A randomised open-label study of tiagabine given two or three times daily in refractory epilepsy.

Efficacy and tolerability of tiagabine was evaluated in patients with non-controlled partial seizures in a multicentre, open-label, parallel group study. Tiagabine was administered either two (b.i.d.) or three times daily (t.i.d.) as adjunctive therapy and titrated stepwise to a target of 40 mg/day during a 12-week, fixed-schedule titration period; this was followed by a 12-week flexible continuation period. The primary efficacy endpoint was the proportion of patients completing the fixed-schedule titration period. A total of 243 patients were randomised and received treatment, 123 to b.i.d. and 120 to t.i.d. dosing. Fewer patients in the b.i.d. (76 and 62%) than in the t.i.d. (87 and 72%) group completed the fixed-schedule titration period (OR: 0.562; 95% CI: 0.309-1.008; P=0.0532). The median percentage decrease in all types of seizure (excluding status epilepticus) during the fixed schedule titration period was 33.4% for the b.i.d. and 23.8% for the t.i.d. groups (P=0.9634; Van Elteren's test). The proportion of responders was similar for the b.i.d. and t.i.d. groups. There were no significant differences between dosage regimens in the change in median seizure rates from baseline. Adverse events were more frequent during the titration than the continuation period. Most events were mild and related to the central nervous system. Although their incidence was similar between treatment groups, severity was more frequent in the b.i.d. group. Our results suggest that during titration tiagabine is better tolerated with t.i.d. dosing, but during long-term maintenance, a t.i.d. schedule is as effective and well tolerated as b.i.d.

Remacemide hydrochloride as an add-on therapy in epilepsy: a randomized, placebo-controlled trial of three dose levels (300, 600 and 1200 mg/day) in a Q.I.D. regimen.

Remacemide hydrochloride is a low-affinity, non-competitive N-methyl-D-aspartic acid (NMDA) receptor channel blocker, under investigation in epilepsy. This double-blind, placebo-controlled, multicentre study assessed the safety and efficacy of remacemide hydrochloride or placebo, as adjunctive therapy, in 252 adult patients with refractory epilepsy who were already taking up to three antiepileptic drugs (including an enzyme-inducer). Patients were randomized to one of three doses of remacemide hydrochloride (300, 600 or 1200 mg /day) or placebo Q.I.D., for up to 15 weeks. An increasing percentage of responders (defined as a reduction in seizure frequency from baseline of > or =50%) was seen with increasing remacemide hydrochloride dose. At 1200 mg /day, 23% of patients were responders compared with 7% on placebo. This difference was significant (P = 0.016), as was the overall difference between treatments (P = 0.038). Adverse events: dizziness, abnormal gait, gastrointestinal disturbance, somnolence, diplopia and fatigue were mild or moderate in severity. Carbamazepine and phenytoin plasma concentrations were well controlled and maintained within target ranges, with no evidence of improved seizure control due to increases in the concentrations of these drugs. A dose-dependent, significant, increase in responders following adjunctive remacemide hydrochloride compared with placebo was observed. Remacemide hydrochloride was well tolerated.

Psychiatric symptoms after therapy with new antiepileptic drugs: psychopathological and seizure related variables.

The purpose of this paper is to understand the association between antiepileptic drugs (AEDs), patient characteristics, changes in seizure pattern and emergent psychiatric disorder, i.e. psychosis or affective disorder. To this end we carried out a retrospective casenote study on 89 patients who developed psychiatric symptoms during treatment with topiramate, vigabatrin or tiagabine. The psychiatric problem was either an affective or a psychotic disorder (not including affective psychoses). It was discovered that 99% of the patients suffered from complex partial seizures with or without secondary generalization. More than half were on polytherapy with two or more other AEDs. Nearly two-thirds had a previous psychiatric history. There was a strong association between the type of previous psychiatric illness and the type of emerging psychiatric problem, both for psychoses and for affective disorders. Patients on vigabatrin had an earlier onset of epilepsy and more neurological abnormalities than those on topiramate. Those patients on lower doses had a shorter interval between the start of the AED therapy and the onset of the psychiatric problem. A seizure-free period was observed in more than half of the patients before they developed the psychiatric symptoms, and of these more were likely to develop a psychosis rather than an affective disorder. There seemed to be an association of suppression of right-sided seizures and the onset of the psychiatric problem. The conclusions drawn were that patients with a previous history of psychosis or affective disorder tended to develop the same psychiatric problem with new AEDs. Those with a seizure-free period before the onset of the psychiatric problem were more likely to develop a psychosis than an affective disorder.

