A Homozygous PTRHD1 Missense Variant (p.Arg122Gln) in an Individual with Intellectual Disability, Generalized Epilepsy, and Juvenile Parkinsonism.

Biallelic variants in PTRHD1 have been associated with autosomal recessive intellectual disability, spasticity, and juvenile parkinsonism, with few reported cases. Here, we present the clinical and genetic findings of a female of Austrian origin exhibiting infantile neurodevelopmental abnormalities, intellectual disability, and childhood-onset parkinsonian features, consistent with the established phenotypic spectrum. Notably, she developed genetic generalized epilepsy at age 4, persisting into adulthood. Using diagnostic exome sequencing, we identified a homozygous missense variant (c.365G > A, p.(Arg122Gln)) in PTRHD1 (NM_001013663). In summary, our findings not only support the existing link between biallelic PTRHD1 variants and parkinsonism with neurodevelopmental abnormalities but also suggest a potential extension of the phenotypic spectrum to include generalized epilepsy.

Visual outcomes after anterior temporal lobectomy and transsylvian selective amygdalohippocampectomy: A quantitative comparison of clinical and diffusion data.

OBJECTIVE: Anterior temporal lobectomy (ATL) and transsylvian selective amygdalohippocampectomy (tsSAHE) are effective treatment strategies for intractable temporal lobe epilepsy but may cause visual field deficits (VFDs) by damaging the optic radiation (OpR). Due to the OpR's considerable variability and because it is indistinguishable from surrounding tissue without further technical guidance, it is highly vulnerable to iatrogenic injury. This imaging study uses a multimodal approach to assess visual outcomes after epilepsy surgery. METHODS: We studied 62 patients who underwent ATL (n = 32) or tsSAHE (n = 30). Analysis of visual outcomes was conducted in four steps, including the assessment of (1) perimetry outcome (VFD incidence/extent, n = 44/40), (2) volumetric OpR tractography damage (n = 55), and the (3) relation of volumetric OpR tractography damage and perimetry outcome (n = 35). Furthermore, (4) fixel-based analysis (FBA) was performed to assess micro- and macrostructural changes within the OpR following surgery (n = 36). RESULTS: Altogether, 56% of all patients had postoperative VFDs (78.9% after ATL, 36.36% after tsSAHE, p = .011). VFDs and OpR tractography damage tended to be more severe within the ATL group (ATL vs. tsSAHE, integrity of contralateral upper quadrant: 65% vs. 97%, p = .002; OpR tractography damage: 69.2 mm3 vs. 3.8 mm3 , p = .002). Volumetric OpR tractography damage could reliably predict VFD incidence (86% sensitivity, 78% specificity) and could significantly explain VFD extent (R2  = .47, p = .0001). FBA revealed a more widespread decline of fibre cross-section within the ATL group. SIGNIFICANCE: In the context of controversial visual outcomes following epilepsy surgery, this study provides clinical as well as neuroimaging evidence for a higher risk and greater severity of postoperative VFDs after ATL compared to tsSAHE. Volumetric OpR tractography damage is a feasible parameter to reliably predict this morbidity in both treatment groups and may ultimately support personalized planning of surgical candidates. Advanced diffusion analysis tools such as FBA offer a structural explanation of surgically induced visual pathway damage, allowing noninvasive quantification and visualization of micro- and macrostructural tract affection.

Do all patients in the epilepsy monitoring unit experience the same level of comfort? A quantitative exploratory secondary analysis.

