Superior Verbal Memory Outcome After Stereotactic Laser Amygdalohippocampotomy

Objective: To evaluate declarative memory outcomes in medically refractory epilepsy patients who underwent either a highly selective laser ablation of the amygdalohippocampal complex or a conventional open temporal lobe resection.Methods: Post-operative change scores were examined for verbal memory outcome in epilepsy patients who underwent stereotactic laser amygdalohippocampotomy (SLAH: n = 40) or open resection procedures (n = 40) using both reliable change index (RCI) scores and a 1-SD change metric.Results: Using RCI scores, patients undergoing open resection (12/40, 30.0%) were more likely to decline on verbal memory than those undergoing SLAH (2/40 [5.0%], p = 0.0064, Fisher's exact test). Patients with language dominant procedures were much more likely to experience a significant verbal memory decline following open resection (9/19 [47.4%]) compared to laser ablation (2/19 [10.5%], p = 0.0293, Fisher's exact test). 1 SD verbal memory decline frequently occurred in the open resection sample of language dominant temporal lobe patients with mesial temporal sclerosis (8/10 [80.0%]), although it rarely occurred in such patients after SLAH (2/14, 14.3%) (p = 0.0027, Fisher's exact test). Memory improvement occurred significantly more frequently following SLAH than after open resection.Interpretation: These findings suggest that while verbal memory function can decline after laser ablation of the amygdalohippocampal complex, it is better preserved when compared to open temporal lobe resection. Our findings also highlight that the dominant hippocampus is not uniquely responsible for verbal memory. While this is at odds with our simple and common heuristic of the hippocampus in memory, it supports the findings of non-human primate studies showing that memory depends on broader medial and lateral TL regions.

Radiological identification of temporal lobe epilepsy using artificial intelligence: a feasibility study

Temporal lobe epilepsy is associated with magnetic resonance imaging (MRI) findings reflecting underlying mesial temporal sclerosis. Identifying these MRI features is critical for the diagnosis and management of temporal lobe epilepsy. To date, this process relies on visual assessment by highly trained human experts (e.g. neuroradiologists, epileptologists). Artificial intelligence is increasingly recognized as a promising aid in the radiological evaluation of neurological diseases, yet its applications in temporal lobe epilepsy have been limited. Here, we applied a convolutional neural networks to assess the classification accuracy of temporal lobe epilepsy based on structural MRI. We demonstrate that convoluted neural networks can achieve high accuracy in the identification of unilateral temporal lobe epilepsy cases even when the MRI had been originally interpreted as normal by experts. We show that accuracy can be potentiated by employing smoothed gray matter maps and a direct acyclic graphs approach. We further discuss the foundations for the development of computer-aided tools to assist with the diagnosis of epilepsy.

TREATMENT-RESISTANT EPILEPSY AND TREATMENT-RESISTANT SCHIZOPHRENIA; A REAL CHALLENGE FOR THE PSYCHIATRIC TEAM

Schizophrenia and epilepsy may exist together, but it is very rare to have a resistant form of both illnesses in one patient. We present a case report of a 49-year-old woman who was managed at our psychiatric facility suffering from treatment-resistant schizophrenia and epilepsy. She presented with suspiciousness, fearfulness and with a belief that people in the hostel wanted to harm her and were putting hair on her bed. She was also having recurrent seizures weekly due to her refractory epilepsy secondary to mesial temporal sclerosis. She was non-compliant with medication and refused surgical management of mesial temporal sclerosis. Whilst in the hospital was on five antiepileptic drugs prescribed by the neurology team and these control the seizures. Olanzapine and paliperidone depot was used for schizophrenia which had a partial response. Clozapine was notconsidered in view of her severe uncontrolled epilepsy. Concerns were raised regarding her capacity to decide about treatment options. The possibility of an organic cause for both schizophrenia and epilepsy were considered.

A meta-analysis of case-reports and case-series of dacrystic epilepsy in children and adolescence

This meta-analysis aimed to advance our knowledge about dacrystic epilepsy in children in the present time. PubMed searches for peer-reviewed case reports and case series were conducted using the keywords “dacrystic epilepsy”, “dacrystic seizures”, “crying epilepsy”, “ictal crying”, “crying seizures”. The databases were developed in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The author collected relevant information to characterise the study population including clinical outcome. Eleven studies out of 353 citations between 1998 and 26 May 2021 met the inclusion criteria, including both single cases and series pertaining to dacrystic epilepsy. Eight case reports and three case series were eligible for this meta-analysis and included twenty one cases. The seizure patterns were dacrystic seizures alone in seven cases (33%), and a combination of dacrystic seizures and gelastic seizures in fourteen cases (67%). Neuroimaging revealed structural abnormality in 95% cases. Hypothalamic hamartoma was found in most of the cases (79%) with combined dacrystic seizures and gelastic seizures, whereas it was found in one case (16%) with dacrystic seizures alone. The other underlying lesions in children with dacrystic seizures alone were subependymal nodules and cortical hamartomas (17%), left mesial temporal sclerosis (33%), and cortical dysplasia (17%). Regarding outcome, antiepileptic drugs alone achieved seizure freedom in four cases (22%) only and others (78%) were difficult to treat cases excluding three cases where treatments were not mentioned. Six cases underwent surgical intervention and two cases received ablative radiotherapy. Lesional dacrystic epilepsy is predominant and pharmaco-resistant in children. However, antiepileptic drugs lead to achieving seizure remission in few cases.

