Early recognition of SGCE-myoclonus-dystonia in children.

AIM: To evaluate early dystonic features in children and adolescents with SGCE-myoclonus-dystonia. METHOD: In this cross-sectional study, 49 patients (26 females and 23 males) with SGCE-myoclonus-dystonia (aged 15y 2mo, SD 12y) with childhood-onset (2y 10mo, SD 1y 10mo) dystonia were examined using a standardized video recorded protocol. Dystonia was rated using the Writer's Cramp and Gait Dystonia Rating Scales. Disability and impairment for handwriting and walking were also rated. RESULTS: Dystonia was present at rest (n=1), posture (n=12), and during specific motor tasks (n=45) such as writing (n=35), walking (n=23), and running (n=20). Most children reported disability while performing these tasks. Early dystonic patterns were identified for writer's cramp and gait dystonia, the latter named the 'circular shaking leg', 'dragging leg', and 'hobby-horse gait' patterns. Sensory tricks were used by five and eight children to improve dystonia and myoclonus during writing and walking respectively. The rating scales accurately measured the severity of action dystonia and correlated with self-reported disability. INTERPRETATION: Children with SGCE-myoclonus-dystonia show recognizable dystonic patterns and sensory tricks that may lead to an early diagnosis and timely therapeutic approach. Isolated writer's cramp is a key feature in childhood and should prompt SCGE analysis. The proposed action dystonia scales could be used to monitor disease course and response to treatment. WHAT THIS PAPER ADDS: Most children with SGCE-myoclonus-dystonia got writer's cramp and had walking and running dystonia. Writer's cramp was a key feature and should prompt SGCE genetic investigation. 'Circular shaking leg', 'dragging leg', and 'hobby-horse gait' were recognized as early gait patterns. Children used sensory tricks to improve myoclonus and dystonia, suggesting common pathophysiological mechanisms. Action dystonia rating scales are valid tools to assess severity in children.

Genetic diagnosis of basal ganglia disease in childhood.

AIM: To correlate clinical, radiological, and biochemical features with genetic findings in children with bilateral basal ganglia lesions of unknown aetiology, and propose a diagnostic algorithm for early recognition. METHOD: Children with basal ganglia disease were recruited in a 2-year prospective multicentre study for clinical, biomarker, and genetic studies. Radiological pattern recognition was examined by hierarchical clustering analysis. RESULTS: We identified 22 genetic conditions in 30 out of 62 paediatric patients (37 males, 25 females; mean age at onset 2y, SD 3; range 0-10y; mean age at assessment 11y, range 1-25y) through gene panels (n=11), whole-exome sequencing (n=13), and mitochondrial DNA (mtDNA) sequencing (n=6). Genetic aetiologies included mitochondrial diseases (57%), Aicardi-Goutières syndrome (20%), and monogenic causes of dystonia and/or epilepsy (17%) mimicking Leigh syndrome. Radiological abnormalities included T2-hyperintense lesions (n=26) and lesions caused by calcium or manganese mineralization (n=9). Three clusters were identified: the pallidal, neostriatal, and striatal, plus the last including mtDNA defects in the oxidative phosphorylation system with prominent brain atrophy. Mitochondrial biomarkers showed poor sensitivity and specificity in children with mitochondrial disease, whereas interferon signature was observed in all patients with patients with Aicardi-Goutières syndrome. INTERPRETATION: Combined whole-exome and mtDNA sequencing allowed the identification of several genetic conditions affecting basal ganglia metabolism. We propose a diagnostic algorithm which prioritizes early use of next-generation sequencing on the basis of three clusters of basal ganglia lesions.

Clinical experience with brivaracetam in a series of 46 children.

