Neuromuscular Weakness in Children: Guillain-Barre Syndrome

Guillain-Barre syndrome

Synonyms

Acute Inflammatory Demyelinating Polyneuropathy (AIDP)

Acute Motor and Sensory Axonal Neuropathy (AMSAN)

Acute Motor Axonal Neuropathy (AMAN)

Related conditions

Miller-Fisher Syndrome – ophthalmoparesis, ataxia and areflexia

Polyneuritis Cranialis – multiple cranial neuropathies

Acute Pandysautonomia – orthostasis, syncope, autonomic dysfunction

1. Description of the problem

What every clinician needs to know

Guillain-Barre syndrome is the most common cause for acute flaccid paralysis in regions where endemic poliomyelitis has been eliminated through public health based immunization programs. Described more than a century ago among soldiers during World War I, GBS is an acute, autoimmune, peripheral neuropathy that can affect motor, sensory or autonomic pathways in any distribution or combination.

Essentially, any executive or reporter neurological function that is transmitted by peripheral axons can be disrupted in this disease. It is not limited by age, sex, or ethnic background. It generally presents with the appearance of pain, weakness or both.

Although the three main subsets of GBS are categorized on the basis of their unique pathophysiology (AIDP, demyelination; AMSAN, motor and sensory axonal degeneration; AMAN, degeneration only of motor axons), their clinical presentations are highly similar. Even AMAN, a purely motor disorder, includes prominent painful symptoms early in the disease.

The clinical evolution of GBS conforms to a triphasic model with an initial period of progressive worsening that occurs on average over 10-12 days. After reaching its nadir, there is a plateau period of a similar length (10-12 days). Recovery then ensues with a slope much more gradual than that of the initial decline and continues for weeks or months.

Clinical features

GBS is classically described as an ascending paralysis, although in light of the multiplicity of clinical manifestations that fall under the rubric of GBS, it is clear that diseases don’t read textbooks. Weakness is the most consistent early manifestation of the disease. The symptoms develop and evolve in a distal to proximal fashion, affecting feet before hands and hips before shoulders. Sensory loss is generally a minor component and rarely spontaneously described.

Because myelinated axons are generally most prominently affected, those sensory modalities transmitted via large caliber myelinated nerve fibers are most vulnerable, therefore proprioception and vibratory deficits can most readily be demonstrated. By contrast, positive sensory symptoms (i.e. pain and dysesthesias) are the rule and are prominent complaints in up to 75% of affected children.

2. Emergency management

Stabilizing the patient

The most urgent concern is prevention of respiratory compromise. Although the disease may evolve slowly in some children, in others weakness can progress rapidly to respiratory failure. Uncommonly, cranial nerve involvement will produce prominent bulbar insufficiency with consequent airway compromise, and intubation may be necessary to protect the airway before ventilation is critically diminished due to muscle weakness.

Management points not to be missed

Clinically significant Injury to the autonomic nervous system occurs in as many as 25% of children with GBS. Initially, this may be manifested as orthostatic lability in blood pressure; however, as the disease evolves, massive swings in blood pressure, heart rate and body temperature can ensue. In the context of autonomic instability, environmental and psychological stressors inherent in the ICU environment can precipitate potentially life-threatening alterations in vital signs.

Urinary retention occurs in 15-20% of patients requiring catheterization. Insensible fluid loss due to diaphoresis can cause sufficient volume loss to alter hemodynamics and is difficult to monitor. Pain is a large component of nerve injury in a majority of children. In surveys of adults with GBS who required admission to an ICU, roughly 75% said that their pain was underestimated and undertreated by their intensive care treatment team.

This was particularly true of physical therapy sessions during the early phase of the disease, which although absolutely necessary, should be undertaken with cognizance of potential patient discomfort. Underlying or nosocomial infections should be treated aggressively, as the resulting immunological response will generate pro-inflammatory molecules that will augment the severity of tissue damage due to GBS.

Action plan

Create a calm, soothing environment.
Communicate with the patient. Surprises are unwelcome.
Provide adequate analgesia. Narcotic analgesics are frequently necessary for neuropathic pain.
Check for bladder retention.
Premedicate for painful manipulations.
Attend to insensible fluid loss.
Prevent protein-calorie deprivation.

Drugs and dosages

There are no prospective, randomized controlled trials of therapy for GBS in children. Consequently, the best strategy for treatment protocols must be extrapolated from experience in adult treatment trials.

Several trials have confirmed the efficacy of plasmapheresis in adults with GBS. In addition, IVIg has been shown to be comparable to plasmapheresis in this population and the combination of both is equivalent in efficacy to either alone. In most settings, IVIg is logistically simpler to administer compared to plasmapheresis.

