Acute Immune Related Neuropathies

Author(s): Amy Kanallakan, MD, Sruthi Pandipati Thomas MD, PhD

Originally published:04/04/2016

Last updated:04/04/2016

1. DISEASE/DISORDER

Definition

Acute immune related neuropathies are acute monophasic illnesses often preceded by infection that classically feature progressive, relatively symmetric, muscle weakness leading to flaccid paralysis with absent or depressed deep tendon reflexes1. These neuropathies are also known as Guillain-Barré Syndrome (GBS) and its variants, including the Miller-Fisher variant.

Etiology

GBS is triggered by the immune response to a preceding infection2. GBS is associated with Campylobacter jejuni, human immunodeficiency virus (HIV), cytomegalovirus (CMV), and Epstein-Barr virus. There is no increased incidence of GBS following any vaccination and all vaccinations combined3. Two-thirds of patients report a preceding gastrointestinal or respiratory illness2.

Epidemiology including risk factors and primary prevention

GBS has a global incidence of 1-2 in 100,000 annually4. All age groups are affected but the incidence increases by twenty percent for every ten years after the first decade of life.  The pretest probability is higher for individuals who have recently been diagnosed with Campylobacter jejuni, CMV or EBV infection.  Those with a known HIV infection are also at higher risk.  Patients who meet these criteria should be more thoroughly worked up when presenting with ascending weakness.

Patho-anatomy/physiology

GBS is pathologically characterized by inflammatory infiltrates, consisting of T cells and macrophages, and areas of segmental demyelination found in spinal roots and large and small motor and sensory nerves. There is often secondary axonal degeneration. The antibody immune response to various infectious agents cross-reacts with peripheral nerve components secondary to shared epitopes, a concept known as molecular mimicry. Autoantibodies against gangliosides bind to myelin antigens resulting in complement activation followed by membrane-attack complex (MAC) formation. This initiates vesicular degeneration of Schwann cells. The particular ganglioside targeted by autoantibodies determines the phenotype, classical GBS versus a variant such as Miller-Fisher1.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

From the onset of illness, the severity of symptoms progresses for up to two weeks, followed by a plateau for two to four weeks. On average, the time to nadir is four weeks post onset without any medical intervention5. The use of plasma exchange or IVIG has decreased the time to onset of recovery by forty to fifty percent6. While most patients with GBS have a good prognosis, up to twenty percent of patients remain severely disabled and five percent die despite immunotherapy7.

Specific secondary or associated conditions and complications

There are numerous secondary consequences of GBS that require supportive care. The most significant of these are respiratory failure and autonomic dysfunction, requiring intensive care unit (ICU) monitoring. Patients with GBS are at high risk for deep vein thrombosis, often require bowel and bladder care, psychological support, and pain control.

2. ESSENTIALS OF ASSESSMENT

History

Patients present with relatively symmetric weakness, often preceded by a gastrointestinal or respiratory illness.  Weakness begins in the legs 90% of the time with accompanying paresthesias in the hands and feet 80% of the time. Sixty-six percent of patients report pain, particularly in the back and extremities8.

Physical examination

Key features on physical examination include:

  • Relatively symmetric muscle weakness, leading to anywhere from mild difficulty walking to complete paralysis of all extremity, facial, respiratory and bulbar muscles
  • Absent or depressed deep tendon reflexes
  • No or mild sensory abnormalities
  • Autonomic dysfunction, with tachycardia, urinary retention, hyper- and hypotension, orthostatic hypotension, bradycardia, ileus, and hypohydrosis9

Less common features include papilledema, facial myokymia, hearing loss, meningeal signs, vocal cord paralysis, mental status changes, and syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Clinical functional assessment: mobility, self care cognition/behavior/affective state

Functional motor gain and recovery are measured using the traditional Functional Independence Measure (FIM) motor scores at admission and discharge. Given the high variability in presentation of each patient with GBS, it is best to develop additional personalized goals after discussion with the patient.

Laboratory studies

Cerebrospinal fluid (CSF) shows albuminocytologic dissociation, elevated CSF protein with a normal white blood cell count, typically one week after the onset of symptoms in up to two-thirds of patients with GBS1. Electromyography and nerve conduction studies show an acute polyneuropathy with demyelination, although some variants can have axonal features.

Imaging

While imaging is not necessary to make a diagnosis of GBS, there are findings that could be useful in confirming the diagnosis.  A small study showed that ultrasound reveals significant enlargement of peripheral nerves in patients with EMG-confirmed GBS, particularly in the median nerve. Vagal nerve enlargement correlated with autonomic dysfunction while C6 root enlargement correlated with CSF protein levels10. Additionally, nerve root enhancement, particularly in the thoracolumbar distribution, has been seen on MRI in the pediatric population11. These imaging modalities could be useful in situations where electrodiagnostic confirmation is not available.

