bluuebunny/crossref_metadata_2025 huggingface dataset:
The Limitations of Antiepileptic Drug Monotherapy
Authors: Krämer G.
Published: November 2007

The success rate for antiepileptic drug (AED) monotherapy varies among seizure types and epilepsy syndromes, although monotherapy has been shown to be suitable for the majority of patients. Certain groups of patients, e.g., patients with partial seizures, with or without secondarily generalizing, are less satisfactorily controlled with monotherapy. Prospective studies have shown that 33–50% of patients with refractory partial epilepsies and symptomatic generalized epilepsies whose seizures are not satisfactorily controlled by monotherapy respond well to a combination of AEDs. Current consensus is that all patients should initially receive monotherapy [e.g., valproate (VPA) or carbamazepine (CBZ)] and, if unsuccessful, an alternative AED should be administered as monotherapy. Only if seizures are still not satisfactorily controlled should combination therapy be instituted. Studies have shown that combination therapy with VPA and CBZ brings seizures of many previously nonresponsive patients with refractory complex partial and secondary generalized epilepsies under control. However, to establish the limitations of monotherapy in an individual, the maximal tolerated dosage must have been administered. Full seizure control may occur in some patients only when the plasma concentration exceeds the therapeutic range.
The Problem of Intractability: The Continuing Need for New Medical Therapies in Epilepsy
Authors: Jallon Pierre
Published: November 2007

Summary: Treatment of epilepsy, one of the most common neurologic disorders, has evolved from “institutional” poly‐therapy to “dogmatic” monotherapy, and, most recently, to “rational” polypharmacy. The introduction of bromides for the treatment of epilepsy was followed first by phenobarbital and then by phenytoin as therapeutic options. Although attempts to combine medications were legion, none was supported by studies that demonstrated the benefit of such combinations. The issue of adverse effects became a principal argument in favor of monotherapy. Monotherapy, using newly developed drugs, avoided problems due to drug interactions but was ineffective in 20–30% of patients. A greater understanding of basic disease mechanisms and developments in molecular biology have led to an increased number of effective drugs for the estimated 6–12% of patients with epilepsy whose condition is intractable. Clinical research continues to build on the work of basic scientists in attempting to develop treatments based on a desire to move beyond the palliative and to affect the causative mechanisms of the disease. Novel medical approaches now under exploration include the use of drugs with complementary mechanisms of action, stimulation of various components of the nervous system, biochemical manipulations, focal intracerebral drug perfusion, and gene therapy.
Identification and Preclinical Testing of Novel Antiepileptic Compounds
Authors: Meldrum Brian S.
Published: November 2007

Summary: Procedures for identifying novel antiepileptic drugs (AEDs) are changing and need to change more. Widespread reliance on two primary screens has led to the identification of novel compounds that resemble either phenytoin (suppressing high‐frequency repetitive firing in cultured neurons and prolonging inactivation of voltage‐dependent sodium channels identified by the maximal electroshock test) or benzodiazepines (potentiating the inhibitory effect of “γ‐aminobutyric acid (GABA), identified by the threshold pentylenetetrazol test). Advances in molecular neurobiology have identified specific molecular targets (subunits of ion channels, neurotransmitter receptors, and transporters) and have made them available in a form permitting high‐throughput screening. AEDs can be designed to interact with specific sites on the target molecules. Alternatively, the molecular screens can be used to identify active components in natural products, including folk remedies. Preclinical in vivo screens can be improved by using animals with genetic or acquired epilepsies that have similar modifications in the properties of the target molecules as do human epilepsy syndromes. Future work is likely to define molecular targets for AEDs that will block or reverse chronic epileptogenesis.
Cardiac Deaths in Epilepsy
Authors: Annegers J. F.
Published: November 2007

Summary: A study of heart disease mortality and morbidity in patients with epilepsy in Rochester, Minnesota, U.S.A., is presented. In a cohort of 725 incident cases of epilepsy followed for approximately 10,000 person‐years, 237 deaths and 48 incident cases of ischemic heart disease were noted. Overall, the cohort mortality rate was 2.1 times that of the general population. For those with idiopathic epilepsy, the mortality rate was 1.6 times that of the general population. For ischemic heart disease, the epilepsy cohort experienced a standardized mortality rate (SMR) of 1.6, slightly higher for remote symptomatic than idiopathic epilepsy. For sudden death as the initial manifestation of heart disease, the SMR was 2.3. The ratio was not significantly higher for those with idiopathic epilepsy but was 3.9 for remote symptomatic epilepsy. The findings show much lower incidence rates and relative incidence of sudden death than all of the more recent sudden unexpected death in epilepsy studies. Reasons for this discrepancy are discussed.
Epilepsy and Sudden Death: A Personal View
Authors: Hanna J.
Published: November 2007

Summary: Epilepsy Bereaved? is a charity that aims to inform, support, and empower partners, relatives, and friends of people affected by sudden unexpected death in epilepsy (SUDEP). It also works toward preventing mortality due to SUDEP through raising awareness and promoting research. The aim of Epilepsy Bereaved? is to enable bereaved families to be heard. The charity represents more than 200 families in the United Kingdom and overseas. This article presents some of their experiences. All the deaths involved young people, many of whom had been recently diagnosed with epilepsy or had experienced only infrequent seizures. Their families report that they have been unaware of the risk for sudden death. Explanations and counseling from health professionals were rare. This was often felt by families of the victims to be symptomatic of a continuing failure to provide adequate information and support to people with epilepsy. In many cases, distress was exacerbated by the belief that death certificates were inaccurate. In supporting this workshop, Epilepsy Bereaved? hopes that further progress will be made to prevent deaths and suffering from this tragic syndrome.
Arrhythmia, Heart Rate Variability, and Antiepileptic Drugs
Authors: Tomson T. , Kennebäck G.
Published: November 2007

