Awake brain surgery for language mapping in pediatric patients: a single-center experience.

OBJECTIVE: The goal of this study was to evaluate the feasibility, benefit, and safety of awake brain surgery (ABS) and intraoperative language mapping in children and adolescents with structural epilepsies. Whereas ABS is an established method to monitor language function in adults intraoperatively, reports of ABS in children are scarce. METHODS: A retrospective chart review of pediatric patients ≤ 18 years of age who underwent ABS and cortical language mapping for supratentorial tumors and nontumoral epileptogenic lesions between 2008 and 2019 was conducted. The authors evaluated the global intellectual and specific language performance by using detailed neuropsychological testing, the patient's intraoperative compliance, results of intraoperative language mapping assisted by electrocorticography (ECoG), and postsurgical language development and seizure outcomes. Descriptive statistics were used for this study, with a statistical significance of p < 0.05. RESULTS: Eleven children (7 boys) with a median age of 13 years (range 10-18 years) underwent ABS for a lesion in close vicinity to cortical language areas as defined by structural and functional MRI (left hemisphere in 9 children, right hemisphere in 2). Patients were neurologically intact but experiencing seizures; these were refractory to therapy in 9 patients. Compliance during the awake phase was high in 10 patients and low in 1 patient. Cortical mapping identified eloquent language areas in 6/10 (60%) patients and was concordant in 3/8 (37.5%), discordant in 3/8 (37.5%), and unclear in 2/8 (25%) patients compared to preoperative functional MRI. Stimulation-induced seizures occurred in 2 patients and could be interrupted easily. ECoG revealed that afterdischarge potentials (ADP) were involved in 5/9 (56%) patients with speech disturbances during stimulation. None of these patients harbored postoperative language dysfunction. Gross-total resection was achieved in 10/11 (91%) patients, and all were seizure free after a median follow-up of 4.3 years. Neuropsychological testing using the Wechsler Intelligence Scale for Children and the verbal learning and memory test showed an overall nonsignificant trend toward an immediate postoperative deterioration followed by an improvement to above preoperative levels after 1 year. CONCLUSIONS: ABS is a valuable technique in selected pediatric patients with lesions in language areas. An interdisciplinary approach, careful patient selection, extensive preoperative training of patients, and interpretation of intraoperative ADP are pivotal to a successful surgery.

Bisphosphonate drug holidays: One size does not fit all.

Bisphosphonates have been safely used to treat osteoporosis, effectively reducing fracture risk after 3 to 5 years of treatment. Recent concerns about long-term safety coupled with posttreatment fracture risk reduction have increased support for drug holidays. The decision to start low-risk patients on drug holidays must be based on current fracture risk assessment.

Efficacy and tolerability of the ketogenic diet versus high-dose adrenocorticotropic hormone for infantile spasms: A single-center parallel-cohort randomized controlled trial.

OBJECTIVE: To compare the efficacy and safety of the ketogenic diet (KD) with standard adrenocorticotropic hormone (ACTH) treatment in infants with West syndrome. METHODS: In this parallel-cohort (PC) randomized controlled trial (RCT), infants were randomly allocated to KD or high-dose ACTH. Those who could not be randomized were followed in a PC. Primary end point was electroclinical remission at day 28. Secondary end points were time to electroclinical remission, relapse after initial response, seizure freedom at last follow-up, adverse effects, and developmental progress. RESULTS: One hundred one infants were included: 32 in the RCT (16 KD; 16 ACTH) and 69 in the PC (37 KD; 32 ACTH). Electroclinical remission at day 28 was similar between KD and ACTH (RCT: 62% vs 69%; PC: 41% vs 38%; combined cohort: 47% vs 48%; KD vs ACTH, respectively). In the combined cohort, time to electroclinical remission was similar between both treatments (14 days for KD, 16 days for ACTH). However, relapse rates were 16% (KD) and 43% (ACTH, P = 0.09), and seizure freedom at last follow-up was 40% (KD) and 27% (ACTH, P = 0.18). Adverse effects needing acute medical intervention occurred more often with ACTH (30% with KD, 94% with ACTH, P < 0.001). Age-appropriate psychomotor development and adaptive behavior were similar. Without prior vigabatrin (VGB) treatment, remission at day 28 was 47% (KD) and 80% (ACTH, P = 0.02); relapse rates were 29% (KD) and 56% (ACTH, P = 0.13). Consequently, seizure freedom at last follow-up was similar. In infants with prior VGB, seizure freedom at last follow-up was 48% (KD) and 21% (ACTH, P = 0.05). SIGNIFICANCE: The study is underpowered; therefore, its results should be interpreted with caution. KD is as effective as ACTH in the long term but is better tolerated. Without prior VGB treatment, ACTH remains the first choice to achieve short-term remission. However, with prior VGB, KD was at least as effective as ACTH in the short term and was associated with lower relapse rates in the long term; therefore, it represents an appropriate second-line treatment after VGB.

Epilepsy surgery in infants : Safety issues and developmental outcome.

