Monophasic Course Research Articles

Clinical and imaging features of patients with late-onset myelin oligodendrocyte glycoprotein antibody-associated disease

BackgroundThere is an age-dependent change in the clinical phenotype of Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, the clinical features of late-onset MOGAD have not been well described. MethodsClinical data of 110 MOGAD patients, including 21 late-onset patients with onset age greater than or equal to 50 years old were retrospectively analyzed. ResultsCompared to pediatric- and younger adult-onset ones, late-onset MOGAD patients experienced milder disease onset (p < 0.001), more monophasic course (p < 0.001), fewer relapses (p = 0.007), less cerebrospinal fluid leukocytosis (p = 0.021), less longitudinally extensive transverse myelitis (onset p = 0.026, whole course p = 0.028), fewer lesions in basal ganglia (whole course p = 0.012), thalamus (whole course p = 0.040) and cerebellum (whole course p = 0.028). However, they had more cerebral symptoms (p = 0.021 onset and whole course), more lesions in white matter (onset p = 0.005, whole course p < 0.001) and periventricular area (onset p = 0.026), along with longer and delayed therapeutic intervention (p < 0.001). The main differences in clinical characteristics between late-onset patients with and without these brain involvements might be comorbidities. ConclusionsLate-onset MOGAD are more likely to experience delayed diagnosis. Brain involvement may be modulated by comorbidities of the elderly, which alter the clinical manifestations of late-onset MOGAD.

Myelin oligodendrocyte glycoprotein antibody‐associated disorders: An overview

AbstractIn recent years, there is growing evidence of associations between antibodies against myelin oligodendrocyte glycoprotein (MOG) and several phenotypes of acute inflammatory demyelinating diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis, brainstem, and cerebral cortical encephalitis, called MOG antibody associated disorders (MOGAD). Monophasic course is known in about half of cases especially in pediatric onset ADEM and optic neuritis, mainly in cases with transient positivity of MOG antibody. Pathological features of MOGAD are considered as acute demyelinating lesions with CD4 dominant cell infiltrations, the deposition of humoral immunity, perivascular inflammation and perivenous demyelination, which is distinct from multiple sclerosis. Now the diagnosis of MOGAD is based on the international panel criteria of MOGAD launched in 2023, which the diagnostic frameworks are three parts, including MOGAD‐specific clinical features, MOG antibody positivity, and the exclusion of other diseases. The prognosis of MOGAD patients is considered relatively mild, but the problem is refractory relapsing cases. For its prevention, there are no approved drugs, but oral tapering corticosteroids, immunosuppressants such as azathioprine and mycophenolic mofetil, rituximab, and the maintenance intravenous immunoglobulin are recommended, and now there are a few clinical trials of promising biological drugs already approved in other neurological disorders.

Acquired hyperexcitable peripheral nerve disorders: Clinical and laboratory features, therapeutic responses, and long-term follow-up.

Hyperexcitable peripheral nerve disorders (HPNDs) are rare. Although their clinical and laboratory features have been well studied, information on treatment and follow-up is limited. The aim of this study is to explore the long-term clinical, investigative, and therapeutic profile of patients with acquired HPNDs. This study retrospectively analyzed patients from a single tertiary care center with HPND (January 2012 to January 2022). Patients were recruited according to published inclusion and exclusion criteria. Details of clinical features, diagnostic tests, therapeutic interventions, and follow-up were recorded. This study included patients with follow-up of 2 or more years. A total of 32 patients (M = 26, F = 6) were studied. The common clinical features included myokymia, neuropathic or shock-like pain, cramps, sleep disturbances, encephalopathy, cerebellar ataxia, and seizures. A total of 81.25% of patients responded favorably to corticosteroids and membrane stabilizers. Among the nonresponders, five received intravenous immunoglobulin (IVIG), and one received plasma exchange (PLEX). Two patients required rituximab due to poor responses to the above treatments. The mean duration of response was 6 weeks (4-24 weeks) from the initiation of treatment. All patients had favorable outcomes, reaching clinical remission within 1-5 years from the initiation of treatment. Only two patients had relapses. Immunotherapy could be stopped in 78% of patients within 3 years and 100% by 5 years. Chronic immunosuppression starting with corticosteroids is required for satisfactory outcomes of HPNDs. These disorders usually run a monophasic course, and relapses are uncommon.

Clinical spectrum of myelin oligodendrocyte glycoprotein antibody-associated disease in Brazil: a single-center experience.

Anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibody-associated disease (MOGAD) is an immune-mediated neurological disorder with a broad spectrum of clinical presentation that is often difficult to distinguish from other demyelinating diseases, such as multiple sclerosis and neuromyelitis optica spectrum disorder. To describe the clinical and paraclinical characteristics of MOGAD in a Brazilian tertiary center. We retrospectively reviewed the records of adult and pediatric patients who tested positive for anti-MOG antibodies and presented with clinical and radiological diseases compatible with MOGAD. Forty-one patients (10 children) were included: 56% female, 58% Caucasian, mean age at onset 31 years (range 6-64), with a mean disease duration of 59.6 months (range 1-264 months). The most frequent onset presentation was optic neuritis (68%), acute disseminated encephalomyelitis (ADEM, 12%), and myelitis (10%). A monophasic disease course was observed in 49%. EDSS median was 2.1 at the last visit. Most patients (83%) were under continuous immunosuppressive treatment. Azathioprine was the first-line treatment in 59%. In all ADEM cases, conus, and root involvement was radiologically observed on MRI. Brazilian MOGAD patients presented with a similar spectrum of previously reported MOGAD phenotypes. Conus and spinal root involvement seems to be frequently present in MOGAD-ADEM and could serve as radiologic characteristics of this clinical entity.

Simultaneous Isolation of Principal Central Nervous System-Resident Cell Types from Adult Autoimmune Encephalomyelitis Mice.

Experimental autoimmune encephalomyelitis (EAE) is the most common murine model for multiple sclerosis (MS) and is frequently used to further elucidate the still unknown etiology of MS in order to develop new treatment strategies. The myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55) EAE model reproduces a self-limiting monophasic disease course with ascending paralysis within 10 days after immunization. The mice are examined daily using a clinical scoring system. MS is driven by different pathomechanisms with a specific temporal pattern, thus the investigation of the role of central nervous system (CNS)-resident cell types during disease progression is of great interest. The unique feature of this protocol is the simultaneous isolation of all principal CNS-resident cell types (microglia, oligodendrocytes, astrocytes, and neurons) applicable in adult EAE and healthy mice. The dissociation of the brain and the spinal cord from adult mice is followed by magnetic-activated cell sorting (MACS) to isolate microglia, oligodendrocytes, astrocytes, and neurons. Flow cytometry was used to perform quality analyses of the purified single-cell suspensions confirming viability after cell isolation and indicating the purity of each cell type of approximately 90%. In conclusion, this protocol offers a precise and comprehensive way to analyze complex cellular networks in healthy and EAE mice. Moreover, required mice numbers can be substantially reduced as all four cell types are isolated from the same mice.

Clinical risk factors for recurrence of myelin oligodendrocyte glycoprotein antibody-associated disease.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a CNS demyelinating disease that targets myelin oligodendrocyte glycoprotein and recurs in approximately 50% of patients after the initial episode. Multiple relapses may have adverse consequences, but the factors influencing relapse are unclear. This study analyzed the clinical risk factors for relapse in patients with MOGAD. Twenty-four MOGAD patients diagnosed at the Department of Neurology, First Hospital of Shanxi Medical University from March 2018 to November 2020 were retrospectively analyzed in this study. The patients were divided into a monophasic course and a relapsing course according to their disease process. The patients' epidemiological characteristics, clinical symptoms, laboratory tests, imaging features, and regression were summarized. Comparisons were made between the monophasic and relapsing course to identify the possible factors associated with the clinical features and recurrence. At a mean follow-up of 15 months (range: 8 to 24 months), seventeen of the 24 patients (70.8%) had monophasic disease, and 7 (29.2%) had relapsing disease. Among the 24 patients, 17 patients (70.9%) had low Myelin oligodendrocyte glycoprotein antibody (MOG-IgG) serum titers (<1:100), and 7 patients (29.1%) had high MOG-IgG serum titers (≥1:100). Compared to the monophasic course group, patients in the relapsing course group had higher serum antibody titers (71.4% vs. 11.7%, P=0.035). Onset phenotypes included encephalitis (50%), myelitis (45.8%), and optic neuritis (45.8%), with 66.7% of patients starting with a single phenotype and 33.3% starting with two or more phenotypes. Optic neuritis was more common in the relapsing course group (85.7%) than the monophasic course group (29.4%) (P=0.023). There was no significant difference between the two groups in the proportion of myelitis and encephalitis. A previous history or background of immunological disease was present in 33.3% of patients, with a significantly higher proportion in the relapsing course group than in the monophasic course group (71.4% vs. 17.6%, P=0.021). Regarding ancillary examinations, the relapsing course group was more likely to have CSF leukocytes higher than 50/mm3 than the monophasic course group (60% vs. 0, P=0.045), while there was no difference in the number and site distribution of the lesions on MRI. Our study suggests that the most common clinical manifestations of MOGAD are diminished visual acuity, limb/facial numbness, and ocular/orbital pain. The onset phenotype consisting of optic neuritis, a history of immune disease, high antibody titers (≥1:100), and high cerebrospinal fluid leukocytes (above 50/mm3) suggests a high likelihood of MOGAD recurrence.

