Perioperative considerations for adult patients with Dravet syndrome in regional centres.

Dravet syndrome (DS) is a rare and intractable severe form of epilepsy presenting in infancy with frequent prolonged myoclonic seizures and neurodevelopmental impairment, associated with a SCN1A gene mutation. Seizures are often triggered by temperature fluctuations and hyperthermia. This report presents a woman in her late adolescence with DS complicated with intractable catamenial epilepsy, a sex-specific form of epilepsy with seizure activity prominent during phases of the menstrual cycle. The patient underwent general anaesthesia for a hysteroscopy, cervical dilatation and endometrial curettage with Mirena insertion to improve seizure control. Her perioperative care was optimised for seizure prevention with continuation of antiepileptic medications, strict temperature monitoring and control, optimised anaesthetic agents encompassing induction with propofol and fentanyl with maintenance sevoflurane, followed by attentive postoperative care and monitoring. This case demonstrates that general anaesthesia can safely be delivered to adult patients with DS in rural and regional areas with thorough perioperative planning.

Epilepsy with myoclonic absences: a case series highlighting clinical heterogeneity and surgical management.

OBJECTIVE: Epilepsy with myoclonic absences is a rare epilepsy syndrome with distinct features and high rates of drug resistance. Identifying this syndrome may help guide treatment decisions. We highlight clinical heterogeneity in this case series and two cases in which corpus callosotomy was performed. METHODS: Medical records were reviewed between 2017 and 2021 to identify demographics, comorbidities, age at onset, EEG findings, diagnostic evaluations, seizure semiologies, seizure frequency, anti-seizure medications, diet therapy and surgical treatments in patients with myoclonic absences. RESULTS: Ten patients were identified including twins with myoclonic absence status epilepticus. Forty percent had an atonic component, 20% presented with myoclonic absence status epilepticus and 60% had incomplete control of seizures at last follow-up visit. Two patients with epilepsy with myoclonic absences with atonia underwent corpus callosotomy; one patient was seizurefree eight months after surgery and the other had greater than 50% seizure reduction over a five-month period. SIGNIFICANCE: Phenotypic heterogeneity was evident based on seizure semiologies, comorbidities, seizure frequency and response to anti-seizure medications and non-medication treatments. Of patients with an atonic component, 75% did not achieve seizure freedom with medication alone. Corpus callosotomy was performed in two of these patients with encouraging seizure response thus far, however, the efficacy of this treatment should be further evaluated in a larger study.

Focal epilepsy in SCN1A-mutation carrying patients: is there a role for epilepsy surgery?

Variants in the gene SCN1A are a common genetic cause for a wide range of epilepsy phenotypes ranging from febrile seizures to Dravet syndrome. Focal onset seizures and structural lesions can be present in these patients and the question arises whether epilepsy surgery should be considered. We report eight patients (mean age 13y 11mo [SD 8y 1mo], range 3-26y; four females, four males) with SCN1A variants, who underwent epilepsy surgery. Outcomes were variable and seemed to be directly related to the patient's anatomo-electroclinical epilepsy phenotype. Patients with Dravet syndrome had unfavourable outcomes, whilst patients with focal epilepsy, proven to arise from a single structural lesion, had good results. We conclude that the value of epilepsy surgery in patients with an SCN1A variant rests on two issues: understanding whether the variant is pathogenic and the patient's anatomo-electroclinical phenotype. Careful evaluation of epilepsy phenotype integrated with understanding the significance of genetic variants is essential in determining a patient's suitability for epilepsy surgery. Patients with focal onset epilepsy may benefit from epilepsy surgery, whereas those with Dravet syndrome do not. WHAT THIS PAPER ADDS: Patients should not automatically be excluded from epilepsy surgery evaluation if they carry an SCN1A variant. Patients with focal epilepsy may benefit from epilepsy surgery; those with Dravet syndrome do not.

Successful corpus callosotomy for Doose syndrome.

Doose syndrome (epilepsy with myoclonic-atonic seizures) is an epilepsy syndrome with an incidence of approximately 1-2% of childhood-onset epilepsies. Although this syndrome is associated with multiple types of generalized seizures, the diagnosis is based on the presence of myoclonic-atonic seizures. Eighteen percent of patients have refractory seizures and intellectual disabilities. There have, however, been a few reports on the efficacy of surgical treatment for Doose syndrome. We describe a case of Doose syndrome in a 10-year-old boy. He developed generalized tonic-clonic seizures at 3years 8months of age and subsequently developed myoclonic-atonic, myoclonic, and tonic seizures. The frequent myoclonic seizures were refractory to multiple antiepileptic medications. His cognitive development was moderately delayed. Anterior four fifths corpus callosotomy was performed at 8years 5months of age. His seizures, especially myoclonic seizures, were markedly reduced. He was given vagus nerve stimulation therapy at 9years and 1month of age, which led to complete resolution of the myoclonic seizures. Corpus callosotomy can be a good treatment strategy in patients with Doose syndrome with medically refractory generalized seizures.

