Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(06)68175-0.pdf

Guillain-Barré syndrome

Celiac disease is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. It occurs in children and adolescents with gastrointestinal symptoms, dermatitis herpetiformis, dental enamel defects, osteoporosis, short stature, delayed puberty and persistent iron deficiency anemia and in asymptomatic individuals with type 1 diabetes, Down syndrome, Turner syndrome, Williams syndrome, selective immunoglobulin (Ig)A deficiency and first degree relatives of individuals with celiac disease. The Celiac Disease Guideline Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has formulated a clinical practice guideline for the diagnosis and treatment of pediatric celiac disease based on an integration of a systematic review of the medical literature combined with expert opinion. The Committee examined the indications for testing, the value of serological tests, human leukocyte antigen (HLA) typing and histopathology and the treatment and monitoring of children with celiac disease. It is recommended that children and adolescents with symptoms of celiac disease or an increased risk for celiac disease have a blood test for antibody to tissue transglutaminase (TTG), that those with an elevated TTG be referred to a pediatric gastroenterologist for an intestinal biopsy and that those with the characteristics of celiac disease on intestinal histopathology be treated with a strict gluten-free diet. This document represents the official recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition on the diagnosis and treatment of celiac disease in children and adolescents.

Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Summary Background The ketogenic diet has been widely and successfully used to treat children with drug-resistant epilepsy since the 1920s. The aim of this study was to test the efficacy of the ketogenic diet in a randomised controlled trial. Methods 145 children aged between 2 and 16 years who had at least daily seizures (or more than seven seizures per week), had failed to respond to at least two antiepileptic drugs, and had not been treated previously with the ketogenic diet participated in a randomised controlled trial of its efficacy to control seizures. Enrolment for the trial ran between December, 2001, and July, 2006. Children were seen at one of two hospital centres or a residential centre for young people with epilepsy. Children were randomly assigned to receive a ketogenic diet, either immediately or after a 3-month delay, with no other changes to treatment (control group). Neither the family nor investigators were blinded to the group assignment. Early withdrawals were recorded, and seizure frequency on the diet was assessed after 3 months and compared with that of the controls. The primary endpoint was a reduction in seizures; analysis was intention to treat. Tolerability of the diet was assessed by questionnaire at 3 months. The trial is registered with ClinicalTrials.gov, number NCT00564915. Findings 73 children were assigned to the ketogenic diet and 72 children to the control group. Data from 103 children were available for analysis: 54 on the ketogenic diet and 49 controls. Of those who did not complete the trial, 16 children did not receive their intervention, 16 did not provide adequate data, and ten withdrew from the treatment before the 3-month review, six because of intolerance. After 3 months, the mean percentage of baseline seizures was significantly lower in the diet group than in the controls (62·0% vs 136·9%, 75% decrease, 95% CI 42.4–107.4%; p Interpretation The results from this trial of the ketogenic diet support its use in children with treatment-intractable epilepsy. Funding HSA Charitable Trust; Smiths Charity; Scientific Hospital Supplies; Milk Development Council.

https://www.gutbrainaxis.org/pdf/cross%20paper%20KD%20vs%20AEDs.pdf

The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial

Inflammatory reactions occur in the brain in various CNS diseases, including autoimmune, neurodegenerative, and epileptic disorders. Proinflammatory and antiinflammatory cytokines and related molecules have been described in CNS and plasma, in experimental models of seizures and in clinical cases of epilepsy. Inflammation involves both the innate and the adaptive immune systems and shares molecules and pathways also activated by systemic infection. Experimental studies in rodents show that inflammatory reactions in the brain can enhance neuronal excitability, impair cell survival, and increase the permeability of the blood-brain barrier to blood-borne molecules and cells. Moreover, some antiinflammatory treatments reduce seizures in experimental models and, in some instances, in clinical cases of epilepsy. However, inflammatory reactions in brain also can be beneficial, depending on the tissue microenvironment, the inflammatory mediators produced in injured tissue, the functional status of the target cells, and the length of time the tissue is exposed to inflammation. We provide an overview of the current knowledge in this field and attempt to bridge experimental and clinical evidence to discuss critically the possibility that inflammation may be a common factor contributing, or predisposing, to the occurrence of seizures and cell death, in various forms of epilepsy of different etiologies. The elucidation of this aspect may open new perspectives for the pharmacologic treatment of seizures.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1167.2005.00298.x

Brain inflammation in epilepsy: experimental and clinical evidence.

