Recognition and perception of emotions in juvenile myoclonic epilepsy.

OBJECTIVE: Perception and recognition of emotions are fundamental prerequisites of human life. Patients with juvenile myoclonic epilepsy (JME) may have emotional and behavioral impairments that might influence socially desirable interactions. We aimed to investigate perception and recognition of emotions in patients with JME by means of neuropsychological tests and functional magnetic resonance imaging (fMRI). METHODS: Sixty-five patients with JME (median age = 27 years, interquartile range [IQR] = 23-34) were prospectively recruited at the Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria. Patients were compared to 68 healthy controls (median age = 24 years, IQR = 21-31), matched for sex, age, and education. All study participants underwent the Networks of Emotion Processing test battery (NEmo), an fMRI paradigm of "dynamic fearful faces," a structured interview for psychiatric and personality disorders, and comprehensive neuropsychological testing. RESULTS: JME patients versus healthy controls demonstrated significant deficits in emotion recognition in facial and verbal tasks of all emotions, especially fear. fMRI revealed decreased amygdala activation in JME patients as compared to healthy controls. Patients were at a higher risk of experiencing psychiatric disorders as compared to healthy controls. Cognitive evaluation revealed impaired attentional and executive functioning, namely psychomotor speed, tonic alertness, divided attention, mental flexibility, and inhibition of automated reactions. Duration of epilepsy correlated negatively with parallel prosodic and facial emotion recognition in NEmo. Deficits in emotion recognition were not associated with psychiatric comorbidities, impaired attention and executive functions, types of seizures, and treatment. SIGNIFICANCE: This prospective study demonstrated that as compared to healthy subjects, patients with JME had significant deficits in recognition and perception of emotions as shown by neuropsychological tests and fMRI. The results of this study may have importance for psychological/psychotherapeutic interventions in the management of patients with JME.

A new nomogram to predict oncological outcome in laryngeal and hypopharyngeal carcinoma patients after laryngopharyngectomy.

BACKGROUND: To create nomograms for better prediction of the oncological outcome in advanced laryngeal (LxCAs) or hypopharyngeal (HpxCAs) cancer after laryngopharyngectomy. MATERIALS: 239 patients who underwent total laryngectomy or laryngopharyngectomy due to LxCA (52.7%) or HpxCA (47.3%) were included in this study. Based on clinical risk factors (tumor site, lymph node involvement, salvage setting), we created nomograms for prediction of disease-specific survival (DSS) and disease-free survival (DFS). RESULTS: HpxCAs showed a higher rate of lymph node involvement (p < 0.001), a 2.47-fold higher risk of a 2nd head and neck cancer (p = 0.009) and significantly worse loco-regional control rates (p = 0.003) compared to LxCAs. Positive neck nodes and salvage procedures were associated with significantly worse outcome. Nomograms demonstrated that hypopharyngeal tumors with positive neck nodes in salvage situations had the worst oncological outcome with a 5-year DSS of 15-20%. CONCLUSIONS: The oncological outcome is worse in hypopharyngeal carcinomas and could be easily quantified by our nomograms that are based on tumor site, lymph node involvement and salvage situation.

Emotional Word Processing in Patients With Juvenile Myoclonic Epilepsy.

Objective: According to Panksepp's hierarchical emotion model, emotion processing relies on three functionally and neuroanatomically distinct levels. These levels comprise subcortical networks (primary level), the limbic system (secondary level), and the neocortex (tertiary level) and are suggested to serve differential emotional processing. We aimed to validate and extend previous evidence of discrete and dimensional emotion processing in patient with juvenile myoclonic epilepsy (JME). Methods: We recorded brain activity of patients with JME and healthy controls in response to lexical decisions to words reflecting the discrete emotion fear and the affective dimension negativity previously suggested to rely on different brain regions and to reflect different levels of processing. In all study participants, we tested verbal cognitive functions, as well as the relationship of psychiatric conditions, seizure types and duration of epilepsy and emotional word processing. Results: In support of the hierarchical emotion model, we found an interaction of discrete emotion and affective dimensional processing in the right amygdala likely to reflect secondary level processing. Brain activity related to affective dimensional processing was found in the right inferior frontal gyrus and is suggested to reflect tertiary level processing. Psychiatric conditions, type of seizure nor mono- vs. polytherapy and duration of epilepsy within patients did not have any effect on the processing of emotional words. In addition, no differences in brain activity or response times between patients and controls were observed, despite neuropsychological testing revealed slightly decreased verbal intelligence, verbal fluency and reading speed in patients with JME. Significance: These results were interpreted to be in line with the hierarchical emotion model and to highlight the amygdala's role in processing biologically relevant stimuli, as well as to suggest a semantic foundation of affective dimensional processing in prefrontal cortex. A lack of differences in brain activity of patients with JME and healthy controls in response to the emotional content of words could point to unaffected implicit emotion processing in patients with JME.

