Disrupting the epileptogenic network with stereoelectroencephalography-guided radiofrequency thermocoagulation.

Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) is a treatment option for focal drug-resistant epilepsy. In previous studies, this technique has shown seizure reduction by ≥50% in 50% of patients at 1 year. However, the relationship between the location of the ablation within the epileptogenic network and clinical outcomes remains poorly understood. Seizure outcomes were analyzed for patients who underwent SEEG-guided RF-TC and across subgroups depending on the location of the ablation within the epileptogenic network, defined as SEEG sites involved in seizure generation and spread. Eighteen patients who had SEEG-guided RF-TC were included. SEEG-guided seizure-onset zone ablation (SEEG-guided SOZA) was performed in 12 patients, and SEEG-guided partial seizure-onset zone ablation (SEEG-guided P-SOZA) in 6 patients. The early spread was ablated in three SEEG-guided SOZA patients. Five patients had ablation of a lesion. The seizure freedom rate in the cohort ranged between 22% and 50%, and the responder rate between 67% and 85%. SEEG-guided SOZA demonstrated superior results for both outcomes compared to SEEG-guided P-SOZA at 6 months (seizure freedom p = .294, responder rate p = .014). Adding the early spread ablation to SEEG-guided SOZA did not increase seizure freedom rates but exhibited comparable effectiveness regarding responder rates, indicating a potential network disruption.

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.

Patients with psychogenic nonepileptic seizures and suspected epilepsy: An antiseizure medication reduction study.

OBJECTIVE: To examine predictors of ASM reduction/discontinuation and PNES reduction/resolution in patients with PNES with a confirmed or strong suspicion of comorbid ES. METHODS: A retrospective analysis of 271 newly diagnosed Patients with PNESs admitted to the EMU between May 2000 and April 2008, with follow-up clinical data collected until September 2015. Forty-seven patients met our criteria of PNES with either confirmed or probable ES. RESULTS: Patients with PNES reduction were significantly more likely to have come off all ASMs by the time of final follow-up (21.7 vs. 0.0%, p = 0.018), while documented generalized (i.e. epileptic) seizures were much more common in patients with no reduction in PNES frequency (47.8 vs 8.7%, p = 0.003). When comparing patients that reduced their ASMs (n = 18) with those that did not (n = 27), the former were more likely to have neurological comorbid disorders (p = 0.004). When comparing patients with PNES resolution (n = 12) vs not (n = 34), those with PNES resolution were more likely to have a neurological comorbid disorder (p = 0.027), had a younger age at EMU admission (29.8 vs 37.4, p = 0.05) and a greater proportion of patients with ASMs reduced in EMU (66.7% vs 30.3%, p = 0.028). Similarly, those with ASM reduction had more unknown (non-generalized, non-focal) seizures (33.3 vs 3.7%, p = 0.029). On hierarchical regression analysis, a higher level of education and absence of generalized epilepsy remain as positive predictors of PNES reduction (p = 0.042, 0.015), while the presence of some other neurological disorder besides epilepsy (p = 0.04) and being on more ASMs at EMU admission (p = 0.03) were positive predictors of ASM reduction by final follow-up. SIGNIFICANCE: Patients with PNES and epilepsy have distinct demographic predictors of PNES frequency and ASM reduction by final follow-up. Patients with PNES reduction and resolution had higher level education, less generalized epileptic seizures, younger age at EMU admission, more likely to have presence of a neurological disorder besides epilepsy, and a greater proportion of patients had a reduction in the number of ASMs in the EMU. Similarly, patients with ASM reduction and discontinuation were on more ASMs at initial EMU admission and also were more likely to have a neurological disorder besides epilepsy. The positive relationship between reduction in psychogenic nonepileptic seizure frequency and discontinuation of ASMs at final follow-up elucidates that tapering medication in a safe environment may reinforce psychogenic nonepileptic seizure diagnosis. This can be reassuring to both patients and clinicians, resulting in the observed improvements at the final follow-up.

"Obvious" indications for Neural antibody testing in Epilepsy or Seizures: The ONES checklist.

