-
Brain, Behavior, & Immunity - Health Jul 2024Coronavirus disease 2019 (COVID-19) vaccination has become the most effective countermeasure in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)... (Review)
Review
Coronavirus disease 2019 (COVID-19) vaccination has become the most effective countermeasure in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, vaccination is associated with side effects. This narrative review focuses on central nervous system (CNS) manifestations following COVID-19 vaccination and provides a summary of the potential underlying mechanisms and methods of diagnosis and management of the vaccination-related CNS manifestations. Headache, myalgia, optic neuritis, seizure, multiple sclerosis, acute disseminated encephalomyelitis and encephalitis, delirium, acute transverse myelitis, and stroke have been reported after COVID-19 vaccination. Constant headache and myalgia are common manifestations that may necessitate further clinical investigation for stroke. To limit consequences, it is imperative to follow standard treatment protocols for each neurological disorder following COVID-19 vaccination. Immunosuppressive medication can be helpful in the treatment of seizures following vaccination since the immune response is involved in their etiology. Clinicians should be aware of the manifestations after COVID-19 vaccination to respond promptly and effectively. Clinical guidelines for the management of CNS manifestations following COVID-19 vaccination are in high demand and would be useful in each new SARS-CoV-2 variant pandemic.
PubMed: 38818372
DOI: 10.1016/j.bbih.2024.100788 -
Brain Hemorrhages Sep 2023A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in December 2019 in Wuhan, China. The new coronavirus disease... (Review)
Review
A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in December 2019 in Wuhan, China. The new coronavirus disease (COVID-19) was declared a global pandemic by the World Health Organization (WHO) in March 2020. SARS-CoV-2 can invade the nervous system aside from infecting the respiratory system as its primary target. The most common nervous system symptoms of COVID-19 are stated as headache, myalgia, fatigue, nausea, vomiting, sudden and unexplained anosmia, and ageusia. More severe conditions such as encephalomyelitis, acute myelitis, thromboembolic events, ischemic stroke, intracerebral hemorrhage, Guillain-Barré-syndrome, Bell's palsy, rhabdomyolysis, and even coma have also been reported. Cohort studies revealed that neurological findings are associated with higher morbidity and mortality. The neurological symptoms and manifestations caused by SARS-CoV-2 and COVID-19 are examined and summarized in this article.
PubMed: 36789140
DOI: 10.1016/j.hest.2023.02.001 -
Multiple Sclerosis (Houndmills,... Jul 2023The N-MOmentum trial investigated safety and efficacy of inebilizumab in participants with neuromyelitis optica spectrum disorder (NMOSD). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The N-MOmentum trial investigated safety and efficacy of inebilizumab in participants with neuromyelitis optica spectrum disorder (NMOSD).
OBJECTIVE
Evaluate the attack identification process and adjudication committee (AC) performance in N-MOmentum.
METHODS
Adults ( = 230) with NMOSD and Expanded Disability Status Scale score ⩽8 were randomized (3:1) to inebilizumab 300 mg or placebo. The randomized controlled period was 28 weeks or until adjudicated attack. Attacks were adjudicated according to 18 predefined criteria. Magnetic resonance imaging (MRI) and biomarker (serum glial fibrillary acidic protein [sGFAP]) analyses were performed.
RESULTS
A total of 64 participant-reported neurological events occurred; 51 (80%) were investigator-determined to be attacks. The AC confirmed 43 of the investigator-determined attacks (84%). There was high inter- and intra-AC-member agreement. In 25/64 events (39%) and 14/43 AC-adjudicated attacks (33%), MRI was reviewed during adjudication. Retrospective analysis revealed new domain-specific T1 and T2 MRI lesions in 90% of adjudicated attacks. Increased mean sGFAP concentrations (>2-fold change) from baseline were observed in 56% of adjudicated attacks versus 14% of investigator-determined attacks rejected by the AC and 31% of participant-reported events determined not to be attacks.
CONCLUSION
AC adjudication of NMOSD attacks according to predefined criteria appears robust. MRI lesion correlates and sGFAP elevations were found in most adjudicated attacks.
