Electrophysiological signatures of veridical head direction in humans.

Information about heading direction is critical for navigation as it provides the means to orient ourselves in space. However, given that veridical head-direction signals require physical rotation of the head and most human neuroimaging experiments depend upon fixing the head in position, little is known about how the human brain is tuned to such heading signals. Here we adress this by asking 52 healthy participants undergoing simultaneous electroencephalography and motion tracking recordings (split into two experiments) and 10 patients undergoing simultaneous intracranial electroencephalography and motion tracking recordings to complete a series of orientation tasks in which they made physical head rotations to target positions. We then used a series of forward encoding models and linear mixed-effects models to isolate electrophysiological activity that was specifically tuned to heading direction. We identified a robust posterior central signature that predicts changes in veridical head orientation after regressing out confounds including sensory input and muscular activity. Both source localization and intracranial analysis implicated the medial temporal lobe as the origin of this effect. Subsequent analyses disentangled head-direction signatures from signals relating to head rotation and those reflecting location-specific effects. Lastly, when directly comparing head direction and eye-gaze-related tuning, we found that the brain maintains both codes while actively navigating, with stronger tuning to head direction in the medial temporal lobe. Together, these results reveal a taxonomy of population-level head-direction signals within the human brain that is reminiscent of those reported in the single units of rodents.

Brain expression profiles of two SCN1A antisense RNAs in children and adolescents with epilepsy.

Objective: Heterozygous mutations within the voltage-gated sodium channel α subunit (SCN1A) are responsible for the majority of cases of Dravet syndrome (DS), a severe developmental and epileptic encephalopathy. Development of novel therapeutic approaches is mandatory in order to directly target the molecular consequences of the genetic defect. The aim of the present study was to investigate whether cis-acting long non-coding RNAs (lncRNAs) of SCN1A are expressed in brain specimens of children and adolescent with epilepsy as these molecules comprise possible targets for precision-based therapy approaches. Methods: We investigated SCN1A mRNA expression and expression of two SCN1A related antisense RNAs in brain tissues in different age groups of pediatric non-Dravet patients who underwent surgery for drug resistant epilepsy. The effect of different antisense oligonucleotides (ASOs) directed against SCN1A specific antisense RNAs on SCN1A expression was tested. Results: The SCN1A related antisense RNAs SCN1A-dsAS (downstream antisense, RefSeq identifier: NR_110598) and SCN1A-usAS (upstream AS, SCN1A-AS, RefSeq identifier: NR_110260) were widely expressed in the brain of pediatric patients. Expression patterns revealed a negative correlation of SCN1A-dsAS and a positive correlation of lncRNA SCN1A-usAS with SCN1A mRNA expression. Transfection of SK-N-AS cells with an ASO targeted against SCN1A-dsAS was associated with a significant enhancement of SCN1A mRNA expression and reduction in SCN1A-dsAS transcripts. Conclusion: These findings support the role of SCN1A-dsAS in the suppression of SCN1A mRNA generation. Considering the haploinsufficiency in genetic SCN1A related DS, SCN1A-dsAS is an interesting target candidate for the development of ASOs (AntagoNATs) based precision medicine therapeutic approaches aiming to enhance SCN1A expression in DS.

Good Outcome of Resective Epilepsy Surgery in a 1-Year-Old Child with Drug-Resistant Focal Epilepsy with a Novel Pathogenic COL4A1 Mutation.

Pathogenic variants in COL4A1, encoding the α chain of type IV collagen, have been associated with cerebrovascular pathology as well as malformations of cortical development, thereby causing structural epilepsy. This case illustrates successful resective epilepsy surgery in a 12-month-old girl with left occipital focal cortical dysplasia (FCD) associated with a heterozygous splice-donor variant in COL4A1. She presented with drug-resistant focal epilepsy with daily seizures from the age of 2 months, refractory to several combinations of antiseizure medications, as well as mild right-sided hemiparesis and developmental delay. All presurgical diagnostic modalities, including ictal and interictal electroencephalography, magnetic resonance imaging, and ictal fluorodeoxyglucose positron emission tomography, showed congruent findings, pointing toward one single left occipital epileptogenic zone (EZ). We performed a left occipital lobectomy, using intraoperative electrocorticography to confirm the boundaries of the EZ. After surgery, the patient has remained seizure free, and both cognitive and motor developments have improved. Histopathology of the resected brain tissue showed FCD type Ia. Resective epilepsy surgery can have a very good outcome, also in patients with genetic mutations in COL4A1, constituting a less invasive option than the previously used more radical surgical procedures such as hemispherectomy.

