SARS-CoV-2 Vaccination and Neuroimmunological Disease

The use of immune checkpoint inhibitors (ICIs) for oncologic indications is associated with immune-related adverse events (irAEs). Patients with pre-existing autoimmune diseases are at increased risk of irAEs and have largely been excluded from clinical trials of ICIs. Therefore, there is limited data on the safety of safety of ICIs in patients with pre-existing neurologic autoimmune diseases (nAIDs) such as myasthenia gravis and multiple sclerosis. This review aims to synthesize the literature on the post-marketing experience with ICI in patients with pre-existing nAID and to discuss possible strategies for mitigating the risk of post-ICI nAID relapses. Patients with pre-existing myasthenia gravis (MG), myositis, and paraneoplastic encephalitis appear highly susceptible to neurologic relapses of their underlying neurologic disorder following ICI initiation; these relapses can cause considerable morbidity and mortality. In patients with multiple sclerosis (MS), the risk and severity of MS relapses following ICI appears to be relatively lower compared to MG. Preliminary evidence suggests that older MS patients with no recent focal neuroinflammatory activity may be safely treated with ICI. Among the several case reports of ICI in patients with a history of Guillain-Barre syndrome (GBS), neurologic worsening was only recorded in one patient who was in the acute phase of GBS at the time of ICI start. Initiating an ICI in a patient with pre-existing nAID involves a complex risk-benefit discussion between the patient, their oncologist, and neurologist. Relevant issues to consider before ICI include the choice of disease-modifying therapy for nAID (if any) and strategies for promptly identifying and managing nAID relapses should they occur. Currently, the literature consists mainly of case reports and case series, subject to publication bias. Prospective studies of ICI in patients with nAID are needed to improve the level of evidence.

Immune checkpoint inhibitors (ICIs) are efficacious in many cancer types but can produce immune-related adverse events (irAEs). As such, patients with preexisting autoimmune disorders are often excluded from clinical trials, although subsequent studies have shown that many of these patients have acceptable ICI tolerance. The safety and efficacy of ICIs among patients with preexisting neurologic autoimmune disorders (NAIDs) is not well characterized. To evaluate the safety and clinical outcomes associated with ICI therapy among patients with NAIDs. This multicenter retrospective cohort study included patients with cancer who were treated with ICIs between October 2013 and May 2023 and had preexisting multiple sclerosis (MS), myasthenia gravis (MG), Guillain-Barré syndrome (GBS), and other NAIDs as well as a control cohort of patients with Parkinson disease (PD). ICI therapy. Demographic and clinical characteristics (neurologic disability, active or recent immunosuppression), ICI outcomes (response, progression-free survival [PFS], and overall survival [OS]), and safety outcomes (NAID exacerbation, irAEs) were collected. A total of 135 patients were included; the median (range) age was 72 (40-88) years, 84 (62%) were men, and 51 (38%) were women. A total of 45 patients had MS; 18, MG; 10, GBS; 5, another NAID; and 57, PD. Exacerbations occurred most frequently in MG (12 of 18 patients [67%]), often resulting in hospitalization (6 [50%]) or death (2 [17%]), with much lower rates in the MS cohort (8 of 45 patients [18%]). Ten patients with a history of GBS tolerated ICI without exacerbations, although 1 developed a fatal case of Lambert Eaton myasthenic syndrome following ICI treatment. No differences in response rate, PFS, or OS were observed between NAID groups. In this cohort study of ICI use in NAIDs, patients with MG had frequent and more severe exacerbations, while those with MS had few exacerbations. No obvious differences in survival between groups were observed. ICI may be an option for many patients with appropriate oncologic indications and preexisting NAIDs.

