Respiratory paralysis in a child: The severe axonal variant of childhood Guillain-Barré syndrome.

Guillain-Barre syndrome (GBS) is a common cause of acute flaccid paralysis in children. Axonal variants of this disease are rare, and frequently life-threatening or debilitating. The course and outcome of a 17-month-old child with acute flaccid paralysis including severe respiratory involvement are presented. GBS was suspected. Nerve conduction studies demonstrated acute motor-sensory axonal neuropathy including both phrenic nerves. The difficulties with the diagnosis and management of this severe and life-threatening condition are discussed. Significant morbidity is also highlighted. Axonal variants of GBS although rare cause significant morbidity in children. Diagnosis relies solely on accurate neurophysiologic testing and is important because the available treatment options for GBS are frequently ineffective in these variants.

Introduction

Acute flaccid paralysis in children is an emergency demanding prompt diagnosis and treatment without delay to prevent life-threatening complications. The common causes in India include poliomyelitis, Guillain–Barre syndrome (GBS), toxic neuropathy, and myelitis.[1] There are several variants of GBS described in the literature. Axonal variants of this disease are infrequently encountered in children. They are the most severe forms of GBS causing debilitating disease. Immunotherapy often fails in these conditions, and recovery is incomplete in many patients.[23]

Case Report

A 17-month-old boy developed watery diarrhea requiring treatment at a hospital for dehydration in May 2009. He was discharged home in a stable condition. After 2 days, he had a sudden onset of respiratory distress with no preceding fever, cough, vomiting, seizures, or aspiration. His sensorium was preserved. No weakness was noted at this time. He was a well-thriving child on exclusive breastfeeding, with four elder female siblings, all healthy, and he had attained age-appropriate development.

He was admitted again at another hospital in a critical state: He was acidotic, in distress, heart rate 168/min, respiratory rate 48/min, with nasal flaring, recessions, crackles in bilateral basal areas, moderate hepatomegaly. On examination, he was also hypotonic with normal sensorium and cranial nerve function and bilateral extensor plantar responses. His investigations at this time showed metabolic acidosis (pH 7.09, HCO3 = 3 mmol/L), which gradually improved. He had hyperglycemia (up to 248 mg/dL). Cerebrospinal fluid (CSF) examination was normal. Plain computed tomographic scan of the head was normal. With these findings, he was presumed to have diabetic ketoacidosis and treatment was commenced with insulin infusion, but he developed hypoglycemia soon after, and insulin had to be stopped. During his 5-day stay at this hospital, he developed progressive weakness, generalized hypotonia, flaccid quadriparesis, and paradoxic respiration needing intubation to secure ventilation. He was then transported to our center.

During transport, he suffered significant hypoxia. He was brought in a near respiratory arrest stage to our hospital. At admission, he had no spontaneous eye opening or responses, was hypotonic, areflexic, and with bilateral extensor plantar responses. He was resuscitated and stabilized with fluids, mechanical ventilation, and supportive care. Repeat investigations including blood counts, electrolytes, kidney and liver function tests were normal. Workup for diabetes was negative (HbA1c 6%). Repeat CSF examination (on 10th day after onset of weakness) was normal. Thyroid function and cardiac function by echocardiography were normal. Stool culture for Campylobacter jejuni was negative (at 3 weeks from onset of weakness).

Mechanical ventilation was continued for respiratory muscle weakness and hypoxic lung injury. He failed multiple weaning attempts on spontaneous breathing trials. Diaphragmatic weakness was suspected and confirmed by fluoroscopy. Tracheostomy was performed. By this time, he had developed complete generalized flaccid quadriparesis with areflexia. He also had autonomic dysfunction with sinus tachycardia (up to 180–195/min) and labile hypertension. Nerve conduction studies showed acute motor-sensory axonal neuropathy with decreased velocity and amplitude of compound muscle action potential (CMAP) and sensory neuron action potentials (SNAP), no conduction block, and absent F wave responses. Magnetic resonance imaging (MRI) of the brain revealed bilateral basal ganglia hyperintensities on T2-weighted images. Diagnosis of the axonal variant of GBS was made.