Biannual Differences in Interest Peaks for Web Inquiries Into Ear Pain and Ear Drops: Infodemiology Study.

BACKGROUND: The data retrieved with the online search engine, Google Trends, can summarize internet inquiries into specified search terms. This engine may be used for analyzing inquiry peaks for different medical conditions and symptoms. OBJECTIVE: The aim of this study was to analyze World Wide Web interest peaks for "ear pain," "ear infection," and "ear drops." METHODS: We used Google Trends to assess the public online interest for search terms "ear pain," "ear infection," and "ear drops" in 5 English and non-English-speaking countries from both hemispheres based on time series data. We performed our analysis for the time frame between January 1, 2004, and December 31, 2019. First, we assessed whether our search terms were most relevant to the topics of ear pain, ear infection, and ear drops. We then tested the reliability of Google Trends time series data using the intraclass correlation coefficient. In a second step, we computed univariate time series plots to depict peaks in web-based interest. In the last step, we used the cosinor analysis to test the statistical significance of seasonal interest peaks. RESULTS: In the first part of the study, it was revealed that "ear infection," "ear pain," and "ear drops" were the most relevant search terms in the noted time frame. Next, the intraclass correlation analysis showed a moderate to excellent reliability for all 5 countries' 3 primary search terms. The subsequent analysis revealed winter interest peaks for "ear infection" and "ear pain". On the other hand, the World Wide Web search for "ear drops" peaked annually during the summer months. All peaks were statistically significant as revealed by the cosinor model (all P values <.001). CONCLUSIONS: It can be concluded that individuals affected by otitis media or externa, possibly the majority, look for medical information online. Therefore, there is a need for accurate and easily accessible information on these conditions in the World Wide Web, particularly on differentiating signs and therapy options. Meeting this need may facilitate timely diagnosis, proper therapy, and eventual circumvention of potentially life-threatening complications.

A New Classification System to Predict Functional Outcome after Laryngectomy and Laryngopharyngectomy.

(1) Objective: To evaluate long-term functional outcome in patients who underwent primary or salvage total laryngectomy (TL), TL with partial (TLPP), or total pharyngectomy (TLTP), and to establish a new scoring system to predict complication rate and long-term functional outcome; (2) Material and Methods: Between 1993 and 2019, 258 patients underwent TL (n = 85), TLPP (n = 101), or TLTP (n = 72). Based on the extent of tumor resection, all patients were stratified to (i) localization I: TL; II: TLPP; III: TLTP and (ii) surgical treatment (A: primary resection; B: salvage surgery). Type and rate of complication and functional outcome, including oral nutrition, G-tube dependence, pharyngeal stenosis, and voice rehabilitation were evaluated in 163 patients with a follow-up ≥ 12 months and absence of recurrent disease; (3) Results: We found 61 IA, 24 IB, 63 IIA, 38 IIB, 37 IIIA, and 35 IIIA patients. Complications and subsequently revision surgeries occurred most frequently in IIIB cases but rarely in IA patients (57.1% vs. 18%; p = 0.001 and 51.4% vs. 14.8%; p = 0.002), respectively. Pharyngocutaneous fistula (PCF) was the most common complication (33%), although it did not significantly differ among cohorts (p = 0.345). Pharyngeal stenosis was found in 27% of cases, with the highest incidence in IIIA (45.5%) and IIIB (72.7%) patients (p < 0.001). Most (91.1%) IA patients achieved complete oral nutrition compared to only 41.7% in class IIIB patients (p < 0.001). Absence of PCF (odds ratio (OR) 3.29; p = 0.003), presence of complications (OR 3.47; p = 0.004), and no need for pharyngeal reconstruction (OR 4.44; p = 0.042) represented independent favorable factors for oral nutrition. Verbal communication was achieved in 69.3% of patients and was accomplished by the insertion of voice prosthesis in 37.4%. Acquisition of esophageal speech was reached in 31.9% of cases. Based on these data, we stratified patients regarding the extent of surgery and previous treatment into subgroups reflecting risk profiles and expectable functional outcome; (4) Conclusions: The extent of resection accompanied by the need for reconstruction and salvage surgery both carry a higher risk of complications and subsequently worse functional outcome. Both factors are reflected in our classification system that can be helpful to better predict patients' functional outcome.

