Value of Thyroid Peroxidase Antibodies in Neuroimmune Diseases: Analysis of Interference During Treatment with Intravenous Immunoglobulins.

OBJECTIVE: The absence of specific markers can make the diagnosis of neuroimmune disorders difficult, making other biomarkers such as thyroid peroxidase antibodies (TPO-Abs) more relevant. Laboratory tests are susceptible to interference, especially those tests performed using immunoassay techniques. The effect of treatment with human intravenous immunoglobulin (IVIG) on the results of TPO-Abs assays has not been previously characterized. MATERIALS AND METHODS: We analyzed TPO-Abs levels in 170 children monitored in the neuroimmune disease department of a tertiary hospital. We analyzed the characteristics of patients with increased TPO-Abs values and compared their progress with and without treatment. RESULTS: We found that 97% of patients with elevated TPO-Abs had received IVIG. After withdrawal from IVIG, a mean TPO-Abs decrease of 62.5% at 1 month was observed. The IVIG drug preparation was found to contain 1176 U/mL of TPO-Abs. An interferogram confirmed interference. CONCLUSION: It is advisable to measure levels of TPO-Abs before starting immunotherapy and remain vigilant regarding possible interference in the event of unsubstantiated elevations of this analyte.

Impact of COVID-19 in Immunosuppressed Children With Neuroimmunologic Disorders.

BACKGROUND AND OBJECTIVES: To investigate whether children receiving immunosuppressive therapies for neuroimmunologic disorders had (1) increased susceptibility to SARS-CoV2 infection or to develop more severe forms of COVID-19; (2) increased relapses or autoimmune complications if infected; and (3) changes in health care delivery during the pandemic. METHODS: Patients with and without immunosuppressive treatment were recruited to participate in a retrospective survey evaluating the period from March 14, 2020, to March 30, 2021. Demographics, clinical features, type of immunosuppressive treatment, suspected or confirmed COVID-19 in the patients or cohabitants, and changes in care delivery were recorded. RESULTS: One hundred fifty-three children were included: 84 (55%) female, median age 13 years (interquartile range [8-16] years), 79 (52%) on immunosuppressive treatment. COVID-19 was suspected or confirmed in 17 (11%) (all mild), with a frequency similar in patients with and without immunosuppressive treatment (11/79 [14%] vs 6/74 [8%], p = 0.3085). The frequency of neurologic relapses was similar in patients with (18%) and without (21%) COVID-19. Factors associated with COVID-19 included having cohabitants with COVID-19 (p < 0.001) and lower blood levels of vitamin D (p = 0.039). Return to face-to-face schooling or mask type did not influence the risk of infection, although 43(28%) children had contact with a classmate with COVID-19. Clinic visits changed from face to face to remote for 120 (79%) patients; 110 (92%) were satisfied with the change. DISCUSSION: In this cohort of children with neuroimmunologic disorders, the frequency of COVID-19 was low and not affected by immunosuppressive therapies. The main risk factors for developing COVID-19 were having cohabitants with COVID-19 and low vitamin D levels.

Dystonia and Contractures are Potential Early Signs of CACNA1E-Related Epileptic Encephalopathy.

Epileptic encephalopathy related to CACNA1E has been described as a severe neurodevelopmental disorder presenting with early-onset refractory seizures, hypotonia, macrocephaly, hyperkinetic movements, and contractures and is associated with an autosomal dominant inheritance pattern. Most pathogenic variants described to date are missense variants with a gain of function effect, and the role of haploinsufficiency has yet to be clarified. We describe 2 cases of CACNA1E encephalopathy. Notable findings include congenital contractures and movement disorders predating onset of epilepsy, particularly dystonia. We further compared the key phenotypic features depending on variant location. In conclusion, the appearance of congenital contractures, areflexia, and movement disorders before the onset of epilepsy may provide key guidance in the diagnosis of epileptic CACNA1E encephalopathy. A genotype-phenotype correlation was found between the presence of movement disorders and severe intellectual disability and the location of the variant in the CACNA1E gene.

Síndrome opsoclonus mioclonus. Experiencia en los últimos 12 años en un hospital terciario / Opsoclonus-myoclonus syndrome: Experience in a tertiary hospital in the last 12 years

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Rasmussen's encephalitis and central precocious puberty. Neuroendocrinological characterization of three cases.

