Guillain-Barré syndrome with overlap between the finger drop variant and acute bulbar palsy: a case report.

BACKGROUND: Guillain-Barré syndrome (GBS) is a clinically heterogenous disease and encompasses several distinct clinical variants. Overlap between these variants can pose a diagnostic challenge. We report a case of finger drop variant and acute bulbar palsy overlap as an unusual manifestation of GBS. CASE PRESENTATION: An 81-year-old man presented with dysarthria, dysphagia, and upper limb weakness. Neurological examination revealed impaired tongue protrusion, the finger drop sign, and diminished brachioradial and triceps muscle reflexes. Nerve conduction studies showed reduced amplitudes and decreased velocities in the median and ulnar nerves. Cerebrospinal fluid analysis revealed albuminocytological dissociation and an anti-ganglioside antibody study revealed positivity for GM1, asialo-GM1, GT1a, GD1b, and GQ1b. As GBS was suspected, we initiated intravenous immunoglobulin treatment, resulting in gradual improvement within the next 3 weeks. CONCLUSION: To the best of our knowledge, this is the first reported case of an overlap between the finger drop variant and acute bulbar palsy in GBS, highlighting the importance of considering GBS when patients present with a combination of atypical symptoms. Anti-ganglioside antibodies can be helpful and add diagnostic value in these complex cases.

The spectrum of anti-GQ1B antibody syndrome: beyond Miller Fisher syndrome and Bickerstaff brainstem encephalitis.

INTRODUCTION: Since the initial identification of Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE),significant milestones have been achieved in understanding these diseases.Discoveries of common serum antibodies (IgG anti-GQ1b), antecedent infections, neurophysiological data, andneuroimaging suggested a shared autoimmune pathogenetic mechanism rather than distinct pathogenesis, leadingto the hypothesis that both diseases are part of a unified syndrome, termed "Fisher-Bickerstaff syndrome". The subsequent identification of atypical anti-GQ1b-positive forms expanded the classification to a broader condition known as "Anti-GQ1b-Antibody syndrome". METHODS: An exhaustive literature review was conducted, analyzing a substantial body of research spanning from the initialdescriptions of the syndrome's components to recent developments in diagnostic classification and researchperspectives. RESULTS: Anti-GQ1b syndrome encompasses a continuous spectrum of conditions defined by a common serological profilewith varying degrees of peripheral (PNS) and central nervous system (CNS) involvement. MFS and BBE represent theopposite ends of this spectrum, with MFS primarily affecting the PNS and BBE predominantly involving the CNS.Recently identified atypical forms, such as acute ophthalmoparesis, acute ataxic neuropathy withoutophthalmoparesis, Guillain-Barré syndrome (GBS) with ophthalmoparesis, MFS-GBS and BBE-GBS overlap syndromes,have broadened this spectrum. CONCLUSION: This work aims to provide an extensive, detailed, and updated overview of all aspects of the anti-GQ1b syndromewith the intention of serving as a stepping stone for further shaping thereof. Special attention was given to therecently identified atypical forms, underscoring their significance in redefining the boundaries of the syndrome.

Implications of anti-ganglioside antibodies in isolated dysphagia following COVID-19 infection: Case series.

BACKGROUND: There have been multiple reports about the occurrence of dysphagia after the contraction of coronavirus disease 2019 (COVID-19). However, a detailed pathology and epidemiologic relation between COVID-19 infection and dysphagia have yet to be established. Here, we report three cases of unexplained dysphagia after COVID-19 diagnosis, with atypical clinical presentations. CASE REPORT: All patients showed severe isolated lower cranial nerve involvement with dysphagia and aspiration, which required full tube feeding but showed no evidence of limb weakness or sensory symptoms. All tested positive for anti-ganglioside antibody tests, which all commonly (GD1b, GM1, and GQ1b) are known to have terminal NeuNAc(α2-3)Gal epitope. DISCUSSION: We report a series of cases featuring severe, isolated dysphagia post-COVID-19 infection, concomitant with positive anti-ganglioside antibodies. One potential etiology is a variant of Guillain-Barré syndrome. Because only isolated dysphagia with sparing of the facial and extraocular muscles was evident in these cases, we explore the association between anti-ganglioside antibodies specific to NeuNAc(α2-3)Gal, which has been frequently associated with the development of bulbar dysfunction. Given that NeuNAc(α2-3)Gal exhibits an affinity for the spike glycoprotein of SARS-CoV-2, a cross-reaction against NeuNAc(α2-3)Gal may possibly contribute to isolated dysphagia following COVID-19 infection.

