Globally altered microstructural properties and network topology in Rasmussen's encephalitis.

Rasmussen's encephalitis is an immune-mediated brain disorder characterised by progressive unilateral cerebral atrophy, neuroinflammation, drug-resistant seizures and cognitive decline. However, volumetric changes and epileptiform EEG activity were also observed in the contralateral hemisphere, raising questions about the aetiology of contralateral involvement. In this study, we aim to investigate alterations of white matter integrity, structural network topology and network efficiency in Rasmussen's encephalitis using diffusion-tensor imaging. Fourteen individuals with Rasmussen's encephalitis (11 female, median onset 6 years, range 4-22, median disease duration at MRI 5 years, range 0-42) and 20 healthy control subjects were included. All subjects underwent T1-weighted structural and diffusion-tensor imaging. Diffusion-tensor images were analysed using the fixel-based analysis framework included in the MRtrix3 toolbox. Fibre density and cross-section served as a quantitative measure for microstructural white matter integrity. T1-weighted structural images were processed using FreeSurfer, subcortical segmentations and cortical parcellations using the Desikan-Killiany atlas served as nodes in a structural network model, edge weights were determined based on streamline count between pairs of nodes and compared using network-based statistics. Global efficiency was used to quantify network integration on an intrahemispheric level. All metrics were compared cross-sectionally between individuals with Rasmussen's encephalitis and healthy control subjects using sex and age as regressors and within the Rasmussen's encephalitis group using linear regression including age at onset and disease duration as independent variables. Relative to healthy control subjects, individuals with Rasmussen's encephalitis showed significantly (family-wise-error-corrected P < 0.05) lower fibre density and cross-section as well as edge weights in intrahemispheric connections within the ipsilesional hemisphere and in interhemispheric connections. Lower edge weights were noted in the contralesional hemisphere and in interhemispheric connections, with the latter being mainly affected within the first 2 years after disease onset. With longer disease duration, fibre density and cross-section significantly (uncorrected P < 0.01) decreased in both hemispheres. In the contralesional corticospinal tract, fibre density and cross-section significantly (uncorrected P < 0.01) increased with disease duration. Intrahemispheric edge weights (uncorrected P < 0.01) and global efficiency significantly increased with disease duration in both hemispheres (ipsilesional r = 0.74, P = 0.001; contralesional r = 0.67, P = 0.012). Early disease onset was significantly (uncorrected P < 0.01) negatively correlated with lower fibre density and cross-section bilaterally. Our results show that the disease process of Rasmussen's encephalitis is not limited to the cortex of the lesioned hemisphere but should be regarded as a network disease affecting white matter across the entire brain and causing degenerative as well as compensatory changes on a network level.

Mind wandering in anxiety disorders: A status report.

Many investigations have targeted the subject of worry in anxiety disorders. Worry can be regarded as a subtype of mind wandering (MW), which is undeliberate, perseverative, negatively-valenced, and mainly future-oriented. Nevertheless, until now only a few studies have explored the role of overall MW in the origin and course of anxiety disorders. To foster progress in this field, we briefly describe and discuss relevant studies addressing MW in subjects with anxiety disorders or symptoms or disorders associated with anxiety symptoms. Provisional synthesis suggests that: a) the overall amount of MW is positively correlated with anxiety symptoms; b) MW characteristics reflecting worry and rumination appear to be relevant in anxiety; c) comorbid depressive and ADHD symptoms may contribute to excessive MW in anxiety; d) MW-related therapeutic interventions may be useful as complementary treatments in anxiety disorders. However, more studies related to MW in anxiety disorders or symptoms are necessary to corroborate and extend these initial findings. Such investigations should ideally combine experience sampling with self-rating assessments of both MW and worry/rumination.

Long-term neurocognitive function and quality of life after multimodal therapy in adult glioma patients: a prospective long-term follow-up.

