Incidence of childhood and adolescence epilepsy: a community-based prospective study in the province of Ferrara and in Copparo, Italy, 1996-2005

Background: The annual incidence of childhood and adolescence epilepsy ranges from 41 to 97 diagnoses per 100 000 people in western Countries, with a reported decline over time. We aimed at studying the incidence of epilepsy in children and adolescents (1 month to 14 years) and its temporal trend in the province of Ferrara, northern Italy. Methods: We implemented a community‐based prospective multi‐source registry. All children with newly diagnosed epilepsy in the period 1996–2005 were recorded. Results: The incidence rate of newly diagnosed epilepsy in the considered age range was 57 per 100 000 person‐years, (95% CI: 49.3–65.9), with a peak in the first year of life (109.4; 95% CI: 69.4–164.1), without differences between the two gender. The estimates were significantly lower than those observed previously (97.3; 95% CI: 81.9–115.7). Conclusions: Incidence rates for epilepsy in the Italian population aged 1 month to 14 years are in line with those of other European and Northern American Countries. The incidence of childhood epilepsy has declined over time in our area. A reduced impact of serious perinatal adverse events could partly explain the decline.     

Does adherence to epilepsy quality measures correlate with reduced epilepsy‐related adverse hospitalizations? A retrospective experience

In 2011, the American Academy of Neurology (AAN) established eight epilepsy quality measures (EQMs) for chronic epilepsy treatment to address deficits in quality of care. This study assesses the relationship between adherence to these EQMs and epilepsy‐related adverse hospitalizations (ERAHs). A retrospective chart review of 475 new epilepsy clinic patients with an ICD‐9 code 345.1‐9 between 2010 and 2012 was conducted. Patient demographics, adherence to AAN guidelines, and annual number of ERAHs were assessed. Fisher's exact test was used to assess the relationship between adherence to guidelines (as well as socioeconomic variables) and the presence of one or more ERAH per year. Of the eight measures, only documentation of seizure frequency, but not seizure type, correlated with ERAH (relative risk [RR] 0.343, 95% confidence interval [CI] 0.176–0.673, p = 0.010). Among patients in the intellectually disabled population (n = 70), only review/request of neuroimaging correlated with ERAH (RR 0.128, 95% CI 0.016–1.009, p = 0.004). ERAHs were more likely in African American patients (RR 2.451, 95% CI 1.377–4.348, p = 0.008), Hispanic/Latino patients (RR 4.016, 95% CI 1.721–9.346, p = 0.016), Medicaid patients (RR 2.217, 95% CI 1.258–3.712, p = 0.009), and uninsured patients (RR 2.667, 95% CI 1.332–5.348, p = 0.013). In this retrospective series, adherence to the eight AAN quality measures did not strongly correlate with annual ERAH.     

Prenatal stress and affective disorders in a population birth cohort

Kleinhaus K, Harlap S, Perrin M, Manor O, Margalit‐Calderon R, Opler M, Friedlander Y, Malaspina D. Prenatal stress and affective disorders in a population birth cohort.
Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: Pregnant women exposed to an acute traumatic event are thought to produce offspring with an increased incidence of affective disorders. It is not known whether there are specific times in pregnancy which confer increased vulnerability, or if psychosocial stress alone can increase the incidence of affective disorders in offspring. We examined the relationship of the timing of an acute psychosocial threat during pregnancy to the incidence of affective disorders in offspring using data from a large birth cohort. Methods: Using data on 90079 offspring born in Jerusalem in 1964–1976 and linked to Israel’s psychiatric registry, we constructed proportional hazards models to evaluate the link between gestational age during the Arab–Israeli war of June 1967 and incidence of mood disorders. Results: Those in their first trimester of fetal development during the war were more likely to be admitted to hospitals for any mood disorders [relative risk (RR) = 3.01, 95% confidence interval (CI): 1.68–5.39, p = 0.0002]; for bipolar disorder the risk was doubled (RR = 2.44, 95% CI: 0.996–5.99, p = 0.054) and for all ‘other’ mood disorders the risk was tripled (RR = 3.61, 95% CI: 1.68–7.80, p = 0.001). Mood disorders were also increased in offspring whose mothers had been in the third month of pregnancy in June of 1967 (RR = 5.54, 95% CI: 2.73–11.24, p < 0.0001). Conclusions: A time‐limited exposure to a severe threat during early gestation may be associated with an increased incidence of affective disorders in offspring. The third month of fetal development was a moment of special vulnerability.     

