AED Withdrawal Research Articles

P14.34 Long-term seizure outcomes and tumor recurrence after glioneural tumor surgery: A single-center retrospective cohort

Abstract BACKGROUND Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNET) are glioneural tumors associated with treatment refractory seizures, especially in younger patients. Because there is a relative paucity of data on which factors predispose patients for recurrences, we analyzed our own cohort treated over the last 25 years. MATERIAL AND METHODS We performed a retrospective analysis of all patients undergoing resection of a glioneural tumor with a minimum follow up of one year. Surgery type, histological findings, and seizure outcome were extracted from patient records. Recurrence was defined as new tumor lesions in previously unremarkable parenchyma or tumor growth of a residual lesion. We performed a Mann-Whitney-U test to determine statistical significance of differences in continuous variables and Fisher’s exact test in categorical. RESULTS In total, 109 patients were operated between March 1994 to March and followed for a median of 62.4 months (range 12–281 months). The average age of patients at the time of surgery was 21.2 years with 60 patients belonging to the pediatric population. Complete lesionectomies were the goal in 72 cases, extended resections in 10, and partial resection due to proximity of eloquent areas was performed in 27 cases. 77 tumors were classified histologically as a GG and 32 as a DNET. The temporal lobe was the most common site of origin with 65 tumors (59.6%) being found there. On postoperative MRI, complete resection was achieved in 76 cases. Local tumor recurrences were seen in 14 patients (12 GG and 2 DNET), 9 of which occurred in patients with apparently complete resection. Overall, only one malignant transformation of a GG was observed. Age at surgery was significantly lower for patients with later recurrence (11.9 yrs vs. 22.6 yrs for patients without recurrence, p=0.0047). A second surgery was performed in 11 patients with previously incomplete resections (33%) and 7 patients with complete resection (9.2%), p=0.0038. 95 patients (87.2%) had preoperative seizures for a median of 26 months before surgery. One year after surgery, a documented ILAE outcome was available for 90 of these patients and 63 (70%) were seizure free one year after surgery. While 45 patients with epilepsy (47.4%) had at least one seizure relapse after surgery - most often associated with AED withdrawal or tumor recurrence - medical therapy and repeat resection allowed 76 patients (80%) to be seizure free for over one year at their last follow up. Age at surgery was not a significant predictor of seizure freedom. CONCLUSION Glioneural tumors are highly epileptogenic but neurosurgical resection allows seizure freedom in the large majority of these patients. Tumor recurrences were more likely in younger patients and incomplete resections predisposed patients to need another surgery. Resection extent on MRI does not appear to be a reliable marker for future recurrence risk.

Epilepsy Outcomes and Hippocampal Volumes in Children with Multiple Parenchymal Neurocysticercoses.

ABSTRACTBackground:We aimed to study the radiological and epilepsy outcomes of children with multiple neurocysticercosis (NCC) and the relationship with hippocampus volume.Study Design:Observational study.Materials and Methods:Children between 5 and 18 years of age with NCC lesions and completed more than 2-year follow-up were enrolled. Magnetic resonance imaging (MRI) brain with a predefined protocol was done as per clinical indication, and bilateral hippocampi volume was measured with a region of interest-based manual method. Proportion of children who had radiological resolution of lesions, proportion of children who were seizure-free for at least 3 months after antiepileptic drugs withdrawal, and mean hippocampi volume were calculated.Results:During the study period, 229 children followed up in pediatric NCC clinic were enrolled, the mean age was 10.5 ± 3 years, and 129 (56%) were boys. A total of 159 (65%) children had single-lesion NCC, and 79 (35%) had multiple lesion (> 2) NCC. Resolution of lesions was seen in 8% children with multiple NCC, significantly less as compared to the single NCC group (8% vs. 27%, P = 0.006). Multiple-lesion NCC group had a higher rate of calcification as compared to children with a single lesion (66% vs. 47%, P = 0.008). Twenty-nine (37%) children with multiple-lesion NCC were seizure free for at least 3 months after antiepileptic drug withdrawal. Mean combined hippocampal volume in children with single-lesion NCC was 2.96 (0.62) mL and multiple-lesion NCC was 2.88(0.43) mL.Conclusion:Children with multiple-lesion NCC have lower resolution, and higher calcification during follow-up in comparison to single-lesion NCC. Frequency of children who remained seizure-free 3-month post AED withdrawal was similar in single- and multiple-lesion groups.

