Family Burden and Epilepsy Surgery in Children with Drug-Resistant Epilepsy.

INTRODUCTION: Family burden (FB) in pediatric patients with drug-resistant epilepsy (DRE) is significantly higher than that in children with non-DRE. Epilepsy surgery is an established approach to treat DRE, and this study examines the impact of pediatric epilepsy surgery on FB. METHODS: We retrospectively analyzed data of families and pediatric patients with focal structural DRE treated with epilepsy surgery at our epilepsy center from April 2018 to November 2021. We examined the relationship between cognitive, behavioral, and epilepsy-specific data and the FB measured with the German version of the Impact on Family Scale before and after epilepsy surgery. RESULTS: The study cohort included 31 children with DRE at a mean age of 9 years at surgery (range = 0-16) and a mean epilepsy duration of 3 years (range = 0-14). Cognitive impairment correlated with FB in children with DRE prior to surgery. At the last assessment, 14.5 months (mean, range = 6-24) after epilepsy surgery, 87.2% of patients were seizure-free, FB values had decreased by 75.0%, and behavioral problems had decreased by 85,7%. Cognitive functions remained stable following epilepsy surgery. CONCLUSION: In children with DRE, epilepsy surgery reduces FB. Given the considerable impact of families on the development and wellbeing of their children, the impact of epilepsy surgery should be communicated to affected families.

Ictal EEG recording is not mandatory in all candidates for paediatric epilepsy surgery with clear MRI lesions and corresponding seizure semiology

OBJECTIVE: Epilepsy surgery can potentially cure drug-resistant epilepsy, but careful presurgical evaluation is vital to select patients who will profit from such an intervention. Many epilepsy surgery programs offer extensive presurgical evaluation including several days of video-EEG monitoring. Non-lesional epilepsy cases are rare among epilepsy surgery patients. We set up a lesion-orientated paediatric epilepsy surgery program for patients with clearly localized lesions with limited presurgical diagnostics, in particular, with a maximum of 48 hours of non-invasive EEG monitoring that did not necessarily include ictal EEGs. METHODS: We retrospectively evaluated the outcome of patients who were operated on within our epilepsy surgery program with respect to seizure freedom. RESULTS: Fifty-two children and adolescents with MRI lesions at a mean age of 8.27 ±4.83 years (range: 0.17-18.87) underwent a resective procedure. The most frequent surgery was a hemispherotomy. Overall seizure freedom was 81.8% after 12 months and 85.6% after a median observation period of 20.45 months. Seizure frequency was reduced >50% in all other patients. Preoperative recording of an ictal EEG on the side of surgery had no effect on postoperative seizure outcome (p= 0.697), nor did recording of epileptiform discharges on the ipsilateral (p= 0.538) and contralateral side (p= 0.147). SIGNIFICANCE: Our findings highlight the high success rate using a lesion-orientated epilepsy surgical approach with reduced presurgical video-EEG monitoring in the paediatric epilepsy population. Our data show that it is possible to reduce the complex pre-surgical work-up for epilepsy in children and adolescents by asking the basic question: "Is there any reason why the lesion should not be resected".

Epilepsy surgery in the first six months of life: A systematic review and meta-analysis.

INTRODUCTION: Nearly one-third of all infants with epilepsy develop drug-resistant epilepsy. Although epilepsy surgery is a well-established therapy across all age groups, there might be a reluctance to operate on infants in the first six months of life due to unique surgical and anesthesiologic difficulties. METHODS: We performed a meta-analysis and systematic review to assess the outcome and complication rate of epilepsy surgery in infants operated on ≤ six months of life. RESULTS: 158 infants underwent epilepsy surgery, most frequently a hemispherotomy rather than focal surgery. Overall seizure freedom after surgery was 65.6% [CI: 0.5785; 0.7261], with higher seizure-free rates following hemispherotomy (71%) than after focal surgery (58%). Complications occurred in 27.7% [0.1794; 0.4004] of patients. Most prevalently, a hydrocephalus developed in 20 out of 136 cases (14.71%). Anti-seizure medication (ASM) was discontinued in 21.5% [0.1431; 0.3100] and reduced in 85.9% [0.515; 0.9721] of 93 patients postoperatively. 84.6% of infants displayed cognitive impairment (development quotient (DQ) <85) preoperatively. After surgery, there was a trend toward a cognitive gain. However, cognitive gain was seen almost exclusively in seizure-free patients. DISCUSSION: Excellent seizure control can be achieved with epilepsy surgery in the first six months of life, a large proportion of patients are able to reduce or discontinue ASM. Data regarding cognitive outcome are promising, but also show that the primary goal should be to achieve seizure freedom. Given the more difficult surgical conditions, epilepsy surgery in the first six months of life should only be performed in specialized epilepsy centers.

Case Report: Behavioral Disorder Following Hemispherotomy: A Valproate Effect?

