Mapping interictal discharges using intracranial EEG-fMRI to predict postsurgical outcomes.

Various subjective and objective methods have been proposed to identify which interictal epileptiform discharge (IED)-related EEG-fMRI results are more likely to delineate seizure generating tissue in patients with drug-resistant focal epilepsy for the purposes of surgical planning. In this intracranial EEG-fMRI study, we evaluated the utility of these methods to localize clinically relevant regions pre-operatively and compared the extent of resection of these areas to post-operative outcome. Seventy patients admitted for intracranial video-EEG monitoring were recruited for a simultaneous intracranial EEG-fMRI study. For all analyses of blood oxygen level-dependent responses associated with IEDs, an experienced epileptologist identified the most Clinically Relevant brain activation cluster using available clinical information. The Maximum cluster (the cluster with the highest z-score) was also identified for all analyses and assigned to one of three confidence levels (low, medium, or high) based on the difference of the peak z-scores between the Maximum and Second Maximum cluster (the cluster with the second highest peak z-value). The distance was measured and compared between the peak voxel of the aforementioned clusters and the electrode contacts where the interictal discharge and seizure onset were recorded. In patients who subsequently underwent epilepsy surgery, the spatial concordance between the aforementioned clusters and the area of resection was determined and compared to post-operative outcome. We evaluated 106 different IEDs in 70 patients. Both subjective (identification of the Clinically Relevant cluster) and objective (Maximum cluster much more significant than the second maximum cluster) methods of culling non-localizing EEG-fMRI activation maps increased the spatial concordance between these clusters and the corresponding IED or seizure onset zone contacts. However, only the objective methods of identifying medium and high confidence maps resulted in a significant association between resection of the peak voxel of the Maximum cluster and post-operative outcome. Resection of this area was associated with good post-operative outcomes but was not sufficient for seizure freedom. On the other hand, we found that failure to resect the medium and high confidence Maximum clusters was associated with a poor post-surgical outcome (negative predictive value = 1.0, sensitivity = 1.0). Objective methods to identify higher confidence EEG-fMRI results are needed to localize areas necessary for good post-operative outcomes. However, resection of the peak voxel within higher confidence Maximum clusters is not sufficient for good outcomes. Conversely, failure to resect the peak voxel in these clusters is associated with a poor post-surgical outcome.

Mesial temporal lobe spiking reveals distinct patterns of blood oxygen level-dependent functional magnetic resonance imaging activation using simultaneous intracranial electroencephalography-functional magnetic resonance imaging.

OBJECTIVE: Temporal lobe epilepsy (TLE) has a high probability of becoming drug resistant and is frequently considered for surgical intervention. However, 30% of TLE cases have nonlesional magnetic resonance imaging (MRI) scans, which is associated with worse surgical outcomes. Characterizing interactions between temporal and extratemporal structures in these patients may help understand these poor outcomes. Simultaneous intracranial electroencephalography-functional MRI (iEEG-fMRI) can measure the hemodynamic changes associated with interictal epileptiform discharges (IEDs) recorded directly from the brain. This study was designed to characterize the whole brain patterns of IED-associated fMRI activation recorded exclusively from the mesial temporal lobes of patients with nonlesional TLE. METHODS: Eighteen patients with nonlesional TLE undergoing iEEG monitoring with mesial temporal IEDs underwent simultaneous iEEG-fMRI at 3 T. IEDs were marked, and statistically significant clusters of fMRI activation were identified. The locations of IED-associated fMRI activation for each patient were determined, and patients were grouped based on the location and pattern of fMRI activation. RESULTS: Two patterns of IED-associated fMRI activation emerged: primarily localized (n = 7), where activation was primarily located within the ipsilateral temporal lobe, and primarily diffuse (n = 11), where widespread bilateral extratemporal activation was detected. The primarily diffuse group reported significantly fewer focal to bilateral tonic-clonic seizures and had better postsurgical outcomes. SIGNIFICANCE: Simultaneous iEEG-fMRI can measure the hemodynamic changes associated with focal IEDs not visible on scalp EEG, such as those arising from the mesial temporal lobe. Significant fMRI activation associated with these IEDs was observed in all patients. Two distinct patterns of IED-associated activation were seen: primarily localized to the ipsilateral temporal lobe and more widespread, bilateral activation. Patients with widespread IED associated-activation had fewer focal to bilateral tonic-clonic seizures and better postsurgical outcome, which may suggest a neuroprotective mechanism limiting the spread of ictal events.

