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Vaccines Oct 2023In this Italian population-based study, we aimed to evaluate the neurological complications after the first and/or second dose of COVID-19 vaccines and factors...
OBJECTIVE
In this Italian population-based study, we aimed to evaluate the neurological complications after the first and/or second dose of COVID-19 vaccines and factors potentially associated with these adverse effects.
METHODS
Our study included adults aged 18 years and older who received two vaccine doses in the vaccination hub of Novegro (Milan, Lombardy) between 7 and 16 July 2021. The NEURO-COVAX questionnaire was able to capture the neurological events, onset and duration. That data that were digitized centrally by the Lombardy region were used to match the demographic/clinical characteristics and identify a vulnerability profile. Associations between vaccine lines and the development of complications were assessed. Digital healthcare system matching was also performed to evaluate severe neurological complications (Guillain-Barrè syndrome, Bell's palsy, transverse myelitis, encephalitis) and the incidence of hospital admissions and/or the mortality rate after two doses of the vaccines.
RESULTS
The NEURO-COVAX-cohort included 19.108 vaccinated people: 15.368 with BNT162b2, 2077 with mRNA-1273, 1651 with ChAdOx1nCov-19, and 12 with Ad26.COV2.S who were subsequently excluded. Approximately 31.2% of our sample developed post-vaccination neurological complications, particularly with ChAdOx1nCov-19. A vulnerable clinical profile emerged, where over 40% of the symptomatic people showed comorbidities in their clinical histories. Defining the neurological risk profile, we found an increased risk for ChAdOx1nCov-19 of tremors (vs. BNT162b2, OR: 5.12, 95% CI: 3.51-7.48); insomnia (vs. mRNA-1273, OR: 1.87, 95% CI: 1.02-3.39); muscle spasms (vs. BNT162b2, OR: 1.62, 95% CI: 1.08-2.46); and headaches (vs. BNT162b2, OR: 1.49, 95% CI: 0.96-1.57). For mRNA-1273, there were increased risks of parethesia (vs. ChAdOx1nCov-19, OR: 2.37, 95% CI: 1.48-3.79); vertigo (vs. ChAdOx1nCov-19, OR: 1.68, 95% CI: 1.20-2.35); diplopia (vs. ChAdOx1nCov-19, OR: 1.55, 95% CI: 0.67-3.57); and sleepiness (vs. ChAdOx1nCov-19, OR: 1.28, 95% CI: 0.98-1.67). In the period that ranged from March to August 2021, no one was hospitalized and/or died of severe complications related to COVID-19 vaccinations.
DISCUSSION
This study estimates the prevalence and risk for neurological complications potentially associated with COVID-19 vaccines, thus improving the vaccination guidelines and loading in future personalized preventive medicine.
PubMed: 37897023
DOI: 10.3390/vaccines11101621 -
Journal of Central Nervous System... 2024Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune neuroinflammatory disorder with a prevalence of 1-5/100,000 globally, characterized by attacks of the... (Review)
Review
Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune neuroinflammatory disorder with a prevalence of 1-5/100,000 globally, characterized by attacks of the central nervous system including but not limited to optic neuritis, transverse myelitis and brainstem lesions, including area postrema lesions. These autoimmune attacks can lead to irreversible damage if left untreated, therefore strategies have been developed to prevent relapses. Initial off-label treatments have achieved variable levels of success in relapse prevention, but improved relapse prevention and quality of life remain a goal in the field. A better understanding of the underlying pathophysiology of NMOSD over the last 10 years has led to newer, more specific approaches in treatment, culminating in the first FDA approved treatments in the disease. In this review, we will discuss the seminal trials of PREVENT or Eculizumab in the treatment of aquaporin-4 (AQP4)-IgG positive NMOSD, N-Momentum or Inebilizumab in the study of NMOSD (both AQP4-IgG positive and negative) and SAkura Sky and SAkuraStar which studied satralizumab in AQP4-IgG seropositive and seronegative NMOSD patients. We will also discuss the extension trials of each of these medications and what lead to their approval in AQP4-IgG seropositive NMOSD patients. We will then examine treatments in the pipeline for adult and pediatric NMOSD patients and conclude with discussions on treatment considerations in pregnant patients and how to approach treatment of NMOSD patients during COVID.
PubMed: 38312734
DOI: 10.1177/11795735241231094 -
Therapeutic Advances in Neurological... 2023The terminal complement C5 inhibitor eculizumab is approved in Japan for relapse prevention in aquaporin-4 antibody-positive (AQP4+) neuromyelitis optica spectrum...
