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Introduction: SARS-CoV-2 mainly affects the respiratory system, but the damage caused by this virus also extends to other systems, including the nervous system, and the mechanisms of neurological infection can be direct or indirect. Objective(s): To determine the relationship between neurological manifestations and disease severity in symptomatic COVID-19 positive patients at San Vicente de Paul Hospital in 2021. Material(s) and Method(s): A cross-sectional observational study was conducted using medical records of patients hospitalized with COVID-19 and neurological manifestations, which were classified into manifestations of the central nervous system and manifestations of the peripheral nervous system. Result(s): The results show that 74,1 % of patients presented neurological manifestations;the highest percentage was concentrated in patients who developed severe disease (15 [60 %], CNS;91 [77,1 %], PNS;125 [65,4 %], CNS and PNS). The joint presence of central and peripheral neurological manifestations was significantly associated with critical COVID-19 (P value= 0,011;OR: 2,005). The mortality rate reached 2,69 %. Conclusion(s): Neurological manifestations in hospitalized COVID-19 patients are very common, and critical COVID-19 is more likely to have neurological manifestations.Copyright © 2022 Universidad de Ciencias Medicas de La Hab. All rights reserved.
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Listeriosis is a saprozoonotic infection that occurs when eating foods contaminated with Listeria. Invasive forms of listeriosis can have extremely severe consequences. Respiratory viral diseases predispose to the occurrence of combined viral-bacterial infections. With a mixed infection of listeriosis and COVID-19, a severe course of the disease is observed, which has a serious prognosis. The aim of the study was to analyze the frequency of various variants of invasive listeriosis and their outcomes in the period before the COVID-19 pandemic and against the background of its development, as well as to determine the genetic diversity of L. monocytogenes isolates. Material and methods. We analyzed 55 cases of invasive listeriosis in patients observed in 2018-2021 in various medical organizations in Moscow. The diagnosis was established on the basis of epidemiological, clinical and laboratory data, listeriosis was confirmed by bacteriological and molecular genetic methods, COVID-19 was confirmed by the detection of SARS-CoV-2 RNA in an oropharyngeal swab using real-time RT-PCR, as well as computed tomography of the lungs. Results. During the current COVID-19 pandemic (2020-2021), the incidence of listeriosis in pregnant women and invasive listeriosis occurring in the form of sepsis and/or lesions of the central nervous system did not differ significantly from similar indicators registered in 2018-2019. Listeria sepsis and/or meningitis/meningoencephalitis in association with severe SARS-CoV-2 novel coronavirus infection are at high risk of death. During the years of the COVID-19 pandemic, the diversity and range of L. monocytogenes genotypes in invasive listeriosis changed, new genotypes appeared that were not previously characteristic of the Russian Federation. Conclusion. The likelihood of developing listeriosis sepsis and/or meningitis/meningoencephalitis against the background of a severe course of COVID-19, and a high risk of an adverse outcome, require increased awareness of medical workers in the field of diagnosis and treatment of invasive listeriosis in order to conduct the earliest and most adequate antibiotic therapy.Copyright © 2022 Geotar Media Publishing Group. All Rights Reserved.
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In December 2019, a novel coronavirus outbreak spread rapidly all over the world. The virus is known to be neuroinvasive, but much is still unknown. In this study, we aimed to pres-ent the main neurologic symptoms in patients who were diagnosed with coronavirus disease 2019 (COVID-19). The study was conducted retrospectively by phoning 156 patients in Turkey diagnosed with COVID-19 through real-time polymerase chain reaction;only 100 patients could be reached. Data about their demographics, initial symptoms, neurological symptoms, and sleeping habits were collected. During the disease process, 66% had at least one neurological symptom, 55% had central nervous system symptoms, 42% had peripheral nervous system symptoms, and 64% had sleep disturbances and myalgia. Impaired consciousness, smell and taste impairments, and sleep disturbances were significantly higher in patients with positive chest computed tomography imaging (p < 0.05). Neurological symptoms were observed in COVID-19, as in other coronaviruses. Headache in particular was the most common symptom in our population. In patients with respiratory system findings, the detec-tion of certain neurological symptoms such as smell-taste impairments, impaired consciousness, and sleep disorders were more common. We concluded that COVID-19 patients should be approached in a more holistic way, taking the nervous system into account.Copyright © 2022, Dr. Mladen Stojanovic University Hospital. All rights reserved.
