Bickerstaff's Encephalitis Research Articles

B-080 Development and Validation of a GQ1b IgG ELISA as a Diagnostic Aid for Subacute Demyelinating Polyneuropathies

Abstract Background Autoimmunity targeting GQ1b is associated with group of disorders that includes Miller-Fisher Syndrome (MFS), Bickerstaff Brainstem Encephalitis (BBE) and classic Guillain Barre Syndrome (GBS) with ophthalmoplegia. Collectively these are referred to as GQ1B-IgG related syndromes. The prevalence of GQ1b-IgG in this population of patients is high and has been reported to be >80% in well-defined clinical cohorts. Clinical phenotypic presentation is diverse and requires highly accurate antibody testing. The objective of this study was to evaluate a newly developed custom GQ1b-IgG assay, using a semi-quantitative ELISA-based method. Methods A GQ1b-IgG ELISA was developed and validated. Patient sera along with assay controls and a single-point calibrator are diluted and incubated in duplicate wells in a 96-well plate coated with GQ1b antigen. The plate is washed and incubated with anti-human-IgG secondary antibody conjugated with HRP. After a colorimetric reaction, optical densities (OD) are read. The OD of patient samples are compared against the calibrator, generating a cut-off index (COI). Samples ≥1.0 COI are considered positive. During the validation phase, analytical and clinical performance characteristics were evaluated. Studies included assessment of imprecision at multiple concentrations of GQ1b-IgG, accuracy using method comparison, analytical sensitivity and specificity, reference range, common interferences, plate drift, and clinical performance in relevant disease and control cohorts. Results Intra-assay imprecision (coefficient of variation; %CV) ranged from 1.0 - 16% across all concentrations of GQ1b-IgG. Inter-assay imprecision (%CV) ranged from 12.4 - 44.5% but was <20% at or above the assay cut-off. We found perfect qualitative agreement with an independent ELISA reference method (20 positive and 20 negative samples selected based on reference method results [reference interval <1:100]). Limit of detection (LOD) was calculated at a COI of 0.22. To assess analytical specificity, 40 samples with high concentrations of immunoglobulins (hypergammaglobulinemia [N=15], IgG M-protein [N=15] and systemic lupus erythematosus [N=10] were tested and all were negative. A reference interval study was performed on 140 healthy donor serums, all were negative. Interference studies were conducted on 2 positive and 2 negative serum samples, spiked for highly hemolytic (1000 mg/dL), lipemic (2000 mg/dL) and icteric (60 mg/dL) conditions. There was no impact on the assay even with high levels of a given interferent. Plate drift on 2 distinct patient pools tested across the plate (COI range 0.7 - 1.3) had overall plate CV’s ≤10%. ROC analysis was performed on a cohort of 278 patient samples (15 MFS cases and 263 controls [suspected demyelinating neuropathy or disease mimics]). A cut-off value of 1.0 (COI) was selected based on the Youden index. At this cut-off, clinical sensitivity for MFS was 87% while clinical specificity was 99.2%. Conclusions The observed performance of the GQ1b-IgG ELISA was acceptable for clinical laboratory implementation. A COI of ≥ 1.0 was selected for clinical use.

AN OVERLAP OF GUILLAIN-BARRÉ SYNDROME, MILLER-FISHER SYNDROME, AND BICKERSTAFF BRAINSTEM ENCEPHALITIS PRESENTING AS CLINICAL BRAIN DEATH, A CASE SERIES

Guillain-Barré Syndrome (GBS), Miller-Fisher Syndrome (MFS), and Bickerstaff Brainstem Encephalitis (BBE) are neuroinflammatory disorders that share common immunopathogenic mechanisms. Although overlapping presentations of these conditions are rare, they pose significant diagnostic challenges, especially when mimicking clinical brain death. Objective: To present a case series of three patients who demonstrated an overlap of GBS, MFS, and BBE, with all patients exhibiting profound neurological impairments, including clinical signs of brain death. Methods: A retrospective review of three cases admitted to the ICU over the last three years was conducted. Detailed clinical profiles, cerebrospinal fluid (CSF) analysis, nerve conduction studies (NCS), and electromyography (EMG) results were reviewed. All patients were treated with intravenous immunoglobulins (IVIG) and therapeutic plasma exchange (TPE). Results: All three patients had a history of preceding infections and were presented with ophthalmoplegia, ataxia, and altered levels of consciousness, progressing to coma. CSF analysis revealed albuminocytological dissociation, and NCS/EMG indicated severe polyneuropathy. Two patients responded positively to IVIG and plasmapheresis, showing significant neurological recovery, while the third patient demonstrated a delayed but spontaneous recovery. All patients eventually achieved full or near-full neurological recovery. Conclusions: This case series highlights the clinical continuum and diagnostic complexity of overlapping GBS, MFS, and BBE, particularly in presentations mimicking brain death. Early recognition and prompt immunomodulatory therapy are crucial in improving patient outcomes, even in cases with severe neurological deficits. Further research is warranted to elucidate pathophysiology and optimize treatment strategies for overlapping neuroinflammatory syndromes.