ABSTRACTObjectiveNear real-time vaccine safety surveillance (NRTVSS) using electronic health records (EHR) is an option for post-licensure vaccine safety assessment. NRTVSS requires timely recording of outcomes in the database used. Our study aimed to examine recording delays in the Clinical Practice Research Datalink (CPRD) to inform the feasibility of implementing NRTVSS in England using these data. 
 ApproachTo examine delays we selected 4 outcomes of interest for NRTVSS: Guillain-Barre syndrome (GBS), Bell’s palsy (BP), optic neuritis (ON), and seizures for the period January 2005 to July 2015. Timeliness of CPRD records was assessed in two ways: 1) Using linked CPRD-hospital episode (HES) data to compare the hospital diagnosis date with the date the record was entered in CPRD (system date), 2) Looking at delays in recording (e.g. due to feedback from specialist referral) in stand-alone CPRD. For the latter the event date was compared with the system date. However, system dates can be changed when practice software is updated or there is mass transfer of a patient’s records. After investigation, we excluded these uninformative system dates by excluding records from patients who had more than 100 records with the system date on the same day.
 Results67813 patients were identified in CPRD (GBS:n=1081, BP:n=15835, ON:n=2236, seizures:n=48866), 64527 in HES (GBS:n=1680, BP:n=8468, ON:n=1746, seizures:n=53080) and 14104 in both databases (GBS:n=356, BP:n=1511, ON:n=226, seizures:n=12036). For the CPRD-HES comparison, 11843 patients with a diagnosis of interest both in CPRD and HES were included (GBS:n=321, BP:n=1374, ON:n=190, seizures:n=9976). Of these, the majority had a record in CPRD before or within 1 month of the HES record (GBS:49.5%, BP:83.8%, ON:66.8%, seizures:69.8%). For 6 months the corresponding percentage was more than 85% for all conditions examined (GBS:85.4%, BP:92.9%, ON:90.0%, seizures:86.6%). For stand-alone CPRD 57317 patients were included (GBS:n=972, BP:n=14275, ON:n=1958, seizures:n=40327). The majority had a record within one month of the event date (GBS:67.9%, BP:89.3%, ON:71.8%, seizures:83%). More than 87% of records occurred within 6 months of the event date (GBS:87.9%, BP:94.4%, ON:91.6%, seizures:94.9%).
 ConclusionThis work shows that most diagnoses examined were recorded with a delay of ≤30 days, making NRTVSS possible. The distribution of the delays was condition-specific and the weekly delay distribution could be used to adjust for delays in the NRTVSS analysis. CPRD can be a viable data source to use in this kind of analysis; next steps will include trial implementation of the system using these data.

Increasing literature has linked COVID‐19 to peripheral nervous system (PNS) diseases. In addition, as we move from the pandemic to the vaccination era, literature interest is shifting towards the potential association between COVID‐19 vaccines and PNS manifestations. We reviewed published literature on COVID‐19, COVID‐19 vaccines and PNS manifestations between 1 January 2020 and 1 December 2021. For Guillain‐Barré syndrome (GBS), isolated cranial neuropathy (ICN) and myositis associated with COVID‐19, the demographic, clinical, laboratory, electrophysiological and imaging features were included in a narrative synthesis. We identified 169 studies on COVID‐19‐associated complications, including 63 papers (92 patients) on GBS, 29 papers (37 patients) on ICN and 11 papers (18 patients) on myositis. Additional clinical phenotypes included chronic inflammatory demyelinating polyneuropathy, vasculitic neuropathies, neuralgic amyotrophy, critical care‐related complications, and myasthenia gravis. PNS complications secondary to COVID‐19 vaccines have been reported during randomized clinical trials, in real‐world case reports, and during large‐scale surveillance programs. These mainly include cases of GBS, Bell's palsy, and cases of neuralgic amyotrophy. Based on our extensive review of the literature, any conclusion about a pathophysiological correlation between COVID‐19 and PNS disorders remains premature, and solely supported by their temporal association, while epidemiological and pathological data are insufficient. The occurrence of PNS complications after COVID‐19 vaccines seems limited to a possible higher risk of facial nerve palsy and GBS, to a degree that widespread access to the ongoing vaccination campaign should not be discouraged, while awaiting for more definitive data from large‐scale surveillance studies.

To estimate the burden of disease of Guillain-Barré syndrome (GBS) in Brazil in 2014, 1year before the Zika virus epidemic, and in 2015 and 2016 during the epidemic. The burden of disease of GBS was estimated using the summary measure of population health: Disability Adjusted Life Years (DALY), that combines both mortality (Years of Life Lost YLLs) and morbidity (Years Lived with Disability) components. The study population was composed of GBS hospitalised cases and deaths from the information systems of the Brazilian Unified Health System. The GBS incidence rate in 2014, 2015 and 2016 was 0.74, 0.96, 1.02/100000 respectively, and the mortality rate in the same period was 0.08, 0.009 and 0.11/100000 habitants. The DALYs calculated using the point estimate of GBS disability weight and its values of the confidence interval (0.198 and 0.414) were 5725.90 (5711.79-5742.89) in 2014, 6054.61 (6035.57-6077.54) in 2015 and 7588.49 (7570.20-7610.51) in 2016. The DALYs were high among the male population and in age groups between 20 and 50years. The increase in DALYs in the years 2015 and 2016 compared to 2014 probably resulted from the introduction of ZIKV in Brazil, reinforcing the importance of investments in the prevention of ZIKV infection and in the care of GBS patients.

MuSK Antibody-Associated Myasthenia Gravis With SARS-CoV-2 Infection: A Case Report.