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The relevance of research on a novel coronavirus infection is associated with an increase in the incidence among children since 2021, which may be due to the accumulation of mutations in the virus genome and its evolution towards increased contagiousness, replicative ability, and evasion of immune protection. While there are many studies in adults, data analyzing the clinical course of the disease in pediatric patients infected with SARS-CoV-2 are limited, particularly regarding adolescents. Objective. To study the clinical and laboratory features of the course of a novel coronavirus infection in hospitalized adolescents in Novosibirsk during the first, second and third waves of the pandemic. Materials and methods. A retrospective analysis of case histories of 125 children treated at Novosibirsk Children's Clinical Hospital No 6 with a confirmed diagnosis of coronavirus infection during three pandemic waves was carried out (June- August 2020, October-December 2020, June-August 2021). Based on these time intervals, three groups of adolescents admitted to the hospital during the first, second, and third waves of coronavirus infection were formed. SARS-CoV-2 RNA in nasopharyngeal and oropharyngeal scrapings was determined using the PCR-RT method. Biochemical and general clinical studies were performed in accordance with the guidelines of the Ministry of Health of the Russian Federation. Statistical processing was carried out using the Satistika 7.0 software package (StatSoft, USA). Differences between the groups were assessed using the Z-test and the Mann-Whitney U test. Differences between the compared series were considered statistically significant with a probability level of 95%. Results. It was shown that during three pandemic waves (June 2020 - August 2021), more than half of the hospitalized children were adolescents. At the same time, regardless of the pandemic wave, intoxication, catarrhal and intestinal syndromes predominated in hospitalized adolescents. CNS injury symptoms were significantly less frequent in the first wave, as were skin rashes. Cough in the third wave was observed in 100% of hospitalized adolescents. The average values of the parameters of complete blood count, as well as CRP, D-dimer and ferritin had no statistically significant differences in different pandemic waves, but there was a significant variation in individual values within the groups in each wave.Copyright © 2022, Dynasty Publishing House. All rights reserved.
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Background Vaccination is a recognised trigger of ADEM and approximately 50% paediatric cases have antibodies to MOG. The SARS-CoV-2 mass vaccination programme could therefore trigger cases of MOGAD. Neuromyelitis optica (NMO) is an autoimmune inflammatory condition of the CNS associ- ated with antibodies to AQP4. Method Ten patients (ages 22 - 65 years) with antibodies to MOG or AQP4 were referred to the NHS England NMO service having developed acute onset CNS inflammation within 8 weeks of vaccination. Results Eight patients had MOGAD, seven of whom received the AstraZeneca vaccine (AZV) and one the Pfizer vaccine (PV). Only the post-PV MOGAD patient presented with typical adult-onset phenotype of isolated ON. All post-AZV MOGAD patients presented atypically;85.7% had LETM and 71.4% had intrac- erebral lesions, resembling ADEM more commonly seen in paediatric MOGAD. The atypical presentation supports a causative role of AZV, but the role of PV is less convincing. Two patients had AQP4-NMOSD with typical demographic features. Both received AZV. Less typically, one young adult presented with LETM rather than characteristic young adult ON, the other had a silent short segment myelitis, which is rarely seen in AQP4-NMOSD. Both patients achieved good outcomes. Conclusion We discuss the potential causation and pathophysiological mechanisms.