IVIg 2 gm/kg given as a single dose or divided and given over two days.

There are theoretical reasons to believe that higher peak serum level of IVIg may have greater efficacy at inhibiting production of pro-inflammatory factors than can be achieved with multiple lower divided dose regimens.

Plasmapheresis.

Ideally, the goal should be to perform a triple volume exchange over roughly 5 days employing a QOD schedule. The rationale for this paradigm is to allow 1 day between treatment sessions to permit repletion of clotting factors, thereby minimizing risk of bleeding, and to provide an equilibration interval of the circulating and marginal immunoglobulin pools to enhance maximal removal of circulating antibodies. Placement of a large bore, double lumen catheter n a central vessel is useful to facilitate the plasma exchange process.

Note: Some believe that PPE may be more effective than IVIg in more severe cases; however, there is no prospectively derived evidence to substantiate that assumption.

3. Diagnosis

Establishing a diagnosis

Formal diagnositc criteria are purely clinical and require:

Weakness in more than one extremity.
Diminished or absent reflexes.
Evolution of symptoms over less than 4 weeks.
Exclusion of other causes of acute weakness.

Supportive features include:

Elevation of CSF protein in the absence of significant cellular pleocytosis (less than 50 cells/mm3).
Nerve conduction studies demonstrating evidence of a multifocal demyelinating neuropathy.

Note: Although not codified as such, enhancement of spinal nerve roots on MRI probably falls in this category, but is less specific

Pathophysiology

GBS is an autoimmune disease that is orchestrated through both B-cell and T-cell pathways, with the intensity of the disease modulated by cytokine effects. The autoimmune process is directed towards elements of the peripheral nervous system; in particular, epitopes related to myelin and axolemmal membranes. The autoimmune attack results in injury to axonal elements with dysfunction (primarily demyelination with ensuing conduction failure) or degeneration of peripheral nerve axons.

The disorder may affect motor, sensory or autonomic modalities. It may preferentially affect one or a specific combination of functional populations, resulting in some of the distinctive clinical phenotypes alluded to above. Essentially, any circuit that relies on peripheral axons for executive or reporter functions is susceptible to injury.

The disease has clearly been demonstrated to be triggered by some systemic infections, the best example of which is campylobacter jejuni enteritis. In some locales, particularly rural Northern China, AMAN, a GBS-like illness, occurs in epidemic patterns particularly among children. These outbreaks correlate with campylobacter infection in as many as 70-80% of cases.

The camplyobacter organism has been shown to express lipo-oligosaccharide moieties on the cell surface that have dramatic structural homologies to similar molecules residing on the external surface of the axonal membrane. It is thought that these cytoarchitectural homologies result in “molecular mimicry” between the infectious organism and the host peripheral nervous system, triggering an acute autoimmune mediated peripheral neuropathy.

Similar mechanisms may be in play in other cases of GBS, although it is likely that both genetic and environmental factors have a role in pathogenesis.

Epidemiology

GBS affects roughly 1-2/100,000 individuals under the age of 18 and becomes more frequent in older age groups, particularly among those in the sixth decade of life and beyond. There is a slight male predominance, with a M:F ratio of 1.2:1, the cause of which is unknown.

Roughly 60-70% of patients identify an antecedent event occurring in the 6 weeks prior to the onset of illness that may have been related. The most commonly pointed to are upper respiratory infection and gastroenteritis, respectively. There is a clear epidemiological relationship to antecedent infections, the best characterized of which is with campylobacter jejuni enteritis.

It has been shown that the campylobacter bacterial cell wall includes glycoproteins that express surface oligosaccharide moieties with strong homologies to similar macromolecules found on the outside of the axolemmal membrane. This molecular mimicry is thought to underpin triggering a self-directed autoimmune disease of peripheral nerves based on the similarity of the structure of the bacterial antigen to that of the surface axonal membrane.

Particularly during outbreaks in endemic regions, campylobacter infection can be responsible for the majority of cases of GBS among children. The events listed as potential triggers for GBS in addition to infection include vaccines, trauma, parturition, and insect or animal bites. In roughly 30% no precipitating factors are identified.

It is likely that many of the putative triggers are included by virtue of temporal overlap. This is particularly true of vaccines and upper respiratory infections, where both occur with considerable frequency in children and would be expected to emerge with some consistency in relationship to any random event given a broad enough window of opportunity. Post hoc reasoning, therefore, needs to be avoided in the process of ascribing causality to a relationship between an antecedent event and GBS.

Special considerations for nursing and allied health professionals.

What's the evidence?

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