Retrospective comparison of motor and somatosensory MEG mapping-Considerations for better clinical applications.

While magnetoencephalography (MEG) has proven to be a valuable and reliable tool for presurgical functional mapping of eloquent cortices for at least two decades, widespread use of this technique by clinicians has remained elusive. This modest application may be attributable, at least in part, to misunderstandings regarding the success rate of such mapping procedures, as well as the primary sources contributing to mapping failures. To address this, we conducted a retrospective comparison of sensorimotor functional mapping success rates in 141 patients with epilepsy and 75 tumor patients from the Center for MEG in Omaha, NE. Neurosurgical candidates either completed motor mapping (i.e., finger tapping paradigm), somatosensory mapping (i.e., peripheral stimulation paradigm), or both motor and somatosensory protocols during MEG. All MEG data underwent subsequent time-domain averaging and source localization of left and right primary motor (M1) and somatosensory (S1) cortices was conducted using a single equivalent dipole model. Successful mapping was determined based on dipole goodness of fit metrics âˆ¼ 95%, as well as an accurate and conceivable spatial correspondence to precentral and postcentral gyri for M1 and S1, respectively. Our results suggest that mapping M1 in epilepsy and tumor patients was on average 94.5% successful, when patients only completed motor mapping protocols. In contrast, mapping S1 was successful 45-100% of the time in these patient groups when they only completed somatosensory mapping paradigms. Importantly, Z-tests for independent proportions revealed that the percentage of successful S1 mappings significantly increased to âˆ¼ 94% in epilepsy patients who completed both motor/somatosensory mapping protocols during MEG. Together, these data suggest that ordering more comprehensive mapping procedures (e.g., both motor and somatosensory protocols for a collective sensorimotor network) may substantially increase the accuracy of presurgical functional mapping by providing more extensive data from which to base interpretations. Moreover, clinicians and magnetoencephalographers should be considerate of the major contributors to mapping failures (i.e., low SNR, excessive motion and magnetic artifacts) in order to further increase the percentage of cases achieving successful mapping of eloquent cortices.

Risk of seizure clusters and status epilepticus following rapid and ultra-rapid medication discontinuation during intracranial EEG monitoring.

OBJECTIVE: Anti-seizure medications (ASMs) are discontinued in the course of intracranial EEG (iEEG) monitoring for presurgical evaluation. The ASM withdrawal facilitates an emergence of seizures but may also precipitate seizure clusters (SC) and status epilepticus (SE). The aim of this study was to compare the rates of SC and SE during the ultra-rapid withdrawal (URW) and rapid withdrawal (RW) of ASMs during iEEG. METHODS: We performed a retrospective observational study of all consecutive patients with drug resistant epilepsy who completed iEEG at our comprehensive epilepsy center from 2012-2018. SC was defined as three or more seizures in 24 h with a return to baseline between the events. SE was defined as ≥ 5 min of clinical seizure or ≥ 10 min of ictal electrographic activity or series of seizures with no return to the neurological baseline between the events. RESULTS: Of 107 patients who completed iEEG with intracranial grid or strip electrodes, 46 (43%) were male. Median age at the time of iEEG was 35.4 years (interquartile range [IQR], 26.4 - 44.9). Ninety patients (84.1%) had all AEDs held on admission, while 16 patients (15%) underwent a rapid taper. The median time to first seizure was 15.1 (8.2 - 22.6) h. Sixty-two patients (57.9%) developed SC, while 10 (9.4%) developed SE. Twenty-six patients (36.1%) with these complications required intravenous lorazepam or other rescue ASMs, while the remaining patients had spontaneous resolution of seizures; intubations were not required. While there were differences in the proportions in patients who experienced SC, SE, or neither in the URW and RW groups, these differences were not significant at the 0.05 alpha level. SIGNIFICANCE: Ultra-rapid and rapid ASM withdrawal are accompanied by SC and SE the majority of which terminate spontaneously. These data support the use of either approach of the medication taper for seizure provocation in iEEG.

Time to onset of cannabidiol treatment effects in Dravet syndrome: Analysis from two randomized controlled trials.

