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Latest Research on Epilepsy
     
Br J Neurosurg. 2008 Apr;22(2):224-30.
Characteristics and surgical outcomes for medial temporal post-traumatic epilepsy.
Hartzfeld P, Elisevich K, Pace M, Smith B, Gutierrez JA.
Departments of Neurosurgery.

A common post-traumatic location of epileptogenesis is the medial temporal lobe despite evidence of associated diffuse or remote cerebral injury. We undertook a review of post-traumatic medial temporal lobe epilepsy (MTLE) patients as part of an overall post-traumatic epilepsy population to assess the extent of cerebral injury sustained by this subpopulation and to establish whether surgical outcome differed from that of a non-traumatically-induced epilepsy population. A retrospective review of 57 patients operated for post-traumatic epilepsy (PTE) over a 10-year period (1993 - 2003) was undertaken with particular attention to those undergoing medial temporal resection. Preoperative magnetic resonance imaging (MRI) was assessed for the type and location of abnormalities. Postoperative outcomes were compared with those of patients with MTLE of non-traumatic origin operated by the same surgeon. Of the 57 patients operated, 30 cases underwent medial temporal lobe resection. The most common mechanism of injury was blunt trauma attributable to motor vehicle accidents with imaging abnormalities characterized by medial temporal sclerosis (MTS; 16 cases), T2/FLAIR hyperintensities (nine cases), periventricular gliosis (seven cases), diffuse cerebral atrophy (five cases) and focal encephalomalacia (three cases). Six patients had normal MRI studies. No significant differences in postoperative outcomes were found between post- and non-traumatic MTLE epilepsy groups. The presence of histopathological change in the medial temporal lobe varied greatly and provided no indication of a favourable postoperative outcome. Patients with post-traumatic medial temporal lobe epilepsy respond favourably to surgical treatment. In the case of medial temporal sclerosis, there is substantial variation of histopathological findings which correlate poorly with current imaging applications. The favourable outcomes obtained following surgery in this group attest to a commonality with other risk factors in the genesis of epilepsy in this location.

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Curr Opin Neurol. 2008 Apr;21(2):184-9.
Complementary and alternative medical therapies.
Schachter SC.
Osher Research Center, Harvard Medical School; Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

PURPOSE OF REVIEW: Complementary and alternative medical therapies include herbs, acupuncture, and mind-body therapies. This review highlights the findings of recently published studies of complementary and alternative medical therapies and epilepsy, and provides an update of the US Food and Drug Administration's role in regulating herbal products. RECENT FINDINGS: Complementary and alternative medical therapies are often tried by patients with epilepsy, frequently without physician knowledge. Many modalities have been evaluated in patients with epilepsy, though methodological issues preclude any firm conclusions of efficacy or safety. Some herbal medicines have been shown experimentally to have mechanisms of action relevant to epilepsy and promising actions in animal models. SUMMARY: There is currently a paucity of credible evidence to support the use of complementary and alternative medical therapies in patients with epilepsy. Herbal medicines traditionally used for epilepsy and compounds isolated from them, as well as other herbal medicines and their constituent compounds that have been shown experimentally to have mechanisms of action relevant to epilepsy, should undergo further preclinical evaluation with a view towards clinical development under the new US Food and Drug Administration guidelines. Additional studies of other, nonherbal complementary and alternative medical therapies are also warranted based on anecdotal observations or pilot studies that suggest a favorable risk-benefit ratio.

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Curr Opin Neurol. 2008 Apr;21(2):179-83.
Early surgical treatment for epilepsy.
Langfitt JT, Wiebe S.
aDepartments of Neurology and Psychiatry, University of Rochester School of Medicine, Rochester, New York, USA bDepartments of Clinical Neurosciences and Community Health Sciences, Faculty of Medicine, University of Calgary, Alberta, Canada.

PURPOSE OF REVIEW: To review recent evidence that can assist clinicians facing the challenging question of when to offer brain surgery for epilepsy. RECENT FINDINGS: The most robust recent evidence pertains to temporal lobe epilepsy. We focus on this syndrome to assess the main issues pertaining to early surgery, which include natural history and effectiveness of medication, risks associated with continued seizures, effectiveness and risks of surgery, and cognitive outcomes in relation to timing of surgery. SUMMARY: The evidence for performing surgery earlier is persuasive but incomplete. Recent evidence indicates that intractability, and therefore consideration for surgery, does not develop at a uniform time in surgical candidates, and that late remissions with medical treatment are not rare. Factors that may suggest sustained intractability include a larger number of medications tried, longer duration of seizures, history of status epilepticus, mental retardation, and nonidiopathic epilepsy. Adequate prospective studies, however, need to address this important question systematically. The evidence regarding morbidity, quality of life, mortality, social and cognitive function suggests that earlier surgery may be beneficial, but prospective controlled studies with standardized interventions and outcomes will be required to derive firm conclusions.

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Curr Opin Neurol. 2008 Apr;21(2):161-6.
Epileptic syndromes in infancy and childhood.
Nabbout R, Dulac O.
aDepartment of Neuropediatrics, Centre de référence épilepsies rares, Hôpital Necker-Enfants malades, APHP, Necker-Enfants malades, France bUniversity Paris Descartes, Paris, France.

PURPOSE OF REVIEW: The aim of this article is to review new epilepsy syndromes, acquire a new understanding of older ones and emphasize the impact of this concept on basic research regarding aetiology and treatment. RECENT FINDINGS: In addition to those included in the classification of the International League Against Epilepsy, new epilepsy syndromes comprise febrile seizures plus, benign familial neonatal-infantile seizures (BFNIS), benign infantile focal epilepsy with midline spikes and waves during sleep (BFIS), malignant migrating partial seizures in infancy, devastating epilepsy in school age children and late onset cryptogenic spasms. Genetics played a central role in identifying some new entities (BFNIS, BFIS with choreoathetosis), to delineate older syndromes (Dravet syndrome and myoclonic astatic epilepsy) and determine their mechanisms (infantile spasms, pyridoxine dependent seizures, neonatal encephalopathy with suppression bursts). SUMMARY: A significant number of children, mainly infants, do not fit in any of the described epilepsy syndromes. Still many patients with infantile epilepsy require the identification of cause or recognition of an epilepsy syndrome.

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Curr Opin Neurol. 2008 Apr;21(2):167-72.
Strategy for utilization of new antiepileptic drugs.
Ben-Menachem E.
Institute for Clinical Neuroscience and Rehabilitation, Sahlgrenska Academy, Sahlgrenska University Hospital, Göteborg, Sweden.

PURPOSE OF REVIEW: The paper reviews strategies to incorporate new antiepileptic drugs into the treatment arsenal for patients with epilepsy. RECENT FINDINGS: Ten new antiepileptic drugs have been developed in the last two decades, making selection of optimal therapy complex; they have not been shown to have better efficacy but generally seem to be better tolerated. Newer antiepileptic drugs offer new opportunities to patients who have not had a favorable response to the old ones. Many new antiepileptic drugs exhibit a broad spectrum of activity while only one of the older ones (valproate) has a broad-spectrum profile. There are therefore more choices when trying to match treatment with epileptic seizures and syndromes. The side-effect profiles of the newer antiepileptic drugs differ from the older ones with fewer systemic reactions and better pharmacokinetics for the most part. SUMMARY: Comparative studies are needed to elucidate the specific weaknesses and strengths of each of the new antiepileptic drugs compared with the older ones. Most clinical trials do not help the physician in deciding drug, dose, or titration schedules. Thus the physician needs to understand efficacy spectrum and side-effect profiles of each new antiepileptic drug in order to be able to treat each patient optimally.

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Psychol Health Med. 2008 Mar;13(2):129-45.
Psychological impact of illness intrusiveness in epilepsy - Comparison of treatments.
Poochikian-Sarkissian S, Sidani S, Wennberg RA, Devins GM.
University Health Network, Division of Neurology, Krembil Neuroscience Program, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada.

Chronic illnesses are associated with multiple stressors that compromise quality of life (QOL). Implicit in many of these is the concept of illness intrusiveness, the disruption of lifestyles and activities attributable to constraints imposed by chronic disease and its treatment. This study tested the illness intrusiveness theoretical framework in epilepsy and compared the impact of pharmacological and surgical treatments on illness intrusiveness and QOL. Cross-sectional data compared three epilepsy groups (N = 145): (a) 40 patients admitted for presurgical evaluation to an Epilepsy Monitoring Unit; (b) 52 patients treated pharmacologically; and (c) 53 post-surgical patients. Illness intrusiveness differed significantly across epilepsy patients with the differences primarily related to seizure control. Illness intrusiveness varied inversely with seizure control (p < .05). Seizure freedom, whether achieved by surgical or pharmacological treatments, was associated with maximal reduction of illness intrusiveness. Increased illness intrusiveness correlated significantly with decreased QOL and increased depressive symptoms. Perceived control over diverse life domains correlated positively with QOL and psychosocial outcomes. Path analysis supported the validity of the illness intrusiveness theoretical framework in epilepsy. Illness intrusiveness is an important determinant of the psychosocial impact of epilepsy and its treatment. Effective pharmacological or surgical treatment may reduce illness intrusiveness in epilepsy. Findings also offer encouragement that QOL in epilepsy, as in other chronic conditions, may be enhanced by multidisciplinary bio-psychosocial efforts. Health care providers should consider multifaceted interventions to reduce illness intrusiveness and, thereby, improve QOL.