OBJECTIVE: Numerous predictive scores have been developed to help determine which patients with epilepsy or seizures of unknown etiology should undergo neural antibody testing. However, their diagnostic advantage compared to only performing testing in patients with "obvious" indications (e.g., broader features of autoimmune encephalitis, characteristic seizure semiologies) requires further study. We aimed to develop a checklist that identifies patients who have "obvious" indications for neural antibody testing and to compare its diagnostic performance to predictive scores. METHODS: We developed the "Obvious" indications for Neural antibody testing in Epilepsy or Seizures (ONES) checklist through literature review. We then retrospectively reviewed patients who underwent neural antibody testing for epilepsy or seizures at our center between March 2019 and January 2021, to determine and compare the sensitivity and specificity of the ONES checklist to the recently proposed Antibody Prevalence in Epilepsy and Encephalopathy (APE2)/Antibodies Contributing to Focal Epilepsy Signs and Symptoms (ACES) reflex score. RESULTS: One-hundred seventy patients who underwent neural antibody testing for epilepsy or seizures were identified. Seventy-four of 170 (43.5%) with a known etiology were excluded from sensitivity/specificity analyses; none had a true-positive neural antibody. Of the 96 patients with an unknown etiology, 14 (15%) had a true-positive neural antibody. The proportion of false-positives was significantly higher among patients with a known etiology (3/3, 100%) compared to an unknown etiology (2/16, 13%; p = .01). There was no significant difference of the APE2/ACES reflex score compared to the ONES checklist with regard to sensitivity (93% for both, p > .99) or specificity (71% vs. 78%, p = .18) for true-positive neural antibodies. SIGNIFICANCE: Compared to only performing neural antibody testing in patients with epilepsy or seizures of unknown etiology who have "obvious" indications, predictive scores confer no clear diagnostic advantage. Prespecified definitions of what constitutes a true-positive neural antibody is required in future studies to avoid false-positives that can confound results.

Factors associated with comorbid epilepsy in patients with psychogenic nonepileptic seizures: A large cohort study.

OBJECTIVE: Comorbid epilepsy and psychogenic nonepileptic seizures (PNES) occur in 12-22% of cases and the diagnosis of both simultaneous disorders is challenging. We aimed to identify baseline characteristics that may help distinguish patients with PNES-only from those with comorbid epilepsy. METHODS: We performed a longitudinal cohort study on those patients diagnosed with PNES in our epilepsy monitoring unit (EMU) between May 2001 and February 2011, prospectively followed up until September 2016. Patients were classified into PNES-only, PNES + possible or probable epilepsy, and PNES + definite epilepsy based on the clinical, vEEG, and neuroimaging data. Demographic and basal clinical data were obtained from chart review. Multiple regression models were performed to identify significant predictors of PNES + definite epilepsy, excluding patients with only possible or probable epilepsy for this specific analysis. RESULTS: One-hundred and ninety four patients with PNES-only, 30 with PNES + possible or probable epilepsy and 47 with PNES + definite epilepsy were included. 73.8% were female and the mean age at EMU admission was 37.4 ±â€¯standard deviation 13.5 years. Patients with PNES + definite epilepsy most likely had never worked, had history of febrile seizures, structural brain lesions, developmental disabilities, and maximum reported seizure duration between 0.5 and 2 min. Patients with PNES-only were on fewer anti-seizure medications (ASM), reported more frequently an initial minor head trauma, seizures longer than 10 min, and a higher number of neurological and medical illnesses - being migraine (18.1%), other types of headaches (18.5%), and asthma (15.5%) the most prevalent ones. All p < 0.05. On the hierarchical regression analysis, history of febrile seizures, developmental disabilities, brain lesions, longest reported seizure duration between 0.5 and 2 min, and lack of neurological comorbidity, remained as significant predictors of PNES + epilepsy. The model's performance of a 5-fold cross-validation analysis showed an overall accuracy of 84.7% to classify patients correctly. CONCLUSIONS: Some demographic and clinical characteristics may support the presence of comorbid epilepsy in patients with PNES, being unemployment, the presence of brain lesions, developmental disabilities, history of febrile seizures, seizure duration and lack of comorbid headaches the most relevant ones.

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.

Predicting outcome of patients with psychogenic nonepileptic seizures after diagnosis in an epilepsy monitoring unit.