Clinical, Neurophysiologic, and Pathologic Features in Patients With Early-Onset Postradiation Neuropathy.

The objective of this study was to study early-onset radiation-induced neuropathy reviewing neurologic course, steroid response, and available nerve biopsies. Patients coded with radiation-induced neuropathy within 6 months of radiation were reviewed from January 1,1999, to August 31, 2022. Patients had to have electrodiagnostically confirmed neuropathy localized within or distal to radiation fields. Neurologic course and nerve biopsies were reviewed. Twenty-eight patients (16 male and 12 female patients, mean age 63.8 years) were identified. The average radiation dose was 4,659 cGy (range 1,000-7,208). Tumor infiltration was not observed on MRI and PET. Postradiation onsets averaged 2 months (range 0-5). Localizations included brachial (n = 4) plexopathies, lumbosacral (n = 12) plexopathies, radiculopathies (n = 10), and mononeuropathies (n = 2). Neuropathic pain (n = 25) and weakness (n = 25) were typical. The clinical courses were subacute monophasic (n = 14), chronic progressive (n = 8), or static (n = 1), and 5 were without follow-up. Nerve biopsies (n = 8) showed an inflammatory ischemic process with perivascular inflammatory infiltrates (n = 7) or microvasculitis (n = 2). Nine patients, 7 with monophasic courses, received steroid burst therapy with symptom improvement in 8. No patients recovered entirely back to baseline. In contrast to chronic radiation-induced neuropathy, early-onset patients most commonly have painful monophasic courses with residual deficits, possibly steroid responsive. An ischemic inflammatory pathogenesis is suggested.

Clinical characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease according to their epitopes.

The detection of myelin oligodendrocyte glycoprotein autoantibodies (MOG-Ab) is essential for the diagnosis of MOG-Ab-associated disease (MOGAD). The clinical implications of different epitopes recognized by MOG-Ab are largely unknown. In this study, we established an in-house cell-based immunoassay for detecting MOG-Ab epitopes and examined the clinical characteristics of patients with MOG-Ab according to their epitopes. We conducted a retrospective review of patients with MOG-Ab-associated disease (MOGAD) in our single center registry, and collected serum samples from enrolled patients. Human MOG variants were generated to detect epitopes recognized by MOG-Ab. The differences in clinical characteristics according to the presence of reactivity to MOG Proline42 (P42) were evaluated. Fifty five patients with MOGAD were enrolled. Optic neuritis was the most common presenting syndrome. The P42 position of MOG was a major epitope of MOG-Ab. The patients with a monophasic clinical course and childhood-onset patients were only observed in the group that showed reactivity to the P42 epitope. We developed an in-house cell-based immunoassay to analyze the epitopes of MOG-Ab. The P42 position of MOG is the primary target of MOG-Ab in Korean patients with MOGAD. Further studies are needed to determine the predictive value of MOG-Ab and its epitopes.

The Role of Microorganisms in the Etiopathogenesis of Demyelinating Diseases.

Multiple sclerosis (MS), neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are inflammatory diseases of the central nervous system (CNS) with a multifactorial aetiology. Environmental factors are important for their development and microorganisms could play a determining role. They can directly damage the CNS, but their interaction with the immune system is even more important. The possible mechanisms involved include molecular mimicry, epitope spreading, bystander activation and the dual cell receptor theory. The role of Epstein-Barr virus (EBV) in MS has been definitely established, since being seropositive is a necessary condition for the onset of MS. EBV interacts with genetic and environmental factors, such as low levels of vitamin D and human endogenous retrovirus (HERV), another microorganism implicated in the disease. Many cases of onset or exacerbation of neuromyelitis optica spectrum disorder (NMOSD) have been described after infection with Mycobacterium tuberculosis, EBV and human immunodeficiency virus; however, no definite association with a virus has been found. A possible role has been suggested for Helicobacter pylori, in particular in individuals with aquaporin 4 antibodies. The onset of MOGAD could occur after an infection, mainly in the monophasic course of the disease. A role for the HERV in MOGAD has been hypothesized. In this review, we examined the current understanding of the involvement of infectious factors in MS, NMO and MOGAD. Our objective was to elucidate the roles of each microorganism in initiating the diseases and influencing their clinical progression. We aimed to discuss both the infectious factors that have a well-established role and those that have yielded conflicting results across various studies.