Long-term safety and effectiveness of eculizumab in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: a 2-year interim analysis of post-marketing surveillance in Japan.
BACKGROUND
The terminal complement C5 inhibitor eculizumab is approved in Japan for relapse prevention in aquaporin-4 antibody-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) and is undergoing mandatory post-marketing surveillance (PMS) of clinical use.
OBJECTIVES
The objective of the study is to assess the real-world, long-term safety and effectiveness of eculizumab in Japanese patients with AQP4+ NMOSD.
DESIGN
Regulatory-mandated PMS analysis implemented as an all-case surveillance of all patients with AQP4+ NMOSD who have been treated with eculizumab in Japan since its approval in November 2019.
METHODS
This PMS interim analysis assessed the safety and effectiveness of eculizumab in Japanese patients with AQP4+ NMOSD from November 2019 to April 2022.
RESULTS
Of 147 patients treated with eculizumab who consented to publication, 71 had at least one case report form collected and locked at the interim analysis data cut-off, constituting the safety analysis set; three patients from PREVENT (NCT01892345) were excluded from the effectiveness analysis set. Twelve and 10 patients in the safety and effectiveness analysis sets discontinued, respectively. In the safety analysis set, 67/71 patients (94.4%) were female, mean illness duration was 6.8 [standard deviation (SD): 6.2] years, mean age at eculizumab initiation was 50.7 (SD: 13.3) years, and mean eculizumab treatment duration was 44.6 (SD: 23.7) weeks. At diagnosis of NMOSD, 34/71 patients (47.9%) and 35/71 patients (49.3%) in the safety analysis set had symptoms of optic neuritis and transverse myelitis, respectively. In the safety analysis set, 19/71 patients (26.8%) reported adverse events, 10/71 (14.1%) reported adverse drug reactions (ADRs), and 7/71 (9.9%) reported serious ADRs; no meningococcal infections were observed. In the effectiveness analysis set, 64/68 patients (94.1%) were female, mean disease duration was 6.9 (SD: 6.3) years, mean age at eculizumab initiation was 50.6 (SD: 13.2) years, and 27/68 (39.7%) were tested for C5 genetic polymorphism (all negative). In the 2 years before eculizumab, 51/68 patients (75.0%) experienced relapse. Relapse rate was 0.02/patient-year after eculizumab initiation 0.74/patient-year in the 2 years before eculizumab. Overall, 37/68 patients (54.4%) were prescribed immunosuppressants in the 6 months before and 19/40 (47.5%) in the 6-12 months after starting eculizumab treatment. The proportion of patients taking >10 mg/day of prednisolone decreased from 45.6% at 24-20 weeks before to 23.1% and 0% at 48-52 and 100-104 weeks after eculizumab, respectively.
CONCLUSION
This article reports interim PMS data for Japanese patients and provides updated real-world evidence for the safety of eculizumab and its effectiveness at preventing relapses in patients with AQP4+ NMOSD. Safety and effectiveness results are consistent with those from PREVENT.
PubMed: 37441104
DOI: 10.1177/17562864231181177 -
Frontiers in Immunology 2023Myelin oligodendrocyte glycoprotein antibody-associated autoimmune disease (MOGAD) is a rare monophasic or relapsing inflammatory demyelinating disease of the central...
BACKGROUND
Myelin oligodendrocyte glycoprotein antibody-associated autoimmune disease (MOGAD) is a rare monophasic or relapsing inflammatory demyelinating disease of the central nervous system (CNS) and can mimic multiple sclerosis (MS). The variable availability of live cell-based MOG-antibody assays and difficulties in interpreting low-positive antibody titers can complicate diagnosis. Literature on cerebrospinal fluid (CSF) profiles in MOGAD versus MS, one of the most common differential diagnoses, is scarce. We here analyzed the value of basic CSF parameters to i) distinguish different clinical MOGAD manifestations and ii) differentiate MOGAD from MS.
METHODS
This is retrospective, single-center analysis of clinical and laboratory data of 30 adult MOGAD patients and 189 adult patients with relapsing-remitting multiple sclerosis. Basic CSF parameters included CSF white cell count (WCC) and differentiation, CSF/serum albumin ratio (Q), intrathecal production of immunoglobulins, CSF-restricted oligoclonal bands (OCB) and MRZ reaction, defined as intrathecal production of IgG reactive against at least 2 of the 3 viruses measles (M), rubella (R) and varicella zoster virus (Z).