IQ changes after pediatric epilepsy surgery: a systematic review and meta-analysis.

OBJECTIVE: This systematic review aimed to assess the intellectual outcome of children who underwent surgery for epilepsy. METHODS: A systematic review of electronic databases was conducted on December 3, 2021, for PubMed and January 11, 2022, for Web of Science. The review was conducted according to the PRISMA guidelines. The included studies reported on intelligence quotient (IQ) or developmental quotient (DQ) before and after epilepsy surgery in children. Studies were included, if the patients had medically intractable epilepsy and if the study reported mainly on curative surgical procedures. We conducted a random-effects meta-analysis to determine the mean change of IQ/DQ. RESULTS: Fifty-seven studies reporting on a total of 2593 patients met the inclusion criteria. The mean age at surgery was 9.2 years (± 3.44; range 2.4 months-19.81 years). Thirty-eight studies showed IQ/DQ improvement on a group level, 8 yielded stable IQ/DQ, and 19 showed deterioration. Pooled analysis revealed a significant mean gain in FSIQ of + 2.52 FSIQ points (95% CI 1.12-3.91). The pooled mean difference in DQ was + 1.47 (95% CI - 6.5 to 9.5). The pooled mean difference in IQ/DQ was 0.73 (95% CI - 4.8 to 6.2). Mean FSIQ gain was significantly higher in patients who reached seizure freedom (+ 5.58 ± 8.27) than in patients who did not (+ 0.23 ± 5.65). It was also significantly higher in patients who stopped ASM after surgery (+ 6.37 ± 3.80) than in patients who did not (+ 2.01 ± 2.41). Controlled studies showed a better outcome in the surgery group compared to the non-surgery group. There was no correlation between FSIQ change and age at surgery, epilepsy duration to surgery, and preoperative FSIQ. SIGNIFICANCE: The present review indicates that there is a mean gain in FSIQ and DQ in children with medically intractable epilepsy after surgery. The mean gain of 2.52 FSIQ points reflects more likely sustainability of intellectual function rather than improvement after surgery. Seizure-free and ASM-free patients reach higher FSIQ gains. More research is needed to evaluate individual changes after specific surgery types and their effect on long-term follow-up.

Cognitive phenotype of juvenile absence epilepsy: An investigation of patients and unaffected siblings.

OBJECTIVE: The cognitive profile of juvenile absence epilepsy (JAE) remains largely uncharacterized. This study aimed to: (1) elucidate the neuropsychological profile of JAE; (2) identify familial cognitive traits by investigating unaffected JAE siblings; (3) establish the clinical meaningfulness of JAE-associated cognitive traits; (4) determine whether cognitive traits across the idiopathic generalized epilepsy (IGE) spectrum are shared or syndrome-specific, by comparing JAE to juvenile myoclonic epilepsy (JME); and (5) identify relationships between cognitive abilities and clinical characteristics. METHODS: We investigated 123 participants-23 patients with JAE, 16 unaffected siblings of JAE patients, 45 healthy controls, and 39 patients with JME-who underwent a comprehensive neuropsychological test battery including measures within four cognitive domains: attention/psychomotor speed, language, memory, and executive function. We correlated clinical measures with cognitive performance data to decode effects of age at onset and duration of epilepsy. RESULTS: Cognitive performance in individuals with JAE was reduced compared to controls across attention/psychomotor speed, language, and executive function domains; those with ongoing seizures additionally showed lower memory scores. Patients with JAE and their unaffected siblings had similar language impairment compared to controls. Individuals with JME had worse response inhibition than those with JAE. Across all patients, those with older age at onset had better attention/psychomotor speed performance. SIGNIFICANCE: JAE is associated with wide-ranging cognitive difficulties that encompass domains reliant on frontal lobe processing, including language, attention, and executive function. JAE siblings share impairment with patients on linguistic measures, indicative of a familial trait. Executive function subdomains may be differentially affected across the IGE spectrum. Cognitive abilities are detrimentally modulated by an early age at seizure onset.

