Epileptiform abnormalities in the disconnected hemisphere are common in seizure-free patients after hemispherectomy

Objective: The spectrum of EEG abnormalities in the disconnected hemisphere in seizure-free patients after hemispherectomy has not been well characterized. Methods: Fifty consecutive patients who were seizure-free following hemispheric disconnection were identified. Data on preoperative clinical, EEG and neuroimaging findings and postoperative EEG findings and antiseizure medication status were collected. Results: Forty-seven patients (94%) had functional hemispherectomy, and three (6%) had more extensive tissue resection of the posterior quadrant or frontal region along with hemispheric disconnection. Etiologies included: residual effects from vascular lesions including perinatal stroke in 35 patients, Rasmussen encephalitis in six, malformation of cortical development in seven, and Sturge-Weber syndrome in two. Pre-operative EEG showed focal epileptiform discharges in the affected hemisphere in 26 patients and in both hemispheres in 19. Eleven patients had diffuse bisynchronous epileptiform discharges. Postoperative EEGs at six to 12 months after surgery showed slowing and attenuation of physiological rhythms on the operated side in all patients. Thirty-four patients (68%) had epileptiform discharges exclusively from the operated hemisphere, six (12%) had bilateral independent epileptiform discharges, nine (18%) had no epileptiform discharges on either side, and one (2%) had epileptiform discharges from the contralateral hemisphere only. Lateralized periodic discharges from the operated hemisphere were noted in three patients (6%). EEG seizures from the operated hemisphere without clinical signs were noted in four patients (8%). After a median follow-up of three years, 30 patients (60%) were off all antiseizure medications, including 8/9 (89%) patients with no epileptiform discharges, 20/34 (59%) patients with postoperative epileptiform discharges from the operated hemisphere, and 2/7 (28%) patients with contralateral discharges. Significance: The majority of patients who are seizure-free after disconnective hemispherectomy will continue to show epileptiform discharges in the operated hemisphere. The presence of such discharges should not preclude tapering, nor prompt restarting of antiseizure medication in seizure-free patients.

Seizure Outcomes and Reoperation in Surgical Rasmussen Encephalitis Patients.

BACKGROUND: Rasmussen encephalitis (RE) is a rare inflammatory disease affecting one hemisphere, causing progressive neurological deficits and intractable seizures. OBJECTIVE: To report long-term seizure outcomes, reoperations, and functional outcomes in patients with RE who underwent hemispherectomy at our institution. METHODS: Retrospective review was performed for all patients with RE who had surgery between 1998 and 2020. We collected seizure history, postoperative outcomes, and functional data. Imaging was independently reviewed in a blinded fashion by 2 neurosurgeons and a neuroradiologist. RESULTS: We analyzed 30 patients with RE who underwent 35 hemispherectomies (5 reoperations). Using Kaplan-Meier analysis, seizure-freedom rate was 81.5%, 63.6%, and 55.6% at 1, 5, and 10 years after surgery, respectively. Patients with shorter duration of hemiparesis preoperatively were less likely to be seizure-free at follow-up (P = .011) and more likely to undergo reoperation (P = .004). Shorter duration of epilepsy (P = .026) and preoperative bilateral MRI abnormalities (P = .011) were associated with increased risk of reoperation. Complete disconnection of diseased hemisphere on postoperative MRI after the first operation improved seizure-freedom (P = .021) and resulted in fewer reoperations (P = .034), and reoperation resulted in seizure freedom in every case. CONCLUSION: Obtaining complete disconnection is critical for favorable seizure outcomes from hemispherectomy, and neurosurgeons should have a low threshold to reoperate in patients with RE with recurrent seizures. Rapid progression of motor deficits and bilateral MRI abnormalities may indicate a subpopulation of patients with RE with increased risk of needing reoperation. Overall, we believe that hemispherectomy is a curative surgery for the majority of patients with RE, with excellent long-term seizure outcome.

The Clinical Utility of Surgical Histopathology in Predicting Seizure Outcomes in Patients with Rasmussen Encephalitis Undergoing Hemispherectomy.