OBJECTIVES: The primary objective of the study was to analyze the efficacy of brivaracetam (BRV) in pediatric patients 12 months after starting treatment. The secondary objective was to establish safety 3, 6, and 12 months after starting treatment. MATERIALS AND METHOD: This was an observational and retrospective study. Data were collected from the electronic medical record. Inclusion criteria were as follows: patients under 18 years of age, diagnosis of focal or generalized epilepsy, treatment as an added therapy, initiation of treatment with BRV between June and September 2017, and at least one unprovoked seizure in the year prior to the start of treatment. RESULTS: Forty-six patients were included. The response rate was 65%, including 30% seizure-free patients. The rate of adverse effects was 43.5%, resulting in withdrawal in 16 patients (34.7%). The most common adverse effects were drowsiness (17.3%) and irritability (17.3%). CONCLUSIONS: Brivaracetam is effective in very diverse childhood epilepsies, including some that present with primarily generalized seizures. Given the characteristics of the population studied, we have not been able to confirm a better tolerability of BRV compared with levetiracetam (LEV).

Diagnosis and Treatment of Tuberous Sclerosis Manifestations in Children: A Multicenter Study.

Tuberous sclerosis complex (TSC) is a genetic disease with a significant morbidity and mortality. We conducted a retrospective analysis of two cohorts (Vall d'Hebron University Hospital [HVH], Barcelona, Spain, 1982-2015, and at Saarland University Medical Center [UKS], Homburg, Germany, 1998-2015) to assess prevalence and treatment of TSC associated manifestations and to evaluate if the follow-up was in line with published recommendations. This was considered if more than 15% of patients did not receive adequate examination with regard to potential organ involvement. A definite diagnosis was made in 52 patients (96%), and a possible diagnosis was made in 2 patients (4%). Thirty-four (63%) patients were from HVH and 20 (37%) from UKS. Median age at first presentation was 6 months (interquartile range: 0-38 months), and median time of follow-up was 6 years (interquartile range: 2-13 years). Clinical symptoms that led to a diagnosis of TSC were cardiac rhabdomyoma (22/54), epilepsy (20/54), and cutaneous manifestations (4/54). Assessment of neuropsychiatric, renal, and ocular manifestations was inadequate in both hospitals, whereas cutaneous manifestation was inadequate at UKS only. Our data demonstrate insufficient examinations in a substantial number of TSC patients with regard to neuropsychiatric, renal, ocular, and cutaneous manifestations. The recently published guidelines may prove valuable in establishing a more comprehensive approach.

Brote de enfermedad neurológica aguda asociada a enterovirus en Cataluña: aspectos neuropediátricos / Outbreak of acute neurological disease associated to enterovirus in Catalonia: neuropaediatric aspects

No disponible

Encefalopatía reversible por ácido valproico en un adolescente con epilepsia generalizada idiopática / Reversible encephalopathy caused by valproic acid in an adolescent with idiopathic generalised epilepsy

Introducción. La encefalopatía por ácido valproico (VPA) es una rara complicación que cursa con un trastorno del estado mental de gravedad variable y que puede asociar un agravamiento paradójico de las crisis. El diagnóstico es obvio cuando aparece en el contexto de una hiperamoniemia o hepatopatía, pero puede resultar difícil si lo hace de forma aislada en pacientes que no muestran otros signos de toxicidad por VPA. Caso clínico. Adolescente afecto de una epilepsia generalizada idiopática que presentó un deterioro cognitivo subagudo y un empeoramiento de su patrón de crisis meses después de iniciado el tratamiento con VPA. Estas manifestaciones se acompañaron de un enlentecimiento del trazado de base en el electroencefalograma y no se identificaron signos bioquímicos de sobredosificación o de toxicidad atribuible al fármaco ni otra posible etiología. La retirada de VPA determinó la rápida mejoría de su estado mental y del control de las crisis, así como la normalización del electroencefalograma. Conclusiones. Debe considerarse la encefalopatía por VPA en el paciente que presente un deterioro de su estado neurológico, asociado o no a un agravamiento de las crisis, a pesar de que no se identifiquen signos analíticos que sugieran la toxicidad o la sobredosificación de VPA. En ausencia de afectación de la función hepática, la retirada del fármaco determinará la desaparición de la sintomatología y permitirá, además, confirmar el diagnóstico (AU)