Quantitative analysis of the morphometric analysis program MAP in patients with truly MRI-negative focal epilepsy.

OBJECTIVE: In the presurgical evaluation of epilepsy, identifying the epileptogenic zone is challenging if magnetic resonance imaging (MRI) is negative. Several studies have shown the benefit of using a morphometric analysis program (MAP) on T1-weighted MRI scans to detect subtle lesions. MAP can guide a focused re-evaluation of MRI to ultimately identify structural lesions that were previously overlooked. Data on patients where this additional review after MAP analysis did not reveal any lesions is limited. Here we evaluate the diagnostic yield of MAP in a large group of truly MRI-negative patients. METHODS: We identified 68 patients with MRI-negative focal epilepsy and clear localization of the epileptogenic zone by intracranial EEG or postoperative seizure freedom. High resolution 3D T1 data of patients and 73 healthy controls were acquired on a 3 T scanner. Morphometric analysis was performed with MAP software, creating five z-score maps, reflecting different structural properties of the brain and a patient's deviation from the control population, and a neural network-based focal cortical dysplasia probability map. Ten brain regions were specified to quantify whether MAP findings were located in the correct region. Receiver operating characteristic (ROC) analyses were performed to identify the optimal thresholds for each map. RESULTS: MAP-guided visual re-evaluation of the original MRI revealed overlooked lesions in three patients. The remaining 65 truly MRI-negative patients were included in the statistical analysis. At the optimal thresholds, maximum sensitivity was 84 %, with 35 % specificity. Balanced accuracy (arithmetic mean of sensitivity and specificity) of the respective maps ranged from 51 % to 60 %, creating three to six times more false positive than true positive findings. CONCLUSION: This study confirms that MAP is useful in detecting previously overlooked subtle structural lesions. However, in truly MRI-negative patients, the additional diagnostic yield is very limited.

Seizure-free outcome and safety of repeated epilepsy surgery for persistent or recurrent seizures.

OBJECTIVE: Reoperation may be an option for select patients with unsatisfactory seizure control after their first epilepsy surgery. The aim of this study was to describe the seizure-free outcome and safety of repeated epilepsy surgery in our tertiary referral center. METHODS: Thirty-eight patients with focal refractory epilepsy, who underwent repeated epilepsy surgeries and had a minimum follow-up time of 12 months after reoperation, were included. Systematic reevaluation, including comprehensive neuroimaging and noninvasive (n = 38) and invasive (n = 25, 66%) video-electroencephalography monitoring, was performed. Multimodal 3D resection maps were created for individual patients to allow personalized reoperation. RESULTS: The median time between the first operation and reoperation was 74 months (range 5-324 months). The median age at reoperation was 34 years (range 1-74 years), and the median follow-up was 38 months (range 13-142 months). Repeat MRI after the first epilepsy surgery showed an epileptogenic lesion in 24 patients (63%). The reoperation was temporal in 18 patients (47%), extratemporal in 9 (24%), and multilobar in 11 (29%). The reoperation was left hemispheric in 24 patients (63%), close to eloquent cortex in 19 (50%), and distant from the initial resection in 8 (21%). Following reoperation, 27 patients (71%) became seizure free (Engel class I), while 11 (29%) continued to have seizures. There were trends toward better outcome in temporal lobe epilepsy and for unilobar resections adjacent to the initial surgery, but there was no difference between MRI lesional and nonlesional patients. In all subgroups, Engel class I outcome was at least 50%. Perioperative complications occurred in 4 patients (11%), with no fatalities. CONCLUSIONS: Reoperation for refractory focal epilepsy is an effective and safe option in patients with persistent or recurrent seizures after initial epilepsy surgery. A thorough presurgical reevaluation is essential for favorable outcome.

Disorganization of language and working memory systems in frontal versus temporal lobe epilepsy.