Immuno markers in newly diagnosed glioblastoma patients underwent Stupp protocol after neurosurgery: a retrospective series.

PURPOSE: The aims of our retrospective study investigated the role of immune system in glioblastoma (GBM), which is the most aggressive primary brain tumor in adults characterized by a poor prognosis. The recurrence rate remains high, probably due to "immune-desert" tumor microenvironment (TME) making GBM hidden from the anti-tumoral immune clearance. Considering this, we aimed to create a panel of prognostic markers from blood and tumor tissue correlating with overall survival (OS) and progression-free survival (PFS). METHODS: Firstly, we analyzed the inflammatory markers NLR and PLR as the ratio of the absolute neutrophil count and absolute platelet count by the absolute lymphocyte count respectively, collected at different time points in the peripheral blood of 95 patients. Furthermore, in 31 patients of the same cohort, we analyzed the formalin-fixed paraffin embedded samples to further compare the impact of circulating and inflammatory markers within the TME. RESULTS: Patients aged < 60 years and with methylated MGMT showed better OS. While, pre-chemotherapy Systemic Inflammatory Index (SII) < 480 was related to a better OS and PFS, we observed that only CD68+macrophage and CD66b+neutrophils expressed in vascular/perivascular area (V) showed a statistically significant prognostic role in median OS and PFS. CONCLUSIONS: Thus, we underscored a role of SII as predictive value of response to STUPP protocol. Regarding the TME-related markers, we suggested to take into consideration for future studies with new immunotherapy combinations, each component relating to expression of immune infiltrating subsets.

Primary care electronic medical records can be used to predict risk and identify potentially modifiable factors for early and late death in adult onset epilepsy.

OBJECTIVE: To use clinically informed machine learning to derive prediction models for early and late premature death in epilepsy. METHODS: This was a population-based primary care observational cohort study. All patients meeting a case definition for incident epilepsy in the Health Improvement Network database for inclusive years 2000-2012 were included. A modified Delphi process identified 30 potential risk factors. Outcome was early (within 4 years of epilepsy diagnosis) and late (4 years or more from diagnosis) mortality. We used regularized logistic regression, support vector machines, Gaussian naive Bayes, and random forest classifiers to predict outcomes. We assessed model calibration, discrimination, and generalizability using the Brier score, mean area under the receiver operating characteristic curve (AUC) derived from stratified fivefold cross-validation, plotted calibration curves, and extracted measures of association where possible. RESULTS: We identified 10 499 presumed incident cases from 11 194 182 patients. All models performed comparably well following stratified fivefold cross-validation, with AUCs ranging from 0.73 to 0.81 and from 0.71 to 0.79 for early and late death, respectively. In addition to comorbid disease, social habits (alcoholism odds ratio [OR] for early death = 1.54, 95% confidence interval [CI] = 1.12-2.11 and OR for late death = 2.62, 95% CI = 1.66-4.16) and treatment patterns (OR for early death when no antiseizure medication [ASM] was prescribed at baseline = 1.33, 95% CI = 1.07-1.64 and OR for late death after receipt of enzyme-inducing ASM at baseline = 1.32, 95% CI = 1.04-1.66) were significantly associated with increased risk of premature death. Baseline ASM polytherapy (OR = 0.55, 95% CI = 0.36-0.85) was associated with reduced risk of early death. SIGNIFICANCE: Clinically informed models using routine electronic medical records can be used to predict early and late mortality in epilepsy, with moderate to high accuracy and evidence of generalizability. Medical, social, and treatment-related risk factors, such as delayed ASM prescription and baseline prescription of enzyme-inducing ASMs, were important predictors.

