Dementia in western Europe: epidemiological evidence and implications for policy making

Dementia is receiving increasing attention from governments and politicians. Epidemiological research based on western European populations done 20 years ago provided key initial evidence for dementia policy making, but these estimates are now out of date because of changes in life expectancy, living conditions, and health profiles. To assess whether dementia occurrence has changed during the past 20–30 years, investigators of five different studies done in western Europe (Sweden [Stockholm and Gothenburg], the Netherlands [Rotterdam], the UK [England], and Spain [Zaragoza]) have compared dementia occurrence using consistent research methods between two timepoints in well-defined geographical areas. Findings from four of the five studies showed non-significant changes in overall dementia occurrence. The only significant reduction in overall prevalence was found in the study done in the UK, powered and designed explicitly from its outset to detect change across generations (decrease in prevalence of 22%; p=0·003). Findings from the study done in Zaragoza (Spain) showed a significant reduction in dementia prevalence in men (43%; p=0·0002). The studies estimating incidence done in Stockholm and Rotterdam reported non-significant reductions. Such reductions could be the outcomes from earlier population-level investments such as improved education and living conditions, and better prevention and treatment of vascular and chronic conditions. This evidence suggests that attention to optimum health early in life might benefit cognitive health late in life. Policy planning and future research should be balanced across primary (policies reducing risk and increasing cognitive reserve), secondary (early detection and screening), and tertiary (once dementia is present) prevention. Each has their place, but upstream primary prevention has the largest effect on reduction of later dementia occurrence and disability.

Lancet Neurology 2015

Early prediction of long-term upper limb spasticity after stroke Part of the SALGOT study

Objective: To identify predictors and the optimal time point for the early prediction of the presence and severity of spasticity in the upper limb 12 months poststroke.

Methods: In total, 117 patients in the Gothenburg area who had experienced a stroke for the first time and with documented arm paresis day 3 poststroke were consecutively included. Assessments were made at admission and at 3 and 10 days, 4 weeks, and 12 months poststroke. Upper limb spasticity in elbow flexion/extension and wrist flexion/extension was assessed with the modified Ashworth Scale (MAS). Any spasticity was regarded as MAS ≥1, and severe spasticity was regarded as MAS ≥2 in any of the muscles. Sensorimotor function, sensation, pain, and joint range of motion in the upper limb were assessed with the Fugl-Meyer assessment scale, and, together with demographic and diagnostic information, were included in both univariate and multivariate logistic regression analysis models. Seventy-six patients were included in the logistic regression analysis.

Results: Sensorimotor function was the most important predictor both for any and severe spasticity 12 months poststroke. In addition, spasticity 4 weeks poststroke was a significant predictor for severe spasticity. The best prediction model for any spasticity was observed 10 days poststroke (85% sensitivity, 90% specificity). The best prediction model for severe spasticity was observed 4 weeks poststroke (91% sensitivity, 92% specificity).

Conclusions: Reduced sensorimotor function was the most important predictor both for any and severe spasticity, and spasticity could be predicted with high sensitivity and specificity 10 days poststroke.

Neurology 2015

The unruptured intracranial aneurysm treatment score A multidisciplinary consensus

Objective: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. Methods: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* 5 0 indicating excellent agreement and vr* 5 1 indicating poor agreement). Results: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1–4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1–4.4) for panel members and 4.5 (95% CI 4.3–4.6) for external reviewers (p 5 0.017). Mean Likert scores were 4.2 (95% CI 4.1–4.3) for interventional reviewers (n 5 56) and 4.1 (95% CI 3.9–4.4) for noninterventional reviewers (n 5 12) (p 5 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019–0.033). Conclusions: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.