Supplemental assessment tools

The Medical Research Council (MRC) Scale for Muscle Strength is also used for assessment, which is based on both the patient’s effort as well as clinical functional assessment. Additional assessment tools used commonly with GBS include the Perceived Impact of Problem Profile (PIPP) and Depression Anxiety Stress Scale (DASS). The PIPP focuses on the impact and distress of health conditions from the patient’s perspective. Meanwhile, the DASS is used to isolate and identify aspects of emotional disturbance that might not be apparent to the patient.

Early prediction of outcomes

Poor prognostic factors:

  • Older age
  • Quick onset of symptoms, particularly if <7 days
  • Severe muscle weakness at presentation
  • Need for ventilatory support
  • Preceding diarrheal illness
  • Average distal motor response <20 percent of normal in nerve conduction studies
  • Small rise in serum IgG after administration of IVIG

Environmental

Approximately twenty percent of patients who suffer from GBS will have some residual physical deficits1. This deficit can range from minor weakness to complete wheelchair dependence.  Changes in the home and workplace may be necessary to maintain previous functionality.

Social role and social support system

Patients with GBS often have significant anxiety and affective lability due to the sudden and severe nature of the illness. Not only is it important for patients to have the support of their family, friends and care team, but they often benefit from selective serotonin reuptake inhibitors (SSRIs) and/or anticonvulsants12.

Professional issues

Physiatrists should advocate for aggressive treatment and implementation of therapies early in the illness course. As there is a large gradient of disability among patients with GBS (full recovery to vent dependent), it is essential to define individualized treatment goals soon after diagnosis.

3. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

Due to the clinical heterogeneity of GBS, rehabilitation plans must be custom tailored to a particular patient’s deficits. Approximately 40% of patients with GBS require inpatient rehabilitation13. Ideally, rehabilitation begins in the acute stages with contracture prevention, a bowel and bladder regimen, pressure ulcer prevention and pain management. Once the illness has hit its nadir, attention switches to regaining strength and gait training.

At different disease stages

Initial Onset/Acute Illness
Initial management of GBS patients should focus on prevention of contracture, nerve compression and pressure ulcer formation secondary to paralysis. This can be accomplished with range of motion exercises and positioning with static splinting. DVT prophylaxis should be considered for all patients with significant paralysis. In addition, both musculoskeletal and neuropathic pain can be a significant problem for some patients. Oral and intravenous pharmacological management as well as topical capsaicin and transcutaneous electrical stimulation for localized pain have proven beneficial8. Patients with GBS typically present with lower motor neuron dysfunction of bowel and bladder and will require a scheduled program.

Stable Illness
Once out of the acute phase of GBS, focus should turn to strengthening with high repetitions and low weight to avoid overworking muscles, which could lead to paradoxical weakening. Gentle strengthening with isometric, isotonic, isokinetic, manual-resistive, and progressive resistive exercises should be incorporated to fit the patient’s condition. Some patients will also need to progress to gait training with use of the tilt table due to prolonged bed rest and dysautonomia. A small contingent of patients develops dysfunctional vibratory sensation and proprioception. These patients require sensory reintegration and repetitive exercises to redevelop coordination.

Coordination of care

Rehabilitation of a patient with GBS requires a team-based approach, ideally with a physiatrist as the team leader. Physical, occupational, respiratory and possibly speech therapists are essential. Rehabilitation psychologists also play a valuable role in recovery.

Patient & family education

Educating the patient, family, and additional caregivers on GBS and its recovery pattern is essential. The patient will face new disability, some of which could be permanent, and will need assistance in making adaptations in his/her life. It should be emphasized that full recovery can take up to two years.

Measurement of Treatment Outcomes including those that are impairment-based, activity participation-based and environmentally-based.

Measurement of treatment outcomes is determined by comparing scores on the FIM, MRC, PIPP, and/or DASS scales at admission, discharge and at outpatient follow-up.

Translation into Practice:  practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

  • Begin the rehabilitation process early in the ICU
  • Initially focus on maintaining range of motion by preventing contracture
  • Once the illness has hit its nadir, switch gears to work on gentle strengthening, with particular focus on gait and sensory abnormalities that will affect mobility
  • Pain management is important throughout rehabilitation for patient comfort and to maximize gains through therapy
  • Recovery from GBS can take up to two years, therefore continued therapy as an outpatient and independently at home is essential for maximal recovery

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

  • The addition of yogic relaxation, pranayama, and meditation to the treatment plans of patients with GBS significantly improves sleep quality but does not reduce disability14.
  • The use of a virtual motor rehabilitation system improves clinical outcomes in patients with GBS while entertaining patients15.
  • Higher intensity rehabilitation, compared with traditional less intense interventions, reduce disability in patients with GBS when implemented in the later stages of recovery15.

