Vigabatrin pediatric dosing information for refractory complex partial seizures: Results from a population dose–response analysis

We predicted vigabatrin dosages for adjunctive therapy for pediatric patients with refractory complex partial seizures (rCPS) that would produce efficacy comparable to that observed for approved adult dosages. A dose–response model related seizure‐count data to vigabatrin dosage to identify dosages for pediatric rCPS patients. Seizure‐count data were obtained from three pediatric and two adult rCPS clinical trials. Dosages were predicted for oral solution and tablet formulations. Predicted oral solution dosages to achieve efficacy comparable to that of a 1 g/day adult dosage were 350 and 450 mg/day for patients with body weight ranges 10–15 and >15–20 kg, respectively. Predicted oral solution dosages for efficacy comparable to a 3 g/day adult dosage were 1,050 and 1,300 mg/day for weight ranges 10–15 and >15–20 kg, respectively. Predicted tablet dosage for efficacy comparable to a 1 g/day adult dosage was 500 mg/day for weight ranges 25–60 kg. Predicted tablet dosage for efficacy comparable to a 3 g/day adult dosage was 2,000 mg for weight ranges 25–60 kg. Vigabatrin dosages were identified for pediatric rCPS patients with body weights ≥10 kg.     

Prognostic significance of acute postoperative seizures in extra-temporal lobe epilepsy surgery

ObjectiveThis study aims to assess the prognostic value of acute postoperative seizures (APOS) in patients surgically treated for drug-resistant extra-temporal lobe (ET) epilepsy.MethodsWe studied 77 consecutive patients with ET epilepsy who underwent epilepsy surgery and were followed up for at least 2 years (mean duration of follow-up 6.2 years, range 2–14). Medical charts were reviewed to identify APOS, defined as ictal events with the exception of auras occurring within the first 7 days after surgery. Seizure outcome was determined at annual intervals. Patients who were in Engel Class I at the last contact were classified as having a favourable outcome.ResultsSeizure outcome was favourable in 47 patients (61%). The occurrence of APOS and incompleteness of resection were found to be independently associated with unfavourable outcome in a multiple regression model including all preoperative factors identified as outcome predictors in univariate analysis. Duration of illness was the only independent preoperative predictor of APOS.ConclusionsOur study suggests that APOS may predict long-term outcome in patients undergoing resective surgery for ET epilepsy. Given some study limitations, our findings should be regarded as preliminary and need confirmation from future larger, prospective, multicentre studies.SignificanceCaution may be required in the clinical management of patients experiencing APOS.     

Abuse,Not Financial Incentive,Predicts Non-Credible Cognitive Performance in Patients With Psychogenic Non-Epileptic Seizures

Participants with psychogenic non-epileptic seizures (PNES) who fail symptom validity testing (SVT) perform worse on neuropsychological testing than those who do not, consistent with results found in participants with different clinical presentations (e.g., mild traumatic brain injury). However, little is known about how variables typically associated with SVT failure in other populations (e.g., the presence of financial incentives, exaggerated report of psychopathology) correlate with SVT failure in participants with PNES. Likewise the relationship between SVT failure and reported abuse, one of the most frequently described demographic characteristics of the PNES population, has not been examined. We found that failure on the Word Memory Test (WMT) in 91 participants with PNES was strongly associated with reported abuse but, contrary to expectations, was not associated with the presence of financial incentives or severity of reported psychopathology. These results indicate that the factors driving WMT failure may differ significantly in participants with PNES in ways that are potentially clinically relevant.     

Epileptic seizures as a manifestation of cow’s milk allergy: a studied relationship and description of our pediatric experience

Adverse reactions after ingestion of cow’s milk proteins can occur at any age, from birth and even amongst exclusively breast-fed infants, although not all of these are hypersensitivity reactions. The most common presentations related to cow’s milk protein allergy are skin reactions, failure to thrive, anaphylaxis as well as gastrointestinal and respiratory disorders. In addition, several cases of cow’s milk protein allergy in the literature have documented neurological involvement, manifesting with convulsive seizures in children. This may be due to CNS spread of a peripheral inflammatory response. Furthermore, there is evidence that pro-inflammatory cytokines are responsible for disrupting the blood–brain barrier, causing focal CNS inflammation thereby triggering seizures, although further studies are needed to clarify the pathogenic relationship between atopy and its neurological manifestations. This review aims to analyze current published data on the link between cow’s milk protein allergy and epileptic events, highlighting scientific evidence for any potential pathogenic mechanism and describing our clinical experience in pediatrics.     

Degree of mucositis and duration of neutropenia are the major risk factors for early post-transplant febrile neutropenia and severe bacterial infections after reduced-intensity conditioning

Background and objectives: Whether the intensity of the conditioning regimen affects febrile neutropenia (FN) and severe bacterial infections (SBIs) is not well established. We analyzed the risk factors (RFs) for the development of FN and SBI in the first 100 d post‐transplant in 195 consecutive adult recipients of a reduced‐intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC‐allo). Materials and methods: The RIC regimens consisted of fludarabine plus melphalan (62%) or busulphan (38%) (FluMel or FluBu). SBIs include pneumonia, urinary tract infections, and bacteremia. Results: FN occurred in 141 patients (72%), always in the first 30 d post‐allo‐RIC. However, a SBI occurred in only 27 patients (14%) during this early post‐transplant period (P < 0.02) and NCI CTC grade III–IV mucosal damage in the first 10 d post‐transplantation (P = 0.03). RFs identified to SBI by multivariate analysis included corticosteroid therapy before day +100 (P < 0.01), mycophenolate mofetil‐based graft‐versus‐host disease (GVHD) prophylaxis (P < 0.01), and previous SBI before day +30 (P < 0.01). The rate of SBI from day +30 to +100 varied according to the number of RFs; thus, the rate of SBI was 1% in patients without any RF, 17% in patients with one RF, 29% with one RFs, and 53% in those with all three RFs. Conclusions: After an RIC‐allo, FN and early SBI occurred mostly in patients with severe mucositis and early‐onset neutropenia, while postengraftment high‐dose steroid therapy for acute GVHD was the major RF.