Takotsubo cardiomyopathy in Guillain-Barré syndrome.

BACKGROUND AND PURPOSE: Takotsubo cardiomyopathy (TCM) is a serious autonomic complication of Guillain-Barré syndrome (GBS). However, the association between TCM and GBS has not been investigated in detail. We investigated the characteristics of GBS patients with TCM (GBS-TCM). METHODS: Clinical features and anti-ganglioside antibody between the GBS-TCM patients and 62 classical GBS patients without TCM as control patients were compared. RESULTS: Eight GBS-TCM patients were identified, in whom TCM was diagnosed at a mean of 6.5 [range 3-42] days after the onset of GBS. The age at onset of GBS was elder in the GBS-TCM patients than in the control GBS patients (76.5 [56-87] vs. 52 [20-88] years, p < 0.01). Notably, cranial nerve deficits, particularly in the lower cranial nerves, were observed in all GBS-TCM patients (100% vs. 41.9%, p < 0.01). Additionally, the GBS-TCM patients showed a higher GBS disability score at nadir (5 [4-5] vs. 4 [1-5], p < 0.01), and lower Medical Research Council sum scores at admission and nadir (37 [30-44] vs. 48 [12-60] at admission, p < 0.05, and 20 [12-44] vs. 40 [0-60] at nadir, p < 0.05, respectively). Mechanical ventilation was more frequently required in the GBS-TCM patients (62.5% vs. 11.3%, p < 0.01). Three GBS-TCM patients were positive for anti-ganglioside antibodies. CONCLUSIONS: TCM occurred at a relatively early phase of GBS. The characteristics of GBS-TCM were the elder, lower cranial nerve involvements, severe limb weakness, and respiratory failure.

Distal Chronic Inflammatory Demyelinating Polyneuropathy Following COVID-19 Vaccination in a Patient with Solitary Plasmacytoma: A Case Report and Literature Review.

We herein report a rare case of distal chronic inflammatory demyelinating polyneuropathy (CIDP) following coronavirus disease 2019 (COVID-19) vaccination. A 39-year-old woman with a solitary plasmacytoma developed general weakness 7 days after receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine, which had progressed for 3 months. A neurological examination revealed limb weakness with areflexia. Serological tests identified the presence of IgG antibodies against anti-GM1 and anti-GM2 gangliosides. Comprehensive evaluations met the criteria of distal CIDP. Intravenous immunoglobulin, intravenous methylprednisolone, oral prednisolone, and plasma exchange were administered, and she gradually improved. Physicians should be aware of CIDP as a rare complication of COVID-19 vaccination.

Anti-ganglioside antibody positive neuromyelitis optica spectrum disorders with peripheral neuropathy: a case report.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is a group of autoimmune-mediated disorders of the central nervous system primarily involving the optic nerve and spinal cord. There are limited reports of NMOSD associated with peripheral nerve damage. CASE PRESENTATION: We report a 57-year-old female patient who met the diagnostic criteria for aquaporin 4 (AQP4)-IgG positive NMOSD with undifferentiated connective tissue disease and multiple peripheral neuropathy. In addition, the patient was positive for multiple anti-ganglioside antibodies (anti-GD1a IgG antibodies and anti-GD3 IgM antibodies) and anti-sulfatide IgG antibodies in serum and cerebrospinal fluid. After treatment with methylprednisolone, gamma globulin, plasma exchange, and rituximab, the patient's status improved and was subsequently discharged from our hospital. CONCLUSIONS: The neurologist should be aware of the unusual association between NMOSD and immune-mediated peripheral neuropathy undifferentiated connective tissue disease and nerve damage mediated by multiple antibodies may have combined to cause peripheral nerve damage in this patient.

A Case with Anti-ganglioside Antibodies Showing Multiple Cranial Nerve Palsies Detected on Gadolinium-enhanced Magnetic Resonance Imaging.

