Luigi M. Specchio

Determinants of health-related quality of life in pharmacoresistant epilepsy: Results from a large multicenter study of consecutively enrolled patients using validated quantitative assessments

Purpose:  To evaluate the relative contribution of demographic and epilepsy‐related variables, depressive symptoms, and adverse effects (AEs) of antiepileptic drugs (AEDs) to health‐related quality of life (HRQOL) in adults with pharmacoresistant epilepsy.

Incidence and predictors of acute symptomatic seizures after stroke

Objective: To assess incidence and predictors of acute symptomatic seizures in a prospective cohort of patients with first stroke. Methods: Patients with first stroke hospitalized in 31 Italian centers were recruited. Relevant demographic data, disease characteristics, and risk factors were collected. Acute symptomatic seizures (≤7 days) were recorded and correlated to age, gender, family history of epilepsy, and vascular risk factors. Results: A total of 714 patients (315 women, 399 men; age 27–97 years) were enrolled. A total of 609 (85.3%) had cerebral infarction (32 cerebral infarction with hemorrhagic transformation [CIHT]) and 105 (14.7%) primary intracerebral hemorrhage (PIH). A total of 141 (19.7%) had a large lesion (>3 cm) and 296 (41.5%) cortical involvement. Twelve patients reported family history of seizures. Forty-five patients (6.3%) presented acute symptomatic seizures, 24 with cerebral infarction (4.2%), 4 with CIHT (12.5%), and 17 (16.2%) with PIH. In multivariate analysis, compared to cerebral infarction, PIH carried the highest risk (odds ratio [OR] 7.2; 95% confidence interval [CI] 3.5–14.9) followed by CIHT (OR 2.7; 95% CI 0.8–9.6). Cortical involvement was a risk factor for PIH (OR 6.0; 95% CI 1.8–20.8) and for CI (OR 3.1; 95% CI 1.3–7.8). Hyperlipidemia (OR 0.2; 95% CI 0.03–0.8) was a protective factor for IPH. Conclusion: The incidence of acute symptomatic seizures is the highest reported in patients with first stroke with prospective follow-up. Hemorrhagic stroke and cortical lesion were independent predictors of acute symptomatic seizures. Hyperlipidemia was a protective factor for hemorrhagic stroke.

The adverse event profile of pregabalin: A systematic review and meta-analysis of randomized controlled trials

Purpose:  Despite the widespread use of antiepileptic drugs (AEDs) across different neurologic and psychiatric disorders, no study has systematically reviewed all available randomized controlled trials (RCTs) of a given AED to fully uncover its tolerability profile.

Should Antiepileptic Drugs Be Withdrawn in Seizure-Free Patients?

Discontinuation of antiepileptic drug (AED) treatment is a valuable option in patients with epilepsy who have been seizure free for 2 years or longer. However, the decision to withdraw AEDs must be based on a balanced view of the overall risk of seizure relapse, the factors most likely to affect that risk, and the medical, emotional and social implications of treatment continuation versus treatment withdrawal.In a critical review of 28 studies accounting for 4571 patients (2758 children, 1020 adults and a combined group of 793), most with at least 2 years of seizure remission, the proportion of patients with relapses during or after AED withdrawal ranged from 12 to 66%. Using life-table analysis, the cumulative probability of remaining seizure-free in children was 66–96% at 1 year and 61–91% at 2 years after withdrawal of AEDs. The corresponding values in adults were 39–74% and 35–57%, respectively. The relapse rate was highest in the first 12 months (especially in the first 6 months) after withdrawal and tended to decrease thereafter. Based on a previously published meta-analysis of data published up to 1992, the pooled relapse risk was 25% (95% CI 21, 30%) at 1 year and 29% (95% CI 24, 34%) at 2 years after AED withdrawal.The factors associated with a higher-than-average risk of seizure relapse included adolescent-onset epilepsy, partial seizures, the presence of an underlying neurological condition, and abnormal EEG findings at the time of AED withdrawal in children. Factors associated with a lower-than-average risk were childhood-onset epilepsy, idiopathic generalised epilepsy and — for children — a normal EEG. Selected epilepsy syndromes (e.g. benign epilepsy with centrotemporal spikes and juvenile myoclonic epilepsy) may be associated with significantly different outcomes after AED withdrawal.All these factors and their combinations may contribute to the development of guidelines for practising physicians to help them in making the best decision related to treatment discontinuation. The decision plan should also take into account social factors (driving license, job and leisure activities) as well as emotional and personal factors, and must be tailored to and discussed with the individual patient and his/her family.

Changes in the Disposition of Oxcarbazepine and Its Metabolites during Pregnancy and the Puerperium

Summary:  Purpose: To determine potential changes in the plasma concentrations of oxcarbazepine (OXC) and its metabolites during pregnancy and puerperium.

