Publications by authors named "Seyed M Mirsattari"

85 Publications

Epilepsy surgery in stroke-related epilepsy?

Seizure 2021 Apr 5;88:116-124. Epub 2021 Apr 5.

Epilepsy Program, Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, 339 Windermere Rd. London, Ontario, Canada, N6A 5A5; Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, 339 Windermere Rd. London, Ontario, Canada, N6A 5A5; Neuro-Epidemiology Unit, Schulich School of Medicine and Dentistry, Western University, 339 Windermere Rd. London, Ontario, Canada, N6A 5A5. Electronic address:

Purpose: To provide a descriptive analysis on the presurgical evaluation and surgical management of a cohort of patients with stroke related epilepsy (SRE).

Methods: We retrospectively examined the clinical characteristics, results of non-invasive and invasive presurgical evaluation, surgical management and outcome of consecutive patients with drug-resistant SRE in our institution from January 1, 2013 to January 1, 2020.

Results: Twenty-one of 420 patients (5%) who underwent intracranial EEG (iEEG), resective epilepsy surgery and/or vagus nerve stimulation (VNS) placement, had SRE. Of 13 patients who had iEEG, the ictal onset (IO) was exclusively within the stroke lesion in only one patient. In five patients the IO was extra-lesional and in the remaining seven patients it included the stroke lesion as well as extra-lesional structures. The IO included the mesial temporal region in 11 of the 13 patients (85%). The posterior margin of the stroke lesion was always involved. Five patients underwent surgery without iEEG. In total, 10 patients underwent resective surgery, four VNS placement and two had both corpus callosotomy and VNS placement. Of the patients who had resective surgery, nine were Engel I or II at last follow up.

Conclusion: We found that seizures in patients with drug resistant SRE were more frequently originated in the mesial temporal region than in the stroke lesion itself. Despite the complex epileptic network underlying drug-resistant SRE, a thorough presurgical assessment and adequate use of surgical options can lead to excellent surgical outcomes.
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http://dx.doi.org/10.1016/j.seizure.2021.04.002DOI Listing
April 2021

All that glitters: Contribution of stereo-EEG in patients with lesional epilepsy.

Epilepsy Res 2021 Feb 2;170:106546. Epub 2021 Jan 2.

Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Neuro-Epidemiology Unit, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. Electronic address:

Objective: To determine the contribution of stereo-EEG for localization purpose in patients with a visible lesion on MRI.

Background: Intracranial EEG is often used to localize the epileptogenic focus in patients with non-lesional focal epilepsy. Its role in cases where a lesion is visible on MRI can be even more complex and the relationship between the lesion and the seizure onset has rarely been addressed.

Methods: All consecutive patients between February 2013 and May 2018 who underwent stereo-EEG and had a lesion visible on MRI were included. We assessed the localization of the seizure onset and its relationship with the lesion. Clinical, radiological, and electrographic analyses were performed.

Results: Stereo-EEG revealed a seizure onset with either partial or no overlap with the lesion seen on MRI in 42 (56 %) of the 75 lesions included. Mesial temporal sclerosis was the only lesion type associated with an exclusively lesional seizure onset (p = 0.003).

Conclusion: Epilepsy surgery in MRI-positive cases should rely not only the results of lesions seen on MRI, which might be potentially misleading; SEEG is a gold standard method in these cases to define resective borders.
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http://dx.doi.org/10.1016/j.eplepsyres.2020.106546DOI Listing
February 2021

Practice Guidelines for Canadian Neurophysiology Laboratories During the COVID-19 Pandemic.

Can J Neurol Sci 2021 01 19;48(1):25-30. Epub 2020 Aug 19.

Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada.

The COVID-19 pandemic has had a major impact on clinical practice. Safe standards of practice are essential to protect health care workers while still allowing them to provide good care. The Canadian Society of Clinical Neurophysiologists, the Canadian Association of Electroneurophysiology Technologists, the Association of Electromyography Technologists of Canada, the Board of Registration of Electromyography Technologists of Canada, and the Canadian Board of Registration of Electroencephalograph Technologists have combined to review current published literature about safe practices for neurophysiology laboratories. Herein, we present the results of our review and provide our expert opinion regarding the safe practice of neurophysiology during the COVID-19 pandemic in Canada.
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http://dx.doi.org/10.1017/cjn.2020.184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578631PMC
January 2021

Non-lesional eating epilepsy with temporo-insular onset: A stereo-EEG study.

Epilepsy Behav Rep 2020 1;14:100368. Epub 2020 May 1.

Epilepsy Program, Department of Clinical Neurological Sciences, Western University, London, Ontario, Canada.