Topics: Neuromyelitis Optica; Humans; Magnetic Resonance Imaging; Biomarkers; Glial Fibrillary Acidic Protein; Antibodies, Monoclonal, Humanized; Retrospective Studies
PubMed: 37282545
DOI: 10.1177/13524585231172145 -
The Pan African Medical Journal 2023The Nigeria Polio Emergency Operations Centre (EOC) was established in October 2012 to strengthen coordination, provide strategic direction based on real-time data... (Review)
Review
The Nigeria Polio Emergency Operations Centre (EOC) was established in October 2012 to strengthen coordination, provide strategic direction based on real-time data analysis, and manage all operational aspects of the polio eradication program. The establishment of seven state-level polio EOCs followed. With success achieved in the interruption of wild poliovirus (WPV) transmission as certified in 2020, the future direction of the polio EOC is under consideration. This paper describes the role of the polio EOC in other emergencies and perspectives on future disease control initiatives. A description of the functionality and operations of the polio EOC and a review of documentation of non-polio activities supported by the EOC was done. Key informant insights of national and state-level stakeholders were collected through an electronic questionnaire to determine their perspectives on the polio EOC's contributions and its future role in other public health interventions. The polio EOC structure is based on an incident management system with clear terms of reference and accountability and with full partner coordination. A decline in WPV1 cases was observed from 122 cases in 2012 to 0 in 2015; previously undetected transmission of WPV1 was confirmed in 2016 and all transmission was interrupted under the coordination of the EOCs at national and state levels. During 2014-2019, the polio EOC infrastructure and staff expertise were used to investigate and respond to outbreaks of Ebola, measles, yellow fever, and meningitis and to oversee maternal and neonatal tetanus elimination campaigns. The EOC structure at the national and state levels has contributed to the positive achievements in the polio eradication program in Nigeria and further in the coordination of other disease control and emergency response activities. The transition of the polio EOCs and their capacities to support other non-polio programs will contribute to harnessing the country's capacity for effective coordination of public health initiatives and disease outbreaks.
Topics: Infant, Newborn; Humans; Nigeria; Immunization Programs; Population Surveillance; Poliomyelitis; Poliovirus; Disease Outbreaks; Disease Eradication
PubMed: 38370098
DOI: 10.11604/pamj.supp.2023.45.2.41308 -
Communicable Diseases Intelligence... Aug 2023For 30 years the Australian Paediatric Surveillance Unit (APSU) has conducted national surveillance of rare communicable diseases and rare complications of communicable...
For 30 years the Australian Paediatric Surveillance Unit (APSU) has conducted national surveillance of rare communicable diseases and rare complications of communicable diseases. In this report, we describe the results of thirteen such studies surveyed by the APSU in 2022, including reported case numbers and incidence estimates, demographics, clinical features, management and short-term outcomes. Conditions described are: acute flaccid paralysis (AFP); congenital cytomegalovirus (cCMV); neonatal and infant herpes simplex virus (HSV) infection; perinatal exposure to human immunodeficiency virus (HIV) and paediatric HIV infection; severe complications of influenza; juvenile-onset recurrent respiratory papillomatosis (JoRRP); congenital rubella infection/syndrome; congenital varicella syndrome (CVS) and neonatal varicella infection (NVI); and the new conditions dengue; Q fever; and severe acute hepatitis. In 2022, cases of severe complications of influenza were reported to the APSU for the first time since 2019. This likely reflects the easing of government-mandated restrictions imposed in 2020-2021 to curb the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the re-emergence of a range of infectious diseases. As previously, AFP surveillance by the APSU contributed to Australia achieving a minimum target incidence of one AFP case per 105 children aged less than 15 years. Cases of JoRRP and NVI were reported in 2022. This indicates potential gaps in human papillomavirus (HPV) and varicella vaccination coverage respectively, especially in high-risk groups such as young migrant and refugee women of childbearing age from countries without universal vaccination programs. Paediatric HIV case numbers resulting from mother-to-child-transmission (MTCT) of HIV remain low in Australia due to use of effective intervention strategies. However, there has been an increase in the number of imported cases of HIV in children (mainly perinatally-acquired) from countries with a high HIV prevalence. Without effective vaccines, there has been no decline in the incidence of congenital CMV and neonatal HSV, indicating the importance of early identification and management to reduce morbidity and mortality. The first cases of dengue, Q fever and severe acute hepatitis were received by APSU in 2022, including two cases of acute hepatitis in which aetiology has not been confirmed to date. The APSU has an important ongoing role in monitoring rare childhood infections.
