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Aim: Comprising large areas of association cortex, the parietal lobe is part of an extensive synaptic network elaborately intertwined with other brain regions. We hypothesize that such widespread projections are responsible for producing inaccurate localisation readings on scalp EEG and clinical semiology in patients with parietal lobe epilepsies, as opposed to frontal or temporal lobe epilepsies., Methods: Our study included 50 patients with pharmacoresistant focal epilepsy, who were subsequently rendered seizure-free for ≥12 months (median: 23 months) following resections limited to the frontal (n=17), temporal (n=17), or parietal (n=16) lobes. Interictal and ictal EEG data with accompanying seizure video recordings were extracted from archived files of scalp video-EEG monitoring. Two blinded raters independently reviewed the EEG according to predetermined criteria. Videos of seizures were then observed, as raters formulated their final electroclinical impression (ECI), identifying patients' abnormal neuronal activities with parietal, temporal, and frontal lobe epilepsy, or unspecified localisation., Results: Groups did not differ significantly in demographics, age at epilepsy onset, or presence of MRI abnormalities. Interictal discharges in parietal lobe epilepsy showed the greatest magnitude of scatter outside the lobe of origin; the majority of patients with parietal lobe epilepsy had more than one spike population (p<0.045). Localised ictal EEG recognition was most frequent in temporal, followed by frontal and parietal lobe epilepsy cases (p=0.024). Whenever raters confidently limited their ECI to one lobar subtype, overall accuracy was excellent. Lobar classifications by ECI were highly accurate for temporal lobe epilepsy, vacillating in frontal lobe epilepsy, and least accurate in parietal lobe epilepsy subjects., Conclusion: Scalp EEG readings of parietal lobe epilepsy patients showed a more variable scatter of interictal discharges and a lower localisation value of ictal recordings compared to temporal and frontal lobe epilepsy subjects, suggesting an increased likelihood of misidentification and mislocalisation of parietal lobe epilepsy. Combining seizure semiology with scalp interictal and ictal EEG readings facilitates a more accurate lobar classification in patients with temporal and frontal, but not parietal, lobe epilepsy.

Purpose: Cortical Dysplasia (CD) is the histopathological substrate in almost half of all drug-resistant focal epilepsies. Little is known about the gene expression profile of CD. As such information may help target therapeutics more effectively, our aim was to perform a gene expression analysis of an animal model of cortical dysplasia induced by in utero irradiation., Methods: Nine offspring from irradiated animals, and nine age-matched controls were sacrificed at post-natal day 60. Cortical and hippocampal regions were separated, and total ribonucleic acid (RNA) was extracted using a commercially available kit (Qiagen). RNA was then subjected to a gene expression analysis using an oligonucleotide microarray platform (Illumina). After statistical analysis, genes were considered differentially expressed when a p value less than 0.001 was observed. Real-time, quantitative polymerase chain reaction (RT-qPCR) was used to confirm microarray results for three genes via the Livak method., Results: Twenty three genes from cortical tissue met criteria for altered gene expression. Six genes from cortex seemed relevant to the pathogenesis of CD. Two genes that promoted cell survival (connective tissue growth factor and peroxiredoxin) were upregulated. One gene that promoted excitotoxic neurodegeneration (latrophilin-2) was downregulated. Two genes involved in glutamate (protein kinase C-alpha) and AMPA receptor recycling (NEEP-21) were downregulated. One gene, (Shank-1) involved in the control of dendritic maturation, was downregulated., Conclusion: Gene expression analysis in this animal model revealed some of the potential mechanisms by which CD may lead to the phenotype of intractable epilepsy. The downregulation of genes that are involved in glutamate and AMPA receptor recycling may lead to increased excitability. Disinhibition of aberrant dendritic branching, resulting from a downregulation of Shank-1, may also result in an increase in sprouting, excitation and/or hypersynchrony. Finally, genes promoting cell survival, either directly (connective tissue growth factor, peroxiredoxin) or indirectly (latrophilin-2) may allow CD tissue to survive the excitotoxic injury that it produces, thus allowing it to perpetuate the epileptic condition over time.

Studies have shown a lower risk for verbal memory decline following dominant anterior temporal lobectomy (ATL) among patients with poor, presurgical verbal memory scores. It is unclear however, if the risk of decline is increased in patients who also have reduced visual memory. Objective and subjective memory outcome following left ATL was examined in twelve patients with reduced presurgical visual and verbal memory scores. Only one patient demonstrated a meaningful decline in memory scores, with a decline in visual memory following surgery. Presurgically, this patient demonstrated poor memory bilaterally on Wada testing and small discrepancy in hippocampal volumes. She was also one of two patients who continued to have seizures post-surgery. This preliminary study suggests that patients with unilateral, left TLE and poor verbal and visual memory are unlikely to show meaningful memory declines following left ATL, particularly if they demonstrate expected patterns on Wada testing, hippocampal volume discrepancy (left < right), and postsurgical seizure-freedom.