Eating Epilepsy (EE) is a rare and often under-recognized form of reflex epilepsy, which manifests with seizures triggered during meals, with or without spontaneous seizures. The electro-clinical manifestations of EE are distinct with variable response to antiseizure drugs. We report the case of a 34-year-old man who was seen for a 4-year history of drug-resistant focal impaired awareness seizures associated with eating without a structural cause. Scalp video-EEG delineated a right temporal seizure focus with atypical features. Subsequent stereo-EEG revealed synchronized seizure onset from the right mesial temporal region and the right inferior insula. Resective surgery of the involved areas rendered this patient seizure-free with 3 years' follow-up. In non-lesional cases of drug-resistant EE, the epileptogenic zone can be large and deep, and therefore stereo-EEG was helpful in determining the seizure onset zone.
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http://dx.doi.org/10.1016/j.ebr.2020.100368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334470PMC
May 2020

Can we accurately lateralize the epileptogenic zone in patients who have seizure clusters? A study using stereo-electroencephalography.

Epilepsy Res 2020 10 23;166:106405. Epub 2020 Jun 23.

Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Neuro-epidemiology Unit, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. Electronic address:

Objective: To determine if the ictal onset recorded with stereoelectroencephalography (SEEG) during clusters of seizures is reliable to identify the laterality of the epileptogenic zone.

Background: In the presurgical evaluation of patients with focal drug-resistant epilepsy, the presence of bilateral ictal onset is usually associated with a poor surgical outcome. It has been reported that the laterality of seizures can be influenced during seizure clusters, although this remains controversial. Most studies have addressed this issue using scalp EEG which could erroneously determine the laterality of the ictal onset.

Methods: We examined all consecutive patients who underwent SEEG with bilateral hemispheric coverage at our institution between January 2013 and September 2018. We assessed the presence of seizure clusters (clinical or subclinical), their laterality by SEEG and the surgical outcome of the patients. A descriptive clinical and electrographic analysis was performed.

Results: Of 143 patients who underwent SEEG recordings, we identified only six patients who had bilateral ictal onset that went on to resective surgery. In all six patients the discordant seizures occurred during a seizure cluster. Three of these patients were seizure free at last follow up.

Conclusion: Discordant seizures obtained during a seizure cluster may not necessarily mean that the patient has bilateral epilepsy, and therefore a poor post-surgical outcome. Seizure clusters may not reliably lateralize the epileptogenic zone.
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http://dx.doi.org/10.1016/j.eplepsyres.2020.106405DOI Listing
October 2020

Concordance between fMRI and Wada test for memory lateralization in temporal lobe epilepsy: A meta-analysis and systematic review.

Epilepsy Behav 2020 06 7;107:107065. Epub 2020 Apr 7.

Department of Clinical Neurological Sciences, Western University, London, Ontario, Canada; Department of Medical Biophysics, Western University, London, Ontario, Canada; Department of Medical Imaging, Western University, London, Ontario, Canada; Department of Psychology, Western University, London, Ontario, Canada.

Objective: The Wada test (WT) is increasingly being replaced by functional magnetic resonance imaging (fMRI) to evaluate memory lateralization before temporal lobe epilepsy (TLE) surgery. We aimed to determine, via meta-analysis, agreement between the two tests and identify predictors of disagreement.

Methods: We performed a systematic search for studies comparing WT and fMRI for memory lateralization with individual-patient data. If results were provided as laterality indexes instead of hemispheric lateralization, the cutoff point for memory lateralization was set to the usual ±2 for WT and ±0.20 for fMRI. We also evaluated results at our Epilepsy Center.

Results: Seven published series plus our own were included, comprising 124 patients. Wada test was performed by recognizing objects in half of the studies, and scenes, drawings, and words in the rest. All used scenes or pictures encoding for fMRI. Wada test-fMRI agreement across the studies ranged from 21.1 to 100%, averaging 46.8% (95% confidence interval [CI]: 37.6-56.0%). When cases with bilateral memory in either test were excluded, agreement reached 78.7% (95% CI: 67.6-89.8%), and concordance with contralateral TLE foci 86.4% for the WT and 83.0% for fMRI. Higher agreement was associated with using multiple items during WT (p = 0.001) and higher disagreement with presence of a lesion on MRI (p = 0.024). Binary logistic regression confirmed use of multiple items on WT as the strongest predictor of agreement (odds ratio [OR]: 6.95, 95% CI: 1.84-26.22; p = 0.004) and a bilateral result on the WT or fMRI of disagreement (OR: 0.24, 95% CI: 0.07-0.89 and OR: 0.12, 95% CI: 0.03-0.45; p < 0.05).

Conclusion: Concordance between WT and fMRI for memory lateralization is low in patients with TLE and bilateral memoryl memory distribution or a structural etiology, and it improves with encoding of a varied set of items. Both tests can help to lateralize the TLE foci.
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http://dx.doi.org/10.1016/j.yebeh.2020.107065DOI Listing
June 2020

The authors respond to "Fentanyl patch probably not related to amnesia in case".

