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.

Utility of Brainstem Auditory Evoked Response as a Diagnostic Tool and Rituximab as a Treatment for Severe Bickerstaff Brainstem Encephalitis: A Case Report.

Bickerstaff brainstem encephalitis (BBE) is a rare disorder that is characterized by ophthalmoplegia, ataxia, and disturbance in consciousness. Definite diagnosis is made primarily through clinical presentation and serology testing with anti-GQ1b antibody. However, in a country where access to serologic testing is scarce, electrophysiologic tests such as brainstem auditory evoked response (BAER) may contribute to the diagnosis. Due to its rarity and generally good prognosis, there is no established consensus for the treatment of BBE. Immunomodulatory treatments such as intravenous immunoglobulin (IVIG), plasma exchange, steroids, or a combination of these therapies are often used with good response. However, there are severe cases that respond poorly to these conventional treatments. We report the case of a 26-year-old Filipino man who came in for sudden onset of diplopia, with a one-week history of upper respiratory tract infection. Subsequently, he developed paresthesias, quadriparesis, and an altered level of consciousness. On initial examination, he only had partial third nerve palsy, but eventually became quadriparetic and obtunded during admission. Initial electromyography and nerve conduction velocity (EMG-NCV) study showed a reduced recruitment pattern of the right rectus femoris, absent H reflexes of bilateral posterior tibial nerves, and no abnormal increase in temporal dispersion. Cranial MRI with contrast was unremarkable. Video electroencephalogram (video-EEG) showed intermittent generalized 5-6 Hz and 6-7 Hz theta slowing of the background activity in the stimulated state. BAER was done revealing bilateral partial dysfunction of the auditory pathways to support brainstem involvement of the disease. He received IVIG and methylprednisolone pulse therapy with no significant clinical improvement. Hence, he was given a rituximab infusion. One week post-rituximab, he had sustained wakefulness and was able to move his extremities.

Atypical anti-GQ1b antibody syndrome presenting with vomiting as the initial symptom: a case report and literature review.

BACKGROUND: Anti-GQ1b antibody syndrome is a rare autoimmune neuropathy, and atypical cases are even more rare, only a few cases have been reported. Anti-GQ1b antibody syndrome is difficult in early diagnosis and prone to misdiagnosis. Generally,in children with anti-GQ1b antibody syndrome,extraocular muscle paralysis is the initial symptom. However, anti-GQ1b antibody syndrome with vomiting as the initial symptom followed by abnormal gait has not been reported. CASE PRESENTATION: We reported a case of anti-GQ1b antibody syndrome with vomiting as the initial symptom, followed by abnormal gait. One day after vomiting, the child developed abnormal gait, which primarily manifested as a slight tilt of the upper body during walking as well as an opening and swaying of the legs at fast walking paces,then progressively aggravated, and finally he could not stand on his own.In the auxiliary examination, cerebrospinal fluid routine,biochemical and metagenomic Next-Generation Sequencing (DNA and RNA), brain + spinal cord contrast magnetic resonance imaging (MRI),magnetic Resonance angiography (MRA) and diffusion-weighted image (DWI), hip and knee joint ultrasound showed normal results. Anti-GQ1b antibody syndrome was not confirmed until the positive anti-GQ1b IgG antibody was detected in the serum. After treatment with intravenous immunoglobulin (IVIG) and glucocorticoid, the child recovered well, and a 3-month outpatient follow-up showed that the child was able to walk normally. CONCLUSIONS: There are no previous reports of anti-GQ1b antibody syndrome with vomiting as the initial symptom, followed by abnormal gait. Therefore, this valuable case contributes to expanding the database of clinical manifestation of anti-GQ1b antibody syndrome, so as to improve pediatricians' awareness about such rare diseases and reduce misdiagnosis.

Clinical and antibodies analysis of anti-GQ1b antibody syndrome: a case series of 15 patients.

