Fenfluramine for the treatment of status epilepticus: use in an adult with Lennox-Gastaut syndrome and literature review.

BACKGROUND: Novel treatments are needed to control refractory status epilepticus (SE). This study aimed to assess the potential effectiveness of fenfluramine (FFA) as an acute treatment option for SE. We present a summary of clinical cases where oral FFA was used in SE. METHODS: A case of an adult patient with Lennox-Gastaut syndrome (LGS) who was treated with FFA due to refractory SE is presented in detail. To identify studies that evaluated the use of FFA in SE, we performed a systematic literature search. RESULTS: Four case reports on the acute treatment with FFA of SE in children and adults with Dravet syndrome (DS) and LGS were available. We report in detail a 30-year-old woman with LGS of structural etiology, who presented with generalized tonic and dialeptic seizures manifesting at high frequencies without a return to clinical baseline constituting the diagnosis of SE. Treatment with anti-seizure medications up to lacosamide 600 mg/d, brivaracetam 300 mg/d, valproate 1,600 mg/d, and various benzodiazepines did not resolve the SE. Due to ongoing refractory SE and following an unremarkable echocardiography, treatment was initiated with FFA, with an initial dose of 10 mg/d (0.22 mg/kg body weight [bw]) and fast up-titration to 26 mg/d (0.58 mg/kg bw) within 10 days. Subsequently, the patient experienced a resolution of SE within 4 days, accompanied by a notable improvement in clinical presentation and regaining her mobility, walking with the assistance of physiotherapists. In the three cases reported in the literature, DS patients with SE were treated with FFA, and a cessation of SE was observed within a few days. No treatment-emergent adverse events were observed during FFA treatment in any of the four cases. CONCLUSIONS: Based on the reported cases, FFA might be a promising option for the acute treatment of SE in patients with DS and LGS. Observational data show a decreased SE frequency while on FFA, suggesting a potentially preventive role of FFA in these populations. KEY POINTS: We summarize four cases of refractory status epilepticus (SE) successfully treated with fenfluramine. Refractory SE resolved after 4-7 days on fenfluramine. Swift fenfluramine up-titration was well-tolerated during SE treatment. Treatment-emergent adverse events on fenfluramine were not observed. Fenfluramine might be a valuable acute treatment option for SE in Dravet and Lennox-Gastaut syndromes.

Red blood cell transfusion in patients undergoing elective primary glioblastoma resection.

BACKGROUND: Red blood cell (RBC) transfusion in patients undergoing major elective cranial surgery is associated with increased postoperative morbidity and mortality. This study aims to identify the clinical outcome of transfused glioblastoma patients undergoing primary surgical tumor resection and identify risk factors for RBC transfusion. MATERIAL AND METHODS: Between 2009 and 2019, 406 patients underwent elective primary glioblastoma resection. For multivariate analysis to assess risk factors for RBC transfusion, logistic regression was conducted. The impact of RBC transfusion on overall survival was assessed using Kaplan-Meier analysis. RESULTS: In total, 36 (8.9%) patients received RBC transfusion. Preoperative anemia rate was significantly higher in transfused patients compared to patients without RBC transfusion (33.3 vs 6.5%; p<0.0001). Postoperative complications as well as hospital length of stay (LOS) (p<0.0001) were significantly increased in transfused patients compared to non-transfused patients. After multivariate analysis, risk factors for RBC transfusion were preoperative anemia (p<0.0001), intraoperative blood loss (p<0.0001), female gender (p=0.0056) and radiation (p=0.0064). Kaplan-Meier curves revealed that RBC transfusion and being elderly (age ≥75 years) were relevant for overall survival. DISCUSSION: RBC transfusion is associated with increased postoperative morbidity and mortality in patients undergoing elective primary glioblastoma resection. Preoperative anemia and intraoperative blood loss are major risk factors for RBC transfusion. Preoperative anemia management and blood conservation strategies are crucial in patients undergoing elective primary glioblastoma resection.

Impact of different respiratory monitoring techniques on respiration-dependent stroke-volume measurements assessed by real-time magnetic resonance imaging.

PURPOSE: Quantitative blood flow measurements in thoracic vessels are dependent on the patient's respiration due to intrathoracic pressure changes. Several registration techniques for tracing the patient's breathing curve exist exploiting various physiological characteristics. In the presented study two registration techniques were investigated to estimate the time-shift between the associated respiration curves and the impact on respiration-dependent hemodynamic measures. MATERIALS AND METHODS: Using flow-sensitive real-time magnetic resonance imaging (3.0T, temporal resolution=24-26ms) data were acquired during a 13s time-interval under normal physiological (no) and forced breathing (fo) in the ascending aorta (AAo) and inferior vena cava (IVC). Breathing curves were obtained by using (1) an abdominal placed respiratory belt (=standard, RB) and (2) by applying a self-developed edge-detection software (ED). Respiration curves were divided into four intervals (end-expiration, inspiration, end-inspiration and expiration) to generate respiration-dependent stroke volumes (SVs) and cardiac indices (CIs). Data were available from 12 healthy controls (16.2±8.8yrs) and 18 Fontan-patients (18.6±7.1yrs). RESULTS: Respiration curves acquired with RB differs from and are shifted compared to those obtained by ED (controls: average shift=207±168ms, Fontan-patients: average shift=106±235ms). This time-shift results in statistical significant differences in cardiac indices CIAAo,fo in controls (ΔCIAAo,fo: expiration: +0.16L/min/m2, p=0.018), in CIIVC,no in Fontan-patients (ΔCIIVC,no: end-expiration: +0.94L/min/m2, p=0.002 and end-inspiration: -1.04L/min/m2, p=0.017) and in CIIVC,fo in Fontan-patients (ΔCIIVC,fo: end-expiration: +1.31L/min/m2, p=0.009; inspiration: -2.26L/min/m2, p=0.008 and end-inspiration: -1.87L/min/m2, p=0.029). CONCLUSIONS: A time-shift between both applied respiratory tracking techniques was observed resulting in significant differences in respiration-dependent CIs, which could influence the clinical decision-making.