Localization of interictal discharge origin: A simultaneous intracranial electroencephalographic-functional magnetic resonance imaging study.

OBJECTIVE: Scalp electroencephalographic (EEG)-functional magnetic resonance imaging (fMRI) studies suggest that the maximum blood oxygen level-dependent (BOLD) response to an interictal epileptiform discharge (IED) identifies the area of IED generation. However, the maximum BOLD response has also been reported in distant, seemingly irrelevant areas. Given the poor postoperative outcomes associated with extra-temporal lobe epilepsy, we hypothesized this finding is more common when analyzing extratemporal IEDs as compared to temporal IEDs. We further hypothesized that a subjective, holistic assessment of other significant BOLD clusters to identify the most clinically relevant cluster could be used to overcome this limitation and therefore better identify the likely origin of an IED. Specifically, we also considered the second maximum cluster and the cluster closest to the electrode contacts where the IED was observed. METHODS: Maps of significant IED-related BOLD activation were generated for 48 different IEDs recorded from 33 patients who underwent intracranial EEG-fMRI. The locations of the maximum, second maximum, and closest clusters were identified for each IED. An epileptologist, blinded to these cluster assignments, selected the most clinically relevant BOLD cluster, taking into account all available clinical information. The distances between these BOLD clusters and their corresponding IEDs were then measured. RESULTS: The most clinically relevant cluster was the maximum cluster for 56% (27/48) of IEDs, the second maximum cluster for 13% (6/48) of IEDs, and the closest cluster for 31% (15/48) of IEDs. The maximum clusters were closer to IED contacts for temporal than for extratemporal IEDs (p = .022), whereas the most clinically relevant clusters were not significantly different (p = .056). SIGNIFICANCE: The maximum BOLD response to IEDs may not always be the most indicative of IED origin. We propose that available clinical information should be used in conjunction with EEG-fMRI data to identify a BOLD cluster representative of the IED origin.

Impact of ictal subtraction SPECT and PET in presurgical evaluation.

OBJECTIVE: To assess the relative contribution of ictal subtraction single-photon emission computed tomography (ISSPECT) and 18 F-fluorodeoxyglucose positron emission tomography computed tomography (PET) in epilepsy surgery decision making. MATERIALS AND METHODS: A retrospective 3-year study of consecutive patients with resistant focal epilepsy who underwent ISSPECT and PET to evaluate to what extent these modalities influence decisions in epilepsy surgery and outcomes. ISSPECT imaging was performed in 106 patients and 58 (55%) had PET also. The clinical consensus (ClinC) was the final arbiter for decisions. Post-surgical outcomes were collected from follow-up clinics. Non-parametric statistics were used to assess association and logistic regression to evaluate prediction of outcomes. RESULTS: Of 106 patients, 60 were males (57%). MRI was non-lesional in 46 (43%). Concordance with ClinC was seen in 80 patients (76%) for ISSPECT, in 46 patients (79%) for PET, and in 37 patients (64%) for ISSPECT + PET. Fifty-six patients (53%) were planned for intracranial video-electroencephalography monitoring (IVEM). Those with ClinC-PET concordance were likely to proceed to IVEM (p = 0.02). ClinC-PET concordance and ClinC-ISSPECT concordance did not predict decision to proceed to surgery, but VEM-MRI concordance did in lesional cases (p = 0.018). Forty-five (42%) underwent surgery of which 29 had minimum follow-up for 1 year (mean, 20 months; SD, 8) and 22 (76%) had Engel class I outcomes. ClinC-ISSPECT concordance (p = 0.024) and VEM-MRI concordance (p = 0.016) predicted Engel class I outcomes. CONCLUSION: Those with ClinC-PET concordance were more likely to proceed with IVEM. ClinC-ISSPECT concordance and VEM-MRI concordance predicted good surgical outcomes.