Introduction. Encephalopathy due to valproic acid (VPA) is a rare complication leading to a disorder that affects the patient’s mental status to a greater or lesser extent and which can be accompanied by a paradoxical worsening of the seizures. The diagnosis is obvious when it appears within the context of hyperammonemia or a liver pathology, but can be difficult to diagnose if it appears in isolation in patients who show no other signs of intoxication due to VPA. Case report. We report the case of an adolescent who suffered idiopathic generalised epilepsy and presented sub-acute cognitive impairment and a worsening of his pattern of seizures some months after starting treatment with VPA. These manifestations were accompanied by a slowing of the baseline electroencephalogram (EEG) tracing; no biochemical signs of overdosage or toxicity that could be attributed to the drug or any other possible aetiology were observed. Withdrawing VPA resulted in a swift improvement in the patient’s mental status and in the control of his seizures. Likewise, EEG recordings also returned to normal. Conclusions. Encephalopathy due to VPA should be considered in patients who present a deterioration of their neurological status, whether associated to an aggravation of their seizures or not, despite the absence of any analytical signs suggestive of VPA toxicity or overdosage. If liver functioning is not affected, withdrawal of the drug will determine the disappearance of the symptoms and will also allow confirmation of the diagnosis (AU)

[Reversible encephalopathy caused by valproic acid in an adolescent with idiopathic generalised epilepsy]. / Encefalopatía reversible por ácido valproico en un adolescente con epilepsia generalizada idiopática.

INTRODUCTION: Encephalopathy due to valproic acid (VPA) is a rare complication leading to a disorder that affects the patient's mental status to a greater or lesser extent and which can be accompanied by a paradoxical worsening of the seizures. The diagnosis is obvious when it appears within the context of hyperammonemia or a liver pathology, but can be difficult to diagnose if it appears in isolation in patients who show no other signs of intoxication due to VPA. CASE REPORT: We report the case of an adolescent who suffered idiopathic generalised epilepsy and presented sub-acute cognitive impairment and a worsening of his pattern of seizures some months after starting treatment with VPA. These manifestations were accompanied by a slowing of the baseline electroencephalogram (EEG) tracing; no biochemical signs of overdosage or toxicity that could be attributed to the drug or any other possible aetiology were observed. Withdrawing VPA resulted in a swift improvement in the patient's mental status and in the control of his seizures. Likewise, EEG recordings also returned to normal. CONCLUSIONS: Encephalopathy due to VPA should be considered in patients who present a deterioration of their neurological status, whether associated to an aggravation of their seizures or not, despite the absence of any analytical signs suggestive of VPA toxicity or overdosage. If liver functioning is not affected, withdrawal of the drug will determine the disappearance of the symptoms and will also allow confirmation of the diagnosis.

[Clinical variability of polymicrogiria: report of 35 new cases and review of the literature]. / Variabilidad clínica de la polimicrogiria: a propósito de 35 nuevos casos y revisión de la bibliografía.

INTRODUCTION: The study of polymicrogyria with magnetic resonance imaging (MRI) has made possible the report of several series of patients in which the main clinical manifestations differ considerably. The aims of the study were to review the literature and to know the clinical variability of the patients attended in a neuropediatric service. PATIENTS AND METHODS: A retrospective study was conducted between 1989-2011 for the patients attended in our neuro-pediatric service and diagnosed of polymicrogyria by MRI. RESULTS: On the totality of 44 patients having polymicrogyria, 9 did not satisfy de inclusion criteria (Barkovich's radiological criteria). The polymicrogyria was bilateral in 22/35 patients (1 frontal, 22 perisylvian) and unilateral in 13/35 (2 frontal, the rest perisylvian). All patients with bilateral polymicrogyria had intellectual disability, 71% had global development delay, 75% had oromotor disorder and 40% had epilepsy. Patients with unilateral polymicrogyria had the following symptoms: 65% intellectual disability, 55% global development delay, 55% oromotor disorder, 55% epilepsy and 2 patients where free of symptoms (the oldest 2 year old). The initial symptoms were depending upon the age: the oromotor disorder was the most common in the newborn period, global development delay if the symptoms started before 2 years old and after 2 years epilepsy was the initial most common symptom. CONCLUSION: In our study the most common symptom was intellectual disability (independently of the type of poly-microgyria), followed by oromotor disorder and, with fewer proportion, epilepsy (in contrast with other series).