The anti-GQ1b IgG antibody is often accompanied by other anti-ganglioside antibodies, which induces various neurological symptoms. We herein report a patient with anti-ganglioside antibodies, including anti-GQ1b IgG and anti-GT1a IgG antibodies, showing bilateral ophthalmoplegia, facial nerve palsies, dysarthria, dysphagia, dysesthesia in both hands, and enhancement of the bilateral oculomotor, abducens, and facial nerves on gadolinium (Gd)-enhanced T1-weighted brain magnetic resonance imaging (MRI). He was first treated with intravenous immunoglobulin, which improved ophthalmoplegia, bulbar palsies, and dysesthesia of hands, but the facial nerve palsies worsened, and Gd enhancement of the brain nerves persisted. High-dose methylprednisolone therapy subsequently improved the facial nerve palsies and Gd enhancement of the cranial nerves. This is the first case with anti-ganglioside antibodies presenting with multiple cranial nerve palsies that was followed to track the changes in the Gd enhancement of cranial nerves on MRI.

Recurrent Guillain-Barré Syndrome Associated with the Second Episode of Campylobacter jejuni Infection.

Guillain-Barré syndrome (GBS) cases are generally monophasic, and recurrence is rare. However, the pathogenesis and pathophysiology of recurrent GBS remain to be fully elucidated. There are few detailed reports of patients who have been infected twice with Campylobacter jejuni and have developed GBS twice. We herein report a case of recurrent GBS in a 21-year-old man with a history of GBS caused by C. jejuni infection at 19 years old. Although our patient was reinfected with C. jejuni, several different anti-ganglioside antibodies were identified, and the clinical manifestations were more severe than those in the first GBS episode. We compared the anti-ganglioside antibodies and nerve conduction studies findings between the two GBS episodes. This case suggested that different antibodies are involved and produce different symptoms even when C. jejuni infection is the trigger in recurrent episodes.

Recurrent Guillain-Barré syndrome presenting as pharyngeal-cervical-brachial variant with three species of ganglioside antibodies:case report.

BACKGROUND: Guillain-Barré syndrome (GBS) is generally considered to be monophasic, and recurrent GBS (RGBS) is very rare. Pharyngeal-cervical-brachial (PCB) is a less common variant of GBS. There have been no cases reported describing RGBS showing different phenotype presenting as PCB variant with three species of ganglioside antibodies. CASE PRESENTATION:  We report a case of a 77-year-old female patient with GT1a, GD1a and sulfatide-seropositive PCB-GBS after prior episode of AMAN-GBS 13 years ago. Our patient showed oropharyngeal and cervicobrachial weakness associated with areflexia in the upper limbs and partially improved after 5 days of IVIG and physiotherapy. CONCLUSION: This study reports a rare case characterized as recurrent GBS after a long period, showing different phenotypes in different episodes with three different species of ganglioside antibodies. Further studies are required to obtain better understanding of RGBS and PCB variant.

Sporadic Amyotrophic Lateral Sclerosis Due to a FUS P525L Mutation with Asymmetric Muscle Weakness and Anti-ganglioside Antibodies.

Amyotrophic lateral sclerosis (ALS) due to a fused in sarcoma (FUS) P525L mutation is characterized by a rapidly progressive course. Multifocal motor neuropathy (MMN) may resemble ALS in early stage and is associated with anti-ganglioside antibodies. A 38-year-old woman was admitted to our hospital because of progressive muscle weakness in the right limbs. She had mild mental retardation and minor deformities. Initially, we suspected MMN given the asymmetric muscle weakness and detection of anti-ganglioside antibodies. However, physical and electrophysiological tests did not support MMN, instead suggesting ALS. We confirmed a heterozygous P525L mutation and finally diagnosed this case as ALS due to an FUS mutation.

[An elderly case of Guillain-Barré syndrome with anti-GT1b antibodies].

An 85-year-old Japanese female was admitted with sudden onset of quadriparesis with areflexia. Preceding infection was not present. IgG anti-GT1b antibodies were prominently positive in serum. Nerve conduction study results suggested Guillain-Barré syndrome (GBS) classified as acute motor sensory axonal neuropathy (AMSAN). While intravenous immunoglobulin (IVIg) was started, bulbar palsy and respiratory failure progressed and the condition deteriorated. Although mechanical ventilation was required, second IVIg course led to gradual improvement of quadriparesis and bulbar palsy. In the present case with elderly-onset disease, the levels of anti-GT1b antibodies were elevated, which is relatively rare in GBS. It was suggested that anti-GT1b antibodies may be related to the development of axonal GBS with bulbar palsy.

[Immune-mediated neuropathy with anti-ganglioside antibodies in diffuse large B-cell lymphoma].

