OBJECTIVES: To investigate the efficacy and safety of perampanel (PER) add-on therapy in children with epilepsy of genetic etiology. METHODS: A retrospective analysis was conducted on the clinical data of 53 children who attended the Department of Neurology, Wuhan Children's Hospital, from November 2020 to April 2023. All children received PER add-on therapy and were diagnosed with epilepsy of genetic etiology based on whole-exome sequencing. The primary outcome measure was the proportion of children with a reduction in seizure frequency of ≥50% at month 12 of PER treatment (i.e., response rate), and the secondary outcome measures were response rates at months 3 and 6 of treatment. The influencing factors for the efficacy of PER add-on therapy in the treatment of epilepsy of genetic etiology were analyzed, and adverse events were recorded. RESULTS: The median follow-up duration was 13.10 months. After 12 months of follow-up, 42 children were included in the analysis, comprising 25 boys (60%) and 17 girls (40%). The median initial dose of PER was 1.5 (1.0, 2.0) mg/d, and the median maintenance dose was 4.0 (3.0, 8.0) mg/d. The response rates to PER at months 3, 6, and 12 of treatment were 61% (30/49), 54% (25/46), and 48% (20/42), respectively. No significant difference in the efficacy of PER was observed between children with mutations in genes encoding different protein functions (P>0.05). The most common adverse event reported was fatigue, observed in 3 children (6%). CONCLUSIONS PER add-on therapy demonstrates good efficacy and safety in children with epilepsy of genetic etiology. No influencing factors for the efficacy of PER have been identified to date.
Humans ; Male ; Female ; Nitriles ; Child ; Pyridones/administration & dosage* ; Child, Preschool ; Retrospective Studies ; Anticonvulsants/administration & dosage* ; Epilepsy/etiology* ; Adolescent ; Infant ; Drug Therapy, Combination

BACKGROUND: Studies on the relationship between antiepileptic drug (AED) administration and clinical outcomes in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) remain scarce. Levetiracetam (LEV) is an AED that is neuroprotective in various neurologic disorders. This study aimed to determine the impact of LEV on the outcome of MELAS. METHODS: A retrospective, single-center study was performed based on a large cohort of patients with MELAS with a history of seizures (n = 102). Decisions on antiepileptic therapies were made empirically. Patients were followed up for 1 to 8 years (median, 4 years) and divided into 2 groups based on whether LEV was administered (LEV or non-LEV). The modified Rankin scale (mRS) scores and mortality risks were analyzed in all patients. RESULTS: LEV, carbamazepine, benzodiazepines, topiramate, oxcarbazepine, valproate, and lamotrigine were administered in 48, 37, 18, 13, 11, 9, and 9 patients, singly or in combination, respectively. The mean mRS score of the LEV group (n = 48) was lower than that of the non-LEV group (n = 54; mean ± standard deviation, 2.79 ± 1.47 vs. 3.83 ± 1.93, P = 0.006) up to the end of the study. Nevertheless, there was no difference in the proportion of subjects without disability (mRS ranging 0-1) between the groups (P = 0.37). The multivariate regressions revealed that LEV treatment was associated with lower mRS scores (odds ratio 0.32, 95% confidence interval [CI] 0.15-0.68, P = 0.003) and mortality rates (hazard ratio 0.24, 95% CI 0.08-0.74, P = 0.013). There was a significant difference in the Kaplan-Meier survival curves between the groups (χ = 4.29, P = 0.04). CONCLUSIONS The LEV administration is associated with lower mortality in patients with MELAS in this retrospective study. Further laboratory research and prospective cohort studies are needed to confirm whether LEV has neuroprotective effects on patients with mitochondrial diseases.
Acidosis, Lactic ; drug therapy ; mortality ; Adolescent ; Anticonvulsants ; therapeutic use ; Carbamazepine ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Lamotrigine ; therapeutic use ; Levetiracetam ; administration & dosage ; therapeutic use ; Male ; Mitochondrial Encephalomyopathies ; drug therapy ; mortality ; Oxcarbazepine ; therapeutic use ; Prospective Studies ; Retrospective Studies ; Stroke ; drug therapy ; mortality ; Topiramate ; therapeutic use ; Valproic Acid ; therapeutic use

Anticonvulsants ; adverse effects ; Bone and Bones ; drug effects ; metabolism ; Calcium, Dietary ; administration & dosage ; Humans ; Valproic Acid ; adverse effects ; Vitamin D ; administration & dosage

Adolescent ; Anticonvulsants ; adverse effects ; Bone and Bones ; drug effects ; metabolism ; Calcium ; blood ; Calcium, Dietary ; administration & dosage ; Child ; Child, Preschool ; Dietary Supplements ; Epilepsy ; drug therapy ; metabolism ; Female ; Humans ; Male ; Valproic Acid ; adverse effects ; Vitamin D ; administration & dosage

OBJECTIVETo study the changes in 24-hour video electroencephalogram (EEG) and epileptic attacks after levetiracetam add-on therapy in children with frontal lobe epilepsy and epileptiform discharges.

