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JAMA Neurology Jul 2021Encephalitis is a severe immune-related adverse event secondary to treatment with immune checkpoint inhibitors (ICIs). The spectrum of ICI-induced encephalitis (ICI-iE)...
IMPORTANCE
Encephalitis is a severe immune-related adverse event secondary to treatment with immune checkpoint inhibitors (ICIs). The spectrum of ICI-induced encephalitis (ICI-iE) ranges from disease that resolves fully to lethal forms. Moreover, ICIs may unmask a paraneoplastic encephalitis. To our knowledge, the factors associated with ICI-iE prognosis are unknown.
OBJECTIVES
To evaluate the presentation of ICI-iE and to identify features helpful in assessing outcomes.
EVIDENCE REVIEW
This systematic review pooled case series from the published literature (n = 77) and medical records from 1 center (n = 5) to assess the association between the form of ICI-iE presentation and its prognosis. Eligibility criteria included references identified by searches of PubMed and Web of Knowledge databases in the English literature from June 2000 (first patient dose of ipilimumab) to April 17, 2020, that examined patients with encephalitis with presumed autoimmune etiologic features induced by ICIs. Information regarding clinical, cerebrospinal fluid, and neuroimaging (magnetic resonance imaging) features, as well as treatment given, were extracted.
FINDINGS
A total of 82 patients (52 men [63%]; median age, 61.0 years [interquartile range, 52.5-70.0 years]) were included. Most patients presented with focal syndromes (39 [48%]) or meningoencephalitis (36 [44%]). Seven patients (9%) had nonclassifiable ICI-iE. Neuronal autoantibodies were detected in 23 patients with focal syndromes and 1 patient with nonclassifiable ICI-iE. Most autoantibodies were onconeuronal (17 of 24 [71%]), targeting intracellular antigens. Patients without a focal syndrome or with a negative-antibody focal syndrome had a good prognosis (49 of 55 [89%]). Among patients with autoantibodies, those with anti-glutamic acid decarboxylase or anticell surface responded to treatment and had a favorable prognosis (100%). However, patients with other autoantibodies had poor outcomes (17 of 24 [71%]). Antineuronal autoantibodies (13 of 24 [54%] vs 5 of 41 [12%]; P < .001), focal syndrome (16 of 39 [41%] vs 4 of 43 [9%]; P = .001), and abnormal magnetic resonance imaging findings (14 of 39 [36%] vs 4 of 32 [13%]; P = .02) were associated with poor outcomes. Conversely, fever (21 of 23 [91%] vs 41 of 59 [70%]; P = .04) and more inflammatory changes in cerebrospinal fluid (30 of 31 [97%] vs 21 of 33 [64%]; P = .001) were associated with a better prognosis.
CONCLUSIONS AND RELEVANCE
Immune checkpoint inhibitors may induce mainly 2 different encephalitic syndromes: a focal limbic or extralimbic encephalitis and a meningoencephalitis. Immune checkpoint inhibitor-induced encephalitis is associated with an overall favorable outcome, with a low rate of fatal events. An undetected preexisting paraneoplastic encephalitic syndrome may be triggered by ICIs, and this type of syndrome has the worst outcome among all the different types of ICI-induced encephalitis syndromes. Clinical presentation and systematic measurement of autoantibodies will be a helpful guide for the therapeutic strategy and for counseling regarding prognosis.
Topics: Adult; Aged; Autoantibodies; Encephalitis; Female; Humans; Immune Checkpoint Inhibitors; Ipilimumab; Lung Neoplasms; Magnetic Resonance Imaging; Male; Melanoma; Middle Aged; Nivolumab
PubMed: 33720308
DOI: 10.1001/jamaneurol.2021.0249 -
Seminars in Arthritis and Rheumatism Feb 2021The neurological and psychiatric manifestations of systemic lupus erythematosus (NPSLE) are a heterogeneous group of conditions with variable clinical presentation and... (Review)
Review
BACKGROUND
The neurological and psychiatric manifestations of systemic lupus erythematosus (NPSLE) are a heterogeneous group of conditions with variable clinical presentation and significant morbidity and mortality.
OBJECTIVES
Our aim was to comprehensively assess and present the evidence for treatments used in the management of inflammatory NPSLE.
