Rocío Sánchez-Carpintero

Transient Posterior Encephalopathy Induced by Chemotherapy in Children

The cases of three children, 16, 12, and 12 years of age, who suffered sudden confusional state and cortical blindness lasting 12 to 30 minutes while under treatment with high-dose methotrexate, cyclophosphamide, and dactinomycin for a lower limb osteosarcoma are reported. Transient neuropsychologic deficits arose after the acute phase of treatment: left hemispatial neglect and constructive apraxia (Patient 1); constructive apraxia (Patient 2); and constructive apraxia and alexia without aphasia (Patient 3). The three patients recovered completely from all their deficits within the time frame of 3 hours to 2 weeks. Arterial hypertension and hypomagnesemia were found during the acute phase in all patients. In Patients 2 and 3, magnetic resonance imaging revealed increased parieto-occipital T(2) signal involving gray and white matter. In Patients 1 and 2, HmPAO-SPECT revealed parieto-occipital hypoperfusion that resolved a few days later. The alterations detected by neuroimaging were concurrent with the appearance and disappearance of the clinical symptoms. Such transient acute episodes have been named occipital-parietal encephalopathy. On the basis of our clinical, laboratory, and neuroimaging findings, an explanation for the origin of this syndrome, a migrainelike mechanism, triggered by chemotherapy-induced hypomagnesemia, is proposed.

AULA virtual reality test as an attention measure: Convergent validity with Conners’ Continuous Performance Test

The majority of neuropsychological tests used to evaluate attention processes in children lack ecological validity. The AULA Nesplora (AULA) is a continuous performance test, developed in a virtual setting, very similar to a school classroom. The aim of the present study is to analyze the convergent validity between the AULA and the Continuous Performance Test (CPT) of Conners. The AULA and CPT were administered correlatively to 57 children, aged 6–16 years (26.3% female) with average cognitive ability (IQ mean = 100.56, SD = 10.38) who had a diagnosis of attention deficit/hyperactivity disorder (ADHD) according to DSM-IV-TR criteria. Spearman correlations analyses were conducted among the different variables. Significant correlations were observed between both tests in all the analyzed variables (omissions, commissions, reaction time, and variability of reaction time), including for those measures of the AULA based on different sensorial modalities, presentation of distractors, and task paradigms. Hence, convergent validity between both tests was confirmed. Moreover, the AULA showed differences by gender and correlation to Perceptual Reasoning and Working Memory indexes of the WISC-IV, supporting the relevance of IQ measures in the understanding of cognitive performance in ADHD. In addition, the AULA (but not Conners’ CPT) was able to differentiate between ADHD children with and without pharmacological treatment for a wide range of measures related to inattention, impulsivity, processing speed, motor activity, and quality of attention focus. Additional measures and advantages of the AULA versus Conners’ CPT are discussed.

A Restricted Repertoire of De Novo Mutations in ITPR1 Cause Gillespie Syndrome with Evidence for Dominant-Negative Effect

Gillespie syndrome (GS) is characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, and progressive cerebellar atrophy. Trio-based exome sequencing identified de novo mutations in ITPR1 in three unrelated individuals with GS recruited to the Deciphering Developmental Disorders study. Whole-exome or targeted sequence analysis identified plausible disease-causing ITPR1 mutations in 10/10 additional GS-affected individuals. These ultra-rare protein-altering variants affected only three residues in ITPR1: Glu2094 missense (one de novo, one co-segregating), Gly2539 missense (five de novo, one inheritance uncertain), and Lys2596 in-frame deletion (four de novo). No clinical or radiological differences were evident between individuals with different mutations. ITPR1 encodes an inositol 1,4,5-triphosphate-responsive calcium channel. The homo-tetrameric structure has been solved by cryoelectron microscopy. Using estimations of the degree of structural change induced by known recessive- and dominant-negative mutations in other disease-associated multimeric channels, we developed a generalizable computational approach to indicate the likely mutational mechanism. This analysis supports a dominant-negative mechanism for GS variants in ITPR1. In GS-derived lymphoblastoid cell lines (LCLs), the proportion of ITPR1-positive cells using immunofluorescence was significantly higher in mutant than control LCLs, consistent with an abnormality of nuclear calcium signaling feedback control. Super-resolution imaging supports the existence of an ITPR1-lined nucleoplasmic reticulum. Mice with Itpr1 heterozygous null mutations showed no major iris defects. Purkinje cells of the cerebellum appear to be the most sensitive to impaired ITPR1 function in humans. Iris hypoplasia is likely to result from either complete loss of ITPR1 activity or structure-specific disruption of multimeric interactions.

