Lennox-Gastaut syndrome: a consensus approach to differential diagnosis.

Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy that shares many features and characteristics of other treatment-resistant childhood epilepsies. Accurate and early diagnosis is essential to both prognosis and overall patient management. However, accurate diagnosis of LGS can be clinically challenging. This article summarizes key characteristics of LGS and areas of overlap with other childhood epilepsies. Drawing upon input from a committee of established LGS experts convened in June 2012 in Chicago, Illinois, the authors highlight key diagnostic tests for making the differential diagnosis and propose a diagnostic scheme for people with suspected LGS.

Safety and retention rate of rufinamide in 300 patients: a single pediatric epilepsy center experience.

OBJECTIVE: Reports of studies evaluating rufinamide as an add-on therapy in children and adolescents with refractory epilepsy are restricted to a few publications. Prospective multicenter studies including children and adults have yielded important information about several types of epilepsies and syndromes. We evaluated the use of rufinamide in a single pediatric center with a large cohort and long-term follow-up period. METHODS: We retrospectively included patients taking rufinamide from November 2008 to March 2013. Response was defined by a seizure reduction of ≥50% compared to baseline. RESULTS: Three hundred patients with a median age of 9.1 years (range 0.4-29.6 years) were reviewed. Median follow-up was 9 months (range 1-37 months). Epilepsy etiology was classified as genetic (23.7%), structural/metabolic (41%), and unknown cause (35.3%). Overall, rufinamide treatment led to a median seizure frequency reduction of 59.2% from responders to baseline. Seizure reduction was greater in patients with genetic etiology compared to structural/metabolic (66.2% vs. 45.5% responders, p = 0.005). Rufinamide was discontinued in 110 (36.7%) of 300 patients: 63 (21%) due to unsatisfactory response, 47 (15.7%) due to side effects, and in 18 (6%) of those due to both. Most common adverse effects were sleepiness, vomiting, mood changes, nausea, and loss of appetite. Median time to loss of efficacy was 11.6 months (range 3-28 months). SIGNIFICANCE: Rufinamide provides satisfactory seizure reduction as an adjunctive treatment in refractory epilepsy. Results need to be interpreted in the setting of data acquisition, including inherent biases of retrospective studies. Patients with a known genetic etiology may have better responses than patients with structural/metabolic etiology.

Current dipole orientation and distribution of epileptiform activity correlates with cortical thinning in left mesiotemporal epilepsy.

To evaluate cortical architecture in mesial temporal lobe epilepsy (MTLE) with respect to electrophysiology, we analyze both magnetic resonance imaging (MRI) and magnetoencephalography (MEG) in 19 patients with left MTLE. We divide the patients into two groups: 9 patients (Group A) have vertically oriented antero-medial equivalent current dipoles (ECDs). 10 patients (Group B) have ECDs that are diversely oriented and widely distributed. Group analysis of MRI data shows widespread cortical thinning in Group B compared with Group A, in the left hemisphere involving the cingulate, supramarginal, occipitotemporal and parahippocampal gyri, precuneus and parietal lobule, and in the right hemisphere involving the fronto-medial, -central and -basal gyri and the precuneus. These results suggest that regardless of the presence of hippocampal sclerosis, in a subgroup of patients with MTLE a large cortical network is affected. This finding may, in part, explain the unfavorable outcome in some MTLE patients after epilepsy surgery.

Propagation of epileptic spikes reconstructed from spatiotemporal magnetoencephalographic and electroencephalographic source analysis.

