Relapsing Anti-GAD65-Associated Encephalitis Responsive to Thymoma Resection, Radiation, and Immunomodulatory Therapy.

Herein we describe a case of relapsing anti-GAD65-associated encephalitis which was responsive to the combination of thymoma resection, external beam radiotherapy, and immunomodulatory therapy. The case illustrates the value of remaining vigilant for the possibility of paraneoplastic syndromes in the context of anti-GAD65 antibodies and thymoma. It also illustrates that tumor-directed therapies may offer additional benefit beyond immunomodulatory therapy alone.

Suspected autoimmune encephalitis: A retrospective study of patients referred for therapeutic plasma exchange.

INTRODUCTION: Autoimmune encephalitis (AE) comprises a heterogeneous group of autoantibody-mediated disorders targeting the brain parenchyma. Therapeutic plasma exchange (TPE), one of several first-line therapies for AE, is often initiated when AE is suspected, albeit prior to an established diagnosis. We sought to characterize the role of TPE in the treatment of suspected AE. METHODS: A single-center, retrospective analysis was performed of adults (≥18 years) who underwent at least one TPE procedure for "suspected AE." The following parameters were extracted and evaluated descriptively: clinicopathologic characteristics, treatment course, TPE-related adverse events, outcomes (e.g., modified Rankin scale [mRS]), and diagnosis once investigation was complete. RESULTS: A total of 37 patients (median age 56 years, range 28-77 years, 62.2% male) were evaluated. Autoimmune antibody testing was positive in serum for 43.2% (n = 16) and cerebrospinal fluid for 29.7% (n = 11). Patients underwent a median of five TPE procedures (range 3-16), with 97.3% (n = 36) via a central line and 21.6% (n = 8) requiring at least one unit of plasma as replacement fluid. Fifteen patients (40.5%) experienced at least one TPE-related adverse event. Compared with mRS at admission, the mRS at discharge was improved in 21.6% (n = 8), unchanged in 59.5% (n = 22), or worse in 18.9% (n = 7). Final diagnosis of AE was determined to be definite in 48.6% (n = 18), probable in 8.1% (n = 3) and possible in 27.0% (n = 10). Six (16.2%) patients were ultimately determined to have an alternate etiology. CONCLUSION: Empiric TPE for suspected AE is generally well-tolerated. However, its efficacy remains uncertain in the absence of controlled trials, particularly in the setting of seronegative disease.

Quantitative brain 18F-FDG PET/CT analysis in seronegative autoimmune encephalitis.

OBJECTIVE: Brain 18F-FDG PET/CT is a useful diagnostic in evaluating patients with suspected autoimmune encephalitis (AE). Specific patterns of brain dysmetabolism have been reported in anti-NMDAR and anti-LGI1 AE, and the degree of dysmetabolism may correlate with clinical functional status.18FDG-PET/CT abnormalities have not yet been described in seronegative AE. METHODS: We conducted a cross-sectional analysis of brain18FDG-PET/CT data in people with seronegative AE treated at the Johns Hopkins Hospital. Utilizing NeuroQ™ software, the Z-scores of 47 brain regions were calculated relative to healthy controls, then visually and statistically compared for probable and possible AE per clinical consensus diagnostic criteria to previous data from anti-NMDAR and anti-LGI1 cohorts. RESULTS: Eight probable seronegative AE and nine possible seronegative AE were identified. The group only differed in frequency of abnormal brain MRI, which was seen in all of the probable seronegative AE patients. Both seronegative groups had similar overall patterns of brain dysmetabolism. A common pattern of frontal lobe hypometabolism and medial temporal lobe hypermetabolism was observed in patients with probable and possible seronegative AE, as well as anti-NMDAR and anti-LGI1 AE as part of their respective characteristic patterns of dysmetabolism. Four patients had multiple brain18FDG-PET/CT scans, with changes in number and severity of abnormal brain regions mirroring clinical status. CONCLUSIONS: A18FDG-PET/CT pattern of frontal lobe hypometabolism and medial temporal lobe hypermetabolism could represent a common potential biomarker of AE, which along with additional clinical data may facilitate earlier diagnosis and treatment.

