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

Effect of extended morning fasting upon ad libitum lunch intake and associated metabolic and hormonal responses in obese adults

Background/Objectives: Breakfast omission is positively associated with obesity and increased risk of disease. However, little is known about the acute effects of extended morning fasting upon subsequent energy intake and associated metabolic/regulatory factors in obese adults. Subjects/Methods: In a randomised cross-over design, 24 obese men (n=8) and women (n=16) extended their overnight fast by omitting breakfast consumption or ingesting a typical carbohydrate-rich breakfast of 2183±393 kJ (521±94 kcal), before an ad libitum pasta lunch 3 h later. Blood samples were obtained throughout the day until 3 h post lunch and analysed for hormones implicated in appetite regulation, along with metabolic outcomes and subjective appetite measures. Results: Lunch intake was unaffected by extended morning fasting (difference=218 kJ, 95% confidence interval −54 kJ, 490 kJ; P=0.1) resulting in lower total intake in the fasting trial (difference=−1964 kJ, 95% confidence interval −1645 kJ, −2281 kJ; P<0.01). Systemic concentrations of peptide tyrosine–tyrosine and leptin were lower during the afternoon following morning fasting (Pless than or equal to0.06). Plasma-acylated ghrelin concentrations were also lower following the ad libitum lunch in the fasting trial (P<0.05) but this effect was not apparent for total ghrelin (Pgreater than or equal to0.1). Serum insulin concentrations were greater throughout the afternoon in the fasting trial (P=0.05), with plasma glucose also greater 1 h after lunch (P<0.01). Extended morning fasting did not result in greater appetite ratings after lunch, with some tendency for lower appetite 3 h post lunch (P=0.09). Conclusions: We demonstrate for the first time that, in obese adults, extended morning fasting does not cause compensatory intake during an ad libitum lunch nor does it increase appetite during the afternoon. Morning fasting reduced satiety hormone responses to a subsequent lunch meal but counterintuitively also reduced concentrations of the appetite-stimulating hormone-acylated ghrelin during the afternoon relative to lunch consumed after breakfast

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

Vitamin D deficiency causes inward hypertrophic remodeling and alters vascular reactivity of rat cerebral arterioles

BACKGROUND AND PURPOSE: Vitamin D deficiency (VDD) is a global health problem, which can lead to several pathophysiological consequences including cardiovascular diseases. Its impact on the cerebrovascular system is not well understood. The goal of the present work was to examine the effects of VDD on the morphological, biomechanical and functional properties of cerebral arterioles. METHODS: Four-week-old male Wistar rats (n = 11 per group) were either fed with vitamin D deficient diet or received conventional rat chow with per os vitamin D supplementation. Cardiovascular parameters and hormone levels (testosterone, androstenedione, progesterone and 25-hydroxyvitamin D) were measured during the study. After 8 weeks of treatment anterior cerebral artery segments were prepared and their morphological, biomechanical and functional properties were examined using pressure microangiometry. Resorcin-fuchsin and smooth muscle actin staining were used to detect elastic fiber density and smooth muscle cell counts in the vessel wall, respectively. Sections were immunostained for eNOS and COX-2 as well. RESULTS: VDD markedly increased the wall thickness, the wall-to-lumen ratio and the wall cross-sectional area of arterioles as well as the number of smooth muscle cells in the tunica media. As a consequence, tangential wall stress was significantly lower in the VDD group. In addition, VDD increased the myogenic as well as the uridine 5'-triphosphate-induced tone and impaired bradykinin-induced relaxation. Decreased eNOS and increased COX-2 expression were also observed in the endothelium of VDD animals. CONCLUSIONS: VDD causes inward hypertrophic remodeling due to vascular smooth muscle cell proliferation and enhances the vessel tone probably because of increased vasoconstrictor prostanoid levels in young adult rats. In addition, the decreased eNOS expression results in endothelial dysfunction. These morphological and functional alterations can potentially compromise the cerebral circulation and lead to cerebrovascular disorders in VDD