OBJECTIVES: To investigate the clinical manifestations, immunity, laboratory test, treatment and prognosis of patients with anti-GQ1b antibody syndrome in Chongqing, China. METHODS: We reviewed 15 patients with positive anti-ganglioside antibodies in the First Affiliated Hospital of Chongqing Medical University from 2016 to 2019. RESULTS: Fifteen patients were included in the study (mean age, 54.4 years; age range, 27 to 80 years; 9 men (60%)). Ten patients presented with a history of preinfection, including flu-like syndrome (n = 6, 60%), upper respiratory tract infection (URTI) (n = 3, 30%), and digestive tract infection (GI) (n = 1, 10%). The most common manifestation was ophthalmoplegia (n = 13, 86.67%), followed by weakness (n = 12, 80%), ataxia (n = 11, 73.3%), paresthesia (n = 8, 53.33%) and hypersomnolence (n = 5, 33.33%). All 15 patients underwent antibody testing. Eight patients (53.33%, 7 men (87.5%)) of whom only have positive immunoglobulin G (IgG) against anti-GQ1b antibody while seven (46.67%, 2 men (28.57%)) were positive for multiple anti-ganglioside antibodies apart from anti-GQ1b antibodies. Nine patients (60%) received intravenous immunoglobulin (IVIG) therapy, four (26.67%) received plasma exchange (PE) and two (13.33%) received steroid therapy. Three patients were lost to follow-up at 6 months, 1 patient (6.67%) had persistent back numbness, and the other 11 patients (73.33%) had fully recovered. CONCLUSION: The clinical subtype of anti-GQ1b antibody syndrome correlates with the type of anti-ganglioside antibody. Patients who test positive for only anti-GQ1b antibody are more likely to be men. Most patients exhibit a unidirectional course with a good prognosis, but anti-GQ1b antibody syndrome is also associated with a risk of recurrence.

Case Report: Isolated facial and trigeminal nerve palsy without ataxia in anti-GQ1b antibody syndrome secondary to Mycoplasma pneumonia.

The presence of anti-GQ1b antibodies in serum or cerebrospinal fluid is a diagnostic indicator of the Miller-Fisher variant of Guillain-Barré syndrome (GBS), whereas anti-GQ1b antibody syndrome is rarely presented as acute bilateral pain in the cheeks and masticatory muscle fatigue without ophthalmoplegia, ataxia, or limb weakness. Here, we report a case of a female patient diagnosed with GBS characterized only by the involvement of the facial and trigeminal nerves who was positive for serum anti-GQ1b antibodies secondary to Mycoplasma pneumoniae infection. The patient was treated with macrolide antibiotics and neurotrophic drugs, and her symptoms were significantly alleviated after 1 month. This case indicates a new clinical presentation of GBS and anti-GQ1b antibody syndrome with a differential diagnosis of multiple cranial nerve damage of which neurological physicians should be aware. Positive anti-GQ1b antibodies secondary to infection were observed in this case, and antibiotic treatment resulted in a favorable prognosis. The specific underlying mechanism requires further investigation.

Seasonality in the incidence of anti-GQ1b antibody syndrome-A territory-wide study.

AIMS: To investigate any seasonality in the incidence of anti-GQ1b antibody syndrome (AGS). METHODS: We conducted a retrospective observational study in all hospitalized patients in local public hospitals from January 2013 to December 2018. AGS was defined by hospitalized patients with positive serum anti-GQ1b IgG, presumably encompassing Miller-Fisher syndrome, Bickerstaff brainstem encephalitis and Guillain-Barré syndrome (GBS) variants. GBS cases were retrieved from the computerized database by diagnostic label. Campylobacter jejuni infection (CJI) injection was identified by positive stool culture. Monthly incidence rates of AGS, GBS and CJI were calculated. Poisson and negative binomial regression models with long-term time trend were fitted to characterize the seasonal pattern. RESULTS: A total of 237, 572 and 2434 cases of AGS, GBS and CJI were identified, respectively, in a population of 7.3 million. The annual incidence rate of AGS was 0.54 per 100,000 person-years. AGS was demonstrated to have an annual peak in the spring season, from March to April, which was congruent with that of GBS and slightly lagged the annual peak of CJI from February to March (likelihood ratio tests all p < .001 for the seasonal terms). CONCLUSION: The incidence of AGS peaks in springtime, which is congruent with that of GBS and lags around one month after that of CJI. We demonstrated that AGS has a clear seasonality in occurrence.

[Clinical analysis of 8 cases with anti-GQ1b antibody syndrome].