Neurology 2015

Habenula Recently recognized functions and potential clinical relevance

The habenula (Hb) (from the Latin, little rein) is a phylogenetically old structure located in the dorsomedial portion of the thalamus and is an important link between the forebrain and brainstem monoaminergic nuclei. The Hb includes 2 subdivisions—lateral and medial—which differ in their neurochemical characteristics and connectivity. The lateral Hb receives inputs from the cerebral cortex, lateral hypothalamus, and globus pallidus (GP) and exerts an inhibitory modulation both on dopaminergic neurons of the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) and on serotonergic neurons of the median and dorsal raphe nuclei. This inhibitory effect is primarily mediated by γ-aminobutyric acid (GABA)ergic neurons located in the rostromedial tegmental nucleus (RMTg). The medial Hb receives its main inputs from the medial septum and projects to the interpeduncular nucleus (IPN), which in turn controls the activity of monoaminergic brainstem nuclei. Via all these connections, the Hb has a major role in emotional regulation of behavior. For example, the lateral Hb processes negative emotional state information (including disappointment, punishment, and pain) and inhibits the SNc/VTA neurons involved in learning and motivation. Both the lateral Hb and the medial Hb may also participate in sleep regulation, pain modulation, and the mechanism of drug addiction. Neuroimaging studies allow identification of the Hb and its main connections in humans, and showed its activation in response to negative emotions or pain. The increasing interest in the physiology of the Hb and its involvement in neurologic and psychiatric disease is reflected by a large number of recent reviews.

Neurology 2015

New-onset refractory status epilepticus Etiology, clinical features, and outcome

Objectives: The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus.

Methods: Retrospective review of patients with refractory status epilepticus without etiology identified within 48 hours of admission between January 1, 2008, and December 31, 2013, in 13 academic medical centers. The primary outcome measure was poor functional outcome at discharge (defined as a score >3 on the modified Rankin Scale).

Results: Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies were autoimmune (19%) and paraneoplastic (18%) encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor outcome included duration of status epilepticus, use of anesthetics, and medical complications. Among the 63 patients with available follow-up data (median 9 months), functional status improved in 36 (57%); 79% had good or fair outcome at last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medications. Immune therapies were used less frequently in cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes.

Conclusions: Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation.

Neurology 2015

Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy A randomized tria

Objective: To assess efficacy and safety of adjunctive perampanel in patients with drug-resistant, primary generalized tonic-clonic (PGTC) seizures in idiopathic generalized epilepsy (IGE).

Methods: In this multicenter, double-blind study (ClinicalTrials.gov identifier: NCT01393743; funded by Eisai Inc.), patients 12 years or older with PGTC seizures and IGE were randomized to placebo or perampanel during a 4-week titration period (perampanel uptitrated from 2 to 8 mg/d, or highest tolerated dose) and 13-week maintenance period. The primary endpoint was percent change in PGTC seizure frequency per 28 days (titration plus maintenance vs baseline). The key secondary endpoint (primary endpoint for European Union registration) was 50% PGTC seizure responder rate (patients achieving ≥50% reduction in PGTC seizure frequency; maintenance vs baseline). Treatment-emergent adverse events were monitored.

Results: Of 164 randomized patients, 162 comprised the full analysis set (placebo, 81; perampanel, 81). Compared with placebo, perampanel conferred a greater median percent change in PGTC seizure frequency per 28 days (−38.4% vs −76.5%; p < 0.0001) and greater 50% PGTC seizure responder rate (39.5% vs 64.2%; p = 0.0019). During maintenance, 12.3% of placebo-treated patients and 30.9% of perampanel-treated patients achieved PGTC seizure freedom. For the safety analysis (placebo, 82; perampanel, 81), the most frequent treatment-emergent adverse events with perampanel were dizziness (32.1%) and fatigue (14.8%).

Conclusions: Adjunctive perampanel was well tolerated and improved control of drug-resistant PGTC seizures in patients with IGE.

Classification of evidence: This study provides Class I evidence that adjunctive perampanel reduces PGTC seizure frequency, compared with placebo, in patients with drug-resistant PGTC seizures in IGE.

Neurology 2015