AIMS: To find out which variables may be associated with comfort of patients in an epilepsy monitoring unit. DESIGN: Exploratory, quantitative study design. METHODS: Data were collected from October 2018 to November 2019 in Austria and Southern Germany. A total of 267 patients of 10 epilepsy centres completed the Epilepsy Monitoring Unit Comfort Questionnaire which is based on Kolcaba's General Comfort Questionnaire. Secondary data analysis were conducted by using descriptive statistics and an exploratory model building approach, including different linear regression models and several sensitivity analyses. RESULTS: Total comfort scores ranged from 83 to 235 points. Gender, occupation and centre turned out to be possible influential variables. On average, women had a total comfort score 4.69 points higher than men, and retired persons 28.2 points higher than high school students ≥18 years. Comfort scores of younger patients were lower than those of older patients. However, age did not show a statistically significant effect. The same could be observed in marital status and educational levels. CONCLUSION: When implementing comfort measures, nurses must be aware of variables which could influence the intervention negatively. Especially, high school students ≥18 years should be supported by epilepsy specialist nurses, in order to reduce uncertainty, anxiety and discomfort. But, since the identified variables account only for a small proportion of the inter-individual variability in comfort scores, further studies are needed to find out additional relevant aspects and to examine centre-specific effects more closely. IMPACT: Nurses ensure patient comfort during a hospital stay. However, there are variables that may impair the effectiveness of the nursing measures. Our study showed that the experience of comfort was highly individual and could be explained by sociodemographic variables only to a limited extent. Nurses must be aware that additional factors, such as the situation in the individual setting, may be relevant.

Diagnostic exome sequencing in non-acquired focal epilepsies highlights a major role of GATOR1 complex genes.

BACKGROUND: The genetic architecture of non-acquired focal epilepsies (NAFEs) becomes increasingly unravelled using genome-wide sequencing datasets. However, it remains to be determined how this emerging knowledge can be translated into a diagnostic setting. To bridge this gap, we assessed the diagnostic outcomes of exome sequencing (ES) in NAFE. METHODS: 112 deeply phenotyped patients with NAFE were included in the study. Diagnostic ES was performed, followed by a screen to detect variants of uncertain significance (VUSs) in 15 well-established focal epilepsy genes. Explorative gene prioritisation was used to identify possible novel candidate aetiologies with so far limited evidence for NAFE. RESULTS: ES identified pathogenic or likely pathogenic (ie, diagnostic) variants in 13/112 patients (12%) in the genes DEPDC5, NPRL3, GABRG2, SCN1A, PCDH19 and STX1B. Two pathogenic variants were microdeletions involving NPRL3 and PCDH19. Nine of the 13 diagnostic variants (69%) were found in genes of the GATOR1 complex, a potentially druggable target involved in the mammalian target of rapamycin (mTOR) signalling pathway. In addition, 17 VUSs in focal epilepsy genes and 6 rare variants in candidate genes (MTOR, KCNA2, RBFOX1 and SCN3A) were detected. Five patients with reported variants had double hits in different genes, suggesting a possible (oligogenic) role of multiple rare variants. CONCLUSION: This study underscores the molecular heterogeneity of NAFE with GATOR1 complex genes representing the by far most relevant genetic aetiology known to date. Although the diagnostic yield is lower compared with severe early-onset epilepsies, the high rate of VUSs and candidate variants suggests a further increase in future years.

Non-pulsatile blood flow is associated with enhanced cerebrovascular carbon dioxide reactivity and an attenuated relationship between cerebral blood flow and regional brain oxygenation.