Change in Epidemiology of Creutzfeldt-Jakob Disease in the US, 2007-2020.

This cross-sectional study uses Centers for Disease Control and Prevention multiple cause of death data to examine recent US trends in Creutzfeldt-Jakob disease.

Comparison of quantitative FDG-PET and MRI in anti-LGI1 autoimmune encephalitis.

OBJECTIVES: Anti-leucine glioma-inactivated protein 1 (anti-LGI1) autoimmune encephalitis (AE) presents as subacute memory loss, behavioral changes, and seizures. Diagnosis and treatment delays can result in long term sequelae, including cognitive impairment. 18F-FDG PET/CT may be more sensitive than MRI in patients with AE. Our objective was to determine if anti-LGI1 is associated with a distinct pattern of FDG uptake and whether this pattern persists following treatment. METHODS: Nineteen18F-FDG PET/CT brain scans (13 pre-treatment, 6 convalescent phase) for 13 patients with anti-LGI1 were studied using NeuroQ™ and CortexID™. The sensitivity of the PET images was compared to MRI. The Z scores of 47 brain regions between the pre-treatment and next available follow-up images during convalescence were compared. RESULTS: All 18F-FDG PET/CT scans demonstrated abnormal FDG uptake, while only 6 (42.9%) pre-treatment brain MRIs were abnormal. The pre-treatment scans demonstrated hypermetabolism in the bilateral medial temporal cortices, basal ganglia, brain stem, and cerebellum and hypometabolism in bilateral medial and mid frontal, cingulate, and parietotemporal cortices. Overall, the brain uptake during convalescence showed improvement of the Z scores towards 0 or normalization of previous hypometabolic activity in medial frontal cortex, inferior frontal cortex, Broca's region, parietotemporal cortex, and posterior cingulate cortex and previous hypermetabolic activity in medial temporal cortices, caudate, midbrain, pons and cerebellum. CONCLUSIONS: Brain FDG uptake was more commonly abnormal than MRI in the pre-treatment phase of anti-LGI1, and patterns of dysmetabolism differed in the pre-treatment and convalescent phases. These findings may expedite the diagnosis, treatment, and monitoring of anti-LGI1 patients.

EEG Correlates of Qualitative Hypermetabolic FDG-PET in Patients With Neurologic Disorders.

Background and Objectives: Case reports and case series have described fluorodeoxyglucose (FDG)-PET findings in critically ill patients with rhythmic or periodic EEG patterns, with one reporting that metabolic activity increases with increasing lateralized periodic discharge (LPD) frequency. However, larger studies examining the relationship between FDG-PET hypermetabolism and rhythmic or periodic EEG patterns are lacking. The goal of this study was to investigate the association of FDG-PET hypermetabolism with electroencephalographic features in patients with neurologic disorders. Methods: This was a single-center, retrospective study of adult patients admitted with acute neurologic symptoms who underwent FDG-PET imaging and EEG monitoring within 24 hours. Subjects were divided into 2 groups based on their FDG-PET metabolism pattern: hypermetabolic activity vs hypometabolic or normal metabolic activity. Chi-square tests and logistic regression were used to determine the relationship of FDG-PET metabolism and EEG findings. Results: Sixty patients met the inclusion criteria and underwent 63 FDG-PET studies and EEGs. Twenty-seven studies (43%) showed hypermetabolism while 36 studies (57%) showed either hypometabolism or no abnormalities on FDG-PET. Subjects with hypermetabolic FDG-PET were more likely to have electrographic seizures (44% vs 8%, p = 0.001) and LPDs with/without seizures (44% vs 14%, p = 0.007), but not other rhythmic or periodic EEG patterns (lateralized rhythmic delta activity, generalized periodic discharges, or generalized rhythmic delta activity). Subjects with hypermetabolism and LPDs were more likely to have concurrent electrographic seizures (58% vs 0%, p = 0.03), fast activity associated with the discharges (67% vs 0, p = 0.01), or spike morphology (67% vs 0, p = 0.03), compared with subjects with hypometabolic FDG-PET and LPDs. Discussion: Adults admitted with acute neurologic symptoms who had hypermetabolic FDG-PET were more likely to show electrographic seizures and LPDs, but not other rhythmic or periodic EEG patterns, compared with those with hypometabolic FDG-PET. Subjects with hypermetabolic FDG-PET and LPDs were more likely to have LPDs with concurrent electrographic seizures, LPDs with a spike morphology, and LPDs +F, compared with subjects with hypometabolic FDG-PET.