The purpose of this study is to assess the accuracy of spatiotemporal source analysis of magnetoencephalography (MEG) and scalp electroencephalography (EEG) for representing the propagation of frontotemporal spikes in patients with partial epilepsy. This study focuses on frontotemporal spikes, which are typically characterized by a preceding anterior temporal peak followed by an ipsilateral inferior frontal peak. Ten patients with frontotemporal spikes on MEG/EEG were studied. We analyzed the propagation of temporal to frontal epileptic spikes on both MEG and EEG independently by using a cortically constrained minimum norm estimate (MNE). Spatiotemporal source distribution of each spike was obtained on the cortical surface derived from the patient's MRI. All patients underwent an extraoperative intracranial EEG (IEEG) recording covering temporal and frontal lobes after presurgical evaluation. We extracted source waveforms of MEG and EEG from the source distribution of interictal spikes at the sites corresponding to the location of intracranial electrodes. The time differences of the ipsilateral temporal and frontal peaks as obtained by MEG, EEG and IEEG were statistically compared in each patient. In all patients, MEG and IEEG showed similar time differences between temporal and frontal peaks. The time differences of EEG spikes were significantly smaller than those of IEEG in nine of ten patients. Spatiotemporal analysis of MEG spikes models the time course of frontotemporal spikes as observed on IEEG more adequately than EEG in our patients. Spatiotemporal source analysis may be useful for planning epilepsy surgery, by predicting the pattern of IEEG spikes.

In-session seizures during low-frequency repetitive transcranial magnetic stimulation in patients with epilepsy.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) is emerging as a therapeutic tool for patients with intractable epilepsy. Although seizures during treatment have been reported as adverse events in some patients, the nature and severity of seizures that may be provoked by low-frequency rTMS in patients with epilepsy have not been extensively studied. Accordingly, this article documents seizures in patients (n=5) with intractable epilepsy and average seizure frequency greater than one per day who underwent 1-Hz rTMS for seizure suppression. We report three observations in the present case series: (1) in each instance the in-session seizure was typical in semiology to the patient's habitual seizures, (2) the duration of each documented seizure was either the same as or shorter than the patients' baseline seizures, and (3) the overall neurological outcome on follow-up was not affected by the in-session seizures. More data will be required for valid conclusions with respect to safety and tolerability of low-frequency rTMS in patients with epilepsy, but it is noteworthy from our perspective that seizures during rTMS in this series were similar to the patients' habitual seizures, occurred in patients with epilepsy with baseline seizure frequency exceeding one per day, and did not correlate with a poor neurological outcome or with absence of clinical response to rTMS.

Debate: Does genetic information in humans help us treat patients? PRO--genetic information in humans helps us treat patients. CON--genetic information does not help at all.