Clinical spectrum and prognosis of pathologically confirmed atypical tumefactive demyelinating lesions

To describe the clinical spectrum and prognosis of atypical tumefactive demyelinating lesions (TDLs), which were confirmed by pathology. A total of 11 patients were diagnosed with atypical TDLs confirmed by brain biopsy and surgery between January 2006 and December 2017. The clinical spectrum and prognosis in these patients were analyzed. The patients’ ages ranged from 29 to 62 years, with a mean age of 48.9 years; 72.7% were males. The Expanded Disability Status Scale (EDSS) of the patients with first onset was 2.36. Most of the patients started with limb numbness and weakness (45.5%) or alalia (27.2%). The mean time from symptom onset to biopsy or surgery was 12.9 days (3–30 days). Most of the patients had solitary lesions (72.7%), supratentorial lesions (90.9%, particularly predominant in the frontal, temporal, and parietal lobes), moderate edema (63.6%), mild mass effect (54.5%), and patchy lesions (54.5%). Among them, three patients were positive for myelin basic protein (MBP) and one patient was positive for myelin oligodendrocyte glycoprotein (MOG). The patients were followed up for an average of 6.9 years (2–14 years), and recurrent TDLs were observed in 2 patients. Except for the 2 patients who relapsed, only 1 of the 9 patients died; the other 8 patients improved or maintained the status quo (the EDSS scores were lower or unchanged). The patients did not have any serious nervous system injury at onset, and the main presentation included extremity weakness, headache or dizziness, and alalia. The most common form was patchy on MRI enhancement. Cerebrospinal fluid and demyelination test can be an indicator of TDLs, and seizures may be a poor prognostic indicator. Most atypical TDLs have monophasic courses and good outcomes. The effect of neurosurgery alone was good in our group, and the effect of surgery on atypical TDLs can be further studied.

Clinical, imaging features and outcomes of patients with anti-GFAP antibodies: a retrospective study.

To evaluate and compare the clinical features, imaging, overlapping antibodies, and prognosis of pediatric and adult patients with anti-GFAP antibodies. This study included 59 patients with anti-GFAP antibodies (28 females and 31 males) who were admitted between December 2019 and September 2022. Out of 59 patients, 18 were children (under 18 years old), and 31 were adults. The overall cohort's median age at onset was 32 years old, 7 for children, and 42 for adults. There were 23 (41.1%) patients with prodromic infection, 1 (1.7%) patient with a tumor, 29 (53.7%) patients with other non-neurological autoimmune diseases, and 17 (22.8%) patients with hyponatremia. Fourteen (23.7%) patients had multiple neural autoantibodies, with the AQP4 antibody being the most common. Encephalitis (30.5%) was the most common phenotypic syndrome. Common clinical symptoms included fever (59.3%), headache (47.5%), nausea and vomiting (35.6%), limb weakness (35.6%), and disturbance of consciousness (33.9%). Brain MRI lesions were primarily located in the cortex/subcortex (37.3%), brainstem (27.1%), thalamus (23.7%), and basal ganglia (22.0%). Spinal cord MRI lesions often involved the cervical and thoracic spinal cord. There was no statistically significant difference in the MRI lesion site between children and adults. Out of 58 patients, 47 (81.0%) had a monophasic course, and 4 died. The last follow-up showed that 41/58 (80.7%) patients had an improved functional outcome (mRS <3), and children were more likely than adults to have no residual disability symptoms (p = 0.001). There was no statistically significant difference in clinical symptoms and imaging findings between children and adult patients with anti-GFAP antibodies; Patients with anti-GFAP antibodies may present with normal MRI findings or delayed MRI abnormalities, and patients with overlapping antibodies were common. Most patients had monophasic courses, and those with overlapping antibodies were more likely to relapse. Children were more likely than adults to have no disability. Finally, we hypothesize that the presence of anti-GFAP antibodies is a non-specific witness of inflammation.