Summary: This article reviews the clinical evidence for cardiac arrhythmias and alterations in heart rate variability (HRV) induced by antiepileptic drugs (AEDs). The medical literature was searched for cases with documented arrhythmias induced by AEDs at therapeutic doses, for systematic studies of the prevalence of arrhythmias related to AED therapy, and for studies on HRV in relation to AED treatment. Phenytoin has been associated predominantly with bradyarrhythmias, some of which were fatal. This has occurred almost exclusively with i.v. administration of the drug. Several reports demonstrate car‐bamazepine's depressant effects on the cardiac conduction system. This has occurred mainly in the elderly or in otherwise predisposed patients. There were no reports of arrhythmias induced by other AEDs. Although information on HRV is scarce, treatment with carbamazepine appears to be associated with a decreased HRV. AED‐induced cardiac arrhythmias are rare and occur mainly in patient populations different from those with a high incidence of sudden unexpected death. Further studies of HRV and AEDs are needed.
Sudden Unexpected Death in Epilepsy: Terminology and Definitions
Authors: Nashef L.
Published: November 2007

Summary: Inconsistent and inaccurate death certification, lack of agreed definitions, different terminology, and different understanding of the same terminology hamper research into mortality in epilepsy and result in national statistics that are difficult to interpret. A consensus in death certification and in classification of epilepsy‐related deaths, including sudden unexpected death in epilepsy (SUDEP), is needed. Guidelines for classifying cases as SUDEP are proposed. Their aim is to allow uniformity and comparability between studies. These guidelines take into account the limits of the information usually available in this setting even when these deaths are investigated. The guidelines are complemented by those dealing with identified deaths in epidemiologic studies where data are lacking.
Sudden Unexpected Death in Epilepsy: Impact on Clinical Practice
Authors: Fish D. R.
Published: November 2007

Summary: The possibility of sudden unexpected death in epilepsy (SUDEP) should affect the management of virtually every patient with proven or suspected epilepsy by (a) underlining the need to make all reasonable efforts to render each patient seizure‐free; (b) emphasizing the importance of minimizing avoidable seizures; (c) being incorporated into the risk/benefit analysis of decisions to withdraw or switch antiepiieptic drugs (AEDs); (d) justifying the risks of experimental drugs or surgery in some patients with severe and/or medically intractable seizures; (e) requiring a minimum delay in the investigation and treatment in all patients with possible or confirmed epilepsy; (f) prohibiting abrupt outpatient AED withdrawal in patients suspected but not proved to have solely nonepileptic attacks, lest they have additional seizures; (g) emphasizing the need for a good patient/physician relationship; (h) ensuring suitable monitoring and resuscitation facilities for high‐risk inpatient groups; and (i) taking into account the home environment and attendant risks for seizures in isolated circumstances when outpatient treatment strategies are planned. It is vital to establish what proportion of SUDEP cases occur in relation to avoidable factors and to determine whether improvements in overall quality of care of patients with epilepsy might modify the incidence of SUDEP.
Impact on Priority Setting
Authors: Brown S. W.
Published: November 2007

Summary: It is now acknowledged that an excess mortality is associated with epilepsy, over and above that of the underlying disease. This risk is even greater in uncontrolled epilepsy. Because sudden unexplained death in epilepsy (SUDEP) appears to be seizure‐related, it is likely that this excess mortality would be reduced if seizures were better controlled or, ideally, stopped. Patients and physicians are in the fortunate position of being able to choose from more effective treatments for epilepsy than at any time in the past. Reductions in mortality, however, must go hand in hand with improved epilepsy care in general. In the past, this area has been overlooked and underfunded. There is some evidence that specialist epilepsy clinics are better at managing cases of epilepsy than general neurology clinics or general medical services. Investing in dedicated epilepsy services could arguably lead to a reduction in mortality. Such investment would also lead to improved provision of counseling and information services for people with epilepsy. It is not yet possible to determine the effects of these interventions or to set targets for a reduction in mortality in people with epilepsy, because there is a lack of accurate data on the prevalence of epilepsy and the rate of SUDEP. Obtaining these figures should perhaps be our first aim. The relevance of these issues to the management of SUDEP are discussed with regard to the United Kingdom Health Service.
The Use of Clobazam, Midazolam, and Nitrazepam in Epilepsy
Authors: Shorvon Simon D.
Published: November 2007