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Objective: To describe the burden of COVID-19 in a children's multidisciplinary hospital for two years of the pandemic, taking into account of age, severity of the disease, the spectrum of underlying conditions and the intensive care need. Method(s): An assessment of 6048 cases of COVID-19 in patients under 18 years of age hospitalized from March 26, 2020 to December 31, 2021 was carried out. The diagnosis was confirmed by PCR on an outpatient basis or after hospitalization with the help of diagnostic kits registered in the Russian Federation. The features of the work of a children's multidisciplinary hospital in new conditions, the dynamics of hospitalization, age characteristics and new coronavirus (CV) infection severity in the pandemic development process are presented. The analysis of the underlying condition's structure depending on the severity of the disease, as well as the need and volume of therapy in the intensive care unit. The frequency and main characteristics of children's multisystem inflammatory syndrome (MIS-C) in hospital conditions, long-term PCR positivity and its effect on the duration of inpatient treatment of children have been established. Result(s): The spread of SARS-COV-2 in St. Petersburg required a radical change in the work of the children's multidisciplinary hospital. During the two years of the pandemic, four waves of hospitalization of children with new CV were revealed, differing in duration, intensity, and frequency of lung damage, but having no significant differences in the proportion of severe forms of the disease (1.7-2.8% of cases). Intensive therapy was required in 3.6% of cases, of which only 1/3 was due to the severe course of COVID-19 with a lung lesion volume of up to 100%. In 1/3 of cases, patients had risks of developing severe forms and in 1/3 - other pathology. Severe course of new CV was significantly more often accompanied by the need for respiratory support, anticoagulants and anti-inflammatory therapy. Contributing factors of severe forms and unfavorable outcomes were: pathology of the central nervous system, genetic diseases and malformations, obesity, as well as chronic bronchopulmonary pathology. Mortality in the hospital was recorded only among children with severe underlying conditions (0.1% of cases). D-MVS was registered significantly more often in boys (7 out of every 10 patients), accounting for 1.2% of cases of hospitalization of children with new CV over the entire period. Convalescent PCR-positivity in the outcome of COVID-19 was detected in 1/3 of children, significantly more often during the autumn-winter waves of the pandemic and among patients of high school age. Conclusion(s): New CV is gradually strengthening its position in the structure of acute respiratory pathology in children. Some of SARS-COV-2 infection cases is accompanied by extensive lung damage, as well as severe systemic inflammation independently or in the other infectious diseases structure, induction of the debut of various somatic pathology is not excluded. The presented data confirm the need for increased attention at high risk of adverse respiratory diseases outcomes children. All severe cases of COVID-19 in children require a personalized approach, taking into account the existing background diseases and possible options for the progression of the process. MIS-C should be considered as a systemic inflammatory response syndrome within the framework of an infectious disease of various etiologies, differentiated with Kawasaki disease and the debut of systemic diseases. The long-term PCR-positivity in the outcome of COVID-19 requires further study to address the need and nature of therapy in order to prevent further spread of infection in the population.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.
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Objective: To describe the burden of COVID-19 in a children's multidisciplinary hospital for two years of the pandemic, taking into account of age, severity of the disease, the spectrum of underlying conditions and the intensive care need. Method(s): An assessment of 6048 cases of COVID-19 in patients under 18 years of age hospitalized from March 26, 2020 to December 31, 2021 was carried out. The diagnosis was confirmed by PCR on an outpatient basis or after hospitalization with the help of diagnostic kits registered in the Russian Federation. The features of the work of a children's multidisciplinary hospital in new conditions, the dynamics of hospitalization, age characteristics and new coronavirus (CV) infection severity in the pandemic development process are presented. The analysis of the underlying condition's structure depending on the severity of the disease, as well as the need and volume of therapy in the intensive care unit. The frequency and main characteristics of children's multisystem inflammatory syndrome (MIS-C) in hospital conditions, long-term PCR positivity and its effect on the duration of inpatient treatment of children have been established. Result(s): The spread of SARS-COV-2 in St. Petersburg required a radical change in the work of the children's multidisciplinary hospital. During the two years of the pandemic, four waves of hospitalization of children with new CV were revealed, differing in duration, intensity, and frequency of lung damage, but having no significant differences in the proportion of severe forms of the disease (1.7-2.8% of cases). Intensive therapy was required in 3.6% of cases, of which only 1/3 was due to the severe course of COVID-19 with a lung lesion volume of up to 100%. In 1/3 of cases, patients had risks of developing severe forms and in 1/3 - other pathology. Severe course of new CV was significantly more often accompanied by the need for respiratory support, anticoagulants and anti-inflammatory therapy. Contributing factors of severe forms and unfavorable outcomes were: pathology of the central nervous system, genetic diseases and malformations, obesity, as well as chronic bronchopulmonary pathology. Mortality in the hospital was recorded only among children with severe underlying conditions (0.1% of cases). D-MVS was registered significantly more often in boys (7 out of every 10 patients), accounting for 1.2% of cases of hospitalization of children with new CV over the entire period. Convalescent PCR-positivity in the outcome of COVID-19 was detected in 1/3 of children, significantly more often during the autumn-winter waves of the pandemic and among patients of high school age. Conclusion(s): New CV is gradually strengthening its position in the structure of acute respiratory pathology in children. Some of SARS-COV-2 infection cases is accompanied by extensive lung damage, as well as severe systemic inflammation independently or in the other infectious diseases structure, induction of the debut of various somatic pathology is not excluded. The presented data confirm the need for increased attention at high risk of adverse respiratory diseases outcomes children. All severe cases of COVID-19 in children require a personalized approach, taking into account the existing background diseases and possible options for the progression of the process. MIS-C should be considered as a systemic inflammatory response syndrome within the framework of an infectious disease of various etiologies, differentiated with Kawasaki disease and the debut of systemic diseases. The long-term PCR-positivity in the outcome of COVID-19 requires further study to address the need and nature of therapy in order to prevent further spread of infection in the population.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.