Clinical Manifestation, Auxiliary Examination Features and Prognosis of GFAP Autoimmunity: a Chinese Cohort Study (P5-5.029)

<h3>Objective:</h3> To report the clinical manifestation and auxiliary examination features of 15 Chinese patients with glial fibrillary acidic protein (GFAP) autoimmunity. <h3>Background:</h3> GFAP astrocytopathy is a corticosteroid responsive inflammatory central nervous system (CNS) disorder spectrum predominantly affecting meninges, brain, spinal cord, and optic nerve mimics infectious meningoencephalitis. IgG antibodies binding to GFAP are specific biomarkers with diagnostic significance. <h3>Design/Methods:</h3> From June 2016 to December 2019, patients with suspected neurological autoimmune disease were scanned for autoantibodies by immunohistochemistry. Samples showed a characteristic immunoreactive pattern reminiscent of GFAP of astrocytes were selected and confirmed by cell-based assay. <h3>Results:</h3> Fifteen patients (8 male, 7 female) with a median age at onset of 53 years were identified as GFAP-IgG positive. Eleven of 15 patients presented with an acute monophasic course, of which 10 had antecedent flu-like symptoms. The predominant phenotype was meningoencephalitis (46.7%), followed by meningoencephalomyelitis in 40% of cases. Magnetic resonance imaging revealed enhancement in 10 of 13 patients. Inflammatory CSF showed mild lymphocyte-predominant pleocytosis with a median of 51/μl, elevated protein with a median of 87.5mg/dl. Five of six patients tested for CSF specific oligoclonal bands were positive. Five patients had coexisting antibodies, including NMDAR-IgG in 3 patients, Yo and MOG-IgG in one each patient. One patient underwent stereotactic brain biopsy and neuropathology diagnosis was diffuse large B-cell lymphoma with normal reactive fibrillary astrocytes. One patient had ovarian teratoma. Eleven of 15 patients received both intravenous immunoglobulin and steroids. Among them, 3 patients also received immunosuppressive agents later. During 2-year follow-up, nine of 15 patients achieved complete clinical remission. <h3>Conclusions:</h3> The clinical presentation of GFAP astrocytopathy is heterogeneous, including acute monophasic course or chronic relapsing courses. Patients with an acute monophasic course with antecedent infection symptoms responded well to immunotherapy. In case of primary central nervous system lymphoma, GFAP autoimmunity doesn’t equal to autoimmune GFAP astrocytopathy. <b>Disclosure:</b> Dr. Liu has nothing to disclose. Dr. Zhang has nothing to disclose.

Early Post Radiation Neuropathy: Complex Pathogenesis Including Microvasculitis and Tumor Spread (P14-8.001)

<h3>Objective:</h3> To describe patients with early radiation-induced peripheral nerve injury and investigate potential pathogenic mechanism(s). <h3>Background:</h3> Radiation-induced neuropathy typically occurs up to decades after radiation from neural fibrosis with insidious, painless progressive weakness. Reports of early radiation-associated neuropathies are lacking. <h3>Design/Methods:</h3> Patient cases labeled as “radiation neuropathy” were electronically retrieved from our electromyography (EMG) and Mayo Data Explorer databases between January 2014 to August 2022. Inclusion criteria included neural deficits within 6 months of radiation, EMG testing, and available follow-up nerve imaging. <h3>Results:</h3> Twenty-two patients (9 female, mean age 63 years [range 34–84]) were identified with a history of squamous (n=6), prostate (n=5), breast (n=3), rectal (n=2), hematologic (n=2), and other (n=4) cancers. Average radiation dose was 4491 cGy (range 1000–7208). Time to symptom onset averaged 1.9 months (range 0–4). Pre-radiation chemotherapy occurred in most (n=16). All neuropathies occurred in the same radiation territory, but most neuropathies (n=17) occurred distal to the radiation site. EMG-confirmed neuropathies included radiculopathies (n=10), brachial and lumbosacral plexopathies (n=10), and mononeuropathies (n=2). EMG myokymia was seen in few (n=6). Patients reported primarily painful paresthesias (n=18) and weakness (n=18). Clinical courses were monophasic (n=8), progressive (n=8), static (n=2), and unclear without follow-up (n=4). Follow-up neural MRI did not suggest infiltrative disease (n=21), but based on tumor location and progressive course, microscopic infiltration was suspected. Two patients had nerve biopsies showing prominent inflammation around epineural microvessels with vessel wall injury (microvasculitis). One biopsy revealed neoplastic spread of rectal squamous cell cancer. Steroid burst therapy was attempted in 6 patients; 5 reported benefits, and 4 had monophasic courses. <h3>Conclusions:</h3> Early-onset post radiation neuropathies having pain and monophasic courses are supported by steroid response and biopsy-confirmed microvasculitis to have an inflammatory-immune mechanism. Exclusion of infiltrative cancer and an idiosyncratic radiation injury with progressive course are important to consider. <b>Disclosure:</b> Dr. Skolka has nothing to disclose. Dr. Uhm has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Zai Lab. Dr. Ma has nothing to disclose. Dr. Santilli has nothing to disclose. Mr. Meiling has nothing to disclose. Dr. Sandroni has nothing to disclose. Dr. Staff has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Stem Cell Research &amp; Therapy. Dr. Pinto has nothing to disclose. Dr. Dyck has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Akcea/Ionis. Dr. Klein has a non-compensated relationship as a Klein with Neurology Journal that is relevant to AAN interests or activities.

