La enfermedad SARS-Cov-2 (COVID-19) es responsable de una variedad de síntomas como fiebre, tos y fatiga, si bien es cierto que el padecimiento más frecuente se centra a nivel respiratorio y ...cardiovascular, existen reportes preliminares que han alertó sobre la posibilidad de que el SARS-Cov-2 pueda tener un potencial neuroinvasivo, ya que algunos pacientes han presentado síntomas neurológicos, entre ellos dolor de cabeza, mareos y en casos más severos eventos cerebrovasculares isquémicos, de igual manera ha descrito la aparición de anosmia y ageusia como síntomas tempranos de la infección por COVID-19. La literatura actual sugiere una asociación importante entre la infección por SARS-Cov-2 y el sistema nervioso central, por lo que es importante reconocer y controlar las complicaciones neurológicas potencialmente mortales secundarias a la infección por COVID-19
Background 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. Methods 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. Findings 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). Interpretation 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.
La encefalitis autoinmune es una entidad relativamente nueva que consiste en un proceso inflamatorio del sistema nervioso central mediado por anticuerpos e involucra predominantemente el sistema ...límbico causado por interacción de anticuerpos en contra de antígenos neuronales específicos. La presentación clínica es variable y la resonancia magnética en conjunto con la detección de anticuerpos antineuronales permiten un diagnóstico oportuno. Presentamos un caso clínico de encefalitis autoinmune con anticuerpos anti-GAD positivos y consideramos los aspectos imagenológicos y clínicos relevantes para su diagnóstico.
No es lo que parece Vanessa Gladys Velasquez Acebey; María Irigoyen Otiñano; Jaime Velasquez Centellas ...
Psicosomática y psiquiatría,
10/2023
27
Journal Article
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.
El reciente coronavirus denominado SARS-CoV-2 es el causante de la enfermedad COVID-19, declarada pandemia por la OMS. Inicialmente considerado un virus predominantemente respiratorio, sin embargo, ...con el transcurso del tiempo y la evidencia de múltiples casos reportados se ha observado variabilidad en las manifestaciones clínicas y el compromiso multisistémico, dentro de los cuales es importante resaltar la afectación del sistema nervioso central a través de diversos mecanismos directos o indirectos. Se presenta el caso de un paciente previamente sano, con prueba de COVID-19 positiva que debutó con accidente cerebrovascular isquémico y encefalitis viral más sobre infección por toxoplasma, sin presencia de inmunodeficiencia y con evolución satisfactoria. Las manifestaciones extrapulmonares originadas por el virus cobran cada vez más importancia, en especial las neurológicas por su alta morbimortalidad. Se recomienda la realización de prueba para COVID-19 al ingreso de pacientes con ACV isquémico, y establecer un manejo individualizado e integral teniendo en cuenta los múltiples estudios existentes, pese que aún es tema de estudio al igual que su manejo y pronóstico.
Cognitive impairment, usually associated with seizures and psychosis, is one of the main symptoms of autoimmune encephalitis. The objective of our study is to analyse cognitive impairment in patients ...with autoimmune encephalitis.
We conducted a descriptive cross-sectional study of clinical data from 39 patients older than 18 years diagnosed with autoimmune encephalitis. Twenty-two patients underwent neuropsychological assessment.
All but one of the patients presented cognitive impairment. Memory was the most frequently affected domain (90.91%), followed by language (50%), attention (45.45%), executive function (40.91%), praxis (40.91%), and visuospatial skills (9.09%). No association was found with disease progression time, age, sex, or education level. Results from cerebrospinal fluid analysis, electroencephalography, and brain magnetic resonance imaging studies revealed alterations in 77.27%, 57.89%, and 55% of cases, respectively.
Memory is the most frequently affected cognitive domain; however, other cognitive domains were also altered in our patients. Neuropsychological assessment is crucial to determine which cognitive domains are impaired in patients with autoimmune encephalitis.
El deterioro cognitivo, usualmente asociado a crisis epilépticas y psicosis, es uno de los principales síntomas de la encefalitis autoinmune. El objetivo de nuestro estudio fue describir las alteraciones cognitivas en pacientes con encefalitis autoinmune.
Trabajo descriptivo transversal. Se revisaron 39 registros de pacientes mayores de 18 años con diagnóstico de encefalitis autoinmune, 22 de los cuales tuvieron evaluación neuropsicológica.
de los 22 pacientes sólo uno no presentó deterioro cognitivo. El dominio más comprometido fue la memoria (90,91%), seguido del lenguaje (50%), atención (45,45%), funciones ejecutivas (40,91%), apraxia (40,91%) y habilidades visuoespaciales (9,09%). No se encontró asociación con el tiempo de enfermedad, grado de instrucción, sexo o edad. Los análisis de líquido cefalorraquídeo, encefalograma y resonancia magnética estuvieron alterados en 77,27%, 57,89% y 55% de los casos respectivamente.
El trastorno de memoria es el compromiso más frecuente; sin embargo, nosotros encontramos que nuestros pacientes presentaban alteraciones de otras áreas cognitivas. La evaluación neuropsicológica es fundamental para determinar qué dominios están comprometidos en los pacientes con encefalitis autoinmune.
In 5 prospectively diagnosed patients with relapsing post–herpes simplex encephalitis (HSE), N‐methyl‐D‐aspartate receptor (NMDAR) antibodies were identified. Antibody synthesis started 1 to 4 weeks ...after HSE, preceding the neurological relapse. Three of 5 patients improved postimmunotherapy, 1 spontaneously, and 1 has started to improve. Two additional patients with NMDAR antibodies, 9 with unknown neuronal surface antibodies, and 1 with NMDAR and unknown antibodies, were identified during retrospective assessment of 34 HSE patients; the frequency of autoantibodies increased over time (serum, p = 0.004; cerebrospinal fluid, p = 0.04). The 3 retrospectively identified NMDAR antibody–positive patients also had evidence of relapsing post‐HSE. Overall, these findings indicate that HSE triggers NMDAR antibodies and potentially other brain autoimmunity. Ann Neurol 2014;75:317–323
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