Publications by authors named "Richard McLachlan"

48 Publications

Epilepsy surgery in stroke-related epilepsy.

Seizure 2021 May 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
May 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

Effect of lifetime antiepileptic drug treatment history on efficacy and tolerability of adjunctive brivaracetam in adults with focal seizures: Post-hoc analysis of a randomized, placebo-controlled trial.

Epilepsy Res 2020 11 25;167:106369. Epub 2020 May 25.

Bethel Epilepsy Center, Mara Hospital, Maraweg 21, 33617 Bielefeld, Germany. Electronic address:

Objective: To evaluate the efficacy and tolerability of adjunctive brivaracetam (BRV) in adults with focal seizures by the number of lifetime (previous and concomitant) antiepileptic drugs (AEDs).

Methods: Post-hoc analysis of data from N01358 (NCT01261325), a randomized, double-blind, placebo (PBO)-controlled Phase III trial evaluating BRV 100 and 200 mg/day in patients ≥16 years of age with uncontrolled focal seizures. Efficacy and tolerability outcomes were assessed for the 12-week Treatment Period in subgroups of patients with 1-2, 3-4, 5-6, or ≥7 lifetime AEDs.

Results: 764 patients received at least one dose of trial medication (BRV: 503; PBO: 261; Safety Set), of whom 14.3% had 1-2, 20.8% had 3-4, 21.3% had 5-6, and 43.6% had ≥7 lifetime AEDs. In all lifetime AED subgroups, >85% of patients completed the trial. Patients with a higher number of lifetime AEDs had a younger age at epilepsy onset, longer epilepsy duration, and higher baseline seizure frequency. In patients on BRV, 50% responder rates were 49.3%, 44.4%, 47.2% and 27.4% in patients with 1-2 (n = 75), 3-4 (n = 99), 5-6 (n = 108) and ≥7 (n = 219) lifetime AEDs; 75% responder rates were 36.0%, 21.2%, 22.2% and 12.3%. In patients on PBO, 50% responder rates were 35.3%, 25.9%, 20.4% and 15.9% in patients with 1-2 (n = 34), 3-4 (n = 58), 5-6 (n = 54) and ≥7 (n = 113) lifetime AEDs; 75% responder rates were 26.5%, 6.9%, 3.7% and 4.4%. The Kaplan-Meier estimated probability of patients achieving a sustained 50% or 75% response from the first day of treatment was generally higher in patients with a lower number of lifetime AEDs (both in patients on BRV and PBO). In patients on adjunctive BRV, the incidence of drug related treatment-emergent adverse events (TEAEs) was 34.7%, 26.0%, 44.4% and 47.7% in patients with 1-2 (n = 75), 3-4 (n = 100), 5-6 (n = 108) and ≥7 (n = 220) lifetime AEDs; the incidence of discontinuations due to TEAEs was 1.3%, 3.0%, 8.3% and 10.5%.

Conclusions: This post-hoc analysis suggests a numerically higher response to adjunctive BRV in patients with fewer lifetime AEDs. The lowest response was observed in patients with ≥7 lifetime AEDs, although these patients could also benefit from adjunctive BRV treatment. Patients with fewer lifetime AEDs had lower discontinuation of BRV due to TEAEs.
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http://dx.doi.org/10.1016/j.eplepsyres.2020.106369DOI Listing
November 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

Vagus nerve stimulation in patients with therapy-resistant generalized epilepsy.

Epilepsy Behav 2020 10 29;111:107253. Epub 2020 Jun 29.

Epilepsy Program, Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada; Neuroepidemiology Unit, Schulich School of Medicine, Western University, London, ON, Canada.

Background: For patients with generalized epilepsy who do not respond to antiseizure medications, the therapeutic options are limited. Vagus nerve stimulation (VNS) is a treatment mainly approved for therapy-resistant focal epilepsy. There is limited information on the use of VNS on generalized epilepsies, including Lennox-Gastaut Syndrome (LGS) and genetic generalized epilepsy (GGE).

Methods: We identified patients with a diagnosis of generalized epilepsy (including LGS and GGE), who underwent VNS implantation at the London Health Sciences Centre and Western University, London, Ontario, since this treatment became available in Canada in 1997 until July 2018. We assessed response to the treatment, including admissions to hospital and complications.

