OBJECTIVE: To systematically evaluate the efficacy and safety of levetiracetam (LEV) versus phenytoin (PHT) as second-line drugs for the treatment of convulsive status epilepticus (CSE) in children. METHODS: English and Chinese electronic databases were searched for the randomized controlled trials comparing the efficacy and safety of LEV and PHT as second-line drugs for the treatment of childhood CSE. RevMan 5.3 software was used for data analysis. RESULTS: Seven studies with 1 434 children were included. The Meta analysis showed that compared with the PHT group, the LEV group achieved a significantly higher control rate of CSE ( CONCLUSIONS LEV has a better clinical effect than PHT in the treatment of children with CSE and does not increase the incidence rate of adverse events.
Anticonvulsants/adverse effects* ; Child ; Humans ; Levetiracetam/therapeutic use* ; Pharmaceutical Preparations ; Phenytoin/adverse effects* ; Status Epilepticus/drug therapy*

phenytoin (158, 5.4%). In limited to severe drug eruptions (DRESS, SJS, and TEN; total 241 reports), the causative AEDs were carbamazepine (117, 48.8%), lamotrigine (57, 23.8%), valproic acid (20, 8.3%), phenytoin (15, 6.3%), and oxcarbazepine (10, 4.2%). When comparing aromatic AED with non-aromatic AED, aromatic AEDs were more likely to be associated with severe drug eruption (aromatic AEDs: 204/1,793 versus non-aromatic AEDs: 37/1,149; OR, 3.86; 95% CI, 2.7–5.5). Death was reported in 7 cases; DRESS was the most commonly reported adverse event (n = 5), and lamotrigine was the most common causative AED (n = 5).CONCLUSION: Although most cutaneous drug eruptions in this study were rash or urticaria, approximately 8% of reports were of severe or life-threatening adverse drug reactions, such as SJS, TEN, or DRESS. When hypersensitivity skin reactions occurred, aromatic AEDs were associated with 4 fold the risk of SJS/TEN/DRESS compared with non-aromatic AEDs. Our findings further emphasize that high risk AEDs should be prescribed under careful monitoring, and early detection and prompt interventions are needed to prevent severe complications.]]>
Anticonvulsants ; Carbamazepine ; Drug Eruptions ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Exanthema ; Hypersensitivity ; Korea ; Pharmacovigilance ; Phenytoin ; Risk Management ; Skin ; Stevens-Johnson Syndrome ; Urticaria ; Valproic Acid

Objectives: To identify factors that predict the occurrence of seizures in patients with aneurysmal subarachnoid hemorrhage (SAH) and to evaluate the efficacy of antiepileptic drugs (AEDs) in preventing in-hospital seizures among patients who undergo clip occlusion of ruptured intracranial aneurysms. Methods: In this retrospective study, the medical charts of 205 patients admitted for aneurysmal SAH in Philippine General Hospital (PGH) and who underwent craniotomy and clipping of aneurysm from January 2011 to June 2014 were reviewed. Demographic, radiologic, and clinical factors were converted into categorical variables and their association with the occurrence of seizures analyzed. The incidence of seizures among patients who received an AED (AED cohort) and those who did not receive an AED (No AED cohort) were compared. Secondarily, the effects of seizures and AED use on early postoperative outcomes were determined using the Glasgow Outcome Scale (GOS) on the day of discharge. Results: Among 205 patients with aneurysmal SAH, 31 (15.1%) developed seizures. 21 (10.2%) had seizures at onset of SAH and only seven (3.4%) had in-hospital seizures. Aneurysm re-rupture (OR 5.26, p-value 0.045) and the presence of a parenchymal clot (OR 2.90, p-value 0.043) were independent predictors for seizure occurrence. There was no significant difference in the incidence of seizures in the AED cohort and in the No AED cohort (4/100, 4% vs. 3/99, 3%, p-value 0.714). AED use was associated with a higher proportion of patients with a discharge GOS score of 3 or less (28.0% vs 12.1%, p-value 0.005). Conclusion The results of the study do not support the routine use of AEDs in patients with aneurysmal SAH.
Seizures ; Aneurysm ; Subarachnoid Hemorrhage ; Craniotomy ; Phenytoin ; Levetiracetam ; Anticonvulsants