Summary: The benzodiazepines clobazam (CLB), midazolam (MDL), and nitrazepam (NZP) all have proven efficacy in epilepsy management, but their differences in physical properties, pharmacokinetic characteristics, side‐effect profiles, and intrinsic antiepileptic activity lead to different indications for use. CLB is a 1,5‐benzodiazepine that causes less sedation than 1,4‐benzodiazepines but offers improved antiepileptic action. It has been extensively studied in both open and controlled trials as antiepileptic therapy for a variety of seizure types. It is now widely used in European countries as adjunctive therapy for partial and secondarily generalized seizures. Clinical trial experience, however, indicates that more than 50% of patients develop tolerance to the antiepileptic effects of CLB. Therefore, CLB has had a relatively limited role as a routine antiepileptic drug. It has further use as an intermittent or occasional therapy, in which tolerance is of less concern. MDL is a water‐soluble 1,4‐benzodiazepine. It is the only drug in this class that is useful when given by i.m. injection, although MDL can also be administered rectally or by i.v. bolus or infusion. MDL has a very short elimination half‐life and is used for emergency treatment of status epilepticus or acute seizures. NZP has reported efficacy in acute epilepsy, although it is not routinely used for this situation. Although there have been no controlled studies of NZP for chronic epilepsy treatment, this drug appears to be moderately effective in a wide range of seizure types. NZP is predominantly used in children with severe epilepsy intractable to conventional medications.
An Overview of Benzodiazepines in Seizure Management
Authors: Henriksen Olaf
Published: November 2007

Summary: Benzodiazepines (BZDs) were first synthesized in 1933 but were not introduced for the treatment of epilepsy until 1965, when Henry Gastaut treated status epilepticus with intravenous diazepam. Since then, BZDs have been widely used in the management of epilepsy in both children and adults. At present, seven different BZDs are used in various countries as antiepileptic drugs. Because of their high lipophilicity, rapid brain penetration, and brain receptor binding, BZDs administered either i.v. or rectally are often first‐line agents for acute seizure management. Although they have also been used for epilepsy prophylaxis, chronic treatment with BZDs is sometimes hampered by their propensity to produce sedation and other side effects, including development of tolerance to their anticonvulsant effects. Nevertheless, all patients with a devastating seizure disorder should have the opportunity for prophylaxis with a BZD. Whether or not treatment continues will depend on careful evaluation of the therapeutic response, toxicity, and the development of tolerance.
Management of Acute Seizure Episodes
Authors: Pellock John M.
Published: November 2007

Summary: Acute seizures may represent the initial manifestation of epilepsy or isolated events. Urgent treatment of these episodes is indicated to reduce the risk for permanent neurologic damage. Status epilepticus (SE), one form of acute seizure, has an estimated annual incidence of 100,000–150,000 cases per year in the United States. Management of SE focuses on terminating clinical and electrical seizure activity while providing supportive care and identifying the precipitating factors. Physician preference and patient‐related factors may dictate the choice of pharmacologic treatment of SE. However, benzodiazepines, which enter the brain rapidly and offer the opportunity for most rapid seizure cessation, are the foundation for SE management. At our institution, first‐line treatment consists of i.v. lorazepam followed by a long‐acting antiepileptic drug (AED). When i.v. access cannot be attained, high AED blood levels can be rapidly achieved with rectally administered diazepam (DZP). For management of acute repetitive seizures, it is desirable to have an effective drug that can be safely administered by caregivers outside of the hospital setting. Clinical trial data indicate that rectal administration of a prepackaged viscous DZP solution fulfills these criteria. In these studies, rectal DZP gel reduced seizure frequency and recurrence compared to seizure control, improved patient and family quality of life, and was cost‐effective because it reduced the need for emergency and inpatient treatment.
The Use of Diazepam and Clonazepam in Epilepsy
Authors: Tassinari Carlo A. , Michelucci Roberto , Volpi L. , Dravet C. , Cano J. P. , Roger J.
Published: November 2007

Summary: This article reviews the pharmacokinetics, efficacy, and tolerability of diazepam (DZP) and clonazepam (CZP) in the treatment of epilepsy, with special emphasis on the management of acute seizures and status epilepticus. In these conditions, i.v. DZP and CZP are first‐line agents, resulting in rapid and lasting control in 70–85% of cases. However, the response rate depends largely on the type of epilepsy in epileptics or the underlying cause of seizures in nonepileptic patients. Because of the rapid redistribution pattern of these antiepileptic drugs (AEDs) from the“ brain, co‐administration of a long‐acting drug is often required. In contrast, continuous infusion of DZP and CZP is no longer generally recommended. Rectal DZP instillation is a valuable alternative for immediate treatment at home for serial seizures and prophylaxis of febrile seizures. The side effects of i.v. DZP and CZP include cardiorespiratory depression, sedation, and paradoxical effects such as precipitation of tonic status epilepticus in Lennox‐Gastaut syndrome. Although both AEDs are currently employed for the management of acute seizures, only CZP is also used for oral treatment of chronic epilepsy, especially with refractory absence, myoclonic, atonic, and partial seizures. Side effects and the development of tolerance, however, limit the usefulness of CZP for chronic treatment.
Aggravation of Generalized Epilepsies
Authors: Berkovic Samuel F.
Published: November 2007

Summary: Generalized epilepsies are treatable with a number of antiepileptic drugs (AEDs) that are effective in different seizure types and epilepsy syndromes. The mechanisms of action of these AEDs are incompletely understood but include inhibition of low‐threshold calcium currents and of voltage‐gated sodium channels and facilitation of GABAA receptor currents. The mechanisms of aggravation are also unknown but could include elevation of brain GABA, blockade of voltage‐gated sodium channels, and idiosyncratic toxicity reactions. Anecdotal reports suggest that aggravation of generalized epilepsy can occur with virtually all AEDs. The best‐documented examples are aggravation of absences by carbamazepine and aggravation of symptomatic generalized epilepsies by vigaba‐trin. Therefore, the physician must be constantly aware of the problem of aggravation of seizures by AEDs. With careful diagnosis of the epileptic syndrome and an awareness of the problem, aggravation of seizures can be minimized.
Antiepileptic Drug‐Induced Worsening of Seizures in Children
Authors: Guerrini Renzo , Belmonte Anna , Genton Pierre
Published: November 2007