Time-frequency analysis of intracranial EEG in patients with myoclonic seizures.

Myoclonic seizures are defined as generalized seizures according to the classification of seizure by the International League Against Epilepsy (ILAE). The pathogenesis of myoclonic seizures is not yet clear. There are very few studies on the focal surgical treatment of myoclonic seizures. The aim of this study is to investigate the characteristics of myoclonic seizure onset in different bands of the intracranial electroencephalogram (EEG) and their dynamic changes in temporal and spatial evolution. We studied four patients with myoclonic seizures who were under the focal resection of the epileptogenic zone. We retrospectively analyzed the semiology, electrocorticogram (ECoG) and imaging data of these patients, and conducted time-frequency analysis of broadband ECoG activity. We found that myoclonic seizures without clinical lateralizing signs could be improved by the resection of the epileptogenic zone. The ECoG power in different frequency bands increased to a peak at 0.5s before the clinical seizure onset and decreased quickly afterwards. The power of alpha activity was highest during the preictal and ictal periods. The central zone had higher power than the epileptogenic zone in all frequency bands during the preictal period, but this difference was not statistically significant. Our results suggest that myoclonic seizures in some patients might have a focal origination, with a fast bilateral propagating network in all frequency bands, especially the alpha band.

Palliative epilepsy surgery in Dravet syndrome-case series and review of the literature.

PURPOSE: Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy (SMEI), is a rare genetic disorder that results in severe childhood-onset epilepsy. Children with DS initially present with seizures in the first year of life that are often associated with fevers. With age, multiple seizure types develop. There are few reports and no guidelines regarding palliative surgical treatment for DS. Therefore, we reviewed our surgical experience with DS. METHODS: We conducted a retrospective review of all patients with genetically confirmed DS who underwent either vagal nerve stimulator (VNS) implantation or corpus callosotomy (CC) from May 2001 to April 2014 at our institution. All inpatient and outpatient relevant documentation were reviewed. Demographic information, genetic mutation, operation performed, and preoperative and postoperative seizure frequency were recorded. Inclusion criteria required greater than one-year postoperative follow-up. RESULTS: Seven children with DS were assessed. Six patients were treated with VNS and one patient was treated with CC. In one child, VNS was followed by CC as a secondary procedure. Therefore, in total, eight surgeries were performed on seven patients during the study period. At least 1 year elapsed from presentation to our hospital and surgery for all patients. Average time after the first seizure to VNS was 4.1 years, and the average time after the first seizure to CC was 7.6 years. The mean age of patients undergoing VNS implantation was 4.3 years, and the mean age for patients undergoing CC was eight. Average follow-up for all seven patients was 6.6 years. Seizures were decreased in five of the six patients with VNS and decreased in the two patients after CC. Four of the six patients who had VNS implanted had a greater than 50 % reduction in seizure frequency, and one of the six patients who had VNS implanted had a less than 50 % reduction in seizure frequency. One patient did not respond effectively to the VNS and had very limited change in seizure frequency. Both patients who had a CC had a greater than 50 % reduction in seizure frequency. CONCLUSIONS: Both VNS and CC in patients with DS can be effective at reducing seizure frequency. Patients with DS may benefit from earlier and more aggressive surgical intervention. Studies using larger patient cohorts will help clarify the role that surgery may play in the multidisciplinary approach to controlling seizures in DS. Further studies will help determine the appropriate timing of and type of surgical intervention.

Neurological sequelae from brachiocephalic vein stenosis.