Treatment with intravenous immunoglobulin (IVIG) was given (400 mg/kg for 5 days). Hypertension was controlled with amlodipine and enalapril. Mechanical ventilation was continued. Over the next 4 weeks, weakness improved gradually in his limbs and trunk but diaphragmatic weakness persisted as documented by fluoroscopy. Nerve conduction studies of the phrenic nerves showed severe axonal damage.

With intensive support and attention to nutrition, he recovered gradually with return of normal respiratory function over the next 10 weeks. He was gradually weaned from assisted ventilation and was successfully decannulated from his tracheostomy at this point, and he maintained normal respiratory function thereafter. He had regained full muscle power and was gaining milestones when last seen in September 2009.

Discussion

A child with acute onset of flaccid paralysis presents a challenge to the diagnostic skills of a pediatrician. In India, the primary causes include acute poliomyelitis, acute transverse myelitis, toxic neuropathy, nutritional neuropathies, and dyselectrolytemias.[1] In the critically ill child, often the diagnosis is delayed as attention is diverted to life-support interventions. In such children, critical illness polyneuropathy and GBS must also be considered.

Acute motor-sensory axonal neuropathy is a variant of GBS first described by Feasby et al. in 1986.[4] It is a fulminant, life-threatening condition whose hallmark is prominent motor and sensory involvement due to involvement of both ventral and dorsal nerve roots. Most cases have a documented preceding infection with C. jejuni (6–60%).[2] We investigated our patient for intestinal carriage of this organism as it can persist for up to 6 weeks after infection, but failed to detect it. Molecular mimicry between bacterial endotoxin and axonal gangliosides triggers activated macrophages to invade axons through the nodes of Ranvier and cause degeneration of the axonal cell membrane while sparing the myelin sheath.[2] Retrograde Wallerian degeneration then spreads to involve the nerve roots and sometimes even the neurons themselves leading to permanent neurologic disability. Detection of anti-ganglioside antibodies may help in the diagnosis (anti-GM1, anti-GM1b, anti-GD1a).[3]

Acute motor-sensory axonal neuropathy is characterized by frequent respiratory muscle involvement and ventilator dependence. Hyperreflexia may be seen. Diagnosis can be reliably established only by electrophysiologic studies (showing <80% amplitude in CMAP/SNAP, loss of F waves, with preserved velocity and no conduction block).[5] Recovery in most cases is partial and slow, leaving significant residual deficits. Autonomic dysfunction predicts the need for mechanical ventilation.[567] Reports suggest partial to no response to treatment with plasmapharesis and IVIG especially in children.[89] In our patient, we could not conclude whether he responded to IVIG therapy, as the lag time to treatment response was very long (~4 weeks) and which is also consistent with the natural course of recovery from GBS.

The MRI findings in our child coupled with the initial presentation with ketoacidosis, hyperglycemia, and sudden decompensation after an acute diarrheal illness, had raised the possibility of an inborn error of metabolism, probably an organic acidemia. Of these, propionic acidemia and methylmalonic acidemia were considered. A metabolic screening repeated twice returned inconclusive results. We attribute the MRI findings to hypoxic-ischemic injury. It should also be noted that as this child was predominantly breastfed even at 17 months of age, micronutrient deficiencies (notably Vitamin B12 and iron) could have contributed to the neuropathy and compounded his clinical presentation.

Conclusion

It is important for clinicians to be aware of this rare form of GBS not only for the fact that it is the most severe and life-threatening, but also because its treatment needs prolonged intensive care, close attention to nutrition and preventing complications, surveillance for disability and infections, and substantial morbidity with respect to hospital stay, treatment costs, and social burdens on the family.