Journal of the Neurological Sciences

Article in Press, Corrected Proof - Note to users

1H-MR spectroscopy: a promising method in distinguishing subgroups in temporal lobe epilepsy?

Hammena, H. Stefana, , , E. Paulia, I. Schäfera, W. Hukb and B. Tomandlb

            Proton MR spectroscopy offers an additional noninvasive method of supporting focus lateralization in patients with intractable temporal lobe epilepsy. In this study involving 57 patients, the ability of multivoxel 1H-MRS to differentiate between mesial and lateral TLE was investigated in addition to its ability to lateralize the epileptogenic focus. Temporal lobe epilepsy (TLE) was classified into mesiobasal or lateral temporal lobe epilepsy according to the results of preoperative diagnostics including neurological and neuropsychological examinations, video-EEG monitoring and high resolution MRI. 1H-MR-spectroscopy (1H-MRS) showed that pathological changes in the mesial temporal lobes indicate a predominance in different parts of the ipsilateral temporal lobe (hippocampal and parahippocampal areas) correlating to the clinically defined groups. In addition, mesiobasal TLE tends to have higher concomitant contralateral abnormalities. Our results reveal that 1H-MRS is able to distinguish between mesiobasal and lateral pathologies in patients with TLE and represents a useful tool for noninvasive TLE classification.



Clinical Neurophysiology, In Press

Callosal role in generation of epileptiform discharges: quantitative analysis of EEGs recorded in patients undergoing corpus callosotomy

Atsuko Matsuo, Tomonori Ono, Hiroshi Baba and Kenji Ono

            Objective: Corpus callosotomy tends to decrease seizure frequency and severity rather than transforming the seizure pattern from a generalized form into a lateralized or a partial one. The finding implies that bisection of the corpus callosum (CC) disrupts the epileptogenicity itself. In order to gain further insight into the possible role played by the CC in intractable generalized epilepsy, quantitative analyses of long-term EEGs were performed.  Methods: Analyses were made of epileptiform discharges contained in the pre- and postoperative long-term EEGs in 7 patients who had an anterior callosotomy for intractable epilepsy. The duration, number, and amplitude of all epileptiform burst activities were measured and statistically analyzed.  Results: After callosotomy, the total number of epileptiform burst activities, mean duration, and the total number of spike discharges decreased significantly. The two hemispheres could be divided into dominant and non-dominant ones as to the quantity of the residual epileptiform discharges.  Conclusions: Corpus callosotomy unevenly reduced preoperative epileptiform discharges in both hemispheres, suggesting a facilitatory role played by the callosal neurons that enables the asymmetrical epileptogenic susceptible state of the two hemispheres to develop bisynchronous and bisymmetrical epileptiform discharges. Significance: Corpus callosotomy decreased the quantity of the epileptiform discharges, suggesting the transhemispheric facilitation of seizure mechanisms.




Volume 19, Issue 3 , July 2003, Pages 1228-1232

Language lateralization in patients with temporal lobe epilepsy: a comparison of functional transcranial Doppler sonography and the Wada test

Susanne Knake, , a, Anja Haaga, Hajo M. Hamera, Christine Dittmera, Siegfried Bienb, Wolfgang H. Oertela and Felix Rosenowa

            This study prospectively investigates whether noninvasive functional transcranial Doppler sonography (fTCD) is a useful tool to determine hemispheric language lateralization in the presurgical evaluation of patients with medically intractable temporal lobe epilepsy (TLE). fTCD results were compared with the Wada test as the gold standard. Wada test and fTCD were performed in 13 patients suffering from TLE. fTCD continuously measured blood flow velocities in both middle cerebral arteries, while the patient was performing a cued word generation task. During the Wada test, spontaneous speech, comprehension, reading, naming, and repetition were investigated. A laterality index (LI) was obtained by both procedures. Due to a lack of an acoustic temporal bone window, fTCD could not be performed in two patients (15%). In 9 of the remaining 11 patients hemispheric language dominance was found on the left side, in 1 patient on the right side, and 1 patient showed bihemispheric language representation. In all patients fTCD and the Wada test were in good agreement regarding hemispheric language lateralization, and the LI of both techniques were highly correlated (r = 0.776, P = 0.005). fTCD gives predictions of hemispheric language dominance consistent with the Wada test results even in children, patients with low IQ, and nonnative speakers. It is an alternative to the Wada test in determining language lateralization in patients with temporal lobe epilepsy.



