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Background Case Presentation Conclusions Bickerstaff brainstem encephalitis (BBE) is an autoimmune disease affecting the brainstem, typically caused by a prior infection. However, BBE after coronavirus disease 2019 (COVID‐19) infection is rare. Here, we present a severe case of BBE after COVID‐19 infection, highlighted by increased levels of CXCL‐10.A 28‐year‐old woman presented with symptoms of cold and fever lasting 5 days, accompanied by numbness, weakness and unsteadiness in the distal parts of her limbs before being admitted. Upon admission, her condition was classified with a Glasgow Coma Scale score of E1V1M4, absence of bilateral ocular cephalic reflexes, eyes fixed in the midline position and pathological reflex in lower limbs. COVID‐19 antigen tests were positive, and cerebrospinal fluid CXCL‐10 levels were elevated. Positive serum anti‐GQ1b antibodies, along with other clinical findings, confirmed the diagnosis of BBE. Initial treatment with high‐dose intravenous immunoglobulin was ineffective, leading to mechanical ventilation on day 2 from admission. Additional steroid pulse therapy and plasmapheresis were initiated on day 7. Communication abilities were restored by day 19, and the patient was extubated on day 21. Continuous alleviation of symptoms was observed, with no sequelae at discharge on day 42.BBE related to COVID‐19 with high CXCL‐10 levels can become severe. However, early intensive immunotherapy, including plasmapheresis, might result in favorable prognosis. [ABSTRACT FROM AUTHOR]

A 49-year-old female patient presented at the hospital with a history of herpetic blisters, frequent episodes of vomiting and loose stools, bilateral upper and lower limb weakness, and diminishing sensorium. She was diagnosed with hyponatraemia and respiratory failure and later became unconscious with absent brainstem reflexes. The patient was initially treated for herpetic encephalitis, a chronic obstructive pulmonary disease with acute exacerbation, hyponatraemia and neuroparalytic snake bite. Further evaluation, however, identified the uncommon Guillain Barre syndrome presentation with overlap of Bickerstaff brainstem encephalitis. This is an uncommon disorder characterised by the involvement of higher mental functions, fixed dilated pupils, absent brainstem reflexes and quadriplegia that resembles a neuroparalytic snake bite and brain death. After receiving intravenous immunoglobulins for treatment, the patient completely recovered. [ABSTRACT FROM AUTHOR]

Bickerstaff brainstem encephalitis (BBE) is a variant of Guillain-Barré syndrome (GBS) characterized by inflammation of the brainstem and cranial nerves. We describe a 60-year-old man presenting with acute confusion, bilateral progressive facial drooping, difficulty swallowing, aphasia, and confusion over two days. Examination showed bilateral facial paralysis, impaired eye movements, ptosis, dysarthria, diminished gag reflex and fatigue. MRI brain was unremarkable. Intravenous immunoglobulin (IVIG) was promptly started with noticeable improvement in facial strength and swallowing by day three. At discharge two weeks later, he had near complete resolution. BBE likely involves autoantibodies triggered by infections causing nerve inflammation. Diagnosis is clinical based on bilateral facial and bulbar weakness. Early immunotherapy provides best recovery prospects. Further research can uncover immunological mechanisms to guide treatments. Optimized protocols tailored to BBE compared with GBS are needed. Distinguishing BBE facilitates prompt therapy and favourable outcomes from this rare syndrome. [ABSTRACT FROM AUTHOR]

Background: Bickerstaff brainstem encephalitis (BBE) is a rare disease considered caused by acute demyelination of the brainstem, most often resulting from secondary autoimmune responses. To our knowledge, this is the first probable case report of shingles-associated BBE with anti-sulfatide IgM positivity. Case presentation: We report the case of an 83-year-old woman with symptoms of progressive limb weakness, difficulty swallowing food, and disturbed consciousness that occurred 4 weeks following herpes zoster infection. Autoimmune anti-sulfatide antibodies were positive and fluid-attenuated inversion recovery (FLAIR) sequences revealed clear high signal intensity in pons and bilateral thalamus. Our patient's condition improved markedly with glucocorticoid treatment. After 2 months of treatment, our patient was fully recovered. We considered that for her case, BBE is themost appropriate diagnosis. Conclusions: We emphasize the importance of a careful medical history and assessment of clinical symptoms, performing MRI, testing autoimmune antibodies for rapid diagnosis, and ruling out differential diagnoses. Further studies involving more patients with BBE with IgM anti-sulfatide autoantibodies will increase the understanding of the clinical characteristics and advance the diagnosis and treatment of this syndrome. Meanwhile, it is crucial for dermatologists to know about this severe neurological complication following shingles. [ABSTRACT FROM AUTHOR]