CMAJ 2019 11;191(44):E1226-E1227

Professor, Department of Clinical Neurological Sciences and Division of Radiology, Western University, London, Ont.

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http://dx.doi.org/10.1503/cmaj.73774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834446PMC
November 2019

Relationship between déjà vu experiences and recognition-memory impairments in temporal-lobe epilepsy.

Memory 2019 Jul 24:1-11. Epub 2019 Jul 24.

a The Brain and Mind Institute and Department of Psychology, University of Western Ontario , London , Canada.

Déjà vu is characterised by feelings of familiarity and concurrent awareness that this familiarity is wrong. Previous neuropsychological research has linked déjà vu during seizures in individuals with unilateral temporal-lobe epilepsy (uTLE) to rhinal-cortex abnormalities, and to recognition-memory deficits that selectively affect familiarity assessment. Here, we examined whether bilateral TLE patients with déjà vu (bTLE) show a similar pattern of performance. Using two experimental tasks, we found that bTLE patients exhibit deficits not only for familiarity but also for recollection. Relative to uTLE, this broader impairment also involved hippocampal abnormalities. Our findings confirm rhinal-cortex contributions to the generation of false familiarity in déjà vu that parallel its contributions to familiarity on recognition-memory tasks. While they do not rule out a role for recollection in identifying this familiarity as wrong, the deficits observed in bTLE patients weigh against the notion that any such role is necessary for déjà vu to occur.
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http://dx.doi.org/10.1080/09658211.2019.1643891DOI Listing
July 2019

Comparing the Wada Test and Functional MRI for the Presurgical Evaluation of Memory in Temporal Lobe Epilepsy.

Curr Neurol Neurosci Rep 2019 05 1;19(6):31. Epub 2019 May 1.

Department of Clinical Neurological Sciences, Western University, London, Ontario, Canada.

Purpose Of Review: The usefulness of the Wada test (WT) predicting memory impairment from temporal lobe epilepsy (TLE) surgery has been debated, and it has progressively been replaced by functional MRI (fMRI). We review the current role of WT and fMRI in the presurgical assessment of TLE, and how novel surgical techniques might improve cognitive outcomes.

Recent Findings: fMRI's ability to predict global amnesia has not been assessed. Although WT can produce false-positive results, it is still indicated in patients at risk for developing global amnesia: those with significant bilateral or contralateral memory deficits. In the current review, WT exhibited no added value, beyond preclinical data, for predicting material-specific memory impairment, whereas fMRI was reliable for either verbal or non-verbal memory decline. Abnormal functional connectivity on resting state fMRI (rs-fMRI) between the posterior cingulate and the hippocampus may be a predictor of postsurgical memory outcomes. Restricted resections to the pathogenic tissue, stereotactic laser, radiosurgery, and SEEG-guided thermos-coagulation were associated with better cognitive outcome. fMRI should be used routinely in the presurgical workup of TLE to predict verbal and/or non-verbal memory decline, whereas WT may be indicated when there is a high risk of postsurgical global amnesia. Rs-fMRI is a promising tool for the presurgical workup of TLE, and more restricted resections are recommended to enhance cognitive outcomes.
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http://dx.doi.org/10.1007/s11910-019-0945-8DOI Listing
May 2019

Late adult-onset epilepsy in a patient with hemimegalencephaly.

Epileptic Disord 2019 Apr;21(2):206-208

Departments of Clinical Neurological Sciences (SAC, SMM), Medical Imaging (SMM), Medical Biophysics (SMM), Psychology (SMM), Western University, London, Canada.

Hemimegalencephaly is a malformation of cortical development that normally manifests in childhood with seizures and cognitive impairment. We present a case of hemimegalencephaly in a 55-year-old developmentally-normal woman who developed focal impaired awareness seizures with bilateral tonic-clonic spread. Her interictal EEG showed left-sided multifocal spikes, and ictal EEG showed seizures starting in the left hemisphere. Imaging showed hemimegalencephaly. This case may represent the oldest age for a first seizure in a patient with hemimegalencephaly.
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http://dx.doi.org/10.1684/epd.2019.1041DOI Listing
April 2019

Opioid-associated amnestic syndrome observed with fentanyl patch use.

CMAJ 2019 03;191(12):E337-E339

Department of Clinical Neurological Sciences (Taylor, Budhram, Lee, Mirsattari), and Division of Radiology (Lee), Western University, London, Ont.

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http://dx.doi.org/10.1503/cmaj.181291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435361PMC
March 2019

Teaching NeuroImages: Double cortex: Rare diagnosis in adulthood.

Neurology 2018 10;91(18):e1724-e1725

From the Division of Neurology (K.M.I.), Department of Medicine, Dalhousie University, Halifax Infirmary; and Department of Clinical Neurological Sciences (S.M.M.), Western University, London Health Sciences Centre, Canada.