BACKGROUND: Systemic blood flow in patients on extracorporeal assist devices is frequently not or only minimally pulsatile. Loss of pulsatile brain perfusion, however, has been implicated in neurological complications. Furthermore, the adverse effects of absent pulsatility on the cerebral microcirculation are modulated similarly as CO2 vasoreactivity in resistance vessels. During support with an extracorporeal assist device swings in arterial carbon dioxide partial pressures (PaCO2) that determine cerebral oxygen delivery are not uncommon-especially when CO2 is eliminated by the respirator as well as via the gas exchanger of an extracorporeal membrane oxygenation machine. We, therefore, investigated whether non-pulsatile flow affects cerebrovascular CO2 reactivity (CVR) and regional brain oxygenation (rSO2). METHODS: In this prospective, single-centre case-control trial, we studied 32 patients undergoing elective cardiac surgery. Blood flow velocity in the middle cerebral artery (MCAv) as well as rSO2 was determined during step changes of PaCO2 between 30, 40, and 50 mmHg. Measurements were conducted on cardiopulmonary bypass during non-pulsatile and postoperatively under pulsatile blood flow at comparable test conditions. Corresponding changes of CVR and concomitant rSO2 alterations were determined for each flow mode. Each patient served as her own control. RESULTS: MCAv was generally lower during hypocapnia than during normocapnia and hypercapnia (p < 0.0001). However, the MCAv/PaCO2 slope during non-pulsatile flow was 14.4 cm/s/mmHg [CI 11.8-16.9] and 10.4 cm/s/mmHg [CI 7.9-13.0] after return of pulsatility (p = 0.03). During hypocapnia, non-pulsatile CVR (4.3 ± 1.7%/mmHg) was higher than pulsatile CVR (3.1 ± 1.3%/mmHg, p = 0.01). Independent of the flow mode, we observed a decline in rSO2 during hypocapnia and a corresponding rise during hypercapnia (p < 0.0001). However, the relationship between ΔrSO2 and ΔMCAv was less pronounced during non-pulsatile flow. CONCLUSIONS: Non-pulsatile perfusion is associated with enhanced cerebrovascular CVR resulting in greater relative decreases of cerebral blood flow during hypocapnia. Heterogenic microvascular perfusion may account for the attenuated ΔrSO2/ΔMCAv slope. Potential hazards related to this altered regulation of cerebral perfusion still need to be assessed. TRIAL REGISTRATION: The study was retrospectively registered on October 30, 2018, with Clinical Trial.gov (NCT03732651).

Field testing of ICHD-3 beta criteria of periictal headaches in patients with focal epilepsy - a prospective diary study.

Background To date we are lacking prospective data for field testing of ICHD-3 beta criteria for periictal headache (PIH). Methods Patients with focal epilepsy diagnosed by means of prolonged video-EEG monitoring completed a paper-pencil diary for three months and recorded seizures and headaches on a daily basis. According to ICHD-3 beta, we classified PIH, defined as headache present on a day with at least one seizure, as "7.6 headache related to epileptic seizure", "7.6.1 hemicrania epileptica" or "7.6.2 postictal headache". In addition, we compared the ICHD-3 beta diagnoses to the diagnoses according to ICHD-2. Results Thirty two patients completed the diary. Data analysis included 2,668 patient days, 300 seizures and 37 episodes of PIH. Two of these episodes (5.4%) were classified as headache related to seizure, three (8.1%) fulfilled both the criteria of headache related to seizure and hemicrania epileptica and four (10.8%) were postictal headaches. Twenty eight episodes (75.7%) did not fulfil any of the ICHD-3 beta criteria of seizure-related headaches, mostly because headache onset was before seizure onset. Applying ICHD-2 criteria allowed only one single episode of PIH to be classified as postictal headache. Discussion Our study is the first to present prospective field testing data of the ICHD-3 beta criteria for three types of seizure-related headaches. The majority of PIH episodes do not fulfil any of these criteria. One quarter can be classified according to ICHD-3 beta, whereas purely clinical diagnosis of PIH is markedly restricted in ICHD-2 because of mandatory electroencephalographic evidence.

Seizures After Adult Cardiac Surgery and Interventional Cardiac Procedures.

The aim of this narrative review is to evaluate the incidence of seizures after adult cardiac surgery or cardiac interventions, to describe risk factors, and to provide suggestions regarding diagnostic measures and proper management. Based on published peer-reviewed articles, the authors demonstrate specific procedure-related risks for seizures. Early diagnosis, the identification of underlying causes, and avoidance of amenable risk factors are crucial to reduce associated long-term morbidity and mortality. Methods of early recognition of seizures, particularly focusing on the initiation of appropriate diagnostic measures, their management, and their timely treatment, are presented in the article.