PURPOSE: Multimodal therapies have significantly improved prognosis in glioma. However, in particular radiotherapy may induce long-term neurotoxicity compromising patients' neurocognition and quality of life. The present prospective multicenter study aimed to evaluate associations of multimodal treatment with neurocognition with a particular focus on hippocampal irradiation. METHODS: Seventy-one glioma patients (WHO grade 1-4) were serially evaluated with neurocognitive testing and quality of life questionnaires. Prior to (baseline) and following further treatment (median 7.1 years [range 4.6-11.0] after baseline) a standardized computerized neurocognitive test battery (NeuroCog FX) was applied to gauge psychomotor speed and inhibition, verbal short-term memory, working memory, verbal and non-verbal memory as well as verbal fluency. Mean ipsilateral hippocampal radiation dose was determined in a subgroup of 27 patients who received radiotherapy according to radiotherapy plans to evaluate its association with neurocognition. RESULTS: Between baseline and follow-up mean performance in none of the cognitive domains significantly declined in any treatment modality (radiotherapy, chemotherapy, combined radio-chemotherapy, watchful-waiting), except for selective attention in patients receiving chemotherapy alone. Apart from one subtest (inhibition), mean ipsilateral hippocampal radiation dose > 50 Gy (Dmean) as compared to < 10 Gy showed no associations with long-term cognitive functioning. However, patients with Dmean < 10 Gy showed stable or improved performance in all cognitive domains, while patients with > 50 Gy numerically deteriorated in 4/8 domains. CONCLUSIONS: Multimodal glioma therapy seems to affect neurocognition less than generally assumed. Even patients with unilateral hippocampal irradiation with > 50 Gy showed no profound cognitive decline in this series.

How are they doing as adults? Psychosocial and socioeconomic outcomes 11-30 years after pediatric epilepsy surgery.

OBJECTIVE: Pediatric epilepsy surgery yields cure from epilepsy or complete seizure control with continued medication in many patients early in life. This study aimed to evaluate the long-term (>10 years) psychosocial and socioeconomic outcomes of pediatric epilepsy surgery and examine the role of comorbid disability, type of surgery, seizure freedom, and age at surgery. METHODS: A novel ad hoc parent/patient questionnaire was used to assess educational and occupational attainment, marital/familial status, mobility, and other outcomes in patients who underwent unilobar or multilobar surgery for drug-refractory epilepsy during their childhood. The questionnaire also captured information on comorbid disability. RESULTS: Of the 353 eligible patients, 203 could still be contacted and 101 of these (50%) returned appropriately filled-in questionnaires (follow-up intervals: 11-30 [mean: 19.6] years). The cure from epilepsy rate was 53%. Type of surgery was strongly confounded by comorbid disability. Patients with comorbid disabilities had significantly lower rates of regular school degrees, gainful employment, marriage, and driving license (N = 29; 12%, 4%, 0%, 3%) compared with non-disabled patients (N = 69; 89%, 80%, 43%, and 67%, respectively). Patients achieved lower school degrees than their siblings and parents. Non-disabled seizure-free patients had better employment and mobility outcomes compared with non-seizure-free patients. Age at surgery (<10 vs. ≥10 years of age) did not have any effect on any outcome in patients with preschool seizure onset. SIGNIFICANCE: Pediatric epilepsy surgery can lead to permanent relief from epilepsy in many patients, but comorbid disability strongly impacts adult life achievement. In non-disabled patients, favorable outcomes in academic, occupational, marital, and mobility domains were achieved, approaching respective rates in the German population. Complete seizure freedom had additional positive effects on employment and mobility in this group. However, in case of chronic comorbid disability the overall life prospects may be limited despite favorable seizure outcomes.

Clinical adult outcome 11-30 years after pediatric epilepsy surgery: Complications and other surgical adverse events, seizure control, and cure of epilepsy.