PRO: In the past decade, genotyping has started to help the neurologic practitioner treat patients with three types of epilepsy causing mutations, namely (1) SCN1A, a sodium channel gene mutated in Dravet's sporadic severe myoclonic epilepsy of infancy (SMEI and SMEB); (2) laforin (dual specificity protein phosphatase) and malin (ubiquitin E3 ligase) in Lafora progressive myoclonic epilepsy (PME); and (3) cystatin B in Unverricht-Lundborg type of PME. Laforin, malin, and cystatin B are non-ion channel gene mutations that cause PME. Genotyping ensures accurate diagnosis, helps treatment and genetic counseling, psychological and social help for patients and families, and directs families to organizations devoted to finding cures for specific epilepsy diseases. In SCN1A and cystatin B mutations, treatment with sodium channel blockers (phenytoin, carbamazepine, oxcarbazepine, lamotrigine) should be avoided. Because of early and correct diagnosis by genotyping of SCN1A mutations, the avoidance of sodium channel blockers, and aggressive treatment of prolonged convulsive status, there is hope that Dravet's syndrome may not be as severe as observed in all past reports. Genotyping also identifies nonsense mutations in Lafora PME. Nonsense mutations can be corrected by premature stop codon readthrough drugs such as gentamicin. The community practitioner together with epilepsy specialists in PME can work together and acquire gentamicin (Barton-Davis et al., 1999) for "compassionate use" in Lafora PME, a generalized lysosome multiorgan storage disorder that is invariably fatal. In Unverricht-Lundborg PME, new cohorts with genotyped cystatin B mutations have led to the chronic use of antioxidant N-acetylcysteine and combination valproate clobazam or clonazepam plus antimyoclonic drugs topiramate, zonisamide, piracetam, levetiracetam, or brivaracetam. These cohorts have minimal ataxia and no dementia, questioning whether the syndrome is truly progressive. In conclusion, not only is genotyping a prerequisite in the diagnosis of Dravet's syndrome and the progressive myoclonus epilepsies, but it also helps us choose the correct antiepileptic drugs to treat seizures in Dravet's syndrome and Unverricht-Lundborg PME. Genotyping also portends a brighter future, helping us to reassess the true course, severity, and progressive nature of Dravet's syndrome and Unverricht-Lundborg PME and helping us craft a future curative treatment for Dravet's syndrome and Lafora disease. Without the genotyping diagnosis of epilepsy causing mutations we are stuck with imprecise diagnosis and symptomatic treatment of seizures. CON: Genotyping of epilepsy may help to better understand the genetics of epilepsy, to establish an etiology in a patient with epilepsy, to provide genetic counseling, and to confirm a clinical diagnosis. However, critical analysis reveals that genotyping does not contribute to an improved treatment for the patients. In order to improve treatment, genotyping would have to (1) improve our ability to select the drug of choice for a given epilepsy or epileptic syndrome; (2) improve our ability to predict the individual risk of adverse reactions to certain drugs; (3) improve our ability to avoid unnecessary treatments or treatments that could aggravate seizures. Many example illustrate the lack of impact of genetic information on the treatment outcome: we do not treat Dravet syndrome more successfully since SCN1A testing became available; we do not treat Lafora disease more successfully since testing for laforin and malin became available; we do not need to know the genetic nature of Unverricht-Lundborg disease or test for the cystatin B mutation in order to select or avoid certain drugs; we do not treat Rett syndrome more successfully since MECP2 testing became available; we do not treat JME more successfully since we know its genetic origin; we do not treat autosomal dominant nocturnal frontal lobe epilepsy more successfully since we know its genetic origin and can test for its mutation. The clinical characteristics as well as the response to treatment of these epilepsy syndromes have been well established before genotyping became available. It can not be argued that genotyping is necessary for establishing a diagnosis or ensure accurate diagnosis. Since not all individuals with given syndromes have been shown to have the corresponding mutation, the clinical diagnosis must have been based on well-established clinical criteria. In addition, the presence or absence of the mutation in a given patient has never been shown to specifically predict the response to any form of treatment, positive or negative. Finally, the appropriate psychological and social help in a given patient will not depend on the identification of a mutation. This does not leave any role for genotyping in epilepsy for the sole reason of improving treatment of the patient. Claiming that the result of genotyping predicts optimal treatment in certain epilepsies is equivalent to stating that genotyping for diabetes has become available and that, based on this breakthrough, insulin can now be selected as the treatment of choice in those who test positive.

Antiepileptic drugs--best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies.

Although no randomized studies have demonstrated a positive impact of therapeutic drug monitoring (TDM) on clinical outcome in epilepsy, evidence from nonrandomized studies and everyday clinical experience does indicate that measuring serum concentrations of old and new generation antiepileptic drugs (AEDs) can have a valuable role in guiding patient management provided that concentrations are measured with a clear indication and are interpreted critically, taking into account the whole clinical context. Situations in which AED measurements are most likely to be of benefit include (1) when a person has attained the desired clinical outcome, to establish an individual therapeutic concentration which can be used at subsequent times to assess potential causes for a change in drug response; (2) as an aid in the diagnosis of clinical toxicity; (3) to assess compliance, particularly in patients with uncontrolled seizures or breakthrough seizures; (4) to guide dosage adjustment in situations associated with increased pharmacokinetic variability (e.g., children, the elderly, patients with associated diseases, drug formulation changes); (5) when a potentially important pharmacokinetic change is anticipated (e.g., in pregnancy, or when an interacting drug is added or removed); (6) to guide dose adjustments for AEDs with dose-dependent pharmacokinetics, particularly phenytoin.

Focal cortical malformations can show asymmetrically higher uptake on interictal fluorine-18 fluorodeoxyglucose positron emission tomography (PET).