Levetiracetam may favorably affect seizure outcome after temporal lobectomy

Purpose: To study the prognostic implications of antiepileptic drug (AED) use on seizure freedom following temporal lobe resections for intractable epilepsy. Methods: Seizure outcome implications of epilepsy characteristics and AED use were studied in patients who underwent temporal lobectomy patients at the Cleveland Clinic between September 1995 and December 2006. Survival analysis and multivariate regression with Cox proportional hazard modeling were used. Complete seizure freedom was defined as a favorable outcome. Key Findings: Records of 312 patients were analyzed (mean ± standard deviation follow‐up 3.5 ± 1.7 years). The estimated probability of complete seizure freedom was 69% at 12 months (95% confidence interval [CI] 66–72%), and 48% at 36 months (95% CI 45–52%). The mean number of AEDs used per patient at the time of surgery was 1.78 (range 1–4), dropping to 1.02 at last follow‐up (range 0–4). Following multivariate analysis, a lower preoperative seizure frequency and perioperative use of levetiracetam predicted a favorable outcome (risk ratio [RR] 0.62, 95% CI 0.43–0.89, and RR = 0.57, 95% CI 0.39–0.83, respectively), whereas nonspecific pathology (RR 1.71, 95% CI 1.15–2.47) and a higher number of AEDs used at the time of surgery correlated with higher rates of seizure recurrence (whole‐model log‐rank test p‐value < 0.0001). Better outcomes within the levetiracetam group were seen despite a higher proportion of several poor prognostic indicators within this patient group, and started as early as 4 months after surgery, gradually increasing to a 15–20% survival advantage by 5 years. No similar outcome correlations were identified with another AED. Significance: AED use may be a potential new modifiable seizure‐outcome predictor after temporal lobectomy. This possible prognostic indicator is discussed in light of proposed seizure recurrence mechanisms.     

Critical determinants of the epilepsy treatment gap: A cross‐national analysis in resource‐limited settings

Purpose: Epilepsy is one of the most common serious neurologic disorders worldwide. Our objective was to determine which economic, health care, neurology, and epilepsy‐specific resources were associated with untreated epilepsy in resource‐constrained settings. Methods: A systematic review of the literature identified community‐based studies in resource‐constrained settings that calculated the epilepsy treatment gap, the proportion with untreated epilepsy, from prevalent active epilepsy cases. Economic, health care, neurology, and epilepsy‐specific resources were taken from existing datasets. Poisson regression models with jackknifed standard errors were used to create bivariate and multivariate models comparing the association between treatment status and economic and health resource indicators. Relative risks were reported. Key Findings: Forty‐seven studies of 8,285 individuals from 24 countries met inclusion criteria. Bivariate analysis demonstrated that individuals residing in rural locations had significantly higher risks of untreated epilepsy (relative risk [RR] 1.63; 95% confidence interval [CI] 1.26–2.11). Significantly lower risks of untreated epilepsy were observed for higher physician density (RR 0.65, 95% CI 0.55–0.78), presence of a lay (RR 0.74, 95% CI 0.60–0.91) or professional association for epilepsy (RR 0.73, 95% CI 0.59–0.91), or postgraduate neurology training program (RR 0.67, 95% CI 0.55–0.82). In multivariate models, higher physician density maintained significant effects (RR 0.67; 95% CI 0.52–0.88). Significance: Even among resource‐limited regions, people with epilepsy in countries with fewer economic, health care, neurology, and epilepsy‐specific resources are more likely to have untreated epilepsy. Community‐based epilepsy care programs have improved access to treatment, but in order to decrease the epilepsy‐treatment gap, poverty and inequalities of health care, neurology, and epilepsy resources must be dealt with at the local, national, and global levels.     

