Short Description or Definition
Guillain-Barré syndrome (GBS) is a monophasic illness of immune etiology that presents as an evolving sensorimotor polyneuropathy of varying severity as a result of an inflammation of the peripheral nerves and nerve roots. GBS is a major cause of acute ascending neuromuscular paralysis and is often associated with autonomic dysfunction.
Frequency of features and clinical variants of acute GBS (Reprinted with permission from Ropper (1992))
Fully developed illness
Features of syndrome
CSF protein >0.55 g/l
Abnormal electrophysiologic findings
Weakness without paresthesia or loss
Facial paresis with paresthesia
GBS has an annual incidence of 1–2 per 100,000 worldwide with no geographical clustering. It affects both sexes equally and occurs at all ages, although most commonly between 30 and 50.
Natural History, Prognostic Factors, and Outcomes
The first clinical description of ascending paralytic illness was by Osler (1892), while Guillain et al. (1916) reported the syndrome of radiculoneuritis associated with elevated protein in the cerebrospinal fluid. The etiology of GBS is not fully understood. It is thought that an antecedent infection (most commonly Campylobacter jejuni) evokes an immune response (both cellular and humoral), resulting in demyelination. Within 2–3 weeks, the inflammation resolves and remyelination commences.
GBS generally has a favorable outcome. Eighty percent are ambulatory (ambulation without assistive devices) within 6 months of symptom onset. Fifty percent have minor residual neurological deficits, while 15% have residual functional deficits, and 5% may die of secondary systemic organ failure (Ropper 1992). In the acute phase of GBS, 5–10% may die and 25% require artificial ventilation owing to involvement of respiratory and bulbar muscles (Hughes et al. 2006). The onset, rate, and variability of recovery is unclear (Meythaler 1997), but 80% reach the nadir of the disease at 3 weeks after symptom onset (Pascuzzi and Fleck 1997) and subsequently gradually improve. GBS survivors can continue to improve for 10 years after onset, although slower recovery may occur in those who experienced ICU complications, prolonged mechanical ventilation, and early axonal abnormalities (Dhar et al. 2008).
Poorer prognostic factors are older age, need for respiratory support, rapid onset, progression to quadriplegia, severe disease at presentation, C. jejuni infection, and preceding diarrheal illness (Rees et al. 1995).
Although most patients make good physical recovery, the ongoing impact of GBS is significant. A longitudinal study (n = 76 patients) reported that despite good functional recovery up to 14 years post GBS (median 6 years, range 1–14), 16% of patients continued to report moderate to extreme impact on work, family, and social activities, and 22% reported ongoing substantial impact on mood, confidence, and ability to live independently (Khan et al. 2010a). Psychosocial performance does not necessarily correlate with the severity of impairment in GBS but may be explained by poor conditioning and fatigue (Forsberg et al. 2005).
Neuropsychology and Psychology of Guillain-Barré Syndrome
The psychological, social, and avocational outcomes of GBS are poorly studied. High levels of anxiety (82%), acute stress disorder, depressive episodes (67%), and brief reactive psychosis (25%) in an ICU setting have been reported (Weiss et al. 2002). Ongoing anxiety and fear is common due to sudden onset of symptoms and may accompany with depression in many (Hallum 2007). Psychotic symptoms (hallucinations, delusions, incoherence) have been reported in more severe patients (Hallum 2007) and is closely related to motor deprivation and loss of communication. Therapeutically, continuous psychosocial support and psychopharmacological measures may be valuable tools to ameliorate distress (Weiss et al. 2002).
Cognitive problems have been reported in pwGBS, especially in acute phase and in those with extended ICU stay (Hallum 2007; Khan and Ng 2009). Hydrocephalus and intracranial hypertension in acute stages of GBS are infrequent but well-recognized complications and often resolve spontaneously or after ventriculoperitoneal shunting. Brain imaging is necessary in GBS patients who deteriorate in cognitive function after disease onset, and neuropsychological evaluation should be considered (Liu et al. 2006). Early cognitive screening and implementation of psychological interventions such as good communication with patients and/or their family regarding prognosis and treatment plan, involvement in decision-making, and early counselling from experts (Hallum 2007; Khan and Ng 2009).