Emotional Recognition in Patients With Mesial Temporal Epilepsy Associated With Enlarged Amygdala.

BACKGROUND: Amygdalae play a central role in emotional processing by interconnecting frontal cortex and other brain structures. Unilateral amygdala enlargement (AE) is associated with mesial temporal lobe epilepsy (mTLE). In a relatively large sample of patients with mTLE and AE, we aimed to evaluate functional integration of AE in emotion processing and to determine possible associations between fMRI activation patterns in amygdala and deficits in emotion recognition as assessed by neuropsychological testing. METHODS: Twenty-two patients with drug resistant unilateral mTLE due to ipsilateral AE were prospectively recruited in a large epilepsy unit and compared with 17 healthy control subjects in terms of amygdala volume, fMRI activation patterns and performance in emotion recognition as assessed by comprehensive affect testing system (CATS) and Ekman faces. All patients underwent structural and functional 1.5 Tesla MRI, electro-clinical assessment and neuropsychological testing. RESULTS: We observed BOLD signal ipsilateral to AE (n = 7; group PAT1); contralateral to AE (n = 6; group PAT2) and no activation (n = 9; group PAT3). In the region of interest (ROI) analysis, beta estimates for fearful face > landscape contrast in the left amygdala region did not differ significantly in patients with left TLE vs. patients with right TLE [T (16) = -1.481; p = 0.158]. However, beta estimates for fearful face > landscape contrast in the right amygdala region were significantly reduced in patients with right TLE vs. patients with left TLE [T (16) = -2,922; p = 0.010]. Patients showed significantly lower total scores in CATS and Ekman faces compared to healthy controls. CONCLUSION: In our cohort, patients with unilateral mesial TLE and ipsilateral AE, an amygdala could display either functional integration in emotion recognition or dysfunction as demonstrated by fMRI. Perception and recognition of emotions were impaired more in right-sided mTLE as compared to left-sided mTLE. Neuropsychological tests showed deficits in emotion recognition in patients as compared to healthy controls.

Prediction of Cognitive Decline in Temporal Lobe Epilepsy and Mild Cognitive Impairment by EEG, MRI, and Neuropsychology.

Cognitive decline is a severe concern of patients with mild cognitive impairment. Also, in patients with temporal lobe epilepsy, memory problems are a frequently encountered problem with potential progression. On the background of a unifying hypothesis for cognitive decline, we merged knowledge from dementia and epilepsy research in order to identify biomarkers with a high predictive value for cognitive decline across and beyond these groups that can be fed into intelligent systems. We prospectively assessed patients with temporal lobe epilepsy (N = 9), mild cognitive impairment (N = 19), and subjective cognitive complaints (N = 4) and healthy controls (N = 18). All had structural cerebral MRI, EEG at rest and during declarative verbal memory performance, and a neuropsychological assessment which was repeated after 18 months. Cognitive decline was defined as significant change on neuropsychological subscales. We extracted volumetric and shape features from MRI and brain network measures from EEG and fed these features alongside a baseline testing in neuropsychology into a machine learning framework with feature subset selection and 5-fold cross validation. Out of 50 patients, 27 had a decline over time in executive functions, 23 in visual-verbal memory, 23 in divided attention, and 7 patients had an increase in depression scores. The best sensitivity/specificity for decline was 72%/82% for executive functions based on a feature combination from MRI volumetry and EEG partial coherence during recall of memories; 95%/74% for visual-verbal memory by combination of MRI-wavelet features and neuropsychology; 84%/76% for divided attention by combination of MRI-wavelet features and neuropsychology; and 81%/90% for increase of depression by combination of EEG partial directed coherence factor at rest and neuropsychology. Combining information from EEG, MRI, and neuropsychology in order to predict neuropsychological changes in a heterogeneous population could create a more general model of cognitive performance decline.