OBJECTIVE: Pediatric epilepsy surgery promises seizure freedom or even cure of epilepsy. We evaluated the long-term (≥10 years) adult clinical outcome including surgery-related adverse events and complications, which are generally underreported. METHODS: A monocentric, single-arm, questionnaire study in now adult patients who underwent epilepsy surgery during childhood. A novel ad hoc parental/patient questionnaire, which addressed diverse outcome domains was applied. RESULTS: From a total of 353 eligible patients, 203 could be contacted (3 patients died of causes unknown) and 101 (50%) returned appropriately filled-in surveys. No evidence for a survey-response bias was found. The rate of surgical complications according to the patient records was 9%. As regards the survey, half of the parents/patients reported surgical adverse events (expected and unexpected issues) and one-third reported permanent aversive sequels. Two-thirds of the patients were seizure-free during the last year before follow-up; 63% were Engel class 1A; favorable seizure outcomes (including auras only) were obtained in 73%; and 54% were seizure-free and off antiseizure medicine (ASM), that is, cured of epilepsy. In non-seizure-free patients, seizure relapse occurred at any time during the follow-up interval but 87% of those with a seizure-free first postoperative year were seizure-free at follow-up. One patient experienced a seizure relapse during the ASM withdrawal trial but became seizure-free again with ASMs. Eleven patients reported an increased number of ASMs as compared to the time before surgery. Earlier focal surgery did not affect the long-term clinical outcome. SIGNIFICANCE: Pediatric epilepsy surgery was capable of curing epilepsy in about one-half of the children and to significantly control seizures in about three-fourths. Long-term success of focal surgery did not depend on age at surgery or duration of epilepsy. Surgical adverse events including complications may be underreported and must be assessed more thoroughly.

Anti-seizure efficacy and retention rate of carbamazepine is highly variable in randomized controlled trials: A meta-analysis.

We sought to assess the anti-seizure efficacy of carbamazepine (CBZ) and retention rate (RR) in randomized, controlled trials (RCTs) in epilepsy. Our analysis was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Inclusion criteria were monotherapy of CBZ in adequate dosage for epilepsy treatment and RCT duration of ≥3 months. Outcome measures were seizure freedom rate (SFR) and RR. Random-effects meta-analyses were performed to allow for comparison with other anti-seizure medications (ASMs). Thirty RCTs of 734 were included. SFR at last follow-up ranged from 11% at 36 months to 85% at 3 months. The aggregated SFR at 6 months was 58% (CI 49-66%) and 48% (CI 40-57%) at 12 months. The 6-month SFR among blinded studies was 55% (CI 43-66%), compared with 61% (CI 50-71%) in unblinded studies. The 12-month SFR was not significantly linked to the age of study participants. RR varied from 36% at 24 months to 81% at 6 months. When adjusting for blinding, the aggregated 6-month RR in blinded studies was 59% (CI 52-66%) vs 76% (CI 71-81%) in unblinded studies. The point estimates of SFR of all RCTs showed an upward time trend, with an increase of approximately 15% between the years 1981 and 2018. In conclusion, the SFR and RR of CBZ were highly variable in RCTs and especially affected by study duration and blinding. These results underscore the impact of the design of RCTs investigating ASM and may challenge the wide use of CBZ as a comparator.

Mid-term treatment-related cognitive sequelae in glioma patients.

PURPOSE: Cognitive functioning represents an essential determinant of quality of life. Since significant advances in neuro-oncological treatment have led to prolonged survival it is important to reliably identify possible treatment-related neurocognitive dysfunction in brain tumor patients. Therefore, the present study specifically evaluates the effects of standard treatment modalities on neurocognitive functions in glioma patients within two years after surgery. METHODS: Eighty-six patients with World Health Organization (WHO) grade 1-4 gliomas were treated between 2004 and 2012 and prospectively followed within the German Glioma Network. They received serial neuropsychological assessment of attention, memory and executive functions using the computer-based test battery NeuroCog FX. As the primary outcome the extent of change in cognitive performance over time was compared between patients who received radiotherapy, chemotherapy or combined radio-chemotherapy and patients without any adjuvant therapy. Additionally, the effect of irradiation and chemotherapy was assessed in subgroup analyses. Furthermore, the potential impact of the extent of tumor resection and histopathological characteristics on cognitive functioning were referred to as secondary outcomes. RESULTS: After a median of 16.8 (range 5.9-31.1) months between post-surgery baseline neuropsychological assessment and follow-up assessment, all treatment groups showed numerical and often even statistically significant improvement in all cognitive domains. The extent of change in cognitive functioning showed no difference between treatment groups. Concerning figural memory only, irradiated patients showed less improvement than non-irradiated patients (p = 0.029, η2 = 0.06). Resected patients, yet not patients with biopsy, showed improvement in all cognitive domains. Compared to patients with astrocytomas, patients with oligodendrogliomas revealed a greater potential to improve in attentional and executive functions. However, the heterogeneity of the patient group and the potentially selected cohort may confound results. CONCLUSION: Within a two-year post-surgery interval, radiotherapy, chemotherapy or their combination as standard treatment did not have a detrimental effect on cognitive functions in WHO grade 1-4 glioma patients. Cognitive performance in patients with adjuvant treatment was comparable to that of patients without.