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With the current pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), measures of social isolation were necessary, and this resulted in the interruption of several treatments. Regarding neuro-oncological patients, especially those with central nervous system (CNS) disorders, this interruption can cause serious damage or even compromise the success of the treatment in the future. It is essential that each case be evaluated separately to decide how to continue treatment during the pandemic, always considering the risk of SARS-CoV-2 infection and the benefits that the treatment will bring. The policy of not prescribing potentially toxic drugs, chemotherapy, and immunosuppressive therapies, as well as the use of techniques like stereotactic biopsy and telemedicine are important strategies at this time. Copyright © 2023. Sociedade Brasileira de Neurocirurgia. All rights reserved.
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Background/Purpose: Multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19 infection is a life-threatening condition, required intensive care. The aim of this study was to determine risk factors for severe/life-threatening course of MIS-C. Method(s): The retrospective study included 166 children (99 male, 67 female), aged from 4 months to 17 years (median 8.2 years), who met the WHO criteria for MIS-C. The criterion of severity was the fact of the ICU admission. The analysis of the obtained data was performed using the STATISTICA software package, version 10.0 (StatSoft Inc., USA). Result(s): To assess the factors associated with the severe course of MIS-C, patients were divided into two groups: those who were hospitalized in the ICU (n = 84;50.6%), and those who did not (n = 82;49.4%). Patients with a more severe course of MIS-C were significantly older. They had a high frequency of signs such as rash, edema, hepatomegaly, splenomegaly, neurological and respiratory symptoms. Hypotension/shock and myocardial damage were much more common in patients hospitalized in the ICU. Among the laboratory changes there were significant differences in the levels of hemoglobin, leukocytes and platelets, CRP, creatinine, troponin and D-dimer. The presence of macrophage activation syndrome was higher in patients, admitted in the ICU. Children, required intensive care required high dose corticosteroids and IVIG more often (table 1). FIGURE: 1) The first symptoms of progeria in infancy: scleroderma-like changes in the skin of the lower extremities and stiffness of knee joints at the age of 2 months. 2) Girl at the age of 3 years 5 months. Almost total alopecia with the absence of eyebrows and eyelashes. Pronounced venous pattern in the forehead, nasal bridge and nasolabial triangle. Conclusion(s): MIS-C is potentially a severe life-threatening condition, in which more than half (50.6%) of patients needed the ICU admission. The main factors determining the severity of MIS-C were: cardiovascular, resiratory and central nervous system disorders. It has been found that factors such as hepatomegaly, splenomegaly, D-dimer >2568 ng/ml, troponin >10 pg/ml, make it possible to identify a group of patients with high risk of severe MIS-C who may potentially need hospitalization in the ICU.
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Introduction: Mortality data reveals much about the health of the population. Traditionally and universally, most epidemiological studies begin with mortality data. Mortality characteristics and the audit give a myriad of information. This helps to identify trends of mortality. Mortality audit of mortality data is essential to improve hospital services and helps in proper allocation of resources. Hence this study was conducted to identify the mortality characteristics of the patients admitted in the year 2021 in the Tertiary care hospital in South India. Material(s) and Method(s): This retrospective study was conducted after Institutional ethical clearance with mortality records pertaining to the patients admitted to Hangal Sri Kumareshwar Hospital and Medical Research Center, Bagalkot, Karnataka during the year 2021. The data retrieved included demographic characteristics like age and sex, place of residence, ward of admission and causes of death classified according to ICD 10th revision and analysed using percentages and chi-square test and a p value of less than 0.05 was considered as significant in all the tests. Result(s): Out of 592 deaths in 2021, 64.19% were males and 35.81% were females. Majority of the deaths (34.46%) occurred between the ages of 41 to 60 years followed by 61 to 80 years (27.20%). Communicable diseases contributed to 54.56% of the total deaths (p= 0.0022). Conclusion(s): Statistical analysis of causes of death from mortality statistics is the backbone of National health policy and planning of health programs. It monitors the trend in public health issues like infant mortality, maternal mortality, infectious diseases, accidents and suicides. Copyright © 2023, Institute of Medico-legal Publication. All rights reserved.