Diagnostic accuracy of functional magnetic resonance imaging, Wada test, magnetoencephalography, and functional transcranial Doppler sonography for memory and language outcome after epilepsy surgery: A systematic review.

OBJECTIVE: The European Union-funded E-PILEPSY project was launched to develop guidelines and recommendations for epilepsy surgery. In this systematic review, we aimed to assess the diagnostic accuracy of functional magnetic resonance imaging (fMRI), Wada test, magnetoencephalography (MEG), and functional transcranial Doppler sonography (fTCD) for memory and language decline after surgery. METHODS: The literature search was conducted using PubMed, Embase, and CENTRAL. The diagnostic accuracy was expressed in terms of sensitivity and specificity for postoperative language or memory decline, as determined by pre- and postoperative neuropsychological assessments. If two or more estimates of sensitivity or specificity were extracted from a study, two meta-analyses were conducted, using the maximum ("best case") and the minimum ("worst case") of the extracted estimates, respectively. RESULTS: Twenty-eight papers were eligible for data extraction and further analysis. All tests for heterogeneity were highly significant, indicating large between-study variability (P < 0.001). For memory outcomes, meta-analyses were conducted for Wada tests (n = 17) using both memory and language laterality quotients. In the best case, meta-analyses yielded a sensitivity estimate of 0.79 (95% confidence interval [CI] = 0.67-0.92) and a specificity estimate of 0.65 (95% CI = 0.47-0.83). For the worst case, meta-analyses yielded a sensitivity estimate of 0.65 (95% CI = 0.48-0.82) and a specificity estimate of 0.46 (95% CI = 0.28-0.65). The overall quality of evidence, which was assessed using Grading of Recommendations Assessment, Development, and Evaluation methodology, was rated as very low. Meta-analyses concerning diagnostic accuracy of fMRI, fTCD, and MEG were not feasible due to small numbers of studies (fMRI, n = 4; fTCD, n = 1; MEG, n = 0). This also applied to studies concerning language outcomes (Wada test, n = 6; fMRI, n = 2; fTCD, n = 1; MEG, n = 0). SIGNIFICANCE: Meta-analyses could only be conducted in a few subgroups for the Wada test with low-quality evidence. Thus, more evidence from high-quality studies and improved data reporting are required. Moreover, the large between-study heterogeneity underlines the necessity for more homogeneous and thus comparable studies in future research.

Integrating the systematic assessment of psychological states in the epilepsy monitoring unit: Concept and compliance.

BACKGROUND: Admission to the epilepsy monitoring unit (EMU) for long-term video-electroencephalography (EEG) monitoring (VEEG) constitutes the gold standard for seizure diagnosis and presurgical evaluation. This study applied the concept of a high-frequency systematic monitoring of psychological states and tested patients' compliance in order to evaluate if its integration in the EMU is feasible and if patients benefit from the graphically underpinned discussion of their EMU stay-related cognitions and emotions. METHODS: The process-monitoring is technically realized by an internet-based device for data collection and data analysis, the Synergetic Navigation System (SNS). A convenient sample was enrolled: All eligible patients who were admitted to the EMU of the Department of Neurology, Christian Doppler Medical Center, Salzburg, Austria, between November 6th 2017 and January 26th 2018 were approached and recruited upon consent. After a short resource-oriented interview, each enrolled patient was provided with a tablet. The daily questionnaire included eight standardized and up to three personalized items. Self-assessments were collected every 5 h prior to meal times (6:30 am, 11:30 am, and 4:30 pm) and at 9:30 pm. The detailed visualizations of the patients' replies were discussed with the participants during a feedback session at the end of the EMU stay. RESULTS: Twenty-one patients (12 women/9 men, median age 29 years [range 18-74 years]) were consecutively recruited (72% of all eligible patients). Compliance rates were high (median: 82%, range 60%-100%) among the respondents. Mood correlated strongly with hopefulness (r = 0.71) and moderately with energy (r = 0.63) in all patients. When correlating the intraindividual medians of the process questionnaire time series with the pretest total scores, energy correlated moderately and negatively with the Perceived Stress Scale (PSS) (r = -0.45), while self-efficacy correlated moderately and negatively with the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) total scores in all patients (r = -0.5). Nine patients (43%) reported that they learned something meaningful about themselves after the feedback discussion of their individual time series. CONCLUSION: The results support the feasibility of high-frequency monitoring of psychological states and processes in routine EMU settings. Repeated daily collections four times per day of psychological surveys allow for the assessment of highly resolved, equidistant time series data, which gives insight into psychological states and processes during EMU admission.

