Idiopathic epilepsy with generalized tonic–clonic seizures only versus idiopathic epilepsy with phantom absences and generalized tonic–clonic seizures: One or two syndromes?

Purpose: To define the relationship between two syndromes of idiopathic generalized epilepsy (IGE) with apparently similar phenotypes: The form with generalized tonic–clonic seizures only (IGE‐GTCS) and that with phantom absences (IGE‐PA). Methods: We compared the electroclinical features of 33 consecutive patients with GTCS and generalized spike wave (GSW); 18 had only GTCS and were diagnosed as IGE‐GTCS, and 15 had hitherto unnoticed mild absences on the electroencephalography (EEG) and were diagnosed as IGE‐PA. All patients were subjected to the same diagnostic workout, including video EEG during hyperventilation with breath counting (HBC). Patients with a clinical history of absences or myoclonic seizures were excluded. Results: PA were easily identified with the first or second EEG in 14 of 15 patients with IGE‐PA and always with sleep‐deprived EEGs; conversely, PA did not occur in the IGE‐GTCS patients despite using more EEGs. GTCS were twice as frequent in the IGE‐GTCS group and tended to occur on awakening, whereas episodes of absence status affected twice as many patients with IGE‐PA. The hereditary risk was 30% in the IGE‐GTCS and 6.7% in IGE‐PA. GSW had a strong polyspike component in IGE‐PA and were briefer in IGE‐GTCS. There is no evidence for a maturational influence on the duration of GSW in either syndrome. Conclusion: Our findings clearly indicate that IGE‐GTCS and IGE‐PA are two distinct IGE syndromes and emphasize the role of PA for patients' diagnosis and management and for syndromic classification. They also appear to validate HBC as a simple, sensitive, and pragmatic method for the clinical identification of typical absences.     

Do partial seizures predict an increased risk of seizure recurrence after antiepilepsy drugs are withdrawn?

Most children who are seizure free on antiepilepsy drugs for 2 or more years remain seizure free when taken off antiepilepsy drugs. We studied 27 children with well-controlled epilepsy in whom seizures unexpectedly recurred after antiepilepsy drug withdrawal. Seizures were focal in 20 of 27 cases (74%). In 11 of the 20 cases (55%), there was also a late onset of seizures (after 2 years) and an abnormal electroencephalogram (EEG) at antiepilepsy drug withdrawal. Of the remaining 9 patients with focal seizures, 3 (15%) had only a late seizure onset, 3 (15%) had only an abnormal EEG, and 3 (15%) had neither a late onset of seizures nor an abnormal EEG. In the 7 patients without focal seizures, 6 of 7 (86%) had a late seizure onset and/or an abnormal EEG. Our study suggests that partial seizures can be the most important predictor of unanticipated seizure recurrence when antiepilepsy drugs are withdrawn, particularly with late onset of seizures and an abnormal EEG at antiepilepsy drug withdrawal. A large, multicenter, prospective study looking at these and other potential risk factors for seizure recurrence is needed.     

Discussing SUDEP: Have we improved?—A retrospective case note analysis

Sudden unexplained death in epilepsy (SUDEP) is the most common cause of death in epilepsy. Controversy surrounds its discussion with patients, with discrepancy between clinical practice and guideline recommendations; a previous audit of local practice in 2012 found that in only 4% of patients’ notes was there documented evidence of SUDEP discussion. The aim of this study was to evaluate current clinical practice and to determine whether there had been a change in practice following publication of the initial audit. A retrospective case note review was undertaken on all patients with a diagnosis of epilepsy attending a specialist epilepsy clinic in Tayside from January 1, 2012 to March 31, 2012. A documented discussion regarding SUDEP was recorded in 81 (34%) of 240 patients, an increase from previous review. Documented discussion was more likely to occur in new referrals and in those with ongoing generalized seizures, and conversely less likely to occur in those with a long history of seizures and drug‐resistant epilepsy. This repeat audit demonstrates improvement in practice; however, the minority of patients are still being informed, with those at higher risk statistically less likely to be informed.     

Do antiphospholipid antibodies increase the long‐term risk of thrombotic complications in young patients with a recent TIA or ischemic stroke?

BACKGROUND: The purpose of our study was to determine the relative risk of thrombotic events in young patients with a recent TIA or ischemic stroke and positive antiphospholipid antibodies (aPL). METHODS: We included 128 consecutive patients aged 18-45 years with a recent TIA or ischemic stroke. All patients underwent computed tomography scanning and were screened for cardiovascular risk factors, cardiac disorders and large vessel disease. Lupus anticoagulant (LA) was screened for by an APTT-based assay and a diluted PT-assay. Anticardiolipin antibodies (aCL) were tested by enzyme-linked immunosorbent assay, using cardiolipin and anti-human IgG and IgM. Thrombotic events could be TIA, stroke, myocardial infarction, deep venous thrombosis or pulmonary embolism. Product limit estimates of the time free of TIA or stroke and of the time free of any thrombotic event were made. The relative risk was estimated by means of a Cox proportional hazards regression model. RESULTS: Of the 128 patients, 22 (17.2%) had aPL. The mean follow-up was 3 years and 3 months (range 41 days to 6 yrs). The incidence of any thrombotic event per 100 patient years of follow-up was 9.0, and the incidence of recurrent stroke or TIA was 7.9. The relative risk of any thrombotic event in patients with aPL was 0.9 (95% CI: 0.3-2.4) and for recurrent ischemic stroke or TIA 0.7 (95% CI: 0.3-2.2). CONCLUSION: In young patients with a recent TIA or ischemic stroke, aPL do not seem to be a strong risk factor for recurrent stroke or TIA, nor for other thrombotic complications.     

