Efficacy and tolerability of perampanel in pediatric patients with Dravet syndrome.

Background: In 1978, Charlotte Dravet first described a form of epilepsy termed Dravet syndrome (DS). It is a form of genetic epilepsy with early-onset, intractable epilepsy episodes, and neurodevelopmental delay. In children, DS can lead to refractory seizures that are resistant to standard therapy. Recently, perampanel (PER) was approved as an antiepileptic drug for patients as young as 4 years old. Methods: The medical records were retrospectively reviewed and patients with DS who used PER were included in this study. The diagnosis was established using whole-exome sequencing, and the collected data included the patients' demographic characteristics, seizure pattern, PER dosage, laboratory and imaging findings. Results: This study included 18 pediatric patients with a clinical diagnosis of DS. The mean age of PER initiation was 7.67±3.865. Most patients had two types of seizures (61.1%) followed by three types (22.2%), with generalized tonic-clonic being the most frequently reported type of seizure. The mean efficacy of PER was 29.17%±29.368%, and only one patient had an efficacy of 100%. Moreover, patients aged 8 years and younger presented with higher efficacy than those who were older (49.17%±34.120% vs. 19.17%±21.829%, P=0.03). Conclusions: This study presented supporting evidence of the promising therapeutic effect of PER among patients with DS. PER can be considered one of the treatment options for this group of patients. However, several patients presented with unfavorable side effects that led to medication cessation. Future multicenter studies are required to explore further treatment options for patients with DS.

GAMT Deficiency Among Pediatric Population: Clinical and Molecular Characteristics and Management.

Objective: Analyze the treatment modalities used in real practice by synthesizing available literature. Methods: We reviewed and evaluated 52 cases of GAMT deficiency including 4 novel cases from Saudi Arabia diagnosed using whole-exome sequencing. All data utilized graphical presentation in the form of line charts and illustrated graphs. Results: The mean current age of was 117 months (±29.03) (range 12-372 months). The mean age of disease onset was 28.32 months (±13.68) (range 8 days - 252 months). The most prevalent symptom was developmental delays, mainly speech and motor, seizures, and intellectual disability. The male-to-female ratio was 3:1. Multiple treatments were used, with 54 pharmacological interventions, valproic acid being the most common. Creatinine monohydrate was the prevalent dietary intervention, with 25 patients reporting an improvement. Conclusion: The study suggests that efficient treatment with appropriate dietary intervention can improve patients' health, stressing that personalized treatment programs are essential in managing this disorder.

Sickle cell nephropathy: A review of novel biomarkers and their potential roles in early detection of renal involvement.

Whether the underlying mutations are homozygous, heterozygous, or co-inherited with other hemoglobinopathies, sickle cell disease is known to afflict the kidneys, leading to the clinical entity known as sickle cell nephropathy (SCN). Although common, SCN remains diagnostically elusive. Conventional studies performed in the context of renal disorders often fail to detect early stage SCN. This makes the quest for early diagnosis and treatment more challenging, and it increases the burden of chronic kidney disease-related morbidity among patients. Novel diagnostic tools have been employed to overcome this limitation. In this study, we discuss various biomarkers of SCN, including those employed in clinical practice and others recently identified in experimental settings, such as markers of vascular injury, endothelial dysfunction, tubulo-glomerular damage, and oxidative stress. These include kidney injury molecule-1, monocyte chemoattractant protein-1, N-acetyl-B-D-glucosaminidase, ceruloplasmin, orosomucoid, nephrin, and cation channels, among others. Furthermore, we explore the potential of novel biomarkers for refining diagnostic and therapeutic approaches and describe some obstacles that still need to be overcome. We highlight the importance of a collaborative approach to standardize the use of promising new biomarkers. Finally, we outline the limitations of conventional markers of renal damage as extensions of the pathogenic process occurring at the level of the organ and its functional subunits, with a discussion of the expected pattern of clinical and biochemical progression among patients with SCN.