Results: A total of 46 patients were included in this study with a history of therapy-resistant generalized epilepsy. The mean age at implantation was 24 years (interquartile range [IQR] = 17.8-31 years), significantly younger in the LGS group (p = 0.02) and 50% (n = 23) were female. The most common etiologies were GGE in 37% (n = 17) and LGS in 63% (n = 29). Median follow-up since VNS implantation was 63 months (IQR: 31-112.8 months). Of the LGS group 41.7% (n = 12) of patients had an overall seizure reduction of 50% or more, and 64.7% (n = 11) in the GGE group without statistical significance between the groups. The best response in seizure reduction was seen in generalized tonic-clonic seizures, with a significant reduction in the GGE group (p = 0.043). There was a reduction of seizure-related hospital admissions from 91.3% (N = 42) preimplantation, to 43.5% (N = 20) postimplantation (p < 0.05). The frequency of side effects due to the stimulation was almost equal in both groups (62.1% in LGS and 64.7% in GGE).

Conclusions: Vagus nerve stimulation should be considered as a treatment in patients with therapy-resistant generalized epilepsy, especially in cases with GGE.
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http://dx.doi.org/10.1016/j.yebeh.2020.107253DOI Listing
October 2020

Stereoelectroencephalography Versus Subdural Strip Electrode Implantations: Feasibility, Complications, and Outcomes in 500 Intracranial Monitoring Cases for Drug-Resistant Epilepsy.

Neurosurgery 2020 07;87(1):E23-E30

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

Background: Both stereoelectroencephalography (SEEG) and subdural strip electrodes (SSE) are used for intracranial electroencephalographic recordings in the invasive investigation of patients with drug-resistant epilepsy.

Objective: To compare SEEG and SSE with respect to feasibility, complications, and outcome in this single-center study.

Methods: Patient characteristics, periprocedural parameters, complications, and outcome were acquired from a pro- and retrospectively managed databank to compare SEEG and SSE cases.

Results: A total of 500 intracranial electroencephalographic monitoring cases in 450 patients were analyzed (145 SEEG and 355 SSE). Both groups were of similar age, gender distribution, and duration of epilepsy. Implantation of each SEEG electrode took 13.9 ± 7.6 min (20 ± 12 min for each SSE; P < .01). Radiation exposure to the patient was 4.3 ± 7.7 s to a dose area product of 14.6 ± 27.9 rad*cm2 for SEEG and 9.4 ± 8.9 s with 21 ± 22.4 rad*cm2 for SSE (P < .01). There was no difference in the length of stay (12.2 ± 7.2 and 12 ± 6.3 d). The complication rate was low in both groups. No infections were seen in SEEG cases (2.3% after SSE). The rate of hemorrhage was 2.8% for SEEG and 1.4% for SSE. Surgical outcome was similar.

Conclusion: SEEG allows targeting deeply situated foci with a non-inferior safety profile to SSE and seizure outcome comparable to SSE.
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http://dx.doi.org/10.1093/neuros/nyaa112DOI Listing
July 2020

Seizure Freedom in Temporal Plus Epilepsy Surgery Following Stereo-Electroencephalography.

Can J Neurol Sci 2020 05;47(3):374-381

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

Background: "Temporal plus" epilepsy (TPE) is a term that is used when the epileptogenic zone (EZ) extends beyond the boundaries of the temporal lobe. Stereotactic electroencephalography (SEEG) has been essential to identify additional EZs in adjacent structures that might be part of the temporal lobe/limbic network.

Objective: We present a small case series of temporal plus cases successfully identified by SEEG who were seizure-free after resective surgery.

Methods: We conducted a retrospective analysis of 156 patients who underwent SEEG in 5 years. Six cases had TPE and underwent anterior temporal lobectomy (ATL) with additional extra-temporal resections.

Results: Five cases had a focus on the right hemisphere and one on the left. Three cases were non-lesional and three were lesional. Mean follow-up time since surgery was 2.9 years (SD ± 1.8). Three patients had subdural electrodes investigation prior or in addition to SEEG. All patients underwent standard ATL and additional extra-temporal resections during the same procedure or at a later date. All patients were seizure-free at their last follow-up appointment (Engel Ia = 3; Engel Ib = 2; Engel Ic = 1). Pathology was nonspecific/gliosis for all six cases.

Conclusion: TPE might explain some of the failures in temporal lobe epilepsy surgery. We present a small case series of six patients in whom SEEG successfully identified this phenomenon and surgery proved effective.
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http://dx.doi.org/10.1017/cjn.2020.26DOI Listing
May 2020

Position Statement on the Use of Medical Cannabis for the Treatment of Epilepsy in Canada.