Clinical experience with generic levetiracetam in people with epilepsy

Purpose: To describe the clinical outcomes of a compulsory switch from branded to generic levetiracetam (LEV) among people with epilepsy (PWE) in an outpatient setting. Methods: We conducted a retrospective chart review of 760 unduplicated consecutive adult patients attending a tertiary care epilepsy clinic at Ben Taub General Hospital. On November 1, 2008 hospital policy required all patients receiving branded LEV to be automatically switched to generic LEV. We calculated the proportion of patients switching back to branded LEV and reasons for the switch back. Key Findings: Of the 260 patients (34%) being prescribed LEV (generic and brand name) during the study period, 105 (42.9%) were switched back to brand name LEV by their treating physicians. Reasons for switch back included increase in seizure frequency (19.6% vs. 1.6%; p < 0.0001) and adverse effects (AEs) (3.3%). AEs included headache, fatigue, and aggression. Patient age was associated with switchback when controlling for gender, epilepsy classification, and treatment characteristics [relative risk (RR) 2.44; 95% confidence interval (CI) 2.09–2.84; p < 0.05)]. An increase in seizure frequency subsequent to generic substitution was associated with polytherapy compared to monotherapy (3.225; 1.512–6.880; p < 0.05). Significance: A significant proportion of patients in our cohort on generic LEV required switch back to the branded drug. Careful monitoring is imperative because a compulsory switch from branded to generic LEV may lead to poor clinical outcomes, with risk of AEs and increased seizure frequency.     

The incidence of injuries in persons with and without epilepsy—A population‐based study

Purpose: To compare the 1‐year population‐based incidence and types of injuries in persons with and without epilepsy. Methods: Three administrative databases (inpatient visits, physician claims, and emergency room visits) were linked from fiscal years 1996–2003 using a provincial insurance plan registry, which captures 99% of a population of 1.4 million in a large Canadian health region. Epilepsy cases (all age groups) from fiscal year 1996–2002 were identified. Three people without epilepsy were matched to one person with epilepsy for age (±1 year) and sex. Injuries were defined as any of 16 types of injuries for which medical attention was sought that occurred within fiscal year 2003. Results: Eight thousand eight hundred ninety subjects with epilepsy were identified and matched to 26,670 controls for age and sex. The mean age was 37.4 years (range 0.01–96.4 years), and 51.3% of subjects were male. The 1‐year incidence of one or more injuries was 20.6% among persons with epilepsy and 16.1% among those without epilepsy (p < 0.001). Of the 16 types of injuries studied, 11 were higher in persons with epilepsy compared to those without epilepsy, and included fractures, crushing injuries, intracranial injuries, other types of head injuries, and multiple injuries. The difference was still significant after adjusting for age, gender, and comorbidities. Discussion: The 1‐year incidence of injuries in this study was greater in persons with epilepsy compared to those without epilepsy, for nearly all injury types. Injury prevention should be discussed during routine visits in persons with epilepsy.     

A longitudinal study of epilepsy in Kolkata, India

Purpose: This study aimed to determine the prevalence, incidence, and mortality rates of epilepsy in the city of Kolkata, India. This is the first such longitudinal study in a heterogeneous urban Indian population. Methods: A two‐stage door‐to‐door survey of a stratified random sample was undertaken within the municipal limits of Kolkata. Trained field workers detected and interviewed the cases using a simple screening questionnaire, and the detailed follow‐up was done by neurologists. The survey was conducted annually for five consecutive years from March 2003 through February 2008. Results: A total of 52,377 (52.74% men) individuals were screened. There were 309 prevalent and 66 incident cases of active epilepsy. The prevalence and average annual incidence rate (AAIR) with 95% confidence interval (CI), age‐standardized to World Standard Population, were 572.8 (509.79–641.54) per 100,000 and 27.27 (21.03–34.80) per 100,000 per year, respectively. The age‐specific incidence rates of epilepsy showed bimodal distribution. During the 5‐year period, 20 cases of active epilepsy died. The average annual mortality rate (AAMR) was 7.63 (95% CI 4.45–11.26) per 100,000 population per year. Compared to the general population of Kolkata, the all‐cause standardized mortality ratio (SMR) for persons with epilepsy was 2.58 overall (men 3.67; women 1.77). There was no significant difference between slum and nonslum dwellers in epidemiologic parameters. Conclusions: The AAIR of epilepsy is comparable to that observed in developed countries, but AAMR is higher. The all‐cause SMR for epilepsy relative to the general population is, however, similar to that of developed nations.     