Antiepileptic drugs (AEDs) can induce severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. We performed HLA genotyping and lymphocyte activation tests (LATs) for five AED-induced SCAR patients (three males and two females; aged 40–66 years old). Three patients were treated with carbamazepine (CBZ) for pain control, one was treated with phenytoin (PHT) for seizure prevention, and one was treated with valproic acid (VPA) for seizure prevention. One patient was diagnosed with CBZ-induced DRESS syndrome and the remaining patients were diagnosed with SJS. All patients recovered from SCARs after stopping suspicious drugs and supportive care. LATs were conducted to confirm the culprit drug responsible for inducing SCARs; and LAT results were positive for the suspected culprit drugs, in all except in one case. HLA-A,
Alleles ; Anticonvulsants ; Carbamazepine ; Cicatrix ; Drug Hypersensitivity Syndrome ; Female ; HLA-A Antigens ; Humans ; Long-Acting Thyroid Stimulator ; Lymphocyte Activation ; Lymphocytes ; Male ; Methods ; Phenytoin ; Seizures ; Stevens-Johnson Syndrome ; Valproic Acid

BACKGROUND AND PURPOSE: There is sparsity of quality evidence for the use of drugs after first-line benzodiazepines in convulsive status epilepticus in children. The aim of the study was to compare the clinical efficacy and safety of intravenous levetiracetam versus intravenous phenytoin as second-line drugs in the management of generalized convulsive status epilepticus in children. METHODS: This open-label randomized controlled trial was conducted in the Emergency Department of The Children's Hospital and The Institute of Child Health, Multan, Pakistan over a period of 4 years and 6 months from January 2014 to June 2018. This study included 600 children with generalized convulsive status epilepticus: 300 in the 40 mg/kg levetiracetam group, and 300 in the 20 mg/kg phenytoin group. Cessation of a clinical seizure (seizure cessation rate) within 30 minutes after the end of drug administration was the primary outcome in this study, and the presence or absence of adverse effects was noted as the secondary outcome. Data were analyzed using SPSS (version 20.0). RESULTS: The children in the levetiracetam and phenytoin were aged 3.5±0.2 and 3.4±0.2 years (mean±SD), respectively, their seizure durations before the start of treatment were 25.1±0.6 and 23.8±0.4 minutes, and their treatment efficacies were 278/300 (92.7%) and 259/300 (83.3%). Levetiracetam was significantly more effective than phenytoin (p=0.012), with no significant difference in safety. Adverse events were observed in eight children in the phenytoin group. CONCLUSIONS: Levetiracetam is significantly more effective than phenytoin for the treatment of convulsive status epilepticus in children who have failed to respond to benzodiazepines.
Benzodiazepines ; Child Health ; Child ; Emergency Service, Hospital ; Humans ; Pakistan ; Phenytoin ; Seizures ; Status Epilepticus ; Treatment Outcome

Paroxysmal dysarthria and ataxia is characterized by abrupt onset of dysarthria and ataxia of unilateral limbs for seconds. We present a 45-year-old female patient with paroxysmal symptoms of dysarthria, right-sided ataxia, and a persistent symptom of upbeating nystagmus. Her brain fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging indicated potential diagnosis of demyelinating disease. The paroxysmal and persistent symptoms have recovered after phenytoin administration. Sodium channel blocker may play a role in reducing the ephaptic transmission in a demyelinated or re-myelinated lesion.
Ataxia ; Brain ; Demyelinating Diseases ; Diagnosis ; Dysarthria ; Extremities ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Phenytoin ; Sodium Channels