Introduction: Anti-sulfatide antibodies are key biomarkers for the diagnosis of Guillain-Barré syndrome (GBS). However, case reports on anti-sulfatide antibody-related GBS are rare, particularly for atypical cases. Case description, case 1: A 63 years-old man presented with limb numbness and diplopia persisting for 2 weeks, with marked deterioration over the previous 4 days. His medical history included cerebral infarction, diabetes, and coronary atherosclerotic cardiomyopathy. Physical examination revealed limited movement in his left eye and diminished sensation in his extremities. Initial treatments included antiplatelet agents, cholesterol-lowering drugs, hypoglycemic agents, and medications to improve cerebral circulation. Despite this, his condition worsened, resulting in bilateral facial paralysis, delirium, ataxia, and decreased lower limb muscle strength. Treatment with intravenous highdose immunoglobulin and dexamethasone resulted in gradual improvement. A 1 month follow-up revealed significant neurological sequelae. Case description, case 2: A 53 years-old woman was admitted for adenomyosis and subsequently experienced sudden limb weakness, numbness, and pain that progressively worsened, presenting with diminished sensation and muscle strength in all limbs. High-dose intravenous immunoglobulin, vitamin B1, and mecobalamin were administered. At the 1 month follow-up, the patient still experienced limb numbness and difficulty walking. In both patients, albuminocytologic dissociation was found on cerebrospinal fluid (CSF) analysis, positive anti-sulfatide antibodies were detected in the CSF, and electromyography indicated peripheral nerve damage. Conclusion: Anti-sulfatide antibody-related GBS can present with Miller-Fisher syndrome, brainstem encephalitis, or a combination of the two, along with severe pyramidal tract damage and residual neurological sequelae, thereby expanding the clinical profile of this GBS subtype. Anti-sulfatide antibodies are a crucial diagnostic biomarker. Further exploration of the pathophysiological mechanisms is necessary for precise treatment and improved prognosis. [ABSTRACT FROM AUTHOR]

Bickerstaff brainstem encephalitis (BBE) is a rare autoimmune disease characterized by the subacute onset of bilateral external ophthalmoplegia, ataxia, and decreased level of consciousness. BBE is part of a group of rare autoimmune diseases in children that can affect the nervous system at any level. The onset of neurological deficits is often sudden and nonspecific. The diagnosis is based on clinical findings and abnormal findings on cerebrospinal fluid (CSF), electroencephalography (EEG), electromyography (EMG), and magnetic resonance imaging (MRI). BBE is associated with the presence of the antiganglioside antibody, anti-GQ1b and anti-GM1. Intravenous immunoglobulin (IVIg) and plasma exchange are often used as treatments for these patients. We conducted a review on clinical presentation, diagnosis, treatment and outcome of reported cases of BBE. 74 cases are reported in the literature from the first cases described in 1951 to today. The prevalence is unknown while the incidence is higher in males. In 50% of cases, BBE occurs following respiratory or gastrointestinal tract infections. The most frequent initial symptoms were consciousness disturbance, headache, vomiting, diplopia, gait disturbance, dysarthria and fever. During illness course, almost all the patients developed consciousness disturbance, external ophthalmoplegia, and ataxia. Lumbar puncture showed pleocytosis or cytoalbuminological dissociation. Abnormal EEG and MRI studies revealed abnormalities in most cases. Anti-GQ1b antibodies were detected in more than half of the patients; anti-GM1 antibodies were detected in almost 40% of patients. Treatment guidelines are missing. In our analysis, steroids and IVIg were administered alone or in combination; as last option, plasmapheresis was used. BBE has a good prognosis and recovery in childhood is faster than in adulthood; 70% of patients reported no sequelae in our analysis. Future studies need to investigate pathogenesis and possible triggers, and therapeutic possibilities. [ABSTRACT FROM AUTHOR]

Bickerstaff brainstem encephalitis (BBE) is a rare autoimmune disease characterized by the subacute onset of bilateral external ophthalmoplegia, ataxia, and decreased level of consciousness. BBE is part of a group of rare autoimmune diseases in children that can affect the nervous system at any level. The onset of neurological deficits is often sudden and nonspecific. The diagnosis is based on clinical findings and abnormal findings on cerebrospinal fluid (CSF), electroencephalography (EEG), electromyography (EMG), and magnetic resonance imaging (MRI). BBE is associated with the presence of the antiganglioside antibody, anti-GQ1b and anti-GM1. Intravenous immunoglobulin (IVIg) and plasma exchange are often used as treatments for these patients. We conducted a review on clinical presentation, diagnosis, treatment and outcome of reported cases of BBE. 74 cases are reported in the literature from the first cases described in 1951 to today. The prevalence is unknown while the incidence is higher in males. In 50% of cases, BBE occurs following respiratory or gastrointestinal tract infections. The most frequent initial symptoms were consciousness disturbance, headache, vomiting, diplopia, gait disturbance, dysarthria and fever. During illness course, almost all the patients developed consciousness disturbance, external ophthalmoplegia, and ataxia. Lumbar puncture showed pleocytosis or cytoalbuminological dissociation. Abnormal EEG and MRI studies revealed abnormalities in most cases. Anti-GQ1b antibodies were detected in more than half of the patients; anti-GM1 antibodies were detected in almost 40% of patients. Treatment guidelines are missing. In our analysis, steroids and IVIg were administered alone or in combination; as last option, plasmapheresis was used. BBE has a good prognosis and recovery in childhood is faster than in adulthood; 70% of patients reported no sequelae in our analysis. Future studies need to investigate pathogenesis and possible triggers, and therapeutic possibilities.

