Management of patients with epilepsy and Intellectual disabilities in group homes vs. Family Homes: Insights into polypharmacy and seizure characteristics.

OBJECTIVES: This study aimed to investigate the differences in ASMs prescription, seizure characteristics and predictors of polypharmacy in patients with epilepsy and Intellectual disabilities (IDs) residing in group homes versus family homes. METHODS: This nine-year retrospective study analyzed patients with epilepsy and IDs who were admitted to the EMU, epilepsy clinics at LHSC and rehabilitation clinics for patients with IDs at Parkwood Institution. The study included individuals aged 16 years and older residing in either group homes or family homes. Data on demographics, epilepsy characteristics, and ASMs use were collected and analyzed using the Statistical Package for Social Sciences. The study utilized binary logistic regression to identify predictors of polypharmacy in patients with epilepsy and IDs. RESULTS: The study enrolled a total of 81 patients, of which 59.3 % resided in family homes. Group home residents were significantly older (41 vs. 24.5 years; p = 0.0001) and were prescribed more ASMs (3 vs. 2; p = 0.002). Specific ASMs were more common in group homes, including valproic acid (54.5 % vs. 25.0 %), lacosamide (54.5 % vs. 22.9 %), topiramate (33.3 % vs. 14.6 %), and phenytoin (30.3 % vs. 6.2 %). Admission to the EMU was more prevalent in group homes (93.9 % vs. 52.1 %; p = 0.0001). Living in a group home increased the risk of polypharmacy (OR = 10.293, p = 0.005), as did older epilepsy onset age (OR = 1.135, p = 0.031) and generalized or focal & generalized epilepsy (OR = 7.153, p = 0.032 and OR = 10.442, p = 0.025, respectively). SIGNIFICANCE: Our study identified notable differences in the demographic and clinical characteristics of patients with epilepsy and IDs living in group homes versus family homes. Age of epilepsy onset, EMU admissions, epilepsy types, and residency setting were significant predictors of polypharmacy. These findings highlight the need for personalized care strategies and increased awareness of the potential risks associated with polypharmacy.

Lack of spontaneous typical seizures during intracranial monitoring with stereo-electroencephalography.

OBJECTIVE: In the presurgical evaluation of patients with drug-resistant epilepsy (DRE), occasionally, patients do not experience spontaneous typical seizures (STS) during a stereo-electroencephalography (SEEG) study, which limits its effectiveness. We sought to identify risk factors for patients who did not have STS during SEEG and to analyze the clinical outcomes for this particular set of patients. METHODS: We conducted a retrospective analysis of all patients with DRE who underwent depth electrode implantation and SEEG recordings between January 2013 and December 2018. RESULTS: SEEG was performed in 155 cases during this period. 11 (7.2%) did not experience any clinical seizures (non-STS group), while 143 experienced at least one patient-typical seizure during admission (STS group). No significant differences were found between STS and non-STS groups in terms of patient demographics, lesional/non-lesional epilepsy ratio, pre-SEEG seizure frequency, number of ASMs used, electrographic seizures or postoperative seizure outcome in those who underwent resective surgery. Statistically significant differences were found in the average number of electrodes implanted (7.0 in the non-STS group vs. 10.2 in STS), days in Epilepsy Monitoring Unit (21.8 vs. 12.8 days) and the number of cases that underwent resective surgery following SEEG (27.3% vs. 60.8%), respectively. The three non-STS patients (30%) who underwent surgery, all had their typical seizures triggered during ECS studies. Three cases were found to have psychogenic non-epileptic seizures. None of the patients in the non-STS group were offered neurostimulation devices. Five of the non-STS patients experienced transient seizure improvement following SEEG. SIGNIFICANCE: We were unable to identify any factors that predicted lack of seizures during SEEG recordings. Resective surgery was only offered in cases where ECS studies replicated patient-typical seizures. Larger datasets are required to be able to identify factors that predict which patients will fail to develop seizures during SEEG.

Pearls & Oy-sters: Salt and Pepper Sign, PLNTY for Drug-Resistant Epilepsy.

Drug-resistant epilepsy, defined as the failure of 2 or more antiseizure medications to achieve seizure freedom, is responsible for 2/3 of epilepsy cases. Tumors are responsible for up to 15% of all adult onset and up to 6% of childhood onset epilepsies. Among these tumors, commonly known subtypes DNET, ganglioglioma, and low-grade astrocytoma are often suspected. New advances in tumor classification have been made, with genetics playing a key role in tumor classification. Polymorphic low-grade neuroepithelial tumor of the young (PLNTY) is a highly epileptogenic subtype of tumors that may mimic low-grade gliomas but offer pathologic and genetic clues: oligodendroglioma-like cellular components and infiltration patterns and strong CD34-immunopositive stain. In addition, a key finding is radiologic: a unifocal abnormality best seen on MRI brain in FLAIR sequence as the "salt and pepper sign" and calcifications appreciated on CT head.

Roles of fMRI and Wada tests in the presurgical evaluation of language functions in temporal lobe epilepsy.

