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T Tomson

Publications and source records attributed to T Tomson.

At least 37 records · Page 2Linked to original sources
PubMed2000

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.

PURPOSE: Our objective was to compare the efficacy and safety of gabapentin and vigabatrin as first-line add-on treatment in patients with partial epilepsy. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Acetates↗
PubMed2000

Cost minimization analysis of antiepileptic drugs in newly diagnosed epilepsy in 12 European countries.

A recent United Kingdom cost minimization analysis (CMA) of four antiepileptic drugs (AEDs) used to treat newly diagnosed adult epilepsy demonstrated that a new drug, lamotrigine (LTG), incurred higher costs than carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA), whose costs were similar. This analysis took account of each drug's side-effect and tolerability profile. The present analysis investigated the costs of treatment with LTG, CBZ, PHT, and VPA in 12 European countries. Data were derived from published sources and from a panel of locally based experts. When no published data were available, estimates were obtained using expert opinion by a consensus method. These data were incorporated into a treatment pathway model, which considered the treatment of patients during the first 12 months after diagnosis. The primary outcome considered was seizure freedom. Randomized controlled trials demonstrate that the drugs considered are equally effective in terms of their ability to achieve seizure freedom, and thus the most appropriate form of economic evaluation is a CMA. These trials provided data on the incidence of side effects, dosages, and retention rates. The economic perspective taken was that of society as a whole and the analysis was calculated on an "intent-to-treat" basis. Only direct medical costs were considered. In each country considered, LTG was twofold to threefold more expensive than the other drugs considered. A sensitivity analysis demonstrated that varying each of the assumptions (range defined by expert panels) did not significantly alter the results obtained.

Anticonvulsants↗
PubMed1999

Risk factors for sudden unexpected death in epilepsy: a case-control study.

BACKGROUND: Sudden unexpected death is substantially more common in people with epilepsy than in the general population. Our objective was to investigate the association between some clinical variables and sudden unexpected death in epilepsy (SUDEP) to identify risk factors. METHODS: This nested case-control study was based on a cohort of people aged between 15 and 70 years, who, during 1980-89, had been admitted to and discharged with a diagnosis of epilepsy from any hospital in the county of Stockholm. The study population was followed up through the National Cause of Death Register until Dec 31, 1991. Cases were individuals who had died, with a diagnosis of epilepsy registered on the death certificate, and who after review of medical and necropsy records were found to meet our SUDEP criteria. Three control participants, who were living epilepsy patients matched for age and sex, were selected from the same cohort for each case. All medical records were examined. Clinical data were collected and analysed on a predesigned protocol. FINDINGS: 57 SUDEP cases were included, of whom 91% had undergone necropsy. The relative risk of SUDEP increased with number of seizures per year. The estimated relative risk was 10.16 (95% CI 2.94-35.18) in patients with more than 50 seizures per year, compared with those with up to two seizures per year. The risk of SUDEP increased with increasing number of antiepileptic drugs taken concomitantly--9.89 (3.20-30.60) for three antiepileptic drugs compared with monotherapy. Other major risk factors were early-onset versus late-onset epilepsy (7.72 [2.13-27.96]), and frequent changes of antiepileptic drug dosage compared with unchanged dosage (6.08 [1.99-18.56]). The association between SUDEP risk and early onset, and SUDEP risk and seizure frequency, was weaker for female than for male patients, whereas frequent dose changes showed a stronger association in female patients. INTERPRETATION: Our data suggest that SUDEP is a seizure-related event, although the pathophysiological substrate that predisposes individuals to SUDEP may be established at an early age, and there may be some sex differences. Improvement of seizure control and possibly the avoidance of polytherapy may be ways to reduce the risk of SUDEP.

Adolescent↗
PubMed1999

Monotherapy trials with the new antiepileptic drugs: study designs, practical relevance and ethical implications.