Psychoses in epilepsy: A comparison of postictal and interictal psychoses.

We retrospectively analyzed data of patients with epilepsy (n=1434) evaluated with prolonged EEG monitoring in order to estimate the prevalence of postictal psychosis (PP) and interictal psychosis (IP), to investigate a potential association of psychosis subtype with epilepsy type, and to assess differences between PP and IP. The overall prevalence of psychosis was 5.9% (N=85); prevalence of PP (N=53) and IP (N=32) was 3.7% and 2.2%, respectively. Of patients with psychosis, 97.6% had localization-related epilepsy (LRE). Prevalence of psychosis was highest (9.3%) in patients with temporal lobe epilepsy (TLE). When comparing PP with IP groups on demographic, clinical, and psychopathological variables, patients with IP were younger at occurrence of first psychosis (P=0.048), had a shorter interval between epilepsy onset and first psychosis (P=0.002), and more frequently exhibited schizophreniform traits (conceptual disorganization: P=0.008; negative symptoms: P=0.017) than those with PP. Postictal psychosis was significantly associated with a temporal seizure onset on ictal EEG (P=0.000) and a higher incidence of violent behavior during psychosis (P=0.047). To conclude, our results support the presumption of a preponderance of LRE in patients with psychosis and that of a specific association of TLE with psychosis, in particular with PP. Given the significant differences between groups, PP and IP may represent distinct clinical entities potentially with a different neurobiological background.

Depressive symptoms predict the quality of sleep in patients with partial epilepsy--A combined retrospective and prospective study.

INTRODUCTION: Epilepsy is one of the most common neurological diseases and has many detrimental effects on the patients' well-being as well as sleep quality. The aim of this study was to assess the subjective quality of sleep and influencing factors on subjective sleep quality in patients with partial epilepsy using a combined retrospective and prospective study design. METHODS: We conducted a combined retrospective and prospective study in patients with partial epilepsy and analyzed subjective ratings of sleep quality in 32 patients (17 female, 15 male; mean age: 40.41 ± 12.67 years, range: 20-64) with partial epilepsy (mean duration of epilepsy diagnosis: 18.31 ± 13.26 years) and 32 healthy gender-matched and age-matched controls. All patients filled out a seizure diary for 90 days, which included the number, duration, and type (partial vs. secondary generalized) of epileptic seizures and intake of antiepileptic and sleep medications. At baseline, all participants completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Beck's Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Poor sleepers were defined by a PSQI score of ≥ 5. RESULTS: Twenty-three patients (72%) reported 15.17 ± 25.54 seizures in the previous three months, and nine (28%) patients reported being seizure-free. During the 90-day diary period, twenty-two patients (69%) documented a total of 319 epileptic seizures, while ten patients (31%) reported that they were seizure-free. The mean PSQI score of all patients was 4.88 ± 2.92 (range: 1-14) and the mean ESS score was 5.25 ± 2.98 (range: 0-10). The mean PSQI score of the control group was 3.25 ± 1.57 (range: 1-6), and their mean ESS score was 6.72 ± 3.48 (range: 0-14). The comparison of the two groups showed a significantly higher PSQI score in the patient group (t = 2.778, p = 0.008), but no statistically significant difference regarding their ESS score (t = -1.811, p = 0.075). Sixteen (50%) patients were poor sleepers. Good sleepers showed a significantly lower PSQI (2.69 ± 1.08 vs. 7.06 ± 2.49; p < 0.001) and BDI scores (2.38 ± 2.50 vs. 9.63 ± 7.63; p < 0.002) than poor sleepers. Linear regression analysis showed that the BDI score was the significant predictor for the PSQI score (estimate: 0.2019; p = 0.00819) and for the ESS score (estimate: 0.2251; p = 0.0321). CONCLUSION: In patients with partial epilepsy, a higher depression score was the best predictor for a poor subjective sleep quality and increased daytime sleepiness.