OBJECTIVE: The objectives of this study were to determine the relationship between the severity of pathology and seizure outcomes in patients who underwent hemispherectomy for Rasmussen encephalitis (RE) and to investigate which clinical factors correlated with severity of pathology. METHODS: In this retrospective cohort study, we collected and reviewed pathology and clinical variables. We ascertained seizure outcomes using Engel's classification, and Pardo stages were used to grade pathology. RESULTS: We included 29 unique patients who underwent 34 hemispherectomy procedures for analysis. There was no statistically significant correlation between Pardo stage and seizure outcome (P = 1). Increasing duration of epilepsy (ß = 0.011, P = 0.02) and duration of hemiparesis (ß = 0.024, P = 0.01) were significantly associated with a more severe Pardo stage. In contrast, the presence of epilepsia partialis continua had a negative relationship with Pardo stage (ß = -0.49, P = 0.04). Twenty-six (89.75%) patients were Engel class I at the last follow-up, including all 5 patients who underwent redo hemispherectomy in our cohort. CONCLUSIONS: Consistent with the progressive nature of RE, more severe pathology was associated with a longer duration of epilepsy and longer duration of hemiparesis, while the presence of epilepsia partialis continua was associated with less severe pathology. Results from this series suggest the degree of cortical involvement with RE as assessed on surgical histopathology does not correlate with seizure outcome after hemispherectomy, which appears to be more dependent on surgical technique/complete disconnection.

Epilepsy with Eyelid myoclonias - A diagnosis concealed in other genetic generalized epilepsies with photoparoxysmal response.

OBJECTIVE: Epilepsy with eyelid myoclonias(EMA) is a genetic generalized epilepsy (GGE) characterized by eyelid myoclonia, eye-closure sensitivity and photosensitivity. Data on EMA patients who specifically present with photoparoxysmal response on EEG is lacking. EMA is an under-recognized syndrome which is frequently misclassified as another GGE. The main objective of our research is to describe the occurrence of EMA versus other GGEs among patients with photoparoxysmal response and evaluate their distinguishing features. METHODS: We retrospectively identified all patients who had photoparoxysmal response on EEGs performed at Cleveland clinic between 01/01/2012 and 12/31/2019. Initial epilepsy diagnosis and clinical data were collected. EEGs were reviewed for eyelid myoclonia and eye-closure-sensitivity which were used as main diagnostic clues for EMA. If clinical criteria was met, diagnosis was revised as EMA. RESULTS: Of 249 patients with photoparoxysmal response, 70(28.1%) met EMA criteria. Sixty-two (88.6%) were females. Mean age of onset of epilepsy was 7 years (+7.9) and 120(48.2%) had other GGEs. Fifty-four (77.1%) patients with EMA were initially classified as another epilepsy. Initial diagnosis included CAE or JME in 40(57.1%) patients with EMA so we compared EMA with these syndromes. Female preponderance, drug refractoriness, older age of onset and generalized myoclonia were more common in EMA than CAE. Earlier age of onset, absence seizures, and lack of generalized myoclonic jerks were more common EMA than JME. SIGNIFICANCE: Our study demonstrates that EMA is under-recognized among GGE patients with photoparoxysmal response. It highlights distinguishing clinical and electrographic features which separate EMA from other GGEs. It emphasizes the diverse treatments utilized and the need for therapeutic options for patients with refractory EMA.

Surgical candidates in children with epileptic spasms can be selected without invasive monitoring: A report of 70 cases.