Traditional randomized clinical trials for the monotherapy assessment of antiepileptic drugs (AED) involve allocation of newly diagnosed patients to long-term treatment with different AEDs in order to determine remission rates and side effect profile. Apart from being time-consuming, however, these trials are unlikely to show significant differences in seizure control between the various drugs, which may lead some regulatory agencies to argue that remission rates could be related to the natural history of the disease rather than to efficacy of the administered drugs. To circumvent this problem, a number of innovative designs for the monotherapy assessment of new AEDs have been developed in recent years. They all share the common feature of being aimed at demonstrating a difference in response rate over a short treatment period between a high dosage of a new AED and some form of suboptimal treatment (placebo or low-dose active control). Patients allocated to suboptimal treatment show unacceptable seizure control more rapidly than patients on high-dose active treatment and therefore they exit the trial at a faster rate: evidence of antiepileptic activity is therefore based on demonstration of differences in rate of deterioration rather than improvement. These trials are conducted with titration schedules, dosages and durations of treatment which are totally unrelated to optimal use of the same AEDs in routine clinical practice. No comparative data with an established reference agent are provided, and allocation of patients to suboptimal treatment raises serious ethical concerns. For these reasons, justification for the continued implementation of these trials is questionable. Randomized long-term comparative trials should be considered the gold-standard for the monotherapy assessment of new AEDs. A review of the literature, however, reveals that long-term trials with new AEDs completed to date had significant shortcomings in their design, including excessively rigid or inappropriate dosing schedules, enrollment of patients with heterogeneous seizure disorders, low statistical power and insufficient duration of follow-up. Because these studies are usually aimed at addressing regulatory requirements, the information obtained cannot be meaningfully applied to routine clinical practice. Large longer-term randomized comparative trials using more pragmatic approaches are highly needed to determine the real value of first-line therapy with new AEDs in patients with well defined seizure disorders.

Anticonvulsants↗
PubMed1999

Visual and ocular outcome in children after prenatal exposure to antiepileptic drugs.

PURPOSE: To prospectively study the incidence of structural and/or functional ophthalmological abnormalities in the offspring to an unselected population of women with epilepsy, subjected to a well controlled antiepileptic drug (AED) treatment during pregnancy. METHODS: Forty-three children prenatally exposed to antiepileptic drugs and 47 controls were included. Blinded ophthalmological examinations including fundus photography were performed at a median age of 7 years and 4 months. RESULTS: No major eye anomalies were found except in one child in the exposed group who had nystagmus and low vision. The visual acuity was lower in the eye with lowest acuity among the exposed children (p < 0.05). No other significant difference was found between the two groups. CONCLUSION: The results suggest that a well-controlled treatment with AEDs, preferably monotherapy, during pregnancy does not have any major adverse effects on the development of the eye and ophthalmological functions.

Anterior Eye Segment↗
PubMed1999

Valproate monotherapy in juvenile myoclonic epilepsy: dose-related effects on electroencephalographic and other neurophysiologic tests.

A neurophysiologic test battery (consisting of a 24-hour, seven-channel electroencephalogram [EEG], EEG spectral analysis, multiple sleep latency test, visual evoked potentials, critical flicker fusion, and visual contrast sensitivity) was administered twice to 16 patients with juvenile myoclonic epilepsy (JME) in a double-blind, randomized, crossover study comparing two daily doses of sodium valproate (VPA), 1000 mg and 2000 mg. Clinical observation time was 6 months for each dose. Mean total VPA concentration during low-dose treatment was 470.4 mmol/L and during high-dose treatment was 700.0 mmol/L. Ten patients had seizures during low-dose treatment, but only three of these showed spike-wave activity on EEGs. During high-dose treatment, nine patients had seizures; five of these had spike-wave activity. EEG power spectrum did not change between doses. The other tests also showed no change between doses. Our results suggested that EEG and our selection of other neurophysiologic tests were of limited value for monitoring seizure frequency and clinical effects of VPA.

Adolescent↗
PubMed1999

Estimation of topiramate in subdural cerebrospinal fluid, subcutaneous extracellular fluid, and plasma: a single case microdialysis study.

PURPOSE: To estimate topiramate (TPM) concentrations in subdural cerebrospinal fluid (CSF), subcutaneous extracellular fluid (ECF), and plasma and to study the correlation of TPM concentrations in these three different compartments. METHODS: In this single case study of a patient with drug-resistant partial epilepsy undergoing presurgical evaluation with subdural EEG monitoring, we used microdialysis to estimate concentrations of unbound TPM in CSF of the subdural space and ECF of abdominal subcutaneous tissue. Blood samples were drawn for estimation of TPM concentrations in plasma. RESULTS: The correlation between unbound TPM concentrations in subdural CSF and abdominal subcutaneous ECF was good. The mean ratio of ECF/CSF TPM concentration was 0.93 (SD+/-0.03) and the correlation coefficient was 0.98. The mean ratio of ECF/total plasma TPM was 0.75 (SD+/-0.06), and the correlation coefficient was 0.99. The mean ratio of CSF/total plasma TPM was 0.81 (SD+/-0.06), and the correlation coefficient was 0.97. CONCLUSIONS: Assuming a protein binding of TPM of approximately 13%. it is concluded that, based on nine microdialysis samples from a single subject, TPM levels in the CSF at the cortical surface are approximately the same as the unbound plasma levels. Additional patients should be studied to confirm the results.