Drug reaction with eosinophilia and systemic symptoms(DRESS), which occurs 2–8 weeks after taking a medication is a rare and potentially life-threatening drug-induced hypersensitivity reaction, which includes skin eruption, hematologic abnormalities, lymphadenopathy, and internal organ such as liver, lung, kidney involvement. Antiepileptic agents (e.g., carbamazepine, lamotrigine, phenytoin, and phenobarbital) and allopurinol are the most commonly reported causes. However, new antiepileptic agents, such as oxcarbazepine, rarely cause drug reaction with eosinophilia and systemic symptoms. A 11-year-old boy who was administered oxcarbazepine for 34 days developed widespread rashes, facial edema, fever, cough, nasal stuffiness, tonsillitis, and cervical lymphadenopathy. Laboratory test results showed leukocytosis, eosinophilia, thrombocytosis, elevated c-reactive protein, and elevated liver transaminase levels. As we suspected drug reaction with eosinophilia and systemic symptoms, we immediately withdrew oxcarbazepine and commenced corticosteroid therapy. The patient's skin lesions and abnormal laboratory results slowly improved. Before change the antiepileptic agents, we performed human leukocyte antigen (HLA) typing to assess the genetic risk factors of the drug reaction and the result was positive for HLA DRB1*04:03 known to cause severe acute drug hypersensitivity, such as Stevens-Johnson syndrome by oxcarbazepine in Koreans. We have presented the first report of drug reaction with eosinophilia and systemic symptoms associated with oxcarbazepine in a patient with HLA DRB1*04:03. Although DRESS by oxcarazepine is extremely rare and unpredictable, when suspected clinical symptoms occur, it is necessary to interrupt the causative drug rapidly and confirming the patient's HLA typing may help to select a safer alternative drug.
Allopurinol ; Anticonvulsants ; C-Reactive Protein ; Carbamazepine ; Child ; Cough ; Drug Eruptions ; Drug Hypersensitivity ; Drug Hypersensitivity Syndrome* ; Edema ; Eosinophilia ; Exanthema ; Fever ; Histocompatibility Testing ; Humans ; Hypersensitivity ; Kidney ; Leukocytes ; Leukocytosis ; Liver ; Lung ; Lymphatic Diseases ; Male ; Palatine Tonsil ; Phenytoin ; Risk Factors ; Skin ; Stevens-Johnson Syndrome ; Thrombocytosis ; Tonsillitis

BACKGROUND AND PURPOSE: It has been reported that taking antiepileptic drugs (AEDs) may increase the risk of atherosclerosis. We performed a meta-analysis to evaluate the carotid artery intima-media thickness (CA-IMT) as a surrogate factor for atherosclerosis in epileptic patients. METHODS: We searched NCBI (PubMed), ISI Web of Knowledge, EMBASE, and the Cochrane Library databases for studies of the association between AEDs and CA-IMT in epileptic patients. A random-effects meta-analysis was used to pool results across studies. RESULTS: Fifteen studies involving 1,775 epileptic patients were included in the analysis. The overall CA-IMT was significantly larger among users of AEDs [mean difference (MD)=0.09 mm, 95% confidence interval (CI)=0.06–0.12 mm). When stratified by age, the MD was similar in adult patients (MD=0.09 mm, 95% CI=0.06–0.13 mm), but no significant difference was observed in children (MD=0.03 mm, 95% CI=0.00–0.07 mm). Regarding specific AEDs, monotherapy with carbamazepine (CBZ) or valproic acid (VPA) was associated with a larger CA-IMT, while phenytoin monotherapy was not and the result for lamotrigine was inconclusive. CONCLUSIONS: This study suggests that using AEDs is associated with the CA-IMT in patients with epilepsy, particularly for adult patients. In particular, CBZ and VPA may be related to a significant increase in CA-IMT.
Adult ; Anticonvulsants* ; Atherosclerosis ; Carbamazepine ; Carotid Arteries* ; Child ; Epilepsy ; Humans ; Phenytoin ; Valproic Acid