A 70-year-old man having a mass lesion on his right lower abdomen for 2 months was admitted to our hospital for diagnosis. Upon admission, the patient experienced bilateral upper and lower limb weakness, which aggravated. He underwent nerve conduction study and was diagnosed with axonal neuropathy. Diagnosis of diffuse large B-cell lymphoma (DLBCL) was accomplished via biopsy of the mass lesion, with positive laboratory tests for anti-ganglioside antibodies. Based on these results, immune-mediated DLBCL-induced polyneuropathy was suspected, and chemotherapy (R-CHOP) was immediately started. Limb weakness improved and completely resolved. After six courses of R-CHOP, no evidence of DLBCL was observed on PET/CT (i.e., complete metabolic remission). The patient lived without DLBCL relapse or neurological symptoms after remission. Only few reports regarding immune-mediated polyneuropathy induced by malignant lymphoma are available in the literature, which, together with this case, suggest that prompt control of malignant lymphoma is crucial for favorable prognosis of neuropathy.

Asymmetrical and Isolated Hypoglossal Nerve Palsy Accompanied by a New Subset of Anti-ganglioside Antibodies in a Patient with Diffuse Large B Cell Lymphoma.

Malignant lymphoma sometimes involves peripheral nerves due to paraneoplastic syndrome associated with anti-ganglioside antibodies. We report a very rare case of malignant lymphoma accompanied by an asymmetrical and isolated hypoglossal nerve palsy associated with a new subset of anti-ganglioside antibodies. Magnetic resonance imaging and 18F-2-deoxy-2-fluoro-D-glucose position emission tomography showed no abnormalities of the hypoglossal nerve nucleus; however, the patient' s serum was positive for anti-sulfated glucuronyl paragloboside IgM antibodies as well as anti-GM1 IgM and anti-GQ1b IgM antibodies. The present case might suggest a paraneoplastic asymmetrical and isolated hypoglossal nerve palsy associated with a new subset of anti-ganglioside antibodies.

Characteristics of single ocular motor nerve palsy associated with anti-GQ1b antibody.

To define the prevalence and characteristics of single ocular motor nerve palsy (OMNP) associated with positive serum anti-GQ1b antibody. We performed a prospective multicenter study that recruited 82 patients with single OMNP without identifiable causes from the history and neuroimaging in six neurology clinics of university hospitals. We measured serum anti-GQ1b antibody in all participants. Twelve patients with multiple OMNP and 30 with identifiable causes served as the controls. Overall, the prevalence of anti-GQ1b antibody syndrome was 10% (8/82) in patients with single OMNP and 6% (5/78) in those with single OMNP in isolation. None of the 14 patients with OMNP with identifiable causes showed positive serum anti-GQ1b antibody. The prevalence of anti-GQ1b antibody syndrome was much higher in patients with multiple OMNP than in those with single OMNP (50% vs. 10%, p < 0.01). Patients with single OMNP and positive anti-GQ1b antibody are younger (42 ± 16 vs. 58 ± 15, p < 0.05) and had a significantly higher frequency of preceding infection (75 vs. 19%, p < 0.05) and other neurological signs (38 vs. 1%, p < 0.05) than those with negative antibody. Eight patients with single OMNP and positive serum anti-GQ1b antibody involved the abducens (n = 6), trochlear (n = 1), or oculomotor nerve (n = 1). Single OMNP accompanying other neurological signs and multiple OMNP are more likely to be associated with anti-GQ1b antibody. Anti-GQ1b antibody syndrome should be considered even in patients with single OMNP, especially when antecedent infection was associated in younger patients.

Pilot trial of the hu14.18-IL2 immunocytokine in patients with completely resectable recurrent stage III or stage IV melanoma.

Phase I testing of the hu14.18-IL2 immunocytokine (IC) in melanoma patients showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5 mg/m2/day. Preclinical data in IC-treated tumor-bearing mice with low tumor burden documented striking antitumor effects. Patients with completely resectable recurrent stage III or stage IV melanoma were scheduled to receive 3 courses of IC at 6 mg/m2/day i.v. on days 1, 2 and 3 of each 28-day course. Patients were randomized to complete surgical resection either following neoadjuvant (Group A) or prior to adjuvant (Group B) IC course 1. Primary objectives were to: (1) evaluate histological evidence of anti-tumor activity and (2) evaluate recurrence-free survival (RFS) and OS. Twenty melanoma patients were randomized to Group A (11 patients) or B (9 patients). Two Group B patients did not receive IC due to persistent disease following surgery. Six of 18 IC-treated patients remained free of recurrence, with a median RFS of 5.7 months (95% confidence interval (CI) 1.8-not reached). The 24-month RFS rate was 38.9% (95% CI 17.5-60.0%). The median follow-up of surviving patients was 50.0 months (range: 31.8-70.4). The 24-month OS rate was 65.0% (95% CI 40.3-81.5%). Toxicities were similar to those previously reported. Exploratory tumor-infiltrating lymphocyte (TIL) analyses suggest prognostic value of TILs from Group A patients. Prolonged tumor-free survival was seen in some melanoma patients at high risk for recurrence who were treated with IC.