Epidemiology of Guillain‐Barré syndrome in Finland 2004–2014

At total mean incidence of 0.84–1.1/100,000 the occurrence of Guillain‐Barré syndrome (GBS) is reported to be low in Finland compared to other Caucasian populations. However, a recent study from Southwestern Finland reported an incidence of 1.82/100,000 which is comparable to other Caucasian populations. We analyzed discharge data covering the years 2004 through 2014 on all neurological admissions in all Finnish university and central hospitals with a primary diagnosis of GBS. A total of 989 admissions due to GBS (917 individuals) were identified. The standardized (European population) annual incidence rate was 1.70/100,000 person‐years (95% confidence interval 1.60–1.81). GBS incidence had an increasing trend with age. The likelihood of GBS was higher among girls and adolescent women than boys and men of same age (male:female incidence rate ratio [IRR] 0.56), while in the older age groups (>19 years) the occurrence of GBS was higher among males than females (male:female IRR 1.59). The incidence of GBS remained stable during the study period. There was no seasonal variation in GBS admission frequencies (p = 0.28). No significant effect of the 2009–2010 H1N1 influenza or vaccination against it for GBS occurrence was observed. We suggest that GBS is as common, and has similar age‐distribution in Finland as in other European countries. Sex‐associated susceptibility for GBS appears to be different in children‐adolescents and adults.     

Seizure-related cardiac repolarization abnormalities are associated with ictal hypoxemia

Purpose: Cardiac arrhythmias and respiratory disturbances have been proposed as likely causes for sudden unexpected death in epilepsy. Oxygen desaturation occurs in one‐third of patients with localization‐related epilepsy (LRE) undergoing inpatient video–electroencephalography (EEG) telemetry (VET) as part of their presurgical workup. Ictal‐related oxygen desaturation is accompanied by hypercapnia. Both abnormal lengthening and shortening of the corrected QT interval (QTc) on electrocardiography (ECG) have been reported with seizures. QTc abnormalities are associated with increased risk of sudden cardiac death. We hypothesized that there may be an association between ictal hypoxemia and cardiac repolarization abnormalities. Methods: VET data from patients with refractory LRE were analyzed. Consecutive patients having at least one seizure with accompanying oxygen desaturation below 90% and artifact‐free ECG data were selected. ECG during the 1 min prior to seizure onset (PRE) and during the ictal/postictal period with accompanying oxygen desaturation below 90% (DESAT) was analyzed. Consecutive QT and RR intervals were measured. In the same patients, DESAT seizures were compared with seizures without accompanying oxygen desaturation below 90% (NODESAT). For NODESAT seizures, QT and RR intervals for 2 min after seizure onset were measured. Key Findings: Thirty‐seven DESAT seizures were analyzed in 17 patients with localization‐related epilepsy. A total of 2,448 QT and RR intervals were analyzed during PRE. During DESAT, 1,554 QT and RR intervals were analyzed. Twelve of the 17 patients had at least one NODESAT seizure. A total of 19 NODESAT seizures were analyzed, including 1,558 QT and RR intervals during PRE and 3,408 QT and RR intervals during NODESAT. The odds ratio for an abnormally prolonged (>457 ms) QTcH (Hodges correction method) during DESAT relative to PRE was 10.64 (p < 0.0001). The odds ratio for an abnormally shortened (<372 ms) QTcH during DESAT relative to PRE was 1.65 (p < 0.0001). Seizure‐related shortening and prolongation of QTc during DESAT were also observed when Fridericia correction of the QT was applied. During DESAT seizures, the mean range of QT values (QTr) (61.14 ms) was significantly different from that during PRE (44.43 ms) (p = 0.01). There was a significant association between DESAT QTr and oxygen saturation nadir (p = 0.025) and between DESAT QTr and duration of oxygen desaturation (p < 0.0001). Both QTcH prolongation and shortening also occurred with NODESAT seizures. A seizure‐associated prolonged QTcH was more likely during DESAT than NODESAT, with an odds ratio of 4.30 (p < 0.0001). A seizure‐associated shortened QTcH was more likely during DESAT than NODESAT with an odds ratio of 2.13 (p < 0.0001). Significance: We have shown that the likelihood of abnormal QTcH prolongation is increased 4.3‐fold with seizures that are associated with oxygen desaturation when compared with seizures that are not accompanied with oxygen desaturation. The likelihood of abnormally shortened QTcH increases with seizures that are accompanied by oxygen desaturation with an odds ratio of 2.13 compared with that in seizures without desaturations. There is a significant association between the depth and duration of oxygen desaturation and QTr increase. These findings may be related to the pathophysiology of SUDEP.     