Summary: Antiepileptic drugs (AEDs) may aggravate preexisting seizures and trigger new seizure types. However, the extent and mechanisms of this problem are unclear, for several reasons. AED trials are not designed to detect worsening of seizures, severe childhood epilepsies may fluctuate in severity, and worsening of seizures may be over‐hastily ascribed to the introduction of a new AED. Moreover, the seizure and the epilepsy type may have been incorrectly diagnosed. The problem is identification of true aggravation of epilepsy in the absence of overdosage or toxicity. This is a common and clinically important problem that concerns both established and newer AEDs, but the biologic mechanisms involved are unknown. An increase in seizure frequency due to overdosage has been reported with phenytoin but is rare with other AEDs. Paradoxical reaction has been reported with carbamazepine (CBZ), benzodiazepines, and vigabatrin (VGB). Exacerbation of seizures may also occur during AED‐induced encephalopathy or hepatopathy. An inappropriate choice of the AED (i.e., a purely pharmacodynamic mechanism) can induce worsening when CBZ or VGB is used in absence and myoclonic seizures. Further research should determine whether seizure exacerbation is associated with the type of epilepsy or with the type of EEG abnormality. Recent evidence indicates that lamotrigine is inappropriate in severe myoclonic epilepsy. Some childhood epileptic encephalopathies have been affected by certain seizure‐worsening mechanisms. Whether this is due to a predisposition in specific syndromes or to an increased risk for adverse effects in patients undergoing multiple AED manipulations is unclear. Furthermore, some syndromes are not the sum of accompanying seizure types but have unique neurobiology.
The EEG Findings in Extratemporal Seizures
Authors: Westmoreland Barbara F.
Published: November 2007

Summary: Extratemporal seizures originate from the frontal, central, parietal, occipital, and midline regions of the brain. The scalp EEG can show various types of interictal and ictal discharges consisting of spikes, spike and wave sharp waves, paroxysmal fast activity, or rhythmic activity in the β, α, θ, or δ frequency ranges. The discharges can occur as focal, regional, lateralized, or secondarily generalized discharges. Discharges arising from the frontal region are varied and at times complex. Centro‐temporal spikes associated with benign epilepsy of childhood have a characteristic blunt spike and wave appearance. Centro‐parietal spikes can occur in children with benign childhood epilepsy or in association with symptomatic epilepsies at any age. Occipital spike discharges have been seen in young children with visual problems, benign occipital epilepsy of childhood, the Sturge‐Weber syndrome, and other symptomatic or structural lesions involving the occipital lobe. There may be problems with detection of the source of origin of seizures secondary to the anatomy of the various regions, deep foci, small restricted foci, rapid spread of epileptiform discharges, and contaminating effects of muscle and movement artifact. Depth or intracranial recordings may help in further localization of foci.
Surgical Treatment for Perirolandic Lesional Epilepsy
Authors: Sandok Evan K. , Cascino Gregory D.
Published: November 2007

Summary: Our purpose was to evaluate the safety and efficacy of surgical treatment for perirolandic lesional epilepsy. We analyzed the records of 14 consecutive patients who underwent a stereotactic lesionectomy for intractable partial epilepsy between 1985 and 1994. All patients had a neuroimaging‐identified lesion in the perirolandic cortex. The mean duration of follow‐up was 6 years (range 1–11 years). Thirteen patients (93%) had a significant improvement in seizure tendency. Eleven patients (78%) were rendered seizure‐free. Morbidity occurred in only one patient, who experienced an increased monoparesis after surgery. Stereotactic lesionectomy is an effective surgical strategy in patients with perirolandic lesional epilepsy. The recent development of functional brain imaging using subtraction ictal single‐photon emission computed tomography co‐registered with volumetric magnetic resonance imaging has been shown to be a reliable indicator of epileptic brain tissue that may significantly alter the preoperative evaluation in patients with extratemporal seizures.

Summary: Stereotactic lesionectomy in a consecutive series of patients with medically refractory partial seizures related to perirolandic lesional epilepsy proved to be safe and effective. The rationale for the operative procedure was to resect the neuroimaging‐identified abnormality. The only patient who did not experience an excellent outcome, i.e., Class I or 11, was an individual who did not have a pathologically verified foreign‐tissue lesion. The advantages of this operative approach include the use of a surgical strategy that does not require extensive preoperative functional mapping and the ability to excise the pathologic lesion using a small cranial trephine. The main disadvantage of stereotactic neurosurgery for epilepsy is the inability to resect the epileptogenic zone, which may be necessary to render the patient seizure‐free. The procedure is also not “risk‐free,” as demonstrated by the patient who experienced an increased hemiparesis.
Mesial Frontal Epilepsy
Authors: So Norman K.
Published: November 2007