Increased plasma insulin levels are often observed in exogenous insulin overdose patients. However, plasma insulin level may decrease with time. We report a case of low plasma insulin level hypoglycemia after insulin lispro overdose. The patient was a 37-year-old man with no previous medical history who suspected insulin lispro overdose. Upon arrival, his Glasgow coma scale was 3 points and his blood sugar level (BSL) was 24 mg/dl. We found five humalog-quick-pen (insulin lispro) in his bag. There was no elevation of glucose level, despite an initial 50 ml bolus of 50% glucose and 150 cc/hr of 10% dextrose continuous intravenous infusion. He also suffered from generalized tonic-clonic seizure, which was treated with lorazepam and phenytoin. We conducted endotracheal intubation, after which he was admitted to the intensive care unit (ICU). There were recurrent events of hypoglycemia below BSL<50 mg/dl after admission. We repeatedly infused 50 ml 50% glucose 10 times and administered 1 mg of glucagon two times. The plasma insulin level was 0.2 uU/ml on initial blood sampling and 0.2 uU/ml after 5 hours. After 13 hours, his BSL stabilized but his mental status had not recovered. Diffuse brain injury was observed upon magnetic resonance imaging (MRI) and severe diffuse cerebral dysfunction was found on electroencephalography (EEG). Despite 35 days of ICU care, he died from ventilator associated pneumonia.
Adult ; Blood Glucose ; Brain Injuries ; Electroencephalography ; Glasgow Coma Scale ; Glucagon ; Glucose ; Humans ; Hypoglycemia* ; Infusions, Intravenous ; Insulin Lispro* ; Insulin* ; Intensive Care Units ; Intubation, Intratracheal ; Lorazepam ; Magnetic Resonance Imaging ; Phenytoin ; Plasma* ; Pneumonia, Ventilator-Associated ; Seizures

Synaptic vesicle protein 2A (SV2A) involvement has been reported in the animal models of epilepsy and in human intractable epilepsy. The difference between pharmacosensitive epilepsy and pharmacoresistant epilepsy remains poorly understood. The present study aimed to observe the hippocampus SV2A protein expression in amygdale-kindling pharmacoresistant epileptic rats. The pharmacosensitive epileptic rats served as control. Amygdaloid-kindling model of epilepsy was established in 100 healthy adult male Sprague-Dawley rats. The kindled rat model of epilepsy was used to select pharmacoresistance by testing their seizure response to phenytoin and phenobarbital. The selected pharmacoresistant rats were assigned to a pharmacoresistant epileptic group (PRE group). Another 12 pharmacosensitive epileptic rats (PSE group) served as control. Immunohistochemistry, real-time PCR and Western blotting were used to determine SV2A expression in the hippocampus tissue samples from both the PRE and the PSE rats. Immunohistochemistry staining showed that SV2A was mainly accumulated in the cytoplasm of the neurons, as well as along their dendrites throughout all subfields of the hippocampus. Immunoreactive staining level of SV2A-positive cells was 0.483 ± 0.304 in the PRE group and 0.866 ± 0.090 in the PSE group (P < 0.05). Real-time PCR analysis demonstrated that 2(-ΔΔCt) value of SV2A mRNA was 0.30 ± 0.43 in the PRE group and 0.76 ± 0.18 in the PSE group (P < 0.05). Western blotting analysis obtained the similar findings (0.27 ± 0.21 versus 1.12 ± 0.21, P < 0.05). PRE rats displayed a significant decrease of SV2A in the brain. SV2A may be associated with the pathogenesis of intractable epilepsy of the amygdaloid-kindling rats.
Amygdala ; drug effects ; metabolism ; physiopathology ; Animals ; Anticonvulsants ; pharmacology ; Disease Models, Animal ; Drug Resistance ; Electric Stimulation ; Epilepsy ; drug therapy ; genetics ; metabolism ; pathology ; Gene Expression Regulation ; Hippocampus ; drug effects ; metabolism ; physiopathology ; Kindling, Neurologic ; drug effects ; genetics ; metabolism ; pathology ; Male ; Membrane Glycoproteins ; genetics ; metabolism ; Nerve Tissue Proteins ; genetics ; metabolism ; Phenobarbital ; pharmacology ; Phenytoin ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Synaptic Transmission ; Synaptic Vesicles ; drug effects ; metabolism ; pathology