Seizure underreporting in LGI1 and CASPR2 antibody encephalitis.

Patients with anti-leucine-rich glioma-inactivated 1 protein (LGI1) or anti-contactin-associated protein 2 (CASPR2) antibody encephalitis typically present with frequent epileptic seizures. The seizures generally respond well to immunosuppressive therapy, and the long-term seizure outcome seems to be favorable. Consequentially, diagnosing acute symptomatic seizures secondary to autoimmune encephalitis instead of autoimmune epilepsy was proposed. However, published data on long-term seizure outcomes in CASPR2 and LGI1 antibody encephalitis are mostly based on patient reports, and seizure underreporting is a recognized issue. Clinical records from our tertiary epilepsy center were screened retrospectively for patients with LGI1 and CASPR2 antibody encephalitis who reported seizure freedom for at least 3 months and received video-electroencephalography (EEG) for >24 h at follow-up visits. Twenty (LGI1, n = 15; CASPR2, n = 5) of 32 patients with LGI1 (n = 24) and CASPR2 (n = 8) antibody encephalitis fulfilled these criteria. We recorded focal aware and impaired awareness seizures in four of these patients (20%) with reported seizure-free intervals ranging from 3 to 27 months. Our results question the favorable seizure outcome in patients with CASPR2 and LGI1 antibody encephalitis and suggest that the proportion of patients who have persistent seizures may be greater. Our findings underline the importance of prolonged video-EEG telemetry in this population.

Mind wandering and depression: A status report.

While many clinical studies and overviews on the contribution of rumination to depression exist, relatively little information regarding the role of mind wandering (MW) in general is available. Therefore, it remains an open question whether patterns of MW are altered in depression and, if so, how these alterations are related to rumination. Here, we review and discuss studies investigating MW in cohorts, showing either a clinically significant depression or with clinically significant disorders accompanied by depressive symptoms. These studies yield first tentative insights into major issues. However, further investigations are required, specifically studies which: i) compare patients with a primary diagnosis of major depression with healthy and appropriately matched controls, ii) implement measures of both MW and rumination, iii) are based on experience sampling (in combination with other key approaches), iv) compare experience sampling during daily life, resting state and attentional tasks, v) explore possible biases in the assessment of MW, vi) acquire data not only related to the propensity and contents of MW, but also regarding meta-awareness and intentionality.

[Role of Clinical, Sociomedical and Psychological Factors on Return to Work of Patients with Breast Cancer 6 Months after Rehabilitation]. / Einfluss klinischer, sozialmedizinischer und psychologischer Faktoren auf die berufliche Reintegration von Patientinnen mit Brustkrebs 6 Monate nach der Rehabilitation.