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http://dx.doi.org/10.1212/WNL.0000000000006433DOI Listing
October 2018

Teratoma-negative anti-NMDA receptor encephalitis presenting with a single generalized tonic-clonic seizure.

Epilepsy Behav Case Rep 2018 13;10:29-31. Epub 2018 Mar 13.

Department of Clinical Neurological Sciences, Western University, London, Ontario, Canada.

Herein, we describe a case report of anti-NMDA receptor encephalitis characterized by a single generalized tonic-clonic seizure and predominantly psychiatric symptoms, persisting long after EEG abnormalities had resolved. We discuss common presentations of anti-NMDA receptor encephalitis and advocate for the inclusion of this disease entity in the differential diagnosis of patients presenting with one generalized tonic-clonic seizure and prominent psychiatric symptoms.
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http://dx.doi.org/10.1016/j.ebcr.2018.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030023PMC
March 2018

Memory loss and memory reorganization patterns in temporal lobe epilepsy patients undergoing anterior temporal lobe resection, as demonstrated by pre-versus post-operative functional MRI.

J Clin Neurosci 2018 Sep 20;55:38-44. Epub 2018 Jun 20.

Department of Clinical Neurological Sciences, Western University, London, Ontario, Canada; Department of Medical Imaging, Western University, London, Ontario, Canada; Department of Medical Biophysics, Western University, London, Ontario, Canada; Department of Psychology, Western University, London, Ontario, Canada. Electronic address:

This study was aimed to longitudinally assess memory function and whole-brain memory circuit reorganization in patients with temporal lobe epilepsy (TLE) by comparing activation potentials before versus after anterior temporal lobe (ATL) resection. Nineteen patients with medically-intractable TLE (10 left TLE, 9 right TLE) and 15 healthy controls were enrolled. Group analyses were conducted pre- and post-ATL of a novelty complex scene-encoding paradigm comparing areas of blood oxygen-level-dependent (BOLD) signal activations on functional magnetic resonance imaging (fMRI). None of the pre-operative patient characteristics we studied predicted the extent of pre- to post-operative memory loss. On fMRI, extra-temporal activations were detected pre-operatively in both LTLE and RTLE, particularly in the frontal lobe. Greater activations also were noted in the contralateral hippocampus and parahippocampus in both groups. Performing within-subject comparisons, post-op relative to pre-op, pronounced ipsilateral activations were identified in the left parahippocampal gyrus in LTLE, versus the right middle temporal gyrus in RTLE patients. Memory function was impaired pre-operatively but declined after ATL resection in both RTLE and LTLE patients. Post-operative fMRI results indicate possible functional adaptations to ATL loss, primarily occurring within the left parahippocampal gyrus versus right middle temporal gyrus in LTLE versus RTLE patients, respectively.
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http://dx.doi.org/10.1016/j.jocn.2018.06.020DOI Listing
September 2018

Intracranial Electroencephalographic Monitoring: From Subdural to Depth Electrodes.

Can J Neurol Sci 2018 05 12;45(3):336-338. Epub 2018 Apr 12.

Epilepsy Program,Department of Clinical Neurological Sciences,Schulich School of Medicine and Dentistry,Western University,London,Ontario,Canada.

At the London Health Sciences Centre Epilepsy Program, stereotactically implanted depth electrodes have largely replaced subdural electrodes in the presurgical investigation of patients with drug-resistant epilepsy over the past 4 years. The rationale for this paradigm shift was more experience with, and improved surgical techniques for, stereoelectroencephalography, a possible lower-risk profile for depth electrodes, better patient tolerability, shorter operative time, as well as increased recognition of potential surgical targets that are not accessible to subdural electrodes.
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http://dx.doi.org/10.1017/cjn.2018.4DOI Listing
May 2018

Novel connectivity map normalization procedure for improved quantitative investigation of structural thalamic connectivity in temporal lobe epilepsy patients.

J Magn Reson Imaging 2018 12 23;48(6):1529-1539. Epub 2018 Mar 23.

Imaging Research Laboratories, Robarts Research Institute - Western University, London, Ontario, Canada.

Background: Connectivity studies targeting the thalamus have revealed patterns of atrophy and deafferentiation in temporal lobe epilepsy (TLE). The thalamus can be parcellated using probabilistic tractography to demonstrate regions of cortical connectivity; however, sensitivity to smaller or less connected regions is low.

Purpose/hypothesis: To investigate thalamic structural connectivity in a wider range of cortical and limbic structures in TLE patients using a novel connectivity map normalization procedure.

Study Type: Retrospective.

Population/subjects: Patients (N = 23) with medication-resistant TLE and 34 healthy age-matched controls.