METHODSA prospective study was carried out in 105 children with the frontal lobe epilepsy who received long-term treatment with 1 or 2 types of antiepileptic drug but still with epileptiform discharges in ECG. Levetiracetam add-on therapy was administered at the initial daily dose of 20 mg/kg (given in 2 doses) for 2 weeks followed by an increase of the dose to 30 mg/kg with a maintenance dose of 30-40 mg/kg. The changes in seizure attacks and 24-hour video-EEG monitoring after a 6-month therapy were observed.

RESULTSLevetiracetam add-on therapy reduced epileptiform discharges in 55 children (52.3%) and resulted in significant changes in EEG (P<0.05). Of the 77 children with clinical seizures, complete seizure control was achieved in 12 cases after the therapy, and the seizure attacks were reduced in 28 cases, showing a total response rate of 51.9%; the reduction in seizure attacks was positively correlated with EEG improvement (P<0.001).

CONCLUSIONLevetiracetam add-on therapy can decrease epileptiform discharges in EEG and reduce clinical seizure attacks in children with frontal lobe epilepsy with only mild adverse reactions.

Adolescent ; Anticonvulsants ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Electroencephalography ; Epilepsy, Frontal Lobe ; drug therapy ; physiopathology ; Female ; Humans ; Infant ; Male ; Piracetam ; administration & dosage ; analogs & derivatives ; therapeutic use ; Prospective Studies ; Treatment Outcome

Nefopam (NFP) is a non-opioid, non-steroidal, centrally acting analgesic drug that is derivative of the non-sedative benzoxazocine, developed and known in 1960s as fenazocine. Although the mechanisms of analgesic action of NFP are not well understood, they are similar to those of triple neurotransmitter (serotonin, norepinephrine, and dopamine) reuptake inhibitors and anticonvulsants. It has been used mainly as an analgesic drug for nociceptive pain, as well as a treatment for the prevention of postoperative shivering and hiccups. Based on NFP's mechanisms of analgesic action, it is more suitable for the treatment of neuropathic pain. Intravenous administration of NFP should be given in single doses of 20 mg slowly over 15-20 min or with continuous infusion of 60-120 mg/d to minimize adverse effects, such as nausea, cold sweating, dizziness, tachycardia, or drowsiness. The usual dose of oral administration is three to six times per day totaling 90-180 mg. The ceiling effect of its analgesia is uncertain depending on the mechanism of pain relief. In conclusion, the recently discovered dual analgesic mechanisms of action, namely, a) descending pain modulation by triple neurotransmitter reuptake inhibition similar to antidepressants, and b) inhibition of long-term potentiation mediated by NMDA from the inhibition of calcium influx like gabapentinoid anticonvulsants or blockade of voltage-sensitive sodium channels like carbamazepine, enable NFP to be used as a therapeutic agent to treat neuropathic pain.
Administration, Intravenous ; Administration, Oral ; Analgesia ; Analgesics, Non-Narcotic ; Anticonvulsants ; Antidepressive Agents ; Calcium ; Carbamazepine ; Dizziness ; Drug-Related Side Effects and Adverse Reactions ; Hiccup ; Long-Term Potentiation ; Molecular Mechanisms of Pharmacological Action ; N-Methylaspartate ; Nausea ; Nefopam* ; Neuralgia* ; Neurotransmitter Agents ; Nociceptive Pain ; Norepinephrine ; Shivering ; Sleep Stages ; Sodium Channels ; Sweat ; Sweating ; Tachycardia

OBJECTIVETo study the efficacy of levetiracetam (LEV) combined with short-term clonazepam (CZP) in the treatment of electrical status epilepticus during sleep (ESES) in children with benign childhood epilepsy with centrotemporal spikes (BECCT).

METHODSFifteen children (9 boys and 6 girls) diagnosed with BECCT with ESES, who had continuous spike-and-wave accounting for over 85% of the non-rapid eye movement sleep as monitored by 24-hours ambulatory EEG or 3-hours video EEG, were enrolled. The clinical manifestations and EEG characteristics of patients were retrospectively analyzed. These children received two months of CZP treatment in addition to oral LEV [20-40 mg/(kg·d)]. All patients were followed up for 6-18 months.

RESULTSThe 15 children were orally given LEV in the early stage, but showed no improvement when reexamined by EEG or had seizures during treatment. Then, they received LEV in combination with short-term CZP. Re-examinations at 1 and 6 months after treatment showed that 14 cases had significantly reduced discharge (only little discharge in the Rolandic area) or no discharge, as well as completely controlled seizure; one case had recurrent ESES and two epileptic seizures during follow-up. The recurrent case received the combination therapy again, and re-examinations 1 and 6 months later revealed normal EEG; no seizure occurred in the 8 months of follow-up.

