Laser interstitial thermal therapy of a single nodule in a complex epileptic network with multiple periventricular nodular heterotopias.

Surgical management of drug-resistant epilepsy (DRE) in patients with multiple periventricular nodular heterotopias (PVNHs) is challenging. Identifying the location of seizure onset within these complex epileptic networks is difficult, and open resection carries risks of injury to surrounding functional white matter tracts such as optic radiations (ORs). The authors demonstrate tractography-assisted laser ablation of a single nodule in a patient with DRE and multiple PVNHs. Following surgery, visual fields were intact, highlighting the benefits of OR tractographic reconstruction. At 12 months postoperatively, the patient remained seizure free, suggesting the potential efficacy of targeting a single heterotopia within complex networks in well-selected cases. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2417.

Development of an online calculator for the prediction of seizure freedom following pediatric hemispherectomy using the Hemispherectomy Outcome Prediction Scale (HOPS).

OBJECTIVES: Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. METHODS: Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). RESULTS: The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. SIGNIFICANCE: Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.

EEG and MRI Abnormalities in Patients With Psychogenic Nonepileptic Seizures.

OBJECTIVE: To compare the rate of EEG and MRI abnormalities in psychogenic nonepileptic seizures (PNES) patients with and without suspected epilepsy. Patients were also compared in terms of their demographic and clinical profiles. METHODS: A retrospective analysis of 271 newly diagnosed PNES patients admitted to the epilepsy monitoring unit between May 2000 and April 2008, with follow-up clinical data collected until September 2015. RESULTS: One hundred ninety-four patients were determined to have PNES alone, 16 PNES plus possible epilepsy, 14 PNES plus probable epilepsy, and 47 PNES plus confirmed epilepsy. Fifty-seven of the 77 patients (74.0%) with possible, probable, or definite epilepsy exhibited epileptiform activity on EEG, versus only 16 of the 194 patients (8.2%) in whom epilepsy was excluded. Twenty-four of these 194 patients (12.4%) had MRI abnormalities. Three of 38 patients (7.9%) with both EEG and MRI abnormalities were confirmed not to have epilepsy. In PNES patients with EEG or MRI abnormalities compared with those without, patients with abnormalities were more likely to have epilepsy risk factors, such as central nervous system structural abnormalities, and less likely to report minor head trauma. The presence of EEG abnormalities in PNES-only patients did not influence antiseizure medication reduction, whereas those with MRI abnormalities were less likely to have their antiseizure medications reduced. CONCLUSIONS: Psychogenic nonepileptic seizure patients without MRI or EEG abnormalities are less likely to have associated epilepsy, risk factors for epilepsy, and had different demographic profiles. There is a higher-than-expected level of EEG and MRI abnormalities in PNES patients without epilepsy.

Neuroimaging of Epilepsy.

PURPOSE OF REVIEW: This article provides an overview of imaging modalities, important imaging pathologies, and the role each imaging modality can play in the diagnosis, evaluation, and treatment of epilepsy, including epilepsy surgery. RECENT FINDINGS: The Harmonized Neuroimaging of Epilepsy Structural Sequences (HARNESS-MRI) protocol was proposed to standardize MRI imaging for all patients with seizures. The role of 7-Tesla MRI in finding previously occult epileptogenic lesions is under investigation, and the technique is increasingly used. Developing MRI postprocessing techniques can increase the sensitivity of MRI. Improvements in functional imaging techniques such as EEG-functional MRI (fMRI) and magnetic source imaging provide complementary methods of identifying seizure foci. New epileptogenic pathologies such as multinodular and vacuolating neuronal tumors (MVNT) are being discovered, and the importance of others, such as encephaloceles, is better appreciated. SUMMARY: Brain imaging is a critical component of the diagnosis and evaluation of patients with epilepsy. Structural imaging modalities such as MRI and CT allow for the identification of a wide variety of potentially epileptogenic lesions. For patients with drug-resistant epilepsy under consideration for resective surgery, both structural and functional neuroimaging may be needed for focus identification and surgical planning for preservation of neurologic function.

Sentinel Epileptiform Discharges Activating Two Seizure Networks on Intracranial EEG.

SUMMARY: Sentinel epileptiform discharges (SEDs) are epileptiform transients preceding the onset of a focal seizure seen on scalp EEG. Despite their potential localizing value, formal study of SED has been limited. The authors report a patient with MRI-negative focal-onset epilepsy whose seizures on scalp and intracranial EEG were always preceded by SED. Although the location and morphology of the SED was invariable, the seizures after the discharge were of two clearly distinct types, each with different semiology and region of spread on intracranial EEG. This suggests that the SED played a role in activating two distinct seizure networks. A right temporal lobectomy with amygdalohippocampectomy was performed. The resection included both the region of the SED as well as the seizure-onset zone of the more common seizure type, achieving seizure freedom at 3 years after surgery. Further research exploring whether the localization of SED is a reliable indicator of the seizure-onset zone could aid surgical planning in patients whose seizures are preceded by SED.

