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Permanent present tense : the unforgettable life of the amnesic patient, H.M.
\"The ... story of H.M., a brain-damaged amnesic whose case dramatically expanded the frontiers of neuroscience. H.M.'s true identity was only made public following his death in December 2008, and now neuroscientist Suzanne Corkin, who worked closely with H.M for nearly fifty years, tells the full story of his life and legacy--a story that encompasses many of the recent breakthroughs in the study of the brain, and which vividly reveals the neurological processes that make us human\"--Provided by publisher.
Book
Long-term outcomes of mesial temporal laser interstitial thermal therapy for drug-resistant epilepsy and subsequent surgery for seizure recurrence: a multi-centre cohort study
BackgroundMagnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to surgical resection for drug-resistant mesial temporal lobe epilepsy (mTLE). Reported rates of seizure freedom are variable and long-term durability is largely unproven. Anterior temporal lobectomy (ATL) remains an option for patients with MRgLITT treatment failure. However, the safety and efficacy of this staged strategy is unknown.MethodsThis multicentre, retrospective cohort study included 268 patients consecutively treated with mesial temporal MRgLITT at 11 centres between 2012 and 2018. Seizure outcomes and complications of MRgLITT and any subsequent surgery are reported. Predictive value of preoperative variables for seizure outcome was assessed.ResultsEngel I seizure freedom was achieved in 55.8% (149/267) at 1 year, 52.5% (126/240) at 2 years and 49.3% (132/268) at the last follow-up ≥1 year (median 47 months). Engel I or II outcomes were achieved in 74.2% (198/267) at 1 year, 75.0% (180/240) at 2 years and 66.0% (177/268) at the last follow-up. Preoperative focal to bilateral tonic-clonic seizures were independently associated with seizure recurrence. Among patients with seizure recurrence, 14/21 (66.7%) became seizure-free after subsequent ATL and 5/10 (50%) after repeat MRgLITT at last follow-up≥1 year.ConclusionsMRgLITT is a viable treatment with durable outcomes for patients with drug-resistant mTLE evaluated at a comprehensive epilepsy centre. Although seizure freedom rates were lower than reported with ATL, this series represents the early experience of each centre and a heterogeneous cohort. ATL remains a safe and effective treatment for well-selected patients who fail MRgLITT.
Journal Article
Personalised virtual brain models in epilepsy
Individuals with drug-resistant focal epilepsy are candidates for surgical treatment as a curative option. Before surgery can take place, the patient must have a presurgical evaluation to establish whether and how surgical treatment might stop their seizures without causing neurological deficits. Virtual brains are a new digital modelling technology that map the brain network of a person with epilepsy, using data derived from MRI. This technique produces a computer simulation of seizures and brain imaging signals, such as those that would be recorded with intracranial EEG. When combined with machine learning, virtual brains can be used to estimate the extent and organisation of the epileptogenic zone (ie, the brain regions related to seizure generation and the spatiotemporal dynamics during seizure onset). Virtual brains could, in the future, be used for clinical decision making, to improve precision in localisation of seizure activity, and for surgical planning, but at the moment these models have some limitations, such as low spatial resolution. As evidence accumulates in support of the predictive power of personalised virtual brain models, and as methods are tested in clinical trials, virtual brains might inform clinical practice in the near future.
Journal Article
Surgery for Drug-Resistant Epilepsy in Children
In children with drug-resistant epilepsy, the rate of freedom from seizures at 1 year was higher with epilepsy surgery than with medical therapy alone. Most measures of cognitive development were better in the surgery group than in the medical-therapy group.
Journal Article
Reduced long-term mortality after successful resective epilepsy surgery: a population-based study
BackgroundWe investigated all-cause and epilepsy-related mortality in patients operated with resective epilepsy surgery and in non-operated patients with drug-resistant epilepsy. Our hypothesis was that patients who proceed to surgery have lower mortality over time compared with non-operated patients.MethodData from 1329 adults and children from the Swedish National Epilepsy Surgery Register and 666 patients with drug-resistant epilepsy who had undergone presurgical work-up but not been operated were analysed. The operated patients had follow-ups between 2 and 20 years. We used the Swedish Cause of Death Register to identify deaths. Autopsy reports were collected for patients with suspected sudden unexpected death in epilepsy (SUDEP). Kaplan-Meier and Cox regression analyses were performed to identify predictors for mortality and SUDEP.ResultsSUDEP accounted for 30% of all deaths. Surgery was associated with lower all-cause mortality (HR 0.7, 95% CI 0.5 to 0.9), also when adjusted for age, sex and tonic–clonic seizures at inclusion. The benefit of surgery seemed to persist and possibly even increase after 15 years of follow-up. Risk factors of mortality for operated patients were persisting seizures and living alone. Of the operated patients, 37% had seizures, and these had a higher risk of mortality (HR 2.1, 95% CI 1.4 to 3.0) and SUDEP (HR 3.5, 95% CI 1.7 to 7.3) compared with patients with seizure freedom at last follow-up.ConclusionsIn this large population-based epilepsy surgery cohort, operated patients had a lower all-cause mortality compared with non-operated patients with drug-resistant epilepsy. Seizure freedom was the most important beneficial factor for both all-cause mortality and SUDEP among operated patients.