Visual Pathway Involvement in NMDA Receptor Encephalitis: A Clinical, Optical Coherence Tomography, and 18-Fluorodeoxyglucose PET/CT Approach.

BACKGROUND: Anti-NMDA receptor (NMDAR) encephalitis patients have been reported to exhibit visual dysfunction without retinal thinning. The objective of our study was to examine the involvement of the visual pathway structure and function in anti-NMDAR encephalitis by assessing postrecovery visual function and retinal structure, and acute-phase occipital cortex function. METHODS: In this cross-sectional study, patients diagnosed with anti-NMDAR encephalitis per consensus criteria underwent postrecovery visual acuity (VA) testing and optical coherence tomography (OCT) with automated retinal layer segmentation. Clinical data and acute-phase brain 18F-fluorodeoxyglucose (FDG) PET/CT (performed within 90 days of symptom onset, assessed qualitatively and semi-quantitatively) were retrospectively analyzed. VA and OCT measures were compared between anti-NMDAR and age, sex, and race-matched healthy controls (HC). When available, FDG-PET/CT metabolism patterns were analyzed for correlations with VA, and OCT measures. RESULTS: A total of 16 anti-NMDAR (32 eyes) and 32 HC (64 eyes) were included in the study. Anti-NMDAR exhibited lower low-contrast VA (2.5% contrast: -4.4 letters [95% CI; -8.5 to -0.3]; P = 0.04, 1.25% contrast: -6.8 letters [95%CI; -12 to -1.7]; P = 0.01) compared with HC, but no differences were found on OCT-derived retinal layer thicknesses. Acute-phase FDG-PET/CT medial occipital cortex metabolism did not correlate with follow-up low-contrast VA or ganglion cell/inner plexiform layer thickness (GCIPL) (n = 7, 2.5% contrast: r = -0.31; P = 0.50, 1.25% contrast: r = -0.34; P = 0.45, GCIPL: r = -0.04; P = 0.94). CONCLUSIONS: Although the visual system seems to be involved in anti-NMDAR encephalitis, no retinal structural or occipital cortex functional abnormalities seem to be responsible for the visual dysfunction. When detected acutely, occipital lobe hypometabolism in anti-NMDAR encephalitis does not seem to associate with subsequent retrograde trans-synaptic degenerative phenomena, potentially reflecting reversible neuronal/synaptic dysfunction in the acute phase of the illness rather than neuronal degeneration.

Development and Validation of a Risk Score to Differentiate Viral and Autoimmune Encephalitis in Adults.

BACKGROUND: Encephalitis represents a challenging condition to diagnose and treat. To assist physicians in considering autoimmune encephalitis (AE) sooner, we developed and validated a risk score. METHODS: The study was conducted as a retrospective cohort of patients with a diagnosis of definite viral encephalitis (VE) and AE from​​ February 2005 to December 2019. Clinically relevant and statistically significant features between cases of AE and VE were explored in a bivariate logistic regression model and results were used to identify variables for inclusion in the risk score. A multivariable logistic model was used to generate risk score values and predict risk for AE. Results were externally validated. RESULTS: A total of 1310 patients were screened. Of the 279 enrolled, 36 patients met criteria for definite AE and 88 criteria for definite VE. Patients with AE compared with VE were more likely to have a subacute to chronic presentation (odds ratio [OR] = 22.36; 95% confidence interval [CI], 2.05-243.7), Charlson comorbidity index <2 (OR = 6.62; 95% CI, 1.05-41.4), psychiatric and/or memory complaints (OR = 203.0; 95% CI, 7.57-5445), and absence of robust inflammation in the cerebrospinal fluid defined as <50 white blood cells/µL and protein <50 mg/dL (OR = 0.06; 95% CI, .005-0.50). Using these 4 variables, patients were classified into 3 risk categories for AE: low (0-1), intermediate (2-3), and high (4). Results were externally validated and the performance of the score achieved an area under the curve of 0.918 (95% CI, .871-.966). DISCUSSION: This risk score allows clinicians to estimate the probability of AE in patients presenting with encephalitis and may assist with earlier diagnosis and treatment.