Adult↗
PubMed1999

Paradoxical GH response to TRH during status epilepticus in man.

Information on GH in relation to epilepsy is sparse, and to our knowledge there is no information on GH levels during status epilepticus in man. We studied GH in serum in six patients during status epilepticus, and in a control group of six seizure-free patients with epilepsy, before and after injection of TRH. The baseline GH values before TRH administration were within the normal range in all patients. After injection of TRH all patients with status epilepticus showed a paradoxical peak-shaped increase of GH to at least twice their baseline levels within 45 min after the injection (median basal GH value 1.5 mU/l and median peak GH value 6. 5 mU/l, mean increase 330%). No uniform reaction to TRH was observed in the control group (median basal GH value 2.7 U/l and median of the highest value within 45 min 5.2mU/l). A paradoxical peak reaction of GH to TRH was significantly more frequent in the status epilepticus group compared with the control group (P=0.008, Fisher exact probability test). TRH is not considered a GH-releasing hormone in humans during normal conditions, but a paradoxical response of GH to TRH, similar to that observed during status epilepticus, has been reported in various other pathological conditions, such as acromegaly, liver cirrhosis, mental depression and hypothyroidism. Our results of GH release after TRH administration in patients with status epilepticus suggest an altered regulation of GH as a result of the long-standing epileptic activity.

Adult↗
PubMed1998

Heart rate variability in patients with epilepsy.

Autonomic function was studied by the use of spectral analysis of heart-rate variability in patients with epilepsy in relation to type of epilepsy and anti-epileptic drug therapy. A total of 21 patients with juvenile myoclonic epilepsy (JME) and 21 with temporal lobe epilepsy (TLE) were included; 18 patients were treated with carbamazepine (CBZ), 16 with valproate (VPA) and seven with phenytoin (PHT). One healthy drug free control, matched for age and sex, was selected for each patient. Patients and controls underwent an ambulatory 24 h EKG. Heart-rate variability was analyzed in time and frequency domains. Patients with TLE had significantly lower S.D. of the RR-intervals, lower low frequency power and a lower low frequency/high frequency power ratio than their controls. A lower low frequency/high frequency power ratio was the only significant difference between the JME patient group and their controls. Treatment, however, may have had a considerable influence on the heart rate variability in the epilepsy patients. Patients on CBZ had significantly lower S.D. of RR-intervals, low frequency power and a low frequency/ high frequency power ratio than did their matched healthy drug free controls. The ratio of low frequency/high frequency power was also lower in patients on VPA compared with their controls, but apart from that no differences could be demonstrated between this treatment group and the controls. In conclusion, patients with epilepsy appear to have an altered autonomic control of the heart, with a reduction in some heart-rate variability measures, suggesting a decreased sympathetic tone, which may be related to the drug therapy or the epilepsy as such. Further studies are warranted to explore these changes and their possible relevance for sudden death in epilepsy.

Adult↗
PubMed1998

Factors associated with the employment problems of people with established epilepsy.

The employment experiences of 245 respondents with epilepsy as their main diagnosis were examined as part of a study into the rehabilitation needs of an epilepsy outpatient clinic. It was found that 9% of the sample was unemployed and a further 16% were in receipt of a disability pension. Patients with seizures in remission were more likely to be employed and less likely to have experienced job problems, to feel limited by the epilepsy or to experience stigma. Job problems per se were experienced by 35% of the population. Of those with uncontrolled seizures, 50% had had job problems; however, 22% thought that their current employment situation had not been unduly influenced by epilepsy. It was those respondents who were younger or who were diagnosed early with epilepsy who were most likely to perceive their current situation as a result of having epilepsy. The survey suggests that unemployment is not the major problem it was once thought to be but that discrimination at work is a more serious problem which could lead to under-employment and restricted career development. Career planning should be instigated early and employment services should include information, practical advice and emotional support.

