Axonal Form Of Guillain-Barré Syndrome Research Articles

P.101 A-waves on electrodiagnostic studies in axonal and demyelinating cases of Guillain-Barré Syndrome (GBS)

Background: A-waves are lesser-known late responses of debated clinical significance, seen in routine motor nerve conduction studies (NCS). They are proposed to be a sensitive marker of demyelination and an early finding in acute demyelinating polyradiculoneuropathy (AIDP). We hypothesized that the presence and distribution of A-waves are discriminative markers in differentiating AIDP from axonal variants of Guillain-Barré Syndrome (GBS). Methods: We identified patients diagnosed with demyelinating and axonal forms of GBS at the Montreal Neurological Institute between 2016 and 2021. Clinical and electrophysiological data including raw NCS responses were retrospectively reviewed for 28 AIDP and 9 axonal GBS cases. Results: 20 of 28 AIDP cases had at least one A-wave in non-tibial nerves compared to 2 of 9 axonal cases. Among patients with NCS available within 2 weeks of symptom onset, 13 of 14 AIDP cases had non-tibial A-waves, compared to 0 of 6 axonal cases. Eight of 14 AIDP cases had one or more nerves with multiple A-waves within 2 weeks, compared to 0 of 6 axonal cases. Conclusions: In patients with GBS, the presence of A-waves in non-tibial nerves and of nerves with multiple A-waves are early indicators of the demyelinating variant. Early identification of GBS subtype is valuable for prognostication.

Nodopathies in the Early Diagnosis of Axonal Forms of Guillain-Barré Syndrome.

Introduction:Guillain-Barré syndrome (GBS) has been classified into demyelinating and axonal subtypes or forms, such as acute motor axonal neuropathy (AMAN) and regional pharyngeal-cervical-brachial variant (PCBv).ObjectiveTo study the relationship between motor nerve conduction blocks (CBs) and prognosis in AMAN and PCBv.Patients and MethodsWe retrospectively analyzed six cases of AMAN and PCBv with serial nerve conduction studies (NCS) and electromyography (EMG).ResultsThe serial NCS (1st−2nd and 3rd week) showed, as the most constant data, a decreased amplitude of the compound muscle action potential (CMAP) in 100% of cases. CBs were present in 66.6% of cases. EMG (3rd week) showed signs of severe denervation in 33.3%. All patients were treated from the 1st−2nd week of evolution with intravenous immunoglobulins (IVIGs). Patients with CBs (1st−2nd and 3rd week), showed reversible CBs or reversible conduction failure (RCF) and complete recovery at 1 month. Patients without CBs, with persistent reduced distal CMAP amplitude (dCMAP), showed severe acute denervation due to axonal degeneration (3rd week and 1st−3rd month) and a slow recovery of several months.ConclusionsNot all axonal forms of GBS have a poor prognosis. This study of AMAN and PCBv shows that patients with CBs can have reversible CBs or RCF, and good prognosis. Patients without CBs, with persistent reduction of dCMAP amplitude decrement, have severe acute denervation, and a worse prognosis. AMAN and PCBv have a continuous spectrum ranging from CBs due to dysfunction/disruption of Nodes of Ranvier, called nodopathies, with reversible CBs or RCF and good prognosis, to axonal degeneration with worse prognosis.

The role of macrophages in Guillain‐Barré syndrome and chronic inflammatory demyelinating polyneuropathy

AbstractMacrophages play an important role in the pathogenesis of immune‐mediated neuropathies, particularly Guillain‐Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Early reports of pathological findings in patients with GBS and CIDP suggested demyelination resulting from phagocytosis of myelin by macrophages as the cause of aberrant nerve conduction in these diseases. Later studies established a concept that molecular mimicry of gangliosides in the peripheral nervous system to surface epitopes of pathogens results in the production of autoantibodies in patients with an axonal form of GBS. In some of the patients diagnosed with CIDP, IgG4 autoantibodies against paranodal junction proteins, such as neurofascin 155 and contactin 1, were found to induce aberrant nerve conduction resulting from the detachment of paranodal myelin terminal loops from axolemma. In contrast, the mechanisms of neuropathy in cases with classical macrophage‐induced demyelination are still to be elucidated. Electron microscopic examination suggested that macrophages recognize specific sites of myelinated fibers as the initial target of demyelination in both GBS and CIDP. It seems that the components that distinguish between the nodal regions, such as the nodes of Ranvier, paranodes, and internodes play a pivotal role in the behavior of macrophages that initiate the phagocytosis of myelin. Further studies are required to clarify the mechanisms of macrophage‐induced demyelination to facilitate the development of new therapeutic strategies directed against the pathology of macrophages.

