Localisation in focal epilepsy: a practical guide

The semiology of epileptic seizures reflects activation, or dysfunction, of areas of brain (often termed the symptomatogenic zone) as a seizure begins and evolves. Specific semiologies in focal epilepsies provide an insight into the location of the seizure onset zone, which is particularly important for presurgical epilepsy assessment. The correct diagnosis of paroxysmal events also depends on the clinician being familiar with the spectrum of semiologies. Here, we summarise the current literature on localisation in focal epilepsies using illustrative cases and discussing possible pitfalls in localisation

Phytochemical Screening and In vitro Evaluation of Pharmacological Activities of Aphanamixis polystachya (Wall) Parker Fruit Extracts

Purpose: To investigate the crude n-hexane, ethyl acetate and methanol extracts of Aphanamixis polystachya fruit for their cytotoxic, antimicrobial, antioxidant and thrombolytic activities.Methods: The fruit extracts were screened for major phytochemical compounds using in vitro established procedures. Antimicrobial and cytotoxic studies of the fruit extracts were conducted using disc diffusion and brine shrimp lethality bioassay methods, respectively, while an in vitro thrombolytic model was used to assess the clot lysis effect of the extracts with streptokinase as positive control. Antioxidant activity was evaluated by free radical scavenging activity using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide assay as well as total phenolic content.Results: The fruit extracts were a rich source of phytochemicals and among the extracts n-hexane extract showed highest antimicrobial activity against Shigella dysenteriae (zone of inhibition: 9.7±0.2 mm) and Candida albicans (zone of inhibition: 8.8±0.3 mm) at a concentration of 1000ìg/disc, whereas at the same concentration methanol extract showed highest zone of inhibition, 10.1±0.4mm, against Staphylococcus aureus. Compared to potassium permanganate with a median lethal concentration(LC50) of 13.23 ìg/ml in the brine shrimp lethality assay, the LC50 of n-hexane, ethyl acetate and methanol extracts were 15.77, 17.51 and 141.37 ìg/ml, respectively. All the extracts showed significant clot lysis activity (p < 0.001) with reference to negative control and % clot lysis of the extracts were approximately 13. Notable antioxidant activity of the methanol extract was observed unlike the other extracts.Conclusion: The results of the study demonstrated the potential cytotoxic, thrombolytic and antioxidant activities of the fruit extracts of A.  polystachya and therefore further studies on the isolation and identification of active principles are required.Keywords: Aphanamixis polystachya, Antimicrobial, Antioxidant, Cytotoxic, Thrombolytic, Phytochemical screenin

Preoperative language mapping using navigated TMS compared with extra-operative direct cortical stimulation using intracranial electrodes: A case report

Highlights 1. rTMS provides a non-invasive means of performing pre-operative language mapping. 2. Sensitivity and specificity in epilepsy patients is lower than reported in tumour surgery. 3. Future methodological improvements may improve this

Slower alpha rhythm associates with poorer seizure control in epilepsy.

OBJECTIVE: Slowing and frontal spread of the alpha rhythm have been reported in multiple epilepsy syndromes. We investigated whether these phenomena are associated with seizure control. METHODS: We prospectively acquired resting-state electroencephalogram (EEG) in 63 patients with focal and idiopathic generalized epilepsy (FE and IGE) and 39 age- and gender-matched healthy subjects (HS). Patients were divided into good and poor (≥4 seizures/12 months) seizure control groups based on self-reports and clinical records. We computed spectral power from 20-sec EEG segments during eyes-closed wakefulness, free of interictal abnormalities, and quantified power in high- and low-alpha bands. Analysis of covariance and post hoc t-tests were used to assess group differences in alpha-power shift across all EEG channels. Permutation-based statistics were used to assess the topography of this shift across the whole scalp. RESULTS: Compared to HS, patients showed a statistically significant shift of spectral power from high- to low-alpha frequencies (effect size g = 0.78 [95% confidence interval 0.43, 1.20]). This alpha-power shift was driven by patients with poor seizure control in both FE and IGE (g = 1.14, [0.65, 1.74]), and occurred over midline frontal and bilateral occipital regions. IGE exhibited less alpha power shift compared to FE over bilateral frontal regions (g = -1.16 [-0.68, -1.74]). There was no interaction between syndrome and seizure control. Effects were independent of antiepileptic drug load, time of day, or subgroup definitions. INTERPRETATION: Alpha slowing and anteriorization are a robust finding in patients with epilepsy and might represent a generic indicator of seizure liability