Field Strength/sequence: For T and diffusion weighting a spoiled gradient sequence was used (41 gradient directions [b = 1000]). For T mapping balanced steady-state free precession was used. Images were acquired at 3T.

Assessment: Probabilistic tractography and a novel normalization procedure allowed comparison of groups with respect to thalamic connected volume, quantitative MRI, and diffusion tensor imaging (DTI) metrics.

Statistical Tests: Independent samples t-test, Cohen's d, and Mann-Whitney tests.

Results: Following normalization, significant differences in thalamic connected volumes were found in left TLE vs. controls bilaterally within the posterior parahippocampal gyrus (L: P = 0.007, confidence interval [CI]: [173.306,1044.41], effect size [ES] = 1.072; R: P = 0.017, CI: [98.677,947.653], ES = 0.945), and contralaterally in the anterior temporal neocortex (P = 0.01, CI: (-2348.09, -333.719), ES = -1.021). This procedure revealed differences in thalamic connected volumes, where previously published procedures could not, and provided a basis for exploratory analysis of quantitative MRI and DTI metrics.

Data Conclusion: The novel connectivity map normalization scheme proposed here successfully allowed comparison between a wider range of cortical and limbic structures. Multiple volumetric and quantitative MRI and DTI-related differences between TLE patients and controls were revealed following normalization. With validation from a larger cohort, thalamo-temporal connection aberrancies may become useful biomarkers of disease states and probabilistic tractography as a procedure for identification of thalamic targets in modulatory therapies for TLE.

Level Of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1529-1539.
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http://dx.doi.org/10.1002/jmri.26013DOI Listing
December 2018

Evidence for Cholinergic Dysfunction in Autosomal Dominant Kufs Disease.

Can J Neurol Sci 2018 03;45(2):150-157

3Department of Medicine (Geriatric Medicine and Neurology),Dalhousie University,Halifax,Nova Scotia,Canada.

Objective: Neuronal ceroid-lipofuscinoses are a heterogeneous group of inherited disorders in which abnormal lipopigments form lysosomal inclusion bodies in neurons. Kufs disease is rare, and clinical symptoms include seizures, progressive cognitive impairment, and myoclonus. Most cases of Kufs disease are autosomal recessive; however, there have been a few case reports of an autosomal dominant form linked to mutations within the DNAJC5 gene.

Methods: We describe a family with Kufs disease in which the proband and three of her four children presented with cognitive impairment, seizures, and myoclonus.

Results: Genetic testing of all four children was positive for a c.346_348delCTC(p.L116del) mutation in the DNAJC5 gene. The proband brain had an abundance of neuronal lipofuscin in the cerebral cortex, striatum, amygdala, hippocampus, substantia nigra, and cerebellum. There were no amyloid plaques or neurofibrillary tangles. Immunohistochemistry demonstrated that the cholinergic neurons and cholinergic projection fibers were spared, but there was a profound loss of choline acetyltransferase within the caudate, putamen, and basal forebrain. This suggests a loss of choline acetyltransferase as opposed to a loss of the neurons.

Conclusions: This report describes the clinical history of autosomal dominant Kufs disease, the genetic mutation within the DNAJC5 gene, and the neuropathological findings demonstrating depletion of choline acetyltransferase in the brain.
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http://dx.doi.org/10.1017/cjn.2017.261DOI Listing
March 2018

Update on Minimal Standards for Electroencephalography in Canada: A Review by the Canadian Society of Clinical Neurophysiologists.

Can J Neurol Sci 2017 11;44(6):631-642

2Department of Medicine,Division of Neurology,University of Saskatchewan,Saskatoon,Saskatchewan,Canada.

Surface electroencephalogram (EEG) recording remains the gold standard for noninvasive assessment of electrical brain activity. It is the most efficient way to diagnose and classify epilepsy syndromes as well as define the localization of the epileptogenic zone. The EEG is useful for management decisions and for establishing prognosis in some types of epilepsy. Electroencephalography is an evolving field in which new methods are being introduced. The Canadian Society of Clinical Neurophysiologists convened an expert panel to develop new national minimal guidelines. A comprehensive evidence review was conducted. This document is organized into 10 sections, including indications, recommendations for trained personnel, EEG yield, paediatric and neonatal EEGs, laboratory minimal standards, requisitions, reports, storage, safety measures, and quality assurance.
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http://dx.doi.org/10.1017/cjn.2017.217DOI Listing
November 2017

Identification of a novel synaptic protein, TMTC3, involved in periventricular nodular heterotopia with intellectual disability and epilepsy.

Hum Mol Genet 2017 11;26(21):4278-4289

Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, N6A 5C1.