Journal Article
Multimodal prognostic features of seizure freedom in epilepsy surgery
ObjectiveAccurate preoperative predictions of seizure freedom following surgery for focal drug resistant epilepsy remain elusive. Our objective was to systematically evaluate all meta-analyses of epilepsy surgery with seizure freedom as the primary outcome, to identify clinical features that are consistently prognostic and should be included in the future models.MethodsWe searched PubMed and Cochrane using free-text and Medical Subject Heading (MeSH) terms according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. This study was registered on PROSPERO. We classified features as prognostic, non-prognostic and uncertain and into seven subcategories: ‘clinical’, ‘imaging’, ‘neurophysiology’, ‘multimodal concordance’, ‘genetic’, ‘surgical technique’ and ‘pathology’. We propose a structural causal model based on these features.ResultsWe found 46 features from 38 meta-analyses over 22 years. The following were consistently prognostic across meta-analyses: febrile convulsions, hippocampal sclerosis, focal abnormal MRI, Single-Photon Emission Computed Tomography (SPECT) coregistered to MRI, focal ictal/interictal EEG, EEG-MRI concordance, temporal lobe resections, complete excision, histopathological lesions, tumours and focal cortical dysplasia type IIb. Severe learning disability was predictive of poor prognosis. Others, including sex and side of resection, were non-prognostic. There were limited meta-analyses investigating genetic contributions, structural connectivity or multimodal concordance and few adjusted for known confounders or performed corrections for multiple comparisons.SignificanceSeizure-free outcomes have not improved over decades of epilepsy surgery and despite a multitude of models, none prognosticate accurately. Our list of multimodal population-invariant prognostic features and proposed structural causal model may serve as an objective foundation for statistical adjustments of plausible confounders for use in high-dimensional models.PROSPERO registration numberCRD42021185232.
Journal Article
IQ changes after pediatric epilepsy surgery: a systematic review and meta-analysis
Objective
This systematic review aimed to assess the intellectual outcome of children who underwent surgery for epilepsy.
Methods
A systematic review of electronic databases was conducted on December 3, 2021, for PubMed and January 11, 2022, for Web of Science. The review was conducted according to the PRISMA guidelines. The included studies reported on intelligence quotient (IQ) or developmental quotient (DQ) before and after epilepsy surgery in children. Studies were included, if the patients had medically intractable epilepsy and if the study reported mainly on curative surgical procedures. We conducted a random-effects meta-analysis to determine the mean change of IQ/DQ.
Results
Fifty-seven studies reporting on a total of 2593 patients met the inclusion criteria. The mean age at surgery was 9.2 years (± 3.44; range 2.4 months–19.81 years). Thirty-eight studies showed IQ/DQ improvement on a group level, 8 yielded stable IQ/DQ, and 19 showed deterioration. Pooled analysis revealed a significant mean gain in FSIQ of + 2.52 FSIQ points (95% CI 1.12–3.91). The pooled mean difference in DQ was + 1.47 (95% CI − 6.5 to 9.5). The pooled mean difference in IQ/DQ was 0.73 (95% CI − 4.8 to 6.2). Mean FSIQ gain was significantly higher in patients who reached seizure freedom (+ 5.58 ± 8.27) than in patients who did not (+ 0.23 ± 5.65). It was also significantly higher in patients who stopped ASM after surgery (+ 6.37 ± 3.80) than in patients who did not (+ 2.01 ± 2.41). Controlled studies showed a better outcome in the surgery group compared to the non-surgery group. There was no correlation between FSIQ change and age at surgery, epilepsy duration to surgery, and preoperative FSIQ.
Significance
The present review indicates that there is a mean gain in FSIQ and DQ in children with medically intractable epilepsy after surgery. The mean gain of 2.52 FSIQ points reflects more likely sustainability of intellectual function rather than improvement after surgery. Seizure-free and ASM-free patients reach higher FSIQ gains. More research is needed to evaluate individual changes after specific surgery types and their effect on long-term follow-up.
