Changes in ganglioside antibody positivity rates during the COVID-19 pandemic.

Reports suggested an association between SARS-CoV-2 infection and GBS, but subsequent studies produced conflicting results regarding the incidence of GBS during the pandemic. This study assessed positivity rates for GQ1b, GM-1, GD1a, and GD1b for tests performed January 2016, through March 2021, at a national laboratory. Relative to pre-pandemic levels, positivity rates during the pandemic declined by 61% for GQ1b and 24% for GM-1, while unchanged for GD1a and GD1b. These findings suggest heterogeneity with positivity rates of GBS-associated ganglioside antibodies during the COVID-19 pandemic. Mitigation strategies during the pandemic may have reduced the frequency of certain forms of GBS.

Reversible conduction block of peroneal nerve associated with SARS-CoV-2.

BACKGROUND: The ongoing SARS-CoV-2 pandemic, which is dramatically spreading worldwide, is well known for its respiratory sequelae. Besides cases of Guillain-Barré Syndrome, encephalitis, hyposmia, the whole range of neurological complications due to SARSCoV-2 is still not well known. METHODS AND FINDINGS: Herein, we report a new case of COVID-19, associated with mononeuropathy with reversible conduction block (CB). After SARS-CoV-2 infection, the patient developed acute weakness of left peroneal muscles. He underwent an endovenous immunoglobulin treatment, and symptoms improved. Two electroneurographic exam (before and after treatment), showed a reversible CB on left peroneal nerve. Dosage of serum antiganglioside antibodies showed anti-GM1 IgM positivity. CONCLUSIONS: The present case gives new informations about reversible CB neuropathy as an acute presentation of SARS-CoV-2. Besides, antiganglioside antibodies evaluation could be useful to understand etiology of the increasing number of neurological manifestations related to SARS-CoV-2.

Neuropathy of the phrenic nerve associated with antiganglioside antibodies.

BACKGROUND AND PURPOSE: Antiganglioside antibodies have been implicated in several autoimmune-mediated neuropathies, and binding of these antibodies can result in inflammatory changes of the nerves. Diaphragmatic paralysis is a rare condition, mostly arising from diseases affecting the phrenic nerve, neuromuscular junction, or skeletal muscle. OBJECTIVES: In this case series, we identified five patients with diaphragmatic paralysis due to unilateral or bilateral neuropathy of the phrenic nerve associated with the presence of antiganglioside antibodies (immunoglobulin G anti-GT1a antibodies and immunoglobulin M anti-GM1 antibodies). DISCUSSION: The combination of an isolated phrenic nerve palsy with anti-GM1 antibodies has only once been described. On the other hand, the association of anti-GT1a antibodies with phrenic nerve palsy has never been reported before. CONCLUSIONS: We report an association between phrenic nerve palsy and the presence of antiganglioside antibodies, but it remains unclear if there is a causal relationship. Further studies are needed to explore this matter.

A rare case of acute motor axonal neuropathy and myelitis related to SARS-CoV-2 infection.

We describe a rare case of post-infective Acute Motor Axonal Neuropathy (AMAN) variant of Guillain-Barrè Syndrome (GBS) associated with myelitis and anti-GD1b positivity after SARS-CoV-2 infection. The patient referred to the hospital reporting a history of ten days lasting moderate fever, myalgia and anosmia, with the onset of progressive quadriparesis and ascending paraesthesias in the four limbs since five days from defervescence. A chest computed tomography demonstrated interstitial pneumonia with "ground glass opacities", suggesting Coronavirus disease (COVID-19). The patient exhibited three negative reverse-transcription polymerase chain reaction (RT-PCR) nasopharyngeal swabs, while SARS-CoV-2 IgG was found in plasma. The electrophysiological examination demonstrated an AMAN and the spinal cord Magnetic Resonance Imaging (MRI) showed a T2-weighted hyperintense lesion in the posterior part of the spinal cord at the C7-D1 levels. Furthermore, anti-GD1b IgM was detected. GBS and myelitis could exceptionally develop simultaneously. Our findings reasonably support a causality link between COVID-19 and the neurological symptoms, suggesting a post-infective autoimmune reaction.

What did he eat?

A 13-year-old boy reported acute horizontal binocular diplopia and headache. Ten days before these symptoms he suffered from a gastrointestinal infection. Ophthalmological examination revealed bilateral ophthalmoparesis and diffuse hyporeflexia. Magnetic resonance imaging of the brain was normal. Lumbar puncture revealed albumin-cytological dissociation. There were no anti-GQ1b antibodies, but serum anti-GM1 antibodies were detected. He received intravenous immunoglobulins and had fully recovered two weeks later. Miller Fisher syndrome and its atypical variants are uncommon in childhood; nevertheless, they should be considered in the differential diagnosis of bilateral acute ophthalmoparesis.