We present a case of acute external ophthalmoplegia, hypersomnolence, and ataxia occurring 5 days after an episode of SARS-CoV-2 upper respiratory tract infection. The patient's serum returned positive for anti-GD1a antibodies. Guided by precedent cases, she was empirically started on a course of intravenous (IV) immunoglobulin for possible para-infectious Bickerstaff brainstem encephalitis (BBE). However, she failed to respond and subsequently developed autoimmune hemolytic anemia as well as renal tubular acidosis (type 1). Corroborative history from her family elucidated constitutional and sicca symptoms and she was eventually diagnosed with primary Sjögren syndrome (pSS) complicated by brainstem and cerebellar involvement. She was treated with IV cyclophosphamide and rituximab, after which her neurological deficits completely resolved at two months. [ABSTRACT FROM AUTHOR]

Bickerstaff brainstem encephalitis (BBE) is a rare inflammatory, demyelinating disease that generally has a good prognosis. It's characterized by an acute dysfunction of brainstem occurring few days after an infection. We report the case of an 11-year-old male child with a history of cold, presented with ataxia in whom a Bickerstaff encephalitis was attested through brain MRI and who has fully recovered after treatment. The main symptoms are ataxia, ophthalmoplegia, and altered consciousness. CSF analysis and serum antiganglioside antibodies are also very suggestive of the diagnosis that can be suspected clinically and confirmed on brain MRI. The interest of this observation lies in its rarity and on the rapid and spectacular clinical improvement under treatment.

Man Li,1,* Xingyu Wang,2,* Mojun Chen,1 Yuan Chang,1 Linfeng Li,1 Shan Zhong1 1Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shan Zhong, Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China, Tel +86-13810056088, Fax +86-10-63139108, Email zhongshan@ccmu.edu.cnBackground: Bickerstaff brainstem encephalitis (BBE) is a rare demyelinating disease of the central nervous system (CNS) that is caused by a direct viral infection or secondary autoimmune responses. BBE secondary to Herpes zoster has rarely been reported.Case Presentation: A 68-year-old man developed a painful vesicular rash and drooping eyelid on the left side of his face for 20 days. Physical examination revealed left-sided blepharoptosis and crusted erythema on the left front side of his face, left upper eyelid, and left nasal tip. Neurological examination showed impaired sensation over the left side of his face and cheek. His left pupil was dilated (4mm compared to 2mm on the right side), and the Pupillary light reflection (PLR) was absent, with an ocular movement disorder (limited adduction) and diplopia. Brain imaging did not reveal abnormalities. Cerebrospinal fluid (CSF) examination showed leukocytosis and increased protein levels. He was treated with intravenous acyclovir for 7 days, but developed disturbance of consciousness and right limb weakness. Neurological examination revealed right lower limb hypoesthesia. The Heel-Knee-Shin test was positive on the left side, and Babinski’s sign was present on the right side. He was diagnosed with Bickerstaff brainstem encephalitis caused by herpes zoster. After 2 days of intravenous acyclovir combined with intravenous immune globulin (IVIG), the patient developed acute kidney injury (AKI). Then, his treatment was changed to systemic steroids. At the 3-month follow-up, his pupils were bilaterally equal and reactive to light, and there was a significant improvement in ocular motility and ptosis. At the 6-month follow-up, his diplopia had completely resolved.Conclusion: BBE associated with herpes zoster is very rare and can be overlooked. Dermatologists should be aware of the expanding spectrum of neurological complications caused by varicella zoster virus (VZV) infections to aid early diagnosis and treatment.Keywords: herpes zoster, Bickerstaff brainstem encephalitis, acute kidney injury, treatment