Endovascular Thrombectomy in Acute Ischemic Stroke: Outcome in Referred Versus Directly Admitted Patients.

PURPOSE: Endovascular mechanical thrombectomy (mTE) in acute ischemic stroke due to large cerebral artery occlusion is effective and safe. The procedure is currently offered by specialized hospitals. Physicians from smaller hospitals need to refer patients to stroke centers. Secondary referrals involve delays for transportation. Little is known about effects of distant referrals on outcome and complications as compared to direct admittance. METHODS: To evaluate the effects of referral patterns on outcome and safety, we analyzed 941 patients with anterior circulation stroke receiving mTE between January 2010 and December 2015. Patients were divided into three groups: directly admitted patients (DAP), inner-city transfers (ICT) and long-distance referrals (LDR). We assessed (1) procedural parameters (2) frequency of good functional outcome (mRS ≤2 at 3 months) and (3) mortality rates. RESULTS: Referrals had a significantly longer imaging-to-groin time compared to DAP (median 150 min vs. 85 min, p <0.001), the same was true for LDR vs. ICT (median 157 min vs. 133.5 min, p <0.001). Time to recanalization was significantly longer for referrals compared to DAP (median 348 min vs. 260 min, p <0.001). There was no significant difference in the frequency of good functional outcome (DAP 39.5%, ICT 35.1%, LDR 37.0%; p =0.709), all-cause mortality at day 90 (DAP 31.5%, ICT 23.0%, LDR 27.0%; p =0.212) and the rate of symptomatic intracranial hemorrhage (p =0.834). CONCLUSION: Timing remains a critical factor in acute ischemic stroke treatment by endovascular means. Long distance referral to specialized neurovascular centers with high recanalization rates, however, does allow for a good functional outcome in a significant number of patients.

Reliability of EEG Interactions Differs between Measures and Is Specific for Neurological Diseases.

Alterations of interaction (connectivity) of the EEG reflect pathological processes in patients with neurologic disorders. Nevertheless, it is questionable whether these patterns are reliable over time in different measures of interaction and whether this reliability of the measures is the same across different patient populations. In order to address this topic we examined 22 patients with mild cognitive impairment, five patients with subjective cognitive complaints, six patients with right-lateralized temporal lobe epilepsy, seven patients with left lateralized temporal lobe epilepsy, and 20 healthy controls. We calculated 14 measures of interaction from two EEG-recordings separated by 2 weeks. In order to characterize test-retest reliability, we correlated these measures for each group and compared the correlations between measures and between groups. We found that both measures of interaction as well as groups differed from each other in terms of reliability. The strongest correlation coefficients were found for spectrum, coherence, and full frequency directed transfer function (average rho > 0.9). In the delta (2-4 Hz) range, reliability was lower for mild cognitive impairment compared to healthy controls and left lateralized temporal lobe epilepsy. In the beta (13-30 Hz), gamma (31-80 Hz), and high gamma (81-125 Hz) frequency ranges we found decreased reliability in subjective cognitive complaints compared to mild cognitive impairment. In the gamma and high gamma range we found increased reliability in left lateralized temporal lobe epilepsy patients compared to healthy controls. Our results emphasize the importance of documenting reliability of measures of interaction, which may vary considerably between measures, but also between patient populations. We suggest that studies claiming clinical usefulness of measures of interaction should provide information on the reliability of the results. In addition, differences between patient groups in reliability of interactions in the EEG indicate the potential of reliability to serve as a new biomarker for pathological memory decline as well as for epilepsy. While the brain concert of information flow is generally variable, high reliability, and thus, low variability may reflect abnormal firing patterns.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.

Imagine There Is No Plegia. Mental Motor Imagery Difficulties in Patients with Traumatic Spinal Cord Injury.