Summary: The mesiofrontal cortex comprises a number of distinct anatomic and functional areas. Structural lesions and cortical dysgenesis are recognized causes of mesial frontal epilepsy, but a specific gene defect may also be important, as seen in some forms of familial frontal lobe epilepsy. The predominant seizure manifestations, which are not necessarily strictly correlated with a specific ictal onset zone, are absence, hyper‐motor, and postural tonic seizures. Other seizure types also occur. The task of localization of the epileptogenic zone can be challenging, whether EEG or imaging methods are used. Successful localization can lead to a rewarding outcome after epilepsy surgery, particularly in those with an imaged lesion.
Lateral Frontal Lobe Seizures
Authors: Kotagal Prakash , Arunkumar G. S.
Published: November 2007

Summary: On the basis of cytoarchitectural and functional studies, the frontal lobe can be subdivided into the primary motor cortex, premotor cortex, prefrontal cortex, and the limbic and paralimbic cortices. However, we are still a long way from clearly identifying individual frontal lobe epilepsies. Instead, we are limited to a discussion of frontal lobe seizures arising from various regions of the frontal lobe. Supplementary motor area epilepsy and perirolandic epilepsy have been quite well defined, in contrast to syndromes involving other regions of the frontal lobe. Recent technological advances in neuroimaging, electroencephalography, magnetoencephalography and detailed videotape analysis of seizure semiology may enable us to delineate these frontal lobe syndromes with better accuracy, thereby improving outcome after epilepsy surgery.
Awareness and Responsiveness During Partial Seizures
Authors: Inoue Yushi , Mihara Tadahiro
Published: November 2007

Summary: We examined the impairment of consciousness during partial seizures (PS) arising from various brain sites according to the operational definition of the international classification, i.e., altered awareness and/or responsiveness. The subjects were 142 patients who underwent intracranial EEG evaluation and subsequent resective surgery. First, the patients were examined to determine whether they usually had been partially or completely aware of their seizures. Second, spontaneous habitual seizures that had been videotaped with simultaneous intracranial EEG recording were reviewed to determine responsiveness and recall during ictal behavioral alterations. In all, 114 patients were partially or completely aware of their seizures. Patients who tended not to be aware of their seizures were those with frontal lobe epilepsy (FLE) with extensive epileptogenic regions on the language nondominant side and those with temporal lobe epilepsy (TLE) with seizure origin in the lateral cortex of the language dominant side. Of the 21 patients with FLE, 88 with TLE, and 4 with occipital lobe epilepsy, 7, 22, and 2 patients responded to stimuli during the seizure, respectively, but only 11 of the patients with FLE and none of the other patients could recall the stimuli applied during the behavioral alterations. Bilateralization of seizure discharges correlated with impaired responsiveness. According to the International Classification, about half of patients with FLE had only simple partial seizures (SPS) and the other patients had complex partial seizures (CPS). Altered awareness and/or responsiveness occurred in most habitual partial seizures in our subjects. The term “complex” appears to be useful in clinical practice, although the contents of ictal behavior and the site or side of seizure origin are not implied.
Epilepsy and Recursive Consciousness with Special Attention to Jackson's Theory of Consciousness
Authors: Kanemoto Kousuke
Published: November 2007

Summary: John Hughlings Jackson's theory of consciousness has been reconsidered. The author stressed that his uniqueness as a neuroscientist lay in his keen interest in the recursive nature of human consciousness. Two clinical symptoms of interest to Jackson were discussed: recurrent utterances and mental diplopia. Recurrent utterances were believed to represent an exceptional state, in which the unconscious process in speech production, otherwise destined to be swept away automatically, became manifest and observable. Jackson regarded mental diplopia as a revelation of otherwise inaccessible duality of all healthy mental actions. Therefore, he supposed that the essence of recursive consciousness resided in a transformation of multiple, multidirectional, unconscious processes into a linear, unidirectional process
Impairment of Consciousness During Epileptic Seizures with Special Reference to Neuronal Mechanisms
Authors: Yamauchi Toshio
Published: November 2007

Summary: Two neuronal structures, i.e., the cerebral cortex and the subcortical structures, were shown by clinical observations to be involved in maintaining consciousness. The alteration of consciousness during epileptic seizures is discussed with respect to these findings: Alterations of consciousness during epileptic seizures may be produced by subcortical, i.e., reticular formation, and/or cortical dysfunction followed by excessive, hypersynchronous neuronal discharges. An impairment of consciousness during absence seizures may be due mainly to cortical dysfunction; during complex partial seizures (CPS), it may be due to dysfunctional subcortical neuronal structures. The mechanisms underlying an alteration of consciousness are defined as causing “irritative” functional disturbances and/or as having “inhibitory” effects on consciousness‐related structures.
Heterogeneity of Ictal SPECT Findings in Nine Cases of West Syndrome
Authors: Haginoya Kazuhiro , Kon Kimiya , Takayanagi Masaru , Yoshihara Yasushi , Kato Rie , Tanaka Soichiro , Yokoyama Hiroyuki , Munakata Mitsutoshi , Nagai Mayumi , Maruoka Shin , Yamazaki Tetsuro , Abe Yoetsu , Iinuma Kazuie
Published: November 2007