Stenosis of central veins (brachiocephalic vein [BCV] and superior vena cava) occurs in 30% of hemodialysis patients, rarely producing intracranial pathology. The authors present the first cases of BCV stenosis causing perimesencephalic subarachnoid hemorrhage and myoclonic epilepsy. In the first case, a 73-year-old man on hemodialysis presented with headache and blurry vision, and was admitted with presumed idiopathic intracranial hypertension after negative CT studies and confirmatory lumbar puncture. The patient mildly improved until hospital Day 3, when he experienced a seizure; emergency CT scans showed perimesencephalic subarachnoid hemorrhage. Cerebral angiography failed to find any vascular abnormality, but demonstrated venous congestion. A fistulogram found left BCV occlusion with jugular reflux. The occlusion could not be reopened percutaneously and required open fistula ligation. Postoperatively, symptoms resolved and the patient remained intact at 7-month follow-up. In the second case, a 67-year-old woman on hemodialysis presented with right arm weakness and myoclonic jerks. Admission MRI revealed subcortical edema and a possible dural arteriovenous fistula. Cerebral angiography showed venous engorgement, but no vascular malformation. A fistulogram found left BCV stenosis with jugular reflux, which was immediately reversed with angioplasty and stent placement. Postprocedure the patient was seizure free, and her strength improved. Seven months later the patient presented in myoclonic status epilepticus, and a fistulogram revealed stent occlusion. Angioplasty successfully reopened the stent and she returned to baseline; she was seizure free at 4-month follow-up. Central venous stenosis is common with hemodialysis, but rarely presents with neurological findings. Prompt recognition and endovascular intervention can restore normal venous drainage and resolve symptoms.

Sturge-Weber syndrome: a favourable surgical outcome in a case with contralateral seizure onset and myoclonic-astatic seizures.

Sturge-Weber syndrome is a neurocutaneous disorder classically characterized by the presence of facial port-wine stain and ipsilateral leptomeningeal angiomatosis. It is often associated with refractory epilepsy which requires surgical treatment. We present a case of a patient who initially presented with partial seizures of temporo-occipital origin, ipsilateral to the pial angiomatosis. During the course of the disease, the patient developed medically refractory epilepsy with partial seizures originating predominantly from the contralateral temporo-occipital area as well as myoclonic and myoclonic-astatic seizures. Resection of the occipital and temporal lobe affected by the pial angioma resulted in favourable outcome. Bilateral dysfunction observed in Sturge-Weber syndrome may result in an increased capability of focal discharges to generate synchronous epileptiform activity leading to an increased incidence of generalised seizures, most probably via a mechanism of secondary bilateral synchrony. [Published with video sequences].

Epilepsy surgery in a pediatric population: a retrospective study of 129 children from a tertiary care hospital in a developing country along with assessment of quality of life.

PURPOSE: To assess the outcome of a pediatric population operated for drug-resistant epilepsy from a large tertiary care center in India. METHODS: Retrospectively: quality of life (QOL); prospectively: preoperative assessment included interictal EEG, MRI (as per epilepsy protocol), video-EEG. Ictal SPECT (with subtraction) and PET were performed when required. QOL scores were assessed using the HASS or SSQ for seizure severity, Quality of Life in Childhood Epilepsy (QOLCE) for QOL, and Child Behavior Check List (CBCL) for behavior. RESULTS: 142 were operated from January 2000 to June 2011 by the senior author. 118 patients with at least 1 year of follow-up were included in the study. Mean age at surgery was 9.8 ± 4.3 years. In addition, 40 patients underwent QOL assessment prospectively both before and after surgery. Mean duration of epilepsy was 5.3 ± 3.3 years. A class I outcome (Engel's) was seen in 79.5% patients, class II in 8.6%, class III in 10.7%, and class IV in 1 patient. As per surgical procedures, class I outcome in patients who underwent temporal resection, hemispherotomy and extratemporal resection was 76, 87 and 72%, respectively. QOL scores correlated with duration of seizures, epileptic encephalopathy and outcome of surgery, but not with side of surgery, age and sex. CONCLUSIONS: This study, the largest reported from India, has demonstrated satisfactory results for epilepsy surgery in children.

Long-term seizure outcome after corpus callosotomy: a retrospective analysis of 95 patients.

OBJECT: The authors report long-term follow-up seizure outcome in patients who underwent corpus callosotomy during the period 1981-2001 at the Montreal Neurological Institute. METHODS: The records of 95 patients with a minimum follow-up of 5 years (mean 17.2 years) were retrospectively evaluated with respect to seizure, medication outcomes, and prognostic factors on seizure outcome. RESULTS: All patients had more than one type of seizure, most frequently drop attacks and generalized tonic-clonic seizures. The most disabling seizure type was drop attacks, followed by generalized tonic-clonic seizures. Improvement was noted in several seizure types and was most likely for generalized tonic-clonic seizures (77.3%) and drop attacks (77.2%). Simple partial, generalized tonic, and myoclonic seizures also benefited from anterior callosotomy. The extent of the callosal section was correlated with favorable seizure outcome. The complications were mild and transient and no death was seen. CONCLUSIONS: This study confirms that anterior callosotomy is an effective treatment in intractable generalized seizures that are not amenable to focal resection. When considering this procedure, the treating physician must thoroughly assess the expected benefits, limitations, likelihood of residual seizures, and the risks, and explain them to the patient, his or her family, and other caregivers.