Topics: Infant; Infant, Newborn; Pregnancy; Humans; Female; Child; HIV Infections; Chickenpox; Influenza, Human; Q Fever; alpha-Fetoproteins; Australia; Infectious Disease Transmission, Vertical; Communicable Diseases; Cytomegalovirus Infections; Rubella Syndrome, Congenital; Hepatitis; Dengue
PubMed: 37817313
DOI: 10.33321/cdi.2023.47.46 -
Virulence Dec 2023Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which...
Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which there is no effective treatment. There is great interest in developing potential biomarkers to predict the pathogenesis of HAM/TSP disease. In this study, Illumina Massive Parallel Sequencing (MPS) technology was used to investigate the cellular global noncoding RNAome expression profile in HAM/TSP patients ( = 10), asymptomatic HTLV-1-infected carriers (ASP, = 8), and a second group of healthy controls ( = 5). Various bioinformatics tools were used to align, annotate, and profile the sRNA-MPS reads. Among the 402 sRNAs detected, 251 were known and 50 were potentially novel sRNAs in the HAM and ASP groups compared with the HC group. Sixty-eight known sRNAs were significantly different between the ASP and HAM groups. Eighty-eight mature miRNAs were downregulated in subjects from HAM compared with ASP. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The seven most deregulated miRs target genes have been associated with a variety of biological processes and molecular functions. The reactome pathways relevant to our findings provide a rich source of data and offer the opportunity to better understand sRNA regulation and function in HTLV-1 pathophysiology. To the best of our knowledge, this study is the first to demonstrate evaluates sRNAs in HTLV-1 patients with HAM/TSP.
Topics: Humans; Prognosis; Paraparesis, Tropical Spastic; Human T-lymphotropic virus 1; MicroRNAs; Biomarkers
PubMed: 37394816
DOI: 10.1080/21505594.2023.2230015 -
European Journal of Physical and... Apr 2024Poliomyelitis is a global disabling disease affecting 12-20 million of people. Post poliomyelitis syndrome (PPS) may affect up to 80% of polio survivors: increased...
BACKGROUND
Poliomyelitis is a global disabling disease affecting 12-20 million of people. Post poliomyelitis syndrome (PPS) may affect up to 80% of polio survivors: increased muscle weakness, pain, fatigue, functional decline. It relies on aging of an impaired neuro-muscular system with ongoing denervation processes. A late involvement of humoral or cellular pro-inflammatory phenomena is also suspected.
AIM
To assess the dysimmune hypothesis of PPS by comparing lymphocyte subpopulations and humoral immune factors between PPS patients and controls.
DESIGN
Cross-sectional study.
SETTING
Montpellier University Hospital.
POPULATION
Forty-seven PPS and 27 healthy controls.
METHODS
PPS patients and controls were compared on their lymphocyte subpopulations and humoral immune factors (IL-1β, IL-6, IL-8, IL-17, IL-21, IL-22, IL-23, IFN-γ, TNF-α, GM-CSF, RANTES, MCP1, MIP-3a, IL-10, TGF-β, IL4, IL13). Patients were further compared according to their dominant clinical symptoms. Sample size guaranteed a power >90% for all comparisons.
RESULTS
PPS patients and controls were comparable in gender, age and corpulence. Most patients had lower limb motor sequelae (N.=45, 95.7%), a minority had upper limb motor impairment (N.=16, 34.0%). Forty-five were able to walk (94%), 35/45 with technical aids. The median of the two-minute walking test was 110 meters (interquartile range 55; 132). Eighteen (38%) required help in their daily life. Their quality of life was low (SF36). All described an increased muscular weakness, 40 (85%) a general fatigue, and 39 (83%) muscular or joint pain. Blood count, serum electrolytes, T and B lymphocyte subpopulations and cytokines were comparable between patients and controls, except for creatine phospho kinase that was significantly higher in PPS patients. None of these variables differed between the 20/47 patients whose late main symptoms were pain or fatigue, and other patients.
CONCLUSIONS
Our results suggest that PPS is not a dysimmune disease.
CLINICAL REHABILITATION IMPACT
Our results do not sustain immunotherapy for PPS. Our work suggest that PPS may be mostly linked to physiological age-related phenomena in a disabled neuromuscular condition. Thus, our results emphasize the role of prevention and elimination of aggravating factors to avoid late functional worsening, and the importance of rehabilitation programs that should be adapted to patients' specific conditions.
