Physiologic-pathologic correlation in Guillain-Barré syndrome in children

OBJECTIVE: To correlate electrophysiologic patterns with sural nerve pathology in children with Guillain-Barré syndrome (GBS). BACKGROUND: Based on electrophysiologic and pathologic observations, GBS has been divided into demyelinating and axonal subtypes. The acute motor axonal neuropathy (AMAN) involves predominantly motor nerve fibers with a physiologic pattern suggesting axonal damage, whereas the acute inflammatory demyelinating polyneuropathy (AIDP) involves both motor and sensory nerve fibers with a physiologic pattern suggesting demyelination. In this study, we sought to confirm these observations by correlating sural nerve pathology with electrophysiologic findings in GBS patients. METHODS: Biopsies of sural nerve from 29 of 50 prospectively studied GBS patients were obtained. Nerves were examined by light and electron microscopy, and with immunocytochemistry for macrophages, lymphocytes, and complement activation products. RESULTS: Sural nerves from AMAN patients were normal or had only a few (0.1% to 0.7%) degenerating fibers without lymphocytic infiltration or complement activation. One patient with reduced sural sensory nerve action potential classified as acute motor sensory axonal neuropathy (AMSAN) had many degenerating fibers (2.3%) in the sural nerve. All three AIDP patients displayed active demyelination, and in two patients, lymphocytic infiltration and complement activation products were observed on the abaxonal Schwann cell surface. CONCLUSION: Classification of Guillain-Barré syndrome subtypes based on motor conduction studies correlates closely with pathologic changes seen in sural nerve. In acute motor axonal neuropathy cases, the sural nerve is almost completely spared pathologically. In acute inflammatory demyelinating polyneuropathy cases, macrophage-mediated demyelination and lymphocytic infiltration are common in the biopsies of sural nerves.     

Guillain-Barré syndrome in children

In industrialized nations with widespread immunization programs, Guillain-Barré syndrome is the most common cause of acute paralytic illness in children and adults. The incidence of the disease has been estimated to range from 0.5 to 1.5 in 100,000 in individuals less than 18 years of age. Approximately 15% of children with Guillain-Barré syndrome develop respiratory failure and require mechanical ventilatory support. Prospective randomized treatment trials in childhood Guillain-Barré syndrome are wanting; however, smaller case series studies using historical controls suggest that both plasmapheresis and administration of human immunoglobulin could be helpful in reducing morbidity in children with Guillain-Barré syndrome. The prognosis for recovery in children is generally excellent, with the majority of children achieving a complete functional recovery within 6 months from the onset of illness. Studies using an animal model of human Guillain-Barré syndrome, experimental allergic neuritis, have expanded our understanding of the pathogenesis of the disease and suggest new directions for exploration in the treatment of this disorder.     

Intravenous immunoglobulin in children with Guillain-Barré syndrome

We report our experience with intravenous immunoglobulin (IVIG), plasmapheresis and supportive care in 13 patients with the Guillain-Barré syndrome. Seven of 13 patients received IVIG, 2 plasmapheresis and 4 supportive care. At 15th day after IVIG administration, all patients in this group had improved at least one disability grade. In the plasmapheresis group, 1 improved at 5th day after the procedure. Two of the 4 patients that received supportive care improved at 20th day of evaluation. In the IVIG group, the final scores were lower and had no relapses. These results suggest faster clinical improvement with IVIG when compared with supportive measures.     

Progress in Guillain-Barré syndrome

This editorial review summarizes and critically analyses reports published in the preceding 18 months on the pathogenesis of Guillain-Barré syndrome, with particular emphasis on the role of ganglioside antibodies, antecedent infections, and the concept of molecular mimicry. It concludes with an appraisal of currently available and proposed therapies.     

Pain in Guillain-Barré syndrome

Evaluation of: Ruts L, Drenthen J, Jongen JL et al. Pain in Guillain-Barré syndrome: a long-term follow-up study. Neurology 75, 1439-1447 (2010). Pain has been recognized as an important symptom of Guillain-Barré syndrome (GBS). The article under review prospectively studied the phenomenon of pain in a cohort of 156 GBS patients for a period of 1 year. It confirmed that pain of significant intensity is relatively common in all subtypes of GBS. It may start before the onset of other symptoms. It correlates with sensory loss, severity of the GBS at its nadir and the presence of diarrhea. In the recovery/chronic stages it correlates with weakness, disability and fatigue. Up to a third of patients have pain at 1 year.     