Barkley, Gregory L. *+; Baumgartner, Christoph ++

MEG and EEG in Epilepsy.[Review]

Journal of Clinical Neurophysiology. 20(3):163-178, May/June 2003.

            Summary: Both EEG and magnetoencephalogram (MEG), with a time resolution of 1 ms or less, provide unique neurophysiologic data not obtainable by other neuroimaging techniques. MEG has now emerged as a mature clinical technology. While both EEG and MEG can be performed with more than 100 channels, MEG recordings with 100 to 300 channels are more easily done because of the time needed to apply a large number of EEG electrodes. EEG has the advantage of the long-term video EEG recordings, which facilitates extensive temporal sampling across all periods of the sleep/wake cycle. MEG and EEG seem to complement each other for the detection of interictal epileptiform discharges, because some spikes can be recorded only on MEG but not on EEG and vice versa. Most studies indicate that MEG seems to be more sensitive for neocortical spike sources. Both EEG and MEG source localizations show excellent agreement with invasive electrical recordings, clarify the spatial relationship between the irritative zone and structural lesions, and finally, attribute epileptic activity to lobar subcompartments in temporal lobe and to a lesser extent in extratemporal epilepsies. In temporal lobe epilepsy, EEG and MEG can differentiate between patients with mesial, lateral, and diffuse seizure onsets. MEG selectively detects tangential sources. EEG measures both radial and tangential activity, although the radial components dominate the EEG signals at the scalp. Thus, while EEG provides more comprehensive information, it is more complicated to model due to considerable influences of the shape and conductivity of the volume conductor. Dipole localization techniques favor MEG due to the higher accuracy of MEG source localization compared to EEG when using the standard spherical head shape model. However, if special care is taken to address the above issues and enhance the EEG, the localization accuracy of EEG and MEG actually are comparable, although these surface EEG analytic techniques are not typically approved for clinical use in the United States. MEG dipole analysis is approved for clinical use and thus gives information that otherwise usually requires invasive intracranial EEG monitoring. There are only a few dozen whole head MEG units in operation in the world. While EEG is available in every hospital, specialized EEG laboratories capable of source localization techniques are nearly as scarce as MEG facilities. The combined use of whole-head MEG systems and multichannel EEG in conjunction with advanced source modeling techniques is an area of active development and will allow a better noninvasive characterization of the irritative zone in presurgical epilepsy evaluation. Finally, additional information on epilepsy may be gathered by either MEG or EEG analysis of data beyond the usual bandwidths used in clinical practice, namely by analysis of activity at high frequencies and near-DC activity.




Volume 44 Issue s7 Page 26  - September 2003

Assessing the Efficacy of Antiepileptic Treatments: The Ketogenic Diet

Elizabeth A. Thiele

            Summary:  Purpose: To evaluate the evidence for determining if the ketogenic diet is an effective treatment for epilepsy.  Methods: A literature review of published data over the past 80 years concerning the ketogenic diet was performed, focusing on efficacy, tolerability, age of patient population, as well as study design.  Results: There have been several studies involving prospective and retrospective studies showing the ketogenic diet to be a very efficacious treatment in epilepsy, particularly epilepsy in childhood. However, no Class 1 studies have been published concerning the efficacy of the ketogenic diet.v  Conclusions: The ketogenic diet appears to be a very effective treatment for epilepsy, particularly in childhood. It would be beneficial to have Class 1 studies available to help better define the role of the diet both in children and adults.  E-mail: ethiele@partners.org



Journal of Clinical Psychology

Volume 59, Issue 9 , Pages 933 - 942

Minimal model to document psychometric change after standard anterior temporal lobectomy for intractable seizure disorder

Raymond M. Costello *, Bruce Mayes, C. Akos Szabo, Dennis G. Vollmer

University of Texas Health Science Center at San Antonio

*Correspondence to Raymond M. Costello, University of Texas Health Science Center at San Antonio, Mail Code 7792, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900; e-mail: costello@uthscsa.edu

            Neuropsychological assessment of persons with epilepsy is recommended whenever neurosurgery is considered as an alternative therapy for seizure disorders refractory to ordinary medical management. Although psychological assessment is common in centers specialized in the care of epilepsy patients, standardized protocols are not common. This study addresses the question of the optimal minimal test battery necessary to differentiate groups of right-handed patients with refractory, complex partial seizure disorder who receive either right or left anterior temporal lobectomy or no surgery. No variable differentiated the groups before surgery. Only Logical Memory-Immediate of the Wechsler Memory Scale differentiated the groups following surgery. This finding is consistent with the literature.