Objective: Malformations of cortical development are frequent causes of human refractory epilepsy. The freeze-lesion model in rats shows histopathological features similar to those found in human polymicrogyria. Previous studies reported in vitro hyperexcitability in this model, but in vivo epileptogenicity has not been confirmed., Methods: Neocortical freeze lesions were induced in Sprague-Dawley rat pups (n = 10) on postnatal day 0 or 1 (P0/P1). Sham-operated animals served as controls (n = 10). On P60, animals were implanted with epidural electrodes for long-term video-EEG monitoring (4 weeks). The threshold for pentylenetetrazol-induced seizures was determined. Animals were sacrificed and brain sections processed for histological staining and in vitro electrophysiological recordings. Epileptiform field potential repetition rate, amplitude and integral were compared between slices containing a cortical freeze lesion, and slices from sham-operated rats., Results: No interictal spikes and no electrographic or clinical seizures occurred in either group. The median threshold for pentylenetetrazol-induced seizures was 60 mg/kg for lesioned, and 45 mg/kg for control animals (difference not significant). No spontaneous epileptiform field potentials were recorded from either freeze-lesion or control slices bathed in normal, artificial cerebrospinal fluid (ACSF). Upon omission of Mg(2+) from the bath, epileptiform field potentials were elicited that showed a significantly higher burst integral in the freeze lesion slices compared to control slices., Conclusion: Neocortical freeze lesions induced in newborn rat pups show histological characteristics reminiscent of human cortical dysplasia. Brain slices containing neocortical freeze lesions display hyperexcitability in vitro, but the same lesion does not appear to show spontaneous epileptogenicity in vivo.

Pharmacoresistant epilepsy arising from the dominant temporal region in patients with intact memory and normal anatomical imaging, presents major challenges in the preoperative definition of the epileptogenic zone, and the planning of the extent of the surgical resection. We report on the case of a 42-year-old, right-handed male who presented with recurrent daily seizures that were resistant to antiepileptic drugs. Multiple, non-invasive (scalp) video-EEG evaluations revealed focal epilepsy arising from the left fronto-temporal region. Multiple high resolution MRIs that were performed at multiple Epilepsy Centers failed to show any abnormality. Fluoro-deoxyglucose PET scan showed extensive, left antero-mesial temporal hypometabolism, and ictal SPECT showed increased perfusion in the left insula in addition to the left mesial and anterior temporal pole. Neuropsychological testing and intracarotid methohexital testing revealed excellent memory to the left, dominant side. A two-stage invasive evaluation with subdural grid electrodes followed by depth electrode recordings allowed the localization of the epileptogenic region to the temporal pole. A selective resection of the left temporal pole (that spared the hippocampal formation) resulted in a seizure-free outcome (one year follow-up) with no significant consequences on memory function. We conclude that targeted, invasive recording techniques should be used for the accurate localization and delineation of the extent of the epileptogenic zone in cases of suspected, non-lesional, dominant hemisphere, temporal lobe epilepsy with preserved memory function. The use of the staged invasive approach may increase the chances for memory (function) sparing through tailored, temporal resection.

The recent proposal by the ILAE Task Force for Epilepsy Classification consists of a multi-axial syndrome-oriented approach. Epilepsy syndromes, as defined by the ILAE, group patients according to various, poorly defined parameters. The resulting syndromes have frequently no biological significance, with overlap among different syndromes and syndromes changing with age. Additionally, only a minority of patients can be classified syndromatically, and the axes of this classification system convey redundant information. We propose a five-dimensional, patient-oriented approach to classifying epilepsies. This approach shifts from the syndrome-oriented approach to a standard, neurological, methodological, patient-oriented approach, using independent criteria in each of the five dimensions. Similar to general neurology, the first step in each patient-physician encounter in epileptology is to take a history of the presenting symptoms and generate a hypothesis regarding the localization and etiology of the symptom within the nervous system. Therefore, the main dimensions of this classification consist of: 1) localization of the epileptogenic zone, 2) seizure semiology classified according to the semiological seizure classification, 3) etiology, 4) seizure frequency, and 5) related medical conditions. These dimensions characterize all of the information necessary for patient management, are independent parameters, and include more pertinent information with regards to patient management than the ILAE axes. All patients can be classified according to this five-dimensional system even at the initial patient encounter when no detailed test results are available. Information from clinical tests, such as MRI and EEG, are translated into the best possible working hypothesis at the time of classification, allowing for increasing precision of the classification as additional information becomes available. This patient-oriented classification envisions an epileptic seizure as an independent symptom of a central nervous system dysfunction due to different causes, with various cortical localizations, occurring at various frequencies, and in conjunction with other diseases and clinical symptoms.