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Eur J Paediatr Neurol. 2008 Mar 13 [Epub ahead of print]
Open-label, long-term safety study of zonisamide administered to children and adolescents with epilepsy.
Shinnar S, Pellock JM, Conry JA.
Departments of Neurology, Pediatrics and Epidemiology and Population Health, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street Bronx, NY 10467, USA.

BACKGROUND: Zonisamide is licensed in the EU and USA for the adjunctive treatment of partial-onset seizures in adults but there are few data about its use in children. AIMS: To assess the long-term safety and efficacy of zonisamide in children and adolescents. METHODS: Zonisamide-naïve patients (n=109, aged 3-15 years, weight 12.5kg) with a clinical diagnosis of epilepsy (4 seizures/month, receiving 1-2 antiepileptic drugs [AEDs] daily) received zonisamide once or twice daily in an open-label trial. The starting dose was 1mg/kg/day, increased by 2mg/kg/day every 1-2 weeks at the investigator's discretion to an initial maximum of 12mg/kg/day. The occurrence of adverse events (AEs) was the primary safety measure. Efficacy was measured via the reductions in seizure frequency and via investigator- and carer-rated global assessment ratings. RESULTS: The mean dose received was 8.5mg/kg/day. Of the 109 children, 52 (48%) completed 15 months' treatment. Treatment-related AEs, mostly
mild-to-moderate in severity, were reported by 58 patients. Seven patients discontinued due to treatment-related AEs. Serious AEs (pancreatitis, decreased sweating, and vertigo) were reported by three patients. A significant (p=0.033) median reduction in 'all seizure' frequency of 2.60 seizures per week was observed. Additionally, a significant (p=0.029) median reduction of 1.80 seizures/week in 'complex partial' seizures was reported. Improvements in investigator- and carer-rated global assessments were noted. CONCLUSIONS: Zonisamide treatment was generally well tolerated and was associated with significant reductions in seizure frequency in this pediatric population with a variety of both partial and generalized medically refractory epilepsy syndromes.

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Epilepsy Behav. 2008 Feb 29 [Epub ahead of print]
Modern management of epilepsy: A practical approach.
Elger CE, Schmidt D.
Clinic for Epileptology, University Bonn, Bonn, Germany.

The epilepsies are among the most common serious brain disorders, can occur at all ages, and are characterized by a variety of presentations and causes. Diagnosis of epilepsy remains clinical, and neurophysiological investigations support the diagnosis of the syndrome. Brain imaging is able to identify many of the structural causes of the epilepsies. Current antiepileptic drugs (AEDs) block seizures without influencing the underlying tendency to generate seizures, and are effective in 60-70% of individuals. Several modern drugs are as efficacious as the older medications, but have important advantages including the absence of adverse drug interactions and hypersensitivity reactions. Epilepsy is associated with an increased prevalence of mental health disorders including anxiety, depression, and suicidal thoughts. An understanding of the psychiatric correlates of epilepsy is important to the adequate management of people with epilepsy. Anticipation of common errors in the diagnosis and management of epilepsy is important. Frequent early diagnostic errors include nonepileptic psychogenic seizures, syncope with myoclonus, restless legs syndrome, and REM behavioral disorders, the last mostly in elderly men. Overtreatment with too rapid titration and too high doses or too many AEDs should be avoided. For people with refractory focal epilepsy, vagus nerve stimulation offers palliative treatment with possible mood improvement and neurosurgical resection offers the possibility of a life-changing cure. Potential advances in the management of epilepsy are briefly discussed. This short review summarizes the authors' how-to-do approach to the modern management of people with epilepsy.

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Epilepsy Behav. 2008 Jan;12(1):187-190.
A randomized trial of polyunsaturated fatty acids for refractory epilepsy.
Bromfield E, Dworetzky B, Hurwitz S, Eluri Z, Lane L, Replansky S, Mostofsky D.
Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA.

OBJECTIVE: Though polyunsaturated fatty acids (PUFA) reduce seizures in several animal models, results have been inconsistent in humans. The goal of the present study was to assess the effectiveness of a PUFA supplement as adjunctive treatment for intractable focal or generalized epilepsy in humans. METHODS: Adults with uncontrolled epilepsy were randomized to either mineral oil placebo or a PUFA supplement (eicosapentanoic acid (EPA) plus docosahexanoic acid (DHA), 2.2 mg/day in a 3:2 ratio). Following a 4-week prospective baseline and 1-week titration, subjects entered a 12-week treatment period, followed by an optional 4-week open-label phase. RESULTS: Of 21 subjects (12 PUFA and 9 placebo), 0 on PUFA versus 2 on placebo had at least a 50% decrease in seizure frequency from baseline (P=0.17). Overall, seizure frequency increased 6% on PUFA and decreased 12% on placebo (P=0.21). During optional open-label administration, however, 15 of 19 subjects had fewer seizures than during baseline (P=0.02). CONCLUSIONS: Based on the randomized, blinded portion of this study, the PUFA preparation used was not superior to placebo as adjunctive treatment for intractable epilepsy. It is not known whether different doses or different EPA:DHA ratios would be effective.

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Drugs. 2008;68(1):17-25.
Antiepileptic drug development in children : considerations for a revisited strategy.
Chiron C, Dulac O, Pons G.
Inserm, U663, Paris; University Rene Descartes, Paris, FranceAPHP, Department of Pediatric Neurology and Metabolism, Hospital Necker - Enfants Malades, Paris, France.

The European Commission and the European Parliament have acknowledged the specific need for a proper evaluation of new drugs in children. The evaluation of the antiepileptic drugs (AEDs) available on the market illustrates the deficit in therapeutic trials for childhood epilepsy syndromes. Currently, the development of AEDs is mainly performed in children with focal epilepsy, whereas infants and the specific age-related epilepsy syndromes, particularly epileptic encephalopathies, are neglected. Infantile epilepsies remain 'therapeutic orphans', although they are the most frequent and deleterious disorders in the area of epilepsy. In order to circumvent the difficulties faced when conducting AED trials in children, we addressed the question of improving feasibility without decreasing quality, while optimally taking into account paediatric ethical requirements.For this review, we first raise the issues of paediatric epilepsies that require special considerations for randomized controlled trials (RCTs) in children. Then, we attempt to determine to what extent adult data could be extrapolated to children. Finally, we review innovative approaches that could be used in the evaluation of AEDs in children.The main specificities of paediatric epilepsies (heterogeneity, severity, cognitive impact, pharmacoresistance, syndrome-specific efficacy profile) are related to brain development and should be taken into consideration when establishing specific guidelines for the evaluation of AEDs in children. Extrapolating efficacy data from adults to children may be possible in focal epilepsy except in infants who need age-specific trials. Epileptic encephalopathies do not exist in adults and require specific trials. Pharmacokinetic data are required below a lower age limit for extrapolation of adult data to be determined in a case-to-case approach. Safety data are required at any paediatric age. RCTs in small but homogeneous populations in each paediatric-specific epileptic syndrome, the use of sequential or responder-enrichment designs, and population pharmacokinetics represent potentially promising approaches to evaluate drugs in children in an efficient way.

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Seizure. 2007 Dec 22 [Epub ahead of print]
Seizure control and pharmacokinetics of antiepileptic drugs in pregnant women with epilepsy.
Brodtkorb E, Reimers A.
Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Neurology and Clinical Neurophysiology, St. Olav's University Hospital, 7006 Trondheim, Norway.

The main concerns associated with epilepsy during pregnancy consist of maternal and fetal risks from uncontrolled seizures, and harmful effects of the treatment on the development of the offspring. Although seizure control is maintained in the majority, worsening occurs in a fraction of childbearing women with epilepsy. As multiple factors associated with pregnancy may have a negative impact on epilepsy, a careful analysis of the situation should be performed in those who deteriorate. Emotional and behavioural influence, including insufficient sleep and treatment non-compliance, as well as physical factors, such as emesis and pelvic distortion, should receive attention. The serum concentrations of almost all antiepileptic drugs decrease during pregnancy, particularly those which are metabolised by glucuronidation. The inter-individual variability is pronounced. In highly protein-bound drugs, such as phenytoin and valproate, unbound drug is less affected than total concentrations. Lamotrigine and levetiracetam concentrations may decrease by more than 50% in the course of pregnancy; monohydroxyoxcarbazepine by up to 30-40%. Appropriate clinical follow-up tailored to individual needs and supported by therapeutic drug monitoring should be performed in pregnant women with epilepsy. Education concerning reproductive issues is an essential part of the epilepsy service to fertile women.