Surgical treatment of pharmacoresistant temporal lobe epilepsy (TLE) carries risks for language function that can significantly affect the quality of life. Predicting the risks of decline in language functions before surgery is, consequently, just as important as predicting the chances of becoming seizure-free. The intracarotid amobarbital test, generally known as the Wada test (WT), has been traditionally used to determine language lateralization and to estimate their potential decline after surgery. However, the test is invasive and it does not localize the language functions. Therefore, other noninvasive methods have been proposed, of which functional magnetic resonance (fMRI) has the greatest potential. Functional MRI allows localization of language areas. It has good concordance with the WT for language lateralization, and it is of predictive value for postsurgical naming outcomes. Consequently, fMRI has progressively replaced WT for presurgical language evaluation. The objective of this manuscript is to review the most relevant aspects of language functions in TLE and the current role of fMRI and WT in the presurgical evaluation of language. First, we will provide context by revising the language network distribution and the effects of TLE on them. Then, we will assess the functional outcomes following various forms of TLE surgery and measures to reduce postoperative language decline. Finally, we will discuss the current indications for WT and fMRI and the potential usefulness of the resting-state fMRI technique.

Stereo-Encephalographic Presurgical Evaluation of Temporal Lobe Epilepsy: An Evolving Science.

Drug-resistant epilepsy is present in nearly 30% of patients. Resection of the epileptogenic zone has been found to be the most effective in achieving seizure freedom. The study of temporal lobe epilepsy for surgical treatment is extensive and complex. It involves a multidisciplinary team in decision-making with initial non-invasive studies (Phase I), providing 70% of the required information to elaborate a hypothesis and treatment plans. Select cases present more complexity involving bilateral clinical or electrographic manifestations, have contradicting information, or may involve deeper structures as a part of the epileptogenic zone. These cases are discussed by a multidisciplinary team of experts with a hypothesis for invasive methods of study. Subdural electrodes were once the mainstay of invasive presurgical evaluation and in later years most Comprehensive Epilepsy Centers have shifted to intracranial recordings. The intracranial recording follows original concepts since its development by Bancaud and Talairach, but great advances have been made in the field. Stereo-electroencephalography is a growing field of study, treatment, and establishment of seizure pattern complexities. In this comprehensive review, we explore the indications, usefulness, discoveries in interictal and ictal findings, pitfalls, and advances in the science of presurgical stereo-encephalography for temporal lobe epilepsy.

Extraoperative electrical stimulation mapping in epilepsy presurgical evaluation: a proposal and review of the literature.

BACKGROUND: Electrical stimulation mapping (ESM) is an important tool for the localization of the seizure onset zone (SOZ) in patients with medically resistant epilepsy (MRE). ESM is the gold standard for the identification of eloquent cortex in epilepsy surgery candidates. However, there is no standard protocol outlining how to perform ESM, to obtain the most useful information possible. The objective of this study, after reviewing the literature concerning ESM, is to propose a unifying technique to validate reliable data across different centers. METHODS: In this manuscript we summarize this technique from its origin to present, and review protocols used in other centers. We also describe a protocol that has been used in our institution, which utilizes depth electrodes. RESULTS: The most common type of ESM uses a "close-loop" system, bipolar and high frequency stimulation (50 Hz). We propose to use a pulse width of 300 µs, current spanning 1-6 mA in depth electrodes and 1-11 mA in subdural-grids. Stimulation time of 5 s maximum and at least 10 s break in between the stimulations. CONCLUSIONS: ESM is a useful tool for understanding eloquent cortex as well as the epilepsy network, although there is no clear consensus regarding how it should be performed.

Ultra-High Field 7-Tesla Magnetic Resonance Imaging and Electroencephalography Findings in Epilepsy.

PURPOSE: Assessment of patients for temporal lobe epilepsy (TLE) surgery requires multimodality input, including EEG recordings to ensure optimal surgical planning. Often EEG demonstrates abnormal foci not detected on 1.5T MRI. Ultra-high field MRI at 7T provides improved resolution of the brain. We investigated the utility of 7T MRI to detect potential anatomical abnormalities associated with EEG changes. METHODS: Ultra-high field data were acquired on a 7T MRI scanner for 13 patients with history of drug resistant TLE who had had EEG telemetry recordings. Qualitative evaluation of 7T imaging for presence of focal abnormalities detected on EEG was performed. Correlation of 7T MRI findings with EEG recordings of focal slowing or interictal epileptic spikes (IEDs), and seizures was performed. RESULTS: Assessment of 7T MRI demonstrated concordance with TLE as determined by the multidisciplinary team in 61.5% of cases (n = 8). Among these, 3 patients exhibited supportive abnormal 7T MRI abnormalities not detected by 1.5T MRI. In patients who underwent surgery, 72.7% had concordant histopathology findings with 7T MRI findings (n = 8). However, qualitative assessment of 7T images revealed focal anatomical abnormalities to account for EEG findings in only 15.4% of patients (n = 2). Other regions that were found to have localized IEDs in addition to the lesional temporal lobe, included the contralateral temporal lobe (n = 5), frontal lobe (n = 3), and parieto-occipital lobe (n = 2). CONCLUSION: Ultra-high field 7T MRI findings show concordance with clinical data. However, 7T MRI did not reveal anatomical findings to account for abnormalities detected by EEG.

Epilepsy surgery in stroke-related epilepsy.

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

Intracranial Electroencephalographic Monitoring: From Subdural to Depth Electrodes.

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.

Evidence for Cholinergic Dysfunction in Autosomal Dominant Kufs Disease.

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.

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

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.

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

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.

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

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.