OBJECTIVE: Prior surgical series in children with drug-resistant epileptic spasms have reported use of intracranial EEG monitoring in up to two-third of patients. We report outcome after epilepsy surgery for drug-resistant epileptic spasms in a cohort of children without the use of intracranial EEG monitoring in any of the patients. METHODS: Medical records of all consecutive children aged 5 years or under who had epilepsy surgery for epileptic spasms at Cleveland Clinic between 2000 and 2018 were reviewed. Post-operative seizure outcome and predictors of prognosis of seizure outcome were analyzed. RESULTS: Seventy children with active epileptic spasms underwent surgical resections during the study period. Mean age at seizure onset was 6.8 (+9.31) months and median age at surgery was 18.5 months. An epileptogenic lesion was identified on brain MRI in all patients; 17 (24%) had bilateral abnormalities. Etiologies included malformations of cortical development (58%), perinatal infarct/encephalomalacia (39%), and tumor (3%). None of the patients had intracranial EEG. Surgical procedures included hemispherectomy (44%), lobectomy/ lesionectomy (33%), and multilobar resections (23%). Twelve children needed repeat surgery; six (50%) became seizure free after the second surgery. At six months follow-up, 73% (51/70) were seizure-free since surgery. At a mean follow-up of 4.7 years, 60% (42/70) had Engel 1 outcome. In those with seizure recurrence, 17 (60%) reported improvement. Shorter epilepsy duration (p = 0.05) and lobar or sub-lobar epileptogenic lesions (p = 0.02) predicted favorable seizure outcome at 6 months after surgery. For long term outcome, patients with bilateral abnormalities on MRI (p = 0.001), and multilobar extent on MRI (p = 0.02) were at higher risk for recurrence. SIGNIFICANCE: Children with drug-resistant epileptic spasms secondary to an epileptogenic lesion detected on MRI could be selected for epilepsy surgery without undergoing intracranial EEG monitoring. A surgical selection paradigm without intracranial monitoring may allow early surgery without the risks of invasive monitoring.

Hemispherectomy in adults and adolescents: Seizure and functional outcomes in 47 patients.

OBJECTIVE: To examine longitudinal seizure and functional outcomes after hemispherectomy in adults and adolescents. METHODS: We reviewed 47 consecutive patients older than 16 years who underwent hemispherectomy between 1996 and 2016 at our center. Clinical, electroencephalographic (EEG), imaging, neuropsychological, surgical, and functional status data were analyzed. RESULTS: Thirty-six patients were 18 years or older at surgery; 11 were aged between 16 and 18 years. Brain injury leading to hemispheric epilepsy occurred before 10 years of age in 41 (87%) patients. At a mean follow-up of 5.3 postoperative years (median = 2.9 years), 36 (77%) had Engel class I outcome. Longitudinal outcome analysis showed 84% seizure freedom (Engel IA) at 6 months, 76% at 2 years, and 76% at 5 years and beyond, with stable longitudinal outcomes up to 12 years from surgery. Multivariate analysis demonstrated that acute postoperative seizures and contralateral interictal spikes at 6-month follow-up EEG were associated with seizure recurrence. Patients who could walk unaided preoperatively and had no cerebral peduncle atrophy on brain magnetic resonance imaging were more likely to experience worsening of motor function postoperatively. Otherwise, postoperative ambulatory status and hand function were unchanged. Of the 19 patients who completed neuropsychological testing, 17 demonstrated stable or improved postoperative outcomes. SIGNIFICANCE: Hemispherectomy in adults is a safe and effective procedure, with seizure freedom rates and functional outcome similar to those observed in children.

Skills for safe practice - A qualitative study to evaluate the use of simulation in safeguarding children teaching for pre-registration children's nurses.

Safeguarding children teaching is a required component in all pre-registration nursing curricula. A structured approach to this teaching as part of preparation for registration as a children's nurse was developed jointly by the Course Leader and the Designated Nurse for Safeguarding Children. This approach aims to equip children's nurses with the necessary theoretical knowledge and practical skills needed for safe practice. A key element in this curriculum is simulation, where students must assess injuries on manikins, select and complete appropriate documentation, and perform a nursing handover. Simulation has recognised value in nurse education but its use in safeguarding children teaching for student children's nurses has not previously been widely reported. This small-scale qualitative study explored the student experience and the impact of simulation teaching in the development of relevant knowledge and the core safeguarding skill set of observation, interpretation, documentation and communication. The methodology for this small, qualitative study was triangulated, comprising observation of the simulation teaching and two sets of semi-structured interviews. The resultant data was investigated using thematic analysis. The outcome of the study suggested that students were able to transfer learning from the simulation into clinical practice, and that simulation as an approach to safeguarding children teaching resonated with the students' preferred learning style and merits further consideration and evaluation.

Robot-assisted stereoelectroencephalography in children.