RESULTS
MOGAD patients with myelitis were more likely to have a pleocytosis, a Q elevation and a higher WCC than those with optic neuritis, and, after review and combined analysis of our and published cases, they also showed a higher frequency of intrathecal IgM synthesis. Compared to MS, MOGAD patients had significantly more frequently neutrophils in CSF and WCC>30/µl, Q>10×10, as well as higher mean Q values, but significantly less frequently CSF plasma cells and CSF-restricted OCB. A positive MRZ reaction was present in 35.4% of MS patients but absent in all MOGAD patients. Despite these associations, the only CSF parameters with relevant positive likelihood ratios (PLR) indicating MOGAD were Q>10×10 (PLR 12.60) and absence of CSF-restricted OCB (PLR 14.32), whereas the only relevant negative likelihood ratio (NLR) was absence of positive MRZ reaction (NLR 0.00).
CONCLUSION
Basic CSF parameters vary considerably in different clinical phenotypes of MOGAD, but Q>10×10 and absence of CSF-restricted OCB are highly useful to differentiate MOGAD from MS. A positive MRZ reaction is confirmed as the strongest CSF rule-out parameter in MOGAD and could be useful to complement the recently proposed diagnostic criteria.
Topics: Adult; Humans; Multiple Sclerosis; Retrospective Studies; Autoimmune Diseases; Antibodies; Immune System Diseases
PubMed: 37744325
DOI: 10.3389/fimmu.2023.1237149 -
Yonsei Medical Journal Nov 2023Acute ascending hemorrhagic longitudinally extensive transverse myelitis is a rare inflammatory demyelinating disorder, which invades several vertebral segments and...
Acute ascending hemorrhagic longitudinally extensive transverse myelitis is a rare inflammatory demyelinating disorder, which invades several vertebral segments and progresses rapidly and manifests severe symptoms. We present a case of acute necrotizing myelitis associated with COVID-19 infection. A 10-year-old female, with no previous medical history and no prior administration of COVID-19 vaccination, contracted COVID-19 in early April 2022. Two weeks later, she suffered from severe posterior neck pain and also presented with motor weakness and numbness in both lower extremities, making it difficult to walk independently and spontaneously void urine. Initial spinal cord MR showed longitudinally segmental extensive T2 hyperintensities. Cerebrospinal fluid (CSF) analysis revealed elevated red blood cell, normal white blood cell, and elevated protein levels and absence of oligoclonal bands. CSF culture and viral polymerase chain reaction were negative. Autoimmune work-up was negative. She was started on intravenous methylprednisolone 1g/day for 5 days and immunoglobulin (Ig) 2 g/kg for 5 days. She was also treated with six courses of therapeutic plasma exchange. Nevertheless, her pain and motor weakness persisted. She eventually developed respiratory failure. Follow-up MR presented a newly noted small hemorrhagic component. She was consequently treated with two additional courses of methylprednisolone and Ig. At 6-months follow-up, neurological examination showed improvement with normal sensory function and motor grade IV function in both upper extremities. We present the case of acute necrotizing myelitis associated with COVID-19 infection. Multiple courses of methylprednisolone and Ig showed mild improvement in motor and sensory function. However, poor prognosis was unavoidable due to rapid progression of the disease.
Topics: Humans; Female; Child; Myelitis, Transverse; COVID-19 Vaccines; COVID-19; Methylprednisolone
PubMed: 37880851
DOI: 10.3349/ymj.2023.0202 -
Frontiers in Immunology 2024COVID-19 vaccines have been approved due to their excellent safety and efficacy data and their use has also permitted to reduce neurological complications of SARS-CoV-2....
BACKGROUND
COVID-19 vaccines have been approved due to their excellent safety and efficacy data and their use has also permitted to reduce neurological complications of SARS-CoV-2. However, clinical trials were underpowered to detect rare adverse events. Herein, the aim was to characterize the clinical spectrum and immunological features of central nervous system (CNS) immune-related events following SARS-CoV-2 vaccination.
METHODS
Multicenter, retrospective, cohort study (December 1, 2020-April 30, 2022). Inclusion criteria were (1) CNS disorders developing after SARS-CoV-2 vaccination (probable causal relationship as per 2021 Butler criteria) (2); evidence for an immune-mediated etiology, as per (i) 2016 Graus criteria for autoimmune encephalitis (AE); (ii) 2015 Wingerchuk criteria for neuromyelitis optica spectrum disorders; (iii) criteria for myelitis.