GFAP astrocytopathy presenting after COVID-19 infection with meningoencephalomyelitis and good recovery with immunotherapy (P14-4.001)

<h3>Objective:</h3> To describe a case of post-COVID-19 GFAP astrocytopathy presenting with meningoencephalomyelitis. <h3>Background:</h3> Glial fibrillary acidic protein (GFAP) astrocytopathy is a newly described autoimmune disorder that presents with meningoencephalitis, myelitis and cerebellar dysfunction. Differential diagnosis includes inflammatory, neoplastic and infectious etiologies. GFAP astrocytopathy associated meningoencephalomyelitis is a rare, but treatable neurologic sequela of COVID-19. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 62-year-old man presented with progressive confusion, recurrent falls, and weight loss with initial symptom onset during COVID-19 infection 6 weeks prior. MRI showed patchy parenchymal and ependymal enhancement in the brainstem and temporal lobe as well as T2 hyperintensity throughout the cervical and thoracic cord consistent with transverse myelitis. Four lumbar punctures demonstrated elevated protein between 100–200 mg/dl and significant lymphocytic pleocytosis with 300–600 nucleated cells. Extensive infectious work-up was negative. Malignancy work-up showed PET-CT avidity in the spinal cord and positive MYD88 mutation in the CSF, possibly indicating a lymphoproliferative condition. However, CSF cytology, CSF flow cytometry and a bone marrow biopsy showed no evidence of malignancy on repeated testing. CSF autoimmune encephalopathy panel demonstrated high titers of GFAP antibodies. Initial treatment included pulse-dose steroids and IVIG with minimal improvement in cognition. He was then treated with pulse-dose steroids and rituximab with markedly improved cognition, motor function and appetite. Subsequent 2-month MRI demonstrated partial resolution of his cerebral and spinal lesions. <h3>Conclusions:</h3> Subacute meningoencephalitis, with or without myelitis, is a typical presentation of GFAP astrocytopathy. Other symptoms include ataxia, blurred vision with optic disc edema, dysautonomia, seizures, area postrema syndrome and psychiatric symptoms. Most patients have a steroid responsive monophasic course, but approximately 20% of patients have relapsing disease. GFAP astrocytopathy should be on the differential for meningoencephalomyelitis, especially with infectious prodrome, such as COVID-19 infection. Early recognition and treatment can lead to improvement of neurologic deficits and a good outcome. <b>Disclosure:</b> Dr. Song has nothing to disclose. Dr. Oetjen has nothing to disclose. Dr. Harrold has nothing to disclose. Dr. Dietrich has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Dietrich has received publishing royalties from a publication relating to health care. Kien-Ninh Ly has nothing to disclose. Dr. Venna has nothing to disclose.

Mild Encephalopathy with Reversible Splenium Lesion Associated with SARS-CoV-2 Infection (P14-4.007)

<h3>Objective:</h3> NA <h3>Background:</h3> Encephalopathy secondary to SARS-CoV-2 infection has been previously reported, although neuroimaging in many of these patients is typically unremarkable. There are only a few reported cases of patients with SARS-CoV-2 infection associated with mild encephalopathy with a reversible splenial lesion (MERS) on imaging. MERS has a monophasic course of encephalopathy, marginal pleocytosis in the cerebrospinal fluid, and a characteristic MRI finding of a reversible lesion in the splenium of the corpus callosum. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 68-year-old woman presented to the hospital with altered mental status. The patient was found unresponsive during a welfare check at home. Initial neurological evaluation revealed that the patient was awake, alert, and oriented to name and age but not date and time. Speech was fluent with intact naming, repetition, and comprehension. Polymerase chain reaction for SARS-CoV-2 was positive, and history revealed that patient was not vaccinated. CT of the head was unrevealing. MRI of the brain revealed increased signal in the corpus callosum on FLAIR with low diffusivity on diffusion-weighted imaging. The patient was given tocilizumab, dexamethasone, remdesivir, and ceftriaxone to treat superimposed bacterial pneumonia. Encephalopathy improved gradually throughout the hospital course, and the patient was transitioned to an inpatient rehabilitation facility. Repeat brain MRI five weeks from initial imaging showed resolution of the hyperintensity and focus of low diffusivity in the splenium. <h3>Conclusions:</h3> This is a rare case of MERS triggered by SARS-CoV-2 in a patient who presented with encephalopathy. This case expands the clinical spectrum of neurological manifestations associated with SARS-CoV-2 and adds to the already existing literature. Further investigation is imperative for a better understanding of the pathophysiology and management of this entity to avoid unnecessary invasive diagnostic and therapeutic interventions. <b>Disclosure:</b> Dr. Kokash has nothing to disclose. Dr. Reyes has nothing to disclose. Dr. Yacoub has nothing to disclose.

