The clinical spectrum of Enterovirus-71-associated neurological disease includes acute flaccid paralysis, encephalomyelitis, or brainstem encephalitis with autonomic dysfunction. As no specific ...antiviral treatments are available, intravenous human immunoglobulin is used in early stages of the illness, decreasing serum proinflammatory cytokines, and improving clinical outcomes. Plasma exchange aims to eliminate pathogenic autoantibodies and proinflammatory cytokines, and is used in diverse immune-mediated neurologic conditions. However, its effect in Enterovirus-71 infections is unknown. We report three cases of severe Enterovirus-71 neurological disease treated with plasma exchange during an outbreak in Catalonia (Spain) in 2016. We observed a striking improvement in all three patients within 48 h of starting plasma exchange. Patients received four to six sessions every other day. Good outcomes were confirmed at the 1-year follow-up visit. Our observations suggest that plasma exchange is an effective complementary therapy for severe Enterovirus-71 neurological disease.
Neurological complications (NCs) are of major concern following hematological stem cell transplantation (HSCT), most of which present with seizures.
We performed a retrospective study (2002-2018) of ...patients undergoing HSCT in order to analyze the incidence and aetiologies related to seizures.
Of 155 children undergoing HSCT, 27 (17.4%) developed seizures at some point in 2 years of follow-up. The most frequent etiologies were central nervous system (CNS) infection (n = 10), drug toxicity (n = 8), and vascular disease (n = 5). A statistically significant association was found between seizure and the HSCT type (lower risk for a related identical donor, p = .010), prophylactic or therapeutic mycophenolate use (p = .043 and .046, respectively), steroid use (p = .023), selective CD45RA+ depletion (p = .002), pre-engraftment syndrome (p = .007), and chronic graft-versus-host disease (GVHD) severity (p = .030). Seizures predicted evolution to life-threatening complications and admission to intensive care (p < .001) and higher mortality (p = .023). A statistically significant association was also found between seizures and sequelae in survivors (p = .029). Children who developed seizures had a higher risk of CNS infection and vascular disease (odds ratio 37.25 95% CI: 7.45-186.05 and 12.95 95% CI 2.24-74.80, respectively).
Neurological complications highly impact survival and outcomes and need to be addressed when facing an HSCT procedure.
Herpes simplex encephalitis can trigger autoimmune encephalitis that leads to neurological worsening. We aimed to assess the frequency, symptoms, risk factors, and outcomes of this complication.
We ...did a prospective observational study and retrospective analysis. In the prospective observational part of this study, we included patients with herpes simplex encephalitis diagnosed by neurologists, paediatricians, or infectious disease specialists in 19 secondary and tertiary Spanish centres (Cohort A). Outpatient follow-up was at 2, 6, and 12 months from onset of herpes simplex encephalitis. We studied another group of patients retrospectively, when they developed autoimmune encephalitis after herpes simplex encephalitis (Cohort B). We compared demographics and clinical features of patients who developed autoimmune encephalitis with those who did not, and in patients who developed autoimmune encephalitis we compared these features by age group (patients ≤4 years compared with patients >4 years). We also used multivariable binary logistic regression models to assess risk factors for autoimmune encephalitis after herpes simplex encephalitis.
Between Jan 1, 2014, and Oct 31, 2017, 54 patients with herpes simplex encephalitis were recruited to Cohort A, and 51 were included in the analysis (median age 50 years IQR 5–68). At onset of herpes simplex encephalitis, none of the 51 patients had antibodies to neuronal antigens; during follow-up, 14 (27%) patients developed autoimmune encephalitis and all 14 (100%) had neuronal antibodies (nine 64% had NMDA receptor NMDAR antibodies and five 36% had other antibodies) at or before onset of symptoms. The other 37 patients did not develop autoimmune encephalitis, although 11 (30%) developed antibodies (n=3 to NMDAR, n=8 to unknown antigens; p<0·001). Antibody detection within 3 weeks of herpes simplex encephalitis was a risk factor for autoimmune encephalitis (odds ratio OR 11·5, 95% CI 2·7–48·8; p<0·001). Between Oct 7, 2011, and Oct 31, 2017, there were 48 patients in Cohort B with new-onset or worsening neurological symptoms not caused by herpes simplex virus reactivation (median age 8·8 years IQR 1·1–44·2; n=27 male); 44 (92%) patients had antibody-confirmed autoimmune encephalitis (34 had NMDAR antibodies and ten had other antibodies). In both cohorts (n=58 patients with antibody-confirmed autoimmune encephalitis), patients older than 4 years frequently presented with psychosis (18 58% of 31; younger children not assessable). Compared with patients older than 4 years, patients aged 4 years or younger (n=27) were more likely to have shorter intervals between onset of herpes simplex encephalitis and onset of autoimmune encephalitis (median 26 days IQR 24–32 vs 43 days 25–54; p=0·0073), choreoathetosis (27 100% of 27 vs 0 of 31; p<0·001), decreased level of consciousness (26 96% of 27 vs seven 23% of 31; p<0·001), NMDAR antibodies (24 89% of 27 vs 19 61% of 31; p=0·033), and worse outcome at 1 year (median modified Rankin Scale 4 IQR 4–4 vs 2 2–3; p<0·0010; seizures 12 63% of 19 vs three 13% of 23; p=0·001).