Finger drop sign as a new variant of acute motor axonal neuropathy.

We propose the finger drop sign as a new clinical variant of acute motor axonal neuropathy (AMAN) defined by immunological and radiological evidence. We identified eight consecutive patients who had AMAN. All of them developed prominent involvement of the finger extensors. We performed magnetic resonance imaging (MRI) of the extremity muscles and serological assays for antiganglioside antibodies and Campylobacter jejuni. Patients with AMAN showed characteristic and a markedly sustained weakness of the finger extensors with a distinctive pattern of the finger drop sign. Limb MRI revealed unevenly distributed abnormal signals in the muscles mainly innervated by the posterior interosseous nerve. All tested patients showed positivity for immunoglobulin G antibody against ganglioside complex of GM1 and phosphatidic acid. A pathophysiological understanding of this unique syndrome can provide further insight into antiganglioside-antibody-mediated axonal injury in Guillain-Barré syndrome.

Pediatric Miller Fisher Syndrome; Characteristic Presentation and Comparison with Adult Miller Fisher Syndrome.

BACKGROUND: We aimed to investigate the characteristic presentation of Miller Fisher syndrome (MFS) in pediatrics and compare it with that in adults. METHODS: We performed a retrospective review of medical records, laboratory findings, and disease course of pediatric MFS. The data were compared with those of adult MFS, and literature review was done. Unpaired and paired comparisons between groups were made using Wilcoxon rank-sum and signed-rank tests, respectively. RESULTS: Median age for pediatric MFS was 9.8 ± 6.5 years. There were 5 (45.5%) male and 6 (54.5%) female patients. All patients had preceding infection. Two patients (22.2%) had tested positive for anti-GQ1b antibody. Ten patients (90.1%) were treated with intravenous immunoglobulin, and 2 (18.2%) also received intravenous methylprednisolone. Within one month, 8 (72.7%) patients showed recovery, and all 11 (100%) recovered fully within 3 months. Further, the pediatric group had higher frequency of unilateral involvement of ophthalmoplegia, ataxia, and autonomic symptoms but lower antiganglioside antibody positivity and manifestations of areflexia than the adult group. CONCLUSIONS: Neuro-ophthalmic manifestations and disease course of pediatric MFS were similar to those of adult MFS as stated in the literature. However, the presence of autonomic symptoms was higher and anti-GQ1b antibody positivity was lower in pediatric MFS than in adult MFS.

Antiganglioside antibodies and paraneoplastic neuromuscular junction disorder?

Based on the instructions in "Guide for authors", our manuscript is a case reports and was submitted under "Letters to the Editor", which should not include an abstract.

Hepatitis E virus-associated Guillain-Barre syndrome: Revision of the literature.

INTRODUCTION: The association between preceding infection of hepatitis E virus (HEV) and Guillain-Barre syndrome (GBS) has been found for more than a decade, while hepatitis E virus-associated Guillain-Barre syndrome (HEV-associated GBS) still remains poorly understood. Initially discovered in 2000, the association between GBS and HEV has been focused by neurologists increasingly. Five percent of patients with GBS had preceding acute HEV infection in the Netherlands and higher rate was found in Bangladesh (11%) where HEV is endemic. METHOD: An extensive review of relevant literature was undertaken. RESULTS: Hepatitis E virus infection may induce GBS via direct viral damage according to recent research findings. On the other hand, the presence of antiganglioside GM1 or GM2 antibodies in serum of some HEV-associated GBS patients indicates that HEV infection may trigger GBS by activating autoimmune response to destroy myelin or axon mistakenly. Management of HEV-associated GBS has no obvious difference from GBS. It mainly consists of supportive therapy and immunotherapy. Intravenous immunoglobulin (IVIG) or plasma exchange (PLEX) was used in most reported cases, which is the main strategy for clinical treatment of HEV-associated GBS. Whether antiviral therapy could be additional strategy other than the routine therapy to shorten the length of disease course is one of the most urgent problems and requires further study. CONCLUSIONS: An overview of possible pathogenesis will gain a first insight into why HEV, traditionally recognized as only hepatotropic, can induce many neurological disorders represented by GBS. Moreover, understanding of the underlying mechanisms may contribute to development of a novel therapeutic strategy. This review also summarizes management and clinical characteristics of HEV-associated GBS, aiming to achieve early recognition and good recovery.

Antiganglioside antibodies in neurological diseases.