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Epilepsy Behav. 2007 Dec 21 [Epub ahead of print]
The effects of cognitive rehabilitation on memory outcome after temporal lobe epilepsy surgery.
Helmstaedter C, Loer B, Wohlfahrt R, Hammen A, Saar J, Steinhoff BJ, Quiske A, Schulze-Bonhage A.
University Clinic of Epileptology Bonn, Bonn, Germany.

OBJECTIVE: Epilepsy surgery is a valuable treatment option for patients with pharmacoresistant epilepsy, but seizure freedom is often achieved at the cost of cognitive impairments caused by surgery. The aim of this study was to investigate the short-term effects of cognitive rehabilitation on memory outcome after temporal lobe epilepsy surgery. METHODS: Two groups of patients who underwent temporal lobe resection, one followed (n=55) and one not followed (n=57) by postoperative rehabilitation, were evaluated with respect to memory and attention before and 3 months after temporal lobe surgery. The groups came from different epilepsy centers, but were largely matched with respect to age, sex, type of surgery, and seizure outcome. RESULTS: After surgery, 78% of the patients were seizure-free. Repeated-measures MANOVA revealed a significant "sidexsurgery" effect on verbal recognition and a "rehabilitationxsurgery" effect on verbal learning and recognition. There were no effects for loss in verbal delayed recall or figural memory. Detailed analyses indicated gains as a result of rehabilitation, particularly after right temporal lobe surgery. Attention generally improved. The risk of manifesting losses in verbal memory was about four times higher without than with rehabilitation. CONCLUSIONS: Rehabilitation can counteract the verbal memory decline that is normally seen after temporal lobe resection. Its positive effects were evident particularly with respect to the more cortically associated aspects of verbal learning rather than to the mesial aspects of long-term consolidation/retrieval. Figural memory was not affected at all, and attention improved independent of rehabilitation. Interestingly, left temporal lobe-resected patients, who were most in need of an efficacious rehabilitation, profited less than right temporal lobe-resected patients, indicating that left-sided surgery may reduce the capacity needed for efficient training of verbal memory. Thus, rehabilitation has a positive effect on memory outcome, but its usefulness for risk groups and the question of whether training should be performed after or possibly before surgery are debatable. Further research should also address different interventions, longer-term outcome, and the carryover effects on everyday functioning.

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Epilepsy Behav. 2007 Dec 17 [Epub ahead of print]
Lamotrigine in clinical practice: Long-term experience in patients with refractory epilepsy referred to a tertiary epilepsy center.
Bootsma HP, Vos AM, Hulsman J, Lambrechts D, Leenen L, Majoie M, Savelkoul M, Schellekens A, Aldenkamp AP.
Departments of Neurology, Clinical Neurophysiology, Neuropsychology, and Pharmacology, Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands.

Lamotrigine (LTG, Lamictal), one of the newer antiepileptic drugs, was admitted to the Dutch market in 1996. It was first used as adjunctive therapy and later as a monotherapy in partial and generalized epilepsy. All patients who started on LTG in 1996 or 1997 in the Epilepsy Centre Kempenhaeghe (n=314) were enrolled in this study and followed for 48 months. The data indicate that the retention rates for LTG after 1, 2, 3, and 4 years are respectively 74.4, 69.3, 63.1, and 55.6%. Patients with normal cognitive function were more likely to continue than patients with mental retardation. The main reason for discontinuing LTG therapy was lack of efficacy (19.1%). Four patients (1.4%) were seizure-free for the total follow-up period of 48 months. The most frequently reported negative side effects were dizziness and headache, both in patients who continued and in those who discontinued therapy. A large percentage of patients also reported positive side effects like "feeling/being more active" and "feeling more clear/more responsive." For the whole patient group, the plasma level of LTG was measured 277 times. Plasma levels of LTG were influenced by the patients' comedications. Plasma levels of LTG in groups taking LTG in monotherapy, LTG plus an inducer, and LTG plus valproate were 8.7, 4.8, and 8.7mg/L, respectively. The correlation between measured plasma level and dose confirm the manufacturer's dose recommendations. The manufacturer recommends half the dosage of lamotrigine monotherapy when the patient also uses valproate. When the patient uses an inducer, the dosage of LTG must be two times the dose used in monotherapy.

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Seizure. 2007 Dec 14 [Epub ahead of print]
Life 12 years after temporal lobe epilepsy surgery: A long-term, prospective clinical study.
Tanriverdi T, Poulin N, Olivier A.
Department of Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.

It has been suggested that aim of the temporal lobe epilepsy surgery is twofold: first is to decrease seizure frequency and second is to improve quality of life without causing intolerable complications. The aim of this prospective, longitudinal clinical study is to report outcomes with respect to seizure, medication, employment and quality of life in short- and long-term follow-ups after resective temporal lobe epilepsy surgery. Consecutively 63 patients who underwent resective temporal lobe epilepsy surgery between 1993 and 1994 were enrolled. Outcomes at 6 months, 2 and 12 years were evaluated and compared with pre-operative status. The mean follow-up of this study was 12.3+/-0.6 years. Results showed that rates of seizure freedom were 82.5, 76.2, and 70.8% at 6 months, 2 and 12 years, respectively. Significant reduction in antiepileptic drug dose at long-term follow-up was found when compared to baseline. Patients after surgery had net gain of employment and improved quality of life was seen in all seizure outcome groups after surgery. Seizure-free patients showed better quality of life than those who continued to have seizure. Our results suggest that surgery leads to improvement in both seizure outcome and quality of life. Even years after the surgery, patients are still working, have reduced their medication load and have nearly normal life.

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Neurology. 2007 Dec 11;69(24 Suppl 3):S3-9.
Monotherapy in adults and elderly persons.
Faught E.
Department of Neurology, University of Alabama School of Medicine, Birmingham, Alabama, USA. faught@uab.edu

Treatment of epilepsy with a single drug has many advantages. Potential benefits of monotherapy vs polytherapy include fewer adverse events and better tolerability, avoidance of drug-drug interactions, reduced treatment costs, and improved compliance. Initial treatment should always be monotherapy. Avoidance of pharmacokinetic interactions is a major advantage. Some patients who have achieved seizure control with polytherapy may be candidates for conversion to monotherapy because there is no conclusive evidence that polytherapy provides better seizure control in the majority of patients. Recently published treatment guidelines that take into account the efficacy and tolerability profiles of new and old antiepileptic drugs (AEDs) provide recommendations for drug selection in adults. Elderly patients with epilepsy face unique treatment challenges, which include age-related reductions in liver or kidney function that may alter drug pharmacokinetics. Older persons are more sensitive to CNS side effects; some drugs may exacerbate preexisting problems such as tremor, ataxia, and cognitive difficulty. Many common conditions in the elderly are treated with drugs that are subject to interactions with AEDs. Complex dosing schedules and high drug costs are often barriers to proper care. For all these reasons, monotherapy is especially attractive for the elderly.

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Neurology. 2007 Dec 11;69(24 Suppl 3):S17-22.
Monotherapy in children and infants.
Wilfong AA.
Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA. awilfong@bcm.edu

An expanding array of antiepileptic drugs (AEDs) is available to treat childhood epilepsy, offering the potential for improved seizure control and quality of life in this important patient population but also providing challenges in the selection of the best regimen for the individual patient. In addition to correct diagnosis of seizure type and general AED efficacy profile, other important treatment considerations in pediatric patients include age-specific organ toxicity, potential cognitive and behavioral or psychiatric effects of AEDs, compliance, and drug-drug interactions, since children commonly receive more medications than nonelderly adults. Drug dosing may be more difficult in pediatric than in adult epilepsy patients, and doses in children often require adjustment as the patient matures. Because many randomized controlled trials (RCTs) of newer AEDs have not included childhood epilepsy, physicians often have incomplete data on which to base treatment decisions. Therefore, despite the wider array of potential therapies, it is often unclear how to realize the potential they offer. Recently published guidelines from a number of organizations have provided strategies for the use of new AEDs in the treatment of childhood epilepsy. Additional RCTs of monotherapy options for childhood epilepsy are greatly needed. The ketogenic diet provides an alternative to pharmacologic control of seizures in some pediatric patients.