Cognitive impairment is a common comorbidity of epilepsy and adversely impacts people with both frontal lobe (FLE) and temporal lobe (TLE) epilepsy. While its neural substrates have been investigated extensively in TLE, functional imaging studies in FLE are scarce. In this study, we profiled the neural processes underlying cognitive impairment in FLE and directly compared FLE and TLE to establish commonalities and differences. We investigated 172 adult participants (56 with FLE, 64 with TLE and 52 controls) using neuropsychological tests and four functional MRI tasks probing expressive language (verbal fluency, verb generation) and working memory (verbal and visuo-spatial). Patient groups were comparable in disease duration and anti-seizure medication load. We devised a multiscale approach to map brain activation and deactivation during cognition and track reorganization in FLE and TLE. Voxel-based analyses were complemented with profiling of task effects across established motifs of functional brain organization: (i) canonical resting-state functional systems; and (ii) the principal functional connectivity gradient, which encodes a continuous transition of regional connectivity profiles, anchoring lower-level sensory and transmodal brain areas at the opposite ends of a spectrum. We show that cognitive impairment in FLE is associated with reduced activation across attentional and executive systems, as well as reduced deactivation of the default mode system, indicative of a large-scale disorganization of task-related recruitment. The imaging signatures of dysfunction in FLE are broadly similar to those in TLE, but some patterns are syndrome-specific: altered default-mode deactivation is more prominent in FLE, while impaired recruitment of posterior language areas during a task with semantic demands is more marked in TLE. Functional abnormalities in FLE and TLE appear overall modulated by disease load. On balance, our study elucidates neural processes underlying language and working memory impairment in FLE, identifies shared and syndrome-specific alterations in the two most common focal epilepsies and sheds light on system behaviour that may be amenable to future remediation strategies.

Novel 3D video action recognition deep learning approach for near real time epileptic seizure classification.

Seizure semiology is a well-established method to classify epileptic seizure types, but requires a significant amount of resources as long-term Video-EEG monitoring needs to be visually analyzed. Therefore, computer vision based diagnosis support tools are a promising approach. In this article, we utilize infrared (IR) and depth (3D) videos to show the feasibility of a 24/7 novel object and action recognition based deep learning (DL) monitoring system to differentiate between epileptic seizures in frontal lobe epilepsy (FLE), temporal lobe epilepsy (TLE) and non-epileptic events. Based on the largest 3Dvideo-EEG database in the world (115 seizures/+680,000 video-frames/427GB), we achieved a promising cross-subject validation f1-score of 0.833±0.061 for the 2 class (FLE vs. TLE) and 0.763 ± 0.083 for the 3 class (FLE vs. TLE vs. non-epileptic) case, from 2 s samples, with an automated semi-specialized depth (Acc.95.65%) and Mask R-CNN (Acc.96.52%) based cropping pipeline to pre-process the videos, enabling a near-real-time seizure type detection and classification tool. Our results demonstrate the feasibility of our novel DL approach to support 24/7 epilepsy monitoring, outperforming all previously published methods.

Cognitive profiles in pediatric unilobar vs. multilobar epilepsy.

OBJECTIVES: We aimed to determine how cognitive impairment relates to the extent of the presumed epileptogenic zone in pediatric focal epilepsies. We analyzed the cognitive functions in unilobar compared to multilobar focal epilepsy patients that underwent neuropsychological testing at a tertiary epilepsy center. METHODS: We assessed cognitive functions of pediatric focal epilepsy patients with the German version of the Wechsler Intelligence Scales that measures full-scale IQ and subcategories. We assessed differences in IQ and epilepsy-related variables between unilobar and multilobar epilepsy patients. RESULTS: We included 62 patients (37 unilobar, 25 multilobar), aged 10.6 ± 3.7 years. Full-scale IQ values were significantly higher in unilobar (93.6 ± 17.7, 95% CI 87.7-99.6) than in multilobar epilepsy patients (77.3 ± 17.2, 95% CI 69.3-85.0; p = 0.001). In all but one IQ subcategory (working memory), significantly higher values were measured in unilobar than in multilobar epilepsy patients. The proportion of unilobar epilepsy patients with severe cognitive impairment (8.3%) and below-average intelligence (30.5%) was lower compared to multilobar epilepsy patients (47.6% and 61.9%; p = 0.002 and p = 0.021, respectively). Epilepsy onset occurred earlier in multilobar (4.0 years, 95% CI 2.6-5.5, SD ± 3.4 years) than in unilobar epilepsy patients (7.0 years, 95% CI 5.5-8.5, SD ± 4.4 years, p = 0.008). CONCLUSIONS: Pediatric multilobar epilepsy patients face more cognitive issues than unilobar epilepsy patients on average. Our findings should help to identify children and adolescents who are most at risk for impaired cognitive development. A limitation of our study is the simple division into unilobar and multilobar epilepsies, with no specific account being taken of etiology/epilepsy syndrome, which can have a profound effect on cognition.