OBJECTIVEThe goal in the study was to describe the clinical outcomes associated with robot-assisted stereoelectroencephalography (SEEG) in children.METHODSThe authors performed a retrospective, single-center study in consecutive children with medically refractory epilepsy who were undergoing robot-assisted SEEG. Kaplan-Meier survival analysis was used to calculate the probability of seizure freedom. Both univariate and multivariate methods were used to analyze the preoperative and operative factors associated with seizure freedom.RESULTSFifty-seven children underwent a total of 64 robot-assisted procedures. The patients' mean age was 12 years, an average of 6.4 antiepileptic drugs (AEDs) per patient had failed prior to implantation, and in 56% of the patients the disease was considered nonlesional. On average, children had 12.4 electrodes placed per implantation, with an implantation time of 9.6 minutes per electrode and a 10-day postoperative stay. SEEG analysis yielded a definable epileptogenic zone in 51 (89%) patients; 42 (74%) patients underwent surgery, half of whom were seizure free at last follow-up, 19.6 months from resection. In a multivariate generalized linear model, resective surgery, older age, and shorter SEEG-related hospital length of stay were associated with seizure freedom. In a Cox proportional hazards model including only the children who underwent resective surgery, older age was the only significant factor associated with seizure freedom. Complications related to bleeding were the major contributors to morbidity. One patient (1.5%) had a symptomatic hemorrhage resulting in a permanent neurological deficit.CONCLUSIONSThe authors report one of the largest pediatric-specific SEEG series demonstrating that the modern surgical management of medically refractory epilepsy in children can lead to seizure freedom in many patients, while also highlighting the challenges posed by this difficult patient population.

Cognitive Outcome After Epilepsy Surgery in Children.

Cognitive dysfunction in children with epilepsy is primarily contributed by etiology, seizures, frequency of interictal epileptiform discharges, and adverse effects of antiepileptic drugs. The direct effect of epilepsy surgery on cognitive outcome depends on two key factors: the function that is present in the epileptogenic zone to be removed, and the dysfunction outside the epileptogenic zone caused by epilepsy. Studies on cognitive outcome in children after various types of epilepsy surgery estimate "no significant change" in about 70% of children, improvement in cognition in 10%-15%, and decline in 10%-15%. In young children with epileptic encephalopathy, the reversible dysfunction outside the epileptogenic zone is larger and hence carry better chances of improved outcome after successful surgery. If the epileptogenic zone harbors significant cognitive function (memory, language, or other function), then a decline in function may occur with its resection. Understanding the pathophysiological basis for the cognitive changes after epilepsy surgery assists in counseling patients and families before surgery.

Occipito-Frontal Sharp Waves-An Under-Recognized Electroencephalogram Pattern in Self-Limited Idiopathic Childhood Focal Epilepsy.

We report four children who highlight the potentially under-recognized electroencephalogram pattern of bilaterally synchronous occipito-frontal sharp waves, which may occur in children with Panayiotopoulos type self-limited childhood epilepsy but may be easily confused with the patterns of symptomatic generalized epilepsy. Our patients were young, healthy children who had infrequent, predominantly nocturnal, fairly prolonged seizures characterized by altered consciousness, vomiting, and autonomic features, or in one case nocturnal secondary generalized tonic-clonic convulsion. Their electroencephalograms showed stereotyped abundant sleep-activated sharp waves with maximum negativity in bilateral occipital and frontal greater than centro-temporo-parietal regions. On a "double-banana" bipolar montage, the sharp waves had upward deflections in frontal electrodes, downward deflections at occipital electrodes, and a positive phase reversal in the middle of each chain. The lower-amplitude occipital discharges slightly preceded the frontal discharges, consistent with posterior-to-anterior propagation likely originating from mesial occipital regions. In the proper clinical context, recognizing the electroencephalogram pattern of bilateral occipito-frontal sharp waves affords confidence in a favorable prognosis, presents the option to possibly defer daily treatment with antiepileptic medication, and shifts the emphasis to rescue medication for isolated seizures.

Aicardi syndrome: epilepsy surgery as a palliative treatment option for selected patients and pathological findings.