In rehabilitation of patients with spinal cord injury (SCI), imagination of movement is a candidate tool to promote long-term recovery or to control futuristic neuroprostheses. However, little is known about the ability of patients with spinal cord injury to perform this task. It is likely that without the ability to effectively perform the movement, the imagination of movement is also problematic. We therefore examined, whether patients with SCI experience increased difficulties in motor imagery (MI) compared to healthy controls. We examined 7 male patients with traumatic spinal cord injury (aged 23-70 years, median 53) and 20 healthy controls (aged 21-54 years, median 30). All patients had incomplete SCI, with AIS (ASIA Impairment Scale) grades of C or D. All had cervical lesions, except one who had a thoracic injury level. Duration after injury ranged from 3 to 314 months. We performed the Movement Imagery Questionnaire Revised as well as the Beck Depression Inventory in all participants. The self-assessed ability of patients to visually imagine movements ranged from 7 to 36 (Md = 30) and tended to be decreased in comparison to healthy controls (ranged 16-49, Md = 42.5; W = 326.5, p = 0.055). Also, the self-assessed ability of patients to kinesthetically imagine movements (range = 7-35, Md = 31) differed significantly from the control group (range = 23-49, Md = 41; W = 337.5, p = 0.0047). Two patients yielded tendencies for depressive mood and they also reported most problems with movement imagination. Statistical analysis however did not confirm a general relationship between depressive mood and increased difficulty in MI across both groups. Patients with spinal cord injury seem to experience difficulties in imagining movements compared to healthy controls. This result might not only have implications for training and rehabilitation programs, but also for applications like brain-computer interfaces used to control neuroprostheses, which are often based on the brain signals exhibited during the imagination of movements.

Apixaban for treatment of embolic stroke of undetermined source (ATTICUS randomized trial): Rationale and study design.

Rationale Optimal secondary prevention of embolic stroke of undetermined source is not established. The current standard in these patients is acetylsalicylic acid, despite high prevalence of yet undetected paroxysmal atrial fibrillation. Aim The ATTICUS randomized trial is designed to determine whether the factor Xa inhibitor apixaban administered within 7 days after embolic stroke of undetermined source, is superior to acetylsalicylic acid for prevention of new ischemic lesions documented by brain magnetic resonance imaging within 12 months after index stroke. Design Prospective, randomized, blinded, parallel-group, open-label, German multicenter phase III trial in approximately 500 patients with embolic stroke of undetermined source. A key inclusion criterion is the presence or the planned implantation of an insertable cardiac monitor. Patients are 1:1 randomized to apixaban or acetylsalicylic acid and treated for a 12-month period. It is an event-driven trial aiming for core-lab adjudicated primary outcome events. Study outcomes The primary outcome is the occurrence of at least one new ischemic lesion identified by axial T2-weighted FLAIR magnetic resonance imaging and/or axial DWI magnetic resonance imaging at 12 months when compared with the baseline magnetic resonance imaging. Key secondary outcomes are the combination of recurrent ischemic strokes, hemorrhagic strokes, systemic embolism; combination of MACE including recurrent stroke, myocardial infarction, and cardiovascular death and combination of major and clinically relevant non-major bleeding defined according to ISTH, and change of cognitive function and quality of life (EQ-5D, Stroke Impact Scale). Discussion Embolic stroke of undetermined source is caused by embolic disease and associated with a high risk of recurrent ischemic strokes and clinically silent cerebral ischemic lesions. ATTICUS will investigate the impact of atrial fibrillation detected by insertable cardiac monitor and the effects of early anticoagulation with apixaban compared with antiplatelet therapy with acetylsalicylic acid on the incidence of new ischemic lesion after embolic stroke of undetermined source.

Endovascular treatment of acute internal carotid artery dissections: technical considerations, clinical and angiographic outcome.