Summary: We evaluated the ictal and interictal single photon emission computed tomography (SPECT) of 9 patients with West syndrome (WS). In this group, we noted two clear patterns of cortical hyperperfusion and subcortical hyperperfusion in the ictal SPECT. Both patterns were different from the previously documented ictal patterns for complex partial seizures (CPS) or secondarily generalized seizures. Our results suggest that the tonic spasms of WS do not always have a single neu‐rophysiological basis; e.g., patients with hemihypsarrhythmia and focal hypsarrhythmia did not show ictal hyperperfusion of the lesion with hypsarrhythmia. These findings indicate that the origin of hypsarrhythmia as an EEG feature and the origin of tonic spasms may be different in such patients. In particular, hypsarrhythmia appears to originate from cortical lesions, whereas the subcortical structures may be primarily responsible for the tonic spasms. Our report is the first published study of ictal SPECT in patients with WS.
Evolutional Changes and Outcome of West Syndrome: Correlation with Magnetic Resonance Imaging Findings
Authors: Okumura Akihisa , Watanabe Kazuyoshi , Negoro Tamiko , Aso Kosaburo , Natsume Jun , Matsumoto Akiko , Miura Kiyokuni , Furune Jun , Nomura Kazushi , Hayakawa Fumio , Kato Toru
Published: November 2007

Summary: The prognosis and evolutional changes of 77 patients with West syndrome (WS) were studied after patients were classified into four groups on the basis of their magnetic resonance imaging (MRI) findings: anomaly, perinatal injury, normal, and the other groups. The average age at onset of spasms was earliest in the patients with anomalies and latest in patients with normal MRI findings. Patients with normal MRI findings had the shortest duration of spasms, and patients with anomalies had the longest duration of spasms. Antecedent seizures were observed in 6 patients (3 patients with anomalies, 1 patient with normal MRI findings, and 2 patients with other abnormalities). Thirty‐five patients had subsequent seizures. Patients with anomalies often had partial seizures and patients with perinatal injuries often had generalized seizures. Seizures were infrequent in patients with normal MRI findings. Developmental outcome was best in the patients with normal MRI findings and worst in patients with perinatal injuries. Various types of epileptic syndromes occurred subsequent to WS in patients with anomalies, although nonspecific symptomatic generalized epilepsy was common in patients with perinatal injuries. These results suggest that seizure prognosis, evolutional changes in seizures, and developmental outcome are different among the types of brain lesions.
Structure‐Pharmacokinetic‐Pharmacodynamic Relationships of yV‐Alkyl Derivatives of the New Antiepileptic Drug Valproyl Glycinamide
Authors: Spiegelstein Ofer , Yagen Boris , Bialer Meir
Published: November 2007

Summary:Purpose: The purpose of this study was to evaluate the structure‐phartnacokinetie‐pharmacodynamic relationships of a series ofN‐alkyl andN,N‐dialkyl derivatives of the new antiepileptic drug (AED), valproyl glycinamide (VGD).

Methods: The following compounds were synthesized:N‐methyl VGD (M‐VGD),N,N‐dimethyl VGD,N‐ethyl VGD,N.N‐diethyl VGD (DE‐VGD), andN,N‐diisopropyl VGD. These compounds were evaluated for anticonvulsant activity, neurotoxicity, and pharmacokinetics.

Results: After i.p. administration to mice in the maximal electroshock seizure test (MES), DE‐VGD had an ED50value comparable to that of VGD (145 and 152 mg/kg, respectively), whereas in the subcutaneous metrazol test (sc Met) model, M‐VGD had a slightly lower ED50than VGD (108 and 127 mg/kg, respectively). After oral administration to rats, M‐VGD had an MES‐ED50similar to that of VGD (75 and 73 mg/kg, respectively). Of theN‐alkyl VGD derivatives studied, M‐VGD had the best pharmacokinetic profile: the lowest clearance (5.4 L/h), the longest half‐life (1.8 h), and the lowest liver‐extraction ratio (14%).N,N‐dialkylated VGD derivatives underwent two consecutiveN‐dealkylations, whereasN‐alkylated derivatives underwent a singleN‐dealkylation process, yielding VGD as a major active metabolite.

Conclusions: M‐VGD had the most favorable pharmacodynamic and pharmacokinetic profile of the investigatedN‐alkyl VGD derivatives. VGD was found to be a major active metabolite of M‐VGD and to be less neurotoxic than M‐VGD. Therefore VGD rather than one of the investigated /V‐alkyl VGD derivatives should be considered for development as a new AED.
Outcome of Epilepsy Surgery in the First Three Years of Life
Authors: Sugimoto Tateo , Otsubo Hiroshi , Hwang Paul A. , Hoffman Harold J. , Jay Venita , III O. Carter Snead
Published: November 2007

Summary: Purpose: We analyzed our experience over a 6‐year period with early‐chiidhood patients who had undergone epilepsy surgery, and investigated the surgical outcomes.

Method: We reviewed the medical records of 23 children, ages 0–3 years, who underwent epilepsy surgery between 1991 and 1996.

Results: Twenty children had partial seizures; two had infantile spasms; and one had generalized tonic‐clonic seizures at onset. The mean age at onset of seizures was 4.7 months, and the mean age at time of surgery was 15.3 months. A total of 32 operations (21 focal cortical resections and 11 hemispherecto‐mies) was performed. Five of 12 children with seizures secondary to a neuronal migration disorder had reoperations, including three who ultimately underwent complete hemispher‐ectomy. The pathology consisted of hemimegalencephaly in three patients, focal cortical dysplasia (FCD) in eight, tuberous sclerosis in one, Sturge‐Weber syndrome (SWS) in five, infarction in two, low‐grade glioma (LGG) in three, and post‐herpes simplex virus encephalitis (HSE) in one. The follow‐up period ranged from 1 to 6.5 years (mean, 3.2 years) from patients' last operation. The seizure outcome according to Engel's criteria was class 1 in 12 patients, class II in three, class III in six and class IV in two.