METHODS
Medline, Embase, CINHAL and Cochrane CENTRAL were searched from 1990 to end of March 2019 using key words that related to NPSLE and treatment. Included studies comprised clinical trials, observational studies or case series with ≥5 patients and sufficient data related to treatment and outcome in NPSLE patients.
RESULTS
There were 7222 studies identified in the search, of which 90 were included in the review. There was a notable paucity of clinical trials, with only two randomised controlled trials and one pilot study. Treatment categories included corticosteroids (14 studies), cyclophosphamide (18 studies), synthetic DMARDs (7 studies), biologic therapies (14 studies), therapeutic plasma exchange (6 studies), intravenous immunoglobulin (2 studies), autologous stem cell transplant (3 studies), other therapies (8 studies), combination therapies (6 studies), studies with grouped outcome data (5 studies) and observational studies with therapy-specific associations (7 studies). Corticosteroids are accepted as first line treatment in NPSLE and there is low-moderate evidence supporting their benefit. Moderate evidence, based on consistent data in numerous studies and some trial data, supports the use of cyclophosphamide in the treatment of NPSLE. Limited data support some synthetic DMARDs such as mycophenolate, azathioprine and intrathecal methotrexate. In refractory disease, low-moderate evidence supports rituximab therapy and limited evidence supports benefit following autologous stem cell transplant. Regarding adjuvant treatments, limited evidence favours addition of plasma exchange, intravenous immunoglobulin and hydroxychloroquine. There exists very limited data for other therapies.
CONCLUSION
There are multiple therapeutic options for the management of inflammatory NPSLE including systemic, biologic and interventional therapies; however, currently there is a paucity of high-quality trial data to guide firm recommendations. In order to better understand the optimal treatment of NPSLE and its different subtypes, further well-designed clinical trials are needed.
Topics: Azathioprine; Cyclophosphamide; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Vasculitis, Central Nervous System; Pilot Projects; Randomized Controlled Trials as Topic
PubMed: 33360230
DOI: 10.1016/j.semarthrit.2020.12.004 -
BMC Pediatrics Mar 2021Enterovirus (EV) is a common cause of infection in neonates. Neonates are at high risk of enterovirus infection with serious clinical manifestations and high lethality....
BACKGROUND
Enterovirus (EV) is a common cause of infection in neonates. Neonates are at high risk of enterovirus infection with serious clinical manifestations and high lethality. This review systematically summarized the clinical characteristics of neonates with severe enteroviral infection to provide evidence for the identification and treatment of severe neonatal EV infection.
METHODS
PubMed, Embase, and Web of Science were searched for original studies on neonates with severe EV infections from January 1, 2000, to November 27, 2020. Two reviewers independently screened the literature, extracted the data, and performed a descriptive analysis.
RESULTS
In total, 66 articles with 237 cases of severe neonatal enterovirus infection were included. All neonates developed severe complications. Among them, 46.0% neonates had hepatitis or coagulopathy, 37.1% had myocarditis, 11.0% had meningoencephalitis, and 5.9% had other complications such as hemophagocytic lymphohistiocytosis and pulmonary hemorrhage. The lethality rate of neonates with severe infection was 30.4%. The highest lethality rate was 38.6%, which was observed in neonates with myocarditis. In 70.5% neonates, the age at the onset of symptoms was less than 7 days. Coxsackievirus B infection was seen in 52.3% neonates. The most common symptoms included temperature abnormalities (127, 53.6%), rash (88, 37.1%), poor feeding (58, 24.5%), and respiratory symptoms (52, 21.9%). The main treatment included transfusion of empirical antibiotics (127, 53.6%), blood components (100, 42.2%), intravenous immunoglobulin (IVIG; 97, 40.9%), mechanical ventilation (51, 21.5%), and extracorporeal membrane oxygenation (ECMO; 43, 18.1%). Additionally, antiviral medications pleconaril (14, 5.9%) and pocapavir (3, 1.3%) were administered.