Autosomal recessive cortical myoclonic tremor and epilepsy: association with a mutation in the potassium channel associated gene CNTN2.

We characterize a consanguineous Egyptian family with an autosomal recessively inherited familial cortical myoclonic tremor and epilepsy. We used multipoint linkage analysis to map the causative mutation to a 12.7 megabase interval within 1q31.3-q32.2 with a log of odds score of 3.6. For further investigation of the linked region in an efficient and unbiased manner, we performed exome sequencing. Within the suspected region we identified a homozygous single base pair deletion (c.503_503delG) leading to a frameshift in the coding region of the sixth exon of CNTN2 alias TAG-1 (p.Trp168fs), which segregated in the respective family. Many studies point towards an important role of the CNTN2 product contactin 2 in neuronal excitability. Contactin 2, a glycosylphosphatidylinositol-anchored neuronal membrane protein, and another transmembrane protein called contactin associated protein-like 2 (CNTNAP2 alias CASPR2) are together necessary to maintain voltage-gated potassium channels at the juxtaparanodal region. CNTN2 knockout mice were previously reported to suffer from spontaneous seizures and mutations in the CNTNAP2 gene have been described to cause epilepsy in humans. To further delineate the role of CNTN2 in patients with epilepsy, we sequenced the coding exons in 189 Caucasian patients with epilepsy. No recessive mutation was detected and heterozygote carriers of rare CNTN2 variants do not seem to be predisposed to epilepsy. Given the severity of the mutation and the proposed function of the gene, we consider this mutation as the most likely cause for cortical myoclonic tremor and epilepsy in this family.

A navigated, robot-driven laser craniotomy tool for frameless depth electrode implantation. An in-vivo recovery animal study.

Objectives: We recently introduced a frameless, navigated, robot-driven laser tool for depth electrode implantation as an alternative to frame-based procedures. This method has only been used in cadaver and non-recovery studies. This is the first study to test the robot-driven laser tool in an in vivo recovery animal study. Methods: A preoperative computed tomography (CT) scan was conducted to plan trajectories in sheep specimens. Burr hole craniotomies were performed using a frameless, navigated, robot-driven laser tool. Depth electrodes were implanted after cut-through detection was confirmed. The electrodes were cut at the skin level postoperatively. Postoperative imaging was performed to verify accuracy. Histopathological analysis was performed on the bone, dura, and cortex samples. Results: Fourteen depth electrodes were implanted in two sheep specimens. Anesthetic protocols did not show any intraoperative irregularities. One sheep was euthanized on the same day of the procedure while the other sheep remained alive for 1 week without neurological deficits. Postoperative MRI and CT showed no intracerebral bleeding, infarction, or unintended damage. The average bone thickness was 6.2 mm (range 4.1-8.0 mm). The angulation of the planned trajectories varied from 65.5° to 87.4°. The deviation of the entry point performed by the frameless laser beam ranged from 0.27 mm to 2.24 mm. The histopathological analysis did not reveal any damage associated with the laser beam. Conclusion: The novel robot-driven laser craniotomy tool showed promising results in this first in vivo recovery study. These findings indicate that laser craniotomies can be performed safely and that cut-through detection is reliable.

Which parameters influence cognitive, psychiatric and long-term seizure outcome in mesial temporal lobe epilepsy after selective amygdalohippocampectomy?