Clinical presentation and symptomatology of Guillain-Barré syndrome: A literature review.

Guillain-Barré Syndrome (GBS) is a rare but potentially life-threatening neurological disorder characterized by acute onset ascending paralysis and sensory abnormalities. This article provides a comprehensive overview of GBS, covering its epidemiology, etiology, clinical presentation, diagnostic evaluation, management and treatment, prognosis, psychosocial impact, recent advances in research, public health implications, and ethical considerations. Epidemiological data reveal variations in GBS prevalence, incidence rates, and geographical distribution influenced by climate, infectious disease prevalence, and genetic susceptibility. Etiological factors include preceding infections, vaccinations, and autoimmune mechanisms, although the precise pathophysiology remains incomplete. Clinical presentation encompasses prodromal symptoms, motor deficits, sensory abnormalities, autonomic dysfunction, and variants such as Miller-Fisher Syndrome and Bickerstaff brainstem encephalitis. Neurological examination findings include weakness, paralysis, sensory deficits, and reflex changes, while autonomic dysfunction manifests as cardiovascular, respiratory, and gastrointestinal symptoms. Diagnostic evaluation relies on clinical criteria, laboratory tests (e.g., cerebrospinal fluid analysis, nerve conduction studies), and consideration of differential diagnoses. Management strategies encompass supportive care, immunomodulatory therapies (e.g., intravenous immunoglobulin, plasma exchange), and rehabilitation interventions to optimize functional outcomes and promote recovery. Prognosis varies depending on clinical features, treatment response, and complications such as respiratory failure and autonomic instability. Psychosocial impact encompasses psychological effects on patients and caregivers, highlighting the importance of coping strategies and support systems. Recent advances in research focus on emerging treatments, genetic predisposition, and biomarker discovery, offering promise for improving GBS outcomes. Public health implications include vaccination safety concerns and healthcare system considerations for GBS management. Ethical considerations encompass patient autonomy, resource allocation, and end-of-life decision-making.

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

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". 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. 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. 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.

Successful treatment with plasmapheresis of severe Bickerstaff brainstem encephalitis with high cerebrospinal fluid CXCL‐10 levels after COVID‐19 infection: A case report

AbstractBackgroundBickerstaff 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.Case PresentationA 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.ConclusionsBBE related to COVID‐19 with high CXCL‐10 levels can become severe. However, early intensive immunotherapy, including plasmapheresis, might result in favorable prognosis.

Bickerstaff Brainstem Encephalitis With Exceptionally Fast Recovery.

Bickerstaff Brainstem Encephalitis With Exceptionally Fast Recovery.

When Guillain–Barré Syndrome Defies Expectations: A Case of Atypical Features

Abstract Guillain–Barré syndrome (GBS) is one of the most common causes of acute flaccid paralysis. In typical GBS, there are no central nervous system (CNS) features. GBS with prominent CNS involvement can be seen in uncommon variants of GBS (such as Miller Fisher Syndrome and Bickerstaff brainstem encephalitis [BBE]) or rarely, when it coexists with other conditions such as acute disseminated encephalomyelitis (ADEM). We report a case of a 35-year-old male who presented with fever followed by ascending lower motor neuron type paraparesis suggestive of GBS which progressed rapidly to involve the respiratory muscles necessitating invasive mechanical ventilation. The patient had many atypical features, namely, persistent fever, early bladder and bowel involvement, facial twitching, ophthalmoplegia with ptosis, and a comatose state. Based on these clinical features and the investigations done, a diagnosis of GBS with BBE with a possibility of ADEM was made. The patient was managed intensively, but there was no improvement in the neurological manifestations and the patient succumbed to the illness due to ventilator-associated complications.

