-
1.
Effects of Second-Generation Antiepileptic Drugs Compared to First-Generation Antiepileptic Drugs on Bone Metabolism in Patients with Epilepsy: A Meta-Analysis.
Fu, J, Peng, L, Li, J, Tao, T, Chen, Y
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2019;(8):511-521
Abstract
We conducted this meta-analysis to evaluate effects of second-generation anti-epileptic drugs (AEDs; levetiracetam, lamotrigine) compared to first-generation AEDs (valproic acid, carbamazepine) on bone metabolism in epilepsy patients. PubMed, Web of Science, Clinical trials.gov, Wanfang, and China national knowledge infrastructure databases were searched. Ten trials were included. Results showed: (1) The overall SMD for changes of serum calcium, phosphorus, ALP, and PTH levels from baseline of LEV versus first-generation AEDs were 1.00 (95% CI=0.23-1.77, Z=2.56, p=0.01), 0.98 (95% CI=- 0.05 to 2.01, Z=1.86, p=0.06), - 1.17 (95% CI=- 2.08 to - 0.25, Z=2.50, p=0.01), 0.07 (95% CI=- 0.14 to 0.27, Z=0.63, p=0.53), respectively. (2) The overall SMD for changes of serum calcium, phosphorus, ALP, and PTH levels from baseline of LTG versus first-generation AEDs were -0.16 (95% CI=- 0.47 to 0.16, Z=0.99, p=0.32), -0.05 (95% CI=- 0.55 to 0.44, Z=0.22, p=0.83), 0.10 (95% CI=- 0.53 to 0.73, Z=0.31, p=0.75), -0.05 (95% CI=- 0.52 to 0.42, Z=0.22, p=0.83), respectively. Overall, our results indicate that compared to first-generation AEDs, LEV has less adverse effects on blood bone metabolism markers in epilepsy patients, while LTG does not. However, due to small number of included studies, our results warrant additional research.
-
2.
Short-Term Vitamin D3 Supplementation in Children with Neurodisabilities: Comparison of Two Delivery Methods.
Penagini, F, Borsani, B, Maruca, K, Giosia, V, Bova, S, Mastrangelo, M, Zuccotti, GV, Mora, S
Hormone research in paediatrics. 2017;(3-4):281-284
Abstract
BACKGROUND/AIMS: Vitamin D deficiency is common in children with neurodisabilities. Oral vitamin D3 may not be absorbed appropriately due to dysphagia and tube feeding. The aim of this study was to compare efficacy of vitamin D3 buccal spray with that of oral drops. METHODS Twenty-four children with neurodisabilities (5-17 years) and vitamin D deficiency (25(OH)D ≤20 ng/mL) were randomized to receive vitamin D3 buccal spray 800 IU/daily (n = 12) or oral drops 750 IU/daily (n = 12) for 3 months during winter. RESULTS Both groups had a significant increase in 25(OH)D (z = 150; p < 0.0001). The differences between baseline and final parathyroid hormone measurements did not reach significance in both groups. Markers of bone formation and resorption did not change significantly in both groups. The satisfaction with the formulation was significantly higher in the patients using spray. CONCLUSION Vitamin D3 supplementation with buccal spray and oral drops are equally effective in short-term treatment of vitamin D deficiency in children with neurodisabilities. Buccal spray may be more acceptable by the patients.
-
3.
Medium-chain triglyceride ketogenic diet, an effective treatment for drug-resistant epilepsy and a comparison with other ketogenic diets.
Liu, YM, Wang, HS
Biomedical journal. 2013;(1):9-15
Abstract
The ketogenic diet (KD) is one of the most effective therapies for drug-resistant epilepsy. The efficacy of the medium-chain triglyceride KD (MCTKD) is as excellent as the classic KD (CKD), which has been documented in several subsequent retrospective, prospective, and randomized studies. MCT oil is more ketogenic than long-chain triglycerides. Therefore, the MCTKD allows more carbohydrate and protein food, which makes the diet more palatable than the CKD. The MCTKD is not based on diet ratios as is the CKD, but uses a percentage of calories from MCT oil to create ketones. There has also been literature which documents the associated gastrointestinal side effects from the MCTKD, such as diarrhea, vomiting, bloating, and cramps. Therefore, the MCTKD has been an underutilized diet therapy for intractable epilepsy among children.The author has used up to >70% MCTKD diet to maximize seizure control with gastrointestinal side effects optimally controlled. As long as health care professionals carefully manage MCTKD, many more patients with epilepsy who are not appropriate for CKD or modified Atkins diet or low glycemic index treatment will benefit from this treatment. A comparison between the MCTKD and other KDs is also discussed.