Adult↗
PubMed1998

The perceived rehabilitation needs of a hospital-based outpatient sample of people with epilepsy.

A postal survey was carried out to identify the perceived epilepsy rehabilitation needs of a hospital-based outpatient population. A response rate of 70% resulted in 245 patients being surveyed. Data showed that 65% of the total sample wanted more rehabilitation assistance and that 27% required substantial contact with the rehabilitation services. The most common request was for more medical information both via written material and telephone contact with a specially trained epilepsy nurse. Approximately one in six patients would like to attend a course on how to live with epilepsy. Access to a psychologist was most often requested during the first year following diagnosis and demand for courses on how to live with epilepsy was highest in the second to fourth year following diagnosis. Requests for social worker assistance were associated with employment issues. Frequency of seizures, duration of epilepsy and age were significant variables in relation to demands for rehabilitation resources. The general conclusions are that (1) the minimum standards of a rehabilitation service should include greater access to medical information via a variety of authoritative sources; and (2) that team-based resources are wanted by a substantial proportion of the population in relation to specific and definable problems, which would involve intensive input from psychologists and social workers.

Adult↗
PubMed1998

Valproate as monotherapy for juvenile myoclonic epilepsy: dose-effect study.

Sodium valproate enteric-coated tablets were used in this double-blind, randomized, cross-over study of 16 patients with juvenile myoclonic epilepsy comparing 1000 mg and 2000 mg VPA daily in b.i.d. administration with 6 months of observation on each dose. Myoclonic, absence, and generalized tonic-clonic seizures were registered separately. Subjective side-effects were monitored, and a computerized neuropsychologic test battery was performed on each dose. There was no significant difference in seizure frequency between the two doses. Only 25% of the patients were seizure free throughout the study despite concentrations well within the normally proposed therapeutic range for VPA. During the higher dose, 37.5% of the patients had an improved seizure control, but 25% of the patients had an increase in seizure frequency compared to the lower dose. However, there was no correlation between VPA concentrations and subjective side-effects or neuropsychologic test results. Our observations point out the possibility that the common strategy of increasing plasma levels in difficult-to-treat patients until side effects occur should perhaps be reconsidered, but this suggestion needs further confirmation.

Adolescent↗
PubMed1998

Postmortem changes in blood concentrations of phenytoin and carbamazepine: an experimental study.

Observations of low postmortem blood concentrations of antiepileptic drugs in cases of sudden unexpected death in epilepsy (SUDEP) have led to the assumption that noncompliance may play a role in SUDEP. However, the reliability of postmortem drug levels has been questioned. The purpose of this study was to analyze possible postmortem changes in blood concentrations of carbamazepine (CBZ) and phenytoin (PHT). New Zealand white rabbits were fed with PHT or CBZ until assumed steady state. A blood sample was then drawn for determination of serum and whole blood concentrations of CBZ and PHT, after which the rabbits were killed and stored at 6 degrees C. A further blood sample for drug analysis was obtained 72 hours after death. Antemortem serum concentrations of CBZ were not significantly different from whole blood concentration 72 hours after death. In contrast, antemortem whole blood concentrations of PHT were only 65% of the corresponding serum concentrations, and postmortem PHT blood levels were even lower, being 35% of antemortem serum concentrations. In conclusion, blood concentrations of CBZ seem to be stable during 72 hours after death under these experimental conditions. However, postmortem PHT concentrations should be interpreted with caution and low postmortem concentrations do not necessarily imply a poor compliance.

Animals↗
PubMed1998

Validation of microdialysis sampling for subcutaneous extracellular valproic acid in humans.

This article is the second in a series of studies aimed at monitoring valproic acid pharmacokinetics in patients with epilepsy by subcutaneous microdialysis. In the current study, a detailed investigation on healthy volunteers is made of the relationship between total concentrations in plasma, free concentrations in plasma, and dialysate concentrations. Particular emphasis is put on validating that the in vivo recovery under standard conditions (30 mm dialyzing membrane and 0.5 microl/minute perfusion rate) is sufficiently close to 100%. It was found that the recovery was very close to 100% at 0.5 microl/minute and by in vitro studies it could be excluded that valproic acid binds to the dialysis equipment. The correlation between unbound plasma concentrations and microdialysis concentrations of valproic acid was acceptable (r = 0.80), and they did not differ systematically from one another. It is concluded that microdialysis can be used to sample subcutaneous extracellular valproic acid in a clinical setting giving reliable estimates of the unbound concentration in plasma.