Balo’s Concentric Sclerosis presenting as Sensorineural Hearing Loss (P14-3.007)

<h3>Objective:</h3> Multiple sclerosis (MS) can affect other cranial nerves apart from optic nerve. We report an interesting case of Balo’s concentric sclerosis (BCS) that presented with sensorineural hearing loss (SNHL). <h3>Background:</h3> BCS is a rare variant of MS. It derives its name from the concentric pattern of demyelination alternating with preserved myelin seen on magnetic resonance imaging (MRI). It typically has a fulminant monophasic clinical course with a fatal outcome although there has been an increasing number of cases reported with a benign clinical course. <h3>Design/Methods:</h3> NA <h3>Results:</h3> 48-year-old presented to our neuro-immunology clinic for evaluation of abnormal MRI which revealed non-enhancing T2 hyperintensities in juxta-cortical, peri-ventricular and infratentorial cerebellar lesions concerning for demyelination. He had tinnitus and SNHL of right ear ongoing for 3–4 months prior to presentation. Extensive workup was pursued to rule out MS mimics including nutritional, autoimmune, and infectious etiologies. LP revealed no evidence of oligoclonal bands. He was originally diagnosed with radiologically isolated syndrome with plans to monitor with MRI brain annually for surveillance. Repeat MRI brain a year later revealed new non-enhancing concentric juxta-cortical lesion along the right frontal operculum exhibiting a laminated appearance with surrounding perilesional edema consistent with BCS. He had no new neurological symptoms in the interim. On re-evaluation, his auditory symptoms were deemed as a clinical event, and he was diagnosed with MS with subsequent initiation of disease modifying therapy. <h3>Conclusions:</h3> BCS may occur simultaneously with MS like lesions or may herald the onset of MS. SNHL is a rare manifestation of MS with demyelinating lesion along the course of vestibulocochlear nerve or nucleus in brain stem. MRI brain can fail to reveal signs of demyelination either due to timing of MRI brain from symptom onset or sub-optimal diagnostic accuracy as vestibular evoked myogenic potentials have detected demyelinating lesions which are invisible on MRI brain. <b>Disclosure:</b> Dr. Potluri has nothing to disclose. Dr. Samaniego has nothing to disclose. Dr. Lannen has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Genentech. Dr. Lannen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for TG Therapeutics.

High and Persistent Anti-GM1 Antibody Titers Are Associated With Poor Clinical Recovery in Guillain-Barré Syndrome.

Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy that may follow a preceding infection inducing a cross-reactive antibody response to glycosphingolipids in peripheral nerves. The immune response in GBS is considered to be short lasting, explaining its monophasic clinical course. However, the disease course varies between patients, and residual deficits frequently occur. The duration of the antibody response has not been defined extensively in GBS, and the persistence of these antibodies may impair clinical recovery. The aim of this study was to determine the titer course of serum antibody titers to the ganglioside GM1 in relation to clinical course and outcome in patients with GBS. Acute-phase sera from patients with GBS included in previous therapeutic trials were screened for anti-GM1 IgG and IgM antibodies in ELISA. Anti-GM1 antibody titers were determined in sera collected at entry and during a 6-month follow-up. Clinical course and outcomes were compared between groups based on the titer course. Anti-GM1 antibodies were detected in 78 (20.7%) of 377 included patients. The anti-GM1 IgG and IgM antibody titer course was highly variable between patients. A subset of anti-GM1-positive patients had persistent anti-GM1 antibodies at 3 months (n = 27/43 [62.8%]) and 6 months (n = 19/41 [46.3%]). Patients with a high anti-GM1 IgG and IgM titer at entry recovered more slowly and less complete than anti-GM1-negative patients (IgG: p = 0.015, IgM: p = 0.03). High vs low IgG titers were independently associated with poor outcome after correcting for known prognostic factors (p = 0.046). Among patients with a high anti-GM1 IgG titer at entry, a slow titer decline was associated with poor outcome at 4 weeks (p = 0.003) and 6 months (p = 0.032). Persistent high IgG titers at 3 and 6 months were associated with poor outcome at 6 months (3 months: p = 0.022, 6 months: p = 0.004). High anti-GM1 IgG and IgM antibody titers at entry and persistent high anti-GM1 IgG antibody titers are associated with poor outcome in patients with GBS. Antibody persistency indicates ongoing antibody production long after the acute disease state in GBS. Further research is required to determine whether antibody persistency interferes with nerve recovery and is a target for treatments.