Comparison of the real-world effectiveness of vertical versus lateral functional hemispherotomy techniques for pediatric drug-resistant epilepsy: A post hoc analysis of the HOPS study.

OBJECTIVE: This study was undertaken to determine whether the vertical parasagittal approach or the lateral peri-insular/peri-Sylvian approach to hemispheric surgery is the superior technique in achieving long-term seizure freedom. METHODS: We conducted a post hoc subgroup analysis of the HOPS (Hemispheric Surgery Outcome Prediction Scale) study, an international, multicenter, retrospective cohort study that identified predictors of seizure freedom through logistic regression modeling. Only patients undergoing vertical parasagittal, lateral peri-insular/peri-Sylvian, or lateral trans-Sylvian hemispherotomy were included in this post hoc analysis. Differences in seizure freedom rates were assessed using a time-to-event method and calculated using the Kaplan-Meier survival method. RESULTS: Data for 672 participants across 23 centers were collected on the specific hemispherotomy approach. Of these, 72 (10.7%) underwent vertical parasagittal hemispherotomy and 600 (89.3%) underwent lateral peri-insular/peri-Sylvian or trans-Sylvian hemispherotomy. Seizure freedom was obtained in 62.4% (95% confidence interval [CI] = 53.5%-70.2%) of the entire cohort at 10-year follow-up. Seizure freedom was 88.8% (95% CI = 78.9%-94.3%) at 1-year follow-up and persisted at 85.5% (95% CI = 74.7%-92.0%) across 5- and 10-year follow-up in the vertical subgroup. In contrast, seizure freedom decreased from 89.2% (95% CI = 86.3%-91.5%) at 1-year to 72.1% (95% CI = 66.9%-76.7%) at 5-year to 57.2% (95% CI = 46.6%-66.4%) at 10-year follow-up for the lateral subgroup. Log-rank test found that vertical hemispherotomy was associated with durable seizure-free progression compared to the lateral approach (p = .01). Patients undergoing the lateral hemispherotomy technique had a shorter time-to-seizure recurrence (hazard ratio = 2.56, 95% CI = 1.08-6.04, p = .03) and increased seizure recurrence odds (odds ratio = 3.67, 95% CI = 1.05-12.86, p = .04) compared to those undergoing the vertical hemispherotomy technique. SIGNIFICANCE: This pilot study demonstrated more durable seizure freedom of the vertical technique compared to lateral hemispherotomy techniques. Further studies, such as prospective expertise-based observational studies or a randomized clinical trial, are required to determine whether a vertical approach to hemispheric surgery provides superior long-term seizure outcomes.

Hemispherectomy Outcome Prediction Scale: Development and validation of a seizure freedom prediction tool.

OBJECTIVE: To develop and validate a model to predict seizure freedom in children undergoing cerebral hemispheric surgery for the treatment of drug-resistant epilepsy. METHODS: We analyzed 1267 hemispheric surgeries performed in pediatric participants across 32 centers and 12 countries to identify predictors of seizure freedom at 3 months after surgery. A multivariate logistic regression model was developed based on 70% of the dataset (training set) and validated on 30% of the dataset (validation set). Missing data were handled using multiple imputation techniques. RESULTS: Overall, 817 of 1237 (66%) hemispheric surgeries led to seizure freedom (median follow-up = 24 months), and 1050 of 1237 (85%) were seizure-free at 12 months after surgery. A simple regression model containing age at seizure onset, presence of generalized seizure semiology, presence of contralateral 18-fluoro-2-deoxyglucose-positron emission tomography hypometabolism, etiologic substrate, and previous nonhemispheric resective surgery is predictive of seizure freedom (area under the curve = .72). A Hemispheric Surgery Outcome Prediction Scale (HOPS) score was devised that can be used to predict seizure freedom. SIGNIFICANCE: Children most likely to benefit from hemispheric surgery can be selected and counseled through the implementation of a scale derived from a multiple regression model. Importantly, children who are unlikely to experience seizure control can be spared from the complications and deficits associated with this surgery. The HOPS score is likely to help physicians in clinical decision-making.

Increased frequency of proinflammatory CD4 T cells and pathological levels of serum neurofilament light chain in adult drug-resistant epilepsy.