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Neurology. 2007 Dec 11;69(24 Suppl 3):S10-6.
Importance of monotherapy in women across the reproductive cycle.
Montouris G.
Department of Neurology, Boston University Medical Center, Boston, Massachusetts 02118, USA. Georgia.Montouris@bmc.org

Special treatment considerations are warranted in women with epilepsy, particularly those of childbearing age. Treatment guidelines generally recommend the use of antiepileptic drug (AED) monotherapy at the lowest dose possible during pregnancy. The UK Epilepsy and Pregnancy Register reported that the risk for major congenital malformations is higher with AED polytherapy than with monotherapy (6.0% vs 3.7%, respectively) and that valproate carries the highest individual risk. The AEDs that induce hepatic cytochrome CYP450 enzymes carry particular concern both before and after pregnancy. Hepatic enzyme inducers alter steroid metabolism in women receiving oral contraceptives, increase the risk for contraceptive failure, and interfere with calcium absorption and vitamin D metabolism, thus increasing the risk for osteoporosis and fractures. Vitamin K deficiency is another potential consequence of treatment with a hepatic enzyme-inducing AED, increasing the risk for coagulopathy and neonatal intraparenchymal and intracerebral hemorrhage during the first 24 hours of life. Supplemental vitamin K therapy during the last month of pregnancy is warranted. Preconceptional and gestational folate supplementation may also be warranted to prevent neural tube malformation related to AED treatment. Because AED pharmacokinetics may be altered during pregnancy, plasma AED concentrations should be measured before conception and monthly during pregnancy to prevent seizure breakthrough.

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Neurologia. 2007 Aug 1; [Epub ahead of print]
[Immediate switching from carbamazepine to oxcarbazepine. Our experience in children and adolescents.]
[Article in Spanish]
López J, Fernández C, Sáenz I, García A, Cabrerizo R, Peña J.

Objetive: We review retrospectively the clinical histories of patients who were immediately switched from carbamazepine (CBZ) to oxcarbazepine (OXC), being administered a minimum of 1.3 times the CBZ dosis in 2 daily dosis of OXC. Method: The immediate switching was carried out in 22 paediatric cases. 17 patients were taking CBZ in monotherapy and 5 in politherapy. The change was made in 20 cases to lower the number of seizures (and to avoid side effects in 4 of them), and in 2 only to reduce drowsiness and fatigue. The average change was from 18.62 mg/kg of CBZ to 28.89 mg/kg of OXC. The medium change rate was 1.6:1 (maximum: 2:1). Results: In 19 cases there were no side effects. With one boy, the essential tremor worsened and two girls became more tired and drowsy. Three experienced less drowsiness and one less weight increase. Twelve cases showed no seizure changes. Five cases became immediately seizure-free, three of them for a prolongated time. There was a reduction in seizure frequency in 2 cases, with posterior disappearance in one of them. Three cases experienced a reduction in seizure intensity. In two cases OXC was stopped after 24 seizure-free months. Fourteen patients were still taking OXC, 8 in monotherapy, with a mean follow-up of 31.5 months. Conclusion: Given the potential benefits, ease and good tolerability, we advise trying with immediate switching to OXC, before adding another antiepileptic drug to CBZ. Key words: Immediate switching. Carbamazepine. Epilepsy. Oxcarbazepine. Neurología 2007;20(0):0-0.

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Epilepsia. 2007 Jul 25; [Epub ahead of print]
Current Treatment of Myoclonic Astatic Epilepsy: Clinical Experience at the Children's Hospital of Philadelphia.
Kilaru S, Bergqvist AG.
Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.A.

Purpose: Myoclonic astatic epilepsy (MAE) is a generalized epilepsy of early childhood. Little is known about the use of newer antiepileptic treatments (AET) in MAE. The purpose of this study was to describe the characteristics, treatment, and outcome of a contemporary MAE cohort exposed to the new generation AET. Methods: Charts of subjects with MAE treated between 1998 and 2005 were reviewed. Results: Twenty-three subjects (19 boys), with a median (range) follow-up of 38 (2- 86) months were identified. Thirty-nine percent had a family history of epilepsy, and 39% had family history of febrile seizures. Age at seizure onset was a median of 36 (12-24) months. Initial EEG was normal in 30%. When seizures ceased, EEG background and epileptiform abnormalities persisted in 17 and 58%, respectively. On average, each subject was exposed to five AET. The most frequently used AET was valproate (83%). Seizure freedom occurred spontaneously in three subjects, with ethosuximide and levetiracetam in one each, valproate and lamotrigine in two each, topiramate in three and the ketogenic diet (KD) in five subjects. By 36 months after seizure onset, 67% achieved seizure freedom. At the last visit, 43% were developmentally normal, 52% had mild, and 5% had moderate cognitive disabilities. Time to seizure freedom did not correlate with cognitive outcome. Conclusions: The new generation of AET may offer significant benefit to children with MAE. The KD was the most effective AET in this series, and perhaps should be considered earlier in treatment.

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Neurology. 2007 Jul 24;69(4):389-97.
Successful surgery for epilepsy due to early brain lesions despite generalized EEG findings.
Wyllie E, Lachhwani DK, Gupta A, Chirla A, Cosmo G, Worley S, Kotagal P, Ruggieri P, Bingaman WE.
Department of Neurology and Pediatrics, Cleveland Clinic Children's Hospital, Cleveland, OH 44195, USA. wylliee@ccf.org

OBJECTIVE: To understand the role of epilepsy surgery in children with generalized or bilateral findings on preoperative scalp EEG. METHODS: From our pediatric epilepsy surgery series, we identified 50 patients in whom 30 to 100% of preoperative epileptiform discharges (ictal, interictal, or both) were generalized or contralateral to the side of surgery. RESULTS: All patients had severe refractory epilepsy and an epileptogenic lesion on brain MRI. Ninety percent of the lesions were congenital, perinatal, or acquired during infancy, predominantly malformations of cortical development (44%) or cystic encephalomalacia (40%). Age at surgery was 0.2 to 24 (median 7.7) years. Surgeries were hemispherectomy (64%) or lobar or multilobar resection. At last follow-up (median 24.0 months), 72% of patients were seizure-free, 16% had marked improvement with only brief episodes of staring or tonic stiffening, and 12% were not improved. The rate of seizure-free outcome was not significantly associated with age at seizure onset or surgery, presence of hemiparesis or focal clinical features during seizures, type of lesion, or surgery type. Postoperative seizure-free rate did not differ from that in a comparison group of similar patients who matched the study group except for their high percentage (70 to 100%) of ipsilateral ictal and interictal epileptiform discharges on preoperative EEG. CONCLUSIONS: Epilepsy surgery may be successful for selected children and adolescents with a congenital or early-acquired brain lesion, despite abundant generalized or bilateral epileptiform discharges on EEG. The diffuse EEG expression may be due to an interaction between the early lesion and the developing brain.

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Epilepsia. 2007 Jul 21; [Epub ahead of print]
Epilepsy Surgery in Children: Results and Predictors of Outcome on Seizures.
Cossu M, Lo Russo G, Francione S, Mai R, Nobili L, Sartori I, Tassi L, Citterio A, Colombo N, Bramerio M, Galli C, Castana L, Cardinale F.
“C. Munari” Center for Epilepsy Surgery, Ospedale Niguarda, Milan, Italy.

Purpose: To retrospectively analyze the results on seizures of surgery in children with drug-resistant focal epilepsy. To identify the factors predicting seizure control among several presurgical, surgical, and postsurgical variables. Methods: One hundred thirteen patients (67 male, 46 female), younger than 16 years, operated on from 1996 to 2004 and followed-up for at least 2 years were identified. Individualized microsurgical resections, aimed at removal of the epileptogenic zone, were performed according to the results of tailored presurgical evaluations, which included stereo-electroencephalographic recording with intracerebral electrodes when needed. Risk of seizure recurrence was assessed for the considered variables by bivariate and multivariate analysis. Results: Mean age at surgery was 8.8 years, mean duration of epilepsy was 5.7 years, and mean age at seizure onset was 3.1 years. One hundred eight patients (96%) had an abnormal magnetic resonance imaging. At postoperative follow-up (mean duration 55.1 month), 77 patients (68%) were in Engel's class I, with 68 patients (60%) being seizure free (Engel's classes Ia and Ic). At multivariate analysis, variables associated with a significantly lower risk of seizure recurrence were unifocal lesion at MRI and older age at seizure onset (presurgical variables), temporal unilobar resection and complete lesionectomy (surgical variables), diagnosis of glial-neuronal tumors (postsurgical variables). Conclusions: Surgery is a valuable option for children with drug-resistant focal epilepsies which may provide excellent results in a considerable amount of cases. Since results of surgery for epilepsy strongly depend on the presurgical identification of the Epileptogenic Zone, future work should be focused on refinement and implementation of diagnostic strategies.

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Epilepsia. 2007 Jul 21; [Epub ahead of print]
Aggravation of Seizures and/or EEG Features in Children Treated with Oxcarbazepine Monotherapy.
Vendrame M, Khurana DS, Cruz M, Melvin J, Valencia I, Legido A, Kothare SV.
Department of Pediatrics, Division of Neurology, St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, Pennsylvania, U.S.A.