Refractory epilepsy: treatment with new antiepileptic drugs.

Five antiepileptic drugs have been marketed in the last decade. We report here a retrospective study of patients attending our unit who were prescribed one of the new antiepileptic drugs. All these patients had refractory localization related epilepsy and had failed to respond to a first-line drug. The drugs had a different profile of side-effects but topiramate (42%) was the most common drug to be withdrawn due to side-effects as compared with tiagabine (26%), vigabatrin (16%), gabapentin (16%), and lamotrigine (15%). With regard to efficacy, 31% of the patients receiving gabapentin had a greater than 50% reduction in seizures compared with lamotrigine (25%), topiramate (20%), vigabatrin (19%) and tiagabine (11%). The number of patients remaining seizure free with gabapentin was 8% whilst for lamotrigine this was 5%, vigabatrin 5%, topiramate 1% and tiagabine 4%. In conclusion, all these five antiepileptic drugs are useful in treating refractory localization related epilepsy.

Influence of exercise-induced plasma volume changes on the interpretation of biochemical data following high-intensity exercise.

OBJECTIVE: To assess the effects that exercise-induced plasma volume changes (PVCs) have on the interpretation of biochemical and hormonal parameters in the blood of athletes after high-intensity exercise. It was hypothesized that two unrelated high-intensity exercise protocols, performed by two separate subject groups each using different exercise modes, would result in similar percentage changes in plasma volume (% delta PV). It was further hypothesized that the % delta PV, measured in both protocols, would comparably influence the interpretation of biochemical variables measured following exercise. DESIGN: An experimental before-after trial on volunteers was performed. Two different exercise modes employing two different high-intensity acute exercise protocols were investigated. Eight male swimmers performed an interval training session (ITS) consisting of 15 x 100-m freestyle efforts at 95% of their maximal exercise intensity, and eight male runners performed a multistage discontinuous treadmill test (MSD) to volitional exhaustion. SETTING: The Human Performance Laboratory at the Department of Human Movement at the University of Western Australia. MAIN OUTCOME MEASURES: Blood samples obtained before, immediately after, and 30, 60, and 120 min during recovery were analyzed for plasma volume changes, urea, uric acid, creatinine, albumin, calcium, iron, transferrin, testosterone, cortisol, and sex hormone-binding globulin (SHBG). MAIN RESULTS: The ITS and MSD protocols produced similar and significant alterations (p < 0.01) in plasma volume. Both protocols also elicited significant fluctuations (p < 0.01) in the concentration of most of the parameters measured (excluding iron). When albumin, transferrin, testosterone, and SHBG values were adjusted for the significant % delta PV, their concentrations did not change over the experimental period, suggesting that the changes in measured concentration of these parameters may be, in part, due to changes in plasma volume. However, urea, uric acid, creatinine, calcium, and cortisol, when corrected for % delta PVC, still demonstrated significant changes (p < 0.01). CONCLUSIONS: It is recommended, when sampling biochemical and hormonal parameters in blood following an acute bout of exercise, that corrections for PVCs should be conducted. Apparent changes in blood solutes may reflect PVCs. PVCs should be taken into consideration when interpreting results regardless of exercise protocol and exercise mode performed.

Does psychological testing help to predict the response to acupuncture or massage/relaxation therapy in patients presenting to a general neurology clinic with headache?

Patients with chronic headache were offered treatment by acupuncture or massage with relaxation instead of a change in their prescribed medication. They were randomly allocated to either treatment. There was a significant improvement in pain ratings with both treatment types. Specifically a greater effect was seen in migraine patients treated by massage with relaxation when compared to acupuncture. No psychological factors were found to predict response to either treatment. At the end of the study, 13% of patients were significantly more worried that there may be a more serious cause underlying their headache despite reassurance and an improvement in their headache scores.

Trauma-induced Acinetobacter lwoffi endophthalmitis with multi-organism recurrence: strategies with intravitreal treatment.

Endophthalmitis and its treatment are challenging, controversial subjects. We report here a patient whose recurrent endophthalmitis required several modes of treatment.

Epilepsy: a general practice study of knowledge and attitudes among sufferers and non-sufferers.

The aim of this study was to examine epilepsy sufferers' attitudes to and knowledge of their condition, the effect of epilepsy on their lives and their views on the management they had received, and to compare knowledge and attitudes with those of a control group of non-sufferers. A questionnaire was completed by 29 patients with epilepsy and 32 control group subjects from two general practices. It was found that people with epilepsy knew little more than those without epilepsy regarding the nature of the condition, its aetiology and seizure precipitants. Those with epilepsy were concerned about the seizures and the effect these had on various aspects of their lives, and were concerned about long-term side effects of anti-epileptic medication. There were no significant differences between the two groups with respect to educational achievement, employment record and social activities. The findings are discussed and suggestions put forward for improving the care offered to epilepsy sufferers by both general practitioners and hospital clinics.