Epilepsy surgery – the role for earlier intervention and when to wean AEDS

In well-selected children with focal lesional epilepsy, surgery is the most effective – and only curative – treatment option. If the epileptogenic source is well-localized and outside eloquent brain areas, a focal resection or disconnection is considered. Children with hemispheric pathology and existing neurological deficits may undergo hemispherotomy. The overall chance of seizure-freedom in children is 70-80% at 2 years and 60-70% at 5 years following surgery. A recent randomized trial has confirmed the unequivocal benefits of surgery over continued medical treatment. The number of referrals and surgeries steadily increases in children. Surgical indications have broadened over the past decades, now including generalized epileptic encephalopathies in the context of unilateral structural pathology. An increasing number of MRI-negative children – with presumed focal cortical dysplasia – is evaluated for surgery, using improved functional and structural imaging and invasive monitoring. It has been convincingly demonstrated that postoperative seizure-outcome improves with shorter duration of epilepsy. Epilepsy surgery can improve developmental capacities of children with refractory epilepsy, and shorter epilepsy duration predicts better postoperative cognitive outcome and more cognitive improvement. Finally, AED withdrawal – which can be safely considered early after surgery in many children – is an independent predictor of eventual IQ and of IQ increase after surgery. Given the low risks of epilepsy surgery, the small chance of spontaneous “cure” in focal epilepsy, and the high success-rate of surgery, all children with focal lesional epilepsy should be referred for presurgical evaluation early after diagnosis, even when seizures are well-controlled with one or two AEDs. Epilepsy surgery is an early treatment option rather than a last resort.

Postoperative seizure outcome and timing interval to start antiepileptic drug withdrawal: A retrospective observational study of non-neoplastic drug resistant epilepsy

This study aimed to investigate the impact of timing interval to start AED withdraw (TIW) after surgery on the seizure outcome in non-neoplastic drug resistant epilepsy (DRE). TIW were divided into three groups (respectively,<1 year, 1-<2 years, and ≥2 years). The seizure outcome at the different time points after starting AED withdrawal were compared among three groups. Other factors that related to seizure recurrence and TIW were included into the multiple analysis to investigate the predictors of seizure-free. Altogether, 205 patients were involved in the study. 102 individuals (50%) had seizure recurrence and 127 (62%) had seizure-free at the final follow up. 115 of them have attempted AED reduction and had not seizure recurrence before AED reduction. The rate of seizure-free had no significant difference among people with different TIW. Multiple analysis indicated that temporal surgery is a favorable predictor of seizure-free at the first year after starting AED withdrawal, and preoperative secondary generalized seizures is an unfavorable predictor of seizure-free at the final follow up. In patients with non-neoplastic DRE, TIW is not the mainly influence factor on seizure outcome, however, preoperative secondary generalized seizures and extra-temporal surgery are negatively associated with seizure-free.

Is merely surviving childbirth enough?: The importance of respectful maternity care

Focal Cortical Dysplasias (FCDs) represent a common architectural cortical disorder underlying drug-resistant focal epilepsy. So far, studies aimed at evaluating whether age at surgery is a factor influencing surgical outcome are lacking, so that data on the comparison between patients harboring Type II FCD operated at younger age and those operated at adult age are still scarce. We compared presurgical clinical features and surgical outcomes of patients with histopathologically diagnosed Type II FCD undergoing surgery at an earlier age with those operated after 20 years of age.We retrospectively analyzed 1660 consecutive patients operated at the “Claudio Munari” Epilepsy Surgery Centre. There were 289 patients (17.4%) with a neuropathological diagnosis of Type II FCD. We included two different groups of patients, the first one including patients operated on at less than 6 years, the second sharing the same seizure onset age but with delayed surgery, carried out after the age of 20. Seizure characteristics and, neuropsychological and postoperative seizure outcomes were evaluated by study group.Forty patients underwent surgery before the age of 6 and 66 patients after the age of 20. Surgical outcome was favorable in the whole population (72.6% were classified in Engel's Class Ia + Ic), independently from age at surgery. In the children group, 32 patients were classified in Class I, including 30 (75%) children in classes Ia and Ic. In the adult group, 53 belonged to Class I of whom 47 (71%) were in classes Ia and Ic.The percentage of permanent complications, the surgical outcomes, and AED withdrawal did not significantly differ by study group.Our results indicate that there is no difference between the groups, suggesting that outcome depends mainly on the histological findings and not on timing of surgery.