Interictal fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is a component of the presurgical evaluation of patients with medically intractable epilepsy, including patients with malformations of cortical development. The authors describe 3 cases of focal cortical malformations that displayed asymmetrically higher uptake on FDG-PET performed in the interictal state in patients undergoing evaluation for possible focal resection for refractory localization-related epilepsy. The evaluation included routine and prolonged video electroencephalography (EEG), magnetic resonance imaging (MRI), interictal FDG-PET with concurrent EEG, and single-photon emission computed tomography (SPECT). All 3 patients had focal cortical malformations on MRI corresponding to regions of asymmetrically higher uptake on FDG-PET. EEG confirmed that the FDG-PET studies were performed in the interictal state. The lesions included a large region of subcortical heterotopia in the right frontal lobe, a left temporal lobe dysplasia, and a region of subcortical heterotopia in the right occipital lobe. In both patients with subcortical heterotopia, there were other focal regions of cortical malformation that were not associated with abnormal or asymmetric uptake on FDG-PET. Previous reports describe decreased uptake on interictal PET in most cases of focal cortical malformations. Normal to increased uptake has been reported with band heterotopia. The authors demonstrate that other types of focal malformations of cortical development, including focal subcortical heterotopia and lobar dysplasia, can be associated with asymmetrically higher uptake on interictal FDG-PET.

Topiramate in patients with juvenile myoclonic epilepsy.

BACKGROUND: Topiramate is a broad-spectrum agent effective against primarily generalized tonic-clonic seizures (PGTCS) as well as partial-onset seizures. Juvenile myoclonic epilepsy is one of the most common idiopathic generalized epilepsies, with most patients experiencing PGTCS. OBJECTIVE: To evaluate topiramate as add-on therapy in patients with juvenile myoclonic epilepsy. DESIGN: Post-hoc analysis of a patient subset from 2 multicenter, double-blind, randomized, placebo-controlled, parallel-group trials. SETTING: Eighteen centers in the United States; 10 centers in Europe; 1 center in Costa Rica (primary trials). PATIENTS: A total of 22 patients with juvenile myoclonic epilepsy participating in placebo-controlled trials assessing topiramate (target dose, 400 mg/d in adults) in inadequately controlled PGTCS. MAIN OUTCOME MEASURE: Reduction of PGTCS. RESULTS: A 50% or more reduction of PGTCS in 8 of 11 topiramate-treated patients (73%) and 2 of 11 placebo-treated patients (18%) (P = .03). Reductions in myoclonic, absence, and total generalized seizures were also observed, although topiramate vs placebo differences did not achieve statistical significance. CONCLUSION: As a broad-spectrum agent, topiramate is an effective option for patients with juvenile myoclonic epilepsy.

Aggravation of epilepsy by antiepileptic drugs.

Antiepileptic drugs may paradoxically worsen seizure frequency or induce new seizure types in some patients with epilepsy. The mechanisms of seizure aggravation by antiepileptic drugs are mostly unknown and may be related to specific pharmacodynamic properties of these drugs. This article provides a review of the various clinical circumstances of seizure exacerbation and aggravation of epilepsy by antiepileptic drugs as well as a discussion of possible mechanisms underlying the occasional paradoxical effect of these drugs. Antiepileptic drug-induced seizure aggravation can occur virtually with all antiepileptic medications. Drugs that aggravate seizures are more likely to have only one or two mechanisms of action, either enhanced gamma-aminobutyric acid-mediated transmission or blockade of voltage-gated sodium channels. Antiepileptic drug-induced seizure exacerbation should be considered and the accuracy of diagnosis of the seizure type should be questioned whenever there is seizure worsening or the appearance of new seizure types after the introduction of any antiepileptic medication.

Electroencephalography in neonatal seizures: comparison of a reduced and a full 10/20 montage.