Non-parametric combination of multimodal MRI for lesion detection in focal epilepsy

One third of patients with medically refractory focal epilepsy have normal-appearing MRI scans. This poses a problem as identification of the epileptogenic region is required for surgical treatment. This study performs a multimodal voxel-based analysis (VBA) to identify brain abnormalities in MRI-negative focal epilepsy. Data was collected from 69 focal epilepsy patients (42 with discrete lesions on MRI scans, 27 with no visible findings on scans), and 62 healthy controls. MR images comprised T1-weighted, fluid-attenuated inversion recovery (FLAIR), fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging, and neurite density index (NDI) from neurite orientation dispersion and density imaging. These multimodal images were coregistered to T1-weighted scans, normalized to a standard space, and smoothed with 8 mm FWHM. Initial analysis performed voxel-wise one-tailed t-tests separately on grey matter concentration (GMC), FLAIR, FA, MD, and NDI, comparing patients with epilepsy to controls. A multimodal non-parametric combination (NPC) analysis was also performed simultaneously on FLAIR, FA, MD, and NDI. Resulting p-maps were family-wise error rate corrected, threshold-free cluster enhanced, and thresholded at p < 0.05. Sensitivity was established through visual comparison of results to manually drawn lesion masks or seizure onset zone (SOZ) from stereoelectroencephalography. A leave-one-out cross-validation with the same analysis protocols was performed on controls to determine specificity. NDI was the best performing individual modality, detecting focal abnormalities in 38% of patients with normal MRI and conclusive SOZ. GMC demonstrated the lowest sensitivity at 19%. NPC provided superior performance to univariate analyses with 50% sensitivity. Specificity in controls ranged between 96 and 100% for all analyses. This study demonstrated the utility of a multimodal VBA utilizing NPC for detecting epileptogenic lesions in MRI-negative focal epilepsy. Future work will apply this approach to datasets from other centres and will experiment with different combinations of MR sequences

Seizure pathways change on circadian and slower timescales in individual patients with focal epilepsy.

Personalized medicine requires that treatments adapt to not only the patient but also changing factors within each individual. Although epilepsy is a dynamic disorder characterized by pathological fluctuations in brain state, surprisingly little is known about whether and how seizures vary in the same patient. We quantitatively compared within-patient seizure network evolutions using intracranial electroencephalographic (iEEG) recordings of over 500 seizures from 31 patients with focal epilepsy (mean 16.5 seizures per patient). In all patients, we found variability in seizure paths through the space of possible network dynamics. Seizures with similar pathways tended to occur closer together in time, and a simple model suggested that seizure pathways change on circadian and/or slower timescales in the majority of patients. These temporal relationships occurred independent of whether the patient underwent antiepileptic medication reduction. Our results suggest that various modulatory processes, operating at different timescales, shape within-patient seizure evolutions, leading to variable seizure pathways that may require tailored treatment approaches

Detection of covert lesions in focal epilepsy using computational analysis of multimodal magnetic resonance imaging data