Unilateral Blinking: Insights from Stereo-EEG and Tractography.

To study the neuroanatomical correlate of involuntary unilateral blinking in humans, using the example of patients with focal epilepsy. Patients with drug resistant focal epilepsy undergoing presurgical evaluation with stereotactically implanted EEG-electrodes (sEEG) were recruited from the local epilepsy monitoring unit. Only patients showing ictal unilateral blinking or unilateral blinking elicited by direct electrical stimulation were included (n = 16). MRI and CT data were used for visualization of the electrode positions. In two patients, probabilistic tractography with seeding from the respective electrodes was additionally performed. Three main findings were made: (1) involuntary unilateral blinking was associated with activation of the anterior temporal region, (2) tractography showed widespread projections to the ipsilateral frontal, pericentral, occipital, limbic and cerebellar regions and (3) blinking was observed predominantly in female patients with temporal lobe epilepsies. Unilateral blinking was found to be associated with an ipsilateral activation of the anterior temporal region. We suggest that the identified network is not part of the primary blinking control but might have modulating influence on ipsilateral blinking by integrating contextual information.

Living with global amnesia: self-established compensation strategies of a patient with severe memory impairment - a narrative report.

We report the case of C.H., a 48-year-old patient with global amnesia caused by herpes simplex encephalitis at the age of 20 and subsequent extensive bilateral temporal lobe lesions. Neuropsychological examinations performed at various intervals found persistent dense explicit memory impairment and limited vocabulary, yet intact procedural memory. Despite these limitations, C.H. self-developed and acquired a variety of effective strategies. As a result, C.H. achieved a high level of autonomy in everyday life. Her remarkable case is an encouraging and helpful example for successful implementation of creative methods and procedures to compensate and alleviate cognitive limitation, even if extensive.

Uncrossed corticospinal tract in health and genetic disorders: Review, case report, and clinical implications.

BACKGROUND AND PURPOSE: Crossing pathologies of the corticospinal tract (CST) are rare and often associated with genetic disorders. However, they can be present in healthy humans and lead to ipsilateral motor deficits when a lesion to motor areas occurs. Here, we review historical and current literature of CST crossing pathologies and present a rare case of asymmetric crossing of the CST. METHODS: Description of the case and systematic review of the literature were based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed database was searched for peer-reviewed articles in English since 1950. All articles on ipsilateral stroke, uncrossed CST, and associated neurologic disorders were screened. Furthermore, a literature review between the years 1850 and 1980 including articles in other languages, books, opinions, and case studies was conducted. RESULTS: Only a few descriptions of CST crossing pathologies exist in healthy humans, whereas they seem to be more common in genetic disorders such as horizontal gaze palsy with progressive scoliosis or congenital mirror movements. Our patient presented with aphasia and left-sided hemiparesis. Computed tomographic (CT) scan revealed a perfusion deficit in the left middle cerebral artery territory, which was confirmed by diffusion-weighted magnetic resonance imaging (MRI), so that thrombolysis was administered. Diffusion tensor imaging with fibre tracking revealed an asymmetric CST crossing. CONCLUSIONS: The knowledge of CST crossing pathologies is essential if a motor deficit occurs ipsilateral to the lesion side. An ipsilateral deficit should not lead to exclusion or delay of therapeutic options in patients with suspected stroke. Here, a combined evaluation of CT perfusion imaging and MRI diffusion imaging may be of advantage.