Younger Age at Onset Is Associated With Worse Long-term Behavioral Outcomes in Anti-NMDA Receptor Encephalitis.

BACKGROUND AND OBJECTIVES: Anti-NMDA receptor encephalitis (anti-NMDARE) is one of the most common causes of encephalitis. It typically presents in adolescence and young adulthood, but little is known about its potential long-term consequences across the lifespan. Adaptive behavior describes an individual's ability to respond and adapt to environmental demands and unanticipated changes in daily routines. In this study, we evaluate the relationship between features from clinical presentation, including age, and long-term adaptive behavior in participants with anti-NMDARE. METHODS: Cross-sectional informant-reported data were collected between 2017 and 2019 from 41 individuals/caregivers of individuals with anti-NMDARE treated at 3 major academic hospitals. Neurologic disability was assessed by record review using the modified Rankin Scale (mRS). Functional outcomes were assessed using the validated Adaptive Behavior Assessment System, Third Edition (ABAS-3). RESULTS: The mean age at the time of study enrollment was 23.4 years (SD 17.0 years), and the mean time from symptom onset to study enrollment was 4.0 years. Seventeen participants were aged <12 years at symptom onset, 19 participants were aged 12-30 years, and 5 participants were aged >30 years. Mean ABAS-3 scores at study enrollment for all participants were in the average range (mean general adaptive composite standard score 92.5, SD 18.7). Individuals aged <12 years at symptom onset had lower mean ABAS-3 scores and were in the below average range compared with those aged 12-30 years at symptom onset, whose mean scores were in the average range (87 vs 99, p < 0.05). Similar differences were seen in 3 of the individual subscales (functional academics, health and safety, and self-care). There were no significant differences in mRS scores between age groups (p > 0.05). DISCUSSION: Although anti-NMDARE is associated with an overall favorable outcome, younger age at onset associates with worse long-term adaptive behavior despite no differences in neurologic disability. These findings suggest that the disease may have distinct consequences on the early developing brain. Future studies should evaluate behavioral recovery and quality of life after anti-NMDARE and identify additional factors associated with differential recovery.

Neurohospitalist Practice and Well-Being During the COVID-19 Pandemic.

BACKGROUND AND PURPOSE: Neurohospitalists play an important role in, and have been variably affected by, the ongoing COVID-19 pandemic. In this study, we survey neurohospitalists to characterize practice changes and the impact of the pandemic on their well-being. METHODS: A 22-item survey was distributed to neurohospitalists through the Neurohospitalist Society and the American Academy of Neurology Neurohospitalist, Stroke & Vascular Neurology, and Critical Care & Emergency Neurology Sections. RESULTS: After 2 weeks of collection, 123 responses were received, with 57% of respondents practicing in academic settings, 23% in private practice, and 7% in community hospitals. A minority of neurohospitalists (8%) were redeployed to care for COVID-19 or non-COVID-19 medicine patients. The most common neurologic diagnoses they reported in COVID-19 patients were delirium (85%), cerebrovascular events (75%), and seizure (35%); however, most neurohospitalists (59%) had evaluated fewer than 10 patients with COVID-19. Respondents observed that fewer patients with unrelated neurological diseases were admitted to the hospital compared to before the pandemic. Neurohospitalists experienced changes in administrative (27%), educational (15%), and research duties (11%), and had overall worse well-being and work-life balance (77%). CONCLUSIONS: The most common neurologic diagnoses seen in COVID-19 patients by neurohospitalists in this sample are delirium, cerebrovascular disease, and seizure. Though the majority of survey respondents reported not being primary frontline providers, they report key clinical and operational roles during the pandemic, and report worse well-being as compared to before the pandemic. Our data suggests that there are opportunities to improve neurohospitalists' experience through flexible work practices and providing family care support.