Clinical features of the first attack with leukodystrophy-like phenotype in children with myelin oligodendrocyte glycoproteinantibody-associated disorders.

Myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) is identified autoimmune disorder with a predominance in paediatric patients, and the disease spectrum has expanded with clinical and radiological patterns. The aim of the study was to describe the clinical characteristics of the first attack with leukodystrophy-like phenotype with MOGAD in children. Patients hospitalized at the Children's Hospital of Chongqing Medical University from June 2017 to October 2021 with positive MOG antibodies and phenotype of leukodystrophy-like (symmetric white matter lesions) were retrospectively analyzed. Cell-based assays (CBAs) were used to test MOG antibodies. Four cases from 143 MOGAD patients were recruited, with two females and two males. The age of onset is all under 6 years old. At the last follow-up, four cases exhibited a monophasic course, including ADEM in three patients and encephalitis in one patient. The mean EDSS score at onset was 4.62 ± 2.93, and the modified Rankin score (mRS) was 3.00 ± 1.82. First-attack symptoms include fever, headache, vomiting, seizure, loss of consciousness, emotional and behavioural disorder, and ataxia. The brain MRI showed prominent extensive and essentially symmetric distribution lesions in the white matter. All patients showed clinical and partial radiological improvement after intravenous immunoglobulin and/or glucocorticoid treatment. The first attack with MOGAD onset of leukodystrophy-like phenotype was more frequently seen in younger children than other phenotype patients. The patients may show impressive neurologic disorders, but most patients who receive immunotherapy have a good prognosis.

Two case reports and a literature review of typical GBS and rare GBS variants associated with COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019, and is the infectious agent that caused the coronavirus disease 2019 (COVID-19) pandemic. Although respiratory and gastrointestinal manifestations of SARS-CoV-2 are well defined, the spectrum of neurological involvement is less defined. The classic type of Guillain–Barré syndrome (GBS) progresses over days to weeks and has a monophasic course. Areflexia/hyporeflexia and ascending and symmetrical paralysis are observed clinically in patients. It is an autoimmune process that typically leads to the destruction of myelin after infection. There have been numerous reports of adult patients with the coexistence of GBS disease and active COVID-19 illness, but this number is lacking for children. In this study, we present a literature review of the etiological correlation between SARS-CoV-2 and GBS and describe the cases of two pediatric patients with acute monophasic Guillain–Barré syndrome (GBS) during active COVID-19 infection.

Tick-borne encephalitis: Acute clinical manifestations and severity in 581 cases from Germany, 2018–2020

Tick-borne encephalitis (TBE) is a growing public health problem with an average of 361 cases notified annually to Germany's passive surveillance system since 2001. We aimed to assess clinical manifestations and identify covariates associated with severity. We included cases notified 2018-2020 in a prospective cohort study and collected data with telephone interviews, questionnaires to general practitioners, and hospital discharge summaries. Covariates' causal associations with severity were evaluated with multivariable logistic regression, adjusted for variables identified via directed acyclic graphs. Of 1220 eligible cases, 581 (48%) participated. Of these, 97.1% were not (fully) vaccinated. TBE was severe in 20.3% of cases (children: 9.1%, ≥70-year-olds: 48.6%). Routine surveillance data underreported the proportion of cases with central nervous system involvement (56% vs. 84%). Ninety percent required hospitalization, 13.8% intensive care, and 33.4% rehabilitation. Severity was most notably associated with age (odds ratio (OR): 1.04, 95% confidence interval (CI): 1.02-1.05), hypertension (OR: 2.27, 95%CI: 1.37-3.75), and monophasic disease course (OR: 1.67, 95%CI: 1.08-2.58). We observed substantial TBE burden and health service utilization, suggesting that awareness of TBE severity and vaccine preventability should be increased. Knowledge of severity-associated factors may help inform patients' decision to get vaccinated.