OBJECTIVE: We conducted a post hoc analysis of two randomized controlled trials, GWPCARE1 (NCT02091375) and GWPCARE2 (NCT02224703), to estimate the time to onset of cannabidiol (CBD) treatment effects (seizure reduction and adverse events [AEs]) in patients with Dravet syndrome (DS). METHODS: Patients received either plant-derived highly purified CBD (Epidiolex in the United States; 100 mg/ml oral solution) 10 mg/kg/day (CBD10; GWPCARE2) or 20 mg/kg/day (CBD20; GWPCARE1&2), or matching placebo for 14 weeks. Treatment started at 2.5 mg/kg/day, reached 10 mg/kg/day on Day 7, and went up to 20 mg/kg/day on Day 11 during the 14-day titration period. Percentage change from baseline in convulsive seizure frequency was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were also evaluated. RESULTS: Overall, 124 patients received placebo and 194 received CBD (CBD10, n = 64; CBD20, n = 130). Mean age was 9.5 years (range = 2.2-18.9). Patients had discontinued a median of four antiepileptic drugs (range = 0-26) and were currently taking a median of three (range = 1-5). Differences in convulsive seizure reduction between placebo and CBD emerged during titration and became nominally significant by Day 12 for CBD20 (p = .02) and Day 13 for CBD10 (p = .03). Additionally, differences in the 50% responder rate between placebo and CBD became apparent during titration. Onset of the first reported AE occurred during the titration period in 48.4% of placebo patients and 54.1% of CBD patients. The three most common AEs of somnolence, decreased appetite, and diarrhea resolved within 4 weeks of onset in the majority of CBD-treated patients (56.3%-72.9%). SIGNIFICANCE: The therapeutic effect of CBD in DS may start within 2 weeks of treatment in some patients. Although AEs lasted longer for CBD than placebo, most resolved within the 14-week study period.

Global brain network dynamics predict therapeutic responsiveness to cannabidiol treatment for refractory epilepsy.

Refractory epilepsy is a chronic brain network disorder characterized by unresponsiveness to multiple (>2) anti-epileptic drugs. Cannabidiol, a non-psychotropic neuroactive substance, is an emerging anti-epileptic treatment that was recently approved by the US Food and Drug Administration for the treatment of refractory epilepsy, especially Lennox Gastaut syndrome and Dravet syndrome. Here, we evaluated associations between global brain network dynamics and related changes and responsiveness to cannabidiol therapy using a combination of electroencephalography phase coherence and graph theoretical analyses. Refractory epilepsy patients with Lennox Gastaut syndrome or Dravet syndrome underwent serial electroencephalography testing prior to and during cannabidiol treatment. Patients showing greater than 70% seizure frequency reduction were classified as treatment responders for the purposes of this study. We calculated inter-electrode electroencephalography phase coherence in delta (1-3 Hz), theta (4-7 Hz), alpha (8-12 Hz) and beta (13-30 Hz) frequency bands. Graph theoretical analysis of brain network dynamics was extracted from phase coherence to evaluate measures of network integration (i.e. characteristic path length, global efficiency and degree) and segregation (i.e. modularity and transitivity). We found that responders, relative to non-responders, showed increased network integration-as indexed by relatively higher global efficiency and lower degree-and increased network segregation-as indexed by relatively higher modularity-exclusively in the beta-frequency band. We also found that larger cannabidiol dosages were associated with increased network integration-as indexed by higher global efficiency with increasing dose-and increased network segregation-as indexed by lower transitivity with increasing dose-in the delta, theta and alpha frequency bands. In summary, we demonstrate novel effects of cannabidiol on brain network dynamics with important implications for the treatment of refractory epilepsy and, possibly, across broader research applications in the future.

Changes in lipid profiles of epileptic mouse model.

INTRODUCTION: Approximately 1% of the world's population is impacted by epilepsy, a chronic neurological disorder characterized by seizures. One-third of epileptic patients are resistant to AEDs, or have medically refractory epilepsy (MRE). One non-invasive treatment that exists for MRE includes the ketogenic diet, a high-fat, low-carbohydrate diet. Despite the KD's success in seizure attenuation, it has a few risks and its mechanisms remain poorly understood. The KD has been shown to improve metabolism and mitochondrial function in epileptic phenotypes. Potassium channels have implications in epileptic conditions as they have dual roles as metabolic sensors and control neuronal excitation. OBJECTIVES: The goal of this study was to explore changes in the lipidome in hippocampal and cortical tissue from Kv1.1-KO model of epilepsy. METHODS: FT-ICR/MS analysis was utilized to examine nonpolar metabolome of cortical and hippocampal tissue isolated from a Kv1.1 channel knockout mouse model of epilepsy (n = 5) and wild-type mice (n = 5). RESULTS: Distinct metabolic profiles were observed, significant (p < 0.05) features in hippocampus often being upregulated (FC ≥ 2) and the cortex being downregulated (FC ≤ 0.5). Pathway enrichment analysis shows lipid biosynthesis was affected. Partition ratio analysis revealed that the ratio of most metabolites tended to be increased in Kv1.1-/-. Metabolites in hippocampal tissue were commonly upregulated, suggesting seizure initiation in the hippocampus. Aberrant mitochondrial function is implicated by the upregulation of cardiolipin, a common component in the mitochondrial membrane. CONCLUSION: Generally, our study finds that the lipidome is changed in the hippocampus and cortex in response to Kv1.1-KO indicating changes in membrane structural integrity and synaptic transmission.

