A pilot study of donepezil for memory problems in epilepsy.

We performed a pilot 3-month, open-label study of 5-10 mg donepezil, an anticholinesterase inhibitor, as treatment for memory problems in people with epilepsy. The Buschke Selective Reminding Test was administered at baseline and after 3 months of donepezil. In 18 completing patients, the total number of words recalled across learning trials was greater on donepezil (P = 0.4). No change was noted in attention, visual sequencing, mental flexibility, psychomotor speed, or reported quality-of-life scores. Mean 3-month seizure frequency at baseline was 2.70 ± 4.60, and during treatment, 3.06 ± 4.52 (P = 0.19, not significant). Two patients experienced increased tonic-clonic seizures. Side effects included diarrhea, stomach cramps, insomnia, depression, and blurred vision. Cholinergic medication is worthy of investigation as treatment for memory problems in people with epilepsy, but attention must be paid to possible exacerbation of seizures.

An automated drug delivery system for focal epilepsy.

Previous studies have demonstrated the ability to stop seizures in animal models with injection of antiepileptic medication directly onto the seizure focus. The present experiments describe automated detection and focal therapy for seizures in the laboratory setting. Focal seizures were created in Sprague-Dawley rats using bicuculline, a GABA antagonist. Computerized detection of seizures was linked to a programmable infusion pump to deliver either diazepam (DZP) or pH-balanced vehicle (VEH) directly onto the seizure focus. Mean numbers of seizures following initial delivery of drug were 2.9+/-1.45 for the VEH-treated group and 0.2+/-0.42 for the DZP-treated group (P<0.0001, Student's t-test, nonpaired, one-tailed). In another series of experiments, early injection of DZP shortened seizure duration. Three DZP-treated animals died. This model provides proof-in-principle for the development of a clinically applicable treatment for intractable partial epilepsy. Such therapy might avoid some of the problems inherent to systemic administration of antiepileptic drugs.

Frequency of bitemporal independent interictal epileptiform discharges in temporal lobe epilepsy.

PURPOSE: Bitemporal interictal epileptiform discharges (IEDs) occur in < or =42% of scalp EEGs in patients with temporal lobe epilepsy (TLE) studied with routine EEGs or partial analysis of long-term recordings. METHODS: Twenty-eight patients with TLE demonstrating exclusively unilateral temporal IEDs on routine EEGs underwent 24-h continuous recording. The entire record was visually inspected for epileptiform discharges. We used continuous EEG to assess the significance of long-term recording in detecting bilateral IEDs. RESULTS: Twenty-two patients had left temporal IEDs; 21 had right temporal IEDs. Seventeen (61%) patients had IEDs originating from both the right and left temporal lobes. The probability of detecting bilateral independent IEDs was correlated with the duration of continuous EEG recording. There was no correlation between the number of IEDs originating from one side and the probability of detecting independent IEDs on the other side. The frequencies of IEDs were not correlated with the length of time since onset of epilepsy. CONCLUSIONS: The findings suggest that when long-term recordings are performed, the incidence of bilateral discharges in TLE is higher than previously reported in the literature and supports the view that TLE is commonly a bilateral disease.

Computer-based electroencephalography: technical basics, basis for new applications, and potential pitfalls.

EEG has been recorded on paper-based analog systems for over 50 years. In the past 5 years, computer-based digital systems have become more widely used. Digital systems eliminate some artifacts that plagued analog recordings but introduce subtle new problems including aliasing and dynamic range. Digital systems allow reformatting of the same EEG segment using different gain, filter and montage settings. The digital signal allows for measurement and computations on the EEG, leading to applications such as power spectrum, topographic mapping, and spike or seizure detection.

Bilateral temporal hypometabolism in epilepsy.

PURPOSE: Positron emission tomography (PET) has proven useful in epilepsy surgery for its ability to identify unilateral temporal hypometabolism (UTH), which is predictive of good surgical outcome. The significance of bilateral temporal hypometabolism (BTH) is not known. METHODS: We identified all patients who had marked bilateral reduction in temporal lobe metabolism relative to the cerebellar hemispheres and compared their clinical features and treatment outcomes with those of control patients with UTH. RESULTS: BTH was evident in 10% of PET scans for epilepsy at our institution. We compared these patients with age-matched controls with UTH. The BTH patients had a higher percentage of generalized seizures; were more likely to have bilateral, diffuse or extratemporal seizure onsets; and had bilateral or diffuse magnetic resonance imaging (MRI) findings. UTH patients were more likely to have unilateral mesial temporal atrophy on MRI. Even when electrical seizure onsets were well localized, surgical outcomes were markedly worse in these patients than in controls. Medical treatment was also less successful. Social and cognitive functioning was worse in the BTH group. The only death occurred in the group with BTH. CONCLUSIONS: Patients with BTH have features distinct from those with UTH and have a worse prognosis for seizure remission after surgery.