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Given the heterogeneity of GBS, there is lack of agreement on the appropriate clinical approach and most effective forms of intervention. As a result, there is a lack of high quality evidence for the overall effectiveness of rehabilitation for GBS17.

REFERENCES

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  2. Hahn AF. Guillain-Barré Lancet. 1998; 352: 635.
  3. Baxter R, Bakshi N, Fireman B, Lewis E, Ray P, Vellozzi C, Klein NP. Lack of association of Guillain-Barré syndrome with vaccinations. Clin Infect Dis. 2013; 57(2): 197.
  4. Sejvar JJ, Baughman AL, Wise M, Morgan OW. Population incidence of Guillain-Barre syndrome: a systematic review and meta-analysis. Neuroepidemiology. 2011; 36(2): 123-133.
  5. Alter M. The epidemiology of Guillain-Barré. Ann Neurol. 1990; 27: S7-S12.
  6. The Guillain-Barré Study Group. Plasmapheresis and acute Guillain-Barré. Neurology. 1985; 35(8): 1096.
  7. Hughes RAC, Swan AV, Raphael JC, Annane D, van Koningsveld R, van Doorn PA. Immunotherapy for Guillain-Barré syndrome: a systematic review. Brain. 2007; 130: 2245-2257.
  8. Ruts L, Drenthen J, Jongen JL, et al. Pain in Guillain-Barre syndrome: a long-term follow-up study. Neurology. 2010; 75: 1439.
  9. Zochodne DW. Autonomic involvement in Guillain-Barré syndrome: a review. Muscle Nerve. 1994; 17(10): 1145.
  10. Grimm A, Decard BF, Axer H. Ultrasonography of the peripheral nervous system in the early stage of Guillain-Barre syndrome. J Peripher Nerv Syst. 2014; 19(3):234-241.
  11. Yikilmaz A, Doganay S, Gumus H, Per H, Kumandas S, Coskun A. Magnetic resonance imaging of childhood Guillain-Barre Syndrome. Childs Nerv Syst. 2010; 26(8): 1103-1108.
  12. Brousseau K, Arciniegas D, Harris S. Pharmacologic management of anxiety and affective lability during recovery from Guillain-Barré syndrome: some preliminary observations. Neuropsychiatr Dis Treat. 2005; 1(2): 145-149.
  13. Meythaler JM, DeVivo MJ, Clausen GC, Braswell WC. Prediction of outcome in Guillain-Barré syndrome in patients admitted to rehabilitation. Arch Phys Med Rehabil. 1994; 75: 1027.
  14. Sendhilkumar R, Gupta A, Nagarathna R, Taly A. Effect of pranayama and meditation as an add-on therapy in rehabilitation of patients with Guillain-Barré syndrome – a randomized control pilot study. Disabil Rehabil. 2013; 35(1): 57-62.
  15. Albiol-Pérez S, Forcano-García M, Muñoz-Tomás MT, Manzano-Fernández P, Solsona-Hernández S, Mashat MA, Gil-Gómez JA. A novel virtual motor rehabilitation system for Guillain-Barré Two single case studies. Methods Inf Med. 2015; 54(2): Epub ahead of print.
  16. Khan F, Pallant JF, Amatya B, Ng L, Gorelik A, Brand C. Outcomes of high- and low-intensity rehabilitation programme for persons in chronic phase after Guillain-Barré syndrome: a randomized controlled trial. J Rehabil Med. 2011; 43(7): 638-646.
  17. Khan F, Ng L, Amatya B, Brand C, Turner-Stokes L. Multidisciplinary care for Guillain-Barré. Cochrane Database Syst Rev. 2010; 10: CD008505.

Bibliography

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Guillain G, Barré JA, Strohl A. Sur un syndrome de radiculonévrite avec hyperalbuminose du liquide céphalo-rachidien sans réaction cellulaire: remarques sur les caractères cliniques et graphiques des réflexes tendineux. Bulletins et mémoires de la Société des Médecins des Hôpitaux de Paris. 1916; 40: 1462-1470.

Mullings KR, Alleva JT, Hudgins TH. Rehabilitation of Guillain-Barré Syndrome. Dis Mon. 2010; 56: 288-292.

Rajabally YA, Uncini A. Outcome and its predictors in Guillain-Barre syndrome. J Neurol Neurosurg Psychiatry. 2012; 83(7): 711.

Walgaard C, Lingsma HF, Ruts L, van Doom PA, Steyerberg EW, Jacobs BC. Early recognition of poor prognosis in Guillain-Barre syndrome.  Neurology. 2011; 76(11): 968.

Author disclosure

Amy Kanallakan, MD
Nothing to Disclose

Sruthi Pandipati Thomas MD, PhD
Nothing to Disclose

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