GBS has a significant impact on patients’ lives, which goes beyond their residual disability or impairment. Five years on, 27% continue to make substantial changes in their job, hobbies, or social activities despite near complete functional recovery (Bersano et al. 2006). In the transition period following discharge from hospital to the community, various adjustment issues may surface, such as perceptions of self-worth and self-image and role reversals within the family. Families may struggle to cope with new demands resulting from increased care needs, difficulties in returning to driving and work, financial worries, marital stress, and other limitations in societal participation. Ongoing monitoring, education, and counselling of the patient (and family) are important.
Carer support and respite care should be discussed. Referral to local GBS Society and support groups (GBS survivors) is also recommended, as these provide patients and families with ongoing support, resources, and equipment needs.
The features of GBS are shown in Table 1. Most patients present with symmetric limb weakness, absent (or diminished) reflexes, paresthesias and aching pain in large muscles of the back and legs, or sciatica (Ropper 1992). Thirty percent of patients run a fulminating course with rapid progression requiring ventilatory support within a couple of days (Ropper). Disease progression may be stuttering or insidious and generally continues over the next 2 weeks until it plateaus and is subsequently followed by a gradual recovery. The duration of illness in most patients is <12 weeks.
Weakness often commences distally and continues in an ascending fashion, resulting in variable weakness in the limbs, face, and oropharynx (Rees et al. 1995). Facial weakness and cranial nerve involvement occur in >50% (Pascuzzi and Fleck 1997) and 70% have autonomic dysfunction (sinus tachycardia or bradycardia, fluctuating hypertension or hypotension, flushing of the face, loss of or excessive sweating) (Zochodne 1994). Severe dysautonomia should be recognized as this is associated with sudden death (Zochodne). Unusual features of GBS include papilledema, facial myokymia, hearing loss, meningeal signs, vocal cord paralysis, and mental status changes.
Diagnostic criteria for typical GBS (Adapted and reprinted with permission from Asbury and Cornblath (1990))
Features required for diagnosis
Progressive weakness in both arms and both legs
Features strongly supporting the 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
Recovery beginning 2–4 weeks after progression ceases
Absence of fever at the onset
Elevated concentration of protein in cerebrospinal fluid, with fewer than 10 cells/mm3
Typical electrodiagnostic features
Features making the diagnosis doubtful
Diagnosis of botulism, myasthenia, poliomyelitis, or toxic neuropathy
Abnormal porphyrin metabolism
Purely sensory syndrome, without weakness
Proposed electrodiagnostic criteria for demyelination of peripheral nerve (Reprinted with permission from Asbury and Cornblath (1990))
These criteria concern nerve conduction studies (including proximal nerve segments) in which the predominant process is demyelination
Must have three of the following four features:
1. Reduction in conduction velocity in two or more motor nerves
(a) <80% of lower limit of normal (LLN) if amplitude >80% of LLN
(b) <70% of LLN if amplitude <80% of LLN
2. Conduction block or abnormal temporal dispersion in one or more motor nerves: either peroneal nerve between the ankle and below fibular head, median nerve between the wrist and elbow, or ulnar nerve between the wrist and below elbow
Criteria for partial conduction block:
(a) <15% change in duration between proximal and distal sites and >20% drop in negative-peak area of peak-to-peak amplitude between proximal and distal sites
Criteria for abnormal temporal dispersion and possible conduction block:
(a) >15% change in duration between proximal and distal sites and >20% drop in negative-peak area or peak-to-peak amplitude between proximal and distal sites
3. Prolonged distal latencies in two or more nerves
(a) >125% of upper limit or normal (ULN) if amplitude >80% of LLN
(b) >150% of ULN if amplitude <80% of LLN
4. Absent F-waves or prolonged minimum F-wave latencies (10–15 trials) in two or more motor nerves
(a) >120% of ULN if amplitude >80% of LLN
(b) >150% of ULN if amplitude <80% of LLN
Differential diagnoses of GBS
Acute arsenic poisoning
Diseases of the spinal cord
Spinal cord compression
Diseases of the neuromuscular junction
Diseases of muscle
Critical illness myopathy or neuropathy
Specialist units have improved survival rates in patients with GBS and reduced mortality rate to less than 5% (Ropper 1992). Acute medical complications in GBS include development of sepsis, respiratory failure, aspiration pneumonia, deep vein thrombus, pulmonary embolism, and cardiac arrest (Dhar et al. 2008).