Localizing the seizure onset zone by comparing patient postictal hypoperfusion to healthy controls.

Arterial spin labeling (ASL) MRI can provide seizure onset zone (SOZ) localizing information in up to 80% of patients. Clinical implementation of this technique is limited by the need to obtain two scans per patient: a postictal scan that is subtracted from an interictal scan. We aimed to determine whether it is possible to limit the number of ASL scans to one per patient by comparing patient postictal ASL scans to baseline scans of 100 healthy controls. Eighteen patients aged 20-55 years underwent ASL MRI <90 min after a seizure and during the interictal period. Each postictal cerebral blood flow (CBF) map was statistically compared to average baseline CBF maps from 100 healthy controls (pvcASL; patient postictal CBF vs. control baseline CBF). The pvcASL maps were compared to subtraction ASL maps (sASL; patient baseline CBF minus patient postictal CBF). Postictal CBF reductions from pvcASL and sASL maps were seen in 17 of 18 (94.4%) and 14 of 18 (77.8%) patients, respectively. Maximal postictal hypoperfusion seen in pvcASL and sASL maps was concordant with the SOZ in 10 of 17 (59%) and 12 of 14 (86%) patients, respectively. In seven patients, both pvcASL and sASL maps showed similar results. In two patients, sASL showed no significant hypoperfusion, while pvcASL showed significant hypoperfusion concordant with the SOZ. We conclude that pvcASL is clinically useful and although it may have a lower overall concordance rate than sASL, pvcASL does provide localizing or lateralizing information for specific cases that would be otherwise missed through sASL.

Outcomes of stereoelectroencephalography exploration at an epilepsy surgery center.

OBJECTIVES: Epilepsy surgery is offered in resistant focal epilepsy. Non-invasive investigations like scalp video EEG monitoring (SVEM) help delineate epileptogenic zone. Complex cases may require intracranial video EEG monitoring (IVEM). Stereoelectroencephalography (SEEG)-based intracerebral electrode implantation has better spatial resolution, lower morbidity, better tolerance, and superiority in sampling deep structures. Our objectives were to assess IVEM using SEEG with regard to reasoning behind implantation, course, surgical interventions, and outcomes. MATERIALS AND METHODS: Seventy-two admissions for SEEG from January 2014 to December 2018 were included in the study. Demographic and clinical data were retrospectively collected. RESULTS: The cohort comprised of 69 adults of which 34 (47%) had lesional MRI. Reasons for SEEG considering all cases included non-localizing ictal onset (76%), ictal-interictal discordance (21%), discordant semiology (17%), proximity to eloquent cortex (33%), nuclear imaging discordance (34%), and discordance with neuropsychology (19%). Among lesional cases, additional reasons included SVEM discordance (68%) and dual or multiple pathology (47%). Forty-eight patients (67%) were offered resective surgery, and 41 underwent it. Twenty-three (56%) had at least one year post-surgical follow-up of which 14 (61%) had Engels class I outcome. Of the remaining 23 who were continued on medical management, 4 (17%) became seizure-free and 12 (51%) had reduction in seizure frequency. CONCLUSION: SEEG monitoring is an important and safe tool for presurgical evaluation with good surgical and non-surgical outcomes. Whether seizure freedom following non-surgical management could be related to SEEG implantation, medication change, or natural course needs to be determined.

Recommendations for the use of structural magnetic resonance imaging in the care of patients with epilepsy: A consensus report from the International League Against Epilepsy Neuroimaging Task Force.