The results of our prospective study show that autoimmune encephalitis occurred in 27% of patients with herpes simplex encephalitis. It was associated with development of neuronal antibodies and usually presented within 2 months after treatment of herpes simplex encephalitis; the symptoms were age-dependent, and the neurological outcome was worse in young children. Prompt diagnosis is important because patients, primarily those older than 4 years, can respond to immunotherapy.
Mutua Madrileña Foundation, Fondation de l'Université de Lausanne et Centre Hospitalier Universitaire Vaudois, Instituto Carlos III, CIBERER, National Institutes of Health, Generalitat de Catalunya, Fundació CELLEX.
Objective
COASY, the gene encoding the bifunctional enzyme CoA synthase, which catalyzes the last two reactions of cellular de novo coenzyme A (CoA) biosynthesis, has been linked to two exceedingly ...rare autosomal recessive disorders, such as COASY protein‐associated neurodegeneration (CoPAN), a form of neurodegeneration with brain iron accumulation (NBIA), and pontocerebellar hypoplasia type 12 (PCH12). We aimed to expand the phenotypic spectrum and gain insights into the pathogenesis of COASY‐related disorders.
Methods
Patients were identified through targeted or exome sequencing. To unravel the molecular mechanisms of disease, RNA sequencing, bioenergetic analysis, and quantification of critical proteins were performed on fibroblasts.
Results
We identified five new individuals harboring novel COASY variants. While one case exhibited classical CoPAN features, the others displayed atypical symptoms such as deafness, language and autism spectrum disorders, brain atrophy, and microcephaly. All patients experienced epilepsy, highlighting its potential frequency in COASY‐related disorders. Fibroblast transcriptomic profiling unveiled dysregulated expression in genes associated with mitochondrial respiration, responses to oxidative stress, transmembrane transport, various cellular signaling pathways, and protein translation, modification, and trafficking. Bioenergetic analysis revealed impaired mitochondrial oxygen consumption in COASY fibroblasts. Despite comparable total CoA levels to control cells, the amounts of mitochondrial 4′‐phosphopantetheinylated proteins were significantly reduced in COASY patients.
Interpretation
These results not only extend the clinical phenotype associated with COASY variants but also suggest a continuum between CoPAN and PCH12. The intricate interplay of altered cellular processes and signaling pathways provides valuable insights for further research into the pathogenesis of COASY‐associated diseases.
Vanishing White Matter Disease in a Spanish Population Turón-Viñas, Eulàlia; Pineda, Mercè; Cusí, Victòria ...
Journal of Central Nervous System Disease,
01/2014, Letnik:
2014, Številka:
6
Journal Article, Book Review
Recenzirano
Odprti dostop
Vanishing white matter (VWM) leukoencephalopathy is one of the most prevalent hereditary white matter diseases. It has been associated with mutations in genes encoding eukaryotic translation ...initiation factor (eIF2B). We have compiled a list of all the patients diagnosed with VWM in Spain; we found 21 children. The first clinical manifestation in all of them was spasticity, with severe ataxia in six patients, hemiparesis in one child, and dystonic movements in another. They suffered from progressive cognitive deterioration and nine of them had epilepsy too. In four children, we observed optic atrophy and three also had progressive macrocephaly, which is not common in VWM disease. The first two cases were diagnosed before the 1980s. Therefore, they were diagnosed by necropsy studies. The last 16 patients were diagnosed according to genetics: we found mutations in the genes eIF2B5 (13 cases), eIF2B3 (2 cases), and eIF2B4 (1 case). In our report, the second mutation in frequency was c.318A>T; patients with this mutation all followed a slow chronic course, both in homozygous and heterozygous states. Previously, there were no other reports to confirm this fact. We also found some mutations not described in previous reports: c.1090C>T in eIF2B4, c.314A>G in eIF2B5, and c.877C>T in eIF2B5.
Enteroviruses are a type of RNA-strained virus with more than 100 different genotypes. Infection can be asymptomatic, and, if any, symptoms can range from mild to severe. Some patients can develop ...neurological involvement, such as aseptic meningitis, encephalitis, or even cardiorespiratory failure. However, in children, the risk factors for developing severe neurological involvement are not well understood. The aim of this retrospective study was to analyze some characteristics associated with severe neurological involvement in children hospitalized for neurological disease after enterovirus infection.
retrospective observational study analyzing clinical, microbiological and radiological data of 174 children hospitalized from 2009 to 2019 in our hospital. Patients were classified according to the World Health Organization case definition for neurological complications in hand, foot and mouth disease.
Our findings showed that, in children between 6 months old and 2 years of age, the appearance of neurological symptoms within the first 12h from infection onset—especially if associated with skin rash—was a significant risk factor for severe neurological involvement. Detection of enterovirus in cerebrospinal fluid was more likely in patients with aseptic meningitis. By contrast, other biological samples (e.g., feces or nasopharyngeal fluids) were necessary to detect enterovirus in patients with encephalitis. The genotype most commonly associated with the most severe neurological conditions was EV-A71. E-30 was mostly associated with aseptic meningitis.