-
4.
Vagus nerve stimulation in children with intractable epilepsy: a randomized controlled trial.
Klinkenberg, S, Aalbers, MW, Vles, JS, Cornips, EM, Rijkers, K, Leenen, L, Kessels, FG, Aldenkamp, AP, Majoie, M
Developmental medicine and child neurology. 2012;(9):855-61
-
-
Free full text
-
Abstract
AIM: The aim of this study was to evaluate the effects of vagus nerve stimulation (VNS) in children with intractable epilepsy on seizure frequency and severity and in terms of tolerability and safety. METHOD In this study, the first randomized active controlled trial of its kind in children, 41 children (23 males; 18 females; mean age at implantation 11y 2mo, SD 4y 2mo, range 3y 10mo-17y 8mo) were included. Thirty-five participants had localization-related epilepsy (25 symptomatic; 10 cryptogenic), while six participants had generalized epilepsy (four symptomatic; two idiopathic). During a baseline period of 12 weeks, seizure frequency and severity were recorded using seizure diaries and the adapted Chalfont Seizure Severity Scale (NHS3), after which the participants entered a blinded active controlled phase of 20 weeks. During this phase, half of the participants received high-output VNS (maximally 1.75mA) and the other half received low-output stimulation (0.25mA). Finally, all participants received high-output stimulation for 19 weeks. For both phases, seizure frequency and severity were assessed as during the baseline period. Overall satisfaction and adverse events were assessed by semi-structured interviews. RESULTS At the end of the randomized controlled blinded phase, seizure frequency reduction of 50% or more occurred in 16% of the high-output stimulation group and in 21% of the low-output stimulation group (p=1.00). There was no significant difference in the decrease in seizure severity between participants in the stimulation groups. Overall, VNS reduced seizure frequency by 50% or more in 26% of participants at the end of the add-on phase The overall seizure severity also improved (p<0.001). INTERPRETATION VNS is a safe and well-tolerated adjunctive treatment of epilepsy in children. Our results suggest that the effect of VNS on seizure frequency in children is limited. However, the possible reduction in seizure severity and improvement in well-being makes this treatment worth considering in individual children with intractable epilepsy.
-
5.
Sodium valproate versus lamotrigine: a randomised comparison of efficacy, tolerability and effects on circulating androgenic hormones in newly diagnosed epilepsy.
Stephen, LJ, Sills, GJ, Leach, JP, Butler, E, Parker, P, Hitiris, N, Leach, VM, Wilson, EA, Brodie, MJ
Epilepsy research. 2007;(2-3):122-9
Abstract
We have performed a randomised, prospective study to compare the efficacy and tolerability of sodium valproate (VPA) and lamotrigine (LTG) monotherapy, and their effects on circulating androgenic hormones, in newly diagnosed epilepsy. A total of 225 patients (116 male; median age 35 years, range 13-80 years) were followed-up at 6-weekly intervals until they reached an end-point (12 months' seizure freedom; withdrawal due to intolerable side-effects; lack of efficacy despite adequate dosing). Twelve month seizure-free rates were identical (47%) in the VPA (n=111) and LTG (n=114) treatment arms. More patients taking VPA withdrew from the study due to adverse events (26 VPA versus 15 LTG; p=0.046). Eight patients, all taking VPA, dropped out during the first 6 months due to weight gain. There were no changes in mean serum concentrations of testosterone, sex-hormone binding globulin and androstenedione or in the free androgen index after 6 or 12 months' treatment with either drug in 112 patients who fulfilled the criteria for hormone analysis. No difference in efficacy was found between VPA and LTG in our patients with newly diagnosed epilepsy. LTG appeared to be better tolerated. Neither drug appeared to alter the circulating levels of androgenic hormones.
-
6.
Epilepsy-related injuries.