Purpose: Exacerbation of epilepsy may occur following initiation of therapy with antiepileptic drugs (AEDs). The aim of this study is to analyze the clinical and EEG characteristics of a group of pediatric patients with worsening of seizures and/or EEG deterioration while on oxcarbazepine (OXC). Methods: A retrospective analysis of a clinical database was performed to identify patients with epilepsy treated with OXC over the past 3 years. History, neurological examination, and EEG findings were reviewed to identify any who had developed exacerbation of seizures or new abnormalities on EEG. Results: Of 290 patients on OXC, we identified 12 patients with new onset seizures, all with initial normal neurological exam and normal EEG, who developed either worsening of preexisting seizures, new seizure types, and/or EEG deterioration following introduction of OXC monotherapy. EEG changes were primarily characterized by new onset of generalized epileptiform activity not reported on the initial baseline EEG. Following substitution of OXC with a broad spectrum AED, significant improvement of seizure control and improvement in the EEG was observed. Conclusions: These findings suggest that OXC can aggravate seizures and/or worsen EEG features in children. Following initiation of therapy with OXC, monitoring of patients with follow-up EEGs may be important, especially in patients who do not show adequate response to therapy.

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Cochrane Database Syst Rev. 2007 Jul 18;(3):CD005399.
Pharmacological interventions for epilepsy in people with intellectual disabilities.
Beavis J, Kerr M, Marson A.

BACKGROUND: The development of epilepsy in a person with intellectual disabilities is a common occurrence. In view of the fact that seizures in intellectually disabled people are often complex and refractory to treatment and that antiepileptic medication may have a profound effect upon behaviour in this patient group, it is evident that good quality randomised controlled trials are needed in this population. OBJECTIVES: The aim of our study was to assess the data available from randomised controlled trials of antiepileptic drug interventions in people with epilepsy and intellectual disabilities. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 4), MEDLINE OVID (1966 to October 2006), PsychInfo OVID (1806 to October 2006) and EMBASE OVID (1980 to April 2005). SELECTION CRITERIA: Randomised controlled trials (RCTs) of pharmacological interventions for people with epilepsy and a learning disability. RCTs where inadequate methods of allocation concealment had been used were also included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information.Outcome measures included the following.(1) Retention on treatment.(2) Seizure freedom.(3) Reduction in seizure frequency.(4) Seizure severity scales.(5) Global rating scales.(6) Behavioural outcomes.(7) Cognitive outcomes.(8) Adverse effects.(9) Quality of life. MAIN RESULTS: Data were heterogenous and a descriptive analysis is presented. This review confirms that in the majority of cases where antiepileptic drugs (AEDs) were trialled in this population, moderate reduction in seizure frequency and occasional seizure freedom were obtained. In general it seems reasonable to say that AEDs proven effective in the general epilepsy population are also effective in refractory epilepsy in people with intellectual disability. It is not possible to comment on relative efficacy between medications making clinical choice decisions difficult.Clinical decision is also likely to be guided by concern over side effects. The quality of the studies does not aid clinicians greatly to this respect. In general it seems that in trial settings patients continue on treatment, in the majority of cases, and placebo groups often experience less in the way of side effects. Where side effects are experienced they appear similar to those seen in non-intellectual disability studies.One area of key concern is that of behavioural exacerbation. The majority of studies are unhelpful due to lack of or non-reliable measures in this area. However, where measured, little obvious impact on behaviour is seen in terms of behaviour disorder. AUTHORS' CONCLUSIONS: In summary this review broadly supports the use of AEDs to reduce seizure frequency in people with refractory epilepsy and intellectual disability. The evidence suggests that side effects are similar to those in the general population and that behavioural side effects leading to discontinuation are rare but that other effects are under researched.

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Neurology. 2007 Jul 17;69(3):250-4. Comment in: Neurology. 2007 Jul 17;69(3):233-4.
An open-label trial of levetiracetam in severe myoclonic epilepsy of infancy.
Striano P, Coppola A, Pezzella M, Ciampa C, Specchio N, Ragona F, Mancardi MM, Gennaro E, Beccaria F, Capovilla G, Rasmini P, Besana D, Coppola GG, Elia M, Granata T, Vecchi M, Vigevano F, Viri M, Gaggero R, Striano S, Zara F.
Epilepsy Center, Federico II University, Napoli, Italy. pstriano@email.it

OBJECTIVE: To conduct an open-label, add-on trial on safety and efficacy of levetiracetam in severe myoclonic epilepsy of infancy (SMEI). Patients and METHODS: SMEI patients were recruited from different centers according to the following criteria: age > or =3 years; at least four tonic-clonic seizures/month during the last 8 weeks; previous use of at least two drugs. Levetiracetam was orally administrated at starting dose of approximately 10 mg/kg/day up to 50 to 60 mg/kg/day in two doses. Treatment period included a 5- to 6-week up-titration phase and a 12-week evaluation phase. Efficacy variables were responder rate by seizure type and reduction of the mean number per week of each seizure type. Analysis was performed using Fisher exact and Wilcoxon tests. RESULTS: Twenty-eight patients (mean age: 9.4 +/- 5.6 years) entered the study. Sixteen (57.1%) showed SCN1A mutations. Mean number of concomitant drugs was 2.5. Mean levetiracetam dose achieved was 2,016 mg/day. Twenty-three (82.1%) completed the trial. Responders were 64.2% for tonic-clonic, 60% for myoclonic, 60% for focal, and 44.4% for absence seizures. Number per week of tonic-clonic (median: 3 vs 1; p = 0.0001), myoclonic (median: 21 vs 3; p = 0.002), and focal seizures (median: 7.5 vs 3; p = 0.031) was significantly decreased compared to baseline. Levetiracetam effect was not related to age at onset and duration of epilepsy, genetic status, and concomitant therapy. Levetiracetam was well tolerated by subjects who completed the study. To date, follow-up ranges 6 to 36 months (mean, 16.2 +/- 13.4). CONCLUSION: Levetiracetam add-on is effective and well tolerated in severe myoclonic epilepsy of infancy. Placebo-controlled studies should confirm these findings.

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Arq Neuropsiquiatr. 2007 Jun;65(2B):381-4.
Ketogenic diet for the treatment of refractory epilepsy: a 10 year experience in children.
Freitas A, da Paz JA, Casella EB, Marques-Dias MJ.
Médica Pós-Graduanda do Setor de Neuropediatria do ICr, Mestre em Ciências pela FMUSP. alessandra_freitas@msn.com

Ketogenic diet (KD) is a high fat and low carbohydrate diet, which controls refractory epilepsy. We analyzed the KD effects on 54 children of the Children's Institute of the University of São Paulo. Efficacy, tolerability, and adverse effects were studied. Response to KD was effective (E) if seizure control was >75%, good (G) when 50-75%. When possible, we correlated the results with the epileptic syndrome and patient's age. By the second month on diet, 57.4% of the patients had E response and 31.4% G results. At the 6th month, 63.8% had E response and 25.5% G. At the 12th month, 71.8% had E and 25.6% G. At the 24th month, 62.1% had E and 37.9% G. Antiepileptic drugs have been reduced, and generalized epilepsy was the most sensitive. Age-related differences were not observed. Adverse effects were rarely observed. In conclusion, KD proved to be an effective treatment for refractory epilepsy.

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J Child Neurol. 2007 Jun;22(6):693-9.
Topiramate monotherapy in newly diagnosed epilepsy in children and adolescents.
Glauser TA, Dlugos DJ, Dodson WE, Grinspan A, Wang S, Wu SC; EPMN-106/INT-28 Investigators.
Division of Neurology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-2899, USA. tracy.glauser@cchmc.org

A double-blind, dose-controlled study evaluated topiramate as monotherapy in 470 patients with newly diagnosed (< or = 3 months) epilepsy or epilepsy relapse in the absence of therapy. In addition to having at least 2 lifetime-unprovoked seizures, patients had 1 or 2 partial-onset seizures or generalized-onset tonic-clonic seizures during a 3-month retrospective baseline. The trial included a large cohort (N = 151, 32%) of children and adolescents 6 to 15 years of age. Eligible patients were randomized to treatment groups in which topiramate was titrated to target maintenance dosages of either 400 mg/day (n = 77) or 50 mg/day (n = 74). Patients were followed for at least 6 months. Based on Kaplan-Meier analyses, the primary efficacy endpoint of time to first seizure favored the higher topiramate dose in both the overall population and the cohort of children/adolescents. The probability that children/adolescents remaining in the study were seizure free at 6 months was 78% in the 50-mg target dose group and 90% with the higher dose. At 12 months, the probability of being seizure free was 62% and 85%, respectively. The incidence of treatment-limiting adverse events was 4% in the 50-mg target dose group and 14% in the group assigned to 400 mg as a target dose. The most common adverse events, excluding typical childhood illnesses, were headache, appetite decrease, weight loss, somnolence, dizziness, concentration/attention difficulty, and paresthesia. As shown in this subset analysis, topiramate is effective and well tolerated as monotherapy in children and adolescents.

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Neurosurgery. 2007 May;60(5):873-80; discussion 873-80.
Long-term seizure outcome in reoperation after failure of epilepsy surgery.
Gonzalez-Martinez JA, Srikijvilaikul T, Nair D, Bingaman WE.