PURPOSE: Rasmussen's encephalitis (RE) is a chronic neurological disorder characterized by inflammation of the cerebral cortex, mainly unilateral, that leads to drug-resistant epilepsy and progressive neurological impairment. Central Precocious Puberty (CPP) is uncommon, albeit increased in frequency in patients with neurological conditions and the physiopathological bases of these associations remains unclear in most cases. Epilepsy has been proposed to play a role, as well as the accumulation of substances produced as a result of metabolism or tissue degeneration in some neurodegenerative diseases. However, CPP has not been previously described in patients with RE. METHODS: From a series of patients affected by RE followed-up at a referral center, an in-depth review of the characteristics of those who developed CCP was carried out. RESULTS: Three cases were identified, representing a relative frequency of 21.4 % for CPP. They were girls, of Caucasian ethnicity, without family history of CPP or any image-identified abnormalities in the hypothalamic area. In two cases CPP manifested immediately before the onset of the epilepsy (prior to the diagnosis of RE) and in the other, after epilepsy onset but coinciding with a worsening of the seizures. A GnRH test with pubertal response confirmed CPP in the three cases. CONCLUSION: The high proportion of CPP in patients affected by RE suggested a plausible relationship between these two entities. Various factors involved, including neuroinflammation, are hypothesized in the present study. However, further studies are needed to elucidate the pathophysiological bases, which could provide insight in the understanding of both entities.

Utility of the transcranial doppler in the evaluation and follow-up of children with Sturge-Weber Syndrome.

INTRODUCTION: Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome with typical clinical features including seizures, chronic hemiplegia, hemianopsia and intellectual impairment. Progressive clinical decline may be attributable, at least in part, to progressive venous ischemia. Transcranial Doppler (TCD) ultrasonography could be useful to monitor the degree of hemodynamic involvement and its progression. PURPOSE: To determine whether there is an association between the degree of asymmetry in TCD and intensity of clinical and radiological involvement and whether there is a correlation between clinical changes and changes in serial TCD. METHODS: In fourteen SWS pediatric patients and two "possible cases" (infants younger than two years old without previously known brain involvement, but with other typical signs of SWS) mean flow velocity in the middle cerebral arteries (MCA) was measured by TCD in both hemispheres. The percent difference between hemispheres (asymmetry) was calculated. Clinical and radiological severity was scored using scales. The correlation between TCD asymmetry and SWS clinical and radiological scores was analyzed at baseline, as well as the correlation between the changes in the different variables (TCD asymmetry, clinical and radiological cores) during evolution and in relation to the changes due to therapy. RESULTS: The percentage of MCA velocity asymmetry was positively correlated with the clinical severity score (p = 0.04), and with seizure frequency (p = 0.014). Throughout evolution, therapeutic and clinical changes were associated with noticeable changes in transcranial doppler asymmetry in some cases. CONCLUSIONS: TCD may provide a noninvasive method to assess the severity of blood flow abnormalities at baseline and a method to monitor children for progressive changes over time.

Inmunoadsorción y plasmaféresis: ¿posibilidades de tratamiento en la encefalitis de Rasmussen? / No disponible

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Tocilizumab in pediatric refractory status epilepticus and acute epilepsy: Experience in two patients.

There is growing evidence for inflammation as a cause and/or consequence of seizures in epilepsy as certain inflammatory biomarkers are elevated. Interleukin (IL)-6, with pro-inflammatory and epileptogenic effects, can perpetuate seizures. Clinical and experimental data support its involvement in acute refractory situations, with some cases responding to treatment with tocilizumab, a humanized monoclonal antibody against the IL-6 receptor. We describe 2 pediatric cases of refractory epilepsy with an abrupt debut responding to tocilizumab. Advances in the knowledge of inflammatory biomarkers involved in epilepsy and the targeted treatment could have important benefits, especially in cases that are refractory to usual treatments.

Nutrition Risk in Hospitalized Pediatric Patients: Higher Complication Rate and Higher Costs Related to Malnutrition.