CONCLUSIONS
Lethality was high in neonates with severe enterovirus infection, especially in those complicated with myocarditis. The most common symptoms included temperature abnormalities, rash, and poor feeding. The chief supportive treatment consisted of transfusion of blood components, mechanical ventilation, and ECMO. Empirical antibiotics and IVIG were widely used. Antiviral medications included pocapavir and pleconaril; however, more clinical evidence regarding their efficacy is needed.
Topics: Communicable Diseases; Enterovirus; Enterovirus Infections; Extracorporeal Membrane Oxygenation; Humans; Infant, Newborn; Myocarditis
PubMed: 33722228
DOI: 10.1186/s12887-021-02599-y -
Journal of Neurovirology Feb 2021With the growing number of COVID-19 cases in recent times. significant set of patients with extra pulmonary symptoms has been reported worldwide. Here we venture out to...
With the growing number of COVID-19 cases in recent times. significant set of patients with extra pulmonary symptoms has been reported worldwide. Here we venture out to summarize the clinical profile, investigations, and radiological findings among patients with SARS-CoV-2-associated meningoencephalitis in the form of a systemic review. This review was carried out based on the existing PRISMA (Preferred Report for Systematic Review and Meta analyses) consensus statement. The data for this review was collected from four databases: Pubmed/Medline, NIH Litcovid, Embase, and Cochrane library and Preprint servers up till 30 June 2020. Search strategy comprised of a range of keywords from relevant medical subject headings which includes "SARS-COV-2," "COVID-19," and "meningoencephalitis." All peer reviewed, case-control, case report, pre print articles satisfying our inclusion criteria were involved in the study. Quantitative data was expressed in mean ± SD, while the qualitative date in percentages. Paired t test was used for analysing the data based on differences between mean and respective values with a p < 0.05 considered to be statistically significant. A total of 61 cases were included from 25 studies after screening from databases and preprint servers, out of which 54 of them had completed investigation profile and were included in the final analysis. Clinical, laboratory findings, neuroimaging abnormalities, and EEG findings were analyzed in detail. This present review summarizes the available evidences related to the occurrence of meningoencephalitis in COVID-19.
Topics: Adult; Aged; Antiviral Agents; Azithromycin; COVID-19; Confusion; Cough; Dyspnea; Electroencephalography; Fatigue; Female; Fever; Humans; Hydroxychloroquine; Male; Meningoencephalitis; Middle Aged; Neuroimaging; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33367960
DOI: 10.1007/s13365-020-00923-3 -
Acta Parasitologica Jun 2020Toxocariasis is a helminthozoonosis caused by the infection of a human host by the larva of Toxocara spp., predominately involving Toxocara canis and Toxocara cati,...
PURPOSE
Toxocariasis is a helminthozoonosis caused by the infection of a human host by the larva of Toxocara spp., predominately involving Toxocara canis and Toxocara cati, which are common nematodes in dogs and cats, respectively. Human transmission occurs through contact with animals or by consumption of food contaminated with parasite's eggs. The purpose of this article is to review the current knowledge regarding human neurotoxocariasis.
METHODS
We conducted a systematic review of the existing literature concerning toxocariasis of the nervous system.
RESULTS
Clinical spectrum of human toxocariasis varies widely from a subclinical course to significant organ morbidity. Clinical course depends on parasitic load, the migration route of the larvae and host response. Human neurotoxocariasis is a relatively rare entity yet associated with severe sequelae. Manifestations include meningitis (usually eosinophilic), encephalitis, myelitis, cerebellar vasculitis, space-occupying lesion, behavioral abnormalities, and optic neuritis. Even though valid diagnostic criteria are lacking, neurotoxocariasis should be suspected in patients with neurologic symptoms and cerebrospinal fluid (CSF) pleocytosis with eosinophilia, positive serology for anti-Toxocara antibodies, in serum and/or CSF, sterile CSF and clinical improvement after antihelminthic treatment. Neurotoxocariasis is treated by benzimidazole components, most frequently albendazole, corticosteroids, or diethylcarbamazine.
CONCLUSION
Parasite larvae migrate through tissues and are able to reach the nervous system causing neurotoxocariasis. Its clinical spectrum varies and includes myelitis, meningoencephalitis, brain abscess, and vasculitis. Neurotoxocariasis should always be suspected in patients with neurologic symptoms accompanied by eosinophilia in blood and/or CSF. Early diagnosis and treatment could prevent long-term neurologic impairment.