Pregnancy outcome in women with epilepsy in Western China: A prospective hospital based study.

Gaps exist in the diagnosis and treatment of women with epilepsy (WWE) between China and Euro-American countries. We aim to find out and share our experience of the multidisciplinary integrated treatment for WWE. We prospectively registered WWE who were diagnosed by both epileptologists and obstetrician in our green way system for the past 5years (2009-2015). Registration information include years of education, epilepsy history, seizure type and frequency, pregnancy and delivery complications, delivery mode, and Apgar score of newborn. All data were analyzed by SAS 9.3 version. We included 137 cases of maternal epilepsy (155 pregnancies with average maternal age of 26years old). 18 cases underwent epilepsy surgery before pregnancy. 103 pregnancies (66.45%) were cesarean section, 52 (33.55%) were natural childbirth, only 10 pregnancies have pregnancy complications, 2 have delivery complication, and 15 have seizures during delivery process. Most offspring were healthy when they were born (only 11 newborn got Apgar score<7). For drug treatment, patients never took AEDs or withdrew AEDs in 55 (35.48%) pregnancies. For folic acid supplementation, only 9 (5.81%) achieved the dose recommended by ILAE guideline (5mg/day). For the seizure frequency, 108 pregnancies (69.68%) did not changed, 3 (1.94%) reduced, 44(28.39%) increased and mainly increased in the first and last trimesters. For feeding way, 90 (58.06%) chose artificial feeding, followed by 39 (16.77%) of mixed feeding and 26 of breastfeeding. Clinical features and perinatal outcome of Chinese WWE are similar to western WWE. For mode of delivery, even suggested by our epileptologists and obstetrician to deliver naturally, more patients selected cesarean section. Moreover, withdrawal of AEDs during pregnancy is common. Therefore, it is necessary to pay more attention to standard management of WWE and establish a more practical green way for WWE in China, to keep up with developed countries and improve the health level of birth in China.

Long-term Postoperative Outcomes in Patients with Focal Cortical Dysplasia: Predictive Factors and AED Withdrawal (P4.107)

Long-term Postoperative Outcomes in Patients with Focal Cortical Dysplasia: Predictive Factors and AED Withdrawal (P4.107)

Safety in the epilepsy monitoring unit: A retrospective study of 524 consecutive admissions.

The yield of monitoring patients at an epilepsy monitoring unit (EMU) depends on the recording of paroxysmal events in a timely fashion, however, increasing the risk of safety adverse events (AEs). We aimed to retrospectively study the frequency and risk factors for AE occurrences in all consecutive admissions to an adult EMU in a tertiary medical center. We also compared our findings with published data from other centers. Between January 2011 and June 2014, there were 524 consecutive admissions to the adult EMU at the Tel Aviv Sourasky Medical Center. Adverse events were recorded in 47 (9.0%) admissions. The most common AE was 4-hour seizure cluster (58.7% of AEs) and, in decreasing frequency, AEs related to antiepileptic drugs (AEDs, 11.1%), falls and traumatic injuries (9.5%), intravenous line complications (9.5%), electrode-related (4.8%), status epilepticus (SE, 3.2%), and cardiac (1.6%) and psychiatric (1.6%) complications. There were significantly more AEs among patients with a younger age at disease onset (p=0.005), a history of temporal lobe epilepsy (p=0.046), a history of focal seizures with altered consciousness (p=0.008), a history of SE (p=0.022), use of a vagal nerve stimulator (p=0.039), and intellectual disability (p=0.016) and when the indication for EMU monitoring was noninvasive or invasive presurgical evaluation (p=0.001). Adverse events occurred more frequently when patients had more events in the EMU (p=0.001) and among those administered carbamazepine (p=0.037), levetiracetam (p=0.004), clobazam (p=0.008), and sulthiame (p=0.016). Patients with a history of psychogenic nonepileptic seizures (PNESs) had significantly fewer AEs (p=0.013). Adverse events were not associated with the age, gender, duration of hospitalization or monitoring, AED withdrawal and renewal, seizure frequency by history, presence of major psychiatric comorbidities, abnormal neurological exam, or the presence of a lesion as on brain magnetic resonance imaging. In conclusion, this study reveals that AEs are not unusual in the EMU and that seizure clustering is the most common among them. Adverse events occur more frequently in patients with more severe epilepsy and intellectual disability and in patients undergoing presurgical evaluations and less frequently in patients with PNESs.

