What have we learned from the real-world efficacy of FFA in DS and LGS? A post-marketing study in clinical practice.

OBJECTIVE: To evaluate the effectiveness and tolerability of fenfluramine (FFA) in routine clinical practice treating real-world populations with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). METHODS: This was a retrospective analysis of patients with DS or LGS who initiated FFA treatment from 2018 to 2022 at a single center. Patient demographics, medical history, seizure characteristics, and treatment outcomes were collected from electronic medical records. Duration of FFA treatment, dosage regimens, seizure frequency, seizure severity, improvements in cognitive, social, and motor outcomes, and adverse events were extracted and analyzed. Effectiveness was assessed using ≥50 % sustained reduction in monthly seizure frequency vs baseline for ≥2 consecutive months at 12 months; seizure freedom was a secondary measure. RESULTS: Seizure frequency data was available for 56 of 68 patients included in the study. At 12 months, 50 patients (89.3 %) remained on FFA treatment; 58 % of these patients achieved a ≥50 % sustained response and 10 % experienced seizure freedom. Cognitive, motor, and social improvement were noted in 70.7 %, 36.2 %, and 27.6 % of patients, respectively. The total number of concomitant antiseizure medications was reduced by ≥1 in 29.4 % of patients. No differences were found between DS and LGS patients in these outcomes; age at start of FFA and age at the 12-month timepoint did not have an effect. At least one AE was experienced by 59.7% of patients; in 86.5% of the cases, AEs were plausibly related to treatment. While 70.3% of AEs were self-resolving and 81.8% of the remaining patients experienced mild AEs, 1 patient experienced a serious AE unrelated to FFA which resulted in the patient's death. There were no cases of pulmonary arterial hypertension or ventricular heart disease. SIGNIFICANCE: The effectiveness and tolerability of FFA treatment in patients with DS or LGS in this retrospective analysis of real-world data were consistent with those seen in randomized clinical trials.

Gut microbiota manipulation as an epilepsy treatment.

Many studies have documented the important role of the gut microbiota (GM) in the regulation of several central nervous system (CNS) processes through the microbiota-gut-brain (MGB) axis. This latter represents the connection between the CNS, the enteric nervous system, the gut and its microbiota through several ascending and descending pathways. The variation of the GM composition is associated with the pathogenesis and/or progression as well as severity of various neuropsychiatric/neurological diseases such as depression, autism spectrum disorder, multiple sclerosis, Parkinson's, and Alzheimer's diseases. Recently, changes in the bacterial composition of the GM have also been linked to epilepsy and seizures, with some studies exploring the potential role of GM in the regulation of neuronal hyperexcitability, seizure occurrence and epileptogenesis. Accordingly, there are potential novel treatments which are currently being investigated such as probiotics, prebiotics and symbiotic that may represent innovative therapeutic approaches. The aim of this review is to explore the effect of gut microbiota manipulation as a therapeutic strategy in epilepsy and the methodological challenges to design (translational) clinical trial investigating the gut microbiota.

Relationship between sleep quality and cognitive performance in patients with epilepsy.

PURPOSE: To investigate the relationship between self-reported sleep quality and cognitive function in patients with epilepsy (PWE), as well as anxiety and depressive symptoms and patient quality of life (QoL). METHODS: This multicenter cross-sectional study included PWE aged ≥12 years who were receiving ≥1 anti-seizure medication (ASM) and had not been diagnosed with a sleep disorder. Patients completed the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Montreal Cognitive Assessment test (MoCA), the Hospital Anxiety and Depression Scale (HADS), and the Quality of Life in Epilepsy Inventory-10 (QOLIE-10). RESULTS: The study enrolled 150 patients aged 16-83 years, mean age (standard deviation [SD]) 40.6 (15.2) years; 58.7% were female and 75.3% had focal epilepsy. Mean (SD) PSQI score was 4.71 (3.08), 44.4% of patients had impaired sleep quality (PSQI score ≥5), 19.9% had pathologic excessive daytime sleepiness (ESS score >12), and 32.7% had mild cognitive impairment (MoCA score <26). Within the PSQI, sleep disturbance (P = 0.036) and use of sleep medication (P = 0.006) scores were significantly higher in patients with mild cognitive impairment. Multiple regression analysis showed older age (regression coefficient [B], -0.086; 95% confidence interval [CI], -0.127, -0.045; P < 0.001) and the use of sleep medication component of the PSQI [B, -1.157; 95% CI, -2.064, -0.220; P = 0.013) were independently associated with lower MoCA score. Poor sleep quality was associated with probable anxiety and depression symptoms, and directly correlated with reduced QoL. CONCLUSIONS: In PWE, sleep quality was not significantly independently associated with mild cognitive impairment, although poor sleep quality had a negative effect on mood and QoL.

The potential role of interventions impacting on gut-microbiota in epilepsy.

INTRODUCTION: The gut microbiota seems to be implicated in the functioning and development of basic physiological processes and might also influence central neural processes, through the microbiota-gut-brain (MGB) axis. Pre- and clinical studies support the role of the microbiome in seizure modulation and in the pathogenesis of epilepsy. Acting through different interventions (e.g. diet, supplementations, drugs) could perturb directly and indirectly the MGB axis. Investigating the effects of these interventions might possibly allow better understanding of epilepsy itself, identify biomarkers, or providing new therapeutic options. AREAS COVERED: PubMed and Google Scholar searches were used to compile a list of relevant publications until January 2020, using data from preclinical studies and clinical trials and gut microbiome/microbiota projects. Furthermore, we evaluate the impact of the antiepileptic drugs on gut microbiota and the influence of intestinal alterations on seizures occurrence. EXPERT OPINION: Investigating the MGB axis and the role of gut supplementation in epilepsy is challenging due to the numerous potential pathways and variables involved. Few studies have been performed so far and all have been limited making speculation still premature. Studies designed with the similar strictness of pharmaceutical drug development trials, performing taxa, and metabolomic analyses with standard methodologies are needed.