Defects in neuronal migration cause brain malformations, which are associated with intellectual disability (ID) and epilepsy. Using exome sequencing, we identified compound heterozygous variants (p.Arg71His and p. Leu729ThrfsTer6) in TMTC3, encoding transmembrane and tetratricopeptide repeat containing 3, in four siblings with nocturnal seizures and ID. Three of the four siblings have periventricular nodular heterotopia (PVNH), a common brain malformation caused by failure of neurons to migrate from the ventricular zone to the cortex. Expression analysis using patient-derived cells confirmed reduced TMTC3 transcript levels and loss of the TMTC3 protein compared to parental and control cells. As TMTC3 function is currently unexplored in the brain, we gathered support for a neurobiological role for TMTC3 by generating flies with post-mitotic neuron-specific knockdown of the highly conserved Drosophila melanogaster TMTC3 ortholog, CG4050/tmtc3. Neuron-specific knockdown of tmtc3 in flies resulted in increased susceptibility to induced seizures. Importantly, this phenotype was rescued by neuron-specific expression of human TMTC3, suggesting a role for TMTC3 in seizure biology. In addition, we observed co-localization of TMTC3 in the rat brain with vesicular GABA transporter (VGAT), a presynaptic marker for inhibitory synapses. TMTC3 is localized at VGAT positive pre-synaptic terminals and boutons in the rat hypothalamus and piriform cortex, suggesting a role for TMTC3 in the regulation of GABAergic inhibitory synapses. TMTC3 did not co-localize with Vglut2, a presynaptic marker for excitatory neurons. Our data identified TMTC3 as a synaptic protein that is involved in PVNH with ID and epilepsy, in addition to its previously described association with cobblestone lissencephaly.
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http://dx.doi.org/10.1093/hmg/ddx316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886076PMC
November 2017

Focal Cortical Dysplasia Type IIa Manifesting as Epilepsia Partialis Continua for 50 Years.

Can J Neurol Sci 2018 01 2;45(1):106-108. Epub 2017 Oct 2.

2Department of Pathology,Western UniversityLondon,Ontario,Canada.

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http://dx.doi.org/10.1017/cjn.2017.237DOI Listing
January 2018

Functional connectivity of the hippocampus to the thalamocortical circuitry in an animal model of absence seizures.

Epilepsy Res 2017 11 24;137:19-24. Epub 2017 Aug 24.

Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada; Graduate Program in Neuroscience, University of Western Ontario, London, Ontario, Canada; Department of Medical Biophysics, Western University, London, Ontario, Canada; Department of Medical Imaging, Western University, London, Ontario, Canada; Department of Psychology, Western University, London, Ontario, Canada. Electronic address:

Objective: Using the gamma-butyrolactone (GBL) rat model of absence seizures, this study investigated the functional connectivity of the hippocampus, thalamus and cerebral cortex before and during absence seizures.

Methods: Functional connectivity between the hippocampus, thalamus and sensory and motor cortecies, were examined by the temporal correlations of the resting state blood-oxygen-level-dependent (BOLD) signal. Functional connectivity between these regions was calculated at baseline, 5min after saline injection, and at 5, 20 and 52min after GBL injection. This time interval spans the onset of behaviours including chewing and staring spells associated with GBL-induced absence seizures, along with the onset and suppression of spike-and-wave discharges (SWDs).

Results: Overall there was an increase in functional connectivity across most regions. The functional connectivity generally decreased over time and it returned to baseline 52min post-GBL injection. Functional connectivity of the thalamus to the sensory and motor cortecies increased during absence seizure. The results revealed enhanced connectivity of the left dorsal hippocampus and the thalamus shortly after GBL injection, which coincided with the appearance of SWDs in this rat model.

Significance: Increased functional connectivity between the hippocampus and the thalamus suggests that the hippocampus participates in the GBL model of absence seizures. Involvement of the hippocampus during absence seizure has implications for studies into the mechanisms in cognitive impairments in patients with absence epilepsy.
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http://dx.doi.org/10.1016/j.eplepsyres.2017.08.004DOI Listing
November 2017

Comparing the Intracarotid Amobarbital Test and Functional MRI for the Presurgical Evaluation of Language in Epilepsy.

Curr Neurol Neurosci Rep 2017 Jul;17(7):54

Department of Clinical Neurological Sciences, Western University, B10-106, 339 Windermere Road, London, Ontario, N6A 5W9, Canada.

