guideline update:
Plasmapheresis in neurologic disorders: report of the Therapeutics and
Technology Assessment Subcommittee of the American Academy of
Neurology. Neurology. 2011;76:294-300.
17. Patwa HS, Chaudhry V, Katzberg H, et al. Evidence-based guideline:
intravenous immunoglobulin in the treatment of neuromuscular
disorders: report of the Therapeutics and Technology Assessment
Subcommittee of the American Academy of Neurology. Neurology.
2012;78:1009-15.
18. Elovaara I, Apostolski S, van Doorn P, et al. EFNS. EFNS guidelines for
the use of intravenous immunoglobulin in treatment of neurological
diseases: EFNS task force on the use of intravenous immunoglobulin
in treatment of neurological diseases. Eur J Neurol. 2008;15:
893-908.
561