Guillain-Barré syndrome (GBS), Fisher syndrome (FS), and Bickerstaff brainstem encephalitis (BBE) are immune-mediated neuropathies presenting with symptoms such as weakness, ophthalmoplegia, ataxia, and consciousness disturbances. Although the epidemiology of GBS and BBE in patients of all ages has been reported, childhood data have not been well-investigated. We aimed to determine the clinical features, therapeutics, and prognoses of childhood GBS, FS, and BBE in Japan. We sent questionnaires to 1068 pediatric neurologists in Japan from 2014 to 2016 to determine the number of children less than 15 years old with GBS, FS, or BBE and their age and sex. We subsequently performed a secondary survey to investigate the clinical features, laboratory data, treatment, and prognosis. Five-hundred thirty-eight pediatric neurology specialists (50.4%) responded to the first survey. The total number of children with GBS, FS, and BBE in Japan from 2014 to 2016 were 87, 10, and 6, respectively. GBS was classified as acute inflammatory demyelinating neuropathy (35.6%), acute motor axonal neuropathy (20.7%), or acute motor-sensory axonal neuropathy (10.3%), with a male-to-female ratio of 1.29:1.0 and a wide distribution of onset ages. The disease severities of GBS, FS, and BBE were variable, but all children could walk within one year. The prognoses of childhood GBS, FS, and BBE were generally favorable, as long as the patient was promptly treated with either intravenous immunoglobulin or plasma exchange. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but they have been known to cause immune-related adverse events (irAEs) by promoting T-cell activation. Neurological irAEs are rare (1%) but have a high fatality rate (11.5%). Here we report the first case of Bickerstaff brainstem encephalitis (BBE) induced by an ICI. A woman in her 60s with metastatic breast cancer was treated with atezolizumab plus nab-paclitaxel once intravenously. Eighteen days later, she lost consciousness with ophthalmoplegia and was diagnosed with a neurological irAE. She recovered consciousness immediately with the administration of intravenous immunoglobulin (IVIG) but suffered severe permanent peripheral neuropathy. Although it is just one case, this experience shows that BBE occurring as a neurological irAE of ICI cancer treatment may be associated with more severe outcomes than conventional BBE in metastatic cancer. Creating a system for multidisciplinary treatment is essential for ICI therapy., Competing Interests: No potential conflict of interest relevant to this article was reported.

Purpose: To add to the growing literature regarding the possible link between the onset of Guillain Barre syndrome (GBS) and Bickerstaff brainstem encephalitis (BBE) and the coronavirus disease (COVID-19) vaccines. Case reports: The first patient is a 38-year-old man that presented muscle weakness and an unsteady gait for a duration of one week. Initially, he developed an unsteady gait, then gradually worsening generalized muscle fatigue and ascending weakness in all limbs. He tested positive for GM1 and GQ1D antibodies, and magnetic resonance imaging (MRI) of the lumbar spine with contrast and nerve conduction study (NCS) results were both suggestive of acute motor axonal neuropathy (AMAN). The second patient is a 54-year-old man that developed generalized fatigue and subjective fever associated with headache and blurry vision followed by bulbar dysfunction. During hospitalization, his consciousness level started to be affected and he developed ataxia with ophthalmoparesis. A diagnosis of BBE was made based on clinical, imaging, and cerebrospinal fluid (CSF) findings. Conclusion: Since temporal relationships do not signify causation, we cannot draw any conclusions regarding the association between COVID-19 vaccines and these neurological disorders. However, it is vital that new cases are reported so that the knowledge base is built upon, and to increase healthcare workers’ vigilance for early signs of GBS or BBE.

Bickerstaff brainstem encephalitis (BBE) is a rare, immune-mediated disease characterized by the acute onset of external ophthalmoplegia, ataxia, and consciousness disturbance. It has a complex multifactorial etiology, and a preceding infectious illness is seen in the majority of cases. Immune-mediated neurological syndromes following COVID-19 vaccination have been increasingly described. Here we report the case of a child developing BBE 2 weeks after COVID-19 vaccination. Despite nerve conduction studies and CSF analysis showing normal results, BBE was diagnosed on clinical ground and immunotherapy was started early with a complete recovery. Later, diagnosis was confirmed by positive anti-GQ1b IgG in serum. Even if there was a close temporal relationship between disease onset and COVID-19 vaccination, our patient also had evidence of a recent Mycoplasma pneumoniae infection that is associated with BBE. Indeed, the similarity between bacterial glycolipids and human myelin glycolipids, including gangliosides, could lead to an aberrantly immune activation against self-antigens (i.e., molecular mimicry). We considered the recent Mycoplasma pneumoniae infection a more plausible explanation of the disease onset. Our case report suggests that suspect cases of side effects related to COVID-19 vaccines need a careful evaluation in order to rule out well-known associated factors before claiming for a causal relationship. [ABSTRACT FROM AUTHOR]

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The triggering effect of herpes simplex virus infection on the development of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is now well established. However, there are very few reports that has linked a varicella zoster virus (VZV) reactivation with anti-NMDAR encephalitis. In this report, we describe a case of a 57-year-old man presented with atypical clinical presentation of anti-NMDAR encephalitis with gait ataxia, complete ophtalmoplegia, and abolished reflexes followed by drowsiness and confusion. Initial diagnosis of Bickerstaff's brainstem encephalitis was suspected. Few days later, the patient developed herpes zoster in a localized right T1-T2 dermatome. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for VZV was negative. CSF anti-NMDA antibodies were proved positive. A diagnosis of anti-NMDAR encephalitis with concomitant VZV skin reactivation was retained. Favorable outcome with combined antiviral treatment and immunomodulatory therapy was observed. Concomitant VZV reactivation with autoimmune encephalitis is possible. Prognosis and therapeutic options in this rare condition remain to be clarified. [ABSTRACT FROM AUTHOR]