OBJECTIVE: Treatment of patients who fail epilepsy surgery is problematic. Selected patients may be candidates for further surgery, potentially leading to a significant decrease in the frequency and severity of seizures. We present our long-term outcome series of highly investigated patients who failed resective epilepsy surgery and subsequently underwent reoperative resective procedures. METHODS: We performed a retrospective consecutive analysis of patients who underwent reoperative procedures because of medically intractable epilepsy at our institution from 1990 to 2001. Seventy patients underwent reoperative epilepsy surgery, with 57 patients having a minimum follow-up period of 2 years. We assessed the relationship between seizure outcome and categorical variables using chi2 and Fisher's exact tests, and the relationship between outcome and continuous variables using a Wilcoxon rank-sum test. Statistical significance was set at a P value of 0.05. RESULTS: Of the 57 patients (29 male and 28 female patients), the age of seizure onset ranged from 3 months to 39 years (mean, 10.7 +/- 10.3 yr; median, 7 yr). The mean age at reoperation was 24.7 +/- 12 years (range, 4-50 yr). The interval between first and second resection was 7 days to 16 years. The follow-up period ranged from 24 to 228 months (mean, 128 mo; mode, 132 mo). Seizure outcome was classified according to Engel's classification. Fifty-two percent of the patients had a favorable outcome (38.6% were Class I and 14.0% were Class II). Patients with tumors as their initial pathology had better outcome compared with patients with focal cortical dysplasia and mesial temporal sclerosis (P < 0.05). CONCLUSION: Reoperation should be considered in selected patients failing epilepsy resective surgery because approximately 50% of patients may have benefit. Patients with cortical dysplasia and mesial temporal sclerosis are less likely to improve after reoperation.

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Lancet Neurol. 2007 May;6(5):465-8.
Antiepileptic drugs: generic versus branded treatments.
Heaney DC, Sander JW.
Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.

Antiepileptic drugs (AEDs) are relatively cheap but high volumes of prescriptions mean that substantial drug-budget savings may be possible by switching from innovator brands to cheaper generic drugs. Such savings have been achieved in many other treatment areas. However, more caution may be needed in the case of epilepsy because of the narrow therapeutic range of most AEDs; clinical principles of prescribing, which include making only cautious and gradual changes to dosing; the health and socioeconomic impact of breakthrough seizures or toxicity; and the need for long-term consistency of supply. Many physicians and patient groups are insufficiently reassured by current definitions of similarity between generics and innovator brands. Switching to the cheapest generic AED may offer drug-budget savings that outweigh any risk to patient safety. But to date, this cost-benefit analysis has not been done. We propose that all changes to established principles of treating epilepsy are evidence based and that the risks of switching are clearly defined.

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Lancet Neurol. 2007 May;6(5):421-30.
Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management.
van Breemen MS, Wilms EB, Vecht CJ.
Department of Neurology, Medical Centre The Hague, Netherlands.

Epilepsy is common in patients with brain tumours and can substantially affect daily life, even if the tumour is under control. Several factors affect the mechanism of seizures in brain tumours, including tumour type, tumour location, and peritumoral and genetic changes. Prophylactic use of antiepileptic drugs is not recommended, and potential interactions between antiepileptic and chemotherapeutic agents persuades against the use of enzyme-inducing antiepileptic drugs. Multidrug-resistance proteins prevent the access of antiepileptic drugs into brain parenchyma, which partly explains why seizures are frequently refractory to treatment. Lamotrigine, valproic acid, and topiramate are first-line treatments of choice; if insufficient, add-on treatment with levetiracetam or gabapentin can be recommended. On the basis of clinical studies, we prefer to start treatment with valproic acid, adding levetiracetam if necessary. Risks of cognitive side-effects with antiepileptic drugs can add to previous damage by surgery or radiotherapy, and therefore appropriate choice and dose of antiepileptic drug is crucial.

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Int Rev Neurobiol. 2007;81:287-97.
Treatment of nonconvulsive status epilepticus.
Walker MC.
Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London WC1N 3BG, United Kingdom.

Nonconvulsive status epilepticus (NCSE) is relatively common; it comprises at least one third of all cases of status epilepticus. NCSE may be an even more common, yet more elusive, condition in the elderly population. NCSE can be divided into complex partial status epilepticus (CPSE), NCSE in coma, and typical absence status epilepticus (TAS). The clinical manifestations may be subtle, and thus the diagnosis of these conditions is critically dependent on electroencephalography (EEG). When EEG demonstrates typical ictal patterns, the diagnosis is usually straightforward. However, in many circumstances the EEG pattern has to be differentiated from other encephalopathic patterns, and this differentiation can prove troublesome; clinical and electrographic response to treatment can prove helpful in these situations. The prognosis for NCSE in the elderly is generally poor due to the underlying etiology rather than the persistence of electrographic discharges. Whether the neuronal damage that occurs in convulsive status epilepticus and in animal models of limbic status epilepticus also occurs in NCSE in humans is still a matter of debate. Intravenous treatment is not benign, especially in the elderly, who may be at greater risk of systemic complications from hypotensive and sedative agents. Therefore, a more conservative approach to the treatment of NCSE in the elderly is warranted. Oral benzodiazepines should be used for the treatment of TAS and CPSE in noncomatose patients with a prior history of epilepsy, and in some circumstances, intravenous medication may be necessary. Generally, anesthetic coma should not be advised in either of these conditions. A more aggressive approach may be required with NCSE in coma, in the hope of improving a very poor prognosis. Treatment regimens will remain largely speculative until there are more relevant animal models and controlled trials of conservative versus aggressive treatment.

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Epilepsy Res. 2007 Apr 18; [Epub ahead of print]
Evaluation of carisbamate, a novel antiepileptic drug, in photosensitive patients: An exploratory, placebo-controlled study.
Trenite DG, French JA, Hirsch E, Macher JP, Meyer BU, Grosse PA, Abou-Khalil BW, Rosenfeld WE, van Gerven J, Novak GP, Parmeggiani L, Schmidt B, Gibson D, Guerrini R.
University La Sapienza II, Via Vitorchiano 81, 00189 Roma, Italy.

PURPOSE: Carisbamate, a novel neuromodulatory agent with antiepileptic properties, was evaluated in patients with photoparoxysmal responses to intermittent photic stimulation (IPS) in this multicenter, non-randomized, single-blind, placebo-controlled, proof-of-concept study. METHODS: Eighteen Caucasian patients (14 females, 4 males) with a mean age of 30 years (range: 16-51 years) underwent standardized IPS under three eye conditions (during eye closure, eyes closed and eyes open) at hourly intervals for up to 8h after receiving placebo (Day 1), carisbamate (Day 2) and placebo (Day 3). Carisbamate was given at single doses of 250-1000mg. All patients received one or two concomitant antiepileptic drugs, most commonly valproate. RESULTS: Carisbamate produced a dose-dependent reduction in photosensitivity in the 13 evaluable patients, with abolishment of photoparoxysmal responses in 3 patients and clinically significant suppression of such responses in 7 additional patients. Photosensitivity was abolished or reduced in all five patients in the 1000-mg dose group. The onset of carisbamate occurred rapidly, with clinically significant suppression achieved before or near the time peak plasma drug levels were reached. The duration of action was dose-related and long-lasting, with clinically significant reductions of photosensitivity observed for up to 32h after doses of 750 or 1000mg. Carisbamate was generally well tolerated, with dizziness and nausea reported more frequently after active drug than placebo. CONCLUSION: This study shows that carisbamate exhibits dose-related antiepileptic effects in the photosensitivity model. Randomized, controlled studies of carisbamate in epilepsy patients inadequately controlled by their existing AED therapy are warranted.

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Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004724.
Self-management education for children with epilepsy.
Stokes T, Shaw E, Camosso-Stefinovic J, Baker R, Baker G, Jacoby A.

BACKGROUND: Self-management education has been shown to improve the quality of life of children and young people with chronic illnesses. It has been suggested that self-management education may improve seizure control and other outcomes in children and young people with epilepsy. OBJECTIVES: To review systematically the research literature on the effectiveness of self-management education in improving health outcomes for children and young people with epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's Specialised Register (April 2007), MEDLINE (Ovid) (1966 to February 2007), EMBASE (Ovid) (1980 to February 2007), CINAHL (Dialog) (1980 to February 2007), and PsycINFO (Dialog) (1887 to February 2007). We also handsearched Epilepsia and conference abstracts and proceedings. Experts in the field were contacted to identify any additional trials. No language restriction was imposed. SELECTION CRITERIA: Randomised trials of self-management education programmes for children or young people with epilepsy. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the quality of each study and extracted data. MAIN RESULTS: Only one trial involving 167 children was identified that evaluated the effect of a child-centred model of training for the self-management of two chronic illnesses, asthma and epilepsy. The trial was not assessed as being of high quality and the methods used to analyse and report the data did not enable us to precisely determine the effect of the intervention. However, improvements were seen in seizure frequency and other outcomes, such as knowledge and behaviour. AUTHORS' CONCLUSIONS: Self-management education programmes that deliver a child-centred model of training, may improve knowledge about epilepsy, certain behavioural outcomes, and reduce seizure frequency in children and young people with epilepsy. However, based on the evidence reviewed, we are not able to determine how effective it is, or what the key components of the programme should be.