AIM OF THE STUDY: The majority of patients with non-metastatic breast cancer return to work after tumor therapy. A rate of up to 80% is given in national and international studies, which can vary considerably depending on the study population and the various social systems. However, it is unclear how many patients are reintegrated into work after medical rehabilitation and which clinical, sociodemographic and psychological factors play a role. METHODS: In a multicentre study, clinical and sociodemographic data were collected from breast cancer patients at the beginning of their medical rehabilitation. Subjectively experienced deficits in attention performance (FEDA), depressive symptoms (PHQ-9) and health-related quality of life (EORTC QLQ-C30) were recorded using standardized questionnaires. The cognitive performance was also examined using a computer-based test battery (NeuroCog FX). A follow-up survey was carried out 6-9 months after medical rehabilitation. The subjective assessment of one's own cognitive performance (FEDA) was recorded again at this time. RESULTS: 396 of the originally 476 patients were included in the study. In the follow-up survey, 323/396 patients (82%) were again employed. In a regression model, sociodemographic factors proved to be particularly predictive with regard to occupational reintegration: employment at the time of the tumor diagnosis, job preserved after medical rehabilitation, employee status and gradual reintegration according to the Hamburg model (Nagelkerke R2=0.685). This model could not be improved by adding psychological variables. The subjective patient information in all questionnaires was highly correlated (r>0.57; p<0.001). CONCLUSION: The vast majority of breast cancer patients return to work after medical rehabilitation. Socio-demographic factors play a crucial role in this. The regression model developed here, including the employment status, professional orientation and gradual reintegration, is of predictive importance and can be used in medical rehabilitation.

Contralesional White Matter Alterations in Patients After Hemispherotomy.

Cerebral lesions may cause degeneration and neuroplastic reorganization in both the ipsi- and the contralesional hemisphere, presumably creating an imbalance of primarily inhibitory interhemispheric influences produced via transcallosal pathways. The two hemispheres are thought to mutually hamper neuroplastic reorganization of the other hemisphere. The results of preceding degeneration and neuroplastic reorganization of white matter may be reflected by Diffusion Tensor Imaging-derived diffusivity parameters such as fractional anisotropy (FA). In this study, we applied Diffusion Tensor Imaging (DTI) to contrast the white matter status of the contralesional hemisphere of young lesioned brains with and without contralateral influences by comparing patients after hemispherotomy to those who had not undergone neurosurgery. DTI was applied to 43 healthy controls (26 females, mean age ± SD: 25.07 ± 11.33 years) and two groups of in total 51 epilepsy patients with comparable juvenile brain lesions (32 females, mean age ± SD: 25.69 ± 12.77 years) either after hemispherotomy (30 of 51 patients) or without neurosurgery (21 of 51 patients), respectively. FA values were compared between these groups using the unbiased tract-based spatial statistics approach. A voxel-wise ANCOVA controlling for age at scan yielded significant group differences in FA. A post hoc t-test between hemispherotomy patients and healthy controls revealed widespread supra-threshold voxels in the contralesional hemisphere of hemispherotomy patients indicating comparatively higher FA values (p < 0.05, FWE-corrected). The non-surgery group, in contrast, showed extensive supra-threshold voxels indicating lower FA values in the contralesional hemisphere as compared to healthy controls (p < 0.05, FWE-corrected). Whereas lower FA values are suggestive of pronounced contralesional degeneration in the non-surgery group, higher FA values in the hemispherotomy group may be interpreted as a result of preceding plastic remodeling. We conclude that, whether juvenile brain lesions are associated with contralesional degeneration or reorganization partly depends on the ipsilesional hemisphere. Contralesional reorganization as observed in hemispherotomy patients was most likely enabled by the complete neurosurgical deafferentation of the ipsilesional hemisphere and, thereby, the disinhibition of the neuroplastic potential of the contralesional hemisphere. The main argument of this study is that hemispherotomy may be seen as a major plastic stimulus and as a prerequisite for contralesional neuroplastic remodeling in patients with juvenile brain lesions.

Laser interstitial thermotherapy (LiTT) in pediatric epilepsy surgery.