Can J Neurol Sci 2019 11;46(6):645-652

Cumming School of Medicine, University of Calgary, Alberta Children's Hospital, Calgary, Alberta, Canada (JPA); UBC Department of Pediatrics, Division of Neurology, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada (CB); IWK Health Centre, Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada (PMB); Epilepsy Program, Department of Clinical Neurological Sciences and Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada (JGB); Alberta Children's Hospital, Departments of Neurosciences and Pharmacy, Calgary, Alberta, Canada (CSC); Division of Pediatric Neurology, Director of The Epilepsy Program, British Columbia's Children's Hospital, Vancouver, British Columbia, Canada (MBC); The Hospital for Sick Children, Department of Pharmacy, Ontario, Canada (MVTDG); Departments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada (PF); Past President CEA, Halifax, Nova Scotia, Canada (DF); Division of Pediatric Neurology, Department of Pediatrics, University of Saskatchewan, Cannabinoid Research Initiative of Saskatchewan, Saskatoon, Saskatchewan, Canada (RJH); Division of Neurology, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver General Hospital, Vancouver, British Columbia, Canada (MJ); Icahn School of Medicine at Mount Sinai, Department of Neurology and Population Health Science and Policy, New York, NY, USA (NJ); Nurse Practitioner Stollery Childrens Hospital, University of Alberta, Edmonton, Alberta, Canada (LLJ); Faculty of Medicine, Department of Neurosciences and Department of Social and Preventative Medicine, Université de Montréal, Clinician Researcher, Centre de Recherche du CHUM (CRCHUM), Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada (MRK); Department of Clinical Neurological Sciences, Division of Neurosurgery, Western University,Ontario, Canada (JCL); Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada (BM); Western University, London, Ontario, Canada (RSM); Department of Internal Medicine, Section of Neurology, University of Manitoba, Winnipeg, Manitoba, Canada (MCN); Centre Hospitalier de l'Université de Montréal Division of Neurology, Montréal, Quebec, Canada (DKN); Krembil Research Institute, University Health Network, Department of Medicine (Neurology), University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada (AYR); Alberta Children's Hospital Research Institute, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Section of Paediatric Neurology, Alberta Children's Hospital, Calgary, Alberta, Canada (JMR); The Hospital for Sick Children, University of Toronto, Department of Pediatrics, Toronto, Ontario, Canada (OCS); University of Saskatchewan, Saskatchewan Epilepsy Program, Division of Neurology, Department of Medicine Royal University Hospital, Saskatoon, Saskatchewan, Canada (JFTZ); The Hospital for Sick Children, Toronto, Ontario, Canada (LW); The Hospital for Sick Children, Division of Neurology, Toronto, Ontario, Canada (MMZ).

In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
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http://dx.doi.org/10.1017/cjn.2019.282DOI Listing
November 2019

Surgical treatment of extra-hypothalamic epilepsies presenting with gelastic seizures.

Epileptic Disord 2019 Jun;21(3):307-317

Epilepsy Program, Department of Clinical Neurological Sciences, London Health Sciences Centre, University Hospital, London, ON, Canada.

We provide an overview of the surgical outcome of extra-hypothalamic epilepsies with gelastic seizures based on an original case report and a summary of the literature. Twenty-two articles providing information on the outcome of resective surgery in 39 patients with extra-hypothalamic gelastic seizures from the temporal (19 patients) or frontal lobe (20 patients) were selected. We add another case of temporal lobe gelastic seizures to the literature with a video demonstrating the mirthful component of this patient's laughing seizures. Drug-refractory cases of gelastic seizures from the temporal or frontal lobes are amenable to surgical treatment following thorough investigation with imaging, as well as scalp and intracranial EEG.
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http://dx.doi.org/10.1684/epd.2019.1076DOI Listing
June 2019

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

Electroencephalographic and Electrocardiographic Effect of Intravenous Lacosamide in Refractory Focal Epilepsy.

J Clin Neurophysiol 2018 Sep;35(5):365-369

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

Purpose: Lacosamide selectively enhances slow inactivation of voltage-gated sodium channels to achieve seizure reduction. We studied the effect of intravenous lacosamide given as one of three single doses on EEG and electrocardiogram, as well as its tolerability in patients with drug-resistant epilepsy.