Surgery is the treatment of choice for drug-resistant temporal lobe epilepsy (TLE). However, such surgery frequently causes deficits in language function, especially if performed on the dominant hemisphere. In recent years, the intracarotid amobarbital test (IAT) has been gradually replaced by functional magnetic resonance imaging (fMRI) in the preoperative identification of language areas to estimate the risk of postoperative language decline. In this paper, we review the neural substrates for language processing, how language impairment can result both from TLE itself and from surgical attempts to treat it. Subsequently, we discuss the strengths and limitations of, and current indications for fMRI and IAT during the preoperative workup, both by discussion of the studies that have evaluated them individually and through meta-analysis of data from 31 studies deemed eligible for analysis. Electrocortical stimulation mapping (ESM) is also discussed, as is the usefulness of the novel technique of resting-state fMRI. Finally, surgical techniques designed to avoid or reduce language decline in patients at risk are explored.
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http://dx.doi.org/10.1007/s11910-017-0763-9DOI Listing
July 2017

Generalized epilepsy in Baraitser-Winter cerebrofrontofacial syndrome.

Epilepsy Behav Case Rep 2017 18;7:58-60. Epub 2017 Mar 18.

Department of Clinical Neurological Sciences, The University of Western Ontario, London, Canada.

•Baraitser-Winter cerebrofrontofacial syndrome (BWMS) is caused by actin gene mutations.•Key features of BWMS are ptosis, hypertelorism, iris colobomata, and mental retardation.•Generalized epilepsy is seen in half of those with BWMS.•Seizures in BWMS can be absence, myoclonic, tonic, or tonic-clonic.
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http://dx.doi.org/10.1016/j.ebcr.2017.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385583PMC
March 2017

Evolution of epilepsy in hemimegalencephaly from infancy to adulthood: Case report and review of the literature.

Epilepsy Behav Case Rep 2017 1;7:45-48. Epub 2017 Mar 1.

Department of Clinical Neurological Sciences, Western University, Room B10-106, 339 Windermere Road, London, ON N6A 5A5, Canada.

Hemimegalencephaly (HME) is a rare disorder of cortical development with overgrowth of one cerebral hemisphere. Patients have intellectual delay, hemiparesis and severe epilepsy. Drug-resistant epilepsy is often treated with a hemispherectomy. We review the literature on HME natural history and report a 26-year-old man with HME who did not undergo hemispherectomy in childhood with recurrent focal convulsive or non-convulsive status epilepticus. Few patients with HME have been followed into adulthood. Reported adult cases have milder epilepsy or underwent hemispherectomy in childhood. Patients surviving to adulthood have poor outcomes, regardless of treatment method, although seizure burden is improved with hemispherectomy.
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http://dx.doi.org/10.1016/j.ebcr.2017.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369267PMC
March 2017

Resting state functional network disruptions in a kainic acid model of temporal lobe epilepsy.

Neuroimage Clin 2017 3;13:70-81. Epub 2016 Nov 3.

Graduate Program in Neuroscience, Western University, London, Ontario, Canada; Department of Physiology & Pharmacology, Western University, London, Ontario, Canada.

We studied the graph topological properties of brain networks derived from resting-state functional magnetic resonance imaging in a kainic acid induced model of temporal lobe epilepsy (TLE) in rats. Functional connectivity was determined by temporal correlation of the resting-state Blood Oxygen Level Dependent (BOLD) signals between two brain regions during 1.5% and 2% isoflurane, and analyzed as networks in epileptic and control rats. Graph theoretical analysis revealed a significant increase in functional connectivity between brain areas in epileptic than control rats, and the connected brain areas could be categorized as a limbic network and a default mode network (DMN). The limbic network includes the hippocampus, amygdala, piriform cortex, nucleus accumbens, and mediodorsal thalamus, whereas DMN involves the medial prefrontal cortex, anterior and posterior cingulate cortex, auditory and temporal association cortex, and posterior parietal cortex. The TLE model manifested a higher clustering coefficient, increased global and local efficiency, and increased small-worldness as compared to controls, despite having a similar characteristic path length. These results suggest extensive disruptions in the functional brain networks, which may be the basis of altered cognitive, emotional and psychiatric symptoms in TLE.
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http://dx.doi.org/10.1016/j.nicl.2016.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133653PMC
November 2017

Emotional response of a preschooler to her mother's epileptic seizure.

Seizure 2017 Feb 29;45:62-63. Epub 2016 Oct 29.

Department of Clinical Neurological Sciences, Western University, Room B10-106, 339 Windermere Road, London, ON N6A 5A5, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.seizure.2016.10.017DOI Listing
February 2017

Benign mesial temporal lobe epilepsy: A clinical cohort and literature review.

Epilepsy Behav 2016 12 23;65:60-64. Epub 2016 Nov 23.

Epilepsy Program, Department of Clinical Neurological Sciences, Western University, London, Canada; Department of Medical Imaging, Western University, London, Canada; Department of Medical Biophysics, Western University, London, Canada; Department of Psychology, Western University, London, Canada.

Objective: We present a single-center retrospective study of benign mesial temporal lobe epilepsy (bMTLE) between 1995 and 2014.

Methods: Hospital records and clinic charts were reviewed. The clinical, Eelectroencephalographic (EEG), imaging features, and response to treatment with antiepileptic drugs (AEDs) were documented. Patients were included in this study if they were seizure-free for a minimum of 24months with or without an AED.