BACKGROUND: Hospitalized children present higher rates of undernutrition. Malnutrition can lead to a more complex hospitalization process with an increased length of stay and higher costs. Our aim was to analyze nutrition risk in hospitalized children and its relationship with clinical outcomes in a tertiary level hospital. METHODS: This is a single institution prospective observational study. The research involved 282 consecutive children admitted along 3 months. Anthropometric measurements and nutrition risk by means of the Screening Tool for Risk on Nutritional Status and Growth (STRONGkids) tool were performed at admission. The incidence of infectious complications, length of hospital stay, weight loss, hospital expenses, and need of nutrition support were recorded. RESULTS: The percentage of children with high, moderate, and low nutrition risk was 12.8%, 45%, and 42%, respectively. The prevalence of acute and chronic malnutrition was 13.7% and 7.4%. STRONGkids score correlated with clinical outcomes: longer stay, higher hospital expenses, and need of nutrition support were observed in children with high nutrition risk scores compared with the other groups (P < 0.001). The overall incidence of infectious complications was low (3.5%); a higher STRONGkids score did not predict a higher rate. CONCLUSION: Hospitalized children exposed to high nutrition risk have poorer clinical outcomes: longer stay, higher hospital expenses, and need of nutrition support. More studies are required to assess if applying STRONGkids and starting a nutrition intervention would result in lower costs and a shorter length of stay.

Encefalitis por anticuerpos contra el receptor de NMDA con afectación hemisférica unilateral / Anti-NMDA receptor encephalitis with unilateral hemispheric affectation

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Complicaciones neurológicas en casos de bronquiolitis por virus respiratorio sincitial: estado febril y otras manifestaciones neurológicas / Neurological complications in cases of bronchiolitis due to respiratory syncytial virus: febrile status and other neurological manifestations

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Dos nuevos casos de síndrome de Leigh por mutación m.13513G>A en el gen MTND5 / Two new cases of Leigh syndrome caused by mutation m.13513G> A in the MTND5 gene

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Síndrome de West secundario a duplicación patogénica en la citobanda 14q12 / West syndrome associated with 14q12 duplication

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Politerapia racional en epilepsia infantil / Rational polytherapy in infantile epilepsy

Se acepta globalmente que el tratamiento inicial de la epilepsia debe realizarse en monoterapia. Sin embargo, dado que hasta un 30% de los pacientes son refractarios a una o varias monoterapias, es común asociar pautas combinadas de dos o más fármacos antiepilépticos (FAE). En estos supuestos de politerapia, hay que considerar el mecanismo de acción de cada FAE, su espectro, su seguridad, y sus interacciones farmacocinéticas y farmacodinámicas. La politerapia racional es un concepto terapéutico basado en la combinación de FAE con mecanismos de acción complementarios que actúan sinérgicamente para maximizar su e cacia y minimizar los potenciales efectos adversos. Para diseñar una buena politerapia racional en epilepsia es básico conocer los distintos mecanismos de acción de cada FAE y analizar la evidencia empírica existente para con cada una de las posibles combinaciones de FAE. Se sugiere que puede ser útil combinar FAE inhibidores de canales de sodio con FAE gabaérgicos, o con FAE con múltiples mecanismos de acción, y evitar aquellas combinaciones que potencien la toxicidad. Sin embargo, existe muy escasa evidencia empírica y clínica respecto a la politerapia racional y sólo está demostrado el sinergismo entre valproato y lamotrigina. La politerapia racional supone una estrategia diseñada para mejorar el balance entre e cacia y tolerabilidad de las distintas combinaciones de FAE. Sin embargo, dada la ausencia de ensayos clínicos en politerapia racional, sólo podemos hacer sugerencias sobre asociaciones de FAE potencialmente útiles o perjudiciales en base a las características farmacocinéticas y farmacodinámicas de los diversos FAE implicados.