Plasmapheresis, Intravenous Immunoglobulin, and Steroids
Acute management of GBS includes intensive care and ventilatory support, and immune-modulating treatments (plasma exchange and intravenous immunoglobulin (IVIg)) to reduce nerve damage. Early treatment with either IVIg or plasma exchange (both are equally effective) within 2–4 weeks after symptom onset may decrease recovery time (Hughes et al. 2003), although there is a higher risk of relapse following treatment with IVIg.
Once medically stable, approximately 40% of patients with GBS need inpatient rehabilitation, particularly patients requiring ventilatory support, more severe disability, and medical complications (Meythaler 1997).
Medical complications from GBS such as dysautonomia, cranial nerve involvement, early de-afferent pain syndromes (Meythaler 1997), and complications resulting from immobility, pneumonia, deep vein thrombus, and musculoskeletal deconditioning (Dhar et al. 2008) can persist for some time and interfere with rehabilitation. Multidisciplinary rehabilitation programs in inpatient settings are effective in terms of improvements in activity (disability) and participation for up to 6 months (Khan et al. 2010b). A high-intensity (two to three times per week) outpatient rehabilitation program in the post-acute phase (median 6.5 years since diagnosis) is more effective than a low-intensity program in reducing motor disability (mobility, self-care, continence program) and improving participation (relationships) (Khan et al. 2011).
Supportive Ventilatory Care
Up to 30% of patients develop respiratory failure and pneumonia in the first 12 weeks of illness and many will recover adequately (Ropper 1992). Those requiring ventilatory support have longer hospital lengths of stay and increased rehabilitation costs (Meythaler 1997).
Patients are monitored closely in rehabilitation settings for signs of respiratory distress. Intubation is required if the vital capacity decreases to <18 ml/kg, maximum inspiratory and expiratory pressures are < than 30 cmH2O, and < than 40 cmH2O, respectively (Lawn et al. 2001). Weaning from ventilation depends on improvements in strength and serial lung function testing; tracheostomy may be required if lung function tests show no improvements from baseline at the 2–3-week mark (Hughes et al. 2003). Pulse oximetry and BiPAP may be indicated at nighttime for patients with hypoxia or hypercapnia. Physical therapy addresses the clearance of respiratory secretions, reduction in the work of breathing, breathing exercises, and resistive inspiratory training. Special weaning protocols are required to prevent over fatigue of respiratory muscles in tracheostomy patients (Meythaler 1997). Those with cranial nerve involvement are at risk of aspiration and respiratory complications.
Deep Venous Thrombus (DVT)
Pulmonary embolism can occur in up to a third of patients with GBS (Raman et al. 1971). The exact incidence or risk factors for DVT in GBS are unknown. Although prophylaxis (such as subcutaneous heparin and support stockings) is recommended, the type and length of prophylaxis is unclear. In rehabilitation settings, early mobilization using progressive mobilization strategies for improving bed mobility, practicing safe transfer techniques, and gait training is encouraged.
Dysautonomia can occur in up to 70% of patients with GBS and is associated with significant morbidity and mortality, need for mechanical ventilation (Dhar et al. 2008), and cardiac arrhythmias (Zochodne 1994). It extends duration of acute care (Zochodne) and rehabilitation (Meythaler 1997). Close monitoring of fluid balance, blood pressure, cardiac rhythm, and sensitivity to vasoactive medications is essential in managing these patients and should continue until adequate recovery is under way (Meythaler). Rehabilitation involves education of staff, patients, and their families, use of compression socks, adequate hydration, postural training, and use of tilt tables where appropriate, to allow for cardiovascular and autonomic adaptation.