This study compares a reduced electrode montage (9 electrodes) with the full 10/20 electrode montage for the ability to detect and characterize neonatal seizures and background electroencephalographic (EEG) characteristics, utilizing new digital technology allowing "remontage" of previously acquired records. A total of 151 neonatal EEG records were retrospectively and blindly analyzed by two readers. Records were first analyzed for seizure number, topography, duration, and characteristics of EEG background using the reduced montage, before reanalysis with the full montage. One hundred eighty-seven seizures were identified in 31 ictal recordings using the full montage. Using the reduced montage, 166 seizures were identified in 30 records. The sensitivity and specificity of the reduced montage for detecting electrographic seizures was 96.8% and 100% respectively. In only one patient's record, the single seizure was missed altogether. For grading background abnormalities, the sensitivity and specificity of reduced montage was 87% and 80%. Although there are inherent weaknesses in reduced montages with respect to both underestimation and overestimation of seizure number, a nine-electrode reduced montage can be a sensitive tool for identification of neonatal seizures and assessment of background characteristics of neonatal electroencephalography.

Reducing overtreatment.

Although treatment of epilepsy easily evolves into a situation of overtreatment, reversing the process can be difficult and time consuming. Benefits of reducing overtreatment may include a decrease in side effects, better seizure control, a simplification in the medication regimen, improved compliance, and reduced costs. The risks include seizure exacerbation due to withdrawal or due to loss of protection. Reversal of pharmacokinetic interactions may also lead to seizure aggravation or to drug toxicity. When reducing overtreatment, there are three main challenges: to select the drugs that should be eliminated, to choose an appropriate rate of reduction, and to anticipate reversible pharmacokinetic interactions that can have clinically significant consequences. Overall, there is a lack of published data to properly support recommendations for implementing reduction of overtreatment. This is particularly the case in the pediatric population and for the newer antiepileptic drugs.

No seizure exacerbation from risperidone in youth with comorbid epilepsy and psychiatric disorders: a case series.

OBJECTIVE: The aim of this study was to study risperidone use in pediatric patients with comorbid epilepsy and psychiatric disorders. METHOD: We retrospectively reviewed the outpatient psychopharmacology medical records of patients with epilepsy, aged 19 and younger, who received risperidone for psychiatric disorders. RESULTS: Twenty-one (21) youths (mean age, 12.0 +/- 4.2 years) met our criteria for review. Mean risperidone dosage was 2.4 +/- 3.5 mg/day. Target symptoms included severe aggression, severe agitation, psychosis, and self-injurious behavior. Diagnoses included attention-deficit hyperactivity disorder (ADHD), learning disorder, and impulse control disorder. Seizure type was partial complex in 12 patients, generalized in 6 patients, neonatal in 1 patient, myoclonic in 1 patient, and unclassified in 1 patient. The average number of previous psychotropic trials was 3.5 +/- 3.0. Using a definition of response of a Clinical Global Impressions (CGI) improvement score of 2 or less, 15 patients (71%) were considered responders. Adverse effects were none to slight in 16 patients, moderate in 4 patients, and severe in 1 patient. Seizures did not worsen in any patient. CONCLUSIONS: Risperidone was associated with a clinically significant global improvement, without seizure exacerbation in youths with epilepsy and psychiatric disorders. Despite the limitations of the study design, the 71% responder rate is noteworthy in this treatment-refractory group.

Determining the effects of antiepileptic drugs on cognitive function in pediatric patients with epilepsy.

The majority of children with epilepsy are of normal intelligence; however, a significant subset suffers from temporary or permanent cognitive impairment. Factors that affect cognitive function are myriad and include the neuropathology underlying the epilepsy, seizures, epileptiform activity, psychosocial problems, and antiepileptic drug side effects. Although cognitive impairment is often wrongly attributed to the effects of antiepileptic drugs, antiepileptic drugs do impair cognition in some children. Clinicians should be aware of the differential cognitive effects of antiepileptic drugs and should monitor cognitive function closely when adding or changing therapy. Based on published data from prospective, chronic dosing studies, phenobarbital and topiramate have the highest potential for causing cognitive dysfunction.

Differential cognitive effects of antiepileptic drugs.