Is rapid withdrawal of anti-epileptic drug therapy during video EEG monitoring safe and efficacious?

Video electroencephalographic monitoring (VEM) is used to record ictal and interictal epileptiform activity and to ascertain the level of concordance between the two. Often, taper or discontinuation of anti-epileptic (AED) therapy is needed to facilitate seizure occurrence. The safety of this practice is unclear and long-term sequelae have yet to be elucidated. This is a prospective study of 158 patients subjected to combined sleep-deprived VEM with rapid AED withdrawal, for evaluation of seizure-like episodes over 24 months under the care of an epileptologist with direct nursing observation and EEG technician support in our telemetry unit. In most cases, AEDs were discontinued within 24h of admission. We assessed the diagnostic yield and safety of VEM as well as epilepsy surgery outcomes. VEM answered the study question in 90.5% of cases but failed to record ictal events in 9.5%. This diagnostic yield was achieved over a mean VEM duration of 4.53±1.44 days, with no benefit of longer monitoring. These findings improved quality of life by optimizing medical and surgical therapeutic planning, leading to improved seizure control. Overall, 32.9% of the cohort received epilepsy surgery. The complication rate was 5.06%, characterized largely by musculoskeletal pain secondary to clinical seizure activity, with no mortality observed. In the first month following VEM 2.5% of patients received emergency-room admission for seizure clustering. VEM with combined sleep deprivation and protocolized rapid AED withdrawal is a safe and effective investigative technique with no adverse long-term sequelae. It is a reliable strategy for therapeutic planning and can be used to determine candidacy for surgical treatment.

A consensus-based approach to patient safety in epilepsy monitoring units: Recommendations for preferred practices

Patients in an epilepsy monitoring unit (EMU) with video‐EEG telemetry have a risk for seizure emergencies, injuries and adverse events, which emphasizes the need for strategies to prevent avoidable harm. An expert consensus process was used to establish recommendations for patient safety in EMUs. Workgroups analyzed literature and expert opinion regarding seizure observation, seizure provocation, acute seizures, and activity/environment. A Delphi methodology was used to establish consensus for items submitted by these workgroups. Fifty-three items reached consensus and were organized into 30 recommendations. High levels of agreement were noted for items pertaining to orientation, training, communication, seizure precautions, individualized plans, and patient/family education. It was agreed that seizure observation should include direct observation or use of closed‐circuit camera. The use of continuous observation was strongest in patients with invasive electrodes, at high risk for injury, or undergoing AED withdrawal. This process provides a first step in establishing EMU safety practices.

Antiepileptic monotherapy significantly impairs normative scores on common tests of executive functions

Understanding how antiepileptic (AED) monotherapy influences normative test scores is of importance in the clinic for correct interpretation of neuropsychological profiles. Previous studies have primarily reported minor influence on neuropsychological raw scores, and the clinical relevance of these findings is unclear. To obtain a clinical valid answer to this question, we analysed changes in T-scores after AED withdrawal in a large group of well-controlled epilepsy patients, for tests previously shown to be sensitive to AED withdrawal. We report outcomes on measures of choice reaction time from the California Computerized Assessment Package, on the Controlled Oral Word Association Test and on the Stroop Color-Word Interference Test. Significantly improved T-scores were revealed after AED withdrawal on five of the six tests of executive functions with mean improvement of 5 T-scores. Comparable results were achieved in the subgroup taking carbamazepine, with a mean improvement of 6.2 T-scores. The present results suggest that T-scores for computerized tests of choice reaction time and tests of verbal fluency and response inhibition may be significantly impaired as a consequence of AED monotherapy, and that careful interpretation of these scores is required in diagnostic assessment of patients receiving AED monotherapy.