Newly diagnosed epileptic seizures: focus on an elderly population on the French island of Réunion in the Southern Indian Ocean

Purpose: To describe seizure types and risk factors among elderly people with newly diagnosed epileptic seizures living on La Réunion, a French Island in the Southern Indian Ocean. Methods: We describe an elderly population with newly diagnosed epileptic seizures using data from the EPIREUN study conducted between July 1, 2004 and June 30, 2005. The methodology is described in detail in the EPIREUN study report ( Mignard et al., 2009 ). Key Findings: There were 153 single unprovoked seizures (84.1%); their incidence was 278.1 [95% confidence interval (CI) 237.4–325.9] per 100,000. The incidence of newly diagnosed epilepsy was 125.4 (95% CI, 99.1–158.8) per 100,000. Twenty‐eight acute symptomatic seizures occurred (15.4%); the incidence was 50.9 (95% CI 35.1–73.7) per 100,000. The annual incidence of newly diagnosed epileptic seizure in the elderly was 330.8 (95% CI 286.1–382.6) per 100,000: 403.0 (95% CI 328.5–494.3) per 100,000 in men and 279.6 (95% CI, 227.4–343.8) per 100,000 in women. Sex had a significant (p = 0.014) effect on incidence: elderly men had a risk ratio of 1.44 compared to women of developing a newly diagnosed epileptic seizure. The etiology of single unprovoked seizure was as follows: stroke, 77 cases (50.3%); cryptogenic, 36 (23.5%); alcoholism, 10 (6.6%); a combination of several causes such as polypathology, 9 (5.9%); degenerative disease, 6 (4.0%); HIV infection, 2 (2.0%), and undetermined causes (2.7%). Most patients (170; 93.4%) were hospitalized, and 110 (60.8%) were treated. Among patients treated, 49 (44.5%) were given sodium valproate, 25 (22.7%) benzodiazepines, 12 (10.9%) phenytoin, 9 (8.2%) lamotrigine, 8 (7.3%) Trileptal, and 7 (6.4%) gabapentin. Significance: Our findings show that the incidences of newly diagnosed epileptic seizures and newly diagnosed epilepsy were high in the elderly population of La Réunion. These incidences were significantly higher in men than in women. These results may be attributable to the high incidence of cerebrovascular diseases and comorbidities in this population.     

Placebo-corrected efficacy of modern nonenzyme-inducing AEDs for refractory focal epilepsy: systematic review and meta-analysis