Methods: This Canadian, investigator-initiated, multicenter, double-blind study recruited patients with refractory focal epilepsy admitted to a seizure monitoring unit. Participants received a loading dose of 100, 200, or 400 mg lacosamide over 30 minutes during continuous monitoring by video-EEG and 12-lead electrocardiogram. The number of interictal spikes, frequency and quantity of background EEG rhythms, corrected QT interval (QTc), PR interval, heart rate (HR), blood pressure, and respiration rate during 60 minutes before the administration were compared with 60 minutes after the infusion. We documented any adverse event during and after the infusion.

Results: Seventy-one patients completed the study. There was a significant decrease in interictal spikes (P = 0.039) and decreased frequency of the alpha rhythm (P = 0.003). No significant difference in beta, theta, and delta frequency or amount was noted. There were significant increases in PR interval (153.4-155.8 ms, P = 0.031) and HR (73.4-75.5 bpm, P = 0.022), but QTc, blood pressure, and respiration rate were not affected. Twelve patients (16.9%) experienced transient and mild adverse events, mainly dizziness and leg tingling. More adverse events occurred with 400 mg lacosamide than with the lower doses (P = 0.048).

Conclusions: Intravenous lacosamide is effective in decreasing interictal spikes. Despite a small effect on EEG and electrocardiogram rhythms, it is well tolerated with no serious adverse events.
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http://dx.doi.org/10.1097/WNP.0000000000000479DOI 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

Six adult patients with septo-optic dysplasia and drug-resistant epilepsy: Clinical findings and course.

Epilepsy Behav Case Rep 2017 19;8:73-84. Epub 2017 Apr 19.

Department of Neuroscience, London health science center, Western University, London, Ontario, Canada.

Septo-optic dysplasia (SOD) is a rare disorder associated with optic nerve hypoplasia, pituitary abnormalities and agenesis/dysgenesis of midline brain structures including the septum pellucidum and corpus callosum. Though sometimes associated with drug-resistant epilepsy, this association has not been well studied. We report six SOD patients with associated malformation of cortical development (MCD) and drug-resistant epilepsy who underwent video-EEG telemetry at our centre between 1998 and 2016 for drug-resistant epilepsy. ‬Three then underwent surgery; right temporal neocortical resection, right functional hemispherectomy and placement of a vagus nerve stimulator. Clinical findings and the patients' ultimate courses are discussed.
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http://dx.doi.org/10.1016/j.ebcr.2017.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678750PMC
April 2017

Orbitofrontal epilepsy: Case series and review of literature.

Epilepsy Behav 2017 11 18;76:32-38. Epub 2017 Sep 18.

Division of Neurology, CHUM Notre-Dame, Université de Montréal, Québec, Canada. Electronic address:

Background: Orbitofrontal epilepsy (OFE) is less known and is poorly characterized in comparison with temporal lobe epilepsy, partly because it is rare and possibly because it is unrecognized and therefore underestimated.

Objective: This paper aimed to better characterize seizure semiology, presurgical findings, and surgical outcomes in patients with OFE.

Methods: We retrospectively reviewed all confidently established OFE cases from six Canadian epilepsy monitoring units between 1988 and 2014, and in the literature between 1972 and 2017. Inclusion criteria were identification of an epileptogenic lesion localized in the OFC or if the patient was seizure-free after surgical removal of the OFC in nonlesional cases.

Results: Sixteen cases were identified from our databases. Fifty percent had predominantly sleep-related seizures; 56% had no aura (the remaining had nonspecific or vegetative auras), and 62.5% featured hypermotor (mostly hyperkinetic) behaviors. Interictal epileptiform discharges over frontal and temporal derivations always allowed lateralization. Magnetic resonance imaging (MRI) identified an orbitofrontal lesion in 8/16, positron emission tomography (PET) identified a hypometabolism extending outside the orbital cortex in 4/9, ictal single-photon emission computed tomography (SPECT) identified an orbital hyperperfusion in 1/5, magnetoencephalography (MEG) identified lateral orbital sources in 2/4, and intracranial electroencephalography (EEG) identified an orbitofrontal onset in 9/10. Fourteen patients underwent surgery, all reaching a favorable outcome (71.4% Engel 1; 28.6% Engel 2; mean FU=5.6years). Pre- and postoperative neuropsychological assessments revealed heterogeneous findings. Our review of literature identified 71 possible cases of OFE, 32 with confident focus localization. Extracted data from these cumulated cases supported observations made from our case series.