PURPOSE: To evaluate the efficacy and safety of epilepsy surgery in infants. METHODS: Included were patients with epilepsy onset during the first year of life, epilepsy surgery before the age of 36 months at the study center and a minimum follow-up of 24 months after surgery. Patients who were surgically treated before the age of 12 months were compared with those between 13 and 36 months. Group differences with respect to efficacy (seizure outcomes and developmental progress measured by the social interaction quotient, SIQ) as well as safety (i. e. peri-operative complication rates) were analyzed. RESULTS: A total of 20 patients (10 girls) were included: 10 (five girls) were operated on as infants (median age at surgery 9.0 months, median disease duration prior to surgery 5.0 months) and 10 (5 girls) were operated on as toddlers (median age at surgery 24.0 months, median disease duration prior to surgery 18.0 months). Favorable seizure outcomes (Wieser 1a and 1) were seen in 80% (8/10) of the infants and 60.0% (6/10) of toddlers. Developmental progress was most evident in infants who were seizure-free and off medication (median SIQ 85.5 versus 63.0 in the toddler group). There were no differences between the two groups with respect to safety aspects. CONCLUSION: Despite several limitations due to the small number of patients included, our results are in favor of early epilepsy surgery in infants with drug-resistant epilepsy.

Immediate termination of electrical status epilepticus in sleep after hemispherotomy is associated with significant progress in language development.

AIM: To study the effect of hemispherotomy on electrical status epilepticus in sleep (ESES) and language development. METHOD: Children with a confirmed diagnosis of ESES prior to surgery and a minimum of 24 months of developmental follow-up data were compared with age-matched controls without ESES. Language quotients (LQs) were calculated before and after surgery. RESULTS: Eleven patients (five females, six males) and 21 controls (11 females, 10 males) were included. Before surgery a significantly higher number of children in the study group (n=9) demonstrated severe developmental delay compared with children in the control group (n=13; p=0.015). In the study group ESES remitted immediately after surgery in 10 children, and a significant catch-up in LQs was observed in this group (preoperative mean 40.0 [standard deviation (SD) 22.2, interquartile range (IQR) 30.0-62.0]; postoperative mean 73.0 [SD 33.5, IQR 41.0-97.0]; p=0.037). There was no significant difference compared with controls at last follow-up after surgery (study group: five with severe impairment; control group: eight with severe impairment [p=0.971]). Overall, a favourable developmental outcome was associated with freedom from seizures (seizure-free group: median preoperative LQ 61.5, median postoperative LQ 78.0 [p=0.017]; seizure group: median preoperative LQ 35.5, median postoperative LQ 56.5 [p=0.273]) and antiepileptic drug withdrawal (off medication: median preoperative LQ 49.5, median postoperative LQ 78.0 [p=0.011]; on medication: median preoperative LQ 78.0, median postoperative LQ 83.5 [p=0.889]). INTERPRETATION: Children with ESES showed significantly lower preoperative language abilities than children without ESES. In cases with remission of ESES after surgery, marked improvement in LQs was noticed. This improvement cannot be fully explained by seizure-freedom alone as seizure-free children without preoperative ESES showed less improvement.

Improvement of language development after successful hemispherotomy.

PURPOSE: To investigate language development after functional hemispherotomy and to evaluate prognostic factors for (un-)favourable outcomes. METHODS: Children and adolescents who had vertical perithalamic hemispherotomy at the Medical University Wien (MUW) paediatric epilepsy centre were identified from a prospectively maintained database. Inclusion criteria were: complete clinical, neurophysiological and neuropsychological data, seizure freedom and a minimum follow-up of 12 months after surgery. The language quotients (LQ) prior to surgery and at last follow-up were calculated for each child. In addition, associations between pre- to post-surgical changes in LQ and the following variables were examined: age at epilepsy-onset, age at surgery and duration of epilepsy prior to surgery, aetiology, side of surgery, interictal EEG including sleep organization before and 12 months after surgery and antiepileptic-drug (AED) withdrawal state at last follow-up. Analyses were carried out in SPSS version 20.0 (SPSS Inc., Chicago, IL, USA). Nonparametric Wilcoxon and chi-square tests were applied, as required. RESULTS: Data from 28 children (14 female) were analyzed. The median age at epilepsy surgery was 64.5 months. The median follow-up after surgery was 3.0 years (±2.6 years, range 12 months to 12 years). Significant gains in LQs at last follow-up were found in 31% of the children (p=0.008). Short disease duration prior to surgery, acquired pathology, lack of epileptiform EEG discharges in the contralateral hemisphere and/or normalization of EEG sleep patterns after surgery, and successful AED withdrawal were linked to favourable language outcomes. CONCLUSION: Successful and early hemispherotomy results in improvement of language function in the intact hemisphere.

Semiology of temporal lobe epilepsy in children and adolescents. Value in lateralizing the seizure onset zone [corrected].

PURPOSE: To determine the frequency and lateralizing value of clinical seizure symptoms in children and adolescents with drug-resistant temporal lobe epilepsy (TLE). METHODS: Patients enrolled had to be <18 years of age and seizure free at follow-up for at least 12 months after epilepsy surgery. Patients were assigned to two age groups, children (age<12 years) and adolescents (age>12 and <18 years). Video-tapes were reviewed blinded to patients' demographic data and results of additional investigations by two independent raters. Clinical signs of known lateralizing significance in adults and additional clinical signs without lateralizing value were assessed. RESULTS: 14 patients (eight boys; 2-18 years) fulfilled the inclusion criteria. Inter-observer agreement was excellent (kappa coefficient: 0.82). Compared with adult series, no differences were found concerning overall occurrence of lateralizing signs and lateralizing accuracy. There were age-related differences, however, concerning the occurrence of individual signs: secondary generalization, complex automatisms and version were less frequent in children than in adolescents. CONCLUSIONS: Clinical signs of lateralizing value can also be found in children and adolescents, provided that the evaluation protocols used consider developmental aspects.