Abstract It is an accepted fact that antiepileptic treatment must be started with monotherapy, but 30% of patients do not respond to it or to several monotherapies; in that moment an association of two or more antiepileptic drugs (AEDs) is commonly utilized. It is necessary to consider the mechanism of action of each AED, its spectrum, the safety and pharmacodynamic and pharmacokinetic interactions, and to select the association of AEDs in accordance with these factors. Rational polytherapy is a concept that is predicated on the combination of drugs with complementary mechanisms of action that work synergistically to maximize efficacy and minimize the potential for adverse events. Furthermore, rational polytherapy requires a detailed understanding of the mechanisms of action subclasses among available AEDs and an appreciation of the empirical evidence that supports the use of specific combinations. These theoretical foundations suggest a sodium channel inhibitor should be associated with a GABAergic agent or with an AED with multiple mechanisms and that we should avoid the association between AEDs with additional toxicity or that are likely to interact. However, the experimental and clinical evidence in support of rational polytherapy is sparse, with only the combination of sodium valproate and lamotrigine demonstrating synergism. Rational polytherapy is a theoretical approach designed for improving the balance between efficacy and tolerability of several AEDs combinations. However, the absence of clinical trials only allows us to make suggestions about possible bene cial or harmful associations depending on the pharmacodynamic and pharmacokinetic characteristics of AEDs.

Encefalopatías epilépticas del lactante: lo prioritario es el studio genético / Infantile epileptic encephalopathies: what matters is genetics

Introducción. Las encefalopatías epilépticas del lactante constituyen un grupo de entidades donde la actividad epiléptica mantenida contribuye por sí misma al deterioro neurológico y cognitivo del paciente. Entre ellas se incluyen el síndrome de Ohtahara, la encefalopatía mioclónica precoz, el síndrome de West, el síndrome de Dravet y la epilepsia migratoria maligna del lactante. Estos síndromes se originan por etiologías variadas, incluyendo lesiones estructurales cerebrales, enfermedades metabólicas y heredodegenerativas, y alteraciones genéticas, entre otras. Objetivo. Presentar y discutir el conocimiento actual sobre los hallazgos genéticos en las encefalopatías epilépticas del lactante, el potencial correlato genotipo-fenotipo en las distintas formas de encefalopatías epilépticas y el impacto de estos nuevos hallazgos en la práctica clínica. Desarrollo. En los lactantes con encefalopatías epilépticas, sin una etiología definida tras realizar una resonancia magnética cerebral, debe considerarse un abordaje etiológico que excluya patologías genéticas. En la actualidad, más de 50 genes se han asociado con la etiología de las encefalopatías epilépticas del lactante. Los paneles de múltiples genes analizados por técnicas de secuenciación masiva son una herramienta útil para el diagnóstico genético de estos pacientes. Conclusiones. El conocimiento sobre la genética de las encefalopatías epilépticas del lactante ha revolucionado el abordaje diagnóstico y cada vez se implican más genes y distintos tipos de mutaciones en la patogenia de estas patologías. El desarrollo de clasificaciones específicas para las encefalopatías epilépticas genéticas puede contribuir a un mejor correlato genotipo-fenotipo, a orientar mejor el consejo genético y a considerar terapias específicas (AU)

Introduction. Epileptic encephalopathies in infancy are defined as conditions where the sustained epileptic activity itself may contribute to the severe neurological and cognitive impairment. These epileptic encephalopathies include Ohtahara syndrome, early myoclonic epileptic encephalopathy, West syndrome, Dravet syndrome, and malignant migrating epilepsy in infancy. These syndromes result from identifiable primary causes, such as structural, neurodegenerative, metabolic, or genetic defects. Aim. To present and discuss current knowledge regarding genetic findings in epileptic encephalopathies in infancy, phenotype-genotype correlations in different forms of paediatric epileptic encephalopathies, and the impact of these new findings in clinical practice. Development. Patients with unclear etiologies after performing a brain magnetic resonance imaging should be considered for a further workup, which should include an evaluation for genetic defects. Nowadays, more than 50 genes have been associated with epileptic encephalopathies in infancy. Targeted next-generation sequencing panels show a high diagnostic yield in patients with epileptic encephalopathies. Conclusions. Genetic knowledge about epileptic encephalopathies in infancy has revolutionized the diagnostic approach to these disorders, and an increasing number of gene mutations have been related to their pathogenesis. A more detailed classification of epileptic encephalopathies genotypes will improve the accuracy of genotype-phenotype correlation and genetic counseling. All these developments could yield therapeutic applications such as gene therapy or antiepileptic drugs ‘tailored’ to the specific genetic markers or targets (AU)