Education and information needs for physicians about rare diseases in Spain.

BACKGROUND: Rare diseases are a priority objective for public health systems. Given its complexity, late and misdiagnoses occur very often which causes mental and physical burden for patients and family. This would be caused, in part, for unprepared clinicians in this field. The aim of this study was to report the training needs and the perceived shortcomings of Spanish physicians of the public health system in the diagnosis, treatment and monitoring of patients with rare diseases. METHODS: We used a descriptive cross-sectional study through an "ad hoc" survey of 26 questions was completed by 132 primary care physicians and 37 specialists during April and May 2018. RESULTS: Less than a third of the physicians had received training in rare disease during their undergraduate or postgraduate years, and for hospital professionals, they received more training in the postgraduate period. CONCLUSION: Primary care physicians and specialists showed low training level in rare diseases. An academical and continuous program on rare disease, as well as, multidisciplinary units and high quality practice guidelines are necessary to help to prevention and support clinical decisions and improve quality of care of patients and families.

Levels of anger in epilepsy patients treated with eslicarbazepine acetate.

INTRODUCTION: Aggressive behavior is commonly associated with epilepsy and can be influenced by the antiepileptic drugs (AEDs) taken. Sodium channel blockers, specifically the carboxamides derivatives such as carbamazepine and oxcarbazepine, are some of the AEDs considered to have a favorable psychiatric effect profile. OBJECTIVES: We aimed to assess whether the carboxamide analogue eslicarbazepine acetate (ESL) has any effect on the levels of anger in patients with epilepsy. MATERIAL AND METHODS: We prospectively recruited adult patients with epilepsy on treatment with ≦2 active AEDs, who required AED addition or substitution, excluding patients with active psychiatric disorders. All patients completed anger level (STAXI-2), depression-anxiety (HADS), and quality of life (QOLIE-10) assessments, and were evaluated at baseline and within 3-6 months after treatment initiation. RESULTS: Of 78 patients receiving ESL, as add-on therapy or in substitution of a previous AED, were recruited into the ESL group, with an average age of 48 years and 54% men. We used a control group of 58 patients receiving AEDs other than carboxamides. CONCLUSIONS: Patients overall showed improvements in anger levels, mood, and quality of life during the follow-up. A history of psychiatric disorders was a limiting factor to improve anger levels. As compared to controls, anger levels improved in ESL patients independently from seizure control. Therefore, ESL seems to exert a favorable influence on the anger levels of otherwise healthy patients with epilepsy, including those unresponsive to seizure control. The potential ESL anti-aggressive effect should be studied in patients with epilepsy and active psychiatric disorders.

El eje microbiota-intestino-cerebro y sus grandes proyecciones / The microbiota-gut-brain axis and its great projections

Introducción. Se denomina microbiota al conjunto de millones de microorganismos que conviven de manera simbiótica en nuestro organismo. Este conjunto bacteriano, que se localiza principalmente en el tracto digestivo, se distribuye a lo largo de los diferentes órganos en función de las propiedades químicas. Los factores que influyen en su composición son múltiples (dieta, hábitos individuales, fármacos). La microbiota colabora en varias funciones, como pueden ser el metabolismo o la inmunidad. Desarrollo. En los últimos años se ha puesto de relieve el papel bidireccional de la microbiota del tracto digestivo y del sistema nervioso central, es el denominado eje intestino-cerebro. En lo que a este eje se refiere, se cree que la comunicación se produce a través de tres vías: el nervio vago, la vía sistémica (mediante la liberación de hormonas, metabolitos y neurotransmisores) y el sistema inmune (por la acción de las citocinas). Conclusiones. Aunque aún quedan muchas incógnitas por esclarecer, este eje se postula como una posible base patógena para numerosos trastornos neurológicos de gran impacto sanitario, como la enfermedad de Alzheimer, la enfermedad de Parkinson o la esclerosis múltiple. En el momento actual se están llevando a cabo estudios que intentan evaluar el impacto de los probióticos sobre algunas de estas enfermedades neurológicas

Introduction. The microbiota is the set of millions of microorganisms that coexist in a symbiotic way in our body. It is mainly located in the digestive tract, being distributed in function of the chemical properties and the functions of the different organs. The factors that influence its composition are multiple (diet, individual habits, diseases or drugs). It also participates in several functions of the organism such as metabolism, immunity or even the function of the central nervous system. Development. This last interrelationship is called: gut-brain axis. For years the relationship between the microbiota and the central nervous system has been known and how they influence one over the other. It is postulated that communication occurs through three systems: the vagus nerve, the systemic pathway (with the release of hormones, metabolites and neurotransmitters) and the immune system (by the action of cytokines). Conclusions. There are still many unknowns to be clarified in this field, but this microbiota-intestine-brain relationship is postulated as a possible pathogenic basis for neurological diseases of great health impact such as Alzheimer, Parkinson or multiple sclerosis. There are currently studies with probiotics with hopeful results in patients with Alzheimer's disease