Corpus callosotomy for treatment of pediatric epilepsy in the modern era.

OBJECTIVE: The purpose of this study was to evaluate seizure outcome in children with intractable secondary generalized epilepsy without a resectable focus who underwent complete corpus callosotomy and compare these results to those of anterior two-third callosotomy. METHOD: Data were obtained for all patients who underwent a corpus callosotomy from 2000 to 2005. The study involved 37 patients. Eleven patients had anterior two-third corpus callosotomy compared with 28 patients who underwent complete corpus callosotomy. Two of these patients had completion of their callosotomy following initial partial callosotomy. Seizure type, seizure frequency, and family satisfaction were evaluated for all patients pre- and postoperatively. RESULTS: A reduction of >or=75% in seizures occurred in 75% of the total-callosotomy patients compared to 55% of the partial-callosotomy patients. Family satisfaction for complete and partial callosotomy was 89 and 73%, respectively. No prolonged neurologic deficits were observed in either group. CONCLUSION: Complete corpus callosotomy is the most effective treatment for secondary generalized intractable seizures not amenable to focal resection in children.

Nonpharmacologic treatment of the catastrophic epilepsies of childhood.

The catastrophic epilepsy syndromes of childhood are initially treated with a pharmacologic intervention in most cases. However, due to the poor response patients often have to pharmacologic interventions, nonpharmacologic treatment options are an important part of a comprehensive treatment plan for this group of children. Additionally, nonpharmacologic therapy may offer a method to minimize associated morbidity and mortality. This article discusses the use of epilepsy surgery, the ketogenic diet, and vagus nerve stimulation in the treatment of patients with infantile spasms, Lennox-Gastaut syndrome, and progressive myoclonic epilepsy. Efficacy of the nonpharmacologic treatment options, as measured by reduction in seizure frequency, as well as by developmental progress or behavioral improvement, varies according to the specific catastrophic epilepsy disorder and the treatment option.

Is a cortical spike discharge "transferred" to the contralateral cortex via the corpus callosum?: An intraoperative observation of electrocorticogram and callosal compound action potentials.

PURPOSE: By means of the intraoperative electrophysiologic observation, we reevaluated the "transfer" theory that a transcallosal volley invoked by a cortical spike discharge in one hemisphere directly causes its contralateral counterpart via the corpus callosum (CC). METHODS: Twenty-six patients who underwent corpus callosotomy were the subjects of this study. Intraoperatively, electrocorticograms from both hemispheres were simultaneously monitored with callosal compound action potentials (CCAPs) from the CC. Analysis was conducted on (a) the interhemispheric delay of bilaterally synchronous spike-and-wave discharges (BSSWs), and (b) the chronological relation between BSSWs and CCAPs. RESULTS: The side of prior spike discharges was never fixed but was occasionally reversed. Interhemispheric delays between the BSSWs were not constant, regardless of direction, and fluctuated in all patients. Most of the interhemispheric delays were distributed within 20 ms with a mode of 0 ms. The waveform of the CCAP was characterized by slow-rising negative potential change that attained its peak after a cortical spike discharge. These findings were identical in all the patients regardless of whether the BSSWs were changed or unchanged after callosotomy. CONCLUSIONS: If the "transfer" role of the CC is true, interhemispheric delays between BSSWs must be longer than interhemispheric axonal conduction time (about 20 ms), and a preceding cortical spike discharge must produce a CCAP and then a contralateral one in order of time. However, this hypothesis was not confirmed in the present study. We propose the interhemispheric recruitment of the epileptogenic state as a different role of the CC on epileptogenesis.

Electroencephalographic dipoles of spikes with and without myoclonic jerks caused by epilepsia partialis continua.

We used electroencephalographic (EEG) dipole analysis to investigate the generators of spikes with and without myoclonic jerks in a 12-year-old patient with epilepsia partialis continua secondary to left parietal cortical dysplasia. We recorded EEG and right wrist extensor electromyography (EMG) and collected 42 spikes with jerks (jerking spikes) and 42 spikes without jerks (nonjerking spikes). We applied a single moving dipole model to the individual and averaged spikes. Dipoles at the negative peak of individual jerking and nonjerking spikes were localized in the dysplastic area. At the onset of the averaged jerking spike that preceded the EMG discharges by 20 ms, the dipole was in the motor cortex, whereas for the averaged nonjerking spike, the dipole was in the sensory cortex. The dipole moment at averaged jerking spike onset was twice that of the averaged nonjerking spike. Electroencephalographic dipole analysis of averaged spikes differentiated the generator of jerking and nonjerking spikes in epilepsia partialis continua. Individual dipoles demonstrated the area of epileptogenic cortical dysplasia.