Pain in Guillain-Barré syndrome

The clinical features of pain were prospectively analyzed in 29 consecutive patients with Guillain-Barré syndrome (GBS). Sixteen (55%) had characteristic pain early in the illness described as similar to the muscular discomfort following exercise ("charley horse"). Pain preceded weakness by one to five days in four patients. The anterior and posterior aspects of the thighs, the buttocks, and the low part of the back were most frequently affected. Pain was frequently worse at night. Specific clinical signs or electrophysiologic abnormalities were not associated with pain, but serum creatine kinase level was elevated in ten of 13 patients with pain and only one of eight without pain. A review of previously reported pathologic material in five patients with GBS failed to disclose a relation between inflammation of dorsal root ganglia and pain. These results suggest that alterations in muscle related to neurogenic changes may cause the typical pain of GBS.     

Guillain-Barré syndrome in Chinese children: a retrospective analysis

We reviewed the clinical and electrophysiologic features of 293 children with Guillain-Barré syndrome admitted to the Children’s Hospital of Chongqing Medical University between 2000 and 2009. The male/female ratio was 2.02, and the syndrome occurred most frequently in those between 1 and 4 years of age. There was no seasonal variation. A total of 46.1% patients had experienced an infection 1 to 4 weeks before the onset of the syndrome. The main subtype was acute motor axonal neuropathy (50.0%), with acute inflammatory demyelinating polyradiculoneuropathy (38.1%) ranked as second in frequency. The mean motor disability score at nadir was 3.36 ± 1.00 for all patients, with mild variations among the different subgroups. No significant difference was found in age, seasonal occurrence, cerebrospinal fluid abnormality, and functional status at nadir between the acute motor axonal neuropathy and the acute inflammatory demyelinating polyradiculoneuropathy groups. A total of 36.5% patients had sensory symptoms at admission. Approximately 9.5% of patients required mechanical ventilation. Typical cytoalbuminologic dissociation at cerebrospinal fluid examination was demonstrated in 88.0% of those who underwent lumbar puncture.     

Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is currently divided into the two major subtypes: acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). This review highlights relevant recent publications, particularly on the pathophysiology of AMAN. Molecular mimicry of the bacterial lipo-oligosaccharide by the human gangliosides is now considered an important cause of AMAN. Gangliosides GM1, GM1b, GD1a, and GalNAc-GD1a expressed on the motor axolemma are likely to be the epitopes for antibodies in AMAN. At the nodes or paranodes, deposition of antiganglioside antibodies initially cause reversible conduction block followed by axonal degeneration. Electrodiagnostic findings support this process. Disruption of glycolipids, which are important to maintain ion channel clustering at the nodes and paranode, may impair nerve conduction. Genetic polymorphisms of Campylobacter jejuni determine the expression of the gangliosides on the bacterial wall. In contrast, target molecules in AIDP have not yet been identified. Meta-analyses show efficacy of plasmapheresis and immunoglobulin therapy, but not corticosteroids, in hastening recovery.     

Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute-onset, monophasic, immune-mediated polyneuropathy that often follows an antecedent infection. The diagnosis relies heavily on the clinical impression obtained from the history and examination, although cerebrospinal fluid analysis and electrodiagnostic testing usually provide evidence supportive of the diagnosis. The clinician must also be familiar with mimics and variants to promptly and efficiently reach an accurate diagnosis. Intravenous immunoglobulin and plasma exchange are efficacious treatments. Supportive care during and following hospitalization is also crucial.     

Magnetic resonance imaging diagnosis of acute Guillain-Barré syndrome in children

The present study examined 24 children with acute Guillain-Barré syndrome using magnetic resonance imaging (MRI) plain scans and fat-suppressed enhanced T1-weighted imaging (T1WI) scans.Axial MRI plain scans centering on the medullary conus were positive in nine patients (38%).These displayed variable thickening involving the cauda equina with isointensity on T1WI and isointensity or slight hyperintensity on T2WI.False negatives were obtained in patients with cervical and cranial nerve symptoms.Contrast enhancement of T1WI with fat suppression was positive in all patients in the cauda equina with varied thickening and enhancement centering on the medullary conus.Five patients (36%) were positive in the cervical nerves and 3 patients (50%) were positive in the cranial nerves.These patients had corresponding cervical and cranial nerve symptoms,respectively.Patients with serious clinical symptoms in the lower limbs exhibited obvious involvement of the cauda equina by MRI.Statistical analysis revealed a positive correlation between the extent of enlargement of the cauda equina,centering on the medullary conus,and cerebrospinal fluid protein concentration.     

