Impoverished Conceptions of Gene Causation and Therapy in Developmental Neurology.

We offer a primer to the modifiability of genetic neurological disease, particularly during development. One goal is to harness several unexpected observations made in the course of experimental gene modification or therapy into an explanatory conceptual context based on biological first principles. To this end, we anchor growing, disparate reports of unusual or untoward effects to a plausible framework wherein genes exhibit different degrees of modifiability and may result, when mutated or therapeutically modified, in unsuspected consequences.

A concise study of acetazolamide in glucose transporter type 1 deficiency (G1D) epilepsy.

Epilepsy constitutes the most common paroxysmal manifestation of glucose transporter type 1 deficiency (G1D) and is generally considered medication-refractory. It can also prove therapeutic diet-resistant. We examined acetazolamide effects in G1D motivated by several longstanding and recent observations: First, the electrographic spike-waves characteristic of absence seizures often resemble those of G1D and, since the 1950s, they have occasionally been treated successfully with acetazolamide, well before G1D was segregated from absence epilepsy as a distinct syndrome.

Combination of triheptanoin with the ketogenic diet in Glucose transporter type 1 deficiency (G1D).

Fuel influx and metabolism replenish carbon lost during normal neural activity. Ketogenic diets studied in epilepsy, dementia and other disorders do not sustain such replenishment because their ketone body derivatives contain four carbon atoms and are thus devoid of this anaplerotic or net carbon donor capacity. Yet, in these diseases carbon depletion is often inferred from cerebral fluorodeoxyglucose-positron emission tomography.

Maximum dose, safety, tolerability and ketonemia after triheptanoin in glucose transporter type 1 deficiency (G1D).

Augmentation of anaplerosis, or replenishment of carbon lost during intermediary metabolic transitions, is desirable in energy metabolism defects. Triheptanoin, the triglyceride of 7-carbon heptanoic acid, is anaplerotic via direct oxidation or 5-carbon ketone body generation. In this context, triheptanoin can be used to treat Glucose transporter type 1 deficiency encephalopathy (G1D).

Clinical description, molecular delineation and genotype-phenotype correlation in 340 patients with KBG syndrome: addition of 67 new patients.

Background: KBG syndrome is a highly variable neurodevelopmental disorder and clinical diagnostic criteria have changed as new patients have been reported. Both loss-of-function sequence variants and large deletions (copy number variations, CNVs) involving cause KBG syndrome, but no genotype-phenotype correlation has been reported.

Methods: 67 patients with KBG syndrome were assessed using a custom phenotypical questionnaire.

Therapeutic Decision-Making Under Uncertainty in the Management of Spinal Muscular Atrophy: Results From DECISIONS-SMA Study.

Introduction: There are many uncertainties about treatment selection and expectations regarding therapeutic goals and benefits in the new landscape of spinal muscular atrophy (SMA). Our aim was to assess treatment preferences and expectations of pediatric neurologists caring for patients with SMA.

Methods: DECISIONS-SMA is a non-interventional, cross-sectional pilot study that assessed pediatric neurologists with expertise in SMA from across Spain.

Therapeutic decisions under uncertainty for spinal muscular atrophy: The DECISIONS-SMA study protocol.

Background: The therapeutic landscape for spinal muscular atrophy has changed in the last few years, encompassing respiratory/motor function and life expectancy benefits. However, physicians still have the challenge of tailoring individuals' treatment to therapeutic goals, disease progression, patient/caregiver's preferences, and personal experience to achieve an optimal risk/benefit balance. This study aims to provide insight into the preferred treatment choices of pediatric neurologists managing spinal muscular atrophy in their daily practice and to recognize behavioral factors that may influence decision-making.

Paradigmatic De Novo Variants Recapitulate Pathophysiological Mechanisms Underlying GRIN1-Related Disorder Clinical Spectrum.

Background: GRIN-related disorders (GRD), the so-called grinpathies, is a group of rare encephalopathies caused by mutations affecting genes (mostly , and genes), which encode for the GluN subunit of the -methyl D-aspartate (NMDA) type ionotropic glutamate receptors. A growing number of functional studies indicate that GRIN-encoded GluN1 subunit disturbances can be dichotomically classified into gain- and loss-of-function, although intermediate complex scenarios are often present.

Methods: In this study, we aimed to delineate the structural and functional alterations of disease-associated variants, and their correlations with clinical symptoms in a Spanish cohort of 15 paediatric encephalopathy patients harbouring these variants.

Outbreak of Enterovirus Infection with Neurological Presentations in a Pediatric Population in Northern Spain: A Clinical Observational Study.

Objective: The study aimed to describe the cases of neurological disease related to the outbreak of enterovirus (EV) in three regions in Northern Spain during 2016.

Materials And Methods: Multicenter retrospective observational study. Clinical, radiological, and microbiological data were analyzed from patients younger than 15 years with confirmed EV-associated neurological disease admitted to 10 hospitals of Asturias, Cantabria, and Castile and Leon between January 1 and December 31, 2016.

Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study.

Background: Investigations of myelin oligodendrocyte glycoprotein (MOG) antibodies are usually focused on demyelinating syndromes, but the entire spectrum of MOG antibody-associated syndromes in children is unknown. In this study, we aimed to determine the frequency and distribution of paediatric demyelinating and encephalitic syndromes with MOG antibodies, their response to treatment, and the phenotypes associated with poor prognosis.

Methods: In this prospective observational study, children with demyelinating syndromes and with encephalitis other than acute disseminated encephalomyelitis (ADEM) recruited from 40 secondary and tertiary centres in Spain were investigated for MOG antibodies.