Fatigue in Survivors of Autoimmune Encephalitis.

BACKGROUND AND OBJECTIVES: To evaluate the impact of fatigue after autoimmune encephalitis, determine associations with patients' characteristics, and identify factors that contribute to its development. METHODS: In a first cohort recruited via several encephalitis support organizations, self-reported questionnaires were used to evaluate fatigue, depression, and sleep quality in adults after autoimmune encephalitis. In a second cohort where more in-depth clinical characterization could be performed, adults with encephalitis from 2 tertiary hospitals were evaluated using the same questionnaires. Patients' characteristics were retrospectively captured. RESULTS: In the first cohort (mean [SD] age; 43 [16] years, 220 [65%] female), 220 of 338 participants (65%) reported fatigue, 175 of 307 (57%) depression, and 211 of 285 (74%) poor sleep quality. In the second cohort (48 [19] years; 43 [50%] women), 42 of 69 participants (61%) reported fatigue, whereas 23 of 68 (34%) reported depression and 44 of 66 (67%) poor sleep quality, despite more than 80% having "good" modified Rankin scale (mRS) scores (0-2). Individuals with anti-NMDA receptor encephalitis reported lower fatigue scores than those with other autoimmune encephalitis types. In a multivariate analysis examining factors at discharge that might predict fatigue scores, only anti-NMDA receptor encephalitis was a (negative) predictor of fatigue and remained so when potential confounders were included. DISCUSSION: The impact of fatigue after autoimmune encephalitis is prominent and not fully accounted for by depression or sleep quality, nor adequately captured by mRS scores for disability. Fatigue is pervasive across autoimmune encephalitis, although lower scores are reported in anti-NMDA receptor encephalitis. Fatigue should be screened routinely, considered as an outcome measure in clinical trials, and further studied from a mechanistic standpoint.

Autoimmune encephalitis: proposed recommendations for symptomatic and long-term management.

The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. The most popular bridging therapy was oral prednisone taper chosen by 38% of responders while rituximab was the most popular maintenance therapy chosen by 46%. Most responders considered maintenance immunosuppression after a second relapse in patients with neuronal surface antibodies (70%) or seronegative autoimmune encephalitis (61%) as opposed to those with onconeuronal antibodies (29%). Most responders opted to cancer screening for 4 years in patients with neuronal surface antibodies (49%) or limbic encephalitis (46%) as opposed to non-limbic seronegative autoimmune encephalitis (36%). Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.

Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management.

The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. Corticosteroids alone or combined with other agents (intravenous IG or plasmapheresis) were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis and 48.5% for classical paraneoplastic encephalitis. Half the responders indicated they would add a second-line agent only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in all patients. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies. Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.

MOG-IgG1 and co-existence of neuronal autoantibodies.

BACKGROUND: The presence of co-existent neuronal antibodies (neuronal-IgG) in patients with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG1) is not yet well understood. OBJECTIVES: The aim of this study was to investigate the co-existence of a broad range of neuronal-IgG in MOG-IgG1+ patients. METHODS: MOG-IgG1+ patients were tested for 17 neuronal-IgGs in cerebrospinal fluid (CSF) and serum including NMDA-R-IgG, AMPA-R-IgG, GABAB-R-IgG, LGI1-IgG, CASPR2-IgG, GABAA-R-IgG, GAD65-IgG, mGLUR1-IgG, DPPX-IgG, CRMP5-IgG, amphiphysin-IgG, PCA1,2,Tr, and ANNA1,2,3. Clinical and radiological features of MOG-IgG1+ with NMDA-R-IgG in CSF were compared to a control cohort of MOG-IgG1+ patients without NMDA-R-IgG. RESULTS: A total of 376 MOG-IgG1+ patients underwent testing for neuronal-IgGs. Serum testing for neuronal-IgGs (113 adults, 142 children) identified one child with NMDA-R-IgG (0.7%), one child with CASPR2-IgG (0.7%), one adult with LGI1-IgG (0.9%) and one adult with GABAA-R-IgG (0.9%). CSF testing for neuronal-IgGs (97 adults, 169 children) identified seven children (4%) and seven adults (7%) with NMDA-R-IgG, and one adult with GABAA-R-IgG (1%). The MOG-IgG1+/NMDA-R-IgG+ patients had a median age of 17 (range: 2-39) years. Features associated with MOG-IgG1+/NMDA-R-IgG+ included encephalopathy (p = 0.001), seizures (p = 0.045), and leptomeningeal enhancement (p = 0.045). CONCLUSION: NMDA-R-IgG was the most frequently detected neuronal-IgG to co-exist with MOG-IgG1. MOG-IgG1+/NMDA-R-IgG+ patients most often presented with encephalopathy and seizures. Testing for MOG-IgG1 and NMDA-R-IgG may be warranted in patients with encephalopathy and inflammatory demyelinating syndromes.