Bickerstaff brainstem encephalitis (BBE) is a rare, immune-mediated disease characterized by the acute onset of external ophthalmoplegia, ataxia, and consciousness disturbance. It has a complex multifactorial etiology, and a preceding infectious illness is seen in the majority of cases. Immune-mediated neurological syndromes following COVID-19 vaccination have been increasingly described. Here we report the case of a child developing BBE 2 weeks after COVID-19 vaccination. Despite nerve conduction studies and CSF analysis showing normal results, BBE was diagnosed on clinical ground and immunotherapy was started early with a complete recovery. Later, diagnosis was confirmed by positive anti-GQ1b IgG in serum. Even if there was a close temporal relationship between disease onset and COVID-19 vaccination, our patient also had evidence of a recent Mycoplasma pneumoniae infection that is associated with BBE. Indeed, the similarity between bacterial glycolipids and human myelin glycolipids, including gangliosides, could lead to an aberrantly immune activation against self-antigens (i.e., molecular mimicry). We considered the recent Mycoplasma pneumoniae infection a more plausible explanation of the disease onset. Our case report suggests that suspect cases of side effects related to COVID-19 vaccines need a careful evaluation in order to rule out well-known associated factors before claiming for a causal relationship.

Takotsubo cardiomyopathy (TCM) is a stress-induced cardiomyopathy triggered by critical illness including severe neurological disorders. However, an association between TCM and Bickerstaff brainstem encephalitis (BBE) has rarely been described. During the current coronavirus disease 2019 (COVID-19) pandemic, growing evidence indicates that COVID-19 often leads to various neurological disorders, but there are few reports of an association between COVID-19 and BBE. Here we report a case of TCM associated with BBE triggered by COVID-19, which subsided with immunotherapy for BBE. Both transthoracic echocardiography and electrocardiography led to early and accurate diagnosis of TCM. Sustained hemodynamic instability due to TCM was immediately lessened with immunotherapy whereas additional plasmapheresis and immunotherapy were required to treat BBE. This case indicates that BBE might follow COVID-19 and TCM should be considered when hemodynamic status remains unstable in a patient with BBE. [ABSTRACT FROM AUTHOR]

Takotsubo cardiomyopathy (TCM) is a stress-induced cardiomyopathy triggered by critical illness including severe neurological disorders. However, an association between TCM and Bickerstaff brainstem encephalitis (BBE) has rarely been described. During the current coronavirus disease 2019 (COVID-19) pandemic, growing evidence indicates that COVID-19 often leads to various neurological disorders, but there are few reports of an association between COVID-19 and BBE. Here we report a case of TCM associated with BBE triggered by COVID-19, which subsided with immunotherapy for BBE. Both transthoracic echocardiography and electrocardiography led to early and accurate diagnosis of TCM. Sustained hemodynamic instability due to TCM was immediately lessened with immunotherapy whereas additional plasmapheresis and immunotherapy were required to treat BBE. This case indicates that BBE might follow COVID-19 and TCM should be considered when hemodynamic status remains unstable in a patient with BBE.

Bickerstaff brainstem encephalitis (BBE) is a rare neurological disorder characterised by the presence of the triad of ophthalmoplegia, ataxia and altered consciousness. It is thought to be associated to an autoimmune condition triggered by an antecedent infection. Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi, and it is associated with myriads of neurological complications. We hereby present an unusual case of BBE in a young lady, who was probably a sequalae of scrub typhus infection. Bickerstaff brainstem encephalitis in association with scrub typhus has not been reported till date. [ABSTRACT FROM AUTHOR]

Objective: To summarize the clinical, electrophysiological, neuroimaging, and immunological characteristics of seven cases of Bickerstaff brainstem encephalitis (BBE) in China and to determine whether certain clinical features suggestive of BBE can facilitate diagnosis and treatment.Patients and Methods: The clinical data of seven BBE patients treated at the Children's Hospital of Fudan University between 2016 and 2019 were retrospectively analyzed. The clinical and laboratory characteristics of the BBE patients were studied.Results: The seven patients in this study included four females and three males, and the median age at diagnosis was 5.3 years (interquartile range: 3.0–7.1 years). All seven patients had an acute onset with a preinfection history. Seven cases of acute extraocular paralysis, ataxia, and an impaired level of consciousness, two cases of tendon hyperreflexia, one case of positive pathology, and five cases of cranial nerve involvement (the facial nerve and oculomotor nerve) were noted. Cerebrospinal fluid (CSF) examination of five patients showed albuminocytologic dissociation. Electromyography (EMG) was used to examine seven patients; the results were normal in four patients, showed axonal involvement in two patients, and showed demyelination in one patient. The head magnetic resonance imaging (MRI) results of all seven patients were normal. Electroencephalogram (EEG) background activity in the five monitored patients was slowed down. Seven patients underwent serum antibody testing, three of whom were positive for anti-GQ1b antibody, while one was positive for anti-GM1 antibody. Three patients received glucocorticoid combined with intravenous immunoglobulin (IVIG) therapy, and four received only IVIG therapy. One patient required a nasal catheter for oxygen during the disease course, and left upper limb muscle dysfunction (grade III muscle strength of the left upper limb) was observed during the 6-month follow-up. The other six patients had a good prognosis and no dysfunction.Conclusion: Our study identified clinical, imaging, and treatment characteristics that may have prognostic value for pediatric BBE. The positive rate of head MRI was low, the positive rate of serum anti-GQ1b ganglioside antibody was low, and the therapeutic effect of IVIG therapy was good.