Tuberous sclerosis: epileptogenicity and multimodal presurgical evaluations.

We report on a patient with tuberous sclerosis-related epilepsy who benefited from surgical treatment. Various presurgical evaluations, including positron emission tomography (PET), made it possible for us to localize the epileptic focus accurately. In this paper, we stress the importance of performing multimodal evaluations to determine which tubers really possess epileptogenicity. In addition, the implications of PET in tuberous sclerosis-related epilepsy are described.

Neuropsychology of epilepsy.

PURPOSE: The neuropsychological approach to epilepsy is indispensable for assessment of cognitive function in an interictal period including pre- and postsurgical evaluation, and for disclosing the semiology of nonconvulsive status epilepticus. Another use of the neuropsychological approach is to identify a seizure-precipitating factor by loading systematic cognitive tasking, termed "neuropsychological EEG activation" (NPA), during standard EEG recordings. METHODS: In this study, NPA tasks consisted of reading, speaking, writing, written arithmetic calculation, mental arithmetic calculation, and spatial construction. RESULTS: The NPA tasks provoked epileptic discharges in 7.9% of the 480 epileptic patients and were often accompanied by myoclonic seizures. Among the cognitive tasks, mental activities mainly associated with use of the hands [i.e., writing (68.4%), written calculation (55.3%), and spatial construction (63.2%)] provoked the most discharges. Seizure-precipitating mental activities were found to be almost exclusively related to idiopathic generalized epilepsies (IGEs). CONCLUSIONS: These results suggest that NPA is a useful tool for examining the relationship between cognitive function and epileptic seizures, and that the IGE patients with myoclonic seizures are vulnerable to higher mental activity.

Corpus callosotomy in treatment of medically resistant epilepsy: preliminary results in a pediatric population.

We report the results of 34 patients who underwent corpus callosotomy between 1986 and 1989 with 28-65 months of postoperative follow-up (mean 42 months). Thirty-two patients had mental retardation and 26 had significant behavioral problems. Thirteen patients had total section, 8 had subtotal section with preservation of the posterior half of the splenium, and 13 had section of the anterior two thirds of the callosum. Satisfactory seizure control was achieved in 25 patients (73.5%) Atonic seizures, followed by tonic seizures, generalized tonic-clonic seizures (GTCs), and atypical absence seizures were most improved. Myoclonic and complex partial seizures (CPS) did not improve significantly. No deterioration in seizure status was observed postoperatively. Two patients developed previously unobserved simple seizures and CPS postoperatively, but they were not as disabling as the preoperative seizures. Among the patients with behavioral problems, 81% had significant decrease in aggressiveness, hyperactivity, and/or attention deficit. Patients who underwent total section had interhemispheric disconnection symptoms that improved progressively and did not interfere with daily life. Decreased speech output, dysarthria, and gait dyspraxia occurred after total callosal section and persisted in 5 of the 13 patients. Patients who underwent anterior two thirds or subtotal sections did not have such symptoms. Early postoperative complications consisted of aseptic ventriculitis (5), subdural hematoma (1), and wound infection (4) and resolved without sequelae.

Possible blindsight in infants lacking one cerebral hemisphere.

Patients with damage to the striate cortex have a subjectively blind region of the visual field, but may still be able to detect and localize targets within this region. But the relative roles in this 'blindsight' of subcortical neural systems, and of pathways to extra-striate visual areas, have been uncertain. Here we report results on two infants in whom one cerebral hemisphere, including both striate and extra-striate visual cortex, needed surgical removal in their first year. Single conspicuous targets in the half-field contralateral to the lesion could elicit fixations, implying detection and orienting by a subcortical system. In contrast, binocular optokinetic nystagmus (OKN), for which a subcortical pathway has often been thought adequate, showed a marked asymmetry. In normal neonates, fixation shifts and OKN have both been taken to reflect subcortical control; our results are consistent with subcortical control for fixation but not for OKN.

Soviet investigations in epilepsy.

A wide ranging review of the Soviet literature on epilepsy is provided, detailing historical aspects, pathophysiology, investigations, medical treatment, and the long term results of surgical treatment, including stereotaxic intervention. The features of Kojevnikoff epilepsy are presented.