Antiepileptic Effects of a Novel Non-invasive Neuromodulation Treatment in a Subject With Early-Onset Epileptic Encephalopathy: Case Report With 20 Sessions of HD-tDCS Intervention.

The current clinical investigation examined high-definition transcranial direct current stimulation (HD-tDCS) as a focal, non-invasive, anti-epileptic treatment in a child with early-onset epileptic encephalopathy. We investigated the clinical impact of repetitive (20 daily sessions) cathode-centered 4 × 1 HD-tDCS (1 mA, 20 min, 4 mm ring radius) over the dominant seizure-generating cortical zone in a 40-month-old child suffering from a severe neonatal epileptic syndrome known as Ohtahara syndrome (OS). Seizures and epileptiform activity were monitored and quantified using video-EEG over multiple days of baseline, intervention, and post-intervention periods. Primary outcome measures were changes in seizure frequency and duration on the last day of intervention versus the last baseline day, preceding the intervention. In particular, we examined changes in tonic spasms, tonic-myoclonic seizures (TM-S), and myoclonic seizures from baseline to post-intervention. A trend in TM-S frequency was observed indicating a reduction of 73% in TM-S frequency, which was non-significant [t(4) = 2.05, p = 0.1], and denoted a clinically significant change. Myoclonic seizure (M-S) frequency was significantly reduced [t(4) = 3.83, p = 0.019] by 68.42%, compared to baseline, and indicated a significant clinical change as well. A 73% decrease in interictal epileptic discharges (IEDs) frequency was also observed immediately after the intervention period, compared to IED frequency at 3 days prior to intervention. Post-intervention seizure-related peak delta desynchronization was reduced by 57%. Our findings represent a case-specific significant clinical response, reduction in IED, and change in seizure-related delta activity following the application of HD-tDCS. The clinical outcomes, as noted in the current study, encourage the further investigation of this focal, non-invasive neuromodulation procedure in other severe electroclinical syndromes (e.g., West syndrome) and in larger pediatric populations diagnosed with early-onset epileptic encephalopathy. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02960347, protocol ID: Meiron 2013-4.

High-Definition transcranial direct current stimulation in early onset epileptic encephalopathy: a case study.

PRIMARY OBJECTIVE: Early onset epileptic encephalopathy is characterized by high daily seizure-frequency, multifocal epileptic discharges, severe psychomotor retardation, and death at infancy. Currently, there are no effective treatments to alleviate seizure frequency and high-voltage epileptic discharges in these catastrophic epilepsy cases. The current study examined the safety and feasibility of High-Definition transcranial direct current stimulation (HD-tDCS) in reducing epileptiform activity in a 30-month-old child suffering from early onset epileptic encephalopathy. DESIGN AND METHODS: HD-tDCS was administered over 10 intervention days spanning two weeks including pre- and post-intervention video-EEG monitoring. RESULTS: There were no serious adverse events or side effects related to the HD-tDCS intervention. Frequency of clinical seizures was not significantly reduced. However, interictal sharp wave amplitudes were significantly lower during the post-intervention period versus baseline. Vital signs and blood biochemistry remained stable throughout the entire study. CONCLUSIONS: These exploratory findings support the safety and feasibility of 4 × 1 HD-tDCS in early onset epileptic encephalopathy and provide the first evidence of HD-tDCS effects on paroxysmal EEG features in electroclinical cases under the age of 36 months. Extending HD-tDCS treatment may enhance electrographic findings and clinical effects.

Caloric Requirements of Patients With Brain Impairment and Cerebral Palsy Who Are Dependent on Chronic Ventilation.

BACKGROUND AND OBJECTIVE: Israeli law mandates chronic ventilator support for children and adolescents who are severely brain impaired and show minimal responses. Feeding protocols in these cases have been based on the caloric requirements of healthy children, deducting calories for lack of activity as well as an individual adjustment according to the cerebral palsy growth curves. However, patients are still inclined to gain excessive weight. Our objective was to determine the caloric requirements of these patients. DESIGN AND METHOD: Sixteen patients hospitalized in a dedicated unit who were ventilated through tracheostomies and fed via gastrostomies were included. Patients were aged 3-24 years; duration of ventilation was 1-7.5 years; and diagnoses included congenital genetic or brain malformations (n = 9), hypoxic accidents (n = 4), and postbacterial or postviral encephalitis (n = 3). Resting energy expenditure (REE) was determined by indirect calorimetry. REE values were compared with the caloric requirements of age-comparable healthy children and the calories actually delivered. Data were analyzed with paired t tests, Pearson correlations, and linear regression. RESULTS: The REE of our patients was 46% lower than the estimated caloric requirements of healthy children. In practice, patients received 32% more calories than that measured by REE. These findings were not affected by age, weight, diagnosis, or length of hospitalization. CONCLUSIONS: The caloric expenditure of these patients is very low. A diet guided by indirect calorimetry is proposed to aid in providing optimal nutrition support for this unique population to avoid overfeeding and obesity.

Life expectancy of brain impaired, chronically ventilated children.

We present a 5-year survival profile of 42 children and adolescents between 1 to 21 years of age in an immobile minimally conscious state, chronically dependent on supportive ventilation. Data were collected from a 22-bed pediatric unit dedicated to this unique population, within a 350-bed geriatric hospital, between May 2006 and May 2011. The practice of ventilating children even in minimally conscious state stems from the unique cultural, religious, and ethnic background of the population in Israel. The 5-year survival probability was 48% (52% probability of death within 5 years, 26.5% within 2 years). No significant difference was found in the survival profile of patients admitted following hypoxic accidents (20 children) and those admitted with other problems such as genetic/metabolic diseases or brain anomalies (22). The mortality rate of male patients was higher than that of female patients, but the difference was not statistically significant. No difference in 5-year mortality rates was found between children of different ethnic backgrounds.

A prospective randomized controlled study of phototherapy using blue and blue-green light-emitting devices, and conventional halogen-quartz phototherapy.

OBJECTIVE: To determine the efficacy of blue versus blue-green phototherapy using new light sources with narrow luminous spectra. The devices made of high-intensity gallium nitride light-emitting diodes (LEDs) were also compared to conventional halogen-quartz bulbs phototherapy. DESIGN: Prospective open randomized study. PARTICIPANTS: A total of 114 jaundiced, but otherwise healthy term infants who met the entry criteria for phototherapy set by the American Academy of Pediatrics' Practice Parameter. MAIN OUTCOME MEASURES: The duration of phototherapy and the rate of decrease in total serum bilirubin (TSB). RESULTS: The mean TSB concentrations at initiation and termination of treatment, as well as the duration of phototherapy and the rate of decrease in TSB, were not statistically different in newborns receiving blue LED, blue-green LED or conventional phototherapy. The average rate of decrease in TSB (slope), after adjustment by a linear regression analysis for confounding factors, was -3.61 micromol/hour (95% confidence limits -5.47, -1.75) in the 25 newborns receiving blue LED phototherapy compared with -2.57 micromol/hour (-4.32, -0.82) in the 22 newborns treated with blue-green LED phototherapy and -3.42 micromol/hour (-5.02, -1.81) in the 57 newborns who received conventional phototherapy. CONCLUSIONS: When using low light irradiance, there was no statistically significant difference in the effectiveness of phototherapy using blue-green LEDs, blue LEDs or conventional halogen-quartz bulbs.