Laser interstitial thermotherapy (LiTT) is a novel stereotactic approach to the surgical treatment of severe drug-resistant focal epilepsies. This review extends our recent general review on this topic (Hoppe et al. Laser interstitial thermotherapy [LiTT] in epilepsy surgery. Seizure 2017; 48:45-52) with a focus on children (age <18 years). A PubMed search retrieved 25 uncontrolled case series reports that included a total of 179 pediatric patients as well as 7 review papers that specifically referred to using LiTT in pediatric epilepsy surgery (due August 31, 2018). Hypothalamic hamartomas (HH) represented the most frequent indication (64.2%) while therapeutic evidence for other more frequent etiologies underlying severe focal childhood epilepsies (e.g. focal cortical dysplasia, mesiotemporal sclerosis) is still scarce (n<20). For the published cases, the rate of severe complications was 3.4% and the overall complication rate was 23.5%. The seizure freedom rate (Engel class 1) was 57.5% (including patients with early follow-up and repeat thermoablations). None of the studies included the systematic evaluation of the cognitive outcome. Overall, the published evidence does not yet allow a scientific or clinical judgement on the utility of LiTT for pediatric epilepsy surgery. LiTT is likely to extend the neurosurgical toolbox with regard to deep brain lesions (e.g. HH). However, in cases that are equally accessible for both approaches therapeutic superiority of LiTT over open resective surgery still remains to be demonstrated. Recommendations for controlled though non-randomized outcome studies are provided.

Parents' view of the cognitive outcome one year after pediatric epilepsy surgery.

OBJECTIVES: The cognitive outcome of pediatric epilepsy surgery has mainly been examined on the basis of standardized tests. Here, we analyzed the outcome in six cognitive domains from the parents' view. METHODS: Included were consecutive surgical pediatric patients whose parents filled-in a comprehensive questionnaire on cognitive problems in children and adolescents (Kognitive Probleme bei Kindern und Jugendlichen (KOPKIJ); Gleissner et al. 2006) at the preoperative baseline (T1) as well as twelve months thereafter (T2). All children also underwent standard neuropsychological assessments at T1 and T2. RESULTS: Parents of 96 patients provided pre- and postoperative KOPKIJ data. Overall, 80% of the children became seizure-free at the follow-up. Group means indicated a strong positive effect of time on KOPKIJ and neuropsychological performance. We found postoperative improvements in five out of six cognitive domains (language, memory, executive functions, attention, school; unchanged: visuospatial abilities). Individually, improvements were twice as likely as declines. However, 33 patients (35%) experienced significant decline in at least one cognitive domain. Later onset of epilepsy resulted in better performance but had no effect on change scores. Seizure-free status, lower antiseizure drug load, and stronger drug reduction after surgery contributed to postoperative cognitive improvements as perceived by the parents; no other effects of clinical factors were obtained (e.g., localization/lateralization). Despite their similar outcome patterns, change scores as derived from parental ratings and neuropsychological assessment were not correlated. CONCLUSIONS: Parents acknowledged the overall positive neurocognitive development after pediatric epilepsy surgery as previously shown by standardized tests. Seizure freedom and lower antiseizure drug load contributed to the beneficial cognitive outcome. Even if cognitive improvements outweighed declines, a risk for cognitive decline with impact on everyday functioning does exist.

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.

Evaluating the mediating role of executive functions for antiepileptic drugs' effects on IQ in children and adolescents with epilepsy.

Several studies suggest that antiepileptic drug (AED) treatment may permanently or reversibly affect intelligence (intelligence quotient [IQ]) in children and adolescents with epilepsy. Since AED treatment preferentially affects attention and executive functions, we evaluated the potentially mediating effect of executive functions in regard to the adverse effects of drug treatment on intelligence. In a retrospective observational study, 178 children and adolescents with refractory and mostly localization-related epilepsies were evaluated in regard to the interrelation of IQ (Wechsler Intelligence Scale for Children [WISC III] short-form), executive functions (EpiTrack-Junior®, a cognitive AED screening test), and drug treatment (drug load). The results indicate that a low IQ was evident in 23%, impaired executive functions in 59% of the patients. Executive functions correlated to IQ (r = 0.60) and the symbol digits and picture arrangement subtests (R2 = 0.46) in particular. Odds ratios for impaired executive functions compared to being off drug (33% impaired) increased from 2.0 with one drug (53% impaired) to 9.5 (83% impaired) with at least three drugs. A mediation analysis revealed that drug dependent differences in executive functions mediate the negative effect of the AED load on intelligence. Hence, executive functions appear to link adverse cognitive side effects of AED treatment to intelligence. Considering Catell's two factor model of intelligence, AEDs preferentially affect the aspects of fluid intelligence. The overall impact of AED on intelligence appears mild. It may become relevant, however, when drug-induced impairments persist over longer time intervals during sensitive developmental phases. This issue needs to be addressed in future longitudinal studies.