BACKGROUND Therapeutic plasma exchange is a process where the blood collected from patient is passed through an apheresis instrument where the plasma is removed and discarded and reinfusion of blood cells done with replacement fluids like plasma or albumin to the patient.1 It is to remove pathogenic autoantibodies, immune complexes, cryoglobulins and toxins present in the plasma. Plasma exchange is considered effective and cheaper immunomodulatory treatment when compared to intravenous immunoglobulin (IVIG). 2 We present our institutional experience with therapeutic plasma exchange (TPE) in treatment of various non-neurological and neurological diseases. Our study was conducted to assess the indications, complications and outcome of TPE in the treatment of patients. METHODS A retrospective study of TPE procedures was carried out in the Department of Immunohaematology and blood transfusion, M.G.M Medical College and Hospital, Navi Mumbai from June 2018 to June 2020. A total of 45 procedures were performed among 13 patients between 4 years of age to 66 years of age. Clinical parameters were checked, and laboratory investigations were done before the procedure. Data was collected from the requisition forms by the clinicians and the apheresis database. RESULTS A total of 47 procedures were carried out among 13 patients. TPE is a safe and effective procedure for treating patients with neurologic and non-neurological diseases. Most common indication was Guillain Barre syndrome followed by myasthenia gravis. Incidence of adverse reactions was 7.6 %. CONCLUSIONS TPE is a safe and effective procedure for treating patients with neurologic and nonneurological diseases. It benefited 10 out of 13 patients, and they showed complete recovery. KEY WORDS Therapeutic Plasma Exchange, Guillain Barre syndrome

The Case Files

Objective: To investigate the application of glucocorticoids in children with neurological diseases by pediatricians, and to provide baseline data for further standardization of glucocorticoids application. Methods: This was a cross-sectional survey, an electronic questionnaire survey was conducted online from July 8, 2019 to July 28, 2019 through the Subspecialty Group of Clinical Pharmacology, the Subspecialty Group of Neurology, and Expert Committee on Rational Use of Medicines for Children in the Society of Pediatrics, Chinese Medical Association. This survey was conducted for the application of glucocorticoids in 8 neurological diseases in children, and compared with the current guidelines or consensus to judge whether the application was standard. A total of 1 850 pediatricians from 1 073 hospitals were surveyed. Surveyed diseases included bacterial meningitis, anti-N-methyl-D-aspartate receptor encephalitis, neuromyelitis optica spectrum disease (NMOSD), multiple sclerosis, Guillain-Barre syndrome, myasthenia gravis, juvenile dermatomyositis, and Duchenne muscular dystrophy. In order to explore the associated factors of standardized glucocorticoid application, the level of hospital, whether there was an independent department of pediatric neurology, and working experience of the doctor were used as independent variables. The χ2 test and multivariate Logistic analysis was used for statistical analysis. Results: A total of 1 834 (99.1%) valid questionnaires were collected from 1 073 hospitals in 31 provinces, autonomous regions and municipalities. The coincidence rate with recommendation of the current guideline or consensus on glucocorticoids was 5.8% (51/879) in juvenile dermatomyositis, 13.7% (153/1 115) in myasthenia gravis, 18.2% (142/781) in bacterial meningitis, 18.5% (310/1 680) in anti-N-methyl-D-aspartate receptor encephalitis, 23.0% (248/1 079) in Duchenne muscular dystrophy, 33.4% (322/964) in NMOSD and multiple sclerosis, and 43.5% (477/1 096) in Guillain-Barre syndrome. The most common one was the irregular course of treatment, and the coincidence rate was 36.8% (12.5%-62.2%). The multivariate Logistic regression analysis indicated that the use of glucocorticoids was more standardized in bacterial meningitis (OR=1.83, 95%CI 1.39-2.43, P<0.01), Guillain-Barre syndrome (OR=1.97, 95%CI 1.50-2.59, P<0.01), Duchenne muscular dystrophy (OR=1.85, 95%CI 1.38-2.48, P<0.01), juvenile dermatomyositis (OR=2.08, 95%CI 1.03-4.19, P=0.040) and N-methyl-D-aspartate receptor encephalitis (OR=0.302, 95%CI 0.20-0.46, P<0.01) and by pediatricians with pediatric neurology specialty in the hospital. Conclusions: The coincidence rate with recommendation of the current guideline or consensus on glucocorticoids is less than half in children with neurological diseases, and the use of glucocorticoids is more standardized in a variety of diseases by pediatricians with pediatric neurology specialty in the hospital, which indicates that the study of guidelines or consensus and the special training of pediatric neurologists should be further strengthened.