Vagus nerve stimulation with tachycardia detection provides additional seizure reduction compared to traditional vagus nerve stimulation.

PURPOSE: This study investigates the clinical and cost effectiveness of switching from traditional vagus nerve stimulation (VNS) to responsive VNS (rVNS), which has an additional ictal tachycardia detection and stimulation (AutoStim) mode. METHODS: Retrospective chart review was used to collect data from patients with medically refractory epilepsy who underwent generator replacements. Patients with confounding factors such as medication changes were excluded. Vagus nerve stimulation parameters, seizure frequency, and healthcare costs were collected for the 1-year period following generator replacement with the rVNS device. RESULTS: Documented seizure frequency was available for twenty-five patients. After implant with rVNS, 28% of patients had an additional ≥50% seizure reduction. There was a significant decrease in the average monthly seizure count (p = 0.039). In patients who were not already free of disabling seizures (n = 17), 41.2% had ≥50% additional seizure reduction. There was no difference in healthcare costs during the 1-year follow-up after the rVNS implant compared with one year prior. CONCLUSIONS: Ictal tachycardia detection and stimulation provided a significant clinical benefit in patients who were not free of disabling seizures with treatment from traditional VNS. There was no additional increase in healthcare costs during the first year after device replacement.

Aberrant energy metabolism and redox balance in seizure onset zones of epileptic patients.

Epilepsy is a disorder that affects around 1% of the population. Approximately one third of patients do not respond to anti-convulsant drugs treatment. To understand the underlying biological processes involved in drug resistant epilepsy (DRE), a combination of proteomics strategies was used to compare molecular differences and enzymatic activities in tissue implicated in seizure onset to tissue with no abnormal activity within patients. Label free quantitation identified 17 proteins with altered abundance in the seizure onset zone as compared to tissue with normal activity. Assessment of oxidative protein damage by protein carbonylation identified additional 11 proteins with potentially altered function in the seizure onset zone. Pathway analysis revealed that most of the affected proteins are involved in energy metabolism and redox balance. Further, enzymatic assays showed significantly decreased activity of transketolase indicating a disruption of the Pentose Phosphate Pathway and diversion of intermediates into purine metabolic pathway, resulting in the generation of the potentially pro-convulsant metabolites. Altogether, these findings suggest that imbalance in energy metabolism and redox balance, pathways critical to proper neuronal function, play important roles in neuronal network hyperexcitability and can be used as a primary target for potential therapeutic strategies to combat DRE. SIGNIFICANCE: Epileptic seizures are some of the most difficult to treat neurological disorders. Up to 40% of patients with epilepsy are resistant to first- and second-line anticonvulsant therapy, a condition that has been classified as refractory epilepsy. One potential therapy for this patient population is the ketogenic diet (KD), which has been proven effective against multiple refractory seizure types However, compliance with the KD is extremely difficult, and carries severe risks, including ketoacidosis, renal failure, and dangerous electrolyte imbalances. Therefore, identification of pathways disruptions or shortages can potentially uncover cellular targets for anticonvulsants, leading to a personalized treatment approach depending on a patient's individual metabolic signature.

Mesial temporal resection following long-term ambulatory intracranial EEG monitoring with a direct brain-responsive neurostimulation system.

OBJECTIVE: To describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain-responsive neurostimulator (RNS) system. METHODS: We retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3-month follow-up after MTL resection compared to seizure frequency 3 months before MTL resection. RESULTS: We identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty-five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (mean = 42 months ICEEG); follow-up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow-up was 100% (mean: 94%; range: 50%-100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure-free at last follow-up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%-100%) at last follow-up, with eight of fifteen seizure-free. For those with more than 1 year of follow-up (N = 21), 15 patients (71%) were seizure-free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets. SIGNIFICANCE: Chronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.