Clinical, paraclinical and outcome features of 166 patients with acute anti-GQ1b antibody syndrome.

In this retrospective study, we aimed at defining the clinical, paraclinical and outcome features of acute neurological syndromes associated with anti-GQ1b antibodies. We identified 166 patients with neurological symptoms appearing in less than 1month and anti-GQ1b antibodies in serum between 2012 and 2022. Half were female (51%), mean age was 50years (4-90), and the most frequent clinical features were areflexia (80% of patients), distal upper and lower limbs sensory symptoms (78%), ophthalmoplegia (68%), sensory ataxia (67%), limb muscle weakness (45%) and bulbar weakness (45%). Fifty-three patients (32%) presented with complete (21%) and incomplete (11%) Miller Fisher syndrome (MFS), thirty-six (22%) with Guillain-Barre syndrome (GBS), one (0.6%) with Bickerstaff encephalitis (BE), and seventy-three (44%) with mixed MFS, GBS & BE clinical features. Nerve conduction studies were normal in 46% of cases, showed demyelination in 28%, and axonal loss in 23%. Anti-GT1a antibodies were found in 56% of cases, increased cerebrospinal fluid protein content in 24%, and Campylobacter jejuni infection in 7%. Most patients (83%) were treated with intravenous immunoglobulins, and neurological recovery was complete in 69% of cases at 1year follow-up. One patient died, and 15% of patients relapsed. Age > 70years, initial Intensive Care Unit (ICU) admission, and absent anti-GQ1b IgG antibodies were predictors of incomplete recovery at 12months. No predictors of relapse were identified. This study from Western Europe shows acute anti-GQ1b antibody syndrome presents with a large clinical phenotype, a good outcome in 2/3 of cases, and frequent relapses.

Fisher Syndrome

Fisher syndrome is recognized as a variant of Guillain-Barré syndrome, encompassing acute onset immune-mediated neuropathies marked by the classical triad of ataxia, areflexia, and ophthalmoplegia. Generally, Fisher syndrome follows a self-limited course with a good prognosis. Ophthalmoplegia, typically bilateral, progresses to complete external ophthalmoplegia within 1-2 weeks. Ataxia, often very severe, may cause an inability to walk without support despite normal strength. Fisher syndrome is also frequently concomitant with additional clinical features, including ptosis, internal ophthalmoplegia, facial nerve palsy, sensory deficits, and bulbar palsy. The confirmation of an antecedent infection is often established. Among the ganglioside antibodies, anti-GQ1b antibodies exhibit positivity in over 80% of patients. The syndrome manifests in three distinct types: a partial subtype exhibiting only a subset of the triad symptoms, Bickerstaff's brainstem encephalitis marked by impaired consciousness and pyramidal tract signs, and an overlapping subtype with Guillain-Barré syndrome, characterized by weakness in the extremities.

Bickerstaff encephalitis in childhood: a review of 74 cases in the literature from 1951 to today.

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.

A case of primary Sjögren syndrome masquerading as post-COVID Bickerstaff encephalitis

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.

Bickerstaff brainstem encephalitis, an uncommon presentation in a child: a case report

BackgroundThe typical clinical and radiological presentation of Bickerstaff brainstem encephalitis (BBE) has been highlighted in this case report.Case presentationBickerstaff encephalitis is a rare autoimmune inflammatory disorder and is considered a subtype of Guillain–Barré syndrome (GBS) along with Miller Fisher syndrome. The diagnosis of BBE is largely clinical, though laboratory tests and imaging can be of supportive value. We report a case of a 5-year-old child who presented with a classical clinical triad of BBE with characteristic magnetic resonance imaging (MRI) findings.ConclusionsBBE is a rare disease with very few cases being reported with typical clinical and radiological findings. Hence, we reported a typical case of BBE to make an addition to the available literature.

A case of Fulminant Guillain Barre with concurrent Bickerstaff brainstem encephalitis

A case of Fulminant Guillain Barre with concurrent Bickerstaff brainstem encephalitis

Delayed onset Bickerstaff brainstem encephalitis overlapping Miller-Fisher Syndrome during SARS-CoV-2 infection.