Topics: Animals; Anthelmintics; Humans; Nervous System Diseases; Nitroimidazoles; Toxocariasis
PubMed: 31960218
DOI: 10.2478/s11686-019-00166-1 -
Current Fungal Infection Reports 2023Corticosteroids have a complex relationship with fungal disease - risk for many, benefit for others. This systematic review aims to address the effect of corticosteroids... (Review)
Review
PURPOSE OF REVIEW
Corticosteroids have a complex relationship with fungal disease - risk for many, benefit for others. This systematic review aims to address the effect of corticosteroids on mortality and visual outcome in different fungal diseases.
RECENT FINDINGS
Corticosteroids are a risk factor of aspergillosis for patients who have COVID-19, and they also led to a worse outcome. Similarity, corticosteroids are a risk factor for candidemia and mucormycosis. Some researchers reported that using topical corticosteroid in keratitis was associated with worse visual outcome if fungal keratitis. Some studies showed that corticosteroids are linked to a negative outcome for non-HIV patients with pneumonia (PCP), in contrast to those with HIV and PCP.
SUMMARY
In 59 references, we found that corticosteroid therapy showed a worse clinical outcome in invasive aspergillosis (IA) (HR: 2.50, 95%CI: 1.89-3.31, < 0.001) and chronic pulmonary aspergillosis (CPA) (HR: 2.74, 95%CI: 1.48-5.06, = 0.001), PCP without HIV infection (OR: 1.29, 95%CI: 1.09-1.53, = 0.003), invasive candidiasis and candidaemia (OR: 2.13, 95%CI: 1.85-2.46, < 0.001), mucormycosis (OR: 4.19, 95%CI: 1.74-10.05, = 0.001) and early in the course of fungal keratitis (OR: 2.99, 95%CI: 1.14-7.84, = 0.026). There was equivocal outcome in cryptococcal meningoencephalitis in AIDS and primary coccidioidomycosis, while corticosteroid therapy showed a better outcome in PCP in HIV-infected patients (RR: 0.62, 95%CI: 0.46-0.83, =0.001) and fungal keratitis patients after keratoplasty surgery (OR: 0.01, 95%CI: 0.00-0.41, = 0.041) and probably in cryptococcal meningoencephalitis in non-immunocompromised patients. A sub-analysis in invasive aspergillosis and CPA showed that use of more than 2 mg/kg/day of prednisolone equivalents per day is a significant factor in increasing mortality (HR: 2.94, 95%CI: 2.13-4.05, < 0.001). Corticosteroid therapy during invasive fungal disease was usually associated with a slightly or greatly increased mortality or worse visual outcome (in fungal keratitis), with two disease exceptions. Avoiding the addition of corticosteroids, or minimising dose and duration in those who require them, is likely to improve the outcome of most life- and vision-threatening fungal diseases. This review provides a cornerstone for further research in exploring the accuracy of suitable dose and duration of corticosteroids treatment in fungal diseases.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12281-023-00456-2.
PubMed: 36852004
DOI: 10.1007/s12281-023-00456-2 -
Seminars in Arthritis and Rheumatism Jun 2022Previous studies suggested that patients with Systematic Lupus Erythematosus (SLE) have a higher risk of suicidal behavior, including suicidal ideation, attempt and... (Review)
Review
BACKGROUND
Previous studies suggested that patients with Systematic Lupus Erythematosus (SLE) have a higher risk of suicidal behavior, including suicidal ideation, attempt and complete suicide. Systematic data describing the SLE patients' clinical characteristics and risk factors of suicidal behavior are lacking.
OBJECTIVES
To determine the magnitude of suicidal behavior among SLE patients and to examine predictors associated with suicidal behavior. An additional aim was to identify common genes or coinherited single nucleotide polymorphisms (SNP) implicated in suicidal behavior and SLE.