Bladder (disturbed sensation and areflexia) (Sakakibara et al. 1997; Amatya et al. 2013) and bowel dysfunction (ileus) in GBS can occur early and usually resolves. Ileus can be treated with erythromycin or neostigmine, but promotility agents should be avoided (Hughes et al. 2003). Patients with GBS are initially catheterized to avoid bladder distension and to maintain urinary hygiene. Rehabilitation measures ensure social continence and avoidance of complications such as urinary infections, which occur in 30% of patients (Ropper 1992). Bladder dysfunction may include detrusor acontractility, disturbed bladder sensation, and non-relaxing urethral sphincter, causing symptoms causing symptoms such as voiding difficulty, urinary retention, frequency, and urge incontinence (Sakakibara et al. 2009). Individualized management programs include timed voiding, intermittent catheterization, and anticholinergic medication (Mullings et al. 2010). Pelvic floor muscle training, with or without biofeedback or electrical stimulation, is also commonly used in women with stress leakage and mixed urinary incontinence (Mullings et al. 2010). Similarly, effective bowel management program includes an appropriate diet, adequate fluids, scheduled bowel care, and laxatives for those with bowel dysfunction (Mullings et al. 2010).
Complications from Immobilization
Tilt-table training for immobilized patients can be effectively used in rehabilitation units, as prolonged immobilization leads to reduction of blood volume. Early mobilization of patients counters immobilization hypercalcemia (Meythaler 1997).
Graduated mobility programs include maintenance of posture and alignment, joint range of motion, provision of orthotics, endurance and muscle strengthening, flexibility, and progressive ambulation using adaptive gait aids. Strengthening programs should initially be non-fatiguing to avoid paradoxical weakness. Physical measures using neurodevelopmental sequencing, partial body weight support systems, and podiatrons have been reported.
Other complications from immobility such as compression nerve palsies and pressure sores can be avoided with appropriate positioning and skin and pressure care protocols. Heterotopic ossification is rare but more likely to occur in ventilated patients. Early recognition and modified therapy with joint ranging within the pain-free arc can be helpful.
Up to 70% of patients can develop musculoskeletal and neuropathic pain (Hughes et al. 2003). Effective medications include tricyclic antidepressants, tramadol, GABAmimetic agents (e.g., gabapentin), membrane-stabilizing agents (e.g., carbamazepine), and opiates. Treatment includes patient education and desensitization therapy using functional tasks of everyday life (grooming, dressing).
Severe fatigue can persist in 80% of patients and is unrelated to age, duration, or severity of initial illness, but probably partly related to muscle deconditioning and forced inactivity. Fatigue is associated with a reduced QoL despite good physical recovery, as many patients remain restricted in daily and social activities. Medications (such as amantadine) are not effective. Aerobic exercise improves functional outcome, QoL, and fatigue. Energy conservation and work simplification strategies also help manage fatigue and facilitate patient functional independence. The provision of adaptive equipment and aids facilitate personal and domestic activity, by decreasing task-associated energy expenditure.
References and Readings
- Hallum, A. (2007). Neuromuscular diseases. In D. A. Umphred (Ed.), Neurological rehabilitation (5th ed., pp. 475–531). St. Louis: Mosby.Google Scholar
- Hughes, R. A., Wijdicks, E. F., Barohn, R., Benson, E., Cornblath, D. R., Hahn, A. F., Meythaler, J. M., Miller, R. G., Sladky, J. T., & Stevens, J. C. (2003). Practice parameter: Immunotherapy for Guillain-Barré syndrome: Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 61, 736–740.CrossRefPubMedGoogle Scholar
- Hughes R. A. C., Raphaël, J-C., Swan A. V., & van Doorn, P. A. (2006). Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database of Systematic Reviews.Google Scholar
- Khan, F., Ng, L., Amatya, B., Brand, C., & Turner Stokes, L. (2010b). Multidisciplinary care for Guillain-Barre syndrome. Cochrane Database of Systematic Reviews.Google Scholar
- Khan, F., Pallant, J. F., Amatya, B., Ng, L., Gorelik, A., & Brand, C. (2011). Outcomes of high- and low-intensity rehabilitation programme for persons in chronic phase after Guillain-Barré syndrome: A randomized controlled trial. Journal of Rehabilitation Medicine, 43, 638–646.CrossRefPubMedGoogle Scholar
- Springhouse. (2005). Professional guide to diseases (8th ed.). Philadelphia: Lippincott Williams & Wilkins.Google Scholar