Awareness of the risk factors associated with worse neurological outcomes could help clinicians to better manage these patients to avoid unnecessary admissions and/or ancillary tests.
Los enterovirus son virus ARN con más de 100 genotipos diferentes. Las infecciones que producen pueden ser asintomáticas y, si producen síntomas, estos varían de leves a graves. Algunos pacientes pueden desarrollar afectación neurológica, como meningitis aséptica, encefalitis o incluso fallo cardiorrespiratorio por lesión del tronco encefálico. Sin embargo, en niños, los factores de riesgo para desarrollar clínica neurológica grave no son bien conocidos. El objetivo de este estudio es analizar las características asociadas a la afectación neurológica grave en niños hospitalizados con infección por enterovirus.
Estudio retrospectivo observacional que analiza datos clínicos, radiológicos y microbiológicos de 174 niños ingresados desde 2009 a 2019 en nuestro hospital. Los pacientes fueron clasificados según la definición de caso de la OMS para las complicaciones neurológicas de la enfermedad boca mano pie.
Nuestros resultados muestran que, en niños de 6 meses a 2 años de edad, la aparición de síntomas neurológicos en las primeras 12 horas del inicio de la infección, y especialmente si asocian exantema cutáneo, se asoció a un riesgo estadísticamente significativo para desarrollar formas neurológicas graves. La detección de enterovirus mediante PCR en líquido cefalorraquídeo fue más probable en los niños con meningitis. En cambio, se precisaron estudios en otras muestras biológicas (heces, moco nasofaríngeo) para detectar enterovirus en pacientes con encefalitis. El genotipo que se asoció más frecuentemente con las formas clínicas más graves fue EV-A71. E-30 es el que más frecuentemente se asoció a meningitis.
El conocimiento de los factores de riesgo asociados con las formas más graves podría ayudar al manejo de estos niños, así como evitar pruebas o ingresos innecesarios.
Enteroviruses are a type of RNA-strained virus with more than 100 different genotypes. Infection can be asymptomatic, and, if any, symptoms can range from mild to severe. Some patients can develop ...neurological involvement, such as aseptic meningitis, encephalitis, or even cardiorespiratory failure. However, in children, the risk factors for developing severe neurological involvement are not well understood. The aim of this retrospective study was to analyze some characteristics associated with severe neurological involvement in children hospitalized for neurological disease after enterovirus infection.
retrospective observational study analyzing clinical, microbiological and radiological data of 174 children hospitalized from 2009 to 2019 in our hospital. Patients were classified according to the World Health Organization case definition for neurological complications in hand, foot and mouth disease.
Our findings showed that, in children between 6 months old and 2 years of age, the appearance of neurological symptoms within the first 12h from infection onset—especially if associated with skin rash—was a significant risk factor for severe neurological involvement. Detection of enterovirus in cerebrospinal fluid was more likely in patients with aseptic meningitis. By contrast, other biological samples (e.g., feces or nasopharyngeal fluids) were necessary to detect enterovirus in patients with encephalitis. The genotype most commonly associated with the most severe neurological conditions was EV-A71. E-30 was mostly associated with aseptic meningitis.
Awareness of the risk factors associated with worse neurological outcomes could help clinicians to better manage these patients to avoid unnecessary admissions and/or ancillary tests.
Los enterovirus son virus ARN con más de 100 genotipos diferentes. Las infecciones que producen pueden ser asintomáticas y, si producen síntomas, estos varían de leves a graves. Algunos pacientes pueden desarrollar afectación neurológica, como meningitis aséptica, encefalitis o incluso fallo cardiorrespiratorio por lesión del tronco encefálico. Sin embargo, en niños, los factores de riesgo para desarrollar clínica neurológica grave no son bien conocidos. El objetivo de este estudio es analizar las características asociadas a la afectación neurológica grave en niños hospitalizados con infección por enterovirus.
Estudio retrospectivo observacional que analiza datos clínicos, radiológicos y microbiológicos de 174 niños ingresados desde 2009 a 2019 en nuestro hospital. Los pacientes fueron clasificados según la definición de caso de la OMS para las complicaciones neurológicas de la enfermedad boca mano pie.
Nuestros resultados muestran que, en niños de 6 meses a 2 años de edad, la aparición de síntomas neurológicos en las primeras 12 horas del inicio de la infección, y especialmente si asocian exantema cutáneo, se asoció a un riesgo estadísticamente significativo para desarrollar formas neurológicas graves. La detección de enterovirus mediante PCR en líquido cefalorraquídeo fue más probable en los niños con meningitis. En cambio, se precisaron estudios en otras muestras biológicas (heces, moco nasofaríngeo) para detectar enterovirus en pacientes con encefalitis. El genotipo que se asoció más frecuentemente con las formas clínicas más graves fue EV-A71. E-30 es el que más frecuentemente se asoció a meningitis.
El conocimiento de los factores de riesgo asociados con las formas más graves podría ayudar al manejo de estos niños, así como evitar pruebas o ingresos innecesarios.
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