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- Ben-Menachem, Elinor, 1945
(författare)
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Pregabalin pharmacology and its relevance to clinical practice.
- 2004
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 45 Suppl 6, s. 13-8
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Forskningsöversikt (refereegranskat)abstract
- Pregabalin is a potent ligand for the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system that exhibits potent anticonvulsant, analgesic, and anxiolytic activity in a range of animal models. In addition, pregabalin has been shown to be a highly effective adjunctive therapy for partial seizures in clinical trials. Potent binding to the alpha-2-delta site reduces depolarization-induced calcium influx with a consequential modulation in excitatory neurotransmitter release. Pregabalin has no demonstrated effects on GABAergic mechanisms. Pregabalin demonstrates highly predictable and linear pharmacokinetics, a profile that makes it easy to use in clinical practice. Absorption is extensive, rapid, and proportional to dose. Time to maximal plasma concentration is approximately 1 h and steady state is achieved within 24-48 h. These characteristics reflect the observed onset of efficacy as early as day two in clinical trials. High bioavailability, a mean elimination half life (t(1/2)) of 6.3 h, and dose-proportional maximal plasma concentrations and total exposures predict a dose-response relationship in clinical practice and allow an effective starting dose of 150 mg/day in clinical practice without need for titration. Administration with food has no clinically relevant effect on the amount of pregabalin absorbed, providing for a dosing regimen uncomplicated by meals. Pregabalin does not bind to plasma proteins and is excreted virtually unchanged (<2% metabolism) by the kidneys. It is not subject to hepatic metabolism and does not induce or inhibit liver enzymes such as the cytochrome P450 system. Therefore, pregabalin is unlikely to cause, or be subject to, pharmacokinetic drug-drug interactions--an expectation that has been confirmed in clinical pharmacokinetic studies. However, dose adjustment may be necessary in patients with renal insufficiency. Thus, the pharmacological and pharmacokinetic profiles of pregabalin provide a predictable basis for its use in clinical practice.
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- Kimland, Elin, et al.
(författare)
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Levetiracetam-induced thrombocytopenia
- 2004
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Ingår i: Epilepsia. - : Wiley-Blackwell. - 0013-9580 .- 1528-1167. ; 45:7, s. 877-878
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Tidskriftsartikel (refereegranskat)
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- Azarbayjani, Faranak, et al.
(författare)
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Embryonic arrhythmia by inhibition of HERG channels : a common hypoxia-related teratogenic mechanism for antiepileptic drugs?
- 2002
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 43:5, s. 457-468
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: There is evidence that drug-induced embryonic arrhythmia initiates phenytoin (PHT) teratogenicity. The arrhythmia, which links to the potential of PHT to inhibit a specific potassium channel (Ikr), may result in episodes of embryonic ischemia and generation of reactive oxygen species (ROS) at reperfusion. This study sought to determine whether the proposed mechanism might be relevant for the teratogenic antiepileptic drug trimethadione (TMO). METHODS: Effects on embryonic heart rhythm during various stages of organogenesis were examined in CD-1 mice after maternal administration (125-1,000 mg/kg) of dimethadione (DMO), the pharmacologically active metabolite of TMO. Palatal development was examined after administration of a teratogenic dose of DMO and after simultaneous treatment with DMO and a ROS-capturing agent (alpha-phenyl-N-tert-butyl-nitrone; PBN). The Ikr blocking potentials of TMO and DMO were investigated in HERG-transfected cells by using voltage patch-clamping tests. RESULTS: DMO caused stage-specific (gestation days 9-13 only) and dose-dependent embryonic bradycardia and arrhythmia at clinically relevant maternal plasma concentrations (3-11 mM). Hemorrhage in the nasopharyngeal part of the embryonic palate (within 24 h) preceded cleft palate in fetuses at term. Simultaneous treatment with PBN significantly reduced the incidence of DMO-induced cleft palate, from 40 to 13%. Voltage patch-clamping studies showed that particularly DMO (70% inhibition), but also TMO, had Ikr blocking potential at clinically relevant concentrations. CONCLUSIONS: TMO teratogenicity, in the same way as previously shown for PHT, was associated with Ikr-mediated episodes of embryonic cardiac arrhythmia and hypoxia/reoxygenation damage.
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- Börjesson, L., et al.