Traitement chirurgical de l’épilepsie : avenir et conclusions

Focal Cortical Dysplasias (FCDs) represent a common architectural cortical disorder underlying drug-resistant focal epilepsy. So far, studies aimed at evaluating whether age at surgery is a factor influencing surgical outcome are lacking, so that data on the comparison between patients harboring Type II FCD operated at younger age and those operated at adult age are still scarce. We compared presurgical clinical features and surgical outcomes of patients with histopathologically diagnosed Type II FCD undergoing surgery at an earlier age with those operated after 20 years of age.We retrospectively analyzed 1660 consecutive patients operated at the “Claudio Munari” Epilepsy Surgery Centre. There were 289 patients (17.4%) with a neuropathological diagnosis of Type II FCD. We included two different groups of patients, the first one including patients operated on at less than 6 years, the second sharing the same seizure onset age but with delayed surgery, carried out after the age of 20. Seizure characteristics and, neuropsychological and postoperative seizure outcomes were evaluated by study group.Forty patients underwent surgery before the age of 6 and 66 patients after the age of 20. Surgical outcome was favorable in the whole population (72.6% were classified in Engel's Class Ia + Ic), independently from age at surgery. In the children group, 32 patients were classified in Class I, including 30 (75%) children in classes Ia and Ic. In the adult group, 53 belonged to Class I of whom 47 (71%) were in classes Ia and Ic.The percentage of permanent complications, the surgical outcomes, and AED withdrawal did not significantly differ by study group.Our results indicate that there is no difference between the groups, suggesting that outcome depends mainly on the histological findings and not on timing of surgery.

Frequency, causes and phenomenology of late seizure recurrence in patients with juvenile myoclonic epilepsy after a long period of remission

To determine frequency, causes, and phenomenology of late seizure recurrence (SR) in patients with juvenile myoclonic epilepsy (JME) after remission of at least 1 year. Among 2722 epileptic patients from tertiary referral center, we retrospectively identified 105 patients (62 females; mean age 22.3+/-7.2 years) with an established diagnosis of JME. All patients were treated with valproates (83.3%), or lamotrigine, topiramate, phenobarbital, add-on clobazam, or combinations (16.2%). The median period of follow-up was 4.2+/-3.2 (range: 1-17) years. SR occurred in 74 patients (70.5%) after median period of 2.4+/-3.2 years. Twenty-two patients (29.7%) experienced myoclonic seizures (MS), 13 (17.7%) generalized tonic-clonic seizures (GTCS), 37 (50%) a combination of MS and GTCS, and two (2.6%) a combination of MS, GTCS and absence seizures. SR was associated most frequently with sleep deprivation and AED withdrawal, and rarely with alcohol intake, drug abuse, photostimulation, or menstruation. No provoking factors for SR were identified in 31.1% and 45% of cases with MS and GTCS, respectively. The majority of patients (59/74) had a single SR. A second SR occurred less frequently in patients in whom valproate dosage was increased after the first SR (p=0.0048). Late SR (mainly MS and GTCS) is detected frequently after prolonged follow-up in patients with JME despite the use of best-known therapy, usually due to AED withdrawal or erratic life style. Instead of futile efforts to persuade the patient to conform to restrictive life style, it is probably more efficient to use initial higher doses of AEDs.

Epilepsy in the UK: Misdiagnosis, mistreatment, and undertreatment?: The Wrexham area epilepsy project

To assess the diagnostic and therapeutic difficulties in patients with epilepsy who had never come into contact with specialist services. Assessment was offered to 676 patients diagnosed as having epilepsy and receiving anti-epileptic drug therapy (AED), who had no previous contact with the local epilepsy services. Two hundred and seventy-five patients gave consent and attended for reassessment. We identified the proportion of patients (a) who had previously seen a neurologist, (b) in whom the diagnosis of epilepsy was not secure, (c) in whom planned AED withdrawal could be considered (d) in whom seizure control could be improved. 53/275 (19.3%) of those attending for review had previously been seen by a neurologist. 87/275 (31.6%) patients ultimately received continued specialist care. Diagnostic doubt was expressed in 3/53 (5.6%) and 42/222 (18.9%) of patients diagnosed by neurologist and non-specialist, respectively. Of 133/219 (60.7%) of patients whose epilepsy was in remission, only 6 elected to withdraw or change medication. Of 18 patients with diagnostic doubt who accepted follow-up, 12 successfully stopped treatment. 17/55 (30.9%) patients with active epilepsy (10 partial, 7 generalised) achieved at least a 1 year remission consequent upon treatment in this clinic. In 15 cases this was a first ever remission. Approximately 55% of the population of adults receiving treatment for epilepsy have never received specialist advice. Reassessment of these patients uncovers diagnostic uncertainty, failure to classify (leading to sub-optimal therapy) and lack of information and advice about all aspects of epilepsy care. The development of integrated services for people with epilepsy (PWE) must take account of this hidden need. The new General Medical Services contract for general practitioners will bring this need to our attention, and our experience will help predict the measures required to deal with the under-treatent and mistreatment of this group. The majority of PWE, not currently receiving shared care, merit reassessment and approximately one-third will require continued specialist care. Existing services do not have the capacity to process a marked increase in rate of referral. This project informs prioritisation of referrals and service reorganisation.