Open label, long-term, pragmatic study on levetiracetam in the treatment of juvenile myoclonic epilepsy

PURPOSE Patients with juvenile myoclonic epilepsy (JME) may be resistant or show adverse effects to valproate. We present a multicenter, prospective, long-term, open-label study evaluating the efficacy and safety of levetiracetam in JME. METHODS Patients with newly diagnosed (10) or resistant/intolerant to previous AEDs JME (38) were enrolled. After a 8 week baseline period, levetiracetam was titrated in 2 weeks to 500 mg b.i.d. and then increased up to 3000 mg/day according to the patients response. Efficacy parameters were: number of seizure-free patients, number of days with myoclonus (DWM), and monthly frequency of generalised tonic-clonic (GTC) seizures. Adverse events were recorded. RESULTS The overall mean dose of levetiracetam was 2208 mg/day. The mean study period was 19 (range 0.3-38) months. Five patients dropped out. 11/38 (28.9%) patients with add-on treatment and 5/10 (50%) newly diagnosed patients were seizure-free for a mean period of 17.2 (+/-8.8) months. Eighteen patients (37.5%) were without myoclonia, and 35 (72.9%) had no GTC seizures over the study period. The mean monthly frequency of DWM and of GTC seizures in the entire group was significantly reduced after levetiracetam. Five patients complained of side effects. CONCLUSIONS This open-label study suggests levetiracetam may be effective and well tolerated in resistant cases of JME or may become a reasonable alternative to valproate in newly diagnosed patients.

Effects of rivastigmine on motor and cognitive impairment in Huntington's disease

To evaluate the efficacy of rivastigmine on motor and cognitive impairment in Huntingtons disease (HD), we carried out a prospective, open‐label, randomized, controlled study. Twenty‐one HD patients were enrolled: 14 were randomly sorted into medication and 7 to no‐treatment groups. Clinical and demographic features were similar between groups. After 8 months, an efficacy evaluation was carried out to compare the two groups. The improvement of cholinergic transmission in HD patients seemed to have a slight effect in ameliorating cognitive performance and slowing motor deterioration.

The THRombolysis and STatins (THRaST) study

Objective: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis. Methods: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] ≤ 4 points from baseline or NIHSS = 0) and major neurologic improvement (NIHSS ≤ 8 points from baseline or NIHSS = 0) at 7 days and favorable (modified Rankin Scale [mRS] ≤ 2) and excellent functional outcome (mRS ≤ 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS ≥ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS ≥ 4 points from baseline or death within 36 hours, and 3-month death. Results: Adjusted multivariate analysis showed that statin use in the acute phase was associated with neurologic improvement (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.26–2.25; p < 0.001), major neurologic improvement (OR 1.43, 95% CI 1.11–1.85; p = 0.006), favorable functional outcome (OR 1.63, 95% CI 1.18–2.26; p = 0.003), and a reduced risk of neurologic deterioration (OR: 0.31, 95% CI 0.19–0.53; p < 0.001) and death (OR 0.48, 95% CI 0.28–0.82; p = 0.007). Conclusion: Statin use in the acute phase of stroke after IV thrombolysis may positively influence short- and long-term outcome.

Effects of levetiracetam on EEG abnormalities in juvenile myoclonic epilepsy

Purpose: A multicenter, prospective, long‐term, open‐label study to evaluate the effects of levetiracetam on electroencephalogram (EEG) abnormalities and photoparoxysmal response (PPR) of patients affected by juvenile myoclonic epilepsy (JME).

Patterns of prescription of antiepileptic drugs in patients with refractory epilepsy at tertiary referral centres in Italy

PURPOSE To evaluate the pattern of prescription of antiepileptic drugs (AEDs) and other medications in a representative population of patients with refractory epilepsy attending tertiary referral centres in Italy. METHODS Descriptive analysis of data obtained at baseline from 933 adults and 191 children with refractory epilepsy enrolled consecutively in an observational study at 11 tertiary referral centres in Italy. Multivariate logistic regression analysis was used to assess predictors of utilization of the most commonly prescribed AEDs. RESULTS Polytherapy was used in 79% of adults and 75% of children, with over one-third of adults and children being prescribed ≥3 AEDs. In adults, the most commonly used AEDs were levetiracetam (35%), carbamazepine (34%) and lamotrigine (30%). In children, valproic acid was by far the most commonly used AED (46%), followed by carbamazepine (27%), topiramate (21%), and phenobarbital (20%). The most common AED in partial epilepsy was carbamazepine (331 out of 893 patients, 37%), followed by levetiracetam (33%) and lamotrigine (26%). In generalized or undetermined epilepsies, the AEDs most commonly used were valproic acid (139 out of 223 patients, 62%), lamotrigine (33%) and levetiracetam (28%). Second generation AEDs were prescribed in 81% of adults and 54% of children. Comedications used for indications other than epilepsy were used by 32% of adults and 17% of children. CONCLUSIONS Prescription patterns were consistent with current evidence about the spectrum of efficacy of individual AEDs in different epilepsy syndromes. The high prevalence of polytherapy, including combinations of three or more AEDs, is a cause for concern.