Conclusions: Seizure outcomes after surgery were less favorable in infants with FCD than in those with SWS and LGG. Seizure outcome for the patients with hemispherectomies was excellent, compared with those who had focal cortical resections.
Early and Late Posttraumatic Seizures in Traumatic Brain Injury Rehabilitation Patients: Brain Injury Factors Causing Late Seizures and Influence of Seizures on Long‐Term Outcome
Authors: Asikainen Ilmari , Kaste Markku , Sarna Seppo
Published: November 2007

Summary: Purpose: To demonstrate risk factors involved in the origin of late posttraumatic seizures (LPTSs) in civilian traumatic brain injury (TBI) rehabilitation patients and the occurrence of LPTSs in this population. as well as the time of the first late seizures, and influence of these seizures o n functional and occupational long‐term outcome.

Methods: A consecutive sample of 490 patients (age range, 0.8–71 years) with TBI, and with postinjury problems in their education and employment, were followed up for 5 yearsfrom the time of injury in a rehabilitation and reemployment program. The study was carried out at the outpatient neurologic clinic of the Kauniala Hospital, which specializes in brain injuries in Finland and works in close cooperation with the Department of Clinical Neurosciences at the Helsinki University Central Hospital. Main outcome measures were functional outcome, as measured o n the Clasgow Outcome Scale (GOS), and the capacity for employment at the end of follow‐up. Outcomes were studied separately among patients with late seizures and for the nonseizure group.

Rescuts; Children age 7 years or younger at time of injury more often had early posttraumatic seizures (EPTSs). than did adolescents or adults. The time elapsed between brain injury and the first late seizure also was longer in older age groups. EPTSs and depressed skull fracture had a statistically significant relation to the origin of LPTSs. Permanent posttraumatic neurologic deficit, linear skull fracture, and permanent local brain lesion documented on 21 computed tomography (CT) scan appeared clinically important as risk factors. Late seizures did worsen the functional outcome but had n o significant influence on reemployment at the end of follow‐up.

Conclusions: Young children are more prone to early seizures. and adolescents and adults, to late seizures. The main risk factors for LPTSs are early seizures and depressed skull fracture. Severity of brain injury, as measured by a low GCS score, prolonged unconsciousness, and posttraumatic amnesia (PTA) without local brain lesion, should not be considered risk factor for LPTSs. Thorough follow‐up of patients with TBI with seizures and adequate antiepileptic therapy may help attain rehabilitation goals and reemployment.
Lamotrigine Monotherapy in Newly Diagnosed Untreated Epilepsy: A Double‐Blind Comparison with Phenytoin
Authors: Steiner T. J. , Dellaportas C. I. , Findley L. J. , Gross M. , Gibberd F. B. , Perkin G. D. , Park D. M. , Abbott R.
Published: November 2007

Summary: Purpose: Lamotrigine is an effective add‐on therapy against a range of epileptic seizure types. Comparative studies with carbamazepine (CBZ) as monotherapy in newly diagnosed epilepsy suggest similar efficacy. In this study, lamotrigine (LTG) and phenytoin (PHT) are compared.

Methods: In a double‐blind parallel‐groups study, 181 patients with newly diagnosed untreated partial seizures or secondarily or primary generalised tonic‐clonic seizures were randomised to two treatment groups. One group (n = 86) received LTG titrated over 6 weeks from a starting dose of 100 mg/day. The other (n = 95) received PHT titrated from 200 mg/day. Treatment continued for <48 weeks.

Results: The percentages of patients remaining on each treatment and seizure free during the last 24 and 40 weeks of the study, and times to first seizure after the first 6 weeks of treatment (dose‐titration period), did not differ significantly between the treatment groups. These were measures of efficacy. Time to discontinuation, a composite index of efficacy and safety, likewise did not distinguish between treatments. Adverse events led to discontinuation of 13 (15%) patients from LTG and 18 (19%) from PHT. The adverse‐event profile for LTG was dominated by skin rash [discontinuation of 10 (11.6%) patients compared with five (5.3%) from PHT] rather than central nervous system side effects: asthenia, somnolence, and ataxia were each significantly more frequent in the PHT group. The high rate of rash with LTG was probably due to the high starting dose and may be avoidable. A quality‐of‐life instrument, the SEALS inventory, favoured LTG. Patients taking PHT showed the biochemical changes expected of an enzyme‐inducing drug, whereas those taking LTG did not.

Conclusions: LTG and PHT monotherapy were similarly effective against these seizure types in patients with newly diagnosed epilepsy. LTG was better tolerated, more frequently causing rash, but with a lower incidence of central nervous system side effects.
Prevalence of Epilepsy in Silivri, a Rural Area of Turkey
Authors: Karaaĝaç N. , Yeni S. N. , Şenocak M. , Bozluolgay M. , Savrun F. Karaali , Özdemir H. , Çaĝatay P.
Published: November 2007

Summary: Purpose: To learn the prevalence of epilepsy in Silivri, a western town of Turkey, a randomized door‐to‐door survey was conducted using a standard questionnaire. The method of the study was adopted from the suggestions of the World Health Organization (WHO) for prevalence studies in developing countries, and the criteria were derived from Guidelines for Epidemiologic. Studies on Epilepsy proposed by the Commission on Epidemiology and Prognosis, the International League Against Epilepsy (ILAE) 1993.