Gangliosides are sialylated glycosphingolipids, highly abundant in our nervous system. Antibodies targeting gangliosides are usually developed as a consequence of molecular mimicry following infections. Antiganglioside antibodies are implicated in many neurological disorders such as acute and chronic polyradiculoneuropathies which includes different variants of Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy. Presence of such antibodies in paraneoplastic peripheral neuropathy, neurodegenerative disorders, multiple sclerosis, myasthenia gravis and amyotrophic lateral sclerosis have also been reported. Recent evidence supports a role of antiganglioside antibodies in the pathogenesis of acute vestibular syndrome. Binding of antibodies to gangliosides on axonal membranes, nodes of Ranvier, myelin sheath components, Schwann cells, neuromuscular junctions or other neural cell surfaces may elicit inflammatory damage through complement-dependent and independent mechanisms, resulting in nerve conduction blocks and subsequent axonal degeneration. Gangliosides are essential for proper cell signaling, transduction and influences neuroplasticity, all of which are affected by autoimmune mediated damage. Better insight into the pathophysiological role of antiganglioside antibodies in different neurological diseases may improve their utility as diagnostic and prognostic biomarkers.

Prevalence of antibodies to ganglioside and Hep 2 in Gaucher, Niemann - Pick type C and Sanfilippo diseases.

Lysosomal Storage Diseases (LSDs) are rare genetic diseases, the majority of which are caused by specific lysosomal enzyme deficiencies and all are characterized by malfunctioning lysosomes. Lysosomes are key regulators of many different cellular processes and are vital for the function of the immune system. Several studies have shown the coexistence of LSDs and immune abnormalities. In this study, we investigated the presence of autoantibodies in the plasma of patients with Gaucher disease (GD; n = 6), Sanfilippo Syndrome B (SFB; n = 8) and Niemann - Pick type C disease (NPC; n = 5) before and following Miglustat treatment (n = 3). All were examined for antibodies to antigens of Hep-2 cells and antiganglioside antibodies (AGSA). No autoantibodies were detected in GD patients. 3/8 SFB patients showed only AGSA (2/3 IgM / IgG; 1/3 IgG), 3/8 only anti-Sm E/F and 2/8 showed both IgM / IgG or IgG AGSA and anti-Sm E/F. 3/5 NPC patients showed AGSA (2/3 IgM and IgG, 1/3 IgM) and one anti-Sm E/F and IgM AGSA. Following treatment one patient with no AGSA developed IgM AGSA and two with both IgG and IgM showed only IgG AGSA. In our study, investigating similar numbers of patients, autoantibodies were observed in NPC and SFB patients but not in GD patients. Our findings suggest that, independently of the development of an autoimmune disease in patients with LSDs, there seems to be an autoimmune activation that differs in different disorders. Further studies including more patients, also at different stages of disease and treatment, are needed in order to get further insight into the immune irregularities associated with different LSDs and their significance.

A unicenter, prospective study of Guillain-Barré syndrome in Spain.

OBJECTIVE: We report a prospective study analysing clinical characteristics, subtyping and prognosis in Guillain-Barré syndrome (GBS). METHOD: The study was based on consecutive GBS patients admitted between 2009 and 2017. Disability was serially assessed using the GBS disability scale. RESULTS: Fifty-six GBS patients were identified with an average age of 55 years (range, 5-86 years) and a male/female ratio of 2.1. The interval to nadir was <7 days in 59% of cases, and 7 to 28 days in the remainder; at nadir, 35.5% of patients were able to walk unaided, and 64.5% did not. Mechanical ventilation was needed in 20% of cases. There were two fatal cases. Clinical variants included paraparetic GBS seven cases, Miller Fisher syndrome one case, and acute sensory ataxic neuropathy (ASAN) one case. Serial electrophysiology showed a demyelinating pattern in 62.5% of cases, axonal in 28.5%, inexcitable in 1.8%, equivocal in 1.8%, and normal in 5.4%. Very early (1 to 4 days after onset) electrophysiology was done in 18 patients; equivocal or normal features in six of them evolved into an axonal pattern in four. Reversible conduction failure of sensitive nerves occurred in ASAN. Antiganglioside antibodies were only detected in axonal GBS. At 24-month follow-up, functional outcome did not differ between demyelinating and axonal GBS. Clinico-pathological correlation in an early fatal case is reported. CONCLUSIONS: This GBS study demonstrates comparable clinical features to previous investigations from well-defined populations. There was a relatively high prevalence of axonal GBS. We provide new pathophysiological insights on nerve conduction alterations.