Structural magnetic resonance imaging (MRI) is of fundamental importance to the diagnosis and treatment of epilepsy, particularly when surgery is being considered. Despite previous recommendations and guidelines, practices for the use of MRI are variable worldwide and may not harness the full potential of recent technological advances for the benefit of people with epilepsy. The International League Against Epilepsy Diagnostic Methods Commission has thus charged the 2013-2017 Neuroimaging Task Force to develop a set of recommendations addressing the following questions: (1) Who should have an MRI? (2) What are the minimum requirements for an MRI epilepsy protocol? (3) How should magnetic resonance (MR) images be evaluated? (4) How to optimize lesion detection? These recommendations target clinicians in established epilepsy centers and neurologists in general/district hospitals. They endorse routine structural imaging in new onset generalized and focal epilepsy alike and describe the range of situations when detailed assessment is indicated. The Neuroimaging Task Force identified a set of sequences, with three-dimensional acquisitions at its core, the harmonized neuroimaging of epilepsy structural sequences-HARNESS-MRI protocol. As these sequences are available on most MR scanners, the HARNESS-MRI protocol is generalizable, regardless of the clinical setting and country. The Neuroimaging Task Force also endorses the use of computer-aided image postprocessing methods to provide an objective account of an individual's brain anatomy and pathology. By discussing the breadth and depth of scope of MRI, this report emphasizes the unique role of this noninvasive investigation in the care of people with epilepsy.

Signs and symptoms of the postictal period in epilepsy: A systematic review and meta-analysis.

OBJECTIVE: The postictal period has many physical, behavioral, and cognitive manifestations associated with it. These signs and symptoms are common, can be quite debilitating, and can have a continued impact long after the seizure has ended. The purpose of this systematic review was to quantify the occurrence of postictal signs and symptoms, along with their frequency and duration in persons with epilepsy. METHODS: Cochrane Database of Systematic Reviews, CINAHL, EMBASE, MEDLINE, PsycINFO, Web of Science, and Scopus were searched from inception to November 29, 2017. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting standards were followed. Search terms included subject headings and text words such as convulsion, epilepsy, seizure, postictal, post seizure, seizure recovery, seizure end, Todd's paresis, and Todd's paralysis. Standardized forms were used to collect various study variables. Abstract and full-text review, data abstraction, and quality assessment were all done in duplicate. Study heterogeneity was assessed using the I-squared test, and a random effects model was used to determine estimates. Publication bias was evaluated using funnel plots. RESULTS: From 7811 abstracts reviewed, 78 articles met eligibility criteria, with 31 postictal manifestations (signs and/or symptoms) described and 45 studies included in the meta-analysis. The majority of studies described postictal headaches, migraines, and psychoses, with mean weighted frequency of 33.0% [95% confidence interval (CI) 26.0-40.0], 16.0% [95% CI 10.0-22.0], and 4.0% [95% CI 2.0-5.0], respectively. The mean weighted proportions of manifestations ranged from 0.5% (subacute postictal aggression) to 96.2% (postictal unresponsiveness) with symptom duration usually lasting <24 h but up to 2 months for physical and cognitive/behavioral symptoms respectively. SIGNIFICANCE: Examining data on the various signs and symptoms of the postictal period will have practical applications for physicians by raising their awareness about these manifestations and informing them about the importance of optimizing their prevention and treatment in epilepsy.

CT perfusion measurement of postictal hypoperfusion: localization of the seizure onset zone and patterns of spread.

PURPOSE: Seizures are often followed by a period of transient neurological dysfunction and postictal alterations in cerebral blood flow may underlie these symptoms. Recent animal studies have shown reduced local cerebral blood flow at the seizure onset zone (SOZ) lasting approximately 1 h following seizures. Using arterial spin labelling (ASL) MRI, we observed postictal hypoperfusion at the SOZ in 75% of patients. The clinical implementation of ASL as a tool to identify the SOZ is hampered by the limited availability of MRI on short notice. Computed tomography perfusion (CTP) also measures blood flow and may circumvent the logistical limitations of MRI. Thus, we aimed to measure the extent of postictal hypoperfusion using CTP. METHODS: Fourteen adult patients with refractory focal epilepsy admitted for presurgical evaluation were prospectively recruited and underwent CTP scanning within 80 min of a habitual seizure. Patients also underwent a baseline scan after they were seizure-free for > 24 h. The acquired scans were qualitatively assessed by two reviewers by visual inspection and quantitatively assessed through a subtraction pipeline to identify areas of significant postictal hypoperfusion. RESULTS: Postictal blood flow reductions of > 15 ml/100 g-1/min-1 were seen in 12/13 patients using the quantitative method of analysis. In 10/12 patients, the location of the hypoperfusion was partially or fully concordant with the presumed SOZ. In all patients, additional areas of scattered hypoperfusion were seen in areas corresponding to seizure spread. CONCLUSION: CTP can reliably measure postictal hypoperfusion which is maximal at the presumed SOZ.