Hemispheric differences in the duration of focal onset seizures.

OBJECTIVE: To assess hemispheric differences in the duration of focal onset seizures and its association with clinical and demographic factors. METHODS: A retrospective analysis was performed on adult patients with drug-resistant unifocal epilepsy, who underwent intracranial EEG recording between 01/2006 and 06/2016. Seizure duration was determined based on the subdural and/or stereo-EEG (sEEG) recordings. Hemispheric differences in seizure duration were statistically evaluated with regard to clinical and demographic data. RESULTS: In total, 69 patients and 654 focal onset seizures were included. The duration of seizures with left-hemispheric onset (n = 297) was by trend longer (91.88 ± 93.92 s) than of right-hemispheric seizures (n = 357; 71.03 ± 68.53 s; p = .193). Significant hemispheric differences in seizures duration were found in temporal lobe seizures (n = 225; p = .013), especially those with automotor manifestation (n = 156; p = .045). A prolonged duration was also found for left-hemispheric onset seizures with secondary generalized commencing during waking state (n = 225; p = .034), but not during sleep. A similar hemispheric difference in seizure duration was found in female patients (p = .040), but not in men. CONCLUSIONS: Hemispheric differences in seizure duration were revealed with significantly longer durations in case of left-hemispheric seizure onset. The observed differences in seizure duration might result from brain asymmetry and add new aspects to the understanding of seizure propagation and termination.

What have we learned from 8 years of deep brain stimulation of the anterior thalamic nucleus? Experiences and insights of a single center.

OBJECTIVE: In the absence of a standard or guideline for the treatment of epilepsy patients with deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT), systematic single-center investigations are essential to establish effective approaches. Here, the authors report on the long-term results of one of the largest single-center ANT DBS cohorts. METHODS: The outcome data of 23 consecutive patients with transventricularly implanted electrodes were retrospectively analyzed with regard to adverse events, lead placement, stimulation-related side effects, and changes in seizure frequency. Depression and quality-of-life scores were collected in a subgroup of 9 patients. RESULTS: All but 2 patients initially underwent bilateral implantation, and 84.4% of all DBS leads were successfully located within the ANT. The mean follow-up time was 46.57 ± 23.20 months. A seizure reduction > 50% was documented in 73.9% of patients, and 34.6% achieved an Engel class I outcome. In 3 patients, clinical response was achieved by switching the electrode contact or changing from the monopolar to bipolar stimulation mode. Unilateral implantation seemed ineffective, whereas bilateral stimulation with successful ANT implantation only on one side led to a clinical response. Double stimulation with additional vagus nerve stimulation was safe. Changes in cycling mode or stimulation amplitude influenced therapy tolerability and, only to a lesser extent, seizure frequency. Side effects were rare and typically vanished by lowering the stimulation amplitude or changing the active electrode contact. Furthermore, depression and aspects of quality of life significantly improved with ANT DBS treatment. CONCLUSIONS: The transventricular approach as well as double stimulation proved safe. The anteroventral ANT appeared to be the most efficacious stimulation site. This systematic investigation with reluctant medication changes allowed for the development of a better idea of the association between parameter changes and outcome in ANT DBS patients, but larger samples are still needed to assess the potential of bipolar stimulation and distinct cycling frequencies. Furthermore, more multifaceted and objective assessments of treatment outcome are needed to fully assess the effects of ANT DBS treatment.

Motor hyperactivation during cognitive tasks: An endophenotype of juvenile myoclonic epilepsy.