Macrophages and Autoantibodies in Demyelinating Diseases.

Myelin phagocytosis by macrophages has been an essential feature of demyelinating diseases in the central and peripheral nervous systems, including Guillain–Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and multiple sclerosis (MS). The discovery of autoantibodies, including anti-ganglioside GM1 antibodies in the axonal form of GBS, anti-neurofascin 155 and anti-contactin 1 antibodies in typical and distal forms of CIDP, and anti-aquaporin 4 antibodies in neuromyelitis optica, contributed to the understanding of the disease process in a subpopulation of patients conventionally diagnosed with demyelinating diseases. However, patients with these antibodies are now considered to have independent disease entities, including acute motor axonal neuropathy, nodopathy or paranodopathy, and neuromyelitis optica spectrum disorder, because primary lesions in these diseases are distinct from those in conventional demyelinating diseases. Therefore, the mechanisms underlying demyelination caused by macrophages remain unclear. Electron microscopy studies revealed that macrophages destroy myelin as if they are the principal players in the demyelination process. Recent studies suggest that macrophages seem to select specific sites of myelinated fibers, including the nodes of Ranvier, paranodes, and internodes, for the initiation of demyelination in individual cases, indicating that specific components localized to these sites play an important role in the behavior of macrophages that initiate myelin phagocytosis. Along with the search for autoantibodies, the ultrastructural characterization of myelin phagocytosis by macrophages is a crucial step in understanding the pathophysiology of demyelinating diseases and for the future development of targeted therapies.

Self-reported autonomic dysfunction in a recovery phase of Guillain-Barré syndrome

ObjectiveAutonomic dysfunction occurs in approximately two-thirds of Guillain-Barré syndrome (GBS) patients in the acute phase of the disease. Although improving over time, subclinical autonomic involvement may be present for 3–8 years after the GBS episode. The aim of this study was to determine the frequency of self-reported autonomic disorders in GBS patients three and six months after disease onset compared to healthy controls (HCs). MethodsOur study included adult patients diagnosed with GBS from May 2017 until May 2018 in seven healthcare centers (67.6 % with demyelinating and 13.6 % with axonal syubtype). Functional disability was assessed by the Guillain-Barré syndrome disability scale (GDS). Each subject filled in the Serbian version of the SCOPA-Aut questionnaire. Using GDS and SCOPA-Aut, patients were tested at month 3 (M3) (n = 71) and month 6 (M6) (n = 70) from symptom onset. ResultsDysautonomia was more common in patients with GBS compared to HCs at M3 (p < 0.01), while there was no difference at M6 (p > 0.05). Among autonomic disorders, constipation, complications to pass stool, and orthostatic hypotension were the most frequently reported. Patients with axonal variants had worse total SCOPA-Aut scores at M3 in comparison to AIDP patients (11.7 ± 10.1 vs. 6.1 ± 5.1, p < 0.05). GDS score correlated with the total SCOPA-Aut score. ConclusionAutonomic symptoms are common in GBS patients during the recovery phase. They are more pronounced in patients with axonal forms of GBS and those with a higher degree of functional disability.