The optimal treatment for medically refractory epilepsy in Aicardi syndrome (AS) is still unclear. Palliative surgical treatment, including vagus nerve stimulation and corpus callosotomy, has therefore been used. There is limited data on the role of resective epilepsy surgery as a treatment choice in patients with AS. Here, we describe the seizures, anatomo-pathological findings, and neurodevelopmental outcome of palliative epilepsy surgery in two children with AS who had resective epilepsy surgery at the Cleveland Clinic. The related literature is also reviewed. Case 1 had a left functional hemispherectomy and was free of seizures and hypsarrhythmia for six months after surgery. Her gross motor skills improved after surgery. Outcome at 43 months was 1-3 isolated spasms per day. Case 2 had a right fronto-parietal lobectomy. Her seizures improved in frequency and severity, but remained daily after epilepsy surgery. Neurodevelopment changes included improved alertness and recognition of caregivers. This patient died 21 months after epilepsy surgery of unclear causes. Surgical pathology in both cases showed focal cortical dysplasia associated with other findings, such as nodular heterotopia and polymicrogyria. Epilepsy surgery could be an alternative palliative treatment choice in selective cases of AS, but studies on a larger patient cohort are needed to identify the possible role of surgery in children with AS. The complexity of the pathological findings may offer an explanation for the severity of seizures in AS.

Epileptic encephalopathies: Optimizing seizure control and developmental outcome.

Cognitive and developmental outcomes in patients with epileptic encephalopathy are hypothesized to result from an interplay between the underlying epileptic pathologic substrate and the acquired consequences of frequent and repetitive seizures and epileptiform discharges that often straddle the interictal and ictal boundaries. This article briefly reviews the evidence related to this assumption, presents critical questions that need to be answered to clarify this relationship, and advances a set of concrete steps that may help improve developmental patient outcomes.

Hemispheric malformations of cortical development: surgical indications and approach.

INTRODUCTION: The term "hemispheric malformation of cortical development" (MCD) has come into the medical lexicon in the past 20 years as improvements and availability of advanced imaging techniques have permitted more precise diagnosis of a variety of brain developmental disorders that affect large regions of brain. These conditions are united by their propensity to elicit seizures that are difficult to control with medication in the children who suffer them. PURPOSE: The goal of surgical intervention is always to achieve seizure freedom and thereby give the affected child the best possible hope for neurological development. Even when seizure freedom cannot be achieved, a reduction in seizure burden is necessary to permit the survival of the child in many cases of MCD. EVALUATION: A presurgical evaluation of a patient presenting with severe epilepsy and a possible hemispheric malformation can be divided into three stages. The first includes an evaluation of available imaging, clinical, and genetic data to accurately diagnose the child and help determine if surgical intervention is an option. The next includes an evaluation of EEG and neurological data, although this has limited utility in many clinical circumstances. Finally, a clinical team must decide upon an appropriate surgical strategy among a variety of options. CONCLUSIONS: In this review, we will examine the set of diagnoses and associated imaging characteristics that describe the set of conditions for which surgical intervention is a possibility. We include a discussion of available surgical options, describing our own experience with surgery for MCD and the associated postoperative considerations including rates of seizure freedom, considerations for reoperation, and hydrocephalus.

Stereoelectroencephalography in children and adolescents with difficult-to-localize refractory focal epilepsy.

BACKGROUND: Although stereoelectroencephalography (SEEG) has been shown to be a valuable tool for preoperative decision making in focal epilepsy, there are few reports addressing the utility and safety of SEEG methodology applied to children and adolescents. OBJECTIVE: To present the results of our early experience using SEEG in pediatric patients with difficult-to-localize epilepsy who were not considered candidates for subdural grid evaluation. METHODS: Thirty children and adolescents with the diagnosis of medically refractory focal epilepsy (not considered ideal candidates for subdural grids and strip placement) underwent SEEG implantation. Demographics, electrophysiological localization of the hypothetical epileptogenic zone, complications, and seizure outcome after resections were analyzed. RESULTS: Eighteen patients (60%) underwent resections after SEEG implantations. In patients who did not undergo resections (12 patients), reasons included failure to localize the epileptogenic zone (4 patients); multifocal epileptogenic zone (4 patients); epileptogenic zone located in eloquent cortex, preventing resection (3 patients); and improvement in seizures after the implantation (1 patient). In patients who subsequently underwent resections, 10 patients (55.5%) were seizure free (Engel class I) and 5 patients (27.7%) experienced seizure improvement (Engel class II or III) at the end of the follow-up period (mean, 25.9 months; range, 12 to 47 months). The complication rate in SEEG implantations was 3%. CONCLUSION: The SEEG methodology is safe and should be considered in children/adolescents with difficult-to-localize epilepsy. When applied to highly complex and difficult-to-localize pediatric patients, SEEG may provide an additional opportunity for seizure freedom in association with a low morbidity rate.