Variabilidad clínica de la polimicrogiria: a propósito de 35 nuevos casos y revisión de la bibliografía / Clinical variability of polymicrogiria: report of 35 new cases and review of the literatureepi

Introducción. El estudio diagnóstico de polimicrogiria mediante resonancia magnética ha facilitado la publicación de varias series de pacientes en las que las manifestaciones clínicas predominantes varían considerablemente. Objetivo. Conocer la variabilidad fenotípica de la polimicrogiria basándose en la serie de pacientes atendidos en nuestro servicio y la revisión de la bibliografía. Pacientes y métodos. Estudio retrospectivo de los pacientes diagnosticados de polimicrogiria mediante resonancia magnética y seguidos en consultas durante los años 1989-2011.Resultados. De un total de 44 pacientes, nueve fueron excluidos por no cumplir los criterios diagnósticos radiológicospropuestos por Barkovich. La polimicrogiria fue bilateral en 22/35 pacientes (una frontal, 21 perisilvianas) y unilateral en13/35 (dos frontales, el resto perisilvianas). Todos los pacientes con polimicrogiria bilateral tenían algún tipo de discapacidadintelectual, un 71% tenía retraso global del desarrollo, un 75% tenía trastorno oromotor y un 40% tenía epilepsia. Los pacientes con polimicrogiria unilateral presentaron discapacidad intelectual (65%), retraso global del desarrollo (55%), trastorno oromotor (55%) y epilepsia (55%), estando asintomáticos dos pacientes (2 años de edad). La presentación clínica de los pacientes dependía de la edad: en el período neonatal, el síntoma guía fue el trastorno oromotor; antes de los 2 años, el retraso global del desarrollo; y partir de los 2 años, la epilepsia. Conclusión. En este estudio, a diferencia de otras series, el síntoma más prevalente fue la discapacidad intelectual (independientemente del tipo de polimicrogiria), seguido del trastorno oromotor y, en menor medida, la epilepsia (AU)

Introduction. The study of polymicrogyria with magnetic resonance imaging (MRI) has made possible the report of severalseries of patients in which the main clinical manifestations differ considerably. The aims of the study were to review the literature and to know the clinical variability of the patients attended in a neuropediatric service. Patients and methods. A retrospective study was conducted between 1989-2011 for the patients attended in our neuropediatric service and diagnosed of polymicrogyria by MRI.Results. On the totality of 44 patients having polymicrogyria, 9 did not satisfy de inclusion criteria (Barkovich’s radiological criteria). The polymicrogyria was bilateral in 22/35 patients (1 frontal, 22 perisylvian) and unilateral in 13/35 (2 frontal, the rest perisylvian). All patients with bilateral polymicrogyria had intellectual disability, 71% had global development delay, 75% had oromotor disorder and 40% had epilepsy. Patients with unilateral polymicrogyria had the following symptoms: 65% intellectual disability, 55% global development delay, 55% oromotor disorder, 55% epilepsy and 2 patients wherefree of symptoms (the oldest 2 year old). The initial symptoms were depending upon the age: the oromotor disorder was the most common in the newborn period, global development delay if the symptoms started before 2 years old and after 2 years epilepsy was the initial most common symptom.Conclusion. In our study the most common symptom was intellectual disability (independently of the type of polymicrogyria), followed by oromotor disorder and, with fewer proportion, epilepsy (in contrast with other series) (AU)