OBJECTIVE: Adult drug-resistant epilepsy (DRE) is associated with significant morbidity. Infiltration of immune cells is observed in DRE epileptic foci; however, the relation between DRE and the peripheral immune cell compartment remains only partially understood. We aimed to investigate differences in immune cell populations, cytokines, and neurodegenerative biomarkers in the peripheral blood of subjects with epilepsy versus healthy controls, and in DRE compared to well-controlled epilepsy (WCE). METHODS: Peripheral blood mononuclear cells and serum from >120 age- and sex-matched adults suffering from focal onset epilepsy and controls were analyzed by multipanel flow cytometry, multiplex immunoassays, and ultrasensitive single molecule array. RESULTS: Using a data-driven analytical approach, we identified that CD4 T cells in the peripheral blood are present in a higher proportion in DRE patients. Moreover, we observed that the frequency of CD4 T cells expressing proinflammatory cytokines interleukin (IL)-17A, IL-22, tumor necrosis factor, interferon-γ, and granulocyte-macrophage colony-stimulating factor, but not anti-inflammatory cytokines IL-10 and IL-4, is elevated in the peripheral blood of DRE subjects compared to WCE. In parallel, we found that Th17-related circulating proinflammatory cytokines are elevated, but Th2-related cytokine IL-4 is reduced, in the serum of epilepsy and DRE subjects. As Th17 cells can exert neurotoxicity, we measured levels of serum neurofilament light chain (sNfL), a marker of neuronal injury. We found significantly elevated levels of sNfL in DRE compared to controls, especially among older individuals. SIGNIFICANCE: Our data support that DRE is associated with an expansion of the CD4 Tcell subset in the peripheral blood and with a shift toward a proinflammatory Th17/Th1 CD4 Tcell immune profile. Our results further show that pathological levels of sNfL are more frequent in DRE, supporting a potential neurodegenerative component in adult DRE. With this work, we provide evidence for novel potential inflammatory and degenerative biomarkers in DRE.

Understanding the patient perspective of epilepsy treatment through text mining of online patient support groups.

OBJECTIVE: Epilepsy is among the most common chronic neurologic diseases. There is a need for more data on patient perspectives of treatment to guide patient-centered care initiatives. Patients with epilepsy share their experiences on social media anonymously, but little is known about those discussions. Our aim was to learn what patients with epilepsy discuss regarding their condition and identify treatment-related themes from online patient support groups. METHODS: A total of 355,838 posts were collected from three online support groups for patients with epilepsy through a crawling script, and an analytical pipeline was built to identify patient conversation content through leveraging of multiple text mining methods. Results were also displayed by network visualization methods. RESULTS: Patients with epilepsy sought information about medical treatments, shared their treatment experiences, and sought help from other posters. Key themes related to treatments included the search for optimal personalized treatment strategies as well as identifying and coping with adverse effects. SIGNIFICANCE: This study showed the feasibility of learning about concerns of patients with epilepsy, especially treatment issues, through text mining methods. However, some manual selection and filtering were necessary to ensure quality results for the treatment analysis. Providers should be aware of online discussions and use analyses of such discussions to help guide effective patient engagement during care.

Cortical surface intracranial electrodes identify clinically relevant seizures missed on scalp EEG after traumatic intracranial hemorrhage.

Seizures and other electrophysiological disturbances are an under-recognized cause of coma, focal deficits, and prolonged encephalopathy following subdural hematoma evacuation. In these patients, it is possible that seizures remain unrecognized on scalp EEG. It has been shown that a high burden of seizures and other electrophysiological disturbances exist following surgical evacuation and underlie the encephalopathy commonly seen in this patient population, predisposing them to medical complications and confounding estimates of prognosis. As part of a research protocol, we are performing intraoperative placement of cortical surface (non-parenchyma penetrating) intracranial EEG on patients who present after trauma and require emergent decompressive hemicraniectomy. In this case report of a patient with high-velocity traumatic epidural, subdural, and subarachnoid hemorrhages, we identified frequent non-convulsive seizures or seizure-like SIRPIDs with intracranial cortical surface monitoring that were not identified on simultaneous scalp EEG. Stimulation consistently triggered these electrographic seizures in addition to rhythmic lateralized periodic discharges. His mental status improved rapidly after resolution of these electrographic seizures shortly after increasing antiseizure medications, suggesting that they may have been contributing to his encephalopathy. More research is needed to determine the frequency of this phenomenon and determine whether treatment of such seizures improves patient outcomes.

Imaging for Adults With Seizures and Epilepsy.