Objective: To compare the location of suspect lesions detected by computational analysis of multimodal magnetic resonance imaging data with areas of seizure onset, early propagation, and interictal epileptiform discharges (IEDs) identified with stereoelectroencephalography (SEEG) in a cohort of patients with medically refractory focal epilepsy and radiologically normal magnetic resonance imaging (MRI) scans. Methods: We developed a method of lesion detection using computational analysis of multimodal MRI data in a cohort of 62 control subjects, and 42 patients with focal epilepsy and MRI-visible lesions. We then applied it to detect covert lesions in 27 focal epilepsy patients with radiologically normal MRI scans, comparing our findings with the areas of seizure onset, early propagation, and IEDs identified at SEEG. Results: Seizure-onset zones (SoZs) were identified at SEEG in 18 of the 27 patients (67%) with radiologically normal MRI scans. In 11 of these 18 cases (61%), concordant abnormalities were detected by our method. In the remaining seven cases, either early seizure propagation or IEDs were observed within the abnormalities detected, or there were additional areas of imaging abnormalities found by our method that were not sampled at SEEG. In one of the nine patients (11%) in whom SEEG was inconclusive, an abnormality, which may have been involved in seizures, was identified by our method and was not sampled at SEEG. Significance: Computational analysis of multimodal MRI data revealed covert abnormalities in the majority of patients with refractory focal epilepsy and radiologically normal MRI that co-located with SEEG defined zones of seizure onset. The method could help identify areas that should be targeted with SEEG when considering epilepsy surgery

Distinct Patterns of Brain Metabolism in Patients at Risk of Sudden Unexpected Death in Epilepsy

Objective: To characterize regional brain metabolic differences in patients at high risk of sudden unexpected death in epilepsy (SUDEP), using fluorine-18-fluorodeoxyglucose positron emission tomography (18FDG-PET). Methods: We studied patients with refractory focal epilepsy at high (n = 56) and low (n = 69) risk of SUDEP who underwent interictal 18FDG-PET as part of their pre-surgical evaluation. Binary SUDEP risk was ascertained by thresholding frequency of focal to bilateral tonic-clonic seizures (FBTCS). A whole brain analysis was employed to explore regional differences in interictal metabolic patterns. We contrasted these findings with regional brain metabolism more directly related to frequency of FBTCS. Results: Regions associated with cardiorespiratory and somatomotor regulation differed in interictal metabolism. In patients at relatively high risk of SUDEP, fluorodeoxyglucose (FDG) uptake was increased in the basal ganglia, ventral diencephalon, midbrain, pons, and deep cerebellar nuclei; uptake was decreased in the left planum temporale. These patterns were distinct from the effect of FBTCS frequency, where increasing frequency was associated with decreased uptake in bilateral medial superior frontal gyri, extending into the left dorsal anterior cingulate cortex. Significance: Regions critical to cardiorespiratory and somatomotor regulation and to recovery from vital challenges show altered interictal metabolic activity in patients with frequent FBTCS considered to be at relatively high-risk of SUDEP, and shed light on the processes that may predispose patients to SUDEP

Complementary structural and functional abnormalities to localise epileptogenic tissue

\ua9 2023 The Authors. Background: When investigating suitability for epilepsy surgery, people with drug-refractory focal epilepsy may have intracranial EEG (iEEG) electrodes implanted to localise seizure onset. Diffusion-weighted magnetic resonance imaging (dMRI) may be acquired to identify key white matter tracts for surgical avoidance. Here, we investigate whether structural connectivity abnormalities, inferred from dMRI, may be used in conjunction with functional iEEG abnormalities to aid localisation of the epileptogenic zone (EZ), improving surgical outcomes in epilepsy. Methods: We retrospectively investigated data from 43 patients (42% female) with epilepsy who had surgery following iEEG. Twenty-five patients (58%) were free from disabling seizures (ILAE 1 or 2) at one year. Interictal iEEG functional, and dMRI structural connectivity abnormalities were quantified by comparison to a normative map and healthy controls. We explored whether the resection of maximal abnormalities related to improved surgical outcomes, in both modalities individually and concurrently. Additionally, we suggest how connectivity abnormalities may inform the placement of iEEG electrodes pre-surgically using a patient case study. Findings: Seizure freedom was 15 times more likely in patients with resection of maximal connectivity and iEEG abnormalities (p = 0.008). Both modalities separately distinguished patient surgical outcome groups and when used simultaneously, a decision tree correctly separated 36 of 43 (84%) patients. Interpretation: Our results suggest that both connectivity and iEEG abnormalities may localise epileptogenic tissue, and that these two modalities may provide complementary information in pre-surgical evaluations. Funding: This research was funded by UKRI, CDT in Cloud Computing for Big Data, NIH, MRC, Wellcome Trust and Epilepsy Research UK