Bickerstaff brainstem encephalitis (BBE) is a neuroimmunologic disease characterized by the acute onset of external ophthalmoplegia, ataxia, and consciousness disturbance, mostly subsequent to an infection. BBE is considered to be a variant of Miller-Fisher syndrome (MFS), which also exhibits external ophthalmoplegia and ataxia but not presenting consciousness alterations. Therefore, these two medical conditions are included in the clinical spectrum of the "Fisher-Bickerstaff syndrome" ( Shahrizaila and Yuki in J Neurol Neurosurg Psychiatry 84(5):576-583) [1]. With regard to the etiopathogenesis, increasing evidence worldwide suggests that SARS-CoV-2 infection-enhanced immune response is involved in a wide range of neurological complications such as Guillain-Barré syndrome (GBS), MFS, acute necrotizing encephalitis (ANE), myelitis, acute disseminated encephalomyelitis (ADEM), and, although very rarely, BBE either (Hosseini et al. in Rev Neurosci 32:671-691) [2]. We report a case of a patient affected by delayed onset BBE overlapping MFS during a mild SARS-CoV-2 infection. To the best of our knowledge, similar cases have never been reported.

Bickerstaff’s brainstem encephalitis: a rare case of neurologic complication in Ulcerative Colitis

Bickerstaff’s brainstem encephalitis is a rare autoimmune disorder that presents with ataxia, ophthalmoplegia, disturbance of consciousness and quadriplegia. A 45-year-old man with a history of ulcerative colitis (UC) taking mesalazine (5-aminosalicylic acid) visited the emergency room presenting with ataxia, ophthalmoplegia and a progressively worsening cognitive impairment. Cerebrospinal fluid analysis showed mild elevation in protein and white blood cell count and increased intracranial pressure. Anti-GQ1b autoantibodies were found positive in the patient’s serum and contrast-enhanced brain magnetic resonance imaging showed diffuse leptomeningeal enhancement and pontine lesions. Based on these findings and the patient’s clinical course and history, he was diagnosed with Bickerstaff’s brainstem encephalitis. Mesalazine was discontinued and high-dose steroid pulse therapy was started, followed by intravenous immunoglobulin, which resulted in gradual improvement of the neurologic symptoms. When an ulcerative colitis patient presents with progressive cognitive impairment, quadriplegia and disturbance of consciousness and gait, Bickerstaff brainstem encephalitis should be considered in the differential diagnosis and prompt immunotherapy may lead to favorable prognosis.

Guillain-Barré Syndrome with multiple cranial neuropathies

Background. Guillain-Barré Syndrome (GBS) is an autoimmune reaction against peripheral nerves that manifests clinically as acute polyradiculoneuropathy. Classic sensory-motor, pure motor, paraparesis, pharyngeal-cervical-brachial, Bickerstaff brainstem encephalitis, pure sensory, bilateral facial palsy with paresthesia, and Miller-Fisher syndrome are all known variants of GBS. This case report seeks to describe a case of GBS with involvement of the cranial nerves. Case report. A 39-year-old right-handed Balinese woman presented with LMN (Lower Motor Neuron) type paraparesis with ascending paralysis and involvement of cranial nerves III through XII. The results of the LCS (Liquor Cerebro-Spinal) demonstrate albuminocytological dissociation. According to the patient’s EMNG (electromyoneurography) findings, Guillain-Barré Syndrome was of the AMAN (acute motor axonal neuropathy) variety. The patient was diagnosed with multiple cranial neuropathies and GBS of the AMAN type. EGRIS (Erasmus GBS Respiratory Insufficiency Score) was 3, and EGOS (Erasmus GBS Obstructive Sleep Apnea Score) was also 3. Following IVIG (Intravenous Immunoglobulin) treatment, the patient exhibited clinical improvement (Hughes score decreased from 4 to 2). Discussion. The patient exhibits clinical manifestations of flaccid tetraparesis and multiple cranial nerve paresis. The clinical condition of the patient did not meet the criteria for GBS clinical variation. Symptoms of flaccid tetraparesis that do not involve the senses are classified as the motor-only variant. This patient’s differential diagnosis includes the possibility of MFS and ophthalmoplegia. This patient, however, had flaccid tetraparesis and no ataxia. Electromyoneurography (EMNG) examination produces AMAN-type GBS. The patient was diagnosed with one of the clinical variants of GBS, AMAN-type GBS with multiple cranial neuropathies. Conclusion. A case of GBS of the AMAN type accompanied by multiple cranial neuropathies has been reported.