METHODS
We conducted a systematic literature review based on PRISMA guidelines using the online databases PubMed/Medline, EMBASE and Web of Science, from inception to August 2021. Full-text original articles that examined the relationship between SLE patients with suicidal behavior were eligible for our review. Two reviewers independently reviewed articles to assess eligibility using the Newcastle-Ottawa Scale and the Joanna Briggs Institute criteria. Systematic reviews, metanalysis, narrative review, case reports, case series, including less than 10 patients, and conference abstracts, were excluded. All registered genome-wide association study (GWAS) data in the GWAS catalog database for SLE and psychiatric traits (suicidal behavior, depression, anxiety, psychosis) were downloaded for further analysis. Special in silico tools were used to examine if any genetic polymorphisms (SNPs) that predispose for SLE or psychiatric traits can be inherited together as a single haplotype. This could be posing a risk factor for a coexisting psychiatric condition in SLE patients.
RESULTS
Of the 64 articles identified, 22 were relevant to the study question; cross-sectional (n = 8) and prospective cohorts (n = 6) were the most frequently retrieved studies. Among the 27,106 SLE patients with SLE, 802 had suicidal behavior (2.9%), and of those, 87.9% were female. Suicide attempt occurred in 573/802 (71.4%) and complete suicide in 18/802 (3%). Major depressive disorder was the most frequently reported coexisting psychiatric condition associated with suicidal behavior, followed by psychosis and social phobia. In addition, several clinical manifestations were linked to suicidal behavior, particularly neuropsychiatric lupus, serositis, mucocutaneous, and renal involvement. Further, high scores in disease activity and damage indices were associated with suicidal behavior. A haplotype in chromosomal region 6p21.33 was found to contain a combination of risk alleles predisposing for SLE and depression, the most common psychiatric disorder associated with suicidal behavior.
CONCLUSION
Suicide behavior in SLE patients was associated with depression, neuropsychiatric lupus, active disease and damage. Further evidence supports a genetic origin of psychiatric symptoms in SLE patients. Awareness of these findings can guide clinicians to recognize suicide behavior promptly and prevent suicide attempts.
Topics: Cross-Sectional Studies; Depressive Disorder, Major; Female; Genome-Wide Association Study; Humans; Linkage Disequilibrium; Lupus Erythematosus, Systemic; Lupus Vasculitis, Central Nervous System; Male; Nervous System Diseases; Prospective Studies; Suicidal Ideation
PubMed: 35344734
DOI: 10.1016/j.semarthrit.2022.151997 -
Medical Hypothesis, Discovery &... 2022The coronavirus disease 2019 (COVID-19) pandemic has been the most challenging health problem in the last 2 years. Post-COVID-19 multisystem inflammatory syndrome of... (Review)
Review
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic has been the most challenging health problem in the last 2 years. Post-COVID-19 multisystem inflammatory syndrome of children (MIS-C) is a severe post-COVID-19 complication in pediatric patients. Ocular manifestations may be the first presentation of MIS-C, wherein prompt treatment may improve outcomes. In this systematic review, we aimed to summarize the acute and sub-acute ocular manifestations in pediatric patients with laboratory-confirmed COVID-19.
METHODS
We included all online primary studies, with no language restriction and published between January 1, 2019 and November 18, 2020, reporting any acute or sub-acute ocular manifestations in children with laboratory-confirmed COVID-19. PubMed/MEDLINE was searched using the following MeSH and Emtree terms: "eye," "ophthalmologic," "ocular," "vision," "conjunctivitis," "severe acute respiratory syndrome coronavirus 2," "SARS-CoV-2," "corona," "2019-nCoV," "COVID19," and "COVID." The eligibility and quality of the selected records were assessed by two independent reviewers as per the Cochrane Handbook for Systematic Review.
RESULTS
A total of 1,192 records were identified electronically. Seven papers were extracted from the reference lists of the eligible records. Thirty-six papers met the inclusion criteria and were categorized into two subgroups according to acute or sub-acute presentation of ocular manifestations. Among 463 pediatric patients with COVID-19, 72 (15.5%) had acute ocular manifestations. There was one patient with central retinal vein occlusion and another with photophobia and diplopia associated with meningoencephalitis. Among 895 pediatric patients with post-COVID-19 MIS-C, 469 (52.4%) had ocular manifestations, which only included non-purulent conjunctivitis.