(författare)
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Comparison between fMRI and Wada test
- 2004
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Ingår i: Epilepsia. - : Wiley-Blackwell. - 0013-9580 .- 1528-1167. ; 45:Suppl. 3, s. 84-84
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Language lateralisation in patients with epilepsy is more often atypical compared to a normal population. The Wada procedure for testing language and memory has some shortcomings; it is invasive and there is always a risk that the patient becomes too sedated, leading to difficulties in performing the tests. fMR1have shown promising results, showing good correlation to the Wadaprocedure concerning language-lateralisation. The aim of this studywas to investigate if fMRI could be used to determine which hemisphere was language dominant and compare the fMR1 results with the Wada-tests with a focus on patients with a complicated lateralisation.Method: 4 subjects were tested and they had a heterogeneous (I left handed, I ambidexter and 2 right handed) lateralisation and one had a severe dyslexia. A standard Wada procedure was used and compared with a fMRl investigation using a language paradigm.Results: The patients studied showed different language lateralisation patterns (2 left hemisphere and 2 bilateral). In two patients the two tests were fully concordant, in the others the fMRI showed a more bilateral pattern.Conclusion: fMR1 adds valuable information in the pre-surgical investigation for patients with a complex language lateralisation.
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- Källén, Kristina, et al.
(författare)
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Hypomotor seizures in infants and children.
- 2002
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 43:8, s. 882-888
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Hypomotor seizures (characterized by diminished behavioral activity with indeterminate level of consciousness) have been identified as an important seizure type in infants. Our goal was to investigate further the clinical and EEG features of hypomotor seizures. METHODS: We retrospectively reviewed 110 hypomotor seizures from 34 patients recorded with video-EEG. RESULTS: Twenty-seven (79%) patients were younger than 48 months, and seven (21%) were aged 4 to 15 years. Seventy-one (64%) seizures had regional or lateralized EEG onset, arising predominantly from temporal or parietal lobe regions. The other 39 (35%) seizures had generalized onset, usually with abrupt onset of diffuse rhythmic high-amplitude theta activity or diffuse electrodecrement and only rarely (two patients) with slow spike-wave complexes or 3-Hz spike-wave complexes. Hypomotor seizures with generalized EEG onset were significantly shorter than those with regional or lateralized onset (p = 0.01, GEE model). Unsustained head or eye movements and subtle mouth automatisms were commonly seen in hypomotor seizures with either focal or generalized onset. Seventeen percent of hypomotor seizures with focal onset evolved to include version of head and eyes or jerking of one arm, whereas 2% of generalized hypomotor seizures evolved to a cluster of spasms. CONCLUSIONS: Hypomotor seizures may be either focal or generalized. Regional EEG onsets were most often temporal or parietal, suggesting that focal hypomotor seizures may be a bland form of "complex partial" seizures with no or minimal automatisms, seen predominantly in infants. Generalized hypomotor seizures were rarely associated with an ictal pattern of generalized spike-wave complexes, suggesting a different mechanism from absence seizures seen later in life.
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- Lindberger, M, et al.
(författare)
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Gabapentin versus vigabatrin as first add-on for patients with partial seizures that failed to respond to monotherapy: a randomized, double-blind, dose titration study. GREAT Study Investigators Group. Gabapentin in Refractory Epilepsy Add-on Treatment.
- 2000
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 41:10, s. 1289-95
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Tidskriftsartikel (refereegranskat)abstract
- Our objective was to compare the efficacy and safety of gabapentin and vigabatrin as first-line add-on treatment in patients with partial epilepsy.This was a multicenter, double-blind, randomized dose titration study. After baseline assessment and randomization, the dose could be increased if seizures persisted and reduced if side effects occurred. Health-related quality of life was assessed at baseline and at the end of the study. By a protocol amendment post hoc, all randomized patients were offered a standardized perimetry examination at the end of the study. Improvement rate was the proportion of patients with a reduction of seizure frequency of at least 50% during an 8-week period without any adverse events causing withdrawal.One hundred two patients were randomized and analyzed on an intent-to-treat basis. The improvement rate was 48% in the gabapentin group and 56% in the vigabatrin group. The improvement rate, when per protocol criteria were fulfilled, was 57% in the gabapentin group and 59% in the vigabatrin group. The proportion of seizure-free patients was 31% in the gabapentin group and 39% in the vigabatrin group. There was no difference in quality-of-life scores between the groups. Perimetry after termination of the study on 64 patients showed abnormal results in 3 of 32 patients in the vigabatrin group.Approximately one third of the patients in both groups became seizure-free. Although no major differences were seen in terms of the improvement rate between the groups, equivalence between the two drugs was not found.
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- Lundberg, Staffan, et al.