Patterns and Perceptions of Smartphone Use Among Academic Neurologists in the United States: Questionnaire Survey.

BACKGROUND: Smartphone technology is ubiquitous throughout neurologic practices, and numerous apps relevant to a neurologist's clinical practice are now available. Data from other medical specialties suggest high utilization of smartphones in routine clinical care. However, the ways in which these devices are used by neurologists for patient care-related activities are not well defined. OBJECTIVE: This paper aims to characterize current patterns of smartphone use and perceptions of the utility of smartphones for patient care-related activities among academic neurology trainees and attending physicians. We also seek to characterize areas of need for future app development. METHODS: We developed a 31-item electronic questionnaire to address these questions and invited neurology trainees and attendings of all residency programs based in the United States to participate. We summarized descriptive statistics for respondents and specifically compared responses between trainees and attending physicians. RESULTS: We received 213 responses, including 112 trainee and 87 attending neurologist responses. Neurology trainees reported more frequent use of their smartphone for patient care-related activities than attending neurologists (several times per day: 84/112, 75.0% of trainees; 52/87, 59.8% of attendings; P=.03). The most frequently reported activities were internet use, calendar use, communication with other physicians, personal education, and health care-specific app use. Both groups also reported regular smartphone use for the physical examination, with trainees again reporting more frequent usage compared with attendings (more than once per week: 35/96, 36.5% of trainees; 8/58, 13.8% of attendings; P=.03). Respondents used their devices most commonly for the vision, cranial nerve, and language portions of the neurologic examination. The majority of respondents in both groups reported their smartphones as "very useful" or "essential" for the completion of patient care-related activities (81/108, 75.0% of trainees; 50/83, 60.2% of attendings; P=.12). Neurology trainees reported a greater likelihood of using their smartphones in the future than attending neurologists ("very likely": 73/102, 71.6% of trainees; 40/82, 48.8% of attendings; P=.005). The groups differed in their frequencies of device usage for specific patient care-related activities, with trainees reporting higher usage for most activities. Despite high levels of use, only 12 of 184 (6.5%) respondents reported ever having had any training on how to use their device for clinical care. Regarding future app development, respondents rated vision, language, mental status, and cranial nerve testing as potentially being the most useful to aid in the performance of the neurologic examination. CONCLUSIONS: Smartphones are used frequently and are subjectively perceived to be highly useful by academic neurologists. Trainees tended to use their devices more frequently than attendings. Our results suggest specific avenues for future technological development to improve smartphone use for patient care-related activities. They also suggest an unmet need for education on effectively using smartphone technology for clinical care.

Neurologic complications of immune checkpoint inhibitors.

Introduction: Immune checkpoint inhibitors (ICI) are associated with a wide spectrum of neurologic immune-related adverse events (irAEs) including meningo-encephalitis, myasthenia gravis and various neuropathies. Although relatively rare, they often present significant diagnostic complexity and may be under-recognized. Permanent neurologic deficits and/or fatality have been described but improvement is noted in most cases with ICI discontinuation and immunosuppressive therapy.Areas covered: This review highlights the most frequently reported ICI-associated neurologic toxicities with a particular focus on those that may be more severe and/or fatal. Data from case series and pharmacovigilance studies is leveraged to provide an overview of associated clinical features, expected outcomes and appropriate management. Various immunobiologic triggers have been proposed to explain why certain patients might develop neurologic irAEs and are also briefly discussed.Expert opinion: All providers who care for patients with cancer should be made aware of common neurologic irAEs and able to recognize when prompt evaluation and consultation with appropriate specialists are indicated. Symptoms suggestive of encephalitis, myasthenia-gravis or an acute polyradiculopathy such as Guillain-Barre Syndrome (GBS) in patients exposed to these agents warrant immediate attention with a low threshold for hospitalization to expedite work-up and monitor for severe and/or life-threatening manifestations.