Towards Successes in the Management of Nonconvulsive Status Epilepticus: Tracing the Detection-to-Needle Trajectories.

PURPOSE: Data on the timeliness of emergent medication delivery for nonconvulsive status epilepticus (NCSE) are currently lacking. METHODS: Retrospective chart reviews (between 2015 and 2018) and analyses of all patients with NCSE were performed at the University of Nebraska Medical Center, a level 4 epilepsy center, to determine the latencies to order and administration of the first, second, and third antiepileptic drugs (AEDs). Recurrent NCSE cases were considered independently and classified as comatose and noncomatose. RESULTS: There were 77 occurrences of NCSE in 53 patients. The first, second, and third AEDs were delivered with substantial delays at median times of 80 (25%-75% interquartile range, 44-166), 126 (interquartile range, 67-239), and 158 minutes (interquartile range, 89-295), respectively, from seizure detection. The median times to the order of the first and second AEDs were 33 and 134.5 minutes longer in comatose NCSE patients compared with those with noncomatose forms, respectively (P = 0.001 and 0.004, respectively). The median times between the AED orders and their administration in these two groups were the same (P = 0.60 and 0.37, respectively). With bivariate analysis, the median latencies to administration of the first, second, and third AEDs were significantly increased by 33, 109.5, and 173 minutes, respectively, in patients who died within 30 days compared with those who survived (P = 0.047, P = 0.02, P = 0.0007, respectively). CONCLUSIONS: The administration of the first, second, and third AEDs for NCSE was delayed. Slow initiation of acute treatment in comatose patients was caused by delays in the placement of the medication order.

Anterior corpus callosotomy in patients with drug-resistant epilepsy: Invasive EEG findings and seizure outcomes.

Corpus callosotomy (CC) is used in patients with drug-resistant seizures who are not candidates for excisional surgery and failed neurostimulation. We examined ictal scalp and intracranial electroencephalogram (iEEG) recordings in 16 patients being evaluated for anterior CC alone or CC in combination with focal resection, to determine the role of the iEEG in predicting postoperative seizure outcomes. In our cohort, CC improved generalized atonic seizures and focal seizures with impaired awareness but did not alter outcomes for generalized tonic-clonic or tonic seizures. Invasive EEG prior to CC did not refine the prediction of postsurgical seizure outcomes in patients with inconclusive scalp EEG.

Adenosine has two faces: Regionally dichotomous adenosine tone in a model of epilepsy with comorbid sleep disorders.

OBJECTIVE: Adenosine participates in maintaining the excitatory/inhibitory balance in neuronal circuits. Studies indicate that adenosine levels in the cortex and hippocampus increase and exert sleep pressure in sleep-deprived and control animals, whereas in epilepsy reduced adenosine tone promotes hyperexcitability. To date, the role of adenosine in pathological conditions that result in both seizures and sleep disorders is unknown. Here, we determined adenosine tone in sleep and seizure regulating brain regions of Kv1.1 knockout (KO) mice, a model of temporal epilepsy with comorbid sleep disorders. METHODS: 1) Reverse phase-high performance liquid chromatography (RP-HPLC) was performed on brain tissue to determine levels of adenosine and adenine nucleotides. 2) Multi-electrode array extracellular electrophysiology was used to determine adenosine tone in the hippocampal CA1 region and the lateral hypothalamus (LH). RESULTS: RP-HPLC indicated a non-significant decrease in adenosine (~50%, p = 0.23) in whole brain homogenates of KO mice. Regional examination of relative levels of adenine nucleotides indicated decreased ATP and increased AMP in the cortex and hippocampus and increased adenosine in cortical tissue. Using electrophysiological and pharmacological techniques, estimated adenosine levels were ~35% lower in the KO hippocampal CA1 region, and 1-2 fold higher in the KO LH. Moreover, the increased adenosine in KO LH contributed to lower spontaneous firing rates of putative wake-promoting orexin/hypocretin neurons. INTERPRETATION: This is the first study to demonstrate a direct correlation of regionally distinct dichotomous adenosine levels in a single model with both epilepsy and comorbid sleep disorders. The weaker inhibitory tone in the dorsal hippocampus is consistent with lower seizure threshold, whereas increased adenosine in the LH is consistent with chronic partial sleep deprivation. This work furthers our understanding of how adenosine may contribute to pathological conditions that underlie sleep disorders within the epileptic brain.