Results: Twenty-seven patients were identified. There were 19 (70%) females, mean age at first seizure was 32.2 (range: 15-80years). In all patients, seizures were mild, and seizure freedom was readily achieved with the initiation of AED therapy. Sixteen patients (59%) had mesial temporal sclerosis (MTS). In three patients, we attempted to discontinue AED therapy after a prolonged period of remission (5-8years), but all had seizure recurrence within 2 to 4weeks.

Significance: Not all temporal lobe epilepsy is refractory to medication, despite the presence of MTS. Until clinical trials indicate otherwise, surgery is not indicated but life-long medical treatment is advocated.
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http://dx.doi.org/10.1016/j.yebeh.2016.09.017DOI Listing
December 2016

Outcome of temporal lobe epilepsy surgery evaluated with bitemporal intracranial electrode recordings.

Epilepsy Res 2016 11 11;127:324-330. Epub 2016 Aug 11.

Epilepsy Program, Department of Clinical Neurological Sciences, Western University, London, Ontario, Canada. Electronic address:

Background: Temporal lobe epilepsy (TLE) with unclear lateralization may require intracranial implantation of electrodes (IIE). We retrospectively assessed the association between the use of IIE and long-term outcomes in patients undergoing anterior temporal lobectomy (ATL).

Participants And Methods: We retrospectively reviewed the records of 1,032 patients undergoing epilepsy surgery at our center from 1977 to 2006. Patients who underwent ATL were included. Seizure outcome was assessed through final follow-up. Those who underwent scalp and IIE (mostly evaluated with temporal subdural strip electrodes) were compared.

Results: From 497 patients who underwent ATL, 139 did so after IIE placement in the temporal lobes. Mean age at surgery was 32.3±12.3years and median duration of follow-up 24 months (range: 6-36). Fifty-three percent of those evaluated with IIE were seizure-free at their last available visit (vs. 68% evaluated with only scalp EEG, p=0.002). Patients with lesional TLE generally had a better outcome (65.5% seizure free) than those without lesions (56.3%, p=0.093), especially for unilateral TLE diagnosed with IIE. In a multivariate Cox regression analyses adjusted for gender, neuropsychological concordance, pathological findings, and post-operative seizures, bilateral TLE predicted seizure recurrence in IIE patients (HR=2.08, 95% CI: 1.08-4.0, p=0.029).

Conclusions: More than a half of those who undergo IIE in suspected TLE are seizure free after ATL. IIE allows for the identification of surgical candidates.
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http://dx.doi.org/10.1016/j.eplepsyres.2016.08.008DOI Listing
November 2016

Usage of SWI (susceptibility weighted imaging) acquired at 7T for qualitative evaluation of temporal lobe epilepsy patients with histopathological and clinical correlation: An initial pilot study.

J Neurol Sci 2016 Oct 2;369:82-87. Epub 2016 Aug 2.

Imaging Research Laboratories, Robarts Research Institute, Western University, 1151 Richmond St. North, London, Ontario, N6A 5B7, Canada; Department of Medical Imaging, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond St. North, London, Ontario, N6A 5B7, Canada; Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond St. North, London, Ontario, N6A 5B7, Canada. Electronic address:

Objectives: Ultra high field MRI at 7T is able to provide much improved spatial and contrast resolution which may aid in the diagnosis of hippocampal abnormalities. This paper presents a preliminary experience on qualitative evaluation of 7T MRI in temporal lobe epilepsy patients with a focus on comparison to histopathology.

Methods: 7T ultra high field MRI data, using T1-weighted, T2*-weighted and susceptibility-weighted images (SWI), were acquired for 13 patients with drug resistant temporal lobe epilepsy (TLE) during evaluation for potential epilepsy surgery. Qualitative evaluation of the imaging data for scan quality and presence of hippocampal and temporal lobe abnormalities were scored while blinded to the clinical data. Correlation of imaging findings with the clinical data was performed. Blinded evaluation of 1.5T scans was also performed.

Results: On the 7T MRI findings, eight out of 13 cases demonstrated concordance with the clinically suspected TLE. Among these concordant cases, three exhibited supportive abnormal 7T MRI findings which were not detected by the clinical 1.5T MRI. Of the ten cases that progressed to epilepsy surgery, seven showed concordance between 7T MRI findings and histopathology; of these, four cases had hippocampal sclerosis. SWI had the highest concordance with the clinical and histopathological findings. Similar clinical and histopathological concordance was found with 1.5T MRI.

Conclusions: There was moderate and high concordance between the 7T imaging findings with the clinical data and histopathology respectively.
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http://dx.doi.org/10.1016/j.jns.2016.07.066DOI Listing
October 2016