Purpose: Given serious concerns over the adverse effects of enzyme induction, modern nonenzyme‐inducing antiepileptic drugs (AEDs) may be preferable, provided they have similar efficacy as enzyme‐inducing AEDs. This is currently unclear. Methods: Therefore, we performed a meta‐analysis of the evidence to determine the placebo‐corrected efficacy of adjunctive treatment with modern nonenzyme‐inducing AEDs versus modern enzyme‐inducing AEDs that are on the market for refractory focal epilepsy. Key Findings: Of 322 potentially eligible articles reviewed in full text, 129 (40%) fulfilled eligibility criteria. After excluding 92 publications, 37 studies dealing with a total of 9,860 patients with refractory focal epilepsy form the basis for the evidence. The overall weighted pooled‐risk ratio (RR) in favor of enzyme‐inducing AEDs over placebo was 2.37 (95% confidence interval [CI] 1.77–3.18, p < 0.001) for at least 50% seizure reduction and 4.45 (2.26–8.76, p < 0.001) for seizure freedom. The corresponding weighted pooled RR in favor of nonenzyme‐inducing AEDs over placebo was 2.28 (95% CI 2.03–2.57, p < 0.001) for at least 50% seizure reduction and 3.23 (95% CI 2.23–4.67, p < 0.001) for seizure freedom. In a meta‐regression analysis in the same sample with at least 50% seizure reduction as outcome, the ratio of RRs for enzyme‐inducing AEDs (eight studies) versus nonenzyme‐inducing AEDs (29 studies) was 1.01 (95% CI 0.77–1.34, p = 0.92)). Similarly, the ratio of RRs for a seizure‐free outcome for enzyme‐inducing AEDs (six studies) versus nonenzyme‐inducing AEDs (19 studies) was 1.38 (95% CI 0.60–3.16, p = 0.43). Significance: Although the presence of moderate heterogeneity may reduce the validity of the results and limit generalizations from the findings, we conclude that the efficacy of adjunctive treatment with modern nonenzyme‐inducing AEDs is similar to that of enzyme‐inducing AEDs. Given the negative consequences of enzyme induction, our data suggest that nonenzyme‐inducing AEDs may be useful alternatives to enzyme‐inducing AEDs for treatment of refractory focal epilepsy.     

Familial aggregation of Parkinson's disease in a multiethnic community‐based case‐control study

To assess the familial aggregation of Parkinson's disease (PD), we compared the cumulative incidence of PD among first‐degree relatives of PD cases and controls. We identified newly diagnosed patients with PD (n = 573) during 1994 to 1995 within Kaiser Permanente Medical Care Program of Northern California and recruited 496 cases (87%) for the case‐control study. Of 720 eligible controls matched by birth year and sex to cases, 541 (75%) agreed to participate. Information on family history of PD and other neurodegenerative diseases was obtained by in‐person structured interview. We used the reconstructed cohort approach that provides a better estimate of the risk. The cumulative incidence of PD was significantly higher among relatives of PD patients compared with relatives of controls (2.0 vs. 0.7%; relative risk (RR) = 3.4, 95% confidence interval (CI) 1.9–5.9; P = 0.0001). The degree of familial aggregation was higher among first‐degree relatives of Hispanic PD cases compared with Hispanic controls (3.7% vs. 0.4%; RR = 8.5, 95% CI 1.0–68.9) than it was among non‐Hispanic Caucasian cases and controls (2.0% vs. 0.8%; RR = 2.7, 95% CI 1.5–5.1; P = 0.02). The familial aggregation of PD was stronger among the siblings of PD cases (RR = 5.4, 95% CI 1.8–16.0) than among parents (RR = 2.7, 95% CI 1.3–5.2). The incidence and familial aggregation of PD is highest among Hispanics, warranting further studies of genetic and environmental risk factors in the Hispanic population. © 2010 Movement Disorder Society     

Long-term changes in the incidence of childhood epilepsy. A population study from Finland

BackgroundThe incidence of childhood epilepsy has changed during the past decades, but it is unclear whether it increased or decreased.MethodsChanges in drug-treated childhood epilepsy between 1968 and 2012 were evaluated using the Finnish nationwide register of all children, aged ≤ 15 years, on antiepileptic drugs (AEDs) prescribed for the treatment of epilepsy. The first registered entitlement to full-refundable AEDs was used as a proxy for newly diagnosed epilepsy. Incidence densities were calculated as ratios of annual new cases per 100,000 person-years in each calendar year during 1968 to 2012.ResultsThe annual incidence density of newly treated childhood epilepsy increased from 35 in the 1960s to 87 per 100,000 person-years in the 1990s and decreased thereafter to 61 per 100,000 person-years. Since 1996, the incidence density decreased 1–2% per year in children aged < 1, 1–5, or 6–10 years (all 95% confidence intervals within 0.3%–3%), while no substantial change was seen in older children.ConclusionThe incidence of drug-treated childhood epilepsy from the late 1960s to the early 1990s distinctly increased. The reasons for the increase are not fully understood but may include increasing ascertainment through improved diagnosis and a wider acceptance of AED treatment. Since the 1990s, a slight decline can be seen, probably reflecting the recent improvement in child health and safety.     