INTRODUCTION: In acute internal carotid artery dissection (a-ICAD) with concomitant intracranial large vessel occlusion or haemodynamic impairment, the effectiveness of medical treatment is limited and endovascular therapy (EVT) can be considered. Feasibility, safety and outcome of EVT in a-ICAD are not well described yet. METHODS: From an institutional database, we retrospectively selected consecutive patients treated for a-ICAD between January 2007 and July 2015. We assessed recanalization results defining <50 % residual stenosis and mTICI ≥2b as successful. Procedural adverse events and symptomatic haemorrhages were reported as well as clinical outcome at 90 days defining a mRS ≤2 as favourable. Follow-up angiographies were reviewed and retreatments reported. RESULTS: In the defined period, 73 patients (mean age 48 years (31-73), mean NIHSS 11 (0-27)) received EVT for a-ICAD. The majority (60 %) had tandem occlusions. Cervical artery reconstruction was successful in 100 % and intracranial thrombectomy in 85 %. Thrombus formation (18 %) and thromboembolism (20 %) were the most frequent adverse events but clinically relevant only in 8 %. Symptomatic haemorrhage occurred in 5 %. Clinical outcome was favourable in 64 %, with a lower chance after tandem occlusion (55 vs. 79 %, p = 0.047). Death rate was 10 %. None of the patients developed recurrent ischaemic symptoms, but control angiography revealed abnormal findings of the reconstructed ICA in 38 % leading to retreatment in 17 %. CONCLUSION: EVT of a-ICAD is feasible with a predominantly favourable clinical outcome. Improvement of devices and techniques is warranted to reduce the risk of thrombus formation and thromboembolism during treatment and insufficient vessel wall healing thereafter.

Impaired consciousness is linked to changes in effective connectivity of the posterior cingulate cortex within the default mode network.

The intrinsic connectivity of the default mode network has been associated with the level of consciousness in patients with severe brain injury. Especially medial parietal regions are considered to be highly involved in impaired consciousness. To better understand what aspect of this intrinsic architecture is linked to consciousness, we applied spectral dynamic causal modeling to assess effective connectivity within the default mode network in patients with disorders of consciousness. We included 12 controls, 12 patients in minimally conscious state and 13 in vegetative state in this study. For each subject, we first defined the four key regions of the default mode network employing a subject-specific independent component analysis approach. The resulting regions were then included as nodes in a spectral dynamic causal modeling analysis in order to assess how the causal interactions across these regions as well as the characteristics of neuronal fluctuations change with the level of consciousness. The resulting pattern of interaction in controls identified the posterior cingulate cortex as the main driven hub with positive afferent but negative efferent connections. In patients, this pattern appears to be disrupted. Moreover, the vegetative state patients exhibit significantly reduced self-inhibition and increased oscillations in the posterior cingulate cortex compared to minimally conscious state and controls. Finally, the degree of self-inhibition and strength of oscillation in this region is correlated with the level of consciousness. These findings indicate that the equilibrium between excitatory connectivity towards posterior cingulate cortex and its feedback projections is a key aspect of the relationship between alterations in consciousness after severe brain injury and the intrinsic functional architecture of the default mode network. This impairment might be principally due to the disruption of the mechanisms underlying self-inhibition and neuronal oscillations in the posterior cingulate cortex.

Solving the Issue of Restenosis After Stenting of Intracranial Stenoses: Experience with Two Thin-Strut Drug-Eluting Stents (DES)-Taxus Element™ and Resolute Integrity™.

PURPOSE: Thin-strut, flexible DES are suitable for intracranial stenting and may improve long-term vessel patency. The purpose of this study was to report our experience with two new-generation DES for the treatment of intracranial atherosclerotic disease. PATIENTS AND METHODS: We retrospectively reviewed all patients treated with Taxus Element™ or Resolute Integrity™ stent for an intracranial atherosclerotic stenosis between March 2011 and August 2013. Technical success was defined as the ability to deploy the device at the desired location and reduce the degree of stenosis below 50 %. All procedure-related strokes were recorded. Control angiography was scheduled after 6 weeks, 3, 6, and 12 months and yearly thereafter. A luminal narrowing ≥50 % was regarded as a restenosis. Stroke recurrence in the territory of the treated artery was reported. RESULTS: In the defined period we treated 101 patients harboring 117 intracranial stenoses. The procedure was successful in 100 (85.5 %) lesions. Procedure-related strokes occurred in 10 (9.9 %) patients with a permanent morbidity in 3 (3.0 %). Follow-up angiography was available for 83 of 100 (83.0 %) successfully treated lesions with an average of 355 days (IQR 153-482 days). Three (3.6 %) asymptomatic restenoses were detected. All occurred after treatment with Resolute Integrity™, none after Taxus Element™ (p = 0.059). New strokes in the territory of the treated artery were encountered in 2 (2.6 %) occasions. CONCLUSION: Thin-strut DES improve long-term patency and reduce the risk of subsequent stroke. Differences between devices may exist. Feasibility is comparable to bare-metal balloon-mounted stents and procedure-related strokes occurred within the expected range.