RESULTS
Nineteen patients were included from 7 tertiary referral hospitals across Italy and France (one of them being a national referral center for AE), over almost 1 year and half of vaccination campaign. Vaccines administered were mRNA-based (63%) and adenovirus-vectored (37%). The median time between vaccination and symptoms onset was 14 days (range: 2-41 days). CSF was inflammatory in 74%; autoantibodies were detected in 5%. CSF cytokine analysis (n=3) revealed increased CXCL-10 (IP-10), suggesting robust T-cell activation. The patients had AE (58%), myelitis (21%), acute disseminated encephalomyelitis (ADEM) (16%), and brainstem encephalitis (5%). All patients but 2 received immunomodulatory treatment. At last follow-up (median 130 days; range: 32-540), only one patient (5%) had a mRS>2.
CONCLUSION
CNS adverse events of COVID-19 vaccination appear to be very rare even at reference centers and consist mostly of antibody-negative AE, myelitis, and ADEM developing approximately 2 weeks after vaccination. Most patients improve following immunomodulatory treatment.
Topics: Humans; SARS-CoV-2; COVID-19 Vaccines; COVID-19; Retrospective Studies; Cohort Studies; Vaccination; Neuromyelitis Optica; Encephalomyelitis, Acute Disseminated; Myelitis; Central Nervous System
PubMed: 38375477
DOI: 10.3389/fimmu.2024.1344184 -
SAGE Open Medicine 2024Arboviruses are RNA viruses and some have the potential to cause neuroinvasive disease and are a growing threat to global health. (Review)
Review
BACKGROUND
Arboviruses are RNA viruses and some have the potential to cause neuroinvasive disease and are a growing threat to global health.
OBJECTIVES
Our objective is to identify and map all aspects of arbovirus neuroinvasive disease, clarify key concepts, and identify gaps within our knowledge with appropriate future directions related to the improvement of global health.
METHODS
: A scoping review of the literature was conducted using PubMed, Scopus, ScienceDirect, and Hinari. : Original data including epidemiology, risk factors, neurological manifestations, neuro-diagnostics, management, and preventive measures related to neuroinvasive arbovirus infections was obtained. Sources of evidence not reporting on original data, non-English, and not in peer-reviewed journals were removed. : An initial pilot sample of 30 abstracts were reviewed by all authors and a Cohen's kappa of = 0.81 (near-perfect agreement) was obtained. Records were manually reviewed by two authors using the Rayyan QCRI software.
RESULTS
A total of 171 records were included. A wide array of neurological manifestations can occur most frequently, including parkinsonism, encephalitis/encephalopathy, meningitis, flaccid myelitis, and Guillain-Barré syndrome. Magnetic resonance imaging of the brain often reveals subcortical lesions, sometimes with diffusion restriction consistent with acute ischemia. Vertical transmission of arbovirus is most often secondary to the Zika virus. Neurological manifestations of congenital Zika syndrome, include microcephaly, failure to thrive, intellectual disability, and seizures. Cerebrospinal fluid analysis often shows lymphocytic pleocytosis, elevated albumin, and protein consistent with blood-brain barrier dysfunction.
CONCLUSIONS
Arbovirus infection with neurological manifestations leads to increased morbidity and mortality. Risk factors for disease include living and traveling in an arbovirus endemic zone, age, pregnancy, and immunosuppressed status. The management of neuroinvasive arbovirus disease is largely supportive and focuses on specific neurological complications. There is a need for therapeutics and currently, management is based on disease prevention and limiting zoonosis.