Conclusions: Orbitofrontal epilepsy should be suspected with sleep-related, hyperkinetic seizures with no specific aura, and frontotemporal interictal discharges. Several patients have nonmotor seizures with or without auras which may resemble temporal lobe seizures. Postoperative seizure outcome was favorable, but there is inherent bias as we only included patients with a seizure-free outcome if the MRI was negative. A larger study is required to address identified gaps in knowledge such as identifying discriminative features between medial and lateral OFE, evaluating the value of more recent diagnostic tools, and assessing the neuropsychological outcome of orbital epilepsy surgery.
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http://dx.doi.org/10.1016/j.yebeh.2017.08.038DOI Listing
November 2017

Antiepileptic drugs and hyponatremia in older adults: Two population-based cohort studies.

Epilepsia 2016 12 29;57(12):2067-2079. Epub 2016 Nov 29.

Department of Epidemiology & Biostatistics, Western University, London, Ontario, Canada.

Objective: To examine the 30-day risk of hospitalization with hyponatremia associated with carbamazepine, valproic acid (V), phenytoin (P), or topiramate (T) use compared to nonuse in the outpatient setting among older adults.

Methods: We conducted two population-based, retrospective cohort studies in Ontario, Canada, between 2003 and 2015 using administrative health care databases of older adults. The first study compared carbamazepine users to a propensity-score matched group of antiepileptic drug nonusers, whereas the second compared V-P-T users to a propensity-score matched group of antiepileptic nonusers. The primary outcome was hospitalization with hyponatremia within 30 days of an antiepileptic prescription.

Results: The baseline characteristics between matched groups were similar in both cohorts. Carbamazepine use versus nonuse was associated with a higher 30-day risk of hospitalization with hyponatremia (82/21,191 [0.39%] versus 30/63,573 [0.05%]; relative risk [RR] 8.20, 95% confidence interval [CI] 5.40-12.46). Similarly, V-P-T use versus nonuse was associated with a higher 30-day risk of hospitalization with hyponatremia (34/20,155 [0.17%] versus 26/40,310 [0.06%]; RR 2.62, 95% CI 1.57-4.36).

Significance: Older adults prescribed carbamazepine and V-P-T have a higher risk of being hospitalized with hyponatremia compared to other adults with similar indicators of baseline health who were not prescribed antiepileptic drugs. Physicians should be mindful of this risk; when a patient presents to a hospital with symptomatic hyponatremia these drugs should be considered as potential causes.
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http://dx.doi.org/10.1111/epi.13593DOI Listing
December 2016

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

Marijuana use in adults admitted to a Canadian epilepsy monitoring unit.

Epilepsy Behav 2016 10 30;63:73-78. Epub 2016 Aug 30.

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

Objectives: Epidemiologic evidence supporting antiseizure properties of cannabis is limited and controversial. We determined the prevalence of marijuana use and its perceived effects in patients with and without epilepsy.

Methods: Information was collected over 14months from consecutive adult patients admitted to an epilepsy monitoring unit using a 27-item anonymous questionnaire. Patients with cognitive impairment unable to understand the questions or give informed consent and readmissions were not recruited. Subjects were divided into 4 groups, those with epileptic seizures, those with psychogenic nonepileptic seizures (PNES), those with both epileptic and PNES, and those with other nonepileptic events. Patients with exclusively epileptic seizures were compared with those with exclusively PNES.

Results: From 310 patients, 18 undiagnosed cases were excluded leaving a cohort of 292 patients with median age 35 (range: 27-49) years; 57.2% female. Epilepsy was documented in 190 (65.1%), PNES in 64 (21.9%), and both types of seizures in 26 (8.9%). Median duration of seizure disorder was longer (2 [1-9] vs. 13 [5.7-25] years; p<0.001) and seizure frequency lower (daily or weekly in 62.3% vs. 44.9%; p=0.03) in patients with epilepsy compared with those in patients with PNES. Overall, 166 (57%) had tried marijuana, and 36.2% used it over the past year. Utilization was 57.1% in sole epilepsy and 64.1% in sole PNES, but daily use was more likely in epilepsy (59% vs. 33.3%). Estimated mean dose was 1g/day. Marijuana use was associated with tobacco smoking (p<0.001) but not alcohol use. Eight patients used other street drugs. Improvement in seizures was perceived by 84% in those with epilepsy and 72.7% in those with PNES. In the 2 groups, stress was decreased in 84.9% and 88%, sleep improved in 77.3% and 88%, and memory/concentration was better in 32% and 28%, respectively. Antiepileptic drug side effects were decreased in 53.2% of marijuana users. Perceived effect on epileptic seizures correlated with effect on stress (r=0.35, p=0.004). Adverse effects of marijuana were mild and reported in 30.7% but included possible seizure precipitation in 5 patients with epilepsy.