Morphometric MRI findings challenge the concept of the "unaffected" hemisphere in Rasmussen encephalitis.

Rasmussen encephalitis (RE) is an immune-mediated brain disease with progressive unihemispheric atrophy. Although it is regarded as a strictly one-sided pathology, volumetric magnetic resonance imaging (MRI) studies have revealed atrophy in the so-called unaffected hemisphere. In contrast to previous studies, we hypothesized that the contralesional hemisphere would show increased gray matter volume in response to the ipsilesional atrophy. We assessed the gray matter volume differences among 21 patients with chronic, late-stage RE and 89 age- and gender-matched healthy controls using voxel-based morphometry. In addition, 11 patients with more than one scan were tested longitudinally. Compared to controls, the contralesional hemisphere of the patients revealed a higher cortical volume but a lower subcortical gray matter volume (all P < 0.001, unpaired t test). Progressive gray matter volume losses in bilateral subcortical gray matter structures were observed (P < 0.05, paired t test). The comparatively higher cortical volume in the contralesional hemisphere can be interpreted as a result of compensatory structural remodeling in response to atrophy of the ipsilesional hemisphere. Contralesional subcortical gray matter volume loss may be due to the pathology or its treatment. Because MRI provides the best marker for determining the progression of RE, an accurate description of its MRI features is clinically relevant.

Low-Temperature Plasma-Enhanced Atomic Layer Deposition of Tin(IV) Oxide from a Functionalized Alkyl Precursor: Fabrication and Evaluation of SnO2-Based Thin-Film Transistor Devices.

A bottom-up process from precursor development for tin to plasma-enhanced atomic layer deposition (PEALD) for tin(IV) oxide and its successful implementation in a working thin-film transistor device is reported. PEALD of tin(IV) oxide thin films at low temperatures down to 60 °C employing tetrakis-(dimethylamino)propyl tin(IV) [Sn(DMP)4] and oxygen plasma is demonstrated. The liquid precursor has been synthesized and thoroughly characterized with thermogravimetric analyses, revealing sufficient volatility and long-term thermal stability. [Sn(DMP)4] demonstrates typical saturation behavior and constant growth rates of 0.27 or 0.42 Å cycle-1 at 150 and 60 °C, respectively, in PEALD experiments. Within the ALD regime, the films are smooth, uniform, and of high purity. On the basis of these promising features, the PEALD process was optimized wherein a 6 nm thick tin oxide channel material layer deposited at 60 °C was applied in bottom-contact bottom-gate thin-film transistors, showing a remarkable on/off ratio of 107 and field-effect mobility of µFE ≈ 12 cm2 V-1 s-1 for the as-deposited thin films deposited at such low temperatures.

Pediatric Temporal Lobe Epilepsy Surgery in Bonn and Review of the Literature.

BACKGROUND: Epilepsy surgery is well established as safe and successful for children with temporal lobe epilepsy (TLE). Despite evidence from available data, there remains some reluctance to refer children with medically refractory epilepsy for preoperative evaluation and workup for possible surgery. OBJECTIVE: To present the largest case series of pediatric (TLE) patients thus far, in order to better understand the predictability of preoperative evaluation on seizure outcome, and to better understand longitudinal outcomes in a large pediatric cohort. METHODS: One hundred eighty-three pediatric patients with TLE who underwent surgical treatment between 1988 and 2012 were retrospectively reviewed. Preoperative seizure history, noninvasive and invasive preoperative evaluation, surgical results, pathological results, long-term seizure outcomes, and complications were evaluated. A review of pediatric TLE in the literature was also undertaken to better understand reported complications and long-term outcomes. RESULTS: Mean follow-up was 42 mo (range 12-152 mo); 155 patients had good seizure outcomes (Engel I/II; 84.8%) and 28 patients had poor seizure outcomes (Engel III/IV; 15.2%); 145 patients were Engel I (78.8%). Only 10 patients did not have worthwhile improvement (Engel class IV; 5.4%). A review of the literature identified 2089 unique cases of pediatric TLE. Satisfactory seizure outcomes occurred in 1629 patients (79%) with unsatisfactory outcomes in 433 patients (21%). CONCLUSION: Pediatric patients benefit from surgery for medically refractory TLE with an acceptable safety profile regardless of histopathological diagnosis, seizure frequency, or seizure type. Seizure freedom appears to have extensive durability in a significant proportion of surgically treated patients.