Ordinal regression increases statistical power to predict epilepsy surgical outcomes

Objective: Studies of epilepsy surgery outcomes are often small and thus underpowered to reach statistically valid conclusions. We hypothesized that ordinal logistic regression would have greater statistical power than binary logistic regression when analyzing epilepsy surgery outcomes. Methods: We reviewed 10 manuscripts included in a recent meta-analysis which found that mesial temporal sclerosis (MTS) predicted better surgical outcome after a stereotactic laser amygdalohippocampectomy (SLAH). We extracted data from 239 patients from eight studies which reported four discrete Engel surgical outcomes after SLAH, stratified by the presence or absence of MTS. Results The rate of freedom from disabling seizures (Engel I) was 64.3% (110/171) for patients with MTS compared to 44.1% (30/68) without MTS. The statistical power to detect MTS as a predictor for better surgical outcome after a SLAH was 29% using ordinal regression, which was significantly more than the 13% power using binary logistic regression (paired t-test, p<0.001). Only 120 patients are needed to achieve 80% power to detect MTS as a predictor using ordinal regression, compared to 210 patients that are needed to achieve 80% power using binary logistic regression. Conclusion: Ordinal regression should be considered when analyzing ordinal outcomes (such as Engel surgical outcome), especially for datasets with small sample sizes.

Outcomes of epilepsy surgery in the older population: not too old, not too late

OBJECTIVE The prevalence of epilepsy in the older adult population is increasing. While surgical intervention in younger patients is supported by level I evidence, the safety and efficacy of epilepsy surgery in older individuals is less well established. The aim of this study was to evaluate seizure freedom rates and surgical outcomes in older epilepsy patients. METHODS The authors’ institutional electronic database was queried for patients older than 50 who had undergone epilepsy surgery during 2002–2018. Cases were grouped into 50–59, 60–69, and 70+ years old. Seizure freedom at the last follow-up constituted the primary outcome of interest. The institutional analysis was supplemented by a literature review and meta-analysis (random effects model) of all published studies on this topic as well as by an analysis of complication rates, mortality rates, and cost data from a nationwide administrative database (Vizient Inc., years 2016–2019). RESULTS A total of 73 patients (n = 16 for 50–59 years, n = 47 for 60–69, and n = 10 for 70+) were treated at the authors’ institution. The median age was 63 years, and 66% of the patients were female. At a median follow-up of 24 months, seizure freedom was 73% for the overall cohort, 63% for the 50–59 group, 77% for the 60–69 group, and 70% for the 70+ group. The literature search identified 15 additional retrospective studies (474 cases). Temporal lobectomy was the most commonly performed procedure (73%), and mesial temporal sclerosis was the most common pathology (52%), followed by nonspecific gliosis (19%). The pooled mean follow-up was 39 months (range 6–114.8 months) with a pooled seizure freedom rate of 65% (95% CI 59%–72%). On multivariable meta-regression analysis, an older mean age at surgery (coefficient [coeff] 2.1, 95% CI 1.1–3.1, p < 0.001) and the presence of mesial temporal sclerosis (coeff 0.3, 95% CI 0.1–0.6, p = 0.015) were the most important predictors of seizure freedom. Finally, analysis of the Vizient database revealed mortality rates of 0.5%, 1.1%, and 9.6%; complication rates of 7.1%, 10.1%, and 17.3%; and mean hospital costs of $31,977, $34,586, and $40,153 for patients aged 50–59, 60–69, and 70+ years, respectively. CONCLUSIONS While seizure-free outcomes of epilepsy surgery are excellent, there is an expected increase in morbidity and mortality with increasing age. Findings in this study on the safety and efficacy of epilepsy surgery in the older population may serve as a useful guide during preoperative decision-making and patient counseling.

The value of double inversion recovery MRI sequence in assessment of epilepsy patients

Background The double inversion recovery (DIR) pulse sequence was introduced several years ago and since that it grew important value in clinical neuroimaging. We aimed to assess the added value of double inversion recovery in evaluation of epileptic patients. Results In mesial temporal sclerosis, the measured contrast parameters (SNR, CR, CNR and AI) were found to be significantly higher in DIR than in FLAIR and T2 sequences. In cases of focal cortical dysplasia, significantly higher CNR and AI in DIR than in T2 and FLAIR. Also DIR showed higher detection of the increased cortical thickness and cortical signal intensity than the T2 and FLAIR sequences. In tuberous sclerosis cases, the DIR showed higher visibility of the lesions than the T2 and FLAIR. Also DIR showed higher ability to detected grey-white matters junction blurring. Conclusions Our study concluded that the greatest value of the double inversion recovery sequence is its higher ability in detecting multiple characteristics of the lesions in a one sequence.