Autistic spectrum disorder, epilepsy, and vagus nerve stimulation.

PURPOSE: In individuals with a comorbid autistic spectrum disorder and medically refractory epilepsy, vagus nerve stimulation may offer the potential of seizure control and a positive behavioral side effect profile. We aimed to examine the behavioral side effect profile using longitudinal and quantitative data and review the potential mechanisms behind behavioral changes. METHODS: We present a case report of a 10-year-old boy with autistic spectrum disorder and epilepsy, who underwent vagus nerve stimulation subsequent to unsuccessful treatment with antiepileptic medication. RESULTS: Following vagus nerve stimulation implantation, initial, if temporary, improvement was observed in seizure control. Modest improvements were also observed in behavior and development, improvements which were observed independent of seizure control. CONCLUSIONS: Vagus nerve stimulation in autistic spectrum disorder is associated with modest behavioral improvement, with unidentified etiology, although several candidates for this improvement are evident.

Whole-brain functional connectivity increases with extended duration of focal epileptiform activity.

The analysis of interictal epileptiform discharges (IEDs) using magnetoencephalography (MEG) is utilized for the localization of seizure onset zones in the presurgical planning of epilepsy patients. Additionally, resting-state functional connectivity analyses using the IED area may provide novel insight into the underlying brain networks. In this study, we evaluate whether chronicity of seizures is related to whole-brain functional connectivity metrics using the area of IED generation (derived from MEG) as the seed region. We found a positive correlation between the duration of seizures and beta-band functional connectivity between the epileptogenic zone and other brain areas. This suggests the presence of inhibitory GABAergic modulation of distal brain regions in response to chronic epileptiform activity.

Somatic presentations of distress in China.

OBJECTIVE: Somatic presentations of distress are common cross-culturally and are thought to predominate in Asian cultures such as that of China. From an etic perspective, researchers utilizing empirically validated standardized assessment measures find that somatic symptoms are no more common in individuals of Chinese descent than they are in individuals of European descent. In contrast, patient presentations are heavily influenced by culture and are associated with patterns of illness behavior. The objective of the current review is to determine the culture-specific factors contributing to somatic presentations and descriptions of distress in China. METHOD: The current review was based on a literature search of PubMed and PsychInfo using the terms 'China,' 'Asia,' 'somatoform,' 'somatization,' and 'psychogenic.' RESULTS: Factors contributing to somatic presentations of distress in China include stigma and help-seeking behavior, and assessment approaches that ignore culture-specific patterns of symptom reporting, fail to incorporate somatic metaphor and Chinese conceptualizations of distress that emphasize bodily sensation, and ignore the role that culture-specific normative data and culture specific response patterns may produce on assessment results. CONCLUSIONS: From an emic perspective, there are numerous factors contributing to the appearance of a predominantly somatic presentation of distress in China. Implications for clinical practice are discussed.

A case of progressive ataxia followed by cognitive and behavioral changes.

The patient is a 60-year-old man who initially presented to his local hospital with complaints of gait difficulties that started suddenly after waking. Results of brain magnetic resonance imaging performed 1 week later were normal. Three weeks after that he developed blurred vision and he complained of a severe headache in the posterior head and neck regions at the onset of symptoms, which necessitated several visits to his local emergency room. The patient presented to our institution 1 month later, with progressive gait difficulty and truncal instability over a 2-week period.

CD40 ligand deficiency: neurologic sequelae with radiographic correlation.

Patients with CD40 ligand deficiency are susceptible to central nervous system infections, but to date the neurologic progression or long-term outcome of central nervous system complications have not been reported in detail. Characterizing the central nervous system complications of immune deficiencies can lead to the identification of new pathogens. For this study, clinical data were reviewed on patients with both CD40 ligand deficiency and neurodegeneration, identified from a larger cohort of 31 patients. Five patients had progressive neurologic and cognitive decline in the absence of clinical signs of acute fulminant encephalitis, with anatomic brain abnormalities and high mortality (60%). Despite multiple evaluations, no pathogens were identified in four patients, all of whom were on standard intravenous immunoglobulin therapy at illness presentation. This clinical phenotype of progressive decline without acute fulminant encephalitis is similar to chronic enteroviral encephalitis in X-linked agammaglobulinemia, another condition with severe humoral immune defects. Whether infection secondary to subtherapeutic levels of central nervous system immunoglobulin G (IgG), inadequately protective levels of serum IgG, or impaired CD40 ligand-dependent IgG-independent antiviral responses contributed remains undetermined. Emerging gene-chip techniques applied in patients with primary immune deficiencies may identify heretofore unknown viruses. Prospective neurocognitive and evaluation of patients with CD40 ligand deficiency may identify affected patients before overt clinical signs appear.