Citing Hippocrates on depression in epilepsy.

OBJECTIVES: When writing about the bidirectional etiological relationship between depression and epilepsy, neuropsychiatrists often cite Lewis (1934) [Lewis AJ. Melancholia: a historical review. Journal of Mental Science 1934; 80: 1-42] who cited Hippocrates - namely, "melancholics ordinarily become epileptics, and epileptics, melancholics". In this paper, the complicated reference for this citation from Lewis (1934) was critically reappraised. METHODS: The Greek-Latin edition of Hippocratic writings by Ermerins to which Lewis (1934) referred and most volumes of the standard Greek-English edition of the Hippocratic writings in The Loeb Classical Library were freely available as facsimile pdf documents in the Internet Archive (archive.org). RESULTS: Melancholia (i.e., "the black bile disease") is defined as a persistent mental state of fear and sadness ("Aphorisms", section 6, aphorism 23) which appears more consistent with a dysthymic disorder or depressive personality disorder than an acute (episodic) depressive disorder. Confusingly, the term melancholia also signifies a humoral etiology, namely a surplus of black bile, which causes several distinct diseases including epilepsy (aphorism vi/56). The quote addressing the conversion of melancholia into epilepsy and vice versa was taken from the writing "Epidemics" (book 6, section 8, paragraph 31). The famous treatise on epilepsy, "De Morbo Sacro", does not mention melancholia but instead, attributes epilepsy to two other humors: phlegm and (yellow) bile. This writing proposes an etiological relationship between (inherited) personality and epilepsy, wherein a phlegmatic temperament represents an epilepsy risk while a bilious (choleric) temperament offers protection against epilepsy. SIGNIFICANCE: With only a few clarifications, the neuropsychiatric quotation from Hippocrates and the reference to Lewis (1934) could generally be approved as appropriate. However, the proper framework of the quote seems to be personality and not mood. A more precise reference to a standard edition of "Epidemics" book 6 is also suggested.

NeuroCog FX study: A multicenter cohort study on cognitive dysfunction in patients with early breast cancer.

OBJECTIVE: Complaints about cognitive dysfunction (CD) reportedly persist in approximately one third of breast cancer patients, but the nature of CD and possible risk factors are unknown. METHODS: A cross-sectional, multicenter study was set up at 9 German oncological rehabilitation centers. Objective cognitive performance was assessed by the NeuroCog FX test, a short computerized screening (duration <30 minutes) which assesses working memory, alertness, verbal/figural memory, and language/executive. Patients' test performance was correlated with treatment factors (chemo-, radiotherapy), subjective performance (FEDA), depression (PHQ-9), quality of life (EORTC QLQ-30), and clinical characteristics. RESULTS: From February 2013 to December 2014, a clinically homogenous sample of 476 patients was recruited (early tumor stage [T0-T2]: 93%; node-negative: 67%; chemotherapy: 61%; radiotherapy: 84%). NeuroCog FX could be administered in 439 patients (92%; median age: 50 [24-62] years). Patients showed decreased performance in attentional-executive functions (but not verbal/figural memory) and a 3-fold rate of CD in terms of below average performance in at least 1 cognitive domain (42%). Approximately 40% of the patients also reported subjective cognitive impairment (FEDA). No therapy-specific effect on test performance was obtained in the NeuroCog FX test. CONCLUSIONS: Breast cancer survivors showed objective attentional-executive and subjective cognitive impairments. No therapy-specific adverse side effect on objective cognitive performance was found. Depression strongly contributed to objective and subjective cognitive complaints and reduced quality of life.