Combining stereo-electroencephalography and subdural electrodes in the diagnosis and treatment of medically intractable epilepsy.

Stereo-electroencephalography (SEEG) has advantages for exploring deeper epileptic foci. Nevertheless, SEEG can only sample isolated cortical areas and its spatial limitation, with the inability to record contiguous cortical regions, may cause difficulties in interpretation. In light of these limitations, the authors describe the hybrid technique of SEEG and subdural strip electrode placement. The hybrid technique was used for a presurgical evaluation in four patients with intractable epilepsy. Initially, the depth electrodes were inserted with a robotic stereotactic system. Thereafter, a skin incision and a small craniectomy were performed at the entry point of the strip electrode trajectory. The dura was opened and, under live fluoroscopic guidance, strip electrodes were slid into the subdural space. In these patients, the additional subdural strip electrodes provided (1) information regarding the precise description of seizure spread in the cortical surface adjacent to the subdural space, (2) identification of epileptogenic zones located near the crown, (3) more precise definition of functional cortex and (4) a better delineation of the interface between epileptogenic zones and functional cortex. This hybrid technique provides additional data compared to either technique alone, offering superior understanding of the dynamics of the epileptic activity and its interaction with functional cortical areas.

Long-term functional outcomes and their predictors after hemispherectomy in 115 children.

PURPOSE: To examine the long-term functional outcomes and their predictors using a patient/family centered approach in a cohort of children who had hemispherectomy. Functional outcome measures studied were the following: ambulation ability, visual symptoms, spoken language, reading skills, and behavioral problems. METHODS: We reviewed 186 consecutive children who underwent hemispherectomy between 1997 and 2009 at our center. Preoperative clinical, electroencephalography (EEG), imaging, and surgical data were collected. One hundred twenty-five families completed a structured questionnaire to assess the functional status and seizure outcome. Prognostic predictors were examined using a multivariate regression analysis. KEY FINDINGS: At a mean follow-up of 6.05 years after hemispherectomy, 70 patients (56%) were seizure-free and 45 (36%) had seizure recurrence; 10 patients (8%) were free of their preoperative seizures but had new-onset nonepileptic spells and were excluded from further analysis. Of 115, at follow-up (mean age at follow-up 12.7 years, range 2-28 years), 96 patients (83%) walked independently, 10 (8.7%) walked with assistance, and 9 (7.8%) were unable to walk. New visual symptoms that were not present preoperatively were reported only in 28 patients (24%). Eighty patients (70%) had satisfactory spoken language skills but only 44 (42%) of the 105 children older than 6 years had satisfactory reading skills. Significant behavioral problems were reported in 30 patients (27%). Only five (6.2%) of the 81 children aged between 6 and 18 years attended mainstream school without assistance; 48 (59%) were in mainstream school with assistance and the rest were in special school for disabled or home cared. Five (21%) of the 24 patients older than 18 years of age were gainfully employed. Multivariate logistic regression analysis identified the following factors as independently associated with poor functional outcome. (1) Seizure recurrence negatively affected all functional domains--ambulation ability, spoken language and reading skills, and behavior (p < 0.05). (2) Abnormalities in the unoperated hemisphere on magnetic resonance imaging (MRI) (p < 0.05) and preexisting quadriparesis (p < 0.01) correlated with poor motor outcome. (3) Multilobar MRI abnormalities in the contralateral hemisphere (odds ratio [OR] = 13.9, p = 0.001) and young age (indeterminate preoperative language status) at hemispherectomy (OR = 11.1, p = 0.01) also correlated with poor language outcome. (4) Younger age at epilepsy onset correlated with poor reading skills (p = 0.01) but not with spoken language skills. SIGNIFICANCE: This study highlights the long-term functional status of patients after hemispherectomy. The majority of patients were ambulant independently; however, impairments in reading and spoken language were frequent. Seizure recurrence after hemispherectomy and contralateral hemisphere abnormalities on MRI were the major predictors of poor outcome in ambulation, spoken language, and reading abilities. This study will assist in presurgical counseling using simple understandable functional outcome measures and may help in planning early interventions after hemispherectomy to improve functional outcome.