Mayo Clin Proc. 2003 Jun;78(6):781-7.

Neuropsychiatric and memory issues in epilepsy.

Bortz JJ.

Department of Psychiatry and Psychology, Mayo Clinic, Scottsdale, Ariz, USA.

            Epilepsy is an extremely complex disorder characterized by marked variability in clinical presentation, etiology, diagnostic certainty, and therapeutic options. Neuropsychiatric and cognitive concomitant disorders are equally diverse and complex. Depression and anxiety, for example, may be preexisting conditions, occur only in peri-ictal or ictal states, or persist as constant interictal phenomena; both place additional burden on memory functions, which are further taxed by the effects of recurrent seizures, temporal lobe insult, and antiseizure medications. Such factors present considerable clinical challenges, particularly in outpatient settings. This article provides an overview of major psychiatric features of epilepsy and of issues regarding the nature of memory deficits in this neurologic population. The importance of identifying and treating potentially reversible causes of memory impairment and related forms of cognitive impairment is emphasized.



Neurosurg Rev. 2003 Aug 22 [Epub ahead of print].

Advances in neuroimaging: management of partial epileptic syndromes.

Schauble B, Cascino GD.

Division of Epilepsy, Department of Neurology, Mayo Clinic Foundation, 200 First Street SW, Rochester, MN 55905, USA.

            Structural and functional neuroimaging studies are essential in the evaluation of individuals with partial epilepsy syndromes. Magnetic resonance imaging (MRI) is important to delineate structural abnormalities underlying seizure disorders, commonly including hippocampal sclerosis or cortical dysplasias. Identification of a structural lesion is often a reliable indicator of the site of seizure onset. Magnetic resonance spectroscopy (MRS) allows us to investigate cerebral metabolites and some neurotransmitters. Reduction in various metabolite concentrations has proven to be prognostically valuable when no structural abnormality is identified. Positron emission tomography (PET) using deoxyglucose demonstrates areas of reduced glucose metabolism, which are the hallmark of epileptogenic zones and usually extend beyond the underlying anatomical region. It is useful in temporal lobe epilepsy for lateralization; however, results in extratemporal lobe epilepsy have been less favorable. More promising is the use of benzodiazepine receptor ligands, which are reduced in the epileptogenic zone in a more restricted distribution. This appears to be helpful in the localization of extratemporal seizure foci. Peri-ictal single photon emission computed tomography measures increased blood flow during the ictal event and is beneficial in patients with normal MRI studies to determine lateralization and localization of the ictal onset zone. All imaging modalities should be correlated with clinical and neurophysiological data.



Journal of the Neurological Sciences Volume 213, Issues 1-2,  Pages 77-82

Complex partial status epilepticus associated with anti-Hu paraneoplastic syndrome

Dina A. Jacobs, Kar-Ming Fung, Noah M. Cook, William W. Schalepfer, Herbert I. Goldberg and Mark M. Stecker

            Although seizures can be a manifestation of paraneoplastic disorders, there are few descriptions of the association between the anti-Hu paraneoplastic syndrome and epilepsia partialis continua. A new case of refractory complex partial status epilepticus in a patient with a paraneoplastic syndrome associated with a poorly differentiated mediastinal tumor that expressed Hu antigen is described clinically, pathologically, and electrographically. We discuss the presentation of focal seizures in a disease that is characterized by diffuse pathologic involvement of the brain. The progression of EEG, MRI, and clinical findings during the course of the illness is also discussed. To our knowledge, this is the first description of paraneoplastic epilepsia partialis continua associated with diffuse pathologic abnormalities.