Dopamine transporter PET in normal aging: Dopamine transporter decline and its possible role in preservation of motor function

Objectives : To determine the impact of age‐related decline in dopamine transporter (DAT) expression on motor function in the elderly. Methods : About 33 normal individuals of a wide age range were scanned with PET employing d‐threo‐[¹¹C]‐methylphenidate (MP, a marker of DAT) and [¹¹C]‐dihydrotetrabenazine (DTBZ, that binds to the vesicular monoamine transporter Type 2). Motor function was assessed using the Purdue Pegboard Test (PPB). We analyzed the relationship between [¹¹C]‐MP and motor performance. Results : Age ranged from 27‐ to 77‐year old (mean ± SD, 54.75 ± 14.14). There was no age‐related decline in binding potentials (BP) for [¹¹C]‐DTBZ. In contrast, [¹¹C]‐MP BP was inversely related to age in all striatal regions analyzed (caudate: reduction of 11.2% per decade, P < 0.0001, r = ?0.86; putamen: reduction of 10.5% per decade, P < 0.0001, r = ?0.80). A differential effect of [¹¹C]‐MP on PPB could be observed according to age group. There was a positive relation between the PPB and [¹¹C]‐MP in young individuals (coefficient = 13.56), whereas in individuals greater than 57 years this relationship was negative (coefficient = ?19.53, P = 0.031). Conclusions : Our findings confirm prior observations of age‐related DAT decline and suggest that this phenomenon is independent of changes in VMAT2. After the fifth decade of life, this reduction in DAT binding is associated with a motor performance comparable to mid‐adult life. These findings imply that biochemical processes associated with healthy aging may offset the naturaldecline in motor function observed in the elderly. Synapse 64:146–151, 2010. © 2009 Wiley‐Liss, Inc.     

When is a postoperative seizure equivalent to “epilepsy recurrence” after epilepsy surgery?

Purpose: Up to one‐half of epilepsy surgery patients will have at least one seizure after surgery. We aim to characterize the prognosis following a first postoperative seizure, and provide criteria allowing early identification of recurrent refractory epilepsy. Methods: Analyzing 915 epilepsy surgery patients operated on between 1990 and 2007, we studied 276 who had ≥1 seizure beyond the immediate postoperative period. The probability of subsequent seizures was calculated using survival analysis. Patients were divided into seizure‐free (no seizures for ≥1 year) and refractory (persistent seizures) and analyzed using multivariate regression analysis. Results: After a first seizure, 50% had a recurrence within 1 month and 77% within a year before the risk slowed down to additional 2–3% increments every two subsequent years. After a second seizure, 50% had a recurrence within 2 weeks, 78% within 2 months, and 83% within 6 months. Having both the first and second seizures within six postoperative months [odds ratio (OR) 4.04; 95% confidence interval (CI) 2.05–8.40; p = 0.0001], an unprovoked initial recurrence (OR 3.92; 95% CI 2.13–7.30; p < 0.0001), and ipsilateral spikes on a 6‐months postoperative electroencephalography (EEG) (OR 2.05; 95% CI 1.10–3.88; p = 0.025) predicted a poorer outcome, with 95% of patients who had all three risk factors becoming refractory. All patients with cryptogenic epilepsy and recurrent seizures developed refractoriness. Discussion: Seizures will recur in most patients who present with their first postoperative event, with one‐third eventually regaining seizure‐freedom. Etiology and early and unprovoked postoperative seizures with epileptiform activity on EEG at six postoperative months may predict recurrent medical refractoriness.     