Clinical experience with the pREset stent retriever for the treatment of acute ischemic stroke--a review of 271 consecutive cases.

INTRODUCTION: The purpose of this study was to evaluate the safety and efficacy of the pREset stent retriever in a real-world clinical setting. METHODS: Patients treated with pREset were selected from a prospectively maintained single-center database. A TICI score ≥2b after ≤3 passes was regarded as successful recanalization. All device-related complications and their clinical significance were reported. Parenchymal hematomas (PH) were classified according to ECASS, adding focal and diffuse subarachnoid hemorrhage (SAH) as categories. A 90-day mRS of 0-2 was defined as favorable outcome. In addition, we separately analyzed patients treated with >3 pREset passes and patients receiving other rescue maneuvers. RESULTS: We included 271 patients. Successful recanalization was achieved in 76.4 %. Device-related complications occurred in 9.2 % of which 2.2 % were clinically significant. PH I, PH II, focal SAH, and diffuse SAH was observed in 5.2, 4.8, 12.2, and 2.2 %, respectively. A total of 39.5 % of patients had favorable clinical outcome. Considering treatments with >3 pREset passes or other rescue procedures, an additional 8.5 and 9.3 % of target vessels were recanalized. The chance of favorable clinical outcome decreased significantly with any kind of rescue therapy. In addition, the rate of PH I was significantly higher in patients treated with >3 pREset passes, whereas all other types of hemorrhage showed no difference. CONCLUSION: In terms of safety and effectiveness, pREset performed comparably to other stent retriever devices. To avoid futile recanalization and potential additional harm, escalation of therapy beyond three thrombectomy passes should only be performed after careful individual consideration of each case.

Connectivity biomarkers can differentiate patients with different levels of consciousness.

OBJECTIVE: In the present study, we searched for resting-EEG biomarkers that distinguish different levels of consciousness on a single subject level with an accuracy that is significantly above chance. METHODS: We assessed 44 biomarkers extracted from the resting EEG with respect to their discriminative value between groups of minimally conscious (MCS, N=22) patients, vegetative state patients (VS, N=27), and - for a proof of concept - healthy participants (N=23). We applied classification with support vector machines. RESULTS: Partial coherence, directed transfer function, and generalized partial directed coherence yielded accuracies that were significantly above chance for the group distinction of MCS vs. VS (.88, .80, and .78, respectively), as well as healthy participants vs. MCS (.96, .87, and .93, respectively) and VS (.98, .84, and .96, respectively) patients. CONCLUSIONS: The concept of connectivity is crucial for determining the level of consciousness, supporting the view that assessing brain networks in the resting state is the golden way to examine brain functions such as consciousness. SIGNIFICANCE: The present results directly show that it is possible to distinguish patients with different levels of consciousness on the basis of resting-state EEG.

Altered network properties of the fronto-parietal network and the thalamus in impaired consciousness.

Recovery of consciousness has been associated with connectivity in the frontal cortex and parietal regions modulated by the thalamus. To examine this model and to relate alterations to deficits in cognitive functioning and conscious processing, we investigated topological network properties in patients with chronic disorders of consciousness recovered from coma. Resting state fMRI data of 34 patients with unresponsive wakefulness syndrome and 25 in minimally conscious state were compared to 28 healthy controls. We investigated global and local network characteristics. Additionally, behavioral measures were correlated with the local metrics of 28 regions within the fronto-parietal network and the thalamus. In chronic disorders of consciousness, modularity at the global level was reduced suggesting a disturbance in the optimal balance between segregation and integration. Moreover, network properties were altered in several regions which are associated with conscious processing (particularly, in medial parietal, and frontal regions, as well as in the thalamus). Between minimally conscious and unconscious patients the local efficiency of medial parietal regions differed. Alterations in the thalamus were particularly evident in non-conscious patients. Most of the regions affected in patients with impaired consciousness belong to the so-called 'rich club' of highly interconnected central nodes. Disturbances in their topological characteristics have severe impact on information integration and are reflected in deficits in cognitive functioning probably leading to a total breakdown of consciousness.