Prognosis after withdrawal of antiepileptic drugs in childhood-onset cryptogenic localization-related epilepsies

The purpose of this study was to clarify the risk factors of relapse following discontinuation of AEDs in patients with childhood-onset cryptogenic localization-related epilepsies. The subjects were 82 patients who fulfilled the following criteria: (1) age at first visit of less than 15 years, (2) follow-up period of more than 5 years, (3) suffering from cryptogenic localization-related epilepsies, and (4) the patient underwent AED withdrawal during the follow-up period. As a basic principle, we decided to start withdrawing AEDs when both of the following two conditions were met: (1) the patient had a seizure-free period of 3 years or more, and (2) there were no epileptic discharges on EEGs just prior to the start of withdrawal. Seizures recurred in eight of the 82 patients (9.8%). Univariate analysis revealed that the following factors were correlated with higher rates of seizure relapse: 6 years of age or higher at onset of epilepsy; 15 years of age or higher at the start of AED withdrawal; 5 years or more from the start of AED treatment to seizure control; five or more seizures before seizure control; and two or more AEDs administered before seizure control. Among these risk factors, 6 years of age or higher at onset and 5 years or more from the start of AED treatment to seizure control were determined by multivariate analysis to be independent risk factors for relapse. Thus, we conclude that the physician should be more careful in discontinuing AEDs in these higher-risk patients groups, and more generous in discontinuing AEDs in lower-risk groups.

Interrelationship between radiologic findings and prognosis of epilepsy in children with neurocysticercosis.

Epileptic manifestations of Neurocysticercosis (NC) appear to depend on number and localization of the cysts. The objective of this study was to investigate the relationship between CT findings, number of parasites and the evolutive stage of the cysts, and the prognosis of epilepsy in children with NC. We studied 28 patients with the parenchymal form of NC, considering: epilepsy duration; seizure frequency before and after AED treatment; seizure control; number of AED and recurrence after AED withdrawal. Clinical information was crossed with the number of lesions and disease activity in univariate comparison. The analysis of the clinical data in relation to the number of lesions and disease activity showed no statistical difference among the variables (p>0.05). We conclude that the course of epilepsy due to NC in childhood cannot be based exclusively on the number or stage of the parasites.

Families’ Views on Discontinuing Anticonvulsants

The opinions of families of 76 children with epilepsy (>3 months seizure-free) and their 4 physician epilepsy specialists regarding acceptable risks of seizure recurrence (RSR) after AED withdrawal were investigated by questionnaire at the IWK Children’s Hospital, Halifax, Nova Scotia, Canada.

AED Withdrawal: Risk Factors

The results of a prospective cohort study to investigate the effects of withdrawal of AEDs in 264 children with epilepsy after a mean seizure-free interval of 2.9 years are reported from the Montefiore/Einstein Epilepsy Management Center, Bronx, NY.

The impact of counselling with a practical statistical model on patients' decision-making about treatment for epilepsy: Findings from a pilot study

To ascertain the impact of a computer-based predictive model on patients' decisions about continuing treatment of their epilepsy, 72 subjects were asked to complete questionnaires prior to and following counselling with the model. The subjects were attending the neurology out-patient clinic in a large UK hospital, and were identified from medical records as eligible for withdrawal of AEDs. The effect of counselling with the model was to make the majority of patients opt to continue AED therapy. Positive or negative framing of risk information appeared to influence the decisions of patients who were initially uncertain about continuing treatment, as did patients' perceptions of the clinician's views. The prognostic model appeared to allow relatively complex statistical information to be conveyed to patients in an accessible form. We suggest its use will aid clinicians in counselling patients and will help patients reach better-informed decisions about treatment.

Clinical Pharmacology of Antiepileptic Drugs: Selected Topics

This article illustrates basic principles of clinical pharmacology presented in article 1 with specific examples from the treatment of seizure disorders. The discussion includes protein binding, the role of a major carbamazepine metabolite, alterations in pharmacology of AEDs in the elderly, and AED withdrawal. The last topic, in particular, is a good example of the interaction of pharmacokinetic and pharmacodynamic considerations in explaining the clinical effects of a drug.