Position Statement on the Use of Medical Cannabis for the Treatment of Epilepsy in Canada.

In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.

Énoncé de position quant à l'utilisation du cannabis médical dans le traitement de l'épilepsie. L'utilisation du cannabis à des fins récréatives a été légalisée au Canada en octobre 2018. Parallèlement à ce changement de politique, de récentes publication visant à évaluer l'efficacité du cannabis dans le traitement de l'épilepsie, de même qu'une sensibilisation médiatique accrue en ce qui concerne son utilisation, ont eu pour effet d'augmenter l'intérêt du grand public à son égard. Le Comité médical thérapeutique de la Ligue canadienne contre l'épilepsie (LCCE), de concert avec un groupe multidisciplinaire d'experts et des représentants de l'Alliance canadienne de l'épilepsie, a ainsi élaboré un énoncé de position en ce qui regarde l'utilisation du cannabis médical dans le traitement de l'épilepsie. Cet article entend donc aborder le cadre légal qui prévaut actuellement au Canada et examiner de récentes publications s'étant penchées sur le profil sécuritaire et sur l'efficacité du cannabis. De plus, nous voulons apporter un éclairage au sujet des aspects cliniques dont il faudrait tenir compte au moment d'envisager l'utilisation du cannabis à des fins médicales.

Transverse relaxometry with transmit field-constrained stimulated echo compensation.

OBJECTIVE: Purely exponential decay is rarely observed in conventional mono-exponential T2 mapping due to transmit field inhomogeneity and calibration errors, which collectively introduce stimulated and indirect echo pathways. Stimulated echo correction (SEC) requires an additional fit parameter for the transmit field, resulting in greater uncertainty in T2 relative to mono-exponential fitting. The aim of this study was to develop an accurate and precise method for T2 mapping using SEC. METHODS: The proposed method, called two-step SEC (tSEC), leverages spatial correlations in the transmit field to reduce the number of fully independent fitting parameters from three to two. The method involves a two-pass fit: the first pass involves a fast but standard SEC fit. The initially estimated transmit field is smoothed and provided as a fixed input to the second pass. RESULTS: Simulations and in vivo experiments demonstrated up to 38% and 27% decreases in relative T2 variance with tSEC relative to SEC. Average T2 values were unchanged between tSEC and SEC fits. The proposed method uses the same input data as SEC and exponential fits, so it is applicable to existing data. DISCUSSION: The proposed method generates reliable and reproducible quantitative T2 maps and should be considered for future relaxometry studies.

A novel cortical target to enhance hand motor output in humans with spinal cord injury.