Wirrell, EC
Epilepsia. 2006;:79-86
-
-
Free full text
-
Abstract
Only one prospective, controlled study has compared the risk of accidental injury in persons with epilepsy to controls without seizures. A mildly increased risk in the epilepsy group was found, predominantly due to injuries that result directly from a seizure. With regard to injury type, this study found significantly higher rates of only head and soft tissue injury; however, most injuries were minor. Several retrospective, population-based studies have suggested increased rates of more serious injury types. Submersion injury has a high mortality; the risk of submersion in children with epilepsy is 7.5-13.9 fold higher than in the general population. The risk of fracture is elevated approximately twofold, either resulting directly from seizure-induced injury or predisposed by drug-induced reduction in bone mineral density. Burns due to seizures account for between 1.6% and 3.7% of burn unit admissions. The risk of motor vehicle accidents in drivers with epilepsy also appears increased, albeit marginally. Several factors predispose to a higher risk of injury among those with epilepsy. Seizures resulting in falls increase the risk of concussion and other injuries. Higher seizure frequency, lack of a prolonged seizure-free interval, comorbid attention deficit disorder, or cognitive handicap may also increase the risk of injury. While some restrictions are necessary to protect the safety of the person with epilepsy, undue limitations may further limit achievement of independence. Given the high morbidity and mortality of submersion injury, those with active epilepsy should bathe or swim only with supervision; however, showering is a reasonable option. Appropriate vitamin D and calcium supplementation and periodic measurement of bone mineral density in those at risk for osteopenia are recommended.
-
7.
Active control trials for epilepsy: avoiding bias in head-to-head trials.
French, JA, Kryscio, RJ
Neurology. 2006;(9):1294-5
-
8.
Susceptibility genes for complex epilepsy.
Mulley, JC, Scheffer, IE, Harkin, LA, Berkovic, SF, Dibbens, LM
Human molecular genetics. 2005;:R243-9
Abstract
Common idiopathic epilepsies are, clinically and genetically, a heterogeneous group of complex seizure disorders. Seizures arise from periodic neuronal hyperexcitability of unknown cause. The genetic component is mostly polygenic, where each susceptibility gene in any given individual is likely to represent a small component of the total heritability. Two susceptibility genes have been so far identified, where genetic variation is associated with experimentally demonstrated changes in ion channel properties, consistent with seizure susceptibility. Rare variants and a polymorphic allele of the T-type calcium channel CACNA1H and a polymorphic allele and a rare variant of the GABA(A) receptor delta subunit gene have differential functional effects. We speculate that these and other as yet undiscovered susceptibility genes for complex epilepsy could act as 'modifier' loci, affecting penetrance and expressivity of the mutations of large effect in those 'monogenic' epilepsies with simple inheritance that segregate through large families. Discovery of epilepsy-associated ion channel defects in these rare families has opened the door to the discovery of the first two susceptibility genes in epilepsies with complex genetics. The susceptibility genes so far detected are not commonly involved in complex epilepsy suggesting the likelihood of considerable underlying polygenic heterogeneity.
-
9.
Bone mineral metabolism changes in epileptic children receiving valproic acid.
Oner, N, Kaya, M, Karasalihoğlu, S, Karaca, H, Celtik, C, Tütüncüler, F
Journal of paediatrics and child health. 2004;(8):470-3
Abstract
OBJECTIVE The aim of this study was to evaluate bone mineral density (BMD) in epileptic children receiving valproic acid (VPA) and to determine differences between osteopenic and non-osteopenic children. METHODS Thirty-three epileptic children, receiving VPA for at least 6 months, were compared with 33 healthy children for BMD. BMD was measured by dual-energy X-ray absorptiometry at lumbar vertebrae, femoral neck and greater trochanter. Serum calcium, phosphorus, alkaline phosphates, osteocalcin and VPA levels were also determined. RESULTS Patient's osteocalcin levels were significantly higher (P = 0.02) and femur and trochanter BMD values were significantly lower (P = 0.04 and P = 0.03, respectively). Duration of VPA therapy was significantly longer and doses of VPA were significantly higher in seven osteopenic patients compared with 26 non-osteopenic patients. Osteopenic patients (4.6 +/- 2.4 years) were younger than non-osteopenic patients (7.8 +/- 3.2 years) (P = 0.01). CONCLUSION Long-term and high dose VPA therapy may cause osteopenia, primarily in younger epileptic children. These patients should be followed closely by BMD measurements.
-
10.
Reversible parkinsonism with normal beta-CIT-SPECT in patients exposed to sodium valproate.
Easterford, K, Clough, P, Kellett, M, Fallon, K, Duncan, S
Neurology. 2004;(8):1435-7
Abstract
After reports of reversible parkinsonism and cognitive impairment with sodium valproate (VPA), the authors examined 50 consecutive patients taking VPA and 20 patients taking carbamazepine. Three patients taking VPA exhibited unequivocal parkinsonism with Unified Parkinson Disease Rating Scale scores >30. VPA was withdrawn from two patients with improvement of symptoms. Reduction in VPA dosage in the third patient produced no improvement. beta-CIT-SPECT scans were normal, suggesting dopaminergic neuronal loss is not the underlying mechanism.