Guillain-Barré syndrome following varicella-zoster virus infection

We describe the frequency, clinical features, and electrophysiological and immunological phenotypes of Guillain-Barré Syndrome (GBS) patients treated at a single institution in Bangladesh who had preceding chicken pox (primary Varicella-zoster virus [VZV] infection) within 4weeks of GBS onset. A literature review of GBS cases preceding VZV infection is also provided. Diagnosis of GBS was based on the National Institute of Neurological Disorders and Stroke criteria for GBS. Serum anti-VZV IgM and IgG antibodies were quantified by indirect chemiluminescence immunoassay (CLIA); anti-Campylobacter jejuni IgG, IgM, and IgA antibodies and anti-ganglioside GM1 IgM and IgG antibodies, by enzyme-linked immunosorbent assays. Neurophysiologic subtypes were categorized following the Hadden criteria. Of 536 patients with GBS, 7 (1.3%) had chicken pox within 4weeks before GBS onset. Four of the seven cases were male (age range, 23 to 40years old). All seven patients were bed-bound, six had sensory symptoms, and three required mechanical ventilation for respiratory failure. All seven patients had CSF albuminocytologic dissociation and evidence of demyelination in nerve conduction studies. Anti-VZV IgM antibodies were present and anti-GM1 and anti-Campylobacter jejuni lipo-oligosaccharides (LOS) were negative in all cases. All patients had excellent outcome at 1year (able to run). A systematic literature review of GBS cases related to VZV revealed 39 previously reported patients with comparable clinical presentations and outcomes, of which 36 had neurophysiologic evidence of demyelination. VZV infection is associated with the demyelinating subtype of GBS, clearly distinct from the axonal form of GBS that predominate in countries like Bangladesh.

CD1A and CD1E gene polymorphisms are not associated with susceptibility to Guillain-Barré syndrome in the Bangladeshi population

The post-infectious autoimmune polyradiculoneuropathy Guillain-Barré syndrome (GBS) is triggered by molecular mimicry between microbial glycolipid antigens and human peripheral nerve gangliosides. Single nucleotide polymorphisms in exon 2 of CD1A (*01/*02) and CD1E (*01/*02) were assessed using PCR-RFLP; no significant differences in genotype or allele frequency were observed between 200 patients with GBS and 200 healthy controls. CD1 gene polymorphisms cannot be recognized as a susceptibility or disease-causative factor for GBS in the Bangladeshi population. However, further studies are necessary to investigate the CD1A*01/CD1E*01 haplotype distribution and its potential causative role in the axonal form of GBS.

Anti-Ganglioside Antibodies Induce Nodal and Axonal Injury via Fcγ Receptor-Mediated Inflammation.

Guillain-Barré syndrome (GBS) is a postinfectious autoimmune neuropathy and anti-ganglioside antibodies (Abs) are strongly associated with this disorder. Several studies have implied that specific anti-ganglioside Abs induce neuropathy in patients with axonal forms of GBS. To study the mechanisms of anti-ganglioside Abs-induced neuropathy, we established a new passive transfer mouse model by L5 spinal nerve transection (L5SNT; modified Chung's model) and systemic administration of anti-ganglioside Abs. L5SNT causes degeneration of a small proportion of fibers that constitute sciatic nerve and its branches, but importantly breaks the blood-nerve barrier, which allows access to circulating Abs and inflammatory cells. Our studies indicate that, in this mouse model, anti-ganglioside Abs induce sequential nodal and axonal injury of intact myelinated nerve fibers, recapitulating pathologic features of human disease. Notably, our results showed that immune complex formation and the activating Fc gamma receptors (FcγRs) were involved in the anti-ganglioside Abs-mediated nodal and axonal injury in this model. These studies provide new evidence that the activating FcγRs-mediated inflammation plays a critical role in anti-ganglioside Abs-induced neuropathy (injury to intact nerve fibers) in GBS.

Antiganglioside antibodies in Guillain–Barré syndrome and its related conditions

Guillain–Barré syndrome (GBS) is typically classified into two major subtypes: acute inflammatory demyelinating neuropathy and acute motor axonal neuropathy. Its most recognizable variant is Fisher syndrome. The last two decades have seen considerable advances in our understanding of GBS. Of note, various autoantibodies against ganglioside antigens have been identified and found to have significant associations with the axonal forms of GBS and Fisher syndrome. In this article, we discuss the different clinical presentations in GBS and the role of antiganglioside antibodies in their underlying pathogenesis. We also discuss the impact that antiganglioside antibodies have had in the development of experimental models and treatment modalities in GBS.