A main goal of rehabilitation strategies in humans with spinal cord injury is to strengthen transmission in spared neural networks. Although neuromodulatory strategies have targeted different sites within the central nervous system to restore motor function following spinal cord injury, the role of cortical targets remain poorly understood. Here, we use 180 pairs of transcranial magnetic stimulation for ∼30 min over the hand representation of the motor cortex at an interstimulus interval mimicking the rhythmicity of descending late indirect (I) waves in corticospinal neurons (4.3 ms; I-wave protocol) or at an interstimulus interval in-between I-waves (3.5 ms; control protocol) on separate days in a randomized order. Late I-waves are thought to arise from trans-synaptic cortical inputs and have a crucial role in the recruitment of spinal motor neurons following spinal cord injury. Motor evoked potentials elicited by transcranial magnetic stimulation, paired-pulse intracortical inhibition, spinal motor neuron excitability (F-waves), index finger abduction force and electromyographic activity as well as a hand dexterity task were measured before and after both protocols in 15 individuals with chronic incomplete cervical spinal cord injury and 17 uninjured participants. We found that motor evoked potentials size increased in spinal cord injury and uninjured participants after the I-wave but not the control protocol for ∼30 to 60 min after the stimulation. Intracortical inhibition decreased and F-wave amplitude and persistence increased after the I-wave but not the control protocol, suggesting that cortical and subcortical networks contributed to changes in corticospinal excitability. Importantly, hand motor output and hand dexterity increased in individuals with spinal cord injury after the I-wave protocol. These results provide the first evidence that late synaptic input to corticospinal neurons may represent a novel therapeutic target for improving motor function in humans with paralysis due to spinal cord injury.

Seizure onset zone localization using postictal hypoperfusion detected by arterial spin labelling MRI.

Neurological dysfunction following epileptic seizures is a well-recognized phenomenon. Several potential mechanisms have been suggested to explain postictal dysfunction, with alteration in cerebral blood flow being one possibility. These vascular disturbances may be long lasting and localized to brain areas involved in seizure generation and propagation, as supported by both animal and human studies. Therefore, measuring perfusion changes in the postictal period may help localize the seizure onset zone. Arterial spin labelling is a non-invasive, rapid and reproducible magnetic resonance imaging technique that measures cerebral perfusion. To this end, we measured postictal perfusion in patients with drug resistant focal epilepsy who were admitted to our seizure-monitoring unit for presurgical evaluation. Twenty-one patients were prospectively recruited and underwent arterial spin labelling scanning within 90 min of a habitual seizure. Patients also underwent a similar scan in the interictal period, after they were seizure-free for at least 24 h. The acquired scans were subtracted to identify the areas of significant postictal hypoperfusion. The location of the maximal hypoperfusion was compared to the presumed seizure onset zone to assess for concordance. Also, the localizing value of this technique was compared to other structural and functional imaging modalities. Postictal perfusion reductions of >15 units (ml/100 g/l) were seen in 15/21 patients (71.4%). In 12/15 (80%) of these patients, the location of the hypoperfusion was partially or fully concordant with the location of the presumed seizure onset zone. This technique compared favourably to other neuroimaging modalities, being similar or superior to structural magnetic resonance imaging in 52% of cases, ictal single-photon emission computed tomography in 60% of cases and interictal positron emission tomography in 71% of cases. Better arterial spin labelling results were obtained in patients in whom the seizure onset zone was discernible based on non-invasive data. Thus, this technique is a safe, non-invasive and relatively inexpensive tool to detect postictal hypoperfusion that may provide useful data to localize the seizure onset zone. This technique may be incorporated into the battery of conventional investigations for presurgical evaluation of patients with drug resistant focal epilepsy.

Distinct Corticocortical Contributions to Human Precision and Power Grip.

The corticospinal tract contributes to the control of finger muscles during precision and power grip. The involvement of different sets of cortical interneuronal circuits during these distinct grasping behaviors remains unknown. To examine this question in humans we used noninvasive transcranial magnetic stimulation (TMS) over the hand representation of the primary motor cortex to elicit motor evoked potentials (MEPs) in an intrinsic finger muscle during index finger abduction (control task), precision grip, and power grip. The TMS coil was oriented to induce currents in the brain in the latero-medial (LM), posterior-anterior (PA), and anterior-posterior (AP) direction to preferentially activate corticospinal axons directly and early and late synaptic inputs to corticospinal neurons, respectively. We found that AP-LM MEP latency differences were consistently longer during power grip compared with index finger abduction and precision grip, while PA-LM differences remained similar across tasks. Short-interval intracortical facilitation, targeting AP but not PA inputs, increased during power grip compared with other tasks. Our novel findings suggest that cortical structures activated by PA and AP stimuli are differentially active during precision and power grip. We propose that a preferential recruitment of late synaptic inputs to corticospinal neurons may be achieved when humans perform a power grip.