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Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004723.
Self-management education for adults with epilepsy.
Shaw E, Stokes T, Camosso-Stefinovic J, Baker R, Baker G, Jacoby A.

BACKGROUND: Self-management education has been shown to improve the quality of life of people with chronic illnesses. It has been suggested that self-management education may improve seizure control and other outcomes in people with epilepsy. OBJECTIVES: To review systematically the research literature on the effectiveness of self-management education in improving health outcomes for adults with epilepsy. SEARCH STRATEGY: We searched MEDLINE (Ovid) (1966 to April 2005), EMBASE (Ovid) (1980 to April 2005), CINAHL (Dialog) (1980 to April 2005), PsycINFO (Dialog) (1887 to April 2005), and the Cochrane Epilepsy Group's Specialised Register (April 2005). We also handsearched Epilepsia and conference abstracts and proceedings. Experts in the field were contacted to identify any additional trials. We did not impose any language restriction. We re-ran the searches in February 2007 and added the identified references to the 'Studies awaiting assessment' table. SELECTION CRITERIA: Randomised trials of self-management education programmes for adults with epilepsy. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the quality of each study and extracted data. MAIN RESULTS: Two trials evaluated the effect of self-management education for adults with epilepsy, neither of which assessed as being of high quality. In total, 483 adults with epilepsy were randomised. Both trials showed improvements in seizure frequency and other outcomes, such as knowledge. However, we were not able to estimate a summary effect for seizure frequency due to a lack of data. AUTHORS' CONCLUSIONS: Self-management education programmes, based on increasing understanding through psychosocial methods, may improve knowledge about epilepsy, certain behavioural outcomes, and reduce seizure frequency. It is, however, not clear how effective self-management programmes of epilepsy would be in a more general population of adults with epilepsy, as both trials had higher proportions of people with partial seizures than would be expected in a community sample.

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Eur J Paediatr Neurol. 2007 Apr 16; [Epub ahead of print]
Long-term use of Levetiracetam in patients with severe childhood-onset epilepsy.
von Stuelpnagel C, Holthausen H, Kluger G.
Department of Paediatrics, Hospital Munich-Harlaching, Sanatoriumsplatz 2, 81545 Harlaching, Germany.

OBJECTIVE: To assess the efficacy and tolerability of Levetiracetam (LEV) in children and adolescents with refractory epilepsy with a special interest in the long-term retention rate. METHOD: One hundred and twenty-nine patients (83 male, 46 female; mean age 10.6 years/range: 6 months-39 years 9 months) were included in a prospective, open-label, add-on trial of LEV for up to 3 years. All patients had severe forms of epilepsy starting before the age of 10 often accompanied by mental retardation. Primary outcome measures were changes in seizure frequency after 6 months on the medication with LEV, with initial responders (>50% seizure reduction). Further objective was the retention rate of LEV therapy after 3 years defined as percentage of patients still taking LEV. RESULTS: Thirty-five patients (27.1%) were initial responders of which 5 became seizure free. The average maximum LEV dosage was 39.8mg/kg/day (range: 6-70mg/kg/day) with no difference responders vs. no responders. The retention rate for responders after 3 years was 22.5%. The rate of side effects was 39.8% in all patients, with the most frequent side effects being fatigue (12.5%), aggressiveness (7.8%) and gastrointestinal disorders (13.3%). CONCLUSIONS: Our study in patients with refractory epilepsy suggests that our initial responders were very likely to be still taking LEV after 3 years. We therefore consider treatment with LEV in this special group of patients with refractory epilepsy a promising therapeutic option, because of its favourable tolerance profile, the option of fast titration and the absence of drug interactions.

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Epilepsia. 2007 Apr 18; [Epub ahead of print]
Choosing a First Drug Treatment for Epilepsy after SANAD: Randomized Controlled Trials, Systematic Reviews, Guidelines and Treating Patients.
Chadwick D, Marson T.
School of Clinical Science, University of Liverpool, Liverpool, United Kingdom.

The ILAE treatment guidelines for initial monotherapy emphasise the poor quality of information available to inform everyday clinical practice. Industry sponsored studies comparing antiepileptic drugs answer restricted licensing questions, rather than those relevant to the clinical community (patients, health professionals and funders of health care). The SANAD study, a pragmatic randomized clinical trial, offers a methodology to address some of these questions. It identifies lamotrigine as a cost-effective alternative to carbamazepine for the treatment of focal epilepsies, but confirms valproate as the most effective drug for the treatment of generalized or unclassified epilepsy.

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Pediatr Neurol. 2007 Apr;36(4):227-230.
Levetiracetam Monotherapy in Children With Epilepsy.
Khurana DS, Kothare SV, Valencia I, Melvin JJ, Legido A.
Section of Neurology, Department of Pediatrics, St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, Pennsylvania.

Although levetiracetam has shown efficacy in children with epilepsy, when used as adjunctive therapy, limited data are available regarding its use as monotherapy. The objective of this study is to evaluate the efficacy and tolerability of levetiracetam monotherapy in a cohort of pediatric patients with epilepsy. A retrospective analysis of pediatric epilepsy patients receiving levetiracetam at a single institution was performed over a 3-year period. Eighty-one patients were identified, 18 of whom received levetiracetam as monotherapy (mean age, 9.6 years). Epilepsy types were partial in 14 and generalized in 4. Conversion to levetiracetam monotherapy occurred in 16 patients due to lack of efficacy or adverse events, and 2 patients were initially started on monotherapy. Dose range of levetiracetam was 14-60 mg/kg, and duration of therapy ranged from 2-24 months. Eleven patients became seizure free on levetiracetam, one had at least 50% reduction in seizures, and six others had no change in seizure frequency. Adverse events included worsening of behavior, irritability, and possible cognitive changes, seen in 4 patients. Levetiracetam was discontinued in seven patients overall. Levetiracetam monotherapy appeared to be effective and well tolerated in this group of children with epilepsy and warrants further investigation in a well-controlled, prospective study.

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Brain. 2007 Feb;130(Pt 2):574-84. Epub 2007 Jan 5.
Surgical outcome and prognostic factors of frontal lobe epilepsy surgery.
Jeha LE, Najm I, Bingaman W, Dinner D, Widdess-Walsh P, Luders H.
Department of Neurology, Section of Epilepsy, Cleveland Clinic, Cleveland, OH 44195, USA. jehil@ccf.org

Frontal lobe epilepsy (FLE) surgery is the second most common surgery performed to treat pharmacoresistant epilepsy. Yet, little is known about long-term seizure outcome following frontal lobectomy. The aim of this study is to investigate the trends in longitudinal outcome and identify potential prognostic indicators in a cohort of FLE patients investigated using modern diagnostic techniques. We reviewed 70 patients who underwent a frontal lobectomy between 1995 and 2003 (mean follow-up 4.1 +/- 3 years). Data were analysed using survival analysis and multivariate regression with Cox proportional hazard models. A favourable outcome was defined as complete seizure-freedom, allowing for auras and seizures restricted to the first post-operative week. The estimated probability of complete seizure-freedom was 55.7% [95% confidence interval (CI) = 50-62] at 1 post-operative year, 45.1% (95% CI = 39-51) at 3 years, and 30.1% (95% CI = 21-39) at 5 years. Eighty per cent of seizure recurrences occurred within the first 6 post-operative months. Late remissions and relapses occurred, but were rare. After multivariate analysis, the following variables retained their significance as independent predictors of seizure recurrence: MRI-negative malformation of cortical development as disease aetiology [risk ratio (RR) = 2.22, 95% CI = 1.40-3.47], any extrafrontal MRI abnormality (RR = 1.75, 95% CI = 1.12-2.69), generalized/non-localized ictal EEG patterns (RR = 1.83, 95% CI = 1.15-2.87), occurrence of acute post-operative seizures (RR = 2.17, 95% CI = 1.50-3.14) and incomplete surgical resection (RR = 2.56, 95% CI = 1.66-4.05) (log likelihood-ratio test P-value < 0.0001). More than half of patients in favourable prognostic categories were seizure-free at 3 years, and up to 40% were seizure-free at 5 years, compared to <15% in those with unfavourable outcome predictors. These data underscore the importance of appropriate selection of potential surgical candidates.

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Ann Neurol. 2007 Jan 25; [Epub ahead of print]
Results of treatment changes in patients with apparently drug-resistant chronic epilepsy.
Luciano AL, Shorvon SD.
Institute of Neurology, UCL, National Hospital for Neurology and Neurosurgery, London, United Kingdom.