PURPOSE OF REVIEW: This article discusses structural and functional neuroimaging findings in patients with seizures and epilepsy. The indications for neuroimaging in these patients and the potential diagnostic utility of these studies are presented. RECENT FINDINGS: Patients presenting with new seizures typically require urgent imaging to rule out a critical underlying cause. MRI is the structural neuroimaging procedure of choice in individuals with epilepsy. Specific epilepsy protocols should be considered to increase the diagnostic yield of neuroimaging in patients with structural lesions associated with focal or generalized seizures. Common epileptogenic pathologic processes include mesial temporal sclerosis, malformations of cortical development, focal encephalomacia, primary brain tumors, vascular malformations, and neurocysticercosis. Functional neuroimaging studies are usually restricted to the evaluation of patients with drug-resistant focal epilepsy who are being considered for surgical treatment. SUMMARY: The role of neuroimaging in epilepsy depends on the appropriate clinical indication. In patients without known epilepsy presenting with acute seizures, structural imaging is essential to rule out an underlying etiology (eg, subdural hematoma) that may require a specific therapeutic intervention. In individuals with new or previously uninvestigated epilepsy, MRI serves multiple purposes, including identifying a causative focal lesion and helping to diagnose the epilepsy type. In a significant number of patients with epilepsy, the MRI results are normal or reveal indeterminate findings. For patients with drug-resistant focal epilepsy, functional neuroimaging techniques, such as fludeoxyglucose-positron emission tomography (FDG-PET), ictal single-photon emission computed tomography (SPECT), or functional MRI (fMRI), may assist in surgical planning, especially in patients with MRI-negative epilepsy, whose prognosis for a seizure-free outcome after surgery is worse than for patients with an epileptogenic lesion on structural MRI.

Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood.

OBJECTIVE: The natural history of succinic semialdehyde dehydrogenase (SSADH) deficiency in adulthood is unknown; we elucidate the clinical manifestations of the disease later in life. METHODS: A 63-year-old man with long-standing intellectual disability was diagnosed with SSADH deficiency following hospitalization for progressive decline, escalating seizures, and prolonged periods of altered consciousness. We present a detailed review of his clinical course and reviewed our SSADH deficiency database adult cohort to derive natural history information. RESULTS: Of 95 patients in the database for whom age at diagnosis is recorded, there are 40 individuals currently aged 18 years or older. Only 3 patients were diagnosed after age 18 years. Of 25 adults for whom data are available after age 18, 60% have a history of epilepsy. Predominant seizure types are generalized tonic-clonic, absence, and myoclonic. EEGs showed background slowing or generalized epileptiform discharges in two-thirds of adults for whom EEG data were collected. History of psychiatric symptoms was prominent, with frequent anxiety, sleep disturbances, and obsessive-compulsive disorder. CONCLUSIONS: We identified patients older than 18 years with SSADH deficiency in our database following identification and review of a patient diagnosed in the seventh decade of life. The illness had a progressive course with escalating seizures in the index case, with fatality at age 63. Diagnosis in adulthood is rare. Epilepsy is more common in the adult than the pediatric SSADH deficiency cohort; neuropsychiatric morbidity remains prominent.

Takayasu arteritis developing during treatment of ulcerative colitis with infliximab.

A 22-year-old female with ulcerative colitis that was successfully treated with infliximab (IFX), and remained stable following tapered discontinuation of prednisolone, developed anterior neck pain and elevation of C-reactive protein following her fourth administration of IFX. She was diagnosed with Takayasu arteritis (TA) based on neck ultrasound and computed tomography angiography. This is the first report describing the development of TA during treatment of UC with IFX.

Effect of Research Questionnaires on Satisfaction with Treatment Care in Suicidal Adolescents and their Parents.

OBJECTIVE: Few psychosocial treatment methods have been empirically validated as effective for the prevention of suicide in suicidal adolescents, in part due to concerns that research could compromise quality of care. The study assessed the impact of research batteries on satisfaction with psychiatric care in suicidal adolescents and their parents. METHOD: Suicidal adolescents presenting to the emergency department of a major urban pediatric hospital were divided into two groups, one receiving treatment as usual and the other exposed to psychometric testing of the type typically used in research protocols both before and after their treatment. Following treatment, the patients of both groups and their parents were given questionnaires to assess satisfaction with the services they had received. Differences between the two groups were analyzed. RESULTS: No significant intergroup differences were found (p>0.05) in either patients or their parents regarding treatment received from the emergency-room team, regardless of whether they had been subjected to the psychometric testing. CONCLUSIONS: There is no evidence in the study to support concerns that extensive psychometric testing of the type frequently encountered in research studies undermines patient satisfaction with the care they receive.