OBJECTIVE: To identify predictors of Psychogenic NonEpileptic Seizure (PNES) improvement and anti-seizure medication (ASM) discontinuation in patients with PNES only. METHODS: This is a retrospective study of a consecutively enrolled cohort of 271 patients diagnosed with PNES by video-EEG (vEEG) telemetry in our Epilepsy Monitoring Unit (EMU) between May 2000 and February 2010. Patients with any possibility of past or present comorbid epilepsy based on clinical, EEG, and neuroimaging, or less than one year of follow-up after discharge were excluded. RESULTS: A total of 109 subjects were included. The mean age at PNES onset was 33 (range 6-89), mean age at EMU admission was 38.3 (16-89.8), 70.6% were female mean video-EEG length was 6.1 days, and the median time of final follow-up 3.3 (CI 1.6-6.4) years. 51/108 patients (47.2%) reported a PNES decrease and 29 (26.8%) experienced PNES resolution. 59/73 (81.9%) subjects on ASM at the time of EMU admission were able to discontinue them by the final visit. On univariate analysis, patients whose PNES frequency improved were significantly younger at time of admission, more likely married or cohabiting, less likely unemployed, less likely to have migraine, and had a higher frequency of PNES. On hierarchical regression analysis, younger age and employment remained significant predictors of PNES improvement and resolution. Patients who achieved ASM discontinuation had significantly more children and subsequent EMU visits, were less likely to have history of minor head trauma immediately preceding PNES onset and structural brain lesions, experienced a greater reduction of ASMs during the EMU admission, and had a greater improvement of their PNES frequency at the final visit (p ≤ 0.05). On hierarchical regression analysis, higher number of children, absence of structural brain lesions, fewer ASMs at EMU discharge, and improvement of PNES frequency remained significant predictors of ASM discontinuation. CONCLUSION: The outcome of PNES is positively correlated with earlier age of diagnosis in an EMU, especially in patients with better social resources. Furthermore, discontinuation of ASM is more likely if the process is initiated during the EMU stay and in the absence of structural brain lesions.

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

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.

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

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.

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.

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

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.

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

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.

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.

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

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 T1 and diffusion weighting a spoiled gradient sequence was used (41 gradient directions [b = 1000]). For T2 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.

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.

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.

Investigation of hippocampal substructures in focal temporal lobe epilepsy with and without hippocampal sclerosis at 7T.

PURPOSE: To provide a more detailed investigation of hippocampal subfields using 7T magnetic resonance imaging (MRI) for the identification of hippocampal sclerosis in temporal lobe epilepsy (TLE). MATERIALS AND METHODS: Patients (n = 13) with drug-resistant TLE previously identified by conventional imaging as having hippocampal sclerosis (HS) or not (nine without HS, four HS) and 20 age-matched healthy controls were scanned and compared using a 7T MRI protocol. Using a manual segmentation scheme to delineate hippocampal subfields, subfield-specific volume changes and apparent transverse relaxation rate ( R2*) were studied between the two groups. In addition, qualitative assessment at 7T and clinical outcomes were correlated with measured subfield changes. RESULTS: Volumetry of the hippocampus at 7T in HS patients revealed significant ipsilateral subfield atrophy in CA1 (P = 0.001) and CA4+DG (P < 0.001). Volumetry also uncovered subfield atrophy in 33% of patients without HS, which had not been detected using conventional imaging. R2* was significantly lower in the CA4+DG subfields (P = 0.001) and the whole hippocampus (P = 0.029) of HS patients compared to controls but not significantly lower than the group without HS (P = 0.077, P = 0.109). No correlation was found between quantitative volumetry and qualitative assessment as well as surgical outcomes (Sub, P = 0.495, P = 0.567, P = 0.528; CA1, P = 0.104 ± 0.171, P = 0.273, P = 0.554; CA2+CA3, P = 0.517, P = 0.952, P = 0.130 ± 0.256; CA4+DG, P = 0.052 ± 0.173, P = 0.212, P = 0.124 ± 0.204; WholeHipp, P = 0.187, P = 0.132 ± 0.197, P = 0.628). CONCLUSION: These preliminary findings indicate that hippocampal subfield volumetry assessed at 7T is capable of identifying characteristic patterns of hippocampal atrophy in HS patients; however, difficulty remains in using imaging to identify hippocampal pathologies in cases without HS. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;45:1359-1370.

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.

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

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.