Methods: From June I to October 1, 1994, 4,803 people out of a total population of 70,394 were surveyed. The questionnaire, which was administered by practitioners and intern doctors, consisted of 15 questions, with a sensitivity of 99.9% and a specificity of 76%. After the survey, neurologists examined all of the 415 people suspected of having epilepsy and classified the seizures of the active cases.

Results: Of the 415 suspected cases, 49 people (24 women, 25 men) were determined as having epilepsy on the assessment day of October 1. 1994. The crude point prevalence of active epilepsy was 10.2 of 1,000 for the region. The prevalence of active epilepsy among women was 10.01 of 1,000 and among men was 10.39 of 1,000. Of the 49 cases, 40.8% had generalized seizures, 53.1% had partial onset seizures, and 6.1% could not be classified. Only 7.7% of the cases with partial onset seizures were defined as probable symptomatic cases.

Conclusions: Onset of the disease peaked at the first decade of life. On the assessment day, 44.9% of those with epilepsy were receiving treatment, and 65.1% had visited religious figures at the onset or during the course of the disease, a figure that reveals the high prevalence of mystical beliefs about the disease in the study area.
Clinical Research Physical Exercise in Outpatients with Epilepsy
Authors: Nakken Karl Otto
Published: November 2007

Summary: Purpose: To compare the exercise habits in a sample of adult outpatients with epilepsy with those of a general population of the same age and sex and furthermore to study physical exercise as a seizure precipitant and the risk of sustaining seizure‐related injuries while exercising.

Methods: Two hundred four adult outpatients with active epilepsy responded to two questionnaires. The first one, addressing exercise habits, was a selected part of a broad self‐assessing screening used every second year by a marketing and media research institute to reveal changes in the average Norwegian's lifestyle. The exercise habits of the epilepsy population were compared with those of the average population. The other questionnaire, addressing seizures and injuries related to physical exercise, consisted of eight sections and was developed at the National Center for Epilepsy in Norway.

Results: The portion of those never exercising was significantly higher among the patient group compared with the average population. Otherwise, the exercise patterns were very similar in the two populations. However, the patients exercised more often in fitness centers and together with friends, whereas individual activities like skiing and swimming were more often preferred by the average Norwegian. Of the 204 patients, 53 and 63% had never experienced seizures during or immediately after exercise, respectively. About 10% of the patients claimed that they had seizures quite often in connection with exercise.

However, only 2% had genuine exercise‐induced seizures, here arbitrarily defined as having seizures in > 50% of the training sessions. Among those prone to have exercise‐related seizures, there was a predominance of patients with symptomatic localization‐related epilepsy (i.e., with an underlying structural brain lesion). Most exercise‐related seizures occurred during strenuous activity. About 38% of the patients claimed to have personal experience regarding whether regular physical exercise influenced their seizure disorder; of these, 53% claimed there was no influence, 36% claimed there was a positive influence, and 10% reported a negative influence. Thirty‐six percent of the patients had experienced injuries in connection with physical exercise, but in only 10% were these injuries associated with seizures. The injuries were mostly mild.

Conclusions: The surveyed sample of epilepsy outpatients was more active than expected, and their exercise pattern closely resembled that of the average Norwegian population. In the majority of the patients, physical exercise had no adverse effects, and a considerable proportion (36%) claimed that regular exercise contributed to better seizure control. However, in ‐10% of the patients, exercise appeared to be a seizure precipitant, and this applied particularly to those with symptomatic partial epilepsy. The risk of sustaining serious seizure‐related injuries exercising seemed modest.
Rapid Cooling Aborts Seizure‐Like Activity in Rodent Hippocampal‐Entorhinal Slices
Authors: Hill Matthew W. , Wong Michael , Amarakone Aloka , Rothman Steven M.
Published: November 2007

Purpose: As a preliminary step in the development of an implantable Peltier device to abort focal neocortical seizures in vivo, we have examined the effect of rapid cooling on seizures in rodent hippocampal‐entorhinal slices.

Methods: Seizure‐like discharges were induced by exposing the slices to extracellular saline containing 4‐aminopyridine (50 μmol/L).

Results: When we manually activated a Peltier device that was in direct contact with the slice, seizures terminated within seconds of the onset of cooling, sometimes preceding a detectable decrease in temperature measured near the top of the slice. However, activation of the Peltier device did not stop seizures when slices were no longer in direct physical contact with the device, indicating that this was not a field effect. When cooling was shut off and temperature returned to 33oC, bursting some‐times returned, but a longer‐term suppressive effect on seizure activity could be observed. In two of our experiments, a custom computer program automatically detected seizure discharges and triggered a transistor‐transistor logic pulse to activate the Peltier device. In these experiments, the Peltier device automatically terminated the slice bursting in less than 4 seconds. When the Peltier device was placed in contact with the normal, exposed cortex of a newborn pig, we found that the cortical temperature decreased rapidly from 36oC to as low as 26oC at a depth of 1.7 mm below the cooling unit.

Conclusions: These experiments show that local cooling may rapidly terminate focal paroxysmal discharges and might be adapted for clinical practice.