Yield of Brain Magnetic Resonance Imaging in Epilepsy Diagnosis from 1998 to 2020: A Large Retrospective Cohort Study

Background We aimed to find the clinical significance of brain abnormalities on magnetic resonance imaging (MRI) in epilepsy and the lateralization of these findings with electroencephalogram (EEG). Methods We retrospectively analyzed the results of all EEGs and brain MRIs of 600 consecutive epilepsy patients from 1998 to 2020. Results Data were available for 563 cases (267 females). Ninety percent of the patients were 18 years old or younger. A total of 345 patients (61.3%) had focal epilepsy, 180 (32%), generalized, and 38 (6.7%), inconclusive. In 187 (33.2%), the first MRI was abnormal and in 81 (out of 108 repeated MRI), the second was pathological. The most frequent brain abnormalities were cortical dysplasia in 41 (18.1%), other structural abnormalities in 25 (11%), various phacomatoses in 23 (10.1%), and mesial temporal sclerosis in 17 (7.5%). Among 226 patients with abnormal MRI, 171 (75.6%) had focal epilepsy when compared with 36 (15.9%) with generalized epilepsy (p <0.001). In 121 patients (53.5%), the result of the abnormal MRI contributed significantly to the understanding of the epilepsy etiology. The side of abnormality was lateralized to the EEG focus in 120 cases (53%); in 10/15 cases with infantile spasms (66%), MRI was significantly abnormal. In 33, in whom the first MRI was normal, a second MRI revealed a significant abnormality. Conclusion Brain MRI is an important tool in epilepsy diagnosis, mainly in focal seizures and infantile spasms. A repeat MRI is mandatory in intractable focal cases to improve the yield of this test.

Analysis of common PI3K-AKT-MTOR mutations in pediatric surgical epilepsy by droplet digital PCR reveals novel clinical and molecular insights

Focal malformations of cortical development (FMCD) including focal cortical dysplasia (FCD), hemimegalencephaly (HMEG) and megalencephaly (MEG), constitute a spectrum of neurodevelopmental disorders associated with brain overgrowth, cellular and architectural dysplasia, intractable epilepsy, autism, and intellectual disability. Importantly, FCD is the most common cause of intractable pediatric focal epilepsy. Gain and loss of function mutations in the PI3K-AKT-MTOR pathway have been identified in this spectrum, with variable levels of mosaicism and tissue distribution. In this study, we aimed to assess droplet digital Polymerase Chain Reaction (ddPCR) as a first-tier molecular diagnostic method, as well as define genotype-phenotype relationships among the most common PI3K-AKT-MTOR pathway mutations in FMCD. A total of 144 specimens, including 113 brain samples, were collected from 58 individuals with intractable focal epilepsy phenotypes including FCD, MEG, HMEG and other types of developmental cortical lesions. We designed an ultra-deep and highly sensitive molecular diagnostic panel using ddPCR for six of the most common mutations in three PI3K-AKT-MTOR pathway genes, namely PIK3CA (p.E542K, p.E545K, p.H1047R), AKT3 (p.E17K) and MTOR (p.S2215F, p.S2215Y). We quantified the level of mosaicism across all samples and correlated genotypes with key phenotype, neuroimaging and neuropathological data. Pathogenic variants were identified in 17 individuals, with an overall molecular solve rate of 29.31%. Variant allele fractions (VAF) ranged from 0.1% to 22.67% across all positive samples. Our data shows that MTOR mutations are mostly associated with FCD, whereas PIK3CA mutations are more frequent in the HMEG-DMEG spectrum. The presence of one of these common PI3K-AKT-MTOR-mutations correlated with earlier onset of seizures. However, levels of mosaicism did not correlate with the severity of the cortical malformation by neuroimaging or neuropathological examination. Interestingly, we could not identify the six most common pathogenic variants in other types of cortical lesions (e.g., polymicrogyria or mesial temporal sclerosis) suggesting that PI3K-AKT-MTOR mutations are specifically causal in the FCD-HMEG-MEG spectrum. Finally, our data suggest that ultra-deep targeted molecular analysis for the most common PI3K-AKT-MTOR mutations via ddPCR is an effective molecular diagnostic approach for FMCD phenotypes with a good diagnostic yield when paired with neuroimaging and neuropathology evaluations. The high sensitivity and low DNA input requirements suggests that ddPCR is an effective molecular diagnostic tool for disorders caused by somatic mutations with a narrow mutational spectrum, including specific subtypes of pediatric epilepsy surgical phenotypes such as FCD and HMEG.