Polyclonal IgM and IgA block in vitro complement deposition mediated by anti-ganglioside antibodies in autoimmune neuropathies.

Intravenous immunoglobulin (IVIG), consisting of IgG, is the first-line treatment for Guillain-Barré syndrome and multifocal motor neuropathy. IgG, but neither IgM nor IgA, has been demonstrated in vitro to inhibit complement deposition mediated by anti-ganglioside autoantibodies in sera from patients with both conditions. The objective of this study is to investigate the in vitro effectiveness of IgM and IgA in inhibiting complement deposition to ganglioside/anti-ganglioside antibody complexes. Serum samples were obtained from patients with multifocal motor neuropathy associated with anti-GM1 IgM antibodies, Guillain-Barré syndrome associated with anti-GM1 IgG antibodies and Miller Fisher syndrome associated with anti-GQ1b IgG antibodies. Inhibition of complement deposition using different immunoglobulin preparations was measured by enzyme-linked immunosorbent assay. IgM/A-enriched IVIG and immunoglobulin isotypes (polyclonal IgM and IgA) showed higher potential in inhibiting complement deposition than standard IVIG. Although the safety concerns about the use of IgM and IgA for an immunotherapy still remain, IgM and IgA may serve as an alternative immunotherapy in those anti-ganglioside antibody-mediated neuropathies.

Anti-ganglioside antibodies are removed from circulation in mice by neuronal endocytosis.

SEE VAN DOORN AND JACOBS DOI101093/BRAIN/AWW078 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE : In axonal forms of Guillain-Barré syndrome, anti-ganglioside antibodies bind gangliosides on nerve surfaces, thereby causing injury through complement activation and immune cell recruitment. Why some nerve regions are more vulnerable than others is unknown. One reason may be that neuronal membranes with high endocytic activity, including nerve terminals involved in neurotransmitter recycling, are able to endocytose anti-ganglioside antibodies from the cell surface so rapidly that antibody-mediated injury is attenuated. Herein we investigated whether endocytic clearance of anti-ganglioside antibodies by nerve terminals might also be of sufficient magnitude to deplete circulating antibody levels. Remarkably, systemically delivered anti-ganglioside antibody in mice was so avidly cleared from the circulation by endocytosis at ganglioside-expressing plasma membranes that it was rapidly rendered undetectable in serum. A major component of the clearance occurred at motor nerve terminals of neuromuscular junctions, from where anti-ganglioside antibody was retrogradely transported to the motor neuron cell body in the spinal cord, recycled to the plasma membrane, and secreted into the surrounding spinal cord. Uptake at the neuromuscular junction represents a major unexpected pathway by which pathogenic anti-ganglioside antibodies, and potentially other ganglioside binding proteins, are cleared from the systemic circulation and also covertly delivered to the central nervous system.

Serial peripheral nerve ultrasound in Guillain-Barré syndrome.

OBJECTIVE: To assess the longitudinal changes of nerve ultrasound in Guillain-Barré syndrome (GBS) patients. METHODS: We prospectively recruited 17 GBS patients and 17 age and gender-matched controls. Serial studies of their nerve conduction parameters and nerve ultrasound, documenting the cross-sectional areas (CSA), were performed at admission and repeated at several time points throughout disease course. RESULTS: Serial nerve ultrasound revealed significantly enlarged CSA in median, ulnar and sural nerves within the first 3 weeks of disease onset. Longitudinal evaluation revealed an improvement in the nerve CSA with time, reaching significance in the ulnar and sural nerves after 12 weeks. There was no significant difference between the demyelinating and axonal subtypes. There was also no significant correlation found between nerve CSA and neurophysiological parameters or changes in nerve CSA and muscle strength. CONCLUSION: In GBS, serial studies of peripheral nerve ultrasound CSA are helpful to detect a gradual improvement in the nerve size. SIGNIFICANCE: Serial nerve ultrasound studies could serve as a useful tool in demonstrating nerve recovery in GBS.