CONCLUSIONS
Ocular manifestations have been reported in less than one-fifth of pediatric patients with acute COVID-19. Furthermore, conjunctivitis was the only ocular manifestation reported in half of the patients with MIS-C, and it may be missed easily due to its non-purulent nature. During the COVID-19 pandemic, pediatricians and health workers must remain vigilant for early detection of signs of this potentially fatal post-COVID-19 inflammatory syndrome.
PubMed: 37641695
DOI: 10.51329/mehdiophthal1440 -
International Journal of Environmental... Feb 2023Primary amoebic meningoencephalitis (PAM) is a rare but lethal infection of the brain caused by a eukaryote called (). The aim of this review is to consolidate the... (Review)
Review
INTRODUCTION
Primary amoebic meningoencephalitis (PAM) is a rare but lethal infection of the brain caused by a eukaryote called (). The aim of this review is to consolidate the recently published case reports of infection by describing its epidemiology and clinical features with the goal of ultimately disseminating this information to healthcare personnel.
METHODS
A comprehensive literature search was carried out using PubMed, Web of Science, Scopus, and OVID databases until 31 December 2022 by two independent reviewers. All studies from the year 2013 were extracted, and quality assessments were carried out meticulously prior to their inclusion in the final analysis.
RESULTS
A total of 21 studies were selected for qualitative analyses out of the 461 studies extracted. The cases were distributed globally, and 72.7% of the cases succumbed to mortality. The youngest case was an 11-day-old boy, while the eldest was a 75-year-old. Significant exposure to freshwater either from recreational activities or from a habit of irrigating the nostrils preceded onset. The symptoms at early presentation included fever, headache, and vomiting, while late sequalae showed neurological manifestation. An accurate diagnosis remains a challenge, as the symptoms mimic bacterial meningitis. Confirmatory tests include the direct visualisation of the amoeba or the use of the polymerase chain reaction method.
CONCLUSIONS
infection is rare but leads to PAM. Its occurrence is worldwide with a significant risk of fatality. The suggested probable case definition based on the findings is the acute onset of fever, headache, and vomiting with meningeal symptoms following exposure to freshwater within the previous 14 days. Continuous health promotion and health education activities for the public can help to improve knowledge and awareness prior to engagement in freshwater activities.
Topics: Aged; Humans; Male; Amoeba; Brain; Central Nervous System Protozoal Infections; Fever; Headache; Naegleria fowleri
PubMed: 36833715
DOI: 10.3390/ijerph20043021 -
Beni-Suef University Journal of Basic... 2022Hand, foot, and mouth disease (HFMD) is a viral infection caused by a virus from the enterovirus genus of picornavirus family that majorly affects children. Though most... (Review)
Review
BACKGROUND
Hand, foot, and mouth disease (HFMD) is a viral infection caused by a virus from the enterovirus genus of picornavirus family that majorly affects children. Though most cases of HFMD do not cause major problems, the outbreaks of Enterovirus 71 (EV71) can produce a high risk of neurological sequelae, including meningoencephalitis, lung difficulties, and mortality. In Asia, HFMD caused by EV71 has emerged as an acutely infectious disease of highly pathogenic potential, which demands the attention of the international medical community.
MAIN BODY OF THE ABSTRACT
Some online databases including NCBI, PubMed, Google Scholar, ProQuest, Scopus, and EBSCO were also accessed using keywords relating to the topic for data mining. The paid articles were accessed through the Centre Library facility of Siksha O Anusandhan University. This work describes the structure, outbreak, molecular epidemiology of Enterovirus 71 along with different EV71 vaccines. Many vaccines have been developed such as inactivated whole-virus live attenuated, subviral particles, and DNA vaccines to cure the patients. In Asia-Pacific nations, inactivated EV71 vaccination still confronts considerable obstacles in terms of vaccine standardization, registration, price, and harmonization of pathogen surveillance and measurements.
SHORT CONCLUSION
HFMD has emerged as a severe health hazard in Asia-Pacific countries in recent decades. In Mainland China and other countries with high HFMD prevalence, the inactivated EV71 vaccination will be a vital tool in safeguarding children's health. When creating inactivated EV71 vaccines, Mainland China ensured maintaining high standards of vaccine quality. The Phase III clinical studies were used to confirm the safety and effectiveness of vaccinations.
PubMed: 35730010
DOI: 10.1186/s43088-022-00258-4