Background: Hemispherotomy is an epilepsy surgery procedure applied to cure particularly pharmacorefractory lesional epilepsy due to unihemispheric pathologies. Such a disconnection of an entire hemisphere is followed by reorganizational processes. Methods: We describe an acute aggravation of behavioral problems following a hemispherotomy in a patient treated with valproic acid, which subsided once valproate was discontinued. Results: A 9-year-old boy with drug-resistant epilepsy caused by the residua of a perinatal stroke treated for several years with valproic acid and lamotrigine underwent hemispherotomy. Shortly after surgery, minimal preoperative behavioral problems intensified dramatically, and aggression occurred as a new symptom. Assuming a correlation between valproate treatment and the postoperative altered neuronal network, we tapered off valproate. The behavioral problems decreased in intensity with the reduction of valproate dose and disappeared after drug discontinuation. Conclusion: We describe severe behavioral problems after hemispherotomy that subsided when valproate was tapered off. While we cannot rule out a spontaneous correction of a post-hemispherotomy network dysregulation, our report raises awareness to possible altered effects of the anticonvulsant valproic acid parallel to reorganizational processes after hemispherotomy.

Infratentorial MRI Findings in Rasmussen Encephalitis Suggest Primary Cerebellar Involvement.

BACKGROUND AND OBJECTIVE: Rasmussen encephalitis (RE) is characterized by its unilateral cerebral involvement. However, both ipsi- and contralesional cerebellar atrophy have been anecdotally reported raising questions about the nature and extent of infratentorial findings. Using MRI, we morphometrically investigated the cerebellum and hypothesized abnormalities beyond the effects of secondary atrophy, implicating a primary involvement of the cerebellum by RE. METHODS: Voxel-based morphometry of the cerebellum and brainstem was conducted in 57 patients with RE and in 57 matched controls. Furthermore, patient-specific asymmetry indices (AIs) of cerebellar morphometry and fluid-attenuated inversion recovery (FLAIR) intensity were calculated. Using diffusion tensor imaging, the integrity of the cortico-ponto-cerebellar (CPC) tract was assessed. Finally, a spatial independent component analysis (ICA) was used to compare atrophy patterns between groups. RESULTS: Patients with RE showed bilateral cerebellar and predominantly ipsilesional mesencephalic atrophy (p < 0.01). Morphometric AIs revealed ipsilesional < contralesional asymmetry in 27 and ipsilesional > contralesional asymmetry in 30 patients. In patients with predominant ipsilesional atrophy, morphometric AIs strongly correlated with FLAIR intensity AIs (r = 0.86, p < 0.0001). Fractional anisotropy was lower for ipsilesional-to-contralesional CPC tracts than opposite tracts (T = 2.30, p < 0.05). ICA revealed bilateral and strictly ipsi- and contralesional atrophy components in patients with RE (p < 0.05). DISCUSSION: We demonstrated atrophy of the ipsilesional-to-contralesional CPC pathway and, consequently, interpret the loss of contralesional gray matter as secondary crossed cerebellar atrophy. The ipsilesional cerebellar atrophy, however, defies this explanation. Based on FLAIR hyperintensities, we interpret ipsilesional atrophy to be due to inflammation in the scope of a primary involvement of the cerebellum by RE.

Case Report: Hemispherotomy in the First Days of Life to Treat Drug-Resistant Lesional Epilepsy.

Background: Neonatal drug-resistant epilepsy is often caused by perinatal epileptogenic insults such as stroke, ischemia, hemorrhage, and/or genetic defects. Rapid seizure control is particularly important for cognitive development. Since early surgical intervention and thus a short duration of epilepsy should lead to an optimal developmental outcome, we present our experience with hemispherotomy in an infant at the corrected age of 1 week. Methods: We report successful hemispherotomy for drug-resistant epilepsy in an infant with hemimegalencephaly at a corrected age of 1 week. Results: The infant was diagnosed with drug-resistant lesional epilepsy due to hemimegalencephaly affecting the left hemisphere. Given congruent electroclinical findings, we performed a left vertical parasagittal transventricular hemispherotomy after critical interdisciplinary discussion. No complications occurred during the surgery. Intraoperatively; 118 ml of red blood cells (30 ml/kg) and 80 ml of plasma were transfused. The patient has been seizure-free since discharge without further neurological deficits. Conclusion: We demonstrate that early epilepsy surgery is a safe procedure in very young infants if performed in a specialized center experienced with age-specific surgical conditions and perioperative management. The specific surgical difficulties should be weighed against the risk of life-long developmental drawbacks of ongoing detrimental epilepsy.

[Brittle cornea syndrome type 1 caused by compound heterozygosity of two mutations in the ZNF469 gene]. / Brittle-Cornea-Syndrom Typ 1 durch Compound-Heterozygotie zweier Mutationen im ZNF469-Gen.

We report the case of a 3-year-old boy presenting with bilateral keratoglobus and blue sclera in addition to hallux valgus, arachnodactyly, small joint hypermobility, mitral valve dysfunction and a history of generalized muscular hypotonia in early infancy. Molecular genetics provided evidence of two pathogenic mutations in the ZNF469 gene (compound heterozygosity) leading to the diagnosis of brittle cornea syndrome type 1. In addition to neuropediatric care, spectacles were prescribed to correct refractive error and for ocular protection. Owing to the thin cornea and sclera, eye injuries are the main cause for irreversible visual loss in this disease.