Guillain-Barré syndrome in northwest Greece

OBJECTIVES: We present the epidemiological and clinical-laboratory features of Guillain-Barré syndrome (GBS) in northwest Greece over a 9.5-year period. MATERIALS AND METHODS: We studied all the patients with GBS who were admitted to our neurology inpatient service from January 1996 to May 2005 and compared them with previously published series. RESULTS: Forty-six patients were hospitalized during this period. The average crude incidence rate was 1.22/100,000 populations per year, and males were more susceptible than females. There was a spring clustering, as 52.17% presented the syndrome during spring. The axonal type of GBS was recorded in 13.04% of the patients. The most frequent presenting symptom was dysesthetic numbness (52.17%). A large number of patients (56.52%) had up to three times the elevation of liver function values that resolved in a few weeks. Most patients had an excellent recovery and no deaths were recorded. CONCLUSIONS: In our series, there was no difference in the incidence rate and subtypes of GBS but there was a significant seasonality with spring clustering. A transient elevation of transaminases of undetermined etiology was noted in more than a half of our patients. Although seven patients (15.21%) had significant neurologic sequelae, no deaths occurred.     

Guillain-Barré syndrome: perspectives with infants and children

An acute flaccid paraparesis or ascending quadriparesis in an infant or child constitutes a very important pediatric neurology emergency. The Guillain-Barré syndrome (GBS) is the most frequent cause. This is primarily an autoimmune, post-infectious, demyelinating, peripheral nervous system process. A small percentage of children develop a primary axonal process not unlike that identified more commonly in China. Because of the potential for acute respiratory compromise, any child suspected of having GBS needs immediate hospitalization. The major considerations in differential diagnosis include transverse myelitis, toxic neuropathies, tick paralysis, infantile botulism, myasthenia gravis, and dermatomyositis. On occasion, some younger children present with an acute severe pain syndrome that may mask as a pseudo-encephalopathy. Another clinical variant is the Miller-Fisher syndrome characterized by ataxia, ophthalmoparesis, and areflexia. This is associated with a high frequency of the anti-GQ-1-b antibodies. Although most children with GBS have a relatively benign clinical course, some become very ill and require intubation with intensive care monitoring. Immunomodulating treatment should be used for any child who loses the ability to walk. To date, no well-controlled study has been completed analyzing the relative merits of the two most commonly used therapies, namely plasmapheresis or intravenously administered immunoglobulin.     

A-waves in Guillain-Barré syndrome: correlation with electrophysiological subtypes and antiganglioside antibodies

ObjectiveTo investigate the relationship of A-waves with conventional electrophysiological subtypes of Guillain–Barré syndrome (GBS), as well as with anti-ganglioside antibodies.MethodsThe subjects consisted of 30 GBS patients who were classified into acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy, and unclassified based on the results of nerve conduction studies. “Abundant A-waves” were defined for the upper-limb nerves (median and ulnar nerves) using receiver–operator characteristic curves. The presence or absence of IgG anti-ganglioside antibodies was also noted.ResultsAbundant A-waves at weeks 3–6 from onset were observed in 64% of the 14 AIDP patients and 0% of 16 non-AIDP patients, and in 60% of 15 antibody-negative patients and 0% of 15 antibody-positive patients. In the earlier period, this relationship was less clear. The correlation between the conventional electrophysiological subtypes and antibodies was present, but was much weaker.ConclusionsAbundant A-waves in GBS after the acute phase were strongly associated with demyelination that was not mediated by antiganglioside antibodies, possibly through the mechanism of proximal re-excitation induced by electrical inhomogeneities due to segmental demyelination.SignificanceAbundant A-waves are promising as a novel reliable marker of demyelination.     

Outcome of axonal and demyelinating forms of Guillain-Barré syndrome in children

Previous reports have suggested that outcome is worse in the axonal compared with the demyelinating form of Guillain-Barré syndrome (GBS). We performed a retrospective study of 23 children with electrophysiologically confirmed cases of predominant subtypes of GBS to investigate this issue. The patients were classified based on the electrodiagnostic features: Ten (44%) had acute inflammatory demyelinating polyradiculoneuropathy, eight (35%) had acute motor axonal neuropathy, and five (21%) had acute motor-sensory axonal neuropathy. All patients received a standard intravenous immunoglobulin therapy (0.4 g /kg /day for 5 consecutive days). In the acute phase of the disease, patients with the axonal forms of GBS were more disabled than were those with the demyelinating GBS, as measured by GBS scores. Mechanical ventilation was required in five (38%) patients in the axonal group compared with one (10%) patient in the demyelinating group. There was no significant difference at 6 months in GBS scores between demyelinating and axonal forms of GBS. All 20 survivors recovered completely by 12 months. After standard intravenous immunoglobulin therapy, children with axonal forms of GBS recover more slowly than those with the demyelinating form, but outcome at 12 months appears to be equally favorable in two groups.