International meeting on Wolf-Hirschhorn syndrome: Update on the nosology and new insights on the pathogenic mechanisms for seizures and growth delay.

"An International Meeting on Wolf-Hirschhorn Syndrome (WHS)" was held at The University Hospital La Paz in Madrid, Spain (October 13-14, 2017). One hundred and twenty-five people, including physicians, scientists and affected families, attended the meeting. Parent and patient advocates from the Spanish Association of WHS opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances.

[New anti-epileptic drugs in Paediatrics].

It is estimated that about 70 million people all over the world suffer from epilepsy, half of which are children, in whom the prevalence is around 0.5 to 0.8%.

[Prevalence of autism spectrum disorders in USA, Europe and Spain: coincidences and discrepancies].

Autism spectrum disorders are a heterogeneous group of disorders that share the presence of two core symptoms: problems in social interaction / communication and the tendency to present restricted interests and repetitive behavior. Over the last years, several epidemiologic studies have been published by different authors in diverse countries, having all of them shown two common characteristics: a global increase in the prevalence rates of autism spectrum disorders, and the existence of a great geographical variability no only between geographical areas, but also within the same geographical areas. At the present manuscript, we analyze some of the most recent prevalence data published in USA and some European countries (including Spain).

Identifying the educational needs of physicians in pediatric epilepsy in order to improve care: results from a needs assessment in Germany, Spain, and the United States.

The objective of this study was to gather evidence-based data on the educational needs of neuropediatricians. A needs assessment was conducted to identify the clinical challenges of physicians when diagnosing, medically treating, and managing pediatric patients with epilepsy; which could be addressed through educational interventions. A two-phase mixed-methods approach was used to conduct the needs assessment in Germany, Spain, and the US.

Insertion of fully covered self-expanding metal stents in benign biliary diseases.

Introduction: Benign biliary diseases are traditionally treated using plastic stents. However, fully covered self-expanding metal stents are currently gaining acceptance for the treatment of these pathologies.

Objective: To assess the effectiveness and complications associated with the placement of temporary endoscopic fully covered self-expanding metal stents for the treatment of benign biliary diseases.

Autoimmune post-herpes simplex encephalitis of adults and teenagers.

Objective: To report 14 patients with immune-mediated relapsing symptoms post-herpes simplex encephalitis (HSE) and to compare the clinical and immunologic features of the teenage and adult group with those of young children.

Methods: Prospective observational study of patients diagnosed between June 2013 and February 2015. Immunologic techniques have been reported previously.

Follow-up of folinic acid supplementation for patients with cerebral folate deficiency and Kearns-Sayre syndrome.

Background: Kearns-Sayre syndrome (KSS) is a mitochondrial DNA deletion syndrome that presents with profound cerebral folate deficiency and other features. Preliminary data support the notion that folinic acid therapy might be useful in the treatment of KSS patients. Our aim was to assess the clinical and neuroimaging outcomes of KSS patients receiving folinic acid therapy.

Recommendations for the radiological diagnosis and follow-up of neuropathological abnormalities associated with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a genetic condition with multisystem involvement, characterized by the development of tumors and other abnormalities in organs such as the brain, retina, skin, heart, kidneys, and lungs. Most patients have neuropathological abnormalities such as cortical tubers, white matter radial migration lines, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs). These lesions are associated with different neurological manifestations that are frequently associated with TSC.

Herpes simplex virus encephalitis is a trigger of brain autoimmunity.

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.

[Wolf-Hirschhorn syndrome. A series of 27 patients: their epidemiological and clinical characteristics. The current situation of the patients and the opinions of their caregivers regarding the diagnostic process].

Introduction: Wolf-Hirschhorn syndrome (WHS) is a chromosome pathology produced by a deletion in the distal region of the short arm of chromosome 4. It is characterised by the presence of a peculiar phenotype, delayed growth, delayed psychomotor development and epilepsy.

Aims: To describe the characteristics of a series of children with WHS, including the mean amount of time spent on reaching the diagnosis, and to evaluate the opinion of the families about the diagnostic process.

Pediatric anti-N-methyl-D-aspartate receptor encephalitis-clinical analysis and novel findings in a series of 20 patients.

Objective: To report the clinical features of 20 pediatric patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.

Study Design: Review of clinical data, long-term follow-up, and immunologic studies performed in a single center in Spain in the last 4 years.

Results: The median age of the patients was 13 years (range, 8 months-18 years), 70% were female.

Natalizumab use in pediatric patients with relapsing-remitting multiple sclerosis.

Background: Not all pediatric patients with relapsing-remitting multiple sclerosis (MS) may respond to traditional disease-modifying therapies. Natalizumab has been shown to be effective but is currently only approved in adults.

Objective: To analyze the safety and efficacy of natalizumab in patients under 18 years of age diagnosed with MS.

Biochemical parameters to assess choroid plexus dysfunction in Kearns-Sayre syndrome patients.

Our aim was to assess biochemical parameters to detect choroid plexus dysfunction in Kearns-Sayre syndrome (KSS) patients. We studied CSF from 7 patients with KSS including total proteins, 5-methyltetrahydrofolate, homovanillic acid (HVA) and Selenium (Se) concentrations. High Se values, increased HVA and total protein concentrations and decreased 5-MTHF values were observed in all cases.

C-reactive protein is elevated in the offspring of parents with essential hypertension.

Background: Hypertension is a risk factor for cardiovascular disease (CVD). Studies in adults have shown that high sensitivity C-reactive protein (CRP) levels are associated with increased risk of CVD and essential hypertension (EHT). Genetic background is widely accepted as a risk factor for CVD.