Altered corticospinal function during movement preparation in humans with spinal cord injury.

KEY POINTS: In uninjured humans, transmission in the corticospinal pathway changes in a task-dependent manner during movement preparation. We investigated whether this ability is preserved in humans with incomplete chronic cervical spinal cord injury (SCI). Our results show that corticospinal excitability is altered in the preparatory phase of an upcoming movement when there is a need to suppress but not to execute rapid index finger voluntary contractions in individuals with SCI compared with controls. This is probably related to impaired transmission at a cortical and spinal level after SCI. Overall our findings indicate that deficits in corticospinal transmission in humans with chronic incomplete SCI are also present in the preparatory phase of upcoming movements. ABSTRACT: Corticospinal output is modulated in a task-dependent manner during the preparatory phase of upcoming movements in humans. Whether this ability is preserved after spinal cord injury (SCI) is unknown. In this study, we examined motor evoked potentials elicited by cortical (MEPs) and subcortical (CMEPs) stimulation of corticospinal axons and short-interval intracortical inhibition in the first dorsal interosseous muscle in the preparatory phase of a reaction time task where individuals with chronic incomplete cervical SCI and age-matched controls needed to suppress (NOGO) or initiate (GO) ballistic index finger isometric voluntary contractions. Reaction times were prolonged in SCI participants compared with control subjects and stimulation was provided ∼90 ms prior to movement onset in each group. During NOGO trials, both MEPs and CMEPs remained unchanged compared to baseline in SCI participants but were suppressed in control subjects. Notably, during GO trials, MEPs increased to a similar extent in both groups but CMEPs increased only in controls. The magnitude of short-interval intracortical inhibition increased in controls but not in SCI subjects during NOGO trials and decreased in both groups in GO trials. These novel observations reveal that humans with incomplete cervical SCI have an altered ability to modulate corticospinal excitability during movement preparation when there is a need to suppress but not to execute upcoming rapid finger movements, which is probably related to impaired transmission at a cortical and spinal level. Thus, deficits in corticospinal transmission after human SCI extend to the preparatory phase of upcoming movements.

Postictal hypoperfusion/hypoxia provides the foundation for a unified theory of seizure-induced brain abnormalities and behavioral dysfunction.

A recent article by Farrell et al. characterizes the phenomenon, mechanisms, and treatment of a local and severe hypoperfusion/hypoxia event that occurs in brain regions following a focal seizure. Given the well-established role of cerebral ischemia/hypoxia in brain damage and behavioral dysfunction in other clinical settings (e.g., stroke, cerebral vasospasm), we put forward a new theory: postictal hypoperfusion/hypoxia is responsible for the negative consequences associated with seizures. Fortunately, inhibition of two separate molecular targets, cyclooxygenase-2 (COX-2) and l-type calcium channels, can prevent the expression of postictal hypoperfusion/hypoxia. These inhibitors are important experimental tools used to separate the seizure from the resulting hypoperfusion/hypoxia and can allow researchers to address the contribution of this phenomenon to negative outcomes associated with seizures. Herein we address the implications of this postictal stroke-like event in acute behavioral dysfunction (e.g., Todd's paresis) and sudden unexpected death in epilepsy (SUDEP). Moreover, anatomic alterations such as increased blood-brain barrier permeability, glial activation, central inflammation, and neuronal loss could also be a consequence of repeated hypoperfusion/hypoxic events and, in turn, underlie chronic interictal cognitive and behavioral comorbidities (e.g., memory deficits, anxiety, depression, and psychosis) and exacerbate epileptogenesis. Thus these seemingly disparate and clinically important observations may share a common point of origin: postictal hypoperfusion/hypoxia.