PubMed: 38711470
DOI: 10.1177/20503121241229847 -
The Pan African Medical Journal 2023Nigeria made a coordinated effort to be certified by the World Health Organization's African Region for interrupting endemic transmission of wild poliovirus type-1... (Review)
Review
Nigeria made a coordinated effort to be certified by the World Health Organization's African Region for interrupting endemic transmission of wild poliovirus type-1 (WPV1) in August 2020 as a response to the resurgence of WPV1 cases in August 2016 after going two years without a case. The NEOC Data Working Group (DWG) was instrumental in providing quality and timely surveillance and campaign information for decision-making in order to interrupt WPV1 transmission and provide data toward documentation of its elimination for regional certification. The polio pre-campaign dashboard was used to assess the level of preparedness for Oral Poliovirus Vaccine (OPV) polio supplementary immunization activities (SIA) at three weeks, two weeks, one week, and three days to the start of each campaign implemented during 2016-2020. The administrative tally sheet, independent monitoring survey, and Lot Quality Assurance Sampling (LQAS) survey data collected and shared from the implementation level were analyzed by the EOC DWG to provide information by person, place, and time. Using a 90% threshold in LQAS surveys defining quality SIAs, the proportion of Local Government Areas (LGAs) in Nigeria's states in which post-SIA LQAS surveys were conducted that met this threshold were assessed over time. The highest level of preparedness attained by 3 days to a polio campaign during August 2016-February 2020 was 95% and the lowest attained was 77%. The admin, independent monitoring, and LQAS data analysis results were given to EOC working groups for assessing the performance and quality of each campaign. Twenty-twenty five percent of LGAs that failed LQAS were identified for repeat vaccination. Further, acute flaccid paralysis and environmental surveillance data and laboratory results were analyzed and shared with NEOC and partners. The government and partners used the information generated by the Data Working Group to take evidence-based action including determining the scope of the polio campaign, intensification of surveillance and routine immunization activities, and special intervention activities. On average, 12% of the 774 LGAs were identified as polio high risk LGAs for intervention using selected surveillance, routine immunization (RI), SIAs, and other relevant data sets. National Emergency Operation Centre Data Working Group provided quality and timely information that supported decision-making processes for the polio program in Nigeria. The quality and timely information enabled the NEOC to make evidence-based and timely decisions that contributed to gap identification and decision-making.
Topics: Humans; Lot Quality Assurance Sampling; Disease Eradication; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Nigeria; Immunization Programs
PubMed: 38370106
DOI: 10.11604/pamj.supp.2023.45.2.39489 -
Clinical Medicine (London, England) Jul 2023We present a case where a 63-year-old right-handed man who presented with a 6-month history of progressive asymmetrical sensorimotor symptoms in lower limbs. This was...
We present a case where a 63-year-old right-handed man who presented with a 6-month history of progressive asymmetrical sensorimotor symptoms in lower limbs. This was associated with concomitant rash on the lower limbs, and mild sicca symptoms. MRI spine showed focal T2 hyperintensity in the left hemicord at C3-4 level. Skin biopsy of the rash revealed urticarial vasculitis, and lip biopsy revealed lymphocytic sialadenitis. Initial anti-Ro antibody was negative, but subsequent Ro52 antibody testing returned positive. There was also matched serum and cerebrospinal fluid oligoclonal bands. He was subsequently diagnosed as Sjogren's myelitis and treated with intravenous methylprednisolone, then transitioned to a steroid sparing agent. This case highlights the difficulties in reaching a rheumatological diagnosis in the early stages with typical negative antibodies, and shows a rare neurological manifestation of a systemic rheumatological condition.
Topics: Male; Humans; Middle Aged; Sjogren's Syndrome; Brown-Sequard Syndrome; Myelitis; Magnetic Resonance Imaging; Exanthema
PubMed: 37524434
DOI: 10.7861/clinmed.2023-0158 -
Nature Jul 2023Vaccination with Sabin, a live attenuated oral polio vaccine (OPV), results in robust intestinal and humoral immunity and has been key to controlling poliomyelitis. As...
Vaccination with Sabin, a live attenuated oral polio vaccine (OPV), results in robust intestinal and humoral immunity and has been key to controlling poliomyelitis. As with any RNA virus, OPV evolves rapidly to lose attenuating determinants critical to the reacquisition of virulence resulting in vaccine-derived, virulent poliovirus variants. Circulation of these variants within underimmunized populations leads to further evolution of circulating, vaccine-derived poliovirus with higher transmission capacity, representing a significant risk of polio re-emergence. A new type 2 OPV (nOPV2), with promising clinical data on genetic stability and immunogenicity, recently received authorization from the World Health Organization for use in response to circulating, vaccine-derived poliovirus outbreaks. Here we report the development of two additional live attenuated vaccine candidates against type 1 and 3 polioviruses. The candidates were generated by replacing the capsid coding region of nOPV2 with that from Sabin 1 or 3. These chimeric viruses show growth phenotypes similar to nOPV2 and immunogenicity comparable to their parental Sabin strains, but are more attenuated. Our experiments in mice and deep sequencing analysis confirmed that the candidates remain attenuated and preserve all the documented nOPV2 characteristics concerning genetic stability following accelerated virus evolution. Importantly, these vaccine candidates are highly immunogenic in mice as monovalent and multivalent formulations and may contribute to poliovirus eradication.
Topics: Animals; Mice; Disease Models, Animal; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Vaccines, Attenuated; Disease Eradication
PubMed: 37316671
DOI: 10.1038/s41586-023-06212-3