Spinal extradural arachnoid cysts in lymphedema-distichiasis syndrome

Purpose: Lymphedema-distichiasis syndrome is characterized by the presence of lower limb lymphedema and supernumerary eyelashes arising from the Meibomian glands. Spinal extradural arachnoid cysts have been observed in some families but their true frequency is unknown. The aim of this study is to determine the frequency of spinal extradural arachnoid cysts in lymphedema distichiasis syndrome.Methods: We collected clinical information from all 45 living members of a complete family of 48 members and performed molecular analysis of the FOXC2 gene in 30 individuals. We obtained spinal magnetic resonance imaging from all family members with a FOXC2 gene mutation.Results: Twelve family members carried a mutation in the FOXC2 gene and had clinical features of lymphedema-distichiasis syndrome. Of these, 58% (seven individuals) had extradural arachnoid cysts.Discussion: We suggest that a follow-up protocol for lymphedema-distichiasis syndrome families should include spinal magnetic resonance imaging for all affected members so that the timing of surgery for removal of these cysts can be optimized.

Temporal lobectomy in acute complicated herpes simplex encephalitis: technical case report.

OBJECTIVE Herpes virus encephalitis is a rare, life-threatening complication of therapy in patients with brain tumors. A surgical therapeutic approach may be needed because the infection can be resistant to acyclovir in immunocompromised patients, and complications and long-term sequelae are frequent. CLINICAL PRESENTATION We present the case of a right-handed, 6-year-old girl with a brainstem tumor who had herpes virus encephalitis with refractory seizures while on immunosuppressive treatment. The virus was resistant to acyclovir but responded to gancyclovir. The patient developed local refractory brain edema with right uncal herniation. INTERVENTION To reduce the intracranial pressure, internal decompressive craniotomy was performed, which consisted of a right temporal lobectomy that allowed us to remove the focal necrotic-hemorrhagic tissue, decrease inflammation, and avoid subsequent chronic gliotic scarring. Clinical improvement was clear with prompt recovery and acute control of seizures. The only remaining deficits were mild memory and attention impairments. Seizures did not recur in the next 6 months. CONCLUSION Antiviral resistance should be suspected in immunocompromised patients with herpes virus encephalitis if there is no early response to acyclovir. If uncal herniation of the nondominant temporal lobe develops, temporal lobectomy, as an internal decompressive procedure, can be lifesaving. Lobectomy stopped the acute refractory seizures and can be considered a good approach to prevent later epilepsy, with only mild residual cognitive deficits.

Prevalence of sleep disorders and their relationship with core symptoms of inattention and hyperactivity in children with attention-deficit/hyperactivity disorder

OBJECTIVES To determine the prevalence of sleep disorders in children with attention-deficit/hyperactivity disorder (ADHD) and in a control population. To examine the relationship between sleep disorders and symptoms of inattention, hyperactivity/impulsiveness and executive dysfunction. MATERIALS AND METHODS We studied 126 children with ADHD and 1036 control children aged between 5 and 18 years old. Caregivers completed the Pediatric Sleep Questionnaire and the ADHD Rating Scale (ADHD-RS). Children with ADHD were subsequently assessed for executive function with the Conners Continuous Performance Test (CPT) or with AULA Nesplora. RESULTS Children with ADHD slept less at night and were more likely to display sleep-related rhythmic movements. Children in the ADHD group who were under 12 years old and who had total ADHD-RS scores over the 90th percentile had more difficulty falling asleep than other children; there was also a relationship between total ADHD-RS scores over the 90th percentile and certain parasomnias in the control population. There was a correlation between shorter duration of night-time sleep and omission errors in children who were 12 or older and who were under pharmacological treatment for ADHD. Bedtime resistance and difficulty falling sleep were more frequent in children with ADHD whose symptoms were not treated pharmacologically, than in children receiving treatment. INTERPRETATION Symptoms of inattention and hyperactivity are correlated with impaired sleep duration and quality; specifically, there is an association between ADHD symptoms and problems falling asleep and parasomnias, however, the current study does not address the nature and direction of causality. Children with ADHD and receiving methylphenidate had fewer sleep disorders, suggesting that, at least in some children, stimulant treatment is associated with improvement of some aspects of sleep. Shorter sleep duration in adolescents under pharmacological treatment for ADHD tended to result in more errors of omission, suggesting that it is important to promote good sleep habits in this population.