Abstract Background Miller Fisher syndrome (MFS) and Bickerstaff’s Brainstem Encephalitis (BBE) share some clinical features and a common immunological profile characterized by anti-GQ1b antibodies. Some MFS patients overlap with Guillain-Barré syndrome (GBS) or BBE. We report a patient with MFS, BBE, and axonal GBS overlap in whom serial electrophysiological studies showed persistent motor conduction blocks (CBs). Case presentation A 61-year-old man acutely developed ophtalmoparesis, ataxia and areflexia suggesting MFS. Paresthesias, severe weakness, and drowsiness rapidly developed indicating an overlap with BBE and GBS. Preceding infection with Mycoplasma Pneumoniae and anti-GQ1b antibodies were detected. On day 4, nerve conduction study showed reduced or non-recordable compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) without demyelinating features, indicating the electrodiagnosis of acute motor and sensory axonal neuropathy and suggesting a poor prognosis. Intravenous immunoglobulins (IVIg) were given but clinical status worsened to ophthalmoplegia, tetraplegia and coma needing mechanical ventilation. A second IVIg course was given and the patient was weaned off ventilation on day 41 and transferred to rehabilitation on day 57 with partial resolution of the ophthalmoplegia and limited recovery of muscle strength. Electrophysiology showed, after 10 weeks, greatly improved distal CMAP amplitudes suggesting the resolution of distal CBs while CBs in intermediate and proximal nerve segments emerged. CBs unusually persisted for four to 6 months without development of abnormal temporal dispersion. A third IVIg course was started on day 179 and the resolution of CBs mirrored the clinical improvement. Conclusions GQ1b gangliosides are expressed in the nodal region of oculomotor nerves, muscle spindle afferents, peripheral nerves and possibly in the brainstem reticular formation. Anti-GQ1b antibodies may explain the complex symptomatology and the overlap between MFS, BBE, and GBS. CBs that persisted and recovered without the development of temporal dispersion suggest that weakness was due to a sustained, antibody-mediated, attack at the nodal region inducing a non-demyelinating conduction failure as expression of an acute onset, long lasting, nodopathy. Serial electrophysiological studies allowed not only to understand the underlying pathophysiology and formulate a more correct prognosis but also to guide the treatment.

Abstract Background Guillain-Barré syndrome (GBS), Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE) are a group of autoimmune neurological disorders (GBS spectrum disorder) that rarely recur. Recently, anti-ganglioside complex antibodies (GSC-Abs) were identified in patients with GBS spectrum disorder. However, there has been no case report describing GSC-Abs profiles in a recurrent case showing different phenotypes. Case presentation We report the case of a 33-year-old male patient with GQ1b-seronegative BBE-GBS after two prior episodes of MFS-GBS. Our patient showed ophthalmoplegia, ataxia, areflexia and a weakness of the extremities (MFS and GBS symptoms) in all episodes. In the episode reported here, our patient showed disturbed consciousness and an extensor response to cutaneous plantar stimulation was observed (BBE symptoms), with severe disability and requirement for artificial respiration management. GSC-Abs detected in previous episodes were also detected in the subsequent episodes, while new GSC-Abs emerged in each episode. Interestingly, whereas antibodies to GA1/GQ1b and GA1/GT1a, which are commonly identified in patients with GBS, MFS or BBE, appeared in all episodes, antibodies to GD1a/GD1b and GD1b/GT1b, which are predominantly associated with severe disability and the requirement for artificial respiration management in GBS, emerged for the first time in this episode. Conclusion This study reports novel phenomena about the GSC-Abs profiles and its relationship with clinical features in a case with recurrent GBS spectrum disorder, showing different phenotypes in different episodes. Further studies are required to reveal the significance of the GSC-Abs profiles in recurrent GBS spectrum disorder.