Long term clinical and electrophysiological assessment of Croatian children with corticospinal tract involvement in Guillain–Barré syndrome (GBS)

Guillain–Barré syndrome (GBS) is characterized by areflexia. Hyperreflexia is reported in acute motor axonal neuropathy (AMAN ). We present 16 children with GBS at the age of 14 months to 13 years. All children studied fulfilled accepted diagnostic criteria for GBS. Hyperreflexia or positive Babinski sign were obtained in all children studied during follow up. Brain and spinal cord MR scans did not reveal any significant structural and morphological abnormalities of central nervous system. The children were examined clinically and electromyoneurographically 2–5 times successively during 1–8.5 years of follow-up. According to established electrodiagnostic criteria demyelinating form of GBS was most common (68%) compared to axonal (18,7%) or mixed form (12,5%). No children had antecendent Campylobacter jejuni infection. Antiganglioside antibodies were detected in 18,7% of patients associated with demyelinating or mixed (axonal/demyelinating) form. Time to nadir and recovery period of walking ability is prolonged more often in demyelinating GBS. Clinical improvement occur earlier compared to improvement of abnormal electrophysiological parameters.Outcome was excellent in 11 in the period 1 month–8.5 years. Hyperreflexia usually appeared in recovery period suggesting involvement of upper motor neurons or spinal interneurons occurring in Croatian children with both demyelinating and axonal form of GBS usually associated with milder course of disease.

Anti-GM1 antibodies affect the integrity of lipid rafts

Previous studies have shown that patients with the axonal form of Guillain–Barré syndrome (GBS) develop autoantibodies against GM1 ganglioside (GM1). Nerve growth factor (NGF) is essential for neuronal survival in vivo and its functional receptor is Trk-tyrosine kinase. Here, we examined the biological effects of sera from patients with the axonal form of GBS on the morphology and the phosphorylation state of Trk-tyrosine kinase in PC12 cells. Furthermore, we examined the effect of the sera on the integrity of membrane lipid rafts biochemically. The data show that anti-GM1 antibodies found in patients' sera but not control sera inhibit NGF-induced Trk autophosphorylation. Most intriguingly, the autoantibodies alter the distribution of Trk in lipid rafts without shifting the distribution of a rafts marker protein. These data strongly suggest that anti-GM1 antibodies directly influence the integrity of the signaling platform, lipid rafts, implicating the importance of lipid rafts in the development of this disorder.

Keep your knife off, it is an ADEM!

Guillain-Barré syndrome (GBS) is an acute polyneuropathy consisting of different subtypes. Acute inflammatory demyelinating polyradiculoneuropathy, the classic demyelinating form of GBS, accounts for 90% of all GBS cases in the Western world. Acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN) are axonal forms of GBS that are more prevalent in Asia, South and Central America, often preceded by infection by Campylobacter jejuni. AMAN and AMSAN may be mediated by specific anti-ganglioside antibodies that inhibit transient sodium ion (Na+) channels. The efficacy of plasmapheresis and intravenous immunoglobulin has been established in large international randomised trials, with corticosteroids proven ineffective. Although axonal demyelination is an established pathophysiological process in GBS, the rapid improvement of clinical deficits with treatment is consistent with Na+ channel blockade by antibodies or other circulating factors, such as cytokines. This review provides an update on the epidemiology, clinical features, diagnosis, pathogenesis and treatment of GBS.

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.

88th ENMC International Workshop: Childhood chronic inflammatory demyelinating polyneuropathy (including revised diagnostic criteria), Naarden, The Netherlands, December 8–10, 2000

88th ENMC International Workshop: Childhood chronic inflammatory demyelinating polyneuropathy (including revised diagnostic criteria), Naarden, The Netherlands, December 8–10, 2000

Guillain-Barre syndrome and Campylobacter jejuni infection

Guillain-Barre syndrome (GBS) is the most common cause of acute neuromuscular paralysis, usually due to acute inflammatory demyelinating polyradiculoneuropathy. The presence of activated T lymphocytes and antibodies against peripheral nerve myelin suggests an autoimmune pathogenesis, although there is wide heterogeneity. Gangliosides are sialylated glycolipids widely distributed in nervous system membranes. GBS is usually preceded by an infection, most frequently Campylobacter jejuni enteritis, but also cytomegalovirus, Mycoplasma pneumoniae or Epstein-Barr virus. Patients with GBS and C. jejuni infection are more likely to have neurophysiological features of axonal neuropathy, antibodies to ganglioside GM1, pure motor GBS, a less elevated CSF protein concentration and a worse outcome than other GBS patients. Although molecular mimicry between peripheral nerve gangliosides and epitopes present on C. jejuni lipopolysaccharide could explain some of these associations, this hypothesis is inadequate to account for many aspects of the pathogenesis of GBS.