Journal Article
The Bayesian Virtual Epileptic Patient: A probabilistic framework designed to infer the spatial map of epileptogenicity in a personalized large-scale brain model of epilepsy spread
Despite the importance and frequent use of Bayesian framework in brain network modeling for parameter inference and model prediction, the advanced sampling algorithms implemented in probabilistic programming languages to overcome the inference difficulties have received relatively little attention in this context. In this technical note, we propose a probabilistic framework, namely the Bayesian Virtual Epileptic Patient (BVEP), which relies on the fusion of structural data of individuals to infer the spatial map of epileptogenicity in a personalized large-scale brain model of epilepsy spread. To invert the individualized whole-brain model employed in this study, we use the recently developed algorithms known as No-U-Turn Sampler (NUTS) as well as Automatic Differentiation Variational Inference (ADVI). Our results indicate that NUTS and ADVI accurately estimate the degree of epileptogenicity of brain regions, therefore, the hypothetical brain areas responsible for the seizure initiation and propagation, while the convergence diagnostics and posterior behavior analysis validate the reliability of the estimations. Moreover, we illustrate the efficiency of the transformed non-centered parameters in comparison to centered form of parameterization. The Bayesian framework used in this work proposes an appropriate patient-specific strategy for estimating the epileptogenicity of the brain regions to improve outcome after epilepsy surgery.
•We propose a novel framework (namely the BVEP) to link the PPLs and the personalized whole-brain network modeling.•The BVEP relies on efficient sampling algorithms and appropriate form of parameterization.•The BVEP captures well the seizure evolution and recruitment in a virtual epileptic patient.•The BVEP accurately infers the spatial map of epileptogenicity across different brain regions.•The convergence diagnostics and posterior behavior analysis validate the reliability of the estimations.•We point out the capability of BVEP in development of personalized strategies towards therapy and intervention.
Journal Article
Predictors and reasons for epilepsy patients to decline surgery: a prospective study
Background
In patients with drug-resistant focal epilepsy, resective surgery is the most successful treatment option to achieve seizure freedom. However, a surprisingly high rate of patients declines their physicians’ recommendation to undergo removal of the seizure focus or—if necessary—further video-EEG monitoring (VEM).
Methods
In this prospective study, consecutive patients in presurgical assessment with at least one scalp VEM between 2016 and 2018 were included. We assessed both epilepsy-related and psychosocial variables as well as decision-making of physicians and patients, including reasons for decline in the latter.
Results
Out of 116 patients with a total of 165 VEM, 20 patients were eventually found to be ineligible for resection, 51 declined, and 45 agreed on recommendations for resection or further VEM diagnostics. Patients most frequently declined due to general fear of brain surgery (
n =
30, 59%) and currently lower seizure frequency (
n =
11, 22%). An independent predictor of patients’ decline was less epilepsy-related fear (OR 0.43;
p =
0.02) assessed in a standardised questionnaire.
Conclusion
Half of the patients potentially eligible for resective surgery decline the operation or further VEM procedures. Patients who decline are more fearful of brain surgery than of ongoing disabling seizures. More insight is needed to improve counselling of patients.
Journal Article
MR-guided laser interstitial thermal therapy in the treatment of brain tumors and epilepsy
MR-guided Laser Interstitial Thermal Therapy (MRgLITT) is a minimally invasive neurosurgical technique increasingly used for the treatment of drug-resistant epilepsy and brain tumors. Utilizing near-infrared light energy delivery guided by real-time MRI thermometry, MRgLITT enables precise ablation of targeted brain tissues, resulting in limited corridor-related morbidity and expedited postoperative recovery. Since receiving CE marking in 2018, the adoption of MRgLITT has expanded to more than 40 neurosurgical centers across Europe. In epilepsy treatment, MRgLITT can be applied to various types of focal lesional epilepsy, including mesial temporal lobe epilepsy, hypothalamic hamartoma, focal cortical dysplasias, periventricular heterotopias, cavernous malformations, dysembryoplastic neuroepithelial tumors (DNET), low-grade gliomas, tuberous sclerosis, and in disconnective surgeries. In neuro-oncology, MRgLITT is used for treating newly diagnosed and recurrent primary brain tumors, brain metastases, and radiation necrosis. This comprehensive review presents an overview of the current evidence and technical considerations for the use of MRgLITT in treating various pathologies associated with drug-resistant epilepsy and brain tumors.
Journal Article