Significance: Patients with uncontrolled epilepsy or nonepileptic events had a high rate of marijuana use with associated perceived improvements in seizure control, stress, sleep, and drug side effects. Stress reduction may contribute to the perceived impact of marijuana on seizures and nonepileptic events in adults.
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http://dx.doi.org/10.1016/j.yebeh.2016.08.002DOI Listing
October 2016

Coprolalia as a manifestation of epileptic seizures.

Epilepsy Behav 2016 07 16;60:99-106. Epub 2016 May 16.

Department of Clinical Neurological Sciences, Western University, London, Ontario, Canada; Department of Physiology and Pharmacology, 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: The aim of this study was to investigate the lateralizing and localizing value of ictal coprolalia and brain areas involved in its production.

Methods: A retrospective search for patients manifesting ictal coprolalia was conducted in our EMU database. Continuous video-EEG recordings were reviewed, and EEG activity before and during coprolalia was analyzed using independent component analysis (ICA) technique and was compared to the seizures without coprolalia among the same patients.

Results: Nine patients were evaluated (five women), eight with intracranial video-EEG recordings (icVEEG). Four had frontal or temporal lesions, and five had normal MRIs. Six patients showed impairment in the language functions and five in the frontal executive tasks. Two hundred six seizures were reviewed (60.7% from icVEEG). Ictal coprolalia occurred in 46.6% of them, always associated with limbic auras or automatisms. They arose from the nondominant hemisphere in five patients, dominant hemisphere in three, and independently from the right and left hippocampus-parahippocampus in one. Electroencephalographic activity always involved orbitofrontal and/or mesial temporal regions of the nondominant hemisphere when coprolalia occurred. Independent component analysis of 31 seizures in seven patients showed a higher number of independent components in the nondominant hippocampus-parahippocampus before and during coprolalia and in the dominant lateral temporal region in those seizures without coprolalia (p=0.009). Five patients underwent surgery, and all five had an ILAE class 1 outcome.

Significance: Ictal coprolalia occurs in both males and females with temporal or orbitofrontal epilepsy and has a limited lateralizing value to the nondominant hemisphere but can be triggered by seizures from either hemisphere. It involves activation of the paralimbic temporal-orbitofrontal network.
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http://dx.doi.org/10.1016/j.yebeh.2016.04.040DOI Listing
July 2016

Marijuana: a time-honored but untested treatment for epilepsy.

Can J Neurol Sci 2015 Mar 26;42(2):88-91. Epub 2015 Feb 26.

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

The biology of the endocannabinoid system in the brain provides a possible basis for a beneficial pharmacological effect of marijuana on seizures. However, evidence for efficacy of cannabis treatment of epilepsy is anecdotal because no acceptable randomized controlled trials have been done. Proper dosage and means of administration remain unknown. Cannabis is safer than other controlled substances, including tobacco or alcohol, and appears to be relatively safe compared with most pharmaceuticals used to treat epilepsy. This is a review of this topic from a Canadian perspective.
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http://dx.doi.org/10.1017/cjn.2015.11DOI Listing
March 2015

Canadian epileptologists' counseling of drivers amidst guideline inconsistencies.

Can J Neurol Sci 2014 Jul;41(4):413-20

Background: Epilepsy is a common medical condition for which physicians perform driver fitness assessments. The Canadian Medical association (CMA) and the Canadian Council of Motor transportation administrators (CCMTA) publish documents to guide Canadian physicians' driver fitness assessments.

Objectives: We aimed to measure the consistency of driver fitness counseling among epileptologists in Canada, and to determine whether inconsistencies between national guidelines are associated with greater variability in counseling instructions.

Methods: We surveyed 35 epileptologists in Canada (response rate 71%) using a questionnaire that explored physicians' philosophies about driver fitness assessments and counseling practices of seizure patients in common clinical scenarios. Of the nine scenarios, CCMTA and CMA recommendations were concordant for only two. Cumulative agreement for all scenarios was calculated using Kappa statistic. Agreement for concordant (two) vs. discordant (seven) scenarios were split at the median and analyzed using the Wilcoxon signed rank sum test.