(författare)
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Hippocampal region asymmetry assessed by 1H-MRS in rolandic epilepsy
- 2003
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 44:2, s. 205-210
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: In a previous study, we reported hippocampal abnormalities on magnetic resonance imaging (MRI) in six of 18 children with rolandic epilepsy (RE). In this study, metabolic changes were analyzed in the hippocampal region with proton magnetic resonance spectroscopy (1H-MRS). METHODS: In 13 children with electroclinically typical RE and 15 healthy controls, 1H-MRS results of both hippocampal regions were analyzed. The voxels, 2 x 2 x 4-cm each, were placed to include the head and body of the hippocampus. A PRESS sequence with TR 2,000 ms and TE 32 ms was used. Total N-acetylaspartate (tNAA), glutamine and glutamate (Glx), and choline compounds (tCho) were related to total creatine (tCr), and asymmetry indices (AIs) were calculated. MRI was performed in all 13 patients and in 13 controls. RESULTS: The tNAA/tCr AI of the hippocampal region was significantly higher in children with RE than in control children (z = 4.49; p < 0.001). The AIs of Glx/tCr and tCho/tCr did not show a significant difference between the groups. Lateralization of the interictal epileptiform activity corresponded with the lower tNAA/tCr ratio in 10 of 13 patients. MRI revealed a hippocampal asymmetry in four of 13 in the RE group, three of them showed concordance between the lateralization of the lower tNAA/tCr ratio and the smaller hippocampus. In the control group, a subtle asymmetry in four of 13 children was found. CONCLUSIONS: A significant asymmetry of the hippocampal regions, measured by tNAA/tCr ratios, indicates an abnormal neuronal function in children with RE.
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- Öhman, Inger, et al.
(författare)
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Topiramate kinetics during delivery, lactation, and in the neonate : Preliminary observations
- 2002
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 43:10, s. 1157-1160
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To study the pharmacokinetics of topiramate (TPM) during delivery, lactation, and in the neonate. Methods: TPM concentrations in plasma and breast milk were measured with fluorescence polarization immunoassay (FPIA) in five women with epilepsy treated with TPM during pregnancy and lactation. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from the newborns on three occasions (24, 48, and 72 h) after delivery. Blood and breast milk also were collected from mothers 2 weeks, and 1 and 3 months postpartum. Blood samples also were drawn from the infants during breast-feeding. Three of the mother-infant pairs were studied both at delivery and during lactation, two contributed with data from delivery only. Results: The umbilical cord plasma/maternal plasma ratios were close to unity, suggesting extensive transplacental transfer of TPM. The mean milk/maternal plasma concentration ratio was 0.86 (range, 0.67-1.1) at 2-3 weeks after delivery. The milk/maternal plasma concentration ratios at sampling 1 and 3 months after delivery were similar (0.86 and 0.69, respectively). Two to 3 weeks after delivery, two of the breast-fed infants had detectable (>0.9 ╡M) concentrations of TPM, although below the limit of quantification (2.8 ╡M), and one had an undetectable concentration. Conclusions: Our limited data suggest free passage of TPM over the placenta and an extensive transfer into breast milk. Breast-fed infants had very low TPM concentrations, and no adverse effects were observed in the infants.
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- Malmgren, K, et al.
(författare)
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Vigabatrin visual toxicity: evolution and dose dependence.
- 2001
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Ingår i: Epilepsia. - 0013-9580. ; 42:5, s. 609-15
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the prevalence and prognosis of visual field defects (VFDs) in epilepsy patients with and without vigabatrin (VGB) treatment; to investigate the possible relationship between VFDs and cumulative VGB dose, and to characterise the evolution of VFDs.A cohort of 155 presurgical candidates who had undergone full-field Goldmann perimetry (GP) was studied, 99 (64%) of whom had been treated with VGB. All GPs were reevaluated in 1998 by one experienced examiner, blinded to medication. Duration of treatment and total VGB dose were related to perimetric results.Twenty-five (16%) of the 155 patients had VFDs: Nineteen (19%) of the 99 VGB-treated patients, and six (11%) of the 56 patients unexposed to VGB. VGB-treated patients with VFDs had been treated significantly longer than those without VFDs. Cumulative VGB dose could be calculated for 84 patients. The prevalence of VFDs increased significantly with increasing total VGB-dose, from 4% in the 51 patients who had been exposed to
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| 27. |
- Tomson, T
(författare)
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Can we prevent SUDEP?
- 2004
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Ingår i: EPILEPSIA. - 0013-9580. ; 45, s. 24-24
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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