Anticonvulsants↗
PubMed1997

[Epilepsy and pregnancy. Balancing between risks to the mother and child].

Pregnancy may be especially problematic for the epileptic woman, obstetric complications tend to be more frequent, and seizure control and the pharmacokinetics of anticonvulsants may be affected. The risk of seizures is particularly high during labour and delivery-almost 10-fold higher than at other times during pregnancy. As uncontrolled generalised tonic-clonic seizures may be hazardous to both gravida and fetus, the use of anticonvulsants to prevent their occurrence is to be recommended during pregnancy even though all anticonvulsant drugs are potential teratogens. There is a 2- to 3-fold increase in the risk of birth defects in conjunction with fetal exposure to these drugs. Although the mechanisms mediating the teratogenic effects have not been identified, interference with folate metabolism, formation of toxic metabolites and drug-induced fetal hypoxia have been suggested. Despite the incompleteness of our knowledge, some recommendations can be made for the management of pregnant women with epilepsy. Pre-pregnancy counselling is important. Epileptic women contemplating pregnancy need to be informed of the pros and cons, and any major change in anticonvulsant therapy should be made before conception. Monotherapy is preferable, using the drug appropriate to seizure type and epilepsy syndrome at the lowest dosage and serum level that protects against tonic-clonic seizure. The clinical situation needs to be assessed and drug levels need to be monitored more frequently during pregnancy than otherwise. Patients on anticonvulsant treatment during pregnancy also need to be informed of the possibility of antenatal diagnosis. The use of new anticonvulsant drugs during pregnancy represents a particular challenge, since available clinical data may be insufficient to indicate their teratogenic potential Such a drug should be used in pregnancy only if essential to obtain seizure control. Moreover, the outcome of all such pregnancies needs to be carefully documented.

Abnormalities, Drug-Induced↗
PubMed1997

[Drug analysis during epilepsy treatment is valuable].

Therapeutic drug monitoring (TDM) of antiepileptic agents has been an invaluable aid in efforts to individualise epilepsy treatment since the 1970s. In few series, however, have attempts been made to assess the impact of TDM on the outcome of epilepsy therapy. The value of TDM has often been questioned in recent years, mainly due to the poor results obtained with its inappropriate use. Guidelines for the use of TDM of antiepileptic agents are therefore presented and discussed in this review. The usefulness of TDM varies according to the drug monitored, depending on its pharmacokinetic properties and on whether correlation is known to exist between the serum concentration of the drug and its effect. TDM is a prerequisite for the safe use of phenytoin, for example, but is of very limited value in connection with vigabatrin treatment. Of other novel antiepileptics, TDM would probably be useful in connection with lamotrigine treatment, and perhaps in connection with topiramate or gabapentin treatment. However, the rational use of TDM is hampered by the lack of properly designed concentration-effect studies of the new antiepileptic drugs.

Anticonvulsants↗
PubMed1997

Changes in arrhythmia profile and heart rate variability during abrupt withdrawal of antiepileptic drugs. Implications for sudden death.

Sudden unexpected death (SUD) has been associated with low or undetectable concentrations of antiepileptic drugs in patients with epilepsy suggesting that a sudden fall in plasma levels of these drugs might be a critical factor for the occurrence of SUD. We studied the changes in arrhythmia profile and heart-rate variability, during abrupt withdrawal of carbamazepine and phenytoin treatment in 10 patients with side effects on these drugs. Continuous ECG recording and daily measurements of drug plasma concentrations were performed from the last day of steady-state treatment and the following 4 days. Three patients had a 10-fold increase in ventricular premature beats. In addition, there was a significant reduction in heart-rate variability, assessed over 24 hours, in both the time (SDNN index, P = 0.03) and frequency domains from days 1-5. In the frequency domain analysis there was a significant reduction in total power (P = 0.01), very-low-frequency power (P = 0.004) and in low-frequency (LF) power (P = 0.01). Similar reductions in heart-rate variability and increases in ventricular automaticity have been associated with increased mortality in other patient groups. Two factors that might contribute to the increased rate of SUD in patients with epilepsy have thus been identified.

Adult↗