Evaluation of perioperative fatal pulmonary embolism and death in cancer surgical patients: the MC-4 cancer substudy

Cancer patients undergoing surgery are at a high risk of venous thromboembolism, but few studies have described the rate of autopsy-confirmed fatal pulmonary embolism after heparin thromboprophylaxis. In a post hoc analysis of a randomized study (MC-4), which compared the efficacy and safety of certoparin (3000 anti-Xa IU, subcutaneously, once-daily) with unfractionated heparin (5000 IU, subcutaneously, three-times daily) in 23078 patients undergoing surgery lasting more than 30 min, the incidence of autopsy-confirmed fatal pulmonary embolism, death and bleeding in the cancer patients (n=6124) was compared with non-cancer patients (n=16954). Fatal pulmonary embolism was significantly more frequent in cancer patients (0.33% [20/6124]) than in non-cancer patients (0.09% [15/16954], relative risk (RR), 3.7 [95% confidence intervals (CI), 1.80, 7.77], p=0.0001) at 14 days post-prophylaxis. Perioperative mortality was also significantly higher in cancer patients than in noncancer patients (3.14% [192/6124] vs. 0.71% [120/16954], RR, 4.54 [95% CI, 3.59, 5.76], p=0.0001), as were blood loss (p<0.0001), and transfusion requirements (p<0.0001). Prevention of venous thromboembolism in cancer surgical patients remains a clinical challenge.     

Proportion of older people in the community as a predictor of increasing stroke incidence

OBJECTIVES: To compare stroke incidence rates among comparable registries and to make correlations with aging of the resident populations. METHODS: This correlation study included all comparable stroke registries maintained in industrialized countries (Italy, France, United Kingdom, Denmark, Norway, United States, and Australia). Eleven community-based stroke registries with similar high proportions of radiologically confirmed diagnoses based on standard definitions were identified. Incidence rates of first-ever stroke from the prospective L'Aquila registry and from the other registries were compared after age and sex standardization to the 1996 European population. The rates were then correlated with the proportion of individuals aged 65 and over in the corresponding resident populations by means of the Poisson regression analysis. RESULTS: In the L'Aquila registry, the crude annual incidence of first-ever stroke was 281/100,000 (95% confidence interval 271-293) based on 2,515 patients included during a 3-year period. The rate standardized to the European population was 249/100,000. Standardized incidence ratios indicated a significant excess of first-ever strokes in the L'Aquila registry up to 51% with respect to most of the compared studies. A significant correlation was also found between crude (p < 0.0001) and standardized (p = 0.0012) stroke incidence rates and proportions of individuals aged 65 and over in the different populations. CONCLUSIONS: The L'Aquila experience suggests that any further aging of a population will increase the stroke occurrence for both the reasons of a direct and predictable effect of the growing proportion of elderly individuals within that population and a disproportionately increased stroke risk in the older age groups.     

Falling status epilepticus mortality rates in England and Wales: 2001–2013?

Status epilepticus (SE) is associated with significant mortality and accounts for ~10% of epilepsy‐related deaths. Epilepsy and SE mortality data from 2001 to 2013, in addition to annual age group populations for England and Wales, were obtained from the Office of National Statistics website ( www.ons.gov.uk ). Age‐adjusted mortality rates for epilepsy and SE with 95% confidence intervals (CIs) were calculated using the European Standard Population. Trends in mortality rates for both epilepsy and SE were investigated using the Spearman coefficient. The crude mean epilepsy mortality rate per 100,000 person‐years between 2001 and 2013 was 1.87 (95% CI 1.83–1.91), with a corresponding SE mortality rate of 0.14 (95% CI 0.13–0.15). The mean age‐adjusted epilepsy mortality rate per 100,000 person years was 3.24 (95% CI 3.12–3.35), with a corresponding SE mortality rate of 0.24 (95% CI 0.21–0.27). All epilepsy deaths significantly decreased from 2001 to 2013 (Spearman's ρ ?0.733, p = 0.004); this decrease was predominantly due to a decrease in SE deaths (Spearman's ρ ?0.917, p < 0.001). In summary, our finding supports the hypothesis that the policy of early and aggressive treatment of SE may be improving the prognosis of this condition in England and Wales.