Objective: To investigate the clinical characterization, treatment and prognosis of anti-GQ1b antibody syndrome. Methods: The clinical data of 8 patients with positive serum anti-GQ1b antibody from the Department of Neurology of Nanjing Brain Hospital between June 2016 and July 2018 were analyzed retrospectively. Their serums were tested by immunoblotting. Relevant literatures were reviewed to investigate possible pathogenesis. Results: Of the 8 cases, 4 cases were male, 4 cases were female; their age ranged from 16 to 76 (47±21) years old. Seven of them were with acute onset, the time course of the disease ranged from 2 to 15 (7±4) days. Six cases had a history of influenza prior to the onset of the presenting symptoms. In terms of the clinical manifestations of the eight patients, two were affected with Guillain-Barre syndrome (GBS), two with Cavernous sinus syndrome, one with Miller Fisher syndrome, one with both GBS and spinal cord demyelination, one with Bulbar paralysis, and one with chronic inflammatory demyelinating polyneuropathy (CIDP). The anti-GQ1b antibody IgG in serum was positive in 6 patients, two of whom were combined with positive IgG of anti-GD1b antibody in serum. The anti-GQ1b antibody IgM in serum was positive in 1 patient, and the anti-GQ1b antibody IgM and anti-GT1b antibody IgM in cerebrospinal fluid (CSF) were both positive in the other patient. In terms of the treatment, 3 patients (3/8) received vitamin B treatment only, 2 patients (2/8) received steroid plus vitamin B treatment, 2 patients (2/8) received intravenous immunoglobulin (IVIG) plus vitamin B treatment, and 1 patient (1/8) received steroid plus IVIG treatment. During the 8-33 months' follow-up after discharge, 6 patients were significantly improved in their symptoms, one with mild diplopia, one with limbs weakness, numbness and difficulty in walking. The symptoms of one patient (case 3) fluctuated twice and recovered again after treatment. Conclusions: The disease spectrum of anti-GQ1b antibodies syndrome is broad, and main symptom is ophtalmoplegia. Immunotherapy with IVIG and steroid would be beneficial to prognosis.

A case of surgically-associated anti GQ1b antibody syndrome accompanied by saccadic ping pong gaze.

BACKGROUND: Periodic alternating ping-pong gaze (PPG) is a rare disease with few reports. To our knowledge, there was no report on anti GQ1b antibody syndrome accompanied by PPG. This paper reported a case of anti GQ1b antibody syndrome with Bickerstaff's Encephalitis (BBE) overlapping classic Guillain-Barre Syndrome (GBS) after aortic valve replacement, accompanied by an excessive PPG in the course of diagnosis and treatment, this was indeed rarely. CASE PRESENTATION: A 55-year-old male patient was admitted to our hospital with intermittent chest tightness for 3 months, and his condition has worsened in the past 10 days. Aortic valve replacement was performed because of the existence of the moderate and severe stenosis of aortic valve. Horizontal movement of the eyeball was involuntarily slow. The eyeball hovered and returned from one side to the other horizontally for 3-4 s per cycle. In combination with the patient's typical clinical and laboratory tests, the final diagnosis was anti GQ1b antibody syndrome BBE combined with GBS, accompanied by saccadic ping pong gaze. Intravenous immunoglobulin (0.4 g/kg) was given for immunomodulation, methylprednisolone (1000 mg) therapy and symptomatic treatment were performed in the patient. CONCLUSIONS: The patients were discharged from hospital on the thirtieth day because of economic reasons. After 6 months of follow up, the patients left behind a lack of fluency in speech and limb mobility, but the basic life can be taken care of by himself.

[Clinical analysis of four cases of anti GQ1b syndrome].

Objective: To investigate the clinical manifestations, laboratory findings, treatment and outcome of anti-GQ1b antibody syndrome. Method: The clinical manifestations, laboratory examination, diagnosis, treatment and prognosis of (4 patients 4 male patients, from 4 to 12 years) with anti-GQ1b syndrome in Beijing Children's Hospital affiliated to Capital Medical University from 2015 to 2016 were retrospectively analyzed. Result: All 4 children presented with ataxia. Case 1 showed impaired speech, ptosis and weakness of arms; case 2 and 3 had external ophthalmoplegia, weakness of limbs; case 4 presented hypersomnia, irritability and hallucinations. Serum anti-GQ1b-IgG antibody was positive in all cases. Case 1-3 received lumber puncture at the course of 1-2 weeks, CSF presented albuminocytological dissociation, case 4 had CSF pleocytosis and increased protein level. Brain MRI of Case 1-2 were normal; Case 3 showed long T1 and T2 signal in cerebellar dentate nucleus, pons and corpus callosum; Case 4 showed long T1 and T2 signal in bilateral centrum semiovale, basal ganglia, external capsule, insula and cerebellum. Electromyograms of case 1-3 showed peripheral axonal lesion. All children were treated with IVIG. After treatment, condition of all patients were improved. According to the clinical manifestation, laboratory examination, and outcome after treatment, case 1 was diagnosed as anti-GQ1b antibody syndrome (Pharyngeal-Cervical-Brachial weakness overlapped with Miller Fisher syndrome), case 2 and 3 were diagnosed as anti-GQ1b antibody syndrome (Miller Fisher syndrome overlapped with Guillain Barré syndrome) and case 4 was diagnosed as anti-GQ1b antibody syndrome (acute ataxia hypersomnolence). Conclusion: When patients with the presence of prodromic infections, monophasic course, drowsiness, ataxia, ophthalmoplegia, weakness and the symptoms/signs are relatively symmetric, anti-GQ1b antibody syndrome should be considered. Anti-GQ1b antibody has important significance for diagnosis. Most children have a good prognosis. Early correct diagnosis can avoid unnecessary examinations and guide appropriate use of immunotherapy.