The work and proposals regarding classification and terminology of epilepsy syndromes published by the last two committees nominated by the International League Against Epilepsy (ILAE) are considered in this article

Epileptic Syndromes and Diseases

Clinical and electroencephalographic (EEG) features of the three well-defined idiopathic focal epilepsies in childhood (IFEC)—benign childhood epilepsy with centrotemporal spikes (BCECTS), Panayiotopoulos syndrome, and the Gastaut type of idiopathic occipital epilepsy of childhood (IOEC-G)—have been clearly described and reported. It is also known that a significant percentage of children with IFEC present what were named atypical features in seizures and EEG abnormalities. We are studying here the small number of patients with IFEC who not only present atypical features, but also evolve into the spectrum of epileptic encephalopathies related with continuous spike-and-wave during sleep (CSWSS) or electrical status epilepticus during sleep (ESES), which includes atypical benign focal epilepsy of childhood, status of BCECTS, Landau-Kleffner syndrome, and CSWSS or ESES syndrome. We also emphasize that some patients with these encephalopathic course of IFEC present a mix or a sequence in time of the four mentioned subsyndromes.

Atypical Evolutions of Idiopathic Focal Epilepsies in Childhood

Introduccion. Analizamos las caracteristicas clinicas, neurologicas, electroencefalograficas y evolutivas en dos pacientes con encefalopatia sarampionosa subaguda retardada. Casos clinicos. Ambos pacientes, uno a los cinco anos y el otro a los 11 meses, presentaron un deterioro agudo neurologico y de conciencia, epilepsia parcial continua y lesiones progresivas en los estudios de imagenes, con antecedentes de haber padecido sarampion en el primer caso y contacto con el virus en el segundo. El primer paciente tenia linfoma de Hodgkin y el segundo presentaba un deficit familiar de C4. El fondo de ojo evidencio lesiones retinianas, el EEG mostro ondas lentas unilaterales con ondas agudas o espigas intercaladas. La TAC y la RM de cerebro mostraron atrofia cerebral progresiva con lesiones extensas corticosubcorticales unilaterales. El analisis del LCR en el primer caso evidencio anticuerpos contra sarampion elevados, y en el segundo, bandas oligoclonales. El primer paciente fallecio a los tres meses de haber iniciado el cuadro neurologico y el segundo paciente presenta un grave deterioro neurologico. Conclusion. En pacientes inmunosuprimidos con antecedentes de exposicion al virus del sarampion, deterioro agudo neurologico y de conciencia, epilepsia parcial continua y lesiones progresivas en los estudios neurorradiologicos, debemos considerar el diagnostico de encefalopatia sarampionosa subaguda retardada.

Encefalopatía sarampionosa subaguda retardada

INTRODUCTION Mirror movements (MM) are involuntary shudders which occur at the same time as voluntary movements of the homologous contralateral muscles. They may occur alone or associated with other pathology. CLINICAL CASES We present three new cases of congenital MM (CMM) and discuss their clinical, physiopathological and genetic aspects. Case 1. A four year old boy was brought to the clinic because he dropped things held in one hand when he tried to take things with the other. On examination it was seen that when he made a voluntary movement with one hand, the other hand made a similar movement simultaneously and involuntarily. This phenomenon had been observed since he was a few months old. Apart from this, the rest of the neurological examination was normal. Cerebral MR was also normal. Neuropsychological assessment showed borderline intellectual function. Case 2. The first patient's father, who was 26 years old, knew no details of his own family history. Since childhood he had noticed that he himself had made similar movements to those of his son. However, with time, he had managed to partially control and even inhibit these movements. His cerebral MR scan was normal. Case 3. An 11 year old boy consulted for MM, non-fluctuating congenital palpebral ptosis and nocturnal enuresis. The neurological examination and his intelligence were found to be normal. One of his sisters had palpebral ptosis and nocturnal enuresis without MM. His cerebral MR, X-ray of his spine, EMG, electroretinogram, CPK, blood lactate, glucemia, urine and urological examination were normal. CONCLUSIONS MM may be another manifestation within the clinical spectrum of diverse encephalopathies; may be associated with different syndromes (Kallman, Klippel-Feil and Usher amongst others) or may present alone. Both familial and sporadic cases have been described. We consider our cases 1 and 2 to be of the familial CMM condition, with autosomal dominant inheritance, in which MM was the only finding. The association observed in case 3 has not previously been described. It may possibly be a condition transmitted by autosomal recessive inheritance.

Natalio Fejerman

Papers

Epileptic Syndromes and Diseases

Atypical Evolutions of Idiopathic Focal Epilepsies in Childhood

Encefalopatía sarampionosa subaguda retardada

Congenital mirror movements. Three new cases of a rare condition

Parálisis facial periférica aguda