Musicogenic seizures in Dravet syndrome.

Dravet syndrome is an epileptic encephalopathy characterized by multiple types of seizures. We report the first case of musicogenic reflex seizures in a 7‐year‐old male with a mutation in the SCN1A gene causing Dravet syndrome. Reflex seizures have been reported in patients with Dravet syndrome provoked by body temperature elevation, looking at visual patterns, or under intermittent photic stimulation. The case we report widens the spectrum of reflex seizures recorded in patients with Dravet syndrome. Cortical hyperexcitability of genetic origin could explain the tendency of these patients to experience reflex seizures.

Gait Epilepsy. A Case Report of Gait-Induced Seizures

Summary: Reflex epilepsy includes a group of epileptic syndromes in which seizures are induced by a stimulus, either simple (visual, somatosensory, olfactory, auditory) or more complex (e.g., eating, thinking, reading). We document a case of reflex epilepsy in which focal seizures are triggered exclusively by gait. The patient is a young boy whose walking was impaired by abnormal motor phenomena on the left side. These phenomena were elicited by gait and were accompanied by a distinctive ictal pattern with centro‐temporal discharges. After comparing this patient with others reported in the literature, we determined that he has an unusual type of reflex epilepsy for which we coined the term “gait epilepsy.” This disorder must be considered when physicians are making a differential diagnosis in patients who have symptoms that suggest paroxysmal kinesigenic dystonia (PKD) or selective epileptic gait disorder.

Manejo de la crisis convulsiva prolongada en la comunidad: resultados del estudio PERFECT en España

INTRODUCTION The Practices in Emergency and Rescue medication For Epilepsy managed with Community administered Therapy (PERFECT™) Initiative was set up in 2011 to gain a better understanding of how prolonged convulsive seizures are managed, and rescue medication is administered, in out-of-hospital settings across Europe. This paper explores the initial research findings for Spain. MATERIAL AND METHODS A review was made of existing clinical guidelines, guidance to schools, and relevant policy and legal frameworks, as well as a survey of 20 healthcare professionals who treat children with prolonged convulsive seizures in Spain. RESULTS Existing clinical guidelines pertain mainly to the hospital setting, and contain very little information on how prolonged seizures should be managed outside of the hospital. Guidance for schools is unclear as to whether teachers are allowed to administer rescue medication to children, and there is no legal obligation for school staff to administer medication to children under their care. As a result of such uncertainty, whether or not children who experience prolonged seizures receive their rescue medication during school hours depends mostly on the resources and training available in each school. CONCLUSIONS There is a need for more explicit guidance covering educational and healthcare settings, clearer information to parents and schools, and more systematic training to be made available to caregivers. This is to ensure that all children at risk of a prolonged convulsive seizure receive rescue medication in a timely manner, regardless of where their seizure occurs.

Anti-Basal Ganglia Antibodies and Streptococcal Infection in ADHD:

Objective: Group A Streptococcus has been associated with ADHD, tic disorders (TD), and obsessive–compulsive disorder (OCD) through anti-basal ganglia antibodies (ABGA). Method: We investigated the association between ABGA and streptococcal exposure with behavioral, motor, and cognitive measures in 38 children with ADHD not comorbid to OCD or TD (nc-ADHD) and in 38 healthy children. An additional group of 15 children with TD and/or OCD was examined. Results: ABGA titers were present in 3% of nc-ADHD patients and controls but in 27% of TD and/or OCD patients. Evidence of streptococcal exposure was similar between ADHD patients and controls living in the same urban area. Behavioral, motor, and cognitive measures were not associated with anti-streptococcal antibodies. Conclusion: ABGA do not distinguish nc-ADHD from controls. The differences in the frequency of streptococcal exposure in previous studies are determined by the dynamic nature of the infection rather than the behavioral phenotype of ADHD.