Unilateral Oculomotor Nerve Palsy Following Campylobacter Infection: A Mild Form of Miller Fisher Syndrome without Ataxia.

Unilateral oculomotor nerve palsy can result from various neurological disorders. We herein report the case of a 68-year-old man with complete unilateral oculomotor nerve palsy following campylobacter infection. Based on the antecedent infection and the patient's decreased tendon reflexes, incomplete Miller Fisher syndrome (MFS) without ataxia was suspected. His serum tested positive for anti-GQ1b antibodies. He recovered over a period of 87 days without immunotherapy. We conclude that incomplete MFS following campylobacter infection can cause unilateral oculomotor nerve palsy without ataxia. Mild MFS should be considered in patients presenting with unilateral isolated ophthalmoplegia and decreased tendon reflexes.

Clinical analysis of four cases of anti GQ1b syndrome / 中华儿科杂志

Objective@#To investigate the clinical manifestations, laboratory findings, treatment and outcome of anti-GQ1b antibody syndrome.@*Method@#The clinical manifestations, laboratory examination, diagnosis, treatment and prognosis of (4 patients 4 male patients, from 4 to 12 years) with anti-GQ1b syndrome in Beijing Children's Hospital affiliated to Capital Medical University from 2015 to 2016 were retrospectively analyzed.@*Result@#All 4 children presented with ataxia. Case 1 showed impaired speech, ptosis and weakness of arms; case 2 and 3 had external ophthalmoplegia, weakness of limbs; case 4 presented hypersomnia, irritability and hallucinations. Serum anti-GQ1b-IgG antibody was positive in all cases. Case 1-3 received lumber puncture at the course of 1-2 weeks, CSF presented albuminocytological dissociation, case 4 had CSF pleocytosis and increased protein level. Brain MRI of Case 1-2 were normal; Case 3 showed long T1 and T2 signal in cerebellar dentate nucleus, pons and corpus callosum; Case 4 showed long T1 and T2 signal in bilateral centrum semiovale, basal ganglia, external capsule, insula and cerebellum. Electromyograms of case 1-3 showed peripheral axonal lesion. All children were treated with IVIG. After treatment, condition of all patients were improved. According to the clinical manifestation, laboratory examination, and outcome after treatment, case 1 was diagnosed as anti-GQ1b antibody syndrome (Pharyngeal-Cervical-Brachial weakness overlapped with Miller Fisher syndrome), case 2 and 3 were diagnosed as anti-GQ1b antibody syndrome (Miller Fisher syndrome overlapped with Guillain Barré syndrome) and case 4 was diagnosed as anti-GQ1b antibody syndrome (acute ataxia hypersomnolence).@*Conclusion@#When patients with the presence of prodromic infections, monophasic course, drowsiness, ataxia, ophthalmoplegia, weakness and the symptoms/signs are relatively symmetric, anti-GQ1b antibody syndrome should be considered. Anti-GQ1b antibody has important significance for diagnosis. Most children have a good prognosis. Early correct diagnosis can avoid unnecessary examinations and guide appropriate use of immunotherapy.

Three Cases of Anti-GQ1b Antibody Syndrome with Internal Ophthalmoplegia

The anti-GQ1b IgG antibody is associated with Guillain-Barre syndrome (GBS) with ophthalmoplegia, Bickerstaff's brainstem encephalitis, acute ophthalmoparesis without ataxia, and ataxic GBS without ophthalmoplegia as well as Miller Fisher syndrome. Only limited numbers of patients with acute ophthalmoparesis without ataxia are known to show internal ophthalmoplegia. We report three patients with internal ophthalmoplegia from anti-GQ1b antibody syndrome.