Is the computerized assessment of psychomotor speed more sensitive to cognitive effects of antiepileptic pharmacotherapy than tests with a focus on higher-order cognitive processing? Implications for the choice of sensitive test parameters.

The study evaluated whether it is psychomotor speed or higher-order cognitive processing which is primarily affected by antiepileptic drug (AED) treatment in epilepsy and whether computerized testing versus paper-pencil testing of executive functions is more sensitive. In this retrospective observational study, 55 patients with epilepsy underwent NeuroCog FXⓇ, a computerized battery assessing "psychomotor speed/alertness" and "cognitive processing" via 8 tasks, and EpiTrackⓇ, a paper-pencil screening of "executive functions and working memory" based on 6 subtests. Test performance was related to the number of drugs and the Defined Daily Dose and the presence/absence of AEDs with known adverse psychotropic effects. EpiTrackⓇ performance correlated with "cognitive processing" of the NeuroCog FXⓇ but not with "psychomotor speed/alertness". Significant correlations with drug load were mainly yielded for EpiTrackⓇ (number of AEDs: r = -0.551, total DDD: r = -0.452) and "cognitive processing" (number of AEDs: r = -0.433, total DDD: r = -0.415). "Psychomotor speed/alertness" was less related to drug load (number of AEDs: r = -0.285, total DDD: r = -0.232). Statistical control for "psychomotor speed/alertness" hardly changed the correlations of EpiTrackⓇ or "cognitive processing" with drug load indices. AEDs with known adverse profiles negatively affected EpiTrackⓇ and the "cognitive processing" but not the "psychomotor speed/alertness" domain of the computerized test. The results demonstrate that it is less basal psychomotor speed than higher-order cognitive processing which is negatively affected by antiepileptic pharmacotherapy. The results question the value of (computer-)tests with a major emphasis on psychomotor speed and alertness for cognitive drug monitoring.

An inception cohort study assessing the role of pneumococcal and other bacterial pathogens in children with influenza and ILI and a clinical decision model for stringent antibiotic use.

BACKGROUND: Influenza-like illness (ILI) is a common reason for paediatric consultations. Viral causes predominate, but antibiotics are used frequently. With regard to influenza, pneumococcal coinfections are considered major contributors to morbidity/mortality. METHODS: In the context of a perennial quality management (QM) programme at the Charité Departments of Paediatrics and Microbiology in collaboration with the Robert Koch Institute, children aged 0-18 years presenting with signs and symptoms of ILI were followed from the time of initial presentation until hospital discharge (Charité Influenza-Like Disease = ChILD Cohort). An independent QM team performed highly standardized clinical assessments using a disease severity score based on World Health Organization criteria for uncomplicated and complicated/progressive disease. Nasopharyngeal and pharyngeal samples were collected for viral reverse transcription polymerase chain reaction and bacterial culture/sensitivity and MaldiTOF analyses. The term 'detection' was used to denote any evidence of viral or bacterial pathogens in the (naso)pharyngeal cavity. With the ChILD Cohort data collected, a standard operating procedure (SOP) was created as a model system to reduce the inappropriate use of antibiotics in children with ILI. Monte Carlo simulations were performed to assess cost-effectiveness. RESULTS: Among 2,569 ChILD Cohort patients enrolled from 12/2010 to 04/2013 (55% male, mean age 3.2 years, range 0-18, 19% >5 years), 411 patients showed laboratory-confirmed influenza, with bacterial co-detection in 35%. Influenza and pneumococcus were detected simultaneously in 12/2,569 patients, with disease severity clearly below average. Pneumococcal vaccination rates were close to 90%. Nonetheless, every fifth patient was already on antibiotics upon presentation; new antibiotic prescriptions were issued in an additional 20%. Simulation of the model SOP in the same dataset revealed that the proposed decision model could have reduced the inappropriate use of antibiotics significantly (P<0.01) with an incremental cost-effectiveness ratio of -99.55€. CONCLUSIONS: Physicians should be made aware that in times of pneumococcal vaccination the prevalence and severity of influenza infections complicated by pneumococci may decline. Microbiological testing in combination with standardized disease severity assessments and review of vaccination records could be cost-effective, as well as promoting stringent use of antibiotics and a personalized approach to managing children with ILI.

Depression in epilepsy: a critical review from a clinical perspective.

Depression is a serious and frequent comorbidity of epilepsy and other neurological conditions. Here, we review recent studies on the relationship between epilepsy and depression with regard to diagnostic criteria, epidemiology, etiology and treatment. Depression in epilepsy can be described in the general framework of the diathesis-stress model: chronic stress exposure owing to the 'burden of epilepsy' and learned helplessness due to the threat of recurrent seizures as unpredictable aversive events represent psychological risk factors for the development of depression. Epilepsy-related factors (for example, focus site or side) have shown little effect on mood. Nonepileptic individuals who are adversely affected by seizures (for example, parents of pediatric patients with epilepsy, and patients with psychogenic nonepileptic seizures) show increased levels of depression, similar to patients with epilepsy. However, seizures, subclinical hypersynchronous neural discharges and some antiepileptic drugs may cause acute states of depressive mood or depression on a purely neurobiological basis. Antidepressant drugs and psychotherapy have shown moderate efficacy in the treatment of depression comorbidity, but randomized controlled trials in patients with epilepsy are lacking, especially for drugs.

Computer-based assessment of cognitive functions in brain tumor patients.

NeuroCogFX is a short yet comprehensive computer-based neuropsychological battery of tests developed to investigate neurological patients for cognitive dysfunction after potentially neurotoxic therapy. NeuroCogFX had been standardized in a group of 242 healthy controls (Fliessbach et al., Fortschr Neurol Psychiatr 74:643-650, 2006). The present study was conducted to assess the practicability, reliability, and validity of NeuroCogFX in brain tumor patients without active disease after tumor-directed therapy. To evaluate its validity, neuropsychological testing with NeuroCogFX was completed parallel to a battery of established neuropsychological tests in 54 patients with different types of brain tumors and without active disease for at least 6 months. Retest reliability was assessed in a different sample of 49 patients with gliomas. Results showed good practicability with a median test duration of 28 min (range 16-51 min). Most subtests showed medium-sized retest reliability in healthy controls and tumor patients, with the exception of the 2-back test and reaction time measures in tumor patients. Convergent validity was confirmed for the domains psychomotor speed, verbal memory, and verbal short-term memory. NeuroCogFX enables serial scientific neuropsychological assessment of brain tumor patients. It can be carried out within a short period of time by non-academic personnel and is therefore applicable to large cohorts, e.g., within clinical trials.