Classification of patterns of EEG synchronization for seizure prediction.

OBJECTIVE: Research in seizure prediction from intracranial EEG has highlighted the usefulness of bivariate measures of brainwave synchronization. Spatio-temporal bivariate features are very high-dimensional and cannot be analyzed with conventional statistical methods. Hence, we propose state-of-the-art machine learning methods that handle high-dimensional inputs. METHODS: We computed bivariate features of EEG synchronization (cross-correlation, nonlinear interdependence, dynamical entrainment or wavelet synchrony) on the 21-patient Freiburg dataset. Features from all channel pairs and frequencies were aggregated over consecutive time points, to form patterns. Patient-specific machine learning-based classifiers (support vector machines, logistic regression or convolutional neural networks) were trained to discriminate interictal from preictal patterns of features. In this explorative study, we evaluated out-of-sample seizure prediction performance, and compared each combination of feature type and classifier. RESULTS: Among the evaluated methods, convolutional networks combined with wavelet coherence successfully predicted all out-of-sample seizures, without false alarms, on 15 patients, yielding 71% sensitivity and 0 false positives. CONCLUSIONS: Our best machine learning technique applied to spatio-temporal patterns of EEG synchronization outperformed previous seizure prediction methods on the Freiburg dataset. SIGNIFICANCE: By learning spatio-temporal dynamics of EEG synchronization, pattern recognition could capture patient-specific seizure precursors. Further investigation on additional datasets should include the seizure prediction horizon.

Effects of subdural application of lidocaine in patients with focal epilepsy.

Antiepileptic drug (AED) delivery directly into the neocortex has recently been shown to be able to both prevent and terminate focal seizures in rats. The present clinical experiment aimed to test the local effects of lidocaine delivered onto the pia mater adjacent to epileptogenic zones in human patients. Administration of lidocaine resulted in a marked diminishment of spike counts on all patients, with a decremental effect of lidocaine on the faster frequency elements of individual spikes and overall testing epochs. The direct cortical application of lidocaine appears to affect local epileptogenic activity in human patients with intractable focal epilepsy.

Temporal lobe epilepsy: a progressive disorder?

Temporal lobe epilepsy (TLE) can be a progressive disorder, potentially resulting in structural damage and a decline of cognitive abilities over time. This is particularly evident in cases that are refractory to medication. This review examines the changes that occur in refractory TLE over time and the factors associated with these changes. Imaging and histologic studies on the brains of patients with TLE reveal anatomic and metabolic changes associated with continued seizures. These changes can impair cognitive and behavioral function. Seizure control may help minimize or prevent these changes.

Local epileptogenic networks in tuberous sclerosis complex: a case review.

OBJECTIVE: Cortical tubers are a pathognomonic finding in some patients with tuberous sclerosis complex (TSC), and are believed to be epileptogenic foci. Surgery is an effective option in selected patients with TSC who are refractory to medical therapy. This article describes three patients with TSC who underwent three-stage epilepsy surgery at our center, with the intention of examining local electrophysiological changes after each stage of the procedure. METHODS: Magnetic resonance images were obtained after initial implantation of electrodes and after resection and electrode reimplantation. These images were co-registered and overlaid. The intracranial grids were overlaid in a similar procedure and manually traced, and then added to the volumetric image. Mean spike counts were obtained for each patient and expressed in spikes per minute. Statistical analysis was performed on spike counts prior to and after resection. RESULTS: All three patients displayed intense spiking in the regions around the dominant epileptogenic tuber. On tuber removal, spike counts diminished significantly. In each case, new areas of spiking emerged in regions remote from the tuber periphery after tuber resection, with the emergence of secondary ictal onset zones in the resection margin. CONCLUSION: This retrospective study highlights some common electrophysiological features among the patients examined. The observed epileptogenic activity and regions of ictal onset suggest that it may be the region of brain tissue surrounding the tuber that is responsible for the majority of epileptogenic activity in these patients.