Copy number variations (CNVs) have been related to developmental and epileptic encephalopathy (DEE). The 2q24.3 region includes a cluster of genes for voltage-gated sodium channels (SCN) and CNVs in this region cause DEE. However, the long-term course of DEE with a 2q24.3 duplication has not been described. A 20-year-old female developed epileptic encephalopathy in early infancy that was resistant to various antiseizure medications. Her seizures disappeared after starting vitamin B6 therapy. Therefore, her epilepsy was considered pyridoxine-dependent epilepsy. At 16 years old, whole exome sequencing revealed a 2q24.3 microduplication including SCN1A, SCN2A, SCN3A, SCN7A, and SCN9A. Quantitative PCR detected an increased copy number of 1.3 Mb on 2q24.3 involving these genes, but no gene mutation accounting for pyridoxine-dependent epilepsy. Considering that with this duplication she was reported to be seizure-free after infancy, she was able to be off antiseizure medications including vitamin B6. Our case involvingdrug-resistant epilepsy in early infancy had no recurrent seizures during long-term follow up. Detecting CNVs using whole exome sequencing data was useful to identify a 2q24.3 duplication unassociated with pyridoxine-dependent epilepsy, leading to cessation of unnecessary medications.

UNASSIGNED: Clobazam is a benzodiazepine drug, used to treat Lennox-Gastaut syndrome in patients aged 2 years and older.
UNASSIGNED: To support patient care, our laboratory developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the quantification of clobazam (CLB) and its major active metabolite N-desmethylclobazam (N-CLB) in human plasma or serum samples.
UNASSIGNED: The chromatographic separation was achieved with an Agilent Zorbax Eclipse Plus C-18 RRHD column with mobile phase consisting of 0.05% formic acid in 5 mM ammonium formate, pH 3.0 and 0.1% formic acid in acetonitrile at a flow rate of 600 µL/minute and an injection volume of 5 µL. The detection was performed on a triple quadrupole mass spectrometer in multiple reaction monitoring mode to monitor precursor-to-product ion transitions in positive electrospray ionization mode.
UNASSIGNED: The method was validated over a concentration range of 20-2000 ng/mL for CLB and 200-10,000 ng/mL for N-CLB. The lower limit of quantification was 20 ng/mL for CLB and 200 ng/mL for N-CLB with good accuracy and precision. The method performance was successfully evaluated by comparison with two different external laboratories. Retrospective data analysis was performed to evaluate the positivity rate and metabolic patterns for clobazam from our patient population, as a reference laboratory. Among the positive samples, both parent and metabolite were detected in 96.4% of the samples.
UNASSIGNED: The method was developed to support therapeutic drug monitoring and the data generated from retrospective analysis could be useful for result interpretation in conjunction with clinical patient information.

Clobazam (CLB) was approved in October 2011 by the United States FDA as an adjunctive therapy for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients older than the age of 2. Due to its unique chemical design and selective binding to the alpha-2 GABA-receptor, CLB has a decreased tendency for sedation compared to other benzodiazepines. A recent literature review shows that sedation, hypersalivation (drooling), and behavior changes are the most common side effects of CLB. It has also been shown that a patient\'s level of consciousness is indirectly related to the risk of aspiration. Hypersalivation is too is a significant predisposing factor for aspiration. In this report, we present three adult patients with epilepsy who had aspiration pneumonia during treatment with CLB. We would like to raise awareness of increased drooling and somnolence in patients with predisposing factors for aspiration such as treatment with CLB and emphasize vigilance in this regard.

Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is a genetic disorder with several neurological, cutaneous and skeletal manifestations. Epilepsy has been previously reported as a finding in Gorlin-Goltz syndrome but remains ill-described in the context of this disease. We report two new patients with Gorlin-Goltz syndrome featuring epilepsy and review the existing literature on the topic.

We observed that cannabidiol supplements were highly effective in treating an infant boy with drug-resistant early infantile epileptic encephalopathy, eliminating his intractable tonic seizures. The infant began suffering clusters of brief tonic seizures from birth at 39 weeks gestation. EEG showed burst-suppression and seizures could not be controlled by trials of phenobarbital, zonisamide, vitamin B6, clobazam, levetiracetam, topiramate, phenytoin, valproate, high-dose phenobarbital, and ACTH therapy. The boy was discharged from hospital at 130 days of age still averaging tonic seizures 20-30 times per day. We started him on a cannabidiol supplement on day 207, increasing the dosage to 18 mg/kg/d on day 219. His seizures reduced in frequency and completely disappeared by day 234. These effects were maintained, with improved EEG background, even after his other medications were discontinued. Cannabidiol\'s effectiveness in treating drug-resistant epilepsy has been confirmed in large-scale clinical trials in Europe and the United States; however, no such trials have been run in Asia. In addition, no reports to date have documented its efficacy in an infant as young as six months of age. This important case suggests that high-dose artisanal cannabidiol may effectively treat drug-resistant epilepsy in patients without access to pharmaceutical-grade CBD.

OBJECTIVE: Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy syndrome characterized by focal seizures with dominant auditory symptomatology. We present a case report of an 18-year-old patient with acute onset of seizures associated with epilepsy. Based on the clinical course of the disease and the results of the investigation, the diagnosis of ADLTE with a proven mutation in the RELN gene, which is considered causative, was subsequently confirmed. The aim of this study was to use 3 Tesla (3 T) magnetic resonance imaging (MRI) and advanced neuroimaging methods in a patient with a confirmed diagnosis of ADTLE.
METHODS: 3 T MRI brain scan and advanced neuroimaging methods were used in the standard protocols to analyzse voxel-based MRI, cortical thickness, and functional connectivity.
RESULTS: Morphometric MRI analysis (blurred grey-white matter junctions, voxel-based morphometry, and cortical thickness analysis) did not provide any informative results. The functional connectivity analysis revealed higher local synchrony in the patient in the left temporal (middle temporal gyrus), left frontal (supplementary motor area, superior frontal gyrus), and left parietal (gyrus angularis, gyrus supramarginalis) regions and the cingulate (middle cingulate gyrus) as compared to healthy controls.
CONCLUSIONS: Evidence of multiple areas of functional connectivity supports the theory of epileptogenic networks in ADTLE. Further studies are needed to elucidate this theory.