BACKGROUND: We aimed to analyze potentially prognostic factors which could have influence on postoperative seizure, neuropsychological and psychiatric outcome in a cohort of patients with mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS) after selective amygdalohippocampectomy (SAHE) via transsylvian approach. METHODS: Clinical variables of 171 patients with drug-resistant MTLE with HS (88 females) who underwent SAHE between 1994 and 2019 were evaluated using univariable and multivariable logistic regression models, to investigate which of the explanatory parameters can best predict the outcome. RESULTS: At the last available follow-up visit 12.3 ± 6.3 years after surgery 114 patients (67.9%) were seizure-free. Left hemispheric MTLE was associated with worse postoperative seizure outcome at first year after surgery (OR = 0.54, p = 0.01), female sex-with seizure recurrence at years 2 (OR = 0.52, p = 0.01) and 5 (OR = 0.53, p = 0.025) and higher number of preoperative antiseizure medication trials-with seizure recurrence at year 2 (OR = 0.77, p = 0.0064), whereas patients without history of traumatic brain injury had better postoperative seizure outcome at first year (OR = 2.08, p = 0.0091). All predictors lost their predictive value in long-term course. HS types had no prognostic influence on outcome. Patients operated on right side performed better in verbal memory compared to left (VLMT 1-5 p < 0.001, VLMT 7 p = 0.001). Depression occurred less frequently in seizure-free patients compared to non-seizure-free patients (BDI-II Z = - 2.341, p = 0.019). CONCLUSIONS: SAHE gives an improved chance of achieving good postoperative seizure, psychiatric and neuropsychological outcome in patients with in MTLE due to HS. Predictors of short-term outcome don't predict long-term outcome.

Implementation of a 7T Epilepsy Task Force consensus imaging protocol for routine presurgical epilepsy work-up: effect on diagnostic yield and lesion delineation.

OBJECTIVE: Recently, the 7 Tesla (7 T) Epilepsy Task Force published recommendations for 7 T magnetic resonance imaging (MRI) in patients with pharmaco-resistant focal epilepsy in pre-surgical evaluation. The objective of this study was to implement and evaluate this consensus protocol with respect to both its practicability and its diagnostic value/potential lesion delineation surplus effect over 3 T MRI in the pre-surgical work-up of patients with pharmaco-resistant focal onset epilepsy. METHODS: The 7 T MRI protocol consisted of T1-weighted, T2-weighted, high-resolution-coronal T2-weighted, fluid-suppressed, fluid-and-white-matter-suppressed, and susceptibility-weighted imaging, with an overall duration of 50 min. Two neuroradiologists independently evaluated the ability of lesion identification, the detection confidence for these identified lesions, and the lesion border delineation at 7 T compared to 3 T MRI. RESULTS: Of 41 recruited patients > 12 years of age, 38 were successfully measured and analyzed. Mean detection confidence scores were non-significantly higher at 7 T (1.95 ± 0.84 out of 3 versus 1.64 ± 1.19 out of 3 at 3 T, p = 0.050). In 50% of epilepsy patients measured at 7 T, additional findings compared to 3 T MRI were observed. Furthermore, we found improved border delineation at 7 T in 88% of patients with 3 T-visible lesions. In 19% of 3 T MR-negative cases a new potential epileptogenic lesion was detected at 7 T. CONCLUSIONS: The diagnostic yield was beneficial, but with 19% new 7 T over 3 T findings, not major. Our evaluation revealed epilepsy outcomes worse than ILAE Class 1 in two out of the four operated cases with new 7 T findings.

Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry.

BACKGROUND AND OBJECTIVES: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice. METHODS: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes. RESULTS: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported. DISCUSSION: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy. TRIAL REGISTRATION INFORMATION: MORE ClinicalTrials.gov Identifier: NCT01521754, first posted on January 31, 2012.