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COVID-19 is a multisystem disease with considerable heterogeneity of manifestations, including neurological. Neurological manifestations occur in up to 2/3 of patients in the acute phase and include non-specific, central nervous system and peripheral nervous system disorders. This is potentially explained because the SARS-CoV-2 virus has neuroinvasive properties, either directly by retrograde transport via nerve terminations or hematogenous dissemination, and induces neuroinflammation. The persistence of the SARS-CoV-2 in the nervous tissue for an extended period combined with secondary changes determined by neuroinflammation and hypoxia could be potential explanatory mechanisms for the longCOVID neurological manifestations, which occur even more often than those in the acute phase of COVID-19. Since available specialized therapies against neurological manifestations are still lacking, existing treatment options directed against viral invasiveness, the effects of immune dysregulation and hypercoagulable state, along with supportive measures to combat hypoxia, could serve as an efficient treatment for patients with COVID-19 and neurological manifestations. By preventing the SARS-CoV-2 from affecting the nervous tissue in the acute phase, it could also be possible to avoid longCOVID neurological impairment and probably the potential development of neurodegenerative diseases. Copyright © 2022, Romanian Society for Pharmaceutical Sciences. All rights reserved.
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Introduction: Within the last year, cases with multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) associated with SARS-CoV-2-vaccination have been published worldwide. It remains unclear, whether the clinical onset in these patients is either causal and denovo or, alternatively, the initial manifestation of a preexisting demyelinating disease and thus a coincidence in time. Objective(s): We therefore compared clinical, laboratory and neuroimaging data of MS patients with clinical onset after SARSCoV- 2-vaccination (MSpostvacc) with a MS cohort without association to the vaccination (MSreference), respectively, with a single case of MOGAD following SARS-CoV-2-vaccination (MOGADpostvacc). Aim(s): To determine whether there is evidence of a preexisting, chronic inflammatory disease at clinical onset in MSpostvacc and MOGADpostvacc patients. Method(s): We included patients with clinical manifestation of MS or MOGAD <=30 days following SARS-CoV-2-vaccination and analysed clinical, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) and optical coherence tomography (OCT) data. The MSpostvacc characteristics were compared to an age- and gender- matched MS cohort recruited at our neuroimmunological outpatient clinic. Result(s): In 5 patients (3 female) the initial diagnosis of MS was made in association to SARS-CoV-2-vaccination (4 after BNT162b2 vaccine;mean clinical onset after 8 days). CSFspecific oligoclonal bands and indications of a preexisting inflammatory process were detectable on MRI and OCT in all MSpostvacc patients. Their analysed parameters (clinical, CSF, MRI, OCT) were assimilable to those of the MSreference cohort. One woman with onset of MOGAD after ChAdOx1 nCoV-19 vaccination was identified. Here, CSF analysis revealed an acute inflammatory profile (106 cells per mul;no CSF-specific OCB). After treatment with high-dose corticosteroids, the initial cerebral and cerebellar lesions resolved on follow-up MRI. Conclusion(s): Since we found CSF-specific oligoclonal bands, chronic inflammatory lesions on MRI and retinal neuroaxonal damage on OCT a denovo disease seems unlikely for the MSpostvacc cohort. Our data point to the hypothesis that the MSpostvacc patients described had a subclinical disease that first manifested coincidentally with the SARS-CoV-2-vaccination. However, this cannot be assumed for the MOGADpostvacc patient.