Topics: Humans; Postpoliomyelitis Syndrome; Cross-Sectional Studies; Quality of Life; Poliomyelitis; Pain; Fatigue; Muscle Weakness; Immunologic Factors
PubMed: 38252127
DOI: 10.23736/S1973-9087.23.08158-3 -
Annals of Medicine and Surgery (2012) Sep 2023Spinal infection poses a demanding diagnostic and treatment problem for which a multidisciplinary approach with spine surgeons, radiologists, and infectious disease...
INTRODUCTION
Spinal infection poses a demanding diagnostic and treatment problem for which a multidisciplinary approach with spine surgeons, radiologists, and infectious disease specialists is required. Infections are usually caused by bacterial microorganisms, although fungal infections can also occur. Most patients with spinal infections diagnosed in the early stages can be successfully managed conservatively with antibiotics, bed rest, and spinal braces. In cases of gross or pending instability, progressive neurological deficits, failure of conservative treatment, spinal abscess formation, severe symptoms indicating sepsis, and failure of previous conservative treatment, surgical treatment is required.
CASE PRESENTATION
A 64-year-old male presented to the Outpatient Department with a complaint of pain in bilateral upper extremities for 4 months. The pain was shooting in type, radiating to bilateral arms, forearms, and hands with no aggravating and relieving factors. He is a known case of carcinoma pyriform sinus for which he underwent various cycles of chemotherapy. Ten years later, a tracheostomy was performed for laryngeal edema, and again, an endoscopic gastrostomy was performed due to feeding difficulties. He then developed fever and cervical pain along with pain in the bilateral upper extremities. An infectious etiology was suspected for which multiple antibiotics were started with no positive response. An MRI was performed, which was suggestive of spondylodiscitis probably of tubercular origin. A biopsy was done to confirm the diagnosis, following which antitubercular (HRZE) therapy was started. He was also treated with Duloxetine and gabapentin, which resulted in minor improvements. Subsequent MRIs showed diffuse involvement of the multiple cervical vertebrae along with cord compression. Two stages of anterior corpectomy followed by posterior instrumentation were done. Following the procedure, the patient developed an infection, which was managed with antibiotics. The titanium implant was not removed. A muscle graft was planned with the pectoralis muscle and flap closure was done. The tissue was also sent for Gram stain, AFB stain, and GeneXpert, which showed normal findings. Finally, in tissue culture, was isolated. On performing the enzyme immunoassay test, it was found to be (Galactomannan antigen) positive as well. Antitubercular treatment was stopped. Then, he was managed with an antifungal, oral voriconazole, for the duration of 1 and a half years.
CLINICAL DISCUSSION
Patients diagnosed with spondylodiscitis tend to have favorable outcomes, likely linked to timely identification, thorough surgical debridement, and proper azole medication. Our case achieved success by promptly identifying and confirming it through tissue culture, detecting spinal cord compression, decompressing it, and initiating specific antifungal treatment. A delay in commencing antifungal therapy has been associated with poorer outcomes, especially in neurological health. Our patient received voriconazole for a full year, suggesting that favorable outcomes are achievable for fungal spondylodiscitis with swift and appropriate surgery and antifungal medication.
CONCLUSION
In summary, evaluation for fungal infection is essential in all cases of unexplained spinal infection in immunocompromised patients, regardless of presentation. If the antifungal treatment proves ineffective, a surgical approach is typically employed for the management of fungal spondylodiscitis. Our report details a successful case of fungal spondylodiscitis treated with a surgical approach and highlights the potential for a fungal infection to be a causative factor in noncompressive myelopathy, which may be sometimes mistaken for radiation myelitis.
PubMed: 37663715
DOI: 10.1097/MS9.0000000000001114 -
Ticks and Tick-borne Diseases Sep 2023In tick-borne encephalitis (TBE), lymphocytes infiltrating central nervous system are indispensable for the infection control, but also potentially immunopathogenic. To...