Objective: To summarize the clinical, electrophysiological, neuroimaging, and immunological characteristics of seven cases of Bickerstaff brainstem encephalitis (BBE) in China and to determine whether certain clinical features suggestive of BBE can facilitate diagnosis and treatment. Patients and Methods: The clinical data of seven BBE patients treated at the Children's Hospital of Fudan University between 2016 and 2019 were retrospectively analyzed. The clinical and laboratory characteristics of the BBE patients were studied. Results: The seven patients in this study included four females and three males, and the median age at diagnosis was 5.3 years (interquartile range: 3.0–7.1 years). All seven patients had an acute onset with a preinfection history. Seven cases of acute extraocular paralysis, ataxia, and an impaired level of consciousness, two cases of tendon hyperreflexia, one case of positive pathology, and five cases of cranial nerve involvement (the facial nerve and oculomotor nerve) were noted. Cerebrospinal fluid (CSF) examination of five patients showed albuminocytologic dissociation. Electromyography (EMG) was used to examine seven patients; the results were normal in four patients, showed axonal involvement in two patients, and showed demyelination in one patient. The head magnetic resonance imaging (MRI) results of all seven patients were normal. Electroencephalogram (EEG) background activity in the five monitored patients was slowed down. Seven patients underwent serum antibody testing, three of whom were positive for anti-GQ1b antibody, while one was positive for anti-GM1 antibody. Three patients received glucocorticoid combined with intravenous immunoglobulin (IVIG) therapy, and four received only IVIG therapy. One patient required a nasal catheter for oxygen during the disease course, and left upper limb muscle dysfunction (grade III muscle strength of the left upper limb) was observed during the 6-month follow-up. The other six patients had a good prognosis and no dysfunction. Conclusion: Our study identified clinical, imaging, and treatment characteristics that may have prognostic value for pediatric BBE. The positive rate of head MRI was low, the positive rate of serum anti-GQ1b ganglioside antibody was low, and the therapeutic effect of IVIG therapy was good. [ABSTRACT FROM AUTHOR]

Patients with Miller Fisher syndrome (MFS) are characterized by acute ophthalmoplegia (AO) and areflexia. MFS is an immune mediated process, triggered by an infection and includes incomplete forms, such as ophthalmoplegia, ataxia and a central nervous system subtype known as Bickerstaff brainstem encephalitis (BBE). We present two cases admitted to our hospital on the same day. The first case was presented as AO, with elevated levels of anti GQ1b. The second case was presented as AO, oropharyngeal palsy and sensory motor polyneuropathy with borderline levels of anti GQ1b, diagnosed as BBE. There are atypical forms of MFS with different clinical symptoms and elevated levels of antibodies called “Anti GQ1b Antibody syndrome”. The cases of the two patients diagnosed as MFS variants’ AO and BBE.

Abstract Bickerstaff Brainstem Encephalitis (BBE) is a rare autoimmune encephalitis, characterized by acute ophthalmoplegia, ataxia and altered state of consciousness. Together with Guillan-Barrè Syndrome (GBS) and Miller–Fisher Syndrome, it forms a spectrum of post-infectious demyelinating diseases. Overlapping forms between BBE and GBS (BBE/GBS) are described in patients with lower limbs weakness and typical signs of BBE, suggesting a combined involvement of Central and Peripheral Nervous System (PNS), but only few reported cases are focused on pediatric population. We reviewed all cases of pediatric BBE in the literature, to determine if any patient showed features suggestive for BBE/GBS. Data analysis focused on the diagnostic tests performed (e.g. anti-GQ1b antibodies), neuroimaging and nerve conduction studies (NCS). Further attention was given to the therapeutic management and to patients' outcome. We additionally present two previously unreported pediatric cases. Our review retrieved 19 cases of BBE/GBS, only 2 of which were originally and correctly diagnosed by the authors. The prevalence was higher in male subjects (ratio 3:1) and median age at diagnosis was 8 years. Anti-GQ1b were positive in 46% of the patients, while NCS were altered in 64%. Only 25% of the patients that underwent brain MRI showed abnormal findings. The incidence of BBE/GBS has been underrated in the past, mostly due to an underestimation of the PNS involvement. We therefore suggest to investigate all patients with a clinical picture suggestive of BBE/GBS through electroencephalogram, NCS, brain and spine MRI in order to promptly achieve the correct diagnosis. Highlights • Bickerstaff Brainstem Encephalitis (BBE) is rare in children. • Overlapping forms with Guillain-Barré syndrome (BBE/GBS) exist (but underdiagnosed). • BBE/GBS have combined central and peripheral nervous system involvement. • Nerve conduction studies can help to achieve a correct diagnosis. • Pediatric BBE/GBS have good outcome with immunoglobulin or steroid treatment. [ABSTRACT FROM AUTHOR]