CONCLUSIONSLEV combined with short-term CZP is effective and has few side effects in treating ESES syndrome among children with BECCT.

Anticonvulsants ; administration & dosage ; Child ; Child, Preschool ; Clonazepam ; administration & dosage ; Drug Therapy, Combination ; Electroencephalography ; Epilepsy, Rolandic ; drug therapy ; physiopathology ; Female ; Humans ; Male ; Piracetam ; administration & dosage ; analogs & derivatives ; Retrospective Studies ; Sleep ; physiology ; Status Epilepticus ; drug therapy ; physiopathology

OBJECTIVETo investigate the antipyretic and anticonvulsant activities of n-hexane fraction of Viola betonicifolia (V. betonicifolia).

METHODSThe antipyretic effect was scrutinized using brewer's yeast induced pyrexia and anticonvlsion effect was tested using pentylenetetrazol and strychnine induced convulsion in mice.

RESULTSN-hexane fraction of V. betonicifolia demonstrated highly significant antipyretic activity during various assessment times (1-5 h) when challenged in yeast induced pyrexia test. The effect was in a dose dependent manner with maximum attenuation (82.50%) observed at 300 mg/kg i.p. When tested in pentylenetetrazol induced convulsion test, the 1st stage (Ear and facial twitching) and 2nd stage (Convulsive wave through the body) was 100% protected during 24 h at all the test doses (300, 400 and 500 mg/kg i.p.), while the latency time of remaining stages was significantly increased. The maximum effect was observed by n-hexane fraction of V. betonicifolia at 400 and 500 mg/kg i.p., as the latency time for generalized clonic-tonic seizure (5th stage) was increased up to 25.34 min. However, n-hexane fraction of V. betonicifolia had no protection in strychnine induced convulsion test.

CONCLUSIONSIn conclusion, phytopharmacological studies provide scientific foundation to the folk uses of the plant in the treatment of pyrexia and neurological disorders.

Animals ; Anticonvulsants ; administration & dosage ; chemistry ; pharmacology ; Antipyretics ; administration & dosage ; chemistry ; pharmacology ; Disease Models, Animal ; Female ; Fever ; drug therapy ; etiology ; Hexanes ; chemistry ; Male ; Mice ; Plant Extracts ; administration & dosage ; chemistry ; pharmacology ; Seizures ; chemically induced ; drug therapy ; Viola ; chemistry

OBJECTIVETo investigate the effect of ketogenic diet (KD) on the clinical and electroencephalogram features in children with pharmacoresistant epileptic encephalopathy.

METHODThirty-one children (19 boys, 12 girls) aged 7 months to 7 years (mean 2 years 5 month) with epilepsy refractory to conventional antiepileptic drugs (AEDs) were included in this study. In addition to their original AED treatment, the children were assigned to different ketogenic diets based on their age. The prospective electro-clinical assessment was performed prior to the KD and then one week, one month and again 3 months after the initiation of therapy, respectively.

RESULTThe reduction of seizure frequency in 52%, 68% and 71% of all patients exceeded 50% one week, one month and three months after KD treatment respectively. KD is particularly effective in myoclonic astatic epilepsy (MAE; Doose Syndrome) and West syndrome with 100% and 81.25% of the patients having a greater than 50% seizure reduction, respectively. After 3 months of KD treatment, more than 2/3 patients experienced a reduction in interictal epileptiform discharges (IEDs) and improvement in EEG background.

CONCLUSIONThe clinical and electroencephalographic improvement confirms that KD is beneficial in children with refractory epilepsy.

Anticonvulsants ; therapeutic use ; Brain ; diagnostic imaging ; physiopathology ; Child ; Child, Preschool ; Diet, Ketogenic ; methods ; Dietary Fats ; administration & dosage ; Electroencephalography ; Epilepsy ; diagnosis ; diet therapy ; drug therapy ; Female ; Humans ; Infant ; Intellectual Disability ; diet therapy ; drug therapy ; Lennox Gastaut Syndrome ; Male ; Radiography ; Retrospective Studies ; Spasms, Infantile ; diet therapy ; drug therapy ; Syndrome ; Time Factors ; Treatment Outcome

Anticonvulsants ; administration & dosage ; therapeutic use ; Brain ; diagnostic imaging ; physiopathology ; Child ; Child, Preschool ; Chromosome Deletion ; Chromosome Disorders ; diagnosis ; genetics ; Chromosomes, Human, Pair 20 ; genetics ; Electroencephalography ; Epilepsy ; diagnosis ; drug therapy ; genetics ; Epilepsy, Complex Partial ; diagnosis ; drug therapy ; genetics ; Humans ; Karyotyping ; Radiography ; Ring Chromosomes