Results: Overall the agreement between respondents for the clinical scenarios was not acceptable (Kappa=0.28). For the two scenarios where CMa and CCMta guidelines were concordant, specialists had high levels of agreement with recommendations (89% each). A majority of specialists disagreed with CMa recommendations in three of seven discordant scenarios. The lack of consistency in respondents' agreement attained statistical significance (p<0.001).

Conclusions: Canadian epileptologists have variable counseling practices about driving, and this may be attributable to inconsistencies between CMa and CCMta medical fitness guidelines. This study highlights the need to harmonize driving recommendations in order to prevent physician and patient confusion about driving fitness in Canada.
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http://dx.doi.org/10.1017/s0317167100018424DOI Listing
July 2014

Subjective memory evaluation before and after temporal lobe epilepsy surgery.

PLoS One 2014 1;9(4):e93382. Epub 2014 Apr 1.

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

Subjective memory (SM), a self-evaluation of memory, in contrast to objective memory (OM) measured by neuropsychological testing, is less well studied in patients with epilepsy. We assessed SM before and after temporal lobectomy. The Frequency of Forgetting 10 scale (FOF-10), developed to evaluate SM in dementia, was given before and one year after temporal lobectomy. Reliability and validity for use in epilepsy were first assessed. Measures of depression (CES-D) and neuroticism (PANAS) were done before and after surgery as well as complete neuropsychological assessment of OM. Correlation analysis between FOF-10 results and all the other variables was implemented. In 48 patients the FOF-10 was reliable and valid showing high internal consistency in all items (Cronbach's alpha >0.82) and high reproducibility (p<0.01). The FOF-10 also correlated with the memory assessment clinics self rating scale (MAC-S) (p<0.01). FOF-10 scores improved or were unchanged postoperatively in 28 patients (58%) and worsened in 20 (42%). The FOF-10 did not significantly correlate with memory scores from neuropsychological testing but did correlate with perceived word finding difficulty (p<0.001) and postoperative depression (p<0.05). A reduction in number of antiepileptic drugs (AEDs) after surgery distinguished those with improved postoperative SM. No correlation was found between SM and neuroticism, side of surgery or number of seizures. The FOF-10 is a brief and reliable measure of subjective memory in patients with epilepsy. Perceived memory impairment reflects more emotional state, language problems and quantity of AEDs than actual defects in memory function. These results would potentially be useful in presurgical counselling and management of memory issues after temporal lobe surgery.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093382PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972133PMC
December 2015

Temporal lobectomy with delayed amnesia following a new lesion on the other side.

Can J Neurol Sci 2014 Mar;41(2):220-5

Purpose: To describe a delayed severe complication of temporal lobectomy for intractable epilepsy.

Method: A case of amnesia occurring 24 years after surgery is described and five similar cases from the literature reviewed.

Results: Mean age at surgery (5 right) was 40 years (19-62 years), 3 female. Four of five tested had impaired visual and verbal memory preoperatively but not sufficient to contraindicate surgery. Pathology was mesial temporal sclerosis in 3, 1 cavernoma, 1 dysembryoplastic neuroepithelial tumor (DNET) and 1 normal. Postoperatively, four were seizure free 3-12 years off medication and two continued with seizures. There was no unexpected postoperative memory change until incapacitating anterograde amnesia developed 1-24 years after surgery. In five patients, including ours, this followed definite or possible status epilepticus with new mesial temporal sclerosis on the opposite side in the four that were investigated by MRI. One patient developed a glioblastoma in the opposite temporal lobe.

Conclusion: Continuing or late recurrence of seizures from the remaining temporal lobe after temporal lobectomy can result in incapacitating amnesia if status epilepticus occurs. Other new lesions on the opposite side to surgery can have the same effect.
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http://dx.doi.org/10.1017/s0317167100016619DOI Listing
March 2014

Childhood-onset nonprogressive chronic encephalitis.

Epilepsy Behav 2014 Feb 22;31:85-90. Epub 2013 Dec 22.

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. Electronic address:

Purpose: The purpose of this study was to describe a series of patients with pathologically proven chronic encephalitis who had a nonprogressive course during a long follow-up, suggestive of a "benign" variant of Rasmussen's encephalitis (RE).