Prevalence and Improvement of Caine-Positive Wernicke-Korsakoff Syndrome in Psychiatric Inpatient Admissions.

BACKGROUND: Wernicke-Korsakoff Syndrome (WKS) resulting from thiamine deficiency is classically defined as including encephalopathy, ataxia, and ophthalmoplegia. Only 16% of autopsy-confirmed patients with WKS exhibit all three signs. Caine-positive WKS criteria include two or more of the following: nutritional deficiency, delirium or mild memory impairment, cerebellar dysfunction/ataxia, and oculomotor abnormalities. OBJECTIVE: We describe Caine-positive WKS prevalence among psychiatric inpatients and compare pretreatment-versus-posttreatment neurocognitive improvement to an unaffected group. METHODS: This 6-month quality-improvement evaluation included two-stage screening for Caine-positive WKS, administering high-dose intravenous thiamine (day 1: 1200 mg; days 2-4: 200 mg) with reexamination on day 5. We used descriptive statistics and fitted random effects models to examine rate-of-change differences in pre-/posttreatment Montreal Cognitive Assessment (MoCA), delayed 5-item recall, and gait/coordination scores between treated Caine-positive patients with WKS and untreated Caine-negative patients. RESULTS: Of 262 patients, 32 (12%) had Caine-positive WKS; 17 (53%) used alcohol currently. Treated Caine-positive WKS (n = 26) versus Caine-negative comparison (n = 34) before and after treatment observed a mean change (standard deviation) in the MoCA score of 3.6 (2.5) versus 1.8 (2.5) (P < 0.01); 5-item recall: 1.8 (1.4) versus 0.5 (1.4) (P < 0.001); gait/coordination scores: -0.6 (1.2) versus -0.1 (0.6) (P < 0.001). Oculomotor abnormalities were infrequent (n = 4 in Caine-positive WKS, n = 2 in Caine-negative comparison groups). CONCLUSIONS: Caine-positive WKS prevalence among psychiatric inpatients was 12%; only half used alcohol. Patients treated with high-dose thiamine demonstrated clinically significant neurocognitive improvement.

New-onset refractory status epilepticus: A retrospective cohort study.

PURPOSE: To describe the clinical, laboratory, neuroimaging, electroencephalographic features, etiology, treatment, as well as short-term and long-term outcomes of adults with new-onset refractory status epilepticus (NORSE). METHOD: A retrospective, single institution cohort study (2010-2018) of consecutive adult patients with NORSE. RESULTS: Among 20 patients with NORSE, nine (45 %) had prodromal febrile illness, 12 (60 %) had evidence of inflammation on CSF profile. Six patients (30 %) met criteria for definite autoimmune encephalitis (AE) while 8 patients (40 %) had probable AE. Eleven out of 13 (85 %) patients had an abnormal FDG-PET scan with the most common finding being regional hypermetabolism. Fourteen patients (70 %) received immunotherapy and ten (50 %) received the ketogenic diet (KD). Fifteen patients (75 %) progressed to super-refractory status epilepticus (SRSE) and seven patients (35 %) died in the hospital or within six months of discharge. Among the surviving patients, eight (40 %) had a good outcome (i.e., modified Rankin Scale score 0-2); 12 (80 %) received a diagnosis of epilepsy of which nine (75 %) developed drug-resistant epilepsy. CONCLUSIONS: New-onset refractory status epilepticus is a syndrome associated with multiple complications, high mortality, and subsequent intractable epilepsy. There are multiple causes, some of which are autoimmune encephalitides; however, in this series the majority of patients had no clear etiology identified after extensive evaluation. Prospective studies are needed to determine optimal evaluation and treatment.