Idiopathic autoimmune encephalitis with a recurrent course. A case report

We presented a clinical case of idiopathic autoimmune brainstem encephalitis in a 12-year-old female patient. At the onset of the disease, which developed after a respiratory infection, the clinical picture was accompanied by oculomotor and bulbar syndromes. The diagnosis of Bickerstaff brainstem encephalitis was made based on clinical diagnostic criteria and the positive effect of the course of intravenous immunoglobulin therapy. During 3 years of follow-up, there were periods of relapse of the disease, during which symptoms not typical for Bickerstaff stem encephalitis appeared. Against the background of long-term immunosuppressive therapy, there was a long-term remission of about 2 years. The clinical picture, the presence of relapses, the data of additional methods forced to reconsider the diagnosis in favor of idiopathic autoimmune brainstem encephalitis.

Autopsy evidence of central and peripheral demyelination in a case of Guillain-Barré syndrome/ Bickerstaff brainstem encephalitis overlap syndrome

We report a case of a 59-year-old male who had acute, severe, rapidly progressive ascending weakness, which progressed to difficulty of breathing in a span of twelve hours. Neurophysiologic studies showed acute denervation compatible with acute motor axonal neuropathy. He was started on intravenous immunoglobulin therapy on the first day of hospitalization and completed five days of treatment but still developed decrease in sensorium and bilateral ophthalmoplegia. Imaging studies of the brain and cervical spinal cord showed findings that are non-contributory to the clinical presentation, leading to the consideration of Bickerstaff’s brainstem encephalitis. Pulse therapy with high dose methylprednisolone for five days was given however, despite maximal treatment, he expired on the 12th day of illness. Post-mortem immunohistochemical studies of the pons and sural nerve showed areas of inflammation and demyelination in both areas, suggesting combined central and peripheral demyelination in a single patient. Literature review shows that our patient presents with atypical clinical and diagnostic features, different from Bickerstaff’s brainstem encephalitis and combined central and peripheral demyelination, suggesting another disease entity presenting as acute fulminant neuropathy.

The Case Files

The Case Files

Recurrent Bickerstaff Encephalitis: Clinical Manifestation and Potential Treatment Options (P10-5.020)

<h3>Objective:</h3> NA <h3>Background:</h3> Bickerstaff encephalitis is a rare autoimmune disease involving the peripheral and central nervous system, most commonly presenting as a monophasic condition with ophthalmoplegia, ataxia and altered sensorium. <h3>Design/Methods:</h3> We present a rare case of Bickerstaff encephalitis with recurrent episodes along with notable EMG findings and possible therapeutic options to prevent recurrence. <h3>Results:</h3> A 47-year-old woman presented with four days of progressive bilateral ptosis and dysphagia. Her exam was notable for anosognosia, oculobulbar weakness, hyperreflexia, and ophthalmoplegia. Her hospital course was complicated by respiratory failure and autonomic instability. NCS revealed absent F-waves in the left median, ulnar, and radial nerves. MRI, lumbar puncture, malignancy screenings, autoimmune and paraneoplastic panels were all unrevealing. She was found to be ganglioside antibody negative. The patient was treated with IVIg for possible Bickerstaff encephalitis with no improvement. Nine days after completing her IVIg course, she was treated with PLEX followed by rapid recovery. She has since re-presented with dysphagia, ptosis, diplopia and ophthalmoplegia, and has been treated successfully with steroids and PLEX. To prevent further episodes, she was started on immune-modulating therapy, and had been in remission for over one year. Recently, she accidentally discontinued her immune-modulating therapy resulting in a recurrence, which was treated with another session of PLEX. <h3>Conclusions:</h3> Additional studies are needed to guide treatment of Bickerstaff encephalitis and identify which patients are likely to benefit from PLEX over IVIG. Since this disease can lead to life threatening respiratory failure and autonomic instability, immune-modulating therapy might be a reasonable preventive option in rare cases of recurrent Bickerstaff Encephalitis. Further investigation is necessary regarding effective management of this rare clinical syndrome. <b>Disclosure:</b> Dr. Amirkhanashvili has nothing to disclose. Mr. Chang has nothing to disclose. Dr. Shen has nothing to disclose. Dr. Holtzman-Hayes has nothing to disclose. Dr. Friedman has nothing to disclose. Dr. Gluck has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Milstein has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for various law firms. Dr. Milstein has received publishing royalties from a publication relating to health care. Dr. Milstein has a non-compensated relationship as a Board of Directors with New York County Medical Society that is relevant to AAN interests or activities.