Methods: Four patients who were referred to our Comprehensive Epilepsy Program at London Health Science Centre in London, Ontario, were diagnosed with chronic encephalitis on a pathological basis after epilepsy surgery to treat their partial-onset seizures.

Results: None of our four cases followed the typical course of RE despite their childhood-onset seizures between ages 2 and 12years. One was preceded by a mild head trauma and fever at onset. None had epilepsia partialis continua (EPC). Their long-term follow-up revealed a nonprogressive form of the syndrome with respect to the neurological examination, EEG, MRI, and neuropsychological findings.

Conclusion: These cases extend the spectrum of childhood-onset intractable epilepsy with chronic encephalitis to include nonprogressive variants of RE. The absence of EPC may be a prognostic indicator of a nonprogressive course.
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http://dx.doi.org/10.1016/j.yebeh.2013.11.005DOI Listing
February 2014

45-year-old female with a 25 year history of seizures.

Can J Neurol Sci 2013 Jan;40(1):85-8

Department of Pathology, Division of Neuropathology, London Health Sciences Centre and the University of Western Ontario, London, Ontario, Canada.

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http://dx.doi.org/10.1017/s0317167100013007DOI Listing
January 2013

Levetiracetam induced angioedema in a patient with previous anticonvulsant hypersensitivity reaction to phenytoin and lamotrigine.

Seizure 2012 Jun 21;21(5):407-8. Epub 2012 Apr 21.

Umm AlQura University, Makkah, Saudi Arabia.

Allergic reactions to antiepileptic drugs in the form of skin rash are not uncommon but angioedema, an acute life threatening reaction is rare. Angioedema has been reported with the use of oxcarbazepine and carbamazepine. We report a case of a 33-year-old woman with focal epilepsy who developed angioedema following levetiracetam monotherapy. The patient had previous skin rashes with both phenytoin and lamotrigine. Levetiracetam was stopped and she improved after treatment with norepinephrine, antihistamines and corticosteroids.
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http://dx.doi.org/10.1016/j.seizure.2012.03.007DOI Listing
June 2012

Early treatment of a progressive Rasmussen's like syndrome with ganciclovir.

Can J Neurol Sci 2011 Mar;38(2):296-8

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

Background: Escalating focal sensorimotor seizures, progressive neurologic deficit and cognitive decline with associated typical magnetic resonance imaging (MRI) findings or pathological confirmation constitute the syndrome of Rasmussen's encephalitis.

Methods: Three patients with this clinical scenario had long-term follow-up after being given the antiviral drug ganciclovir 10 mg/kg/day IV for ten days within one to three months of disease onset.

Results: Seizures occurred at least hourly and were localized to the Rolandic region. The MRIs were normal in one patient and in two showed changes consistent with ongoing seizures. Two patients, one whose short-term outcome was reported previously, had immediate and sustained cessation of seizures and resolution of their neurologic deficit. One patient with seizures from both hemispheres did not respond and went on to hemispherectomy that confirmed chronic encephalitis. Seizures continued in five other patients treated 6 to 72 months after disease onset.

Conclusion: The sustained seizure control after ganciclovir in two of three patients suggests this drug may be effective when given early in the course of this subacute intractable focal epilepsy syndrome.
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http://dx.doi.org/10.1017/s0317167100011495DOI Listing
March 2011

Julius Caesar's late onset epilepsy: a case of historic proportions.

Can J Neurol Sci 2010 Sep;37(5):557-61

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

This is a case report of Julius Caesar's epilepsy that onset when he was 54-years-old. The differential diagnosis of late onset epilepsy is discussed and the rationale presented for concluding from the clinical presentation that the cause was neurocysticercosis. That this man's disease and its consequences altered the course of history is a very real possibility.
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http://dx.doi.org/10.1017/s0317167100010696DOI Listing
September 2010

Ictal whistling: a rare automatism during temporal lobe seizures.

Epileptic Disord 2010 Jun 18;12(2):133-5. Epub 2010 May 18.

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

One of the most unusual ictal automatisms reported is whistling. Two patients, both males, are described who had prominent whistling as a component of their complex partial seizures. Both had temporal lobe epilepsy with resolution of seizures after a temporal lobectomy. Ictal whistling appears to localize to the temporal lobe but may not be useful for lateralization.
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http://dx.doi.org/10.1684/epd.2010.0309DOI Listing
June 2010
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