OBJECTIVE: Juvenile myoclonic epilepsy (JME) is the most common genetic generalized epilepsy syndrome. Myoclonus may relate to motor system hyperexcitability and can be provoked by cognitive activities. To aid genetic mapping in complex neuropsychiatric disorders, recent research has utilized imaging intermediate phenotypes (endophenotypes). Here, we aimed to (a) characterize activation profiles of the motor system during different cognitive tasks in patients with JME and their unaffected siblings, and (b) validate those as endophenotypes of JME. METHODS: This prospective cross-sectional investigation included 32 patients with JME, 12 unaffected siblings, and 26 controls, comparable for age, sex, handedness, language laterality, neuropsychological performance, and anxiety and depression scores. We investigated patterns of motor system activation during episodic memory encoding and verb generation functional magnetic resonance imaging (fMRI) tasks. RESULTS: During both tasks, patients and unaffected siblings showed increased activation of motor system areas compared to controls. Effects were more prominent during memory encoding, which entailed hand motion via joystick responses. Subgroup analyses identified stronger activation of the motor cortex in JME patients with ongoing seizures compared to seizure-free patients. Receiver-operating characteristic curves, based on measures of motor activation, accurately discriminated both patients with JME and their siblings from healthy controls (area under the curve: 0.75 and 0.77, for JME and a combined patient-sibling group against controls, respectively; P < .005). SIGNIFICANCE: Motor system hyperactivation represents a cognitive, domain-independent endophenotype of JME. We propose measures of motor system activation as quantitative traits for future genetic imaging studies in this syndrome.

Who seizes longest? Impact of clinical and demographic factors.

OBJECTIVE: To investigate the impact of clinical and demographic parameters on the duration of focal onset seizures with and without secondary generalization using precise duration measurements from intracranial electroencephalographic (iEEG) recordings. METHODS: Patients with unifocal epilepsy syndromes and iEEG recording were retrospectively identified from the database of the local epilepsy center (2006-2016). Seizure duration was defined as time difference of iEEG seizure pattern onset and cessation. The seizure semiology was classified based on video recordings. Clinical and demographic data were extracted from patient reports. RESULTS: In total, 69 adults were included, and 654 focal onset seizures were analyzed. Focal to bilateral tonic-clonic seizures (FBTCSs; 98/654) were significantly longer than focal seizures (FSs) without generalization (FS-BTCs; 556/654, P < .001), and most FSs (545/654, 83.3%) terminated within 2 minutes. The duration of FSs was prolonged with increasing age of the patients (P = .003) and was significantly shortened (P < .001) by evolution into an FBTCS. FBTCSs with lateralizing semiologies like version (P = .015) and sign of four (P = .043) were associated with longer bilateral tonic-clonic manifestations. Furthermore, FBTCSs with preceding aura, frontal origin, or onset during sleep were by trend shorter. Age (P < .001) and disease duration (P = .028) were essential for prediction of FS-BTC duration, whereas the vigilance state (P = .085) was the main prediction factor for the duration of FBTCSs. SIGNIFICANCE: The identified modifiers of seizure duration are of great relevance for clinical risk evaluation, especially in the aging epilepsy patient suffering from temporal lobe epilepsy with secondary generalized seizures.

Congruence and Discrepancy of Interictal and Ictal EEG With MRI Lesions in Pediatric Epilepsies.

Purpose. To evaluate the congruence or discrepancy of the localization of magnetic resonance imaging (MRI) lesions with interictal epileptiform discharges (IEDs) or epileptic seizure patterns (ESPs) in surface EEG in lesional pediatric epilepsy patients. Methods. We retrospectively analyzed presurgical MRI and video-EEG monitoring findings of patients up to age 18 years. Localization of MRI lesions were compared with ictal and interictal noninvasive EEG findings of patients with frontal, temporal, parietal, or occipital lesions. Results. A total of 71 patients were included. Localization of ESPs showed better congruence with MRI in patients with frontal lesions (n = 21, 77.5%) than in patients with temporal lesions (n = 24; 40.7%) (P = .009). No significant IED distribution differences between MRI localizations could be found. Conclusions. MRI lesions and EEG findings are rarely fully congruent. Congruence of MRI lesions and ESPs was highest in children with frontal lesions. This is in contrast to adults, in whom temporal lesions showed the highest congruency with the EEG localization of ESP. Lesional pediatric patients should be acknowledged as surgical candidates despite incongruent findings of interictal and ictal surface EEG.

Changes of brain DTI in healthy human subjects after 520 days isolation and confinement on a simulated mission to Mars.