Short-term outcomes of very low birth weight infants born at a tertiary care hospital, istanbul, Turkey.

OBJECTIVE: To evaluate mortality and short-term outcomes in very low birth weight infants admitted to the tertiary neonatal intensive care unit, Istanbul, Turkey. METHODS: Study data were recorded prospectively from January 1, 2010, to December 31, 2010. The clinical findings in neonates with birth weights <1000g were compared with infants with birth weights of between 1000g and 1499g. FINDINGS: In the present study, survival rates were 40% and 86.2% for infants weighing <1000g and 1000g to 1499g, respectively. There was no difference between males and females with respect to mortality (P>0.05). The mean (±standard deviation) birth weight was 985.6±150.15 g and mean gestational age was 27.5±2.04 weeks. The antenatal steroid rate was 37.2%, and the Cesarean section rate was 73%. Respiratory distress syndrome was diagnosed in 89% of the infants, with a 69% surfactant administration rate. Severe intracranial hemorrhage (IVH) (grade >II) was 14%. Grade 4 periventricular leukomalacia was 10%. Twelve (24%) infants had evidence of bronchopulmonary dysplasia (BPD). Retinopathy of prematurity (stage >II) was 4%. The correlation between ROP rate and need for ventilation therapy was present (r=0.52). Proven necrotizing enterocolitis (stage >2) was not observed. Patent ductus arteriosus (PDA) was diagnosed in 67% of the neonates. BPD, IVH, and PDA were statistically higher in neonates with a birth weight <1000g. CONCLUSION: Survival rate of VLBW infants increased with increasing BW. Sex was not a risk factor for mortality. The need for ventilatory therapy may be an important risk factor for ROP in infants <1500g.

Oxygen saturation of healthy term neonates during the first 30 minutes of life.

BACKGROUND: The purpose of this study was to document the oxygen saturation (SpO(2) ), general physical signs and laboratory characteristics during the first 30 min of life. METHODS: Forty healthy singleton full-term neonates delivered vaginally (n = 33) or by cesarean section (n = 7) were included in this prospective observational study. After delivery, the SpO(2) levels of the upper (right hand; 'preductal') and lower (dorsum of the right foot; 'postductal') extremities of the neonates lying on the servo-controlled radiant heater in the delivery room were measured simultaneously with oximeter probes (Oxiprobe BM-270) placed at 1, 5, 10, 15, 20, 25, and 30 min. The correlation between pre- and postductal SpO(2) level and different variables (vital signs, capillary refill time recorded at 1 and 15 min, cord pH and hemoglobin values, and Apgar scores at 1 and 5 min) was examined. RESULTS: The 1 min pre- and postductal SpO(2) were 82.3 ± 7.34% and 79.08 ± 8.16% (P > 0.05), respectively. The preductal values at 5, 10, and 15 min were statistically higher than the postductal values (89.73 ± 6.01%, 93.43 ± 4.06%, and 94.53 ± 3.19% vs 85.53 ± 6.92%, 89.9 ± 4.91%, 92.83 ± 3.92%, respectively). SpO(2) was the same regardless of the mode of delivery. No correlations were found between pre- and postductal SpO(2) and other variables. CONCLUSIONS: Oxygen saturation was not affected by mode of delivery, was independent of Apgar score, cord hemoglobin, cord pH, vital signs, and capillary refill time in the first few minutes of life, and did not reach 90% in the first 5 min of life in healthy full-term neonates.

Close to threshold transcranial electrical stimulation preferentially activates inhibitory networks before switching to excitation with higher intensities.

BACKGROUND: Recently we have shown that transcranial random noise (tRNS) and 140 Hz transcranial alternating current stimulations (tACS), applied over the primary motor cortex (M1) and using 10 min stimulation duration and 1 mA intensity, significantly increases cortical excitability as measured by motor evoked potentials at rest before and after stimulation. OBJECTIVE/HYPOTHESIS: Here, by decreasing the stimulation intensity in 0.2 mA steps from 1.0 mA, we investigate to what extent intensity depends on the induced after-effects. METHODS: All twenty-five subjects participated in two different experimental sessions each. They received tACS using 140 Hz frequency and full spectrum tRNS at five different intensities on separate days. Sham stimulation was used as a control. RESULTS: Instead of receiving a simple threshold, unexpectedly, in these two independent data sets at threshold intensities of 0.4 mA we found a switch of the already known excitation achieved with an intensity of 1 mA to inhibition. The intermediate intensity ranges of 0.6 and 0.8 mA had no effect at all. Interestingly, the inhibition produced by 140 Hz tACS was stronger than that induced by tRNS. CONCLUSIONS: In summary, we have shown here the possibility of selectively controlling the enhancement or reduction of M1 excitability by applying different intensities of high frequency transcranial electrical stimulation.