Epilepsy: major advances in treatment.

1assessed the dose–response association of lamotrigine and TMS in 16 healthy male volunteers in a double-blind, randomised, placebo-controlled, three-way-crossover study. There was a correlation of lamotrigine dose with TMS response. There was also high interindividual variability in the correlation of serum concentration of lamotrigine and TMS response. This first description of a dose–response relationship between an AED and TMS in healthy volunteers is a significant achievement and suggests a role for TMS in the titration of lamotrigine and other AEDs in individual patients. Before this test could be used clinically, however, additional studies are needed in patients with epilepsy to prove that TMS is safe, to relate TMS responses with AED efficacy and tolerability, and to show that TMS is better than serum concentrations as a predictor of efficacy and tolerability. Depression is the most common psychiatric comorbidity in patients with epilepsy, is associated with diminished quality of life, and is a risk factor for suicide. But depression is underdiagnosed and undertreated, perhaps in part because clinicians might falsely assume that all is well in patients without active seizures. Attarian and colleagues 2 investigated the relation between seizure rates and depression in 143 patients with epilepsy from outpatient clinics. 11% of patients who were seizure free more than 6 months were depressed, which was nearly identical to the percentage of patients with active seizures who were depressed (10%). Furthermore, there was no relation between severity of depression and the monthly seizure rate. This study, which needs to be replicated in other settings, suggests that epilepsy— but not current seizure frequency—is a risk factor for depression and that seizure frequency does not predict severity of depression. In light of the significant psychosocial morbidity and risk of suicide associated with depression in patients with epilepsy, this study should prompt clinicians to assess all patients for depression irrespective of degree of seizure control. Epilepsy syndromes are diagnosed on the basis of two or more unprovoked seizures together with other characteristic clinical and demographic features. A possible exception is Panayiotopoulos syndrome, which affects up to one in eight young children and typically manifests as a single, long-lasting seizure with autonomic features. Lada and colleagues 3 studied the clinical features, EEG findings, and prognosis in 43 patients with Panayiotopoulos syndrome who were followed up for up to 17 years (mean 5·6 years). Two-thirds of the patients were female, and the mean age at first seizure was 5 years. Nausea and emesis with retained consciousness heralded seizure onset in more than threequarters of patients. Other characteristic ictal features were confusion or impaired consciousness as the seizure progressed (100%), lateral gaze deviation (56%), and additional autonomic signs—including urinary incontinence, pallor, perioral cyanosis, and hypersalivation. In 36 patients (84%), seizures occurred in association with sleep or near arousal from sleep. Seizures in nearly half the patients lasted for over 30 min, many ended in generalised or half-body convulsions. Most children were treated with AEDs, doses of which were tapered off. Over half the patients experienced only one seizure; others had two or three. EEGs were normal in about a third of the patients and showed epileptiform abnormalities in the others. Six children (14%) were misdiagnosed as having encephalitis, head injury, or gastroenteritis. This study shows for the first time that interictal EEGs are commonly normal. Paediatricians, family physicians, and neurologists should all consider this syndrome when making the differential diagnosis of children newly presenting with seizures, especially prolonged, sleep-related seizures with vomiting at onset. One in three patients with epilepsy will not achieve seizure freedom from available AEDs, and thereby become potential candidates for resective brain surgery. Yet for many patients, referral for presurgical assessment is delayed for years after response to antiseizure therapy is established. Perhaps one factor is the lack of certainty about long-term prognosis. Clinicians are generally aware of the high probability of shortterm seizure freedom from resection for epilepsy, but what about long-term results? Yoon and colleagues 4 assessed long-term seizure outcome in 175 patients at one centre who had lobectomy from 1972 to 1992 and who were seizure-free during the first year after surgery. Over a mean follow-up of 8·4 years, nearly two-thirds of patients were seizure free. After 10 years, the likelihood of continued seizure freedom was 56%. Long duration of preoperative epilepsy and normal pathology were associated with increased risk of relapse. Of those patients whose seizures relapsed, half had at most one seizure per year. These data should reassure clinicians about the excellent long-term prognosis from resection, especially when surgery is compared to the primary alternative—continued use of pharmacological therapy in patients who have not responded to the therapy.