New drugs for persons with epilepsy.

Between 30% and 60% of patients with epilepsy have not achieved adequate control with current medications, and side effects are a significant problem. In the past 2 years, three drugs for epilepsy have been approved. At least six more drugs are in the final stages of development, and there is an active "pipeline." None of the new drugs are panceas, but many have special advantages and meet important specific needs. Felbamate, despite a high incidence of aplastic anemia and hepatic failure, remains useful because of its lack of sedative effects and high efficacy. Gabapentin is remarkable for its favorable side effect profile, lack of interactions, and straightforward kinetics. Lamotrigine is also nonsedating and may be especially useful in generalized epilepsies. Topiramate and vigabatrin are both highly effective, although each is associated with a variety of cognitive or psychiatric side effects that may limit utility. Oxcarbazepine shares the efficacy of carbamazepine, with fewer side effects or drug interactions. Zonisamide seems to be effective and cause mild side effects, although the risk for renal stones indicates a need for cautious use. Tiagabine, like gabapentin, is a mild drug with a favorable side effect profile. New forms of old drugs will make for easier administration; fosphenytoin will increase the safety of parenchymal phenytoin use. The best of the new drugs help, at most, 10% of previously uncontrolled patients to become seizure-free. The development of new drugs remains an important need.

Patient awareness of seizures.

In 31 consecutive patients who were admitted to an epilepsy monitoring unit, we prospectively determined whether the patients were aware of having seizures. On admission, all patients stated that they knew of at least some of their seizures. Eight of 23 with classifiable epileptic seizures recognized that they were occasionally unaware of their seizures. During telemetry, following full recovery of consciousness after each seizure, we asked the patients whether they had recently had a seizure. For control purposes, we asked the patients the same question at random times. Among patients with seizures, there were no false-positive answers. Only 6 of 23 (26%) of the patients with epilepsy were always aware of their seizures, including complex partial and secondarily generalized events, and 7 of 23 (30%) were never aware of any seizures. Self-reporting of seizures was unreliable: Patients reporting the lowest baseline frequency of seizures had the highest fraction of unrecognized seizures. Seizure awareness was lowest for patients with temporal lobe foci, especially on the left side. Patients with primarily generalized epilepsy were more likely to be aware of tonic-clonic seizures than were patients with secondarily generalized partial seizures. All four patients with nonepileptic attacks believed that they always knew of their seizures, but only three of the four patients actually did always know. Unrecognized seizures are frequent and should be considered in patient management and in studies.

Light-stimulated cotyledon expansion in the blu3 and hy4 mutants of Arabidopsis thaliana.

Cotyledon expansion in response to blue light was compared for wild-type Arabidopsis thaliana (L.) Heynh. and the mutants blu3 and hy4, which show reduced inhibition of hypocotyl growth in blue light. White, blue, and red light stimulated cotyledon expansion in both intact and excised cotyledons of wild-type seedlings (ecotypes No-0, WS, Co-0, La-er). Cotyledons on intact blu3 and hy4 seedlings did not grow as well as those on the wild type in response to blue light, but pretreatment of blu3 seedlings with low fluence rates of red light increased their responsiveness to blue light. Excision of cotyledons alleviated the mutant phenotype so that both mutant and wild-type cotyledons grew equally well in blue light. The loss of the mutant cotyledon phenotype upon excision indicates that the blu3 and hy4 lesions affect cotyledon expansion indirectly via a whole-plant response to light. Furthermore, the ability of excised, mutant cotyledons to grow normally in blue light shows that this growth response to blue light is mediated by a photosystem other than the ones impaired by the blu3 and hy4 lesions.

Stimulation of growth and ion uptake in bean leaves by red and blue light.

Red and blue light both stimulate growth and ion accumulation in bean (Phaseolus vulgaris L.) leaves, and previous studies showed that the growth response is mediated by phytochrome and a blue-light receptor. Results of this study confirm that there is an additional photosynthetic contribution from the growing cells that supports ion uptake and growth. Disc expansion in the light was enhanced by exogenous K(+) and Rb(+), but was not specific for anions. Light increased K(+) accumulation and the rate of (86)Rb(+) uptake by discs, over darkness, with no effect of light quality. The photosynthetic inhibitor, 3-(3,4-dichlorophenyl)-1,1-dimethylurea, inhibited light-driven (86)Rb(+) uptake by 75%. Light quality caused differences in short-term kinetics of growth and acidification of the leaf surface. At comparable fluence rates (50 mumol m(-2) s(-1)), continuous exposure to blue light increased the growth rate 3-fold after a 2-min lag, whereas red light caused a smaller growth response after a lag of 12 min. In contrast, the acidification of the leaf surface normally associated with growth was stimulated 3-fold by red light but only slightly (1.3-fold) by blue light. This result shows that, in addition to acidification caused by red light, a second mechanism specifically stimulated by blue light is normally functioning in light-driven leaf growth.