Prominent oligodendroglial response in surgical specimens of patients with temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is characterized by distinct neuropathological findings, such as hippocampal sclerosis and reactive astrogliosis. Recently, MRI studies have revealed the presence of white matter pathology in brains of epilepsy patients. The purpose of this study is to evaluate the involvement of oligodendroglia in the epileptogenic process. Using TPPP/p25 as a marker for mature oligodendroglia, we evaluated the hippocampus in 26 surgical specimens from patients with TLE and 9 autopsy controls without neuropathological alterations for changes in oligodendroglial cell densities (mm2) in hippocampal, entorhinal, and temporal white matter, and the amount of perineuronal oligodendrocytes in CA1 subregion. Oligodendrocyte cell densities were significantly elevated in epilepsy patients compared to controls in all four examined white matter subregions. In addition, in the CA1 sector, the percentage of neurons showing more than one perineuronal oligodendrocyte was significantly higher in epilepsy patients. In conclusion, our study expands the glial reactions beyond astrogliosis and shows that prominent oligodendroglial response is a consistent pathological feature characteristic for TLE.

Psychiatric symptoms and comorbidities in patients with drug-resistant epilepsy in presurgical assessment-A prospective explorative single center study.

Introduction: People with epilepsy (PWE) have a higher prevalence of psychiatric disorders. Some individuals with drug-resistant epilepsy might benefit from surgical interventions. The aim of this study was to perform an assessment of psychiatric comorbidities with a follow-up period of 12 months in patients with drug-resistant epilepsy, comparing those who underwent surgery to those who did not. Material and methods: We assessed psychiatric comorbidities at baseline, after 4 months and after 12 months. Psychiatric symptoms and diagnoses were assessed using SCID-Interview, Hamilton Rating Scale for Depression, Beck-Depression Inventory, Hamilton Anxiety Rating Scale, Prodromal-Questionnaire and the Global Assessment of Functioning Scale. Results: Twenty-five patients were included in the study, 12 underwent surgery, 11 were esteemed as being neurologically unqualified for surgery and two refused surgery. Patients in the no-surgery group were significantly older, reported more substance use, had significantly higher levels of anxiety and were more often diagnosed with a personality disorder. Age and levels of anxiety were significant predictors of being in the surgery or the no-surgery group. The described differences between surgery and no-surgery patients did not change significantly over the follow-up period. Discussion: These data point toward a higher expression of baseline psychiatric symptoms in drug-resistant PWE without surgery. Further studies are warranted to further elucidate these findings and to clarify potential psychotropic effects of epilepsy itself, drug-resistant epilepsy and of epilepsy surgery and their impact on psychopathology. Clinically, it seems highly relevant to include psychiatrists in an interdisciplinary state-of-the-art perioperative management of drug-resistant PWE.

The Impact of Nonconvulsive Status Epilepticus after Cardiac Surgery on Outcome.

Neurological complications after heart surgery are associated with tremendous morbidity and mortality. Nonconvulsive status epilepticus (NCSE), which can only be verified by EEG, may cause secondary brain damage. Its frequency and its impact on outcomes after cardiac surgery is still unclear. We collected the neurological files and clinical data of all our patients after heart surgery who, in the course of their ICU stay, had been seen by a neurologist who ordered an EEG. Within 18 months, 1457 patients had cardiac surgery on cardiopulmonary bypass. EEG was requested for 89 patients. Seizures were detected in 39 patients and NCSE was detected in 11 patients. Open heart surgery was performed in all 11 NSCE patients, of whom eight showed concomitant brain insults. None had a history of epilepsy. Despite the inhibition of seizure activity with antiseizure medication, clinical improvement was only noted in seven NCSE patients, three of whom were in cerebral performance category 2 and four in category 3 at hospital discharge. The four patients without neurological benefit subsequently died in the ICU. The occurrence of NCSE after open cardiac surgery is significant and frequently associated with brain injury. It seems prudent to perform EEG studies early to interrupt seizure activity and mitigate secondary cerebral injury.

Imaging visuospatial memory in temporal lobe epilepsy-Results of an fMRI study.