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Background: Bing-Neel syndrome (BNS) is a rare complication of lymphoplasmacytic lymphoma (LPL) comprising LPL infiltration in the central nervous system (CNS). Clinical and radiological features are diverse;the diagnosis is confirmed by cerebrospinal fluid (CSF) analysis using immunological and molecular techniques. Rarely, a tissue biopsy is required. The pattern of presentation including systemic involvement and CSF features inform treatment strategies, which include CNS-penetrating therapies. Aims: To evaluate the diagnostic characteristics of patients with BNS and their influence on therapy. Methods: Data from patients referred between 2011-2021 for management of BNS to our academic neurohaematology centre were retrospectively reviewed. Those with imaging features alone or where it was not possible to distinguish from high-grade transformation were excluded. Results: Thirty-five patients (22 male, 13 female) were identified. Median age at diagnosis of BNS was 65 years (range 48-85). All patients were symptomatic. In 12 patients (34%) BNS was the de novo presentation of the IgM-related disorder, of which 3 (25%) had no detectable bone marrow (BM) infiltration of LPL at diagnosis. Approximately half (17;49%) had previously received therapy for LPL;median time to BNS diagnosis in these was 49 months (range 3-125). At BNS diagnosis, BM involvement with LPL ranged from 0-95%. More than half (14/26;54%) had <10% infiltrate and almost a fifth (4/26) >60%. All patients had leptomeningeal involvement and 8 (23%) additionally had parenchymal CNS disease. The majority had kappa light-chain predominance: IgMκ (n=26), non-IgMκ (n=5), IgMλ (n=3), one unknown. The BNS diagnosis was made on CSF analysis (n=28;80%), leptomeningeal tissue biopsy (n=3;9%) where CSF was non-informative, or by expert opinion based on supportive clinical, radiological and non-definitive CSF features (n=4;11%). Of those with a diagnosis based on CSF studies, B-cell clonality was confirmed by flow cytometry (27/28;96%), MYD88L265P mutation (18/28;64%) and immunoglobulin gene rearrangement (12/28;43%). In 22 samples with a full dataset, median CSF white cell count was 25/ul (1-233), CSF protein 1.69g/l (0.35-6), CSF IgM 9.49mg/l (1.07-61.5). The majority were treated with intensive regimens (rituximab, methotrexate (MTX), cytarabine (ARA-C) + thiotepa/idarubicin;n=30) due to the presence of CNS disease bulk and clinical need, and less commonly ibrutinib (n=3), bendamustine-rituximab (BR, n=1);one patient had intrathecal therapy (MTX, ARA-C) at the height of the COVID pandemic. Of those who received 2 cycles of intensive chemotherapy, 3 had >4 cycles followed by BCNU/thiotepa autologous stem cell transplant;10 proceeded to 'consolidation' (indefinite) ibrutinib to limit intensive chemotherapy or tackle systemic disease. At a median follow up of 26 months (range 1-121), median survival was not reached;2-year overall survival was 91% (95% CI 74-97). Three patients died during treatment (1 invasive fungal infection post COVID-19 during ibrutinib consolidation post MTX/ARA-C based therapy) and 2 during MTX-ARA-C based therapy;7 patients relapsed or progressed and were treated with ibrutinib: 1 relapsed after ibrutinib use, 1 patient was intolerant of ibrutinib and switched to BR. Image: Summary/Conclusion: Our cohort confirms that BNS may present with leptomeningeal disease and/or parenchymal disease, de novo and without systemic disease. Overall outcomes are excellent with intensive regimens, consolidated with or followed by ibrutinib;however, there are treatment-related toxicities emphasising the need for a tailored approach.
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The proceedings contain 31 papers. The topics discussed include: brain abscess appearing 20 years post craniotomy;postoperative diffusion restriction in the proximal optic nerve: optic neuropathy or central retinal artery occlusion?;magnetic resonance imaging as a prognostic disability marker in clinically isolated syndrome: a systematic review;bilateral internuclear ophthalmoplegia caused by unilateral infarction;neuroaspergillosis in a patient with chronic lymphocytic leukemia as progressively worsening ischemic infarct;neuroimaging in mitochondrial short-chain enoyl-coa hydratase 1 deficiency: a progressive encephalomyelopathy starting in utero;childhood-onset neurodegeneration with brain atrophy: imaging findings of a rare diagnosis;multiple sclerosis associated with Balo-like lesions post-coronavirus disease 2019;and within-subject reproducibility of quantitative proton density mapping.