We aimed to describe the clinical spectrum and burden of COVID-19-associated neurologic disease in Australian children. We extracted Australian national sentinel site surveillance data on COVID-19-associated neurologic disease in children hospitalized in the Paediatric Active Enhanced Disease Surveillance network, 2020-2023. Neurologic complications included encephalitis, encephalopathy, Guillain-Barre syndrome, seizures and cerebrovascular accident among others. We calculated the proportion of hospitalized pediatric COVID-19 cases associated with neurologic disease and described the spectrum of presentations including clinical features and severity. We calculated incidence rates of neurologic disease within COVID-19 variant eras among hospitalized patients. We identified 311 cases of SARS-CoV-2 infection with neurologic disease among 4616 hospitalized pediatric cases of COVID-19 reported through the surveillance network, representing 5.3 cases per 100 pediatric COVID-19 admissions. The most common COVID-19-associated neurologic presentations were seizures (n = 215), including febrile seizures. Nonspecific encephalopathy (n = 62), encephalitis, Guillain-Barre Syndrome, acute cerebellar syndromes, acute demyelinating encephalomyelitis and cerebrovascular accident were also reported. Almost 60% of children were ≤4 years, approximately 30% had pre-existing neurologic conditions and almost half had other medical comorbidities. COVID-19-associated neurologic complications infrequently led to death, although 25% (n = 2/8) of children with COVID-19 encephalitis died. The incidence rate of COVID-19-associated neurologic disease was lowest during the late Omicron era. Neurologic complications among COVID-19 hospitalized children are relatively frequent. While most neurologic complications are transient, including seizures, encephalitis remains a cause of significant morbidity. Children with pre-existing neurologic disease and other comorbidities are at higher risk.

Vaccination in pediatric acquired inflammatory immune-mediated neuromuscular disorders.

Syndrome de Guillain-Barré après vaccination contre Haemophilus influenzae type b

Bell's palsy and SARS-CoV-2 vaccines

Severe forms of Guillain-Barré syndrome (GBS) and myasthenia gravis (MG) may result in prolonged mechanical ventilation in ICUs. Data on weaning from mechanical ventilation are scarce, and our objective was to assess ventilator weaning characteristics in a large-scale multicenter study. Multicenter retrospective cohort study including all patients intubated for at least 48 h for GBS or MG over a 10-year period (from January 2014 to December 2023). The primary outcome was the proportion of patients having experienced prolonged weaning (at least 7 days). Some 886 patients admitted to 47 ICUs in France were retained in the analysis, including 513 (58%) with GBS and 373 (42%) with MG. Patients with GBS were more likely to experience prolonged weaning than those with MG (64% vs. 35%, p < 0.001). An extubation attempt was performed in only 46% of patients with GBS and in 88% patients with MG (p < 0.001). Reintubation rates were 26% in patients with GBS and 29% in patients with MG (p = 0.440). Patients with GBS were more likely to undergo tracheostomy than those with MG (57% vs. 17%, p < 0.001). Patients with GBS required a longer duration of mechanical ventilation and ICU stay. Mortality rates were similar (9.4% for patients with GBS and 9.7% for patients with MG, p = 0.882). Patients with GBS were more likely to experience prolonged weaning and to undergo tracheostomy than patients with MG. More than one-fourth of patients required reintubation after an extubation attempt. Despite prolonged duration of mechanical ventilation, mortality remained relatively low.

PurposeNear real‐time vaccine safety surveillance (NRTVSS) is an option for post‐licensure vaccine safety assessment. NRTVSS requires timely recording of outcomes in the database used. Our main objective was to examine recording delays in the Clinical Practice Research Datalink (CPRD) for outcomes of interest for vaccine safety to inform the feasibility of NRTVSS using these data. We also evaluated completeness of recording and further assessed reporting delays for hospitalized events in CPRD.MethodsWe selected Guillain–Barré syndrome (GBS), Bell's palsy (BP), optic neuritis (ON) and febrile seizures (FS), from January 2005 to June 2014. We assessed recording delays (e.g. due to feedback from specialist referral) in stand‐alone CPRD by comparing the event and system dates and excluding delays >1 year. We used linked CPRD‐hospitalization data to further evaluate delays and completeness of recording in CPRD.ResultsAmong 51 220 patients for the stand‐alone CPRD analysis (GBS: n = 830; BP: n = 12 602; ON: n = 1720; and FS: n = 36 236), most had a record entered within 1 month of the event date (GBS: 73.6%; BP: 93.4%; ON: 76.2%; and FS: 85.6%). A total of 13 482 patients, with a first record in hospital, were included for the analysis of linked data (GBS: n = 678; BP: n = 4060; ON: n = 485; and FS: n = 8321). Of these, <50% had a record in CPRD after 1 year (GBS: 41.3%; BP: 22.1%; ON: 22.4%; and FS: 41.8%).ConclusionThis work shows that most diagnoses in CPRD for the conditions examined were recorded with delays of ≤30 days, making NRTVSS possible. The pattern of delays was condition‐specific and could be used to adjust for delays in the NRTVSS analysis. Despite low sensitivity of recording, implementing NRTVSS in CPRD is worthwhile and could be carried out, at least on a trial basis, for events of interest. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.