PURPOSE: Impairment of cognitive functions is commonly observed in temporal lobe epilepsy (TLE). The aim of this study was to assess visuospatial memory functions and memory-related networks using an adapted version of Roland's Hometown Walking (RHWT) functional MRI (fMRI) task in patients with TLE. METHODS: We used fMRI to study activation patterns based on a visuospatial memory paradigm in 32 TLE patients (9 right; 23 left) and also within subgroups of lesional and non-lesional TLE. To test for performance, a correlational analysis of fMRI activation patterns and out-of-scanner neuropsychological visuospatial memory testing was performed. Additionally, we assessed memory-related networks using functional connectivity (FC). RESULTS: Greater contralateral than ipsilateral mesiotemporal (parahippocampal gyrus/hippocampus) activation was observed in left (n = 23)/right (n = 9) TLE. In lesional left TLE (n = 17), significant activations were seen in right more than left mesiotemporal areas (parahippocampal gyrus), while non-lesional left TLE patients (n = 6) showed significant bilateral (left>right) activations in mesiotemporal structures (parahippocampal gyrus). In left TLE, visuospatial cognitive testing correlated with fMRI activations in left (parahippocampal gyrus) and right mesiotemporal structures (hippocampus), characterized by greater fMRI activation being associated with better memory scores. In right TLE, higher scores in visuospatial memory testing were associated with greater fMRI activations in left and right insular regions. FC patterns of memory-related networks differ in right and left TLE. CONCLUSION: While TLE in general leads to asymmetrical mesiotemporal activation, lesion-induced and non-lesional TLE patients reveal different memory fMRI activation patterns. In right TLE, insular regions try to compensate for impaired right mesiotemporal structures during the performance of visuospatial tasks. Underlying functional visuospatial memory networks differ in right and left TLE.

Awake brain surgery for language mapping in pediatric patients: a single-center experience.

OBJECTIVE: The goal of this study was to evaluate the feasibility, benefit, and safety of awake brain surgery (ABS) and intraoperative language mapping in children and adolescents with structural epilepsies. Whereas ABS is an established method to monitor language function in adults intraoperatively, reports of ABS in children are scarce. METHODS: A retrospective chart review of pediatric patients ≤ 18 years of age who underwent ABS and cortical language mapping for supratentorial tumors and nontumoral epileptogenic lesions between 2008 and 2019 was conducted. The authors evaluated the global intellectual and specific language performance by using detailed neuropsychological testing, the patient's intraoperative compliance, results of intraoperative language mapping assisted by electrocorticography (ECoG), and postsurgical language development and seizure outcomes. Descriptive statistics were used for this study, with a statistical significance of p < 0.05. RESULTS: Eleven children (7 boys) with a median age of 13 years (range 10-18 years) underwent ABS for a lesion in close vicinity to cortical language areas as defined by structural and functional MRI (left hemisphere in 9 children, right hemisphere in 2). Patients were neurologically intact but experiencing seizures; these were refractory to therapy in 9 patients. Compliance during the awake phase was high in 10 patients and low in 1 patient. Cortical mapping identified eloquent language areas in 6/10 (60%) patients and was concordant in 3/8 (37.5%), discordant in 3/8 (37.5%), and unclear in 2/8 (25%) patients compared to preoperative functional MRI. Stimulation-induced seizures occurred in 2 patients and could be interrupted easily. ECoG revealed that afterdischarge potentials (ADP) were involved in 5/9 (56%) patients with speech disturbances during stimulation. None of these patients harbored postoperative language dysfunction. Gross-total resection was achieved in 10/11 (91%) patients, and all were seizure free after a median follow-up of 4.3 years. Neuropsychological testing using the Wechsler Intelligence Scale for Children and the verbal learning and memory test showed an overall nonsignificant trend toward an immediate postoperative deterioration followed by an improvement to above preoperative levels after 1 year. CONCLUSIONS: ABS is a valuable technique in selected pediatric patients with lesions in language areas. An interdisciplinary approach, careful patient selection, extensive preoperative training of patients, and interpretation of intraoperative ADP are pivotal to a successful surgery.