As a group, children and adolescents with epilepsy have a higher prevalence of cognitive and behavioral disorders, although many fall within the normal distribution. For those affected, several causes have been identified, some of which may be interrelated. It has proven to be methodologically sound to isolate the role of specific antiepileptic drugs as a cause of cognitive impairment. The large body of literature that has accumulated on this topic is characterized by a relatively high proportion of inconclusive or contradictory observations. This may be due in part to the many methodological pitfalls in this area of research. The emerging picture is that cognitive effects caused by antiepileptic drugs are neither the rule nor the exception. Although certain drugs appear more likely to be involved, no single drug causes problems in every patient, and no drug can be assumed never to cause any cognitive impairment. The subgroup of patients that are at higher risk cannot be easily defined. Early detection of cognitive effects is based on actively eliciting reports of symptoms. This can be complemented by a screening battery in case of suspicion.

Choosing antiepileptic drugs for developmentally normal children with specific epilepsy syndromes and behavioral disorders.

Antiepileptic drugs are often used for the treatment of both epilepsy and a wide range of behavioral and psychiatric disorders. The treatment of patients with epilepsy has been the proving ground for antiepileptic drugs, not only with respect to their efficacy in the treatment of seizures but also for clarifying their dose-related and idiosyncratic adverse events. This information has been useful in treating patients with behavioral and psychiatric disorders. Indeed, the number of prescriptions written for many antiepileptic drugs for nonepileptic uses far exceeds those written for the same drugs for epilepsy. Because patients with chronic epilepsy have a higher incidence of axis I psychiatric disorders, physicians can choose an antiepileptic drug to treat both the epilepsy and psychiatric comorbidity in selected patients. Guided by the principles of evidence-based medicine as outlined by the American Academy of Neurology and the American Academy of Pediatrics, this article reviews the application of antiepileptic drugs for epilepsy and behavioral and psychiatric disorders in children.

Prognostic value of neonatal discontinuous EEG.

The burst suppression pattern on the neonatal electroencephalogram (EEG) is associated with a poor outcome. However, this serious abnormality constitutes only a small proportion of discontinuous neonatal EEGs. We sought to establish whether any easily measurable parameters among the broad range of excessively discontinuous neonatal EEGs are predictive of outcome. We retrospectively reviewed the EEGs and medical records of 43 term infants with excessively discontinuous EEGs. We quantitated 10 parameters in the bursts and interburst intervals, among them the predominant interburst interval duration (defined as the duration of more than 50% of all interburst intervals of an EEG). Univariate and multivariate analyses were performed on the 10 EEG variables in relation to neurologic outcome and subsequent epilepsy. Based on multivariate analysis, a single easily measurable EEG parameter related significantly to outcome. A predominant interburst interval duration of more than 30 seconds correlated with the occurrence of both unfavorable neurologic outcome and subsequent epilepsy (P = 0.040 and P = 0.033, respectively). In conclusion, a infant whose EEG contains a predominant interburst interval duration of more than 30 seconds has a 100% probability of experiencing severe neurologic disabilities or death and an 86% chance of developing subsequent epilepsy. This easily quantitated EEG parameter could be valuable for the early estimation of neurologic prognosis.

Clinical value of magnetoencephalographic spike propagation represented by spatiotemporal source analysis: correlation with surgical outcome.

OBJECTIVE: To investigate the correlation between spike propagation represented by spatiotemporal source analysis of magnetoencephalographic (MEG) spikes and surgical outcome in patients with temporal lobe epilepsy. METHODS: Thirty-seven patients were divided into mesial (n=27) and non-mesial (n=10) groups based on the presurgical evaluation. In each patient, ten ipsilateral spikes were averaged, and spatiotemporal source maps of the averaged spike were obtained by using minimum norm estimate. Regions of interest (ROIs) were created including temporoparietal, inferior frontal, mesial temporal, anterior and posterior part of the lateral temporal cortex. We extracted activation values from the source maps and the threshold was set at half of the maximum activation at the peak latency. The leading and propagated areas of the spike were defined as those ROIs with activation reaching the threshold at the earliest and at the peak latencies, respectively. Surgical outcome was assessed based on Engel's classification. Binary variables were created from leading areas (restricted to the anterior and mesial temporal ROIs or not) and from propagation areas (involving the temporoparietal ROI or not), and for surgical outcome (Class I or not). Fisher's exact test was used for significance testing. RESULTS: In total and mesial group, restricted anterior/mesial temporal leading areas were correlated with Class I (p<0.05). Temporoparietal propagation was correlated with Class II-IV (p<0.05). For the non-mesial group, no significant relation was found. CONCLUSIONS: Spike propagation patterns represented by spatiotemporal source analysis of MEG spikes may provide useful information for prognostic implication in presurgical evaluation of epilepsy.