In tick-borne encephalitis (TBE), lymphocytes infiltrating central nervous system are indispensable for the infection control, but also potentially immunopathogenic. To clarify their roles, we have evaluated cerebrospinal fluid (CSF) count of the main lymphocyte populations (considered as a proxy of the brain parenchyma lymphocytic infiltrate) in TBE patients and analyzed if they associate with clinical presentation, blood-brain barrier disruption and intrathecal antibody synthesis. We have studied CSF from 96 adults with TBE (50 with meningitis, 40 with meningoencephalitis, 6 with meningoencephalomyelitis), 17 children and adolescents with TBE and 27 adults with non-TBE lymphocytic meningitis. Th CD3+CD4+, Tc CD3+CD8+, double positive T CD3+CD4+CD8+, B CD19+ and NK CD16+/56+ cells were counted cytometrically with a commercial fluorochrome-stained monoclonal antibody set. The associations between the counts and fractions of these cells and clinical parameters were analyzed with non-parametric tests, p<0.05 considered significant. The TBE patients had lower pleocytosis with similar proportions of the lymphocyte populations compared to non-TBE meningitis. The different lymphocyte populations correlated positively with one another, as well as with CSF albumin, IgG and IgM quotients. The higher pleocytosis and expansion of Th, Tc and B cells associated with a more severe disease and neurologic involvement: Th with encephalopathy, myelitis and weakly with cerebellar syndrome, Tc with myelitis and weakly with encephalopathy, B with myelitis and with at least moderately severe encephalopathy. The double-positive T lymphocytes associated with myelitis, but not with other forms of CNS involvement. The fraction of double positive T cells decreased in encephalopathy and the fraction of NK in patients with neurologic deficits. In children with TBE, Tc and B counts were increased at the expense of Th lymphocytes in comparison with adults. The concerted intrathecal immune response, involving the main lymphocyte populations, increases with the clinical severity of TBE, with no evidently protective or pathogenic elements distinguishable. However, the particular populations including B, Th and Tc cells associate with different, though overlapping, spectra of CNS manifestations, suggesting they may be specifically related to TBE manifesting as myelitis, encephalopathy and cerebellitis. The double-positive T and NK cells do not expand evidently with severity and may be most closely associated with the protective anti-TBEV response.
Topics: Adult; Child; Adolescent; Humans; Encephalitis, Tick-Borne; Leukocytosis; Lymphocytes; Myelitis; Brain Diseases
PubMed: 37245253
DOI: 10.1016/j.ttbdis.2023.102204 -
Frontiers in Immunology 2023Extracellular vesicles and particles (EVPs) are released from virtually all cell types, and may package many inflammatory factors and, in the case of infection, viral...
BACKGROUND AND OBJECTIVES
Extracellular vesicles and particles (EVPs) are released from virtually all cell types, and may package many inflammatory factors and, in the case of infection, viral components. As such, EVPs can play not only a direct role in the development and progression of disease but can also be used as biomarkers. Here, we characterized immune signatures of EVPs from the cerebrospinal fluid (CSF) of individuals with HTLV-1-associated myelopathy (HAM), other chronic neurologic diseases, and healthy volunteers (HVs) to determine potential indicators of viral involvement and mechanisms of disease.
METHODS
We analyzed the EVPs from the CSF of HVs, individuals with HAM, HTLV-1-infected asymptomatic carriers (ACs), and from patients with a variety of chronic neurologic diseases of both known viral and non-viral etiologies to investigate the surface repertoires of CSF EVPs during disease.
RESULTS
Significant increases in CD8+ and CD2+ EVPs were found in HAM patient CSF samples compared to other clinical groups ( = 0.0002 and = 0.0003 compared to HVs, respectively, and = 0.001 and = 0.0228 compared to MS, respectively), consistent with the immunopathologically-mediated disease associated with CD8+ T-cells in the central nervous system (CNS) of HAM patients. Furthermore, CD8+ ( < 0.0001), CD2+ ( < 0.0001), CD44+ ( = 0.0176), and CD40+ ( = 0.0413) EVP signals were significantly increased in the CSF from individuals with viral infections compared to those without.
DISCUSSION
These data suggest that CD8+ and CD2+ CSF EVPs may be important as: 1) potential biomarkers and indicators of disease pathways for viral-mediated neurological diseases, particularly HAM, and 2) as possible meditators of the disease process in infected individuals.
Topics: Humans; Paraparesis, Tropical Spastic; Central Nervous System; Extracellular Vesicles; Nervous System Diseases; CD40 Antigens; Chronic Disease
PubMed: 37622115
DOI: 10.3389/fimmu.2023.1235791