OBJECTIVE: It has long been known that the response to treatment in newly diagnosed epilepsy is better than in chronic epilepsy. However, in the past 15 years, 8 major new antiepileptic drugs have been licensed, and the effect of this wider range of treatment options on prognosis has not been fully assessed. The aim of this study was to quantify the effect of adding a previously unused antiepileptic drug to the treatment regimen in adults with uncontrolled chronic epilepsy that had been resistant to previous antiepileptic drug treatment. METHODS: A total of 265 drug additions were studied in 155 adult patients with chronic epilepsy (defined as epilepsy active at least 5 years after and initiation of therapy). RESULTS: About 16% of all drug introductions resulted in seizure freedom (defined as seizure freedom at last follow-up for 12 months or longer), and a 50 to 99% seizure reduction occurred in a further 21%. Of the 155 patients, 28% were rendered seizure free by a drug introduction. Clinical factors associated with a better effect were fewer previously used antiepileptic drugs, shorter duration epilepsy, and idiopathic epilepsy. INTERPRETATION: This study provides a quantitative estimate of the value of changing drug therapy in patients in whom seizures were previously uncontrolled by previous therapy. The application of a systematic protocol to the treatment of chronic epilepsy will improve seizure control in a substantial proportion of cases. The rather nihilistic view that intractability is inevitable if seizure control is not obtained within a few years of the onset of therapy is incorrect. Ann Neurol 2007.

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Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005222.
Corticosteroids including ACTH for childhood epilepsy other than epileptic spasms.
Gayatri N, Ferrie C, Cross H.

BACKGROUND: Epilepsy is a disorder with recurrent epileptic seizures. Corticosteroids have been used in the treatment of children with epilepsy and have significant adverse effects. Their efficacy and tolerability have not been not clearly established. OBJECTIVES: To determine the efficacy of corticosteroids in terms of seizure control, improvements in cognition and in quality of life and tolerability of steroids compared to placebo or other antiepileptic drugs. SEARCH STRATEGY: We searched the following databases: The Cochrane Epilepsy Group Specialized Register (September 2006); Cochrane Central Register of Controlled Trials (CENTRAL)(The Cochrane Library Issue 2, 2006); MEDLINE (1966 - April 2004); EMBASE (1966 - December 2004); Database of Abstracts of Reviews of Effectiveness (DARE) (December 2004).We checked the reference lists of retrieved studies for additional reports of relevant studies. SELECTION CRITERIA: All randomized controlled trials of administration of corticosteroids to children (less than 16 years) with epilepsy. DATA COLLECTION AND ANALYSIS: Three review authors independently selected trials for inclusion and extracted data. Outcomes included cessation of seizures, reduction in seizure frequency, improvement in cognition, quality of life and adverse effects of steroids. MAIN RESULTS: A single RCT was included that recruited five patients in double blind crossover trial. One was withdrawn prematurely from the study and another had infantile spasms and hence was excluded from further analysis. ACTH 4-9 was administered. The overall reduction in seizure frequency of more than 25% and less than 50% occurred in one child at low dose and in two children at higher dose. One child did not show any reduction in seizure frequency. No adverse effects were reported. AUTHORS' CONCLUSIONS: No evidence was found for the efficacy or safety of corticosteroids in treating childhood epilepsies. Clinicians using steroids in childhood epilepsies, other than for epileptic spasms, should take this into account before using these agents.

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J Child Psychol Psychiatry. 2007 Jan;48(1):3-16.
Annotation: Neurofeedback - train your brain to train behaviour.
Heinrich H, Gevensleben H, Strehl U.
Child & Adolescent Psychiatry, University of Erlangen-Nurnberg, Germany.

Background: Neurofeedback (NF) is a form of behavioural training aimed at developing skills for self-regulation of brain activity. Within the past decade, several NF studies have been published that tend to overcome the methodological shortcomings of earlier studies. This annotation describes the methodical basis of NF and reviews the evidence base for its clinical efficacy and effectiveness in neuropsychiatric disorders. Methods: In NF training, self-regulation of specific aspects of electrical brain activity is acquired by means of immediate feedback and positive reinforcement. In frequency training, activity in different EEG frequency bands has to be decreased or increased. Training of slow cortical potentials (SCPs) addresses the regulation of cortical excitability. Results: NF studies revealed paradigm-specific effects on, e.g., attention and memory processes and performance improvements in real-life conditions, in healthy subjects as well as in patients. In several studies it was shown that children with attention-deficit hyperactivity disorder (ADHD) improved behavioural and cognitive variables after frequency (e.g., theta/beta) training or SCP training. Neurophysiological effects could also be measured. However, specific and unspecific training effects could not be disentangled in these studies. For drug-resistant patients with epilepsy, significant and long-lasting decreases of seizure frequency and intensity through SCP training were documented in a series of studies. For other child psychiatric disorders (e.g., tic disorders, anxiety, and autism) only preliminary investigations are available. Conclusions: There is growing evidence for NF as a valuable treatment module in neuropsychiatric disorders. Further, controlled studies are necessary to establish clinical efficacy and effectiveness and to learn more about the mechanisms underlying successful training.

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Epilepsia. 2007 Jan;48(1):133-40.
Hemispheric surgery in children with refractory epilepsy: seizure outcome, complications, and adaptive function.
Basheer SN, Connolly MB, Lautzenhiser A, Sherman EM, Hendson G, Steinbok P.
Division of Neurology, British Columbia Children's Hospital and the University of British Columbia, Vancouver, British Columbia, Canada.

Purpose: To describe seizure control, complications, adaptive function and language skills following hemispheric surgery for epilepsy. Methods: Retrospective chart review of patients who underwent hemispheric surgery from July 1993 to June 2004 with a minimum follow-up of 12 months. Results: The study population comprised 24 children, median age at seizure onset six months and median age at surgery 41 months. Etiology included malformations of cortical development (7), infarction (7), Sturge-Weber Syndrome (6), and Rasmussen's encephalitis (4). The most frequent complication was intraoperative bleeding (17 transfused). Age <2 yr, weight <11 kg, and hemidecortication were risk factors for transfusion. Postoperative complications included aseptic meningitis (6), and hydrocephalus (3). At median follow-up of 7 yr, 79% of patients are seizure free. Children with malformations of cortical development and Rasmussen's encephalitis were more likely to have ongoing seizures. Overall adaptive function scores were low, but relative strengths in verbal abilities were observed. Shorter duration of epilepsy prior to surgery was related significantly to better adaptive functioning. Conclusions: Hemispheric surgery is an effective therapy for refractory epilepsy in children. The most common complication was bleeding. Duration of epilepsy prior to surgery is an important factor in determining adaptive outcome.

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Epilepsia. 2007 Jan;48(1):77-81.
Combined ketogenic diet and vagus nerve stimulation: rational polytherapy?
Kossoff EH, Pyzik PL, Rubenstein JE, Christina Bergqvist AG, Buchhalter JR, Donner EJ, Nordli DR Jr, Wheless JW.
The Johns Hopkins Hospital, Baltimore, Maryland.

Objective: The concept of "rational polypharmacy" has been associated with anticonvulsant management for decades, but the term has not been applied to nonpharmacologic therapies. Methods: We conducted a multicenter, retrospective study of children who received concurrent diet (ketogenic or modified Atkins) and vagus nerve stimulation (VNS) treatment for medically intractable epilepsy. Results: Thirty children in total from six epilepsy centers were treated over a 6-yr period. The median age at the initiation of combination therapy was 10 yr (range, 4-24 yr). Sixteen (53%) received dietary therapy followed by VNS; no differences were noted between centers. After 3 months, 21 (70%) had seizure reduced by >50% over the previous single nonpharmacologic treatment, of whom 13 (62%) had improvement within the first month. A 5-min VNS off-time correlated with >90% seizure reduction (p = 0.02). The median duration of nonpharmacologic polytherapy was 12 months (range, 0.5-96 months); 17 (57%) remain on dual therapy at this time. No side effects were noted. Most patients who discontinued combination therapy did so because of a lack of efficacy rather than restrictiveness. Conclusions: In this small group, the combined use of diet and VNS appeared synergistic and yielded rapid benefits. It may be more effective with longer VNS off-times. Further prospective studies of this combination in refractory pediatric epilepsy are needed to help guide optimal use.

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Seizure. 2007 Jan 17; [Epub ahead of print]
Seizure freedom off antiepileptic drugs after temporal lobe epilepsy surgery.
Al-Kaylani M, Konrad P, Lazenby B, Blumenkopf B, Abou-Khalil B.
Department of Neurology, Vanderbilt University Medical Center, 2311 Pierce Avenue, Nashville, TN 37232, USA.

Data are limited on seizure recurrence after antiepileptic drug (AED) discontinuation in operated seizure-free patients. We reviewed seizure outcome in patients who came off AEDs after being seizure-free for 2 years following temporal lobe surgery in our center. Thirty-nine (68%) of 57 patients who discontinued AED therapy remained seizure-free. They had a younger age at surgery than the group with seizure recurrence (p=0.01). Earlier surgery may be a favorable predictor for seizure freedom after AED discontinuation.
 

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