Pediatric Guillain-Barre Syndrome Clinical Presentation

Patients with Guillain-Barré syndrome (GBS) present with complaints of weakness and/or unsteadiness (ataxia). Weakness is a hallmark of GBS. The weakness typically starts in the legs and ascends to the arms (hence, the description progressive ascending flaccid paralysis). This progression may occur over hours to days to weeks. The weakness is usually symmetric.

Pain and dysesthesias also are noted, particularly in children. Pain may be the initial manifestation in almost half of affected children. The nonspecific nature of the symptoms may distract from the actual diagnosis, for exampe, a pediatric patient presenting with prolonged and unexplained abdominal pain.

Often, onset of these symptoms is within 2-4 weeks of an illness or immunization. The preceding illness often involves fever, muscle pains, diarrhea or upper respiratory infection.

Urinary retention is also noted early in the course of 10-15% of children with GBS. At the peak of illness, about half the pediatric patients with GBS may have associated autonomic dysfunction and cranial nerve (CN) involvement, and about 10-12% require a mechanical ventilator. In those with CN involvement, the facial nerve is most commonly affected, resulting in bilateral facial weakness.

Subtypes of GBS

GBS peripheral nerve damage can be classified histopathologically into 2 main types: demyelinating forms and axonal-degenerating forms. Motor nerves are more susceptible to disease than sensory ones. In 1995, GBS was subdivided into 4 distinct forms based on histopathological and neurophysiological basis: acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and Miller-Fisher syndrome (MFS).^{[25, 26]}

The clinical spectrum of GBS, which includes individual variation and variable severity of presentation, comprises the following:

• Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) - This accounts for 80-90% of GBS cases in Europe and North America. It is characterized by an immune-mediated attack on myelin with infiltration of lymphocytes and macrophages with segmental stripping of myelin. Motor and sensory fibers are usually affected simultaneously, producing corresponding deficits. Electrophysiology shows slow nerve conduction velocity and prolonged F waves.
• Acute motor axonal neuropathy (AMAN) - This form of neuropathy is most commonly seen in China and Japan (50-60% of cases), as apposed to Western countries (10-20% of cases). In this form, axonal degeneration occurs by immune attack within 1-2 weeks after infection. Specific antibodies to axonal membranes of motor fibers attack the nodes of Ranvier. This, in turn, activates complement and intrusion of macrophages into periaxonal space, resulting in destruction of axons. C jejuni is the most common preceding infection, and antiganglioside antibodies are usually found in this type. Electrophysiology shows reduction in muscle action potentials with relatively preserved motor nerve conduction velocity and normal sensory nerve action potentials and F waves.^{[25, 27]}
• Acute motor and sensory axonal neuropathy (AMSAN) - This type is rare and resembles AMAN except sensory nerves are also affected. This type is associated with a severe course and poor prognosis.
• Miller-Fisher syndrome (MFS) - The involvement of CNs is very distinct in this form of GBS. Ocular motor nerves (oculomotor, trochlear, and abducens) are affected and produce a triad of ophthalmoplegia, ataxia, and areflexia. Electrophysiology is normal. The characteristic autoantibodies are against gangliosides GQ1b and GT1a. GQ1b plays a key role in the pathogenesis of MFS.^[27]
• Polyneuritis cranialis - This is an acute onset of multiple CN palsies (usually bilateral CN VII with sparing of CNs I and II), elevated cerebrospinal fluid protein, and slowed nerve conduction velocity with uncomplicated recovery.
• Pharyngo-cervical-brachial syndrome - This variant form of GBS is characterized by localized and regional involvement of autonomic and motor nerves in the pharyngeal-cervical-brachial distribution. The diagnosis of this condition is based on clinical, laboratory, and neurophysiological findings and the exclusion of other conditions mimicking this disorder.
• Acute sensory neuropathy of childhood
• Acute pandysautonomia - Besides the above main forms of GBS, acute pandysautonomia is also a common subtype with which the autonomic nervous system is involved. Parasympathetic and sympathetic involvement is seen along with sensory or motor nerve involvement.

On physical examination, an ascending motor weakness is noted along with areflexia in the classic form. Areflexia is a hallmark of GBS. Occasionally, some of the more proximal reflexes still may be elicited during the early phase of the disease. Of clinical value is documenting reflexes in serial exams; the progression from normoreflexia/hyporeflexia to areflexia is consistent with acute features of GBS.

Occasionally, autonomic instability (26%), ataxia (23%), dysesthesias (20%), and cranial nerve findings (35-50%), predominantly facial palsy, are noted. These latter findings are probably more frequent in children than in adults with this syndrome.

Leg weakness (ie, foot drop) is usually noticed first and weakness eventually involves the calves and thighs. Later, respiratory muscles and upper extremities show involvement. Some children may become non-ambulatory. Weakness also may involve the respiratory muscles, and some children need respiratory support during the course of the disease. Mechanical ventilation is used until respiratory muscle function returns.

The autonomic neuropathy involves both the sympathetic and parasympathetic systems. Manifestations include orthostatic hypotension, hypertension, pupillary dysfunction, sweating abnormalities, and sinus tachycardia.

Complications of GBS

The most common serious complications are weakness of the respiratory muscles and autonomic instability. Pneumonia, adult respiratory distress syndrome, septicemia, pressure sores, pulmonary embolus, ileus, constipation, gastritis and dysesthesias are also important potential complications. Nephropathy has been reported in pediatric patients.^[28]

Features that would put the diagnosis in doubt include (1) marked persistent weakness, (2) bowel and bladder dysfunction at onset, (3) persistent bladder or bowel dysfunction, (4) mononuclear leukocytosis in the cerebrospinal fluid (>50 cells/µL), and (5) a sharp sensory level

Features that rule out the diagnosis include (1) a current history of hexacarbon abuse; (2) abnormal porphyria metabolism; (3) recent diphtheria infection; and (4) evidence of polio, botulism, toxic neuropathy, tic paralysis, or organophosphate poisoning.

Features required for diagnosis are (1) progressive weakness of more than one extremity, (2) hyporeflexia or areflexia, (3) elevated cerebrospinal fluid protein (>45 mg/dL) after 1 week following onset of symptoms, and (4) slow conduction velocity or prolonged F wave on electrophysiology testing.