The development of a seizure severity scale as an outcome measure in epilepsy.

In controlled trials of antiepileptic drugs (AEDs) seizure frequency is often the only variable considered. With little prospect of improving assessment of AEDs, using seizure counts as the only end-point, there is a need for the development of new outcome measures. Clinical experience indicates that seizure severity is equally important to the patient and, by preventing seizure spread, AEDs can influence seizure severity without necessarily reducing seizure frequency. A scale capable of measuring seizure severity and change of severity attributable to treatment could be a useful additional outcome measure. Such a scale should exhibit the basic properties of validity and reliability. An easily administrable 16-point scale, containing 2 subscales--perception of control and ictal/post-ictal effects--has been developed. This scale has been tested on a patient population (n = 159) representative of that seen in trials of novel AEDs. Using standardised statistical methods, the scale has been shown to be both reliable and valid.

Growth hormone response to diazepam, clonidine and glucagon in patients with epilepsy.

The differing actions of phenytoin, carbamazepine and sodium valproate on growth hormone release were studied in 20 patients with recently diagnosed epilepsy using diazepam, clonidine and glucagon as stimulatory tests of growth hormone response. The results are compared with the growth hormone response obtained pre treatment, and those from 20 control patients and 11 patients with chronic treated epilepsy. There was a reduction in growth hormone response to diazepam in both treated and untreated patients with epilepsy compared to controls. Treatment with phenytoin resulted in a significant increase in growth hormone release after diazepam and glucagon, whilst sodium valproate reduced the growth hormone response to diazepam.

CSF gradients for amino acid neurotransmitters.

Amino acid concentrations were measured in CSF samples obtained by lumbar puncture in 51 patients, cervical puncture in 16 patients, spinal drains in nine patients, ventricular taps in five patients and from below a spinal block in six patients. There was evidence of a rostrocaudal gradient for GABA and taurine and a reverse gradient for alanine and asparagine. Lumbar CSF glycine concentrations rose with increasing age whilst GABA concentrations fell. Women had significantly lower concentrations of asparagine and glutamine and elevated taurine compared to men. The influence of biological factors and gradients must be taken into account before the interpretation of changes in CSF amino acid concentrations.

GABA and amino acid concentrations in lumbar CSF in patients with treated and untreated epilepsy.

Lumbar free CSF GABA and amino acid concentrations were measured in 43 patients with newly diagnosed untreated epilepsy and 26 patients with chronic drug-resistant epilepsy. The results were compared with those from 51 control patients. No differences in free CSF GABA concentration could be detected between patients with epilepsy, either treated or untreated, and controls. Untreated patients with primary generalised epilepsy and partial seizures had similar free CSF GABA concentrations. These results would not support the hypothesis that patients with epilepsy have a global disturbance of GABA function. CSF taurine, asparagine, aspartate, glycine and alanine were significantly reduced in patients with epilepsy compared to the control population.

Cerebral arteriovenous malformations and epilepsy: factors in the development of epilepsy.

Sixty-one patients of a population of 343 with cerebral arteriovenous malformations (AVMs) were diagnosed with seizures. Their AVMs were larger (p less than 0.02) and more frequently superficial (p less than 0.05) as compared with the AVMs of patients who were diagnosed with haemorrhage. The factors influencing the development of denovo seizures in patients with diagnosed AVMs were surgical treatment, a presentation with haemorrhage, and age at diagnosis.

Arteriovenous malformations of the brain: natural history in unoperated patients.

Two-hundred and seventeen patients from a total population of 343 patients with arteriovenous malformations, were managed without surgery. Follow up was for a mean of 10.4 years. Using life survival analyses, there was a 42% risk of haemorrhage, 29% risk of death, 18% risk of epilepsy and a 27% risk of having a neurological handicap by 20 years after diagnosis in unoperated patients.

Survey of state funds available for rehabilitation of patients with cleft lip/palate.

An effort was made to determine the amount of funds budgeted in each of the 50 U.S. states for total rehabilitation of patients with cleft lip and/or cleft palate. Questionnaires were sent following a pilot letter to the directors of each state Department of Health. Total funds per patient ranged from $17,442 for Delaware to a low of $426 for Wisconsin. Dental funds per patient ranged from $4,214 dollars for Wyoming to a low of $192 for New York.