Surgery for intractable epilepsy due to unilateral brain disease: a retrospective study comparing hemispherectomy techniques.

BACKGROUND: Hemispherectomy is a surgical procedure used to treat medically intractable epilepsy in children with severe unilateral cortical disease secondary to acquired brain or congenital lesions. The major surgical approaches for hemispherectomy are anatomic hemispherectomy, traditional functional hemispherectomy, and peri-insular hemispherotomy. We describe the epilepsy outcome, including the need for reoperation, after hemispherectomy in patients with brain malformations or acquired brain lesions who underwent hemispherectomy for refractory epilepsy. METHODS: We conducted a retrospective observational study at Children's Hospital Boston. Cases were ascertained from a research database of patients who underwent epilepsy surgery from 1997 to 2011. Data were obtained from electronic medical records and office charts. Outcome after surgery was defined as improvement in seizures (quantity and severity) represented by the Engel classification score measured at last follow-up, with a minimum of 12 months of follow-up. The need for reoperation for completion of hemispheric disconnection. We also examined whether placement of ventriculoperitoneal shunt was required after hemispherectomy was a secondary outcome. RESULTS: We identified 36 patients who underwent hemispherectomy for severe, medically intractable epilepsy. Group 1 (n = 14) had static acquired lesions, and group 2 (n = 22) had malformations of cortical development. Mean age at surgery for group 1 was 9 years (S.D. 5.5) and 2.77 years for group 2 (S.D. 4.01; P < 0.001). The seizure outcome was good in both groups (Engel score I for 25, II for three, III for six, and IV for two patients) and did not differ between the two groups. In group 1, five patients underwent anatomic hemispherectomy (one had prior focal resection), four underwent functional hemispherectomy, and five underwent peri-insular hemispherotomy; none required a second procedure. In group 2, a total of 14 patients had anatomic hemispherectomy (of these, three had had limited prior focal resection), five had functional hemispherectomy, and three had peri-insular hemispherotomy. Among the patients in group 2 who had had functional hemispherectomy, one required reoperation to complete the disconnection and one required peri-insular hemispherotomy because of persistent seizures. In group 1, three patients underwent a ventriculoperitoneal shunt, and from these patients two underwent anatomic hemispherectomy and one had functional hemispherectomy. In group 2, 12 patients had ventriculoperitoneal shunt, and all of them had anatomic hemispherectomy as a first or second procedure. CONCLUSION: Seizure outcome after hemispherectomy is good in patients with acquired lesions and with developmental malformations. Although the seizure outcome was similar in the three procedures, the complication rate was higher with anatomic hemispherectomy than with the more recent functional hemispherectomy and peri-insular hemispherotomy. The group with cortical malformations generally had surgery at a younger age; two patients with malformations of cortical development who underwent functional hemispherectomy required second surgeries. The need for reoperation in these cases may reflect the anatomic complexity of developmental hemispheric malformations, which may lead to incomplete disconnection.

Initiating antiepileptic drug treatment and characteristics of drugs.

This chapter covers the main steps involved in the initiation of antiepileptic drug therapy. Aspects covered specifically include the decision whether or not to initiate treatment, the selection process of a drug of first choice for a given patient with a particular seizure type or epilepsy syndrome, and the process of initiating therapy with the selected drug of first choice. Suggested choices of antiepileptic drugs by seizure type or epilepsy syndrome are summarized in a table. In an appendix, these drugs are reviewed individually with regard to their clinical use. The emphasis is on initial dose, dosage escalation, common and serious adverse effects, baseline evaluation, monitoring of therapy, and relevant drug interactions.