Do certain atypical antipsychotics increase the risk of diabetes? A critical review of 17 pharmacoepidemiologic studies.

BACKGROUND: Some atypical antipsychotics have been linked to hyperglycemia, diabetes mellitus, and diabetic ketoacidosis. We reviewed evidence comparing excess risk and relative risk of type-2 diabetes associated with atypical antipsychotics. METHODS: Studies were identified on MEDLINE (January 1966-June 2003) using "antipsychotics and diabetes," "atypical antipsychotics and diabetes," and "schizophrenia and diabetes" as search terms. Studies presented at psychiatric scientific meetings between January 2000-June 2003 were identified via meeting attendance, conference proceedings, and published abstracts. The authors examined all retrospective epidemiologic studies including secondary data analyses addressing relative risk of developing diabetes in patients receiving atypical antipsychotics. Case reports, prospective trials, review articles, and MedWatch data were excluded. Extracted data were reviewed by all investigators according to predetermined criteria related to study design, treatment and comparison groups, definition of outcome measure, inclusion of covariates, and statistical analysis. RESULTS: Four studies meeting criteria for acceptable methods demonstrated that olanzapine, but not risperidone, is associated with a significantly increased risk of new-onset diabetes versus untreated major psychiatric disorder. Studies of relative risk did not demonstrate greater risk of diabetes with risperidone versus conventional antipsychotics. Of nine studies comparing relative risk of diabetes with olanzapine and risperidone, six demonstrated significantly greater risk with olanzapine. Risk was higher in women in two studies. Definitive conclusions could not be reached for clozapine and quetiapine due to limited data. CONCLUSIONS: The preponderance of current epidemiologic evidence indicates that olanzapine therapy poses a higher risk of diabetes than untreated major psychiatric illness, and that olanzapine confers greater risk of diabetes than risperidone.     

Depressive and anxiety disorders in epilepsy: Do they differ in their potential to worsen common antiepileptic drug–related adverse events?

Purpose: To compare the effect of anxiety disorders, major depressive episodes (MDEs), and subsyndromic depressive episodes (SSDEs) on antiepileptic drug (AED)–related adverse events (AEs) in persons with epilepsy (PWE). Methods: The study included 188 consecutive PWE from five U.S. outpatient epilepsy clinics, all of whom underwent structured interviews (SCID) to identify current and past mood disorders and other current Axis I psychiatric diagnoses according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM‐IV‐TR) criteria. A diagnosis of SSDE was made in patients with total Beck Depression Inventory‐II (BDI‐II) scores >12 or the Centers of Epidemiologic Studies‐Depression (CES‐D) > 16 (in the absence of any DSM diagnosis of mood disorder. The presence and severity of AEs was measured with the Adverse Event Profile (AEP). Key Findings: Compared to asymptomatic patients (n = 103), the AEP scores of patients with SSDE (n = 26), MDE only (n = 10), anxiety disorders only (n = 21), or mixed MDE/anxiety disorders (n = 28) were significantly higher, suggesting more severe AED‐related AEs. Univariate analyses revealed that having persistent seizures in the last 6 months and taking antidepressants was associated with more severe AEs. Post hoc analyses, however, showed that these differences were accounted for by the presence of a depressive and/or anxiety disorders. Significance: Depressive and anxiety disorders worsen AED‐related AEs even when presenting as a subsyndromic type. These data suggest that the presence of psychiatric comorbidities must be considered in their interpretation, both in clinical practice and AED drug trials.     

Does the dorsal hippocampus process navigational routes or behavioral context? A single‐unit analysis

In humans the hippocampus plays a role in both episodic memory and spatial navigation. Similar findings have been shown in other animals including monkeys and rats. The relationship between the processing of episodic and spatial related inputs within the hippocampus remains a puzzle. One approach to understanding how the hippocampus processes information is to examine how hippocampal cell activity corresponds to environmental experience. Hippocampal pyramidal cells can alter their spatial tuning (re-map) in response to changes in task demands. The degree to which this re-mapping is related to contextual/episodic information or to changes in spatial navigation/trajectories is unclear. The current study was designed to examine cell activity under two conditions that differed in contextual information without alterations in the goal-directed trajectories taken by the animals. Adult and aged rats were trained to do an alternation task on a fixed pathway [ J. A. Oler et al. (2005) Neuroscience , 131 , 1–12]. The animals ran this pathway during either 'safe' or 'unsafe' (a tone indicating a shock region) trials, with hesitation during 'unsafe' trials providing a clear behavioral measure of discrimination between these two conditions. Relatively few place cells displayed re-mapping between the two conditions. We propose that the principle source of re-mapping in the dorsal hippocampus is changes in the animal's trajectories rather than behavioral context. Possible reasons why so few cells responded to the change in context are discussed.     

A benefit/risk analysis of the prevention of brain ischaemia with anticoagulant drugs: when, how and whom to treat?

This paper summarises the benefits and risks of anticoagulant treatment in patients who have had cerebral ischaemia. In patients with a cardiac source of embolism (in most studies atrial fibrillation), anticoagulation with a target intensity of an INR of 2.0--3.0 is the therapy of first choice. In the case of a contraindication to such treatment, aspirin and ibuprofen are safe, but less effective alternatives. In patients with cerebral ischaemia of presumed arterial origin, anticoagulation with an achieved intensity of 3.0--4.5 proved not to be safe. Results from trials with more moderate anticoagulation regimes are awaited.