INTRODUCTION: Long-term confinement is known to be a stressful experience with multiple psycho-physiological effects. In the MARS500 project, a real-time simulation of a space-flight to Mars conducted in a hermetically isolated habitat, effects of long-term confinement could be investigated in a unique manner. The aim of this study was to evaluate effects of long-term-confinement on brain cytoarchitecture. MATERIAL & METHODS: The participants of the MARS500 project underwent 3T-MR imaging including a dedicated DTI-sequence before the isolation, right after ending of confinement and 6 months after the experiment. Voxelwise statistical analysis of the DTI data was carried out using tract-based-spatial statistics, comparing an age-matched control group. RESULTS: At all three sessions, significant lower fractional anisotropy (FA) than in controls was found in the anterior parts of the callosal body of the participants. Furthermore, after ending of confinement a wide-spread FA reduction could be seen in the right hemisphere culminating in the temporo-parietal-junction-zone. All these areas with decreased FA predominantly showed an elevated radial diffusivity and mean diffusivity while axial diffusivity was less correlated. DISCUSSION: Long-term confinement does have measurable effects on the microstructure of the brain white matter. We assume effects of sensory deprivation to account for the regional FA reductions seen in the right TPJ. The differences in the Corpus callosum were interpreted as due to preliminary conditions, e.g. personality traits or training effects. FA and radial diffusivity were the predominant DTI parameters with significant changes, suggesting underlying processes of myelin plasticity.

Abnormal hippocampal structure and function in juvenile myoclonic epilepsy and unaffected siblings.

Juvenile myoclonic epilepsy is the most common genetic generalized epilepsy syndrome, characterized by a complex polygenetic aetiology. Structural and functional MRI studies demonstrated mesial or lateral frontal cortical derangements and impaired fronto-cortico-subcortical connectivity in patients and their unaffected siblings. The presence of hippocampal abnormalities and associated memory deficits is controversial, and functional MRI studies in juvenile myoclonic epilepsy have not tested hippocampal activation. In this observational study, we implemented multi-modal MRI and neuropsychological data to investigate hippocampal structure and function in 37 patients with juvenile myoclonic epilepsy, 16 unaffected siblings and 20 healthy controls, comparable for age, gender, handedness and hemispheric dominance as assessed with language laterality indices. Automated hippocampal volumetry was complemented by validated qualitative and quantitative morphological criteria to detect hippocampal malrotation, assumed to represent a neurodevelopmental marker. Neuropsychological measures of verbal and visuo-spatial learning and an event-related verbal and visual memory functional MRI paradigm addressed mesiotemporal function. We detected a reduction of mean left hippocampal volume in patients and their siblings compared with controls (P < 0.01). Unilateral or bilateral hippocampal malrotation was identified in 51% of patients and 50% of siblings, against 15% of controls (P < 0.05). For bilateral hippocampi, quantitative markers of verticalization had significantly larger values in patients and siblings compared with controls (P < 0.05). In the patient subgroup, there was no relationship between structural measures and age at disease onset or degree of seizure control. No overt impairment of verbal and visual memory was identified with neuropsychological tests. Functional mapping highlighted atypical patterns of hippocampal activation, pointing to abnormal recruitment during verbal encoding in patients and their siblings [P < 0.05, familywise error (FWE)-corrected]. Subgroup analyses indicated distinct profiles of hypoactivation along the hippocampal long axis in juvenile myoclonic epilepsy patients with and without malrotation; patients with malrotation also exhibited reduced frontal recruitment for verbal memory, and more pronounced left posterior hippocampal involvement for visual memory. Linear models across the entire study cohort indicated significant associations between morphological markers of hippocampal positioning and hippocampal activation for verbal items (all P < 0.05, FWE-corrected). We demonstrate abnormalities of hippocampal volume, shape and positioning in patients with juvenile myoclonic epilepsy and their siblings, which are associated with reorganization of function and imply an underlying neurodevelopmental mechanism with expression during the prenatal stage. Co-segregation of abnormal hippocampal morphology in patients and their siblings is suggestive of a genetic imaging phenotype, independent of disease activity, and can be construed as a novel endophenotype of juvenile myoclonic epilepsy.