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Background: Cancer-related cognitive impairment (CRCI) can include persistent memory symptoms, and affects many cancer survivors. Memory and Attention Adaptation Training (MAAT) is an evidencebased cognitive behavioral therapy (CBT) that improves CRCI with demonstrated efficacy in telehealth delivery. MAAT consists of 8 weekly (45-minute) video visits. The aims of this study are to confirm MAAT telehealth efficacy in a phase III RCT (MAAT versus Supportive Therapy;ST) across large catchment areas of two comprehensive cancer centers. A secondary aim is to evaluate treatment-induced brain activation as assessed by functional MRI (fMRI) in a subset of participants. We present remote treatment and data capture methods of this open NCI-sponsored (R01CA244673) randomized clinical trial (NCT 04586530). These methods have high success in participant accrual despite COVID-19 pandemic conditions, and can be readily adopted to other clinical trials to enhance rural/underserved enrollment. Methods: We are enrolling 200 adult, stage I-III breast cancer survivors 1-5 years post-chemotherapy with cognitive complaints. Individuals with CNS disease, previous brain injury, dementia or psychiatric disorder are excluded. All study procedures are completed from the participant's home (except fMRI). Eligibility screening is a semi-structured phone interview followed by detailed informed consent online (Research Electronic Data Capture: REDCap) with staff phone guidance. Consented participants complete baseline brief phone-based neurocognitive assessment and validated patient-reported outcome measures (PROs) of cognition and quality of life via REDCap. Participants are randomized to MAAT or ST and assigned treating clinicians at respective cancer centers. All 8 visits are completed through secure telehealth platforms, followed by repeat phone/online assessment posttreatment and again at 6 months. Enrollment began in 3/2021. As of 1/2022 (9 months), 56 participants are enrolled (28% of the planned sample), 47 randomized (MAAT 24;ST 23), with 24 completing post-treatment assessments. If all assessments and treatment visits were in person, travel burden per participant is 968 miles/20.5 hours driven, and $542 (US 2021 Federal rate). Thus, study travel savings to date are $30,352. Participant feedback indicates telehealth makes participation possible, similar to previous MAAT research. The current RCT demonstrates utility, efficiency and cost-savings of telehealth and remote data capture technology in the conduct of cancer control research. Elements of methods described can also be adopted for cancer therapeutic trials. Comprehensive cancer centers, where most clinical trials are based, can enhance participation of remote and/or underserved populations that have higher rates of cancer, more disease burden and less opportunity for trial participation.
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Rationale - The goal of the study was to investigate gender characteristics of functional somatic disorders in adolescents of the indigenous population of Khakassia (using the case study of the Abakan city). Material and methods - The object of the study was 215 (46.8%) boys and 244 (53.2%) girls of four secondary schools in Abakan. Their average age was 14.5±1.3 years. Data collection was conducted by means of an original screening questionnaire developed by Professor S.Yu. Tereshchenko. Results - The incidence of recurrent pain in the total sample of the surveyed youths was 184 (40.1%) for cephalalgia, 225 (49.0%) for abdominal pain, and 269 (58.7%) for back pain. The prevalence and structure of functional somatic disorders in Khakas adolescents depended on their gender. Asthenic syndrome was more common among girls - 42 (17.2%) vs. 14 (6.5%) in boys. In girls, the percentage of frequent headaches was higher than in boys: 22 (9.0%) vs. 8 (3.7%), respectively. Similar trend was observed in case of rare headaches: 100 (41.0%) vs. 54 (25.1%). Also, girls, compared with boys, were characterized by a higher incidence of both frequent and rare abdominal pains: 38 (15.6%) vs. 9 (4.2%) and 106 (43.4%) vs. 72 (33.5%), correspondingly. Conclusion - The case study of surveyed ethnic sample of Abakan school students revealed a high prevalence of recurrent pain syndromes in the indigenous youths of Khakassia. We have also established that incidence, structure and severity of recurrent pain, as well as its negative impact on well-being and daily activities, were associated with gender.
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Objective: To describe the spectrum of acute neurological disorders among hospitalized patients who recently received COVID-19 mRNA vaccination. Background: The unprecedented pace of COVID-19 vaccine development, use of novel mRNA technology and large-scale vaccination programs have engendered concerns of adverse events following immunization. Design/Methods: We performed a multi-centre prospective observational study in 7 public acute hospitals. Hospitalized patients who were referred for neurological complaints and had COVID-19 mRNA vaccines, BNT162b2 and mRNA-1273, in the last 6 weeks were classified into central nervous system(CNS) syndromes, cerebrovascular disorders, peripheral nervous system(PNS) disorders, autonomic nervous system(ANS) disorders and immunization stressrelated responses(ISRR). To contextualize our findings, data from National Immunization Registry was probed for the total number and demographic of individuals vaccinated in the corresponding period. Results: From 30 December 2020 to 20 April 2021, 1,398,074 persons (median age 59 years, 54.5% males) received COVID-19 mRNA vaccine (86.7% BNT162b2, 13.3% mRNA-1273);915,344 (65.5%) completed 2 doses. Four hundred and fifty-seven (0.03%) patients were referred for neurological complaints [median age 67 years, 61.5% males;95.8% received BNT162b2 and 4.2% mRNA-1273];classified into 73 (16.0%) CNS syndromes, 286 (62.6%) cerebrovascular disorders, 59 (12.9%) PNS disorders, 0 ANS disorders and 39 (8.5%) ISRRs. Twenty-seven had cranial mononeuropathy, 11 of whom had Bell's palsy. Of 33 patients with seizures, only 4 were unprovoked and occurred within 2 weeks of vaccination. All strokes occurred among individuals with pre-existing cardiovascular risk factors. We recorded 2 cases of cerebral venous thrombosis;none associated with thrombocytopenia. Five had mild flares of immune-mediated diseases. Conclusions: Our observational study does not establish causality of the described disorders to vaccines and is limited by lack of baseline incidence data of several conditions. Nevertheless, we did not observe any obvious signal of serious neurological morbidity associated with mRNA vaccination. The benefits of COVID-19 vaccination outweigh concerns over neurological adverse events.