Miller Fisher Syndrome Mimicking Tolosa-Hunt Syndrome.

We herein report a patient with Miller Fisher syndrome mimicking Tolosa-Hunt syndrome. A 47-year-old man presented with right orbital pain and diplopia. On a neurological examination, he had right oculomotor nerve palsy and diminished deep tendon reflexes. Brain magnetic resonance imaging failed to show any parenchymal lesions; however, the bilateral oculomotor nerves were gadolinium-enhanced. The presence of a triad of orbital pain, ipsilateral oculomotor nerve palsy, and a rapid response to steroid therapy met the diagnostic criteria for Tolosa-Hunt syndrome. After discharge, antibodies against GQ1b and GT1a were reported to be positive only with phosphatidic acid. The present case was ultimately diagnosed as an incomplete phenotype of Miller Fisher syndrome.

Autoimmune peripheral neuropathies.

Peripheral nervous system axons and myelin have unique potential protein, proteolipid, and ganglioside antigenic determinants. Despite the existence of a blood-nerve barrier, both humoral and cellular immunity can be directed against peripheral axons and myelin. Molecular mimicry may be triggered at the systemic level, as was best demonstrated in the case of bacterial oligosaccharides. The classification of immune neuropathy has been expanded to take into account specific syndromes that share unique clinical, electrophysiological, prognostic and serological features. Guillain-Barré syndrome encompasses a classical syndrome of acute demyelinating polyradiculoneuropathy and many variants: axonal motor and sensory, axonal motor, Miller-Fisher, autonomic, and sensory. Similarly, chronic immune neuropathy is composed of classic chronic inflammatory demyelinating polyradiculoneuropathy and variants characterized as multifocal (motor or sensorimotor), sensory, distal symmetric, and syndromes associated with monoclonal gammopathy. Among putative biomarkers, myelin associated glycoprotein and several anti-ganglioside autoantibodies have shown statistically significant associations with specific neuropathic syndromes. Currently, the strongest biomarker associations are those linking Miller-Fisher syndrome with anti-GQ1b, multifocal motor neuropathy with anti-GM1, and distal acquired symmetric neuropathy with anti-MAG antibodies. Many other autoantibody associations have been proposed, but presently lack sufficient specificity and sensitivity to qualify as biomarkers. This field of research has contributed to the antigenic characterization of motor and sensory functional systems, as well as helping to define immune neuropathic syndromes with widely different clinical presentation, prognosis and response to therapy. Serologic biomarkers are likely to become even more relevant with the advent of new targeted forms of immunotherapy, such as monoclonal antibodies.

Antibodies against gangliosides in patients with dementia.

BACKGROUND: Increasing evidence suggests that gangliosides act as important mediators in both de- and remyelination. The scope of the present research was to investigate the presence of immunoglobulin (Ig) M antibodies against GM1, GD1b, and GQ1b gangliosides in the sera of patients with dementia and the possible connection with clinical parameters of the disease. METHOD: This research topic demonstrates the investigation of 103 patients with dementia and 60 healthy individuals using enzyme-linked immunosorbent assay for the presence of 3 antiganglioside antibodies in their sera. RESULTS: The authors report a positive connection between IgM anti-GM1 and the age (P = .005) and the severity of dementia (P = .005). Most of the patients who revealed increased IgM anti-GD1b levels had Alzheimer's disease (AD; P = .002). CONCLUSION: This study indicates that elevated IgM anti-GM1 may be connected with the neurodegeneration in older patients with severe dementia and that AD may also be associated with increased IgM anti-GD1b levels.

[Acute hepatitis E infection associated with Guillain-Barré syndrome in an immunocompetent patient]. / Hépatite E aiguë associée à un syndrome de Guillain-Barré chez un patient immunocompétent.

INTRODUCTION: Hepatitis E virus (HEV) infection is now recognized to be an emerging autochthonous disease in several countries. There have been several reports of neurological manifestations associated with HEV infections. Immunocompromised patients seem to be particularly vulnerable. CASE REPORT: We report a 73-year-old man who presented with an acute polyradiculopathy and an acute hepatitis. HEV RNA was positive in serum and cerebrospinal fluid. Serum antiganglioside antibodies were also detected. Liver function tests returned to normal rapidly and HEV RNA was undetectable 4 weeks after initial testing. The neurological features improved gradually with the use of intravenous immunoglobulins. CONCLUSION: We report a case of Guillain-Barré syndrome related to acute hepatitis E in an immunocompetent patient. The outcome was favorable after intravenous immunoglobulins administration. HEV screening should be systematic in patients who present with an acute polyradiculopathy and abnormal liver function tests.