A flaccid tetraparesis in Bickerstaff's brainstem encephalitis (BBE) is presumed to be a sign of overlapping Guillain-Barré syndrome (GBS). In addition, BBE and Fisher syndrome, which are clinically similar and are both associated with the presence of the immunoglobulin G anti-GQ1b antibody, represent a specific autoimmune disease with a wide spectrum of symptoms that include ophthalmoplegia and ataxia. A 2-year-old boy presented with rapidly progressive ophthalmoplegia, ataxia, hyporeflexia, weakness of the lower extremities, and, subsequently, disturbance of consciousness. He experienced bronchitis with watery diarrhea and had laboratory evidence of recent infection with Epstein-Barr virus (EBV). He was diagnosed as having overlapping GBS and BBE associated with EBV and received treatment with a combination of immunoglobulin and methylprednisolone, as well as acyclovir, and had recovered completely after 3 months. In addition, he has not experienced any relapse over the past year. We suggest that combinations of symptoms and signs of central lesions (disturbance of consciousness) and peripheral lesions (ophthalmoplegia, facial weakness, limb weakness, and areflexia) are supportive of a diagnosis of overlapping GBS and BBE and can be helpful in achieving an early diagnosis, as well as for the administration of appropriate treatments.

Isolated bilateral internal ophthalmoplegia is a rare and problematic condition affecting activities of daily living. Herein, we describe the cases of 2 patients with postinfectious isolated bilateral internal ophthalmoplegia, i.e., mydriasis without external ophthalmoplegia. One patient demonstrated no other neurological symptom, while the other patient showed mild gait ataxia. Magnetic resonance imaging revealed no abnormal findings in the brain or brainstem. Light-near dissociation of the pupils was not recognized in either patient, and supersensitivity to dilute pilocarpine was observed in 1 of the 2 patients. An increased titer of the anti-GQ1b IgG antibody was noted in 1 patient. A review of the literature revealed five similar cases; the symptomatic characteristics, ratio of positive anti-GQ1b IgG antibody, and effective treatment are discussed.

We report the first case of Listeria monocytogenes meningoencephalitis associated with anti-GQ1b antibody syndrome in an immunocompetent adult. A prompt diagnosis, made thanks to the multidisciplinary contribution, allowed a combined therapeutic approach leading to final favourable outcome, despite several intercurrent complications. [ABSTRACT FROM AUTHOR]

Background and purpose Fisher syndrome (FS) may overlap with Guillain-Barré syndrome (GBS), in particular the pharyngeal-cervical-brachial variant form (PCB-GBS), or Bickerstaff brainstem encephalitis (BBE). Our aim was to elucidate the frequency of this overlap and the patterns of clinical progression in patients with FS. Methods Sixty consecutive patients with FS were studied. FS/PCB-GBS was diagnosed when the patients developed pharyngeal, cervical and/or brachial weakness. Patients with flaccid tetraparesis were diagnosed as having FS/conventional GBS. FS/BBE was defined as the development of consciousness disturbances. Results All 60 patients initially developed the FS clinical triad alone (pure FS). Of these, 30 (50%) patients had pure FS throughout their course, whereas the remaining 50% of patients showed an overlap: PCB-GBS in 14 (23%) patients, conventional GBS in nine (15%) patients and BBE in seven (12%) patients. The median (range) durations from FS onset to progression to FS/PCB-GBS, FS/GBS or FS/BBE were 5 (1-7), 3 (1-4) and 3 (1-5) days, respectively. Patients with overlap syndromes more frequently received immune-modulating treatment, and the outcomes were generally favourable. The frequencies of positivity for anti-GQ1b, GT1a, GD1a, GD1b, GalNAc-GD1a and GM1 antibodies were not significantly different amongst the four groups. Conclusions Of the patients with pure FS, 50% later developed an overlap with PCB-GBS, conventional GBS or BBE. The overlap occurred within 7 days of FS onset; thus, physicians should pay attention to the possible development of this overlap during the first week after FS onset. [ABSTRACT FROM AUTHOR]

Objective Guillain–Barré syndrome (GBS), Miller Fisher syndrome (MFS), and Bickerstaff brainstem encephalitis (BBE) are usually monophasic, but some patients experience recurrences after long asymptomatic intervals. We aimed to investigate clinical features of recurrent GBS, MFS, and BBE at a single hospital. Methods Records from 97 consecutive patients with GBS, MFS or BBE who were admitted to a tertiary hospital between 2001 and 2013 were reviewed. Clinical and laboratory features of patients with recurrent GBS, MFS, or BBE were investigated. Results Patients included 55 (32 males) with GBS, 34 (22 males) with MFS, and 8 (6 males) with BBE. Recurrent cases occurred in 2 (4%) of the 55 patients with GBS, 4 (12%) of the 34 patients with MFS, and 2 (25%) of the 8 patients with BBE. Patients with recurrent MFS had a tendency to be younger at the first episode than patients with non-recurrent MFS (median, 22 versus 37 years old). Symptoms and signs were less severe during relapses than during the initial episode in recurrent patients. Conclusions Recurrences occurred more frequently in patients with MFS or BBE compared with those with GBS. Patients with recurrent MFS might be younger than those with non-recurrent MFS. [ABSTRACT FROM AUTHOR]