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Objective: To identify variants of immune dysregulation genes with potential role in pediatric autoimmune central nervous system (CNS) disorders. Background: Immune system dysregulation gives rise to a broad range of autoimmune diseases. Rare variants of alleles in genes implicated in primary immune dysregulation could have a potential role in autoimmune CNS disorders although are infrequently tested. Design/Methods: We assessed consecutive patients with autoimmune CNS diseases who had undergone genetic analysis with the Invitae Autoinflammatory Syndromes panel. This panel evaluates 155 genes associated with primary autoimmune disorders without CNS involvement. Results: Fifty patients were included (42% male, median age 15, IQR 9.25-17, range 2-21 years). Fourteen patients (28%) had multiple sclerosis (MS), 13 (26%) had Myelin oligodendrocyte glycoprotein associated disorder (MOGAD), 5 (10%) had autoimmune encephalitis, and 4 (8%) CNS vasculitis. Heterozygous variants of unknown significance of 66 genes were identified in 37 patients (72%). Most frequently affected genes included UNC13D (5, 10% of patients), NOD2 (4, 8%), LRBA (3, 6%), and RNASEH2A (3, 6%). Patients with UNC13D single nucleotide variants presented with MOGAD (2/5), MS (1/5) and CNS vasculitis (2/5). All these patients had variants in one or more other genes of immune dysregulation, including STXBP2. Homozygous variants of UNC13D and STXBP2 are associated with familial Hemophagocytic lymphohistiocytosis (HLH) although heterozygous mutations are of unknown significance. Conclusions: We observed a high prevalence (72%) of potentially contributing variants in this cohort of pediatric neuroinflammatory disorders. Pathogenic variants of UNC13D are associated with NK degranulation dysfunction resulting in familial HLH, and heterozygous variants have been described in other immune dysregulation disorders including with severe cytokine storm with COVID-19 infection. Given the striking prevalence of variants in UNC13D in this population, further study is necessary.
ABSTRACT
Objective: To present a single-health system retrospective analysis of post-mRNA-based COVID-19 vaccination CNS autoimmunity conducted in the greater New York City area. Background: There have been rare reports associating mRNA-based COVID-19 vaccines with central nervous system (CNS) inflammation. We report a case series of five patients with newonset neurological disorders of immunological origin temporally associated with these vaccines. Design/Methods: Case-series. Results: Five cases of post-vaccination CNS disorders of immune origin were observed within two weeks of inoculation with either the first or second dose of mRNA-based COVID-19 vaccines (Moderna = 3, Pfizer = 2). This includes: Fatal ADEM (n = 1), new-onset NMO (n = 2), new-onset fulminant MS (n = 1), and meningoencephalitis (n = 1). The age of our patients ranged from 27 to 81, and three were female. None of the patients had pre-existing neurological illnesses and one had a pre-existing autoimmune condition (immune thrombocytopenia purpura). New-onset focal neurological symptoms were present in all five patients, including quadriparesis, numbness, diplopia, and encephalopathy. CSF pleocytosis was present in all patients, and three had elevated protein. All but one patient (meningoencephalitis) had contrastenhancing lesions involving either the cerebrum or spinal cord. Both NMO patients had longitudinally extensive transverse lesions involving the central thoracic cord. Aquaporin-4 serum antibody was present in one NMO patients and aquaporin-4 CSF antibody present in the other. All but one patient (fatal ADEM) clinically improved with pulse steroids or plasmapheresis. Conclusions: These are among the emerging cases of CNS immunological events temporally associated with mRNA-based COVID-19 vaccines. These findings should be interpreted with great caution as they neither prove a link nor imply a potential long-term increased risk in postvaccination CNS autoimmunity. Larger prospective studies are needed. The mRNA-based SARS-CoV-2 vaccines should continue to be strongly encouraged given their high efficacy in overcoming this pandemic.