Volume 44 Issue 9 Page 1241  - September 2003

Increased Frequency of Rolandic Spikes in ADHD Children

Martin Holtmann, Katja Becker, Beate Kentner-Figura, and Martin H. Schmidt

            Summary: Purpose: Some children with rolandic epilepsy have associated neuropsychiatric deficits resembling symptoms of attention deficit-hyperactivity disorder (ADHD), the most common neurobehavioral disorder of childhood. The clinical overlap between both syndromes has received relatively little attention. The study examines the frequency of rolandic spikes in nonepileptic children with ADHD and compares it with a historic control group of 3,726 normal school-aged children. ADHD patients with and without discharges are compared regarding age at admission, sex, global functioning, and distribution of ADHD subtypes. Methods: The EEGs of 483 ADHD outpatients between 2 and 16 years meeting diagnostic criteria for ADHD according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) were evaluated prospectively. If rolandic spikes were present, separate sleep EEGs were performed to exclude a bioelectrical status epilepticus during slow-wave sleep. Results: Rolandic spikes were detected in the EEGs of 27 children (5.6%; 22 boys and five girls). Seizure rate during follow-up tended to be larger in children with rolandic spikes. No significant differences were found between ADHD patients with and without spikes regarding sex and global functioning. ADHD children with rolandic spikes came to our attention significantly earlier than did children without discharges and tended to exhibit more hyperactive-impulsive symptoms, evidenced in a larger proportion of the diagnosis of ADHD combined type than ADHD inattentive type. Conclusions: The frequency of rolandic spikes in children with ADHD is significantly higher than expected from epidemiologic studies. The question arises how ADHD symptoms are related to rolandic spikes in this ADHD subgroup. Possibly rolandic discharges or underlying, not fully understood mechanisms of epileptogenesis decrease the vulnerability threshold, advance the onset, or aggravate the course of ADHD.




Volume 44 Issue 8 Page 1122  - August 2003

Confirmation of Nonconvulsive Limbic Status Epilepticus with the Sodium Amytal Test

*Jorge G. Burneo, *Robert C. Knowlton, Camilo Gomez, *Roy Martin, and *Ruben I. Kuzniecky

            Summary:  Is it a seizure? This question can be difficult for a clinician to answer, and it may be more critical if the possible seizure lasts >30 min. Long-duration questionable seizure activity changes the question to, "Is it status epilepticus?" Status epilepticus (SE) can be divided into convulsive and nonconvulsive types. Convulsive SE is the most easily recognized, whereas nonconvulsive SE is more clinically variable and controversial. The term nonconvulsive SE is more often applied to patients who are severely obtunded or comatose with minimal or no motor movements, or in a stupor of altered consciousness reflecting generalized ictal activity. Nonconvulsive SE also can be caused by focal seizure activity, sometimes restricted to deep small volumes of brain in which scalp EEG may not be diagnostic. We present the case of a patient who had dominant limbic hippocampal SE, but in whom the diagnosis could not be confirmed until a modified novel use of the sodium amytal test was performed.



Journal of the Neurological Sciences Volume 213, Issues 1-2,  Pages 83-86

Bilateral frontal polymicrogyria and epilepsy in a patient with Turner mosaicism: a case report

M. Tombini, M. G. Marciani, A. Romigi, F. Izzi, F. Sperli, A. Bozzao, R. Floris, R. De Simone and F. Placidi

            Turner's syndrome (TS) is rarely associated with serious abnormalities of brain structure or malformations of cortical development. We report a 17-year-old girl with TS and 45,XO/46,XX mosaicism presenting bilateral frontal polymicrogyria (BFP) and epilepsy. To our knowledge, the association between TS and BFP has never been reported to date. Our observation confirms that in humans the X-chromosome plays an important role in the development and specialization of brain structure and function. We hypothesize that the absence or abnormalities of developmental genes localized on the X-chromosome could be involved in the pathogenesis of BFP observed in our patient.



Seizure. 2003 Oct;12(7):519-521.

Caffeinated beverages and decreased seizure control.


Department of Psychiatry, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, Suite #2200, 08901, New Brunswick, NJ, USA

            Seizure control is often affected by seizure threshold lowering behaviours. In this case report, the authors address excessive caffeine ingestion from tea with increased seizure frequency. When decaffeinated beverages were substituted for the tea, seizure frequency returned to baseline. Similar findings occurred when the patient was re-challenged. The authors recommend avoidance of excessive caffeine in patients with epilepsy.



Seizure. 2003 Oct;12(7):448-455.

Magnetoencephalographic analysis of bilaterally synchronous discharges in benign rolandic epilepsy of childhood.


            The purpose of this study was to examine the spatial and temporal relationship between bilateral foci of bilaterally synchronous discharges in benign rolandic epilepsy of childhood (BREC) using a whole-scalp neuromagnetometer. We simultaneously recorded interictal magnetoencephalographic (MEG) and electroencephalographic (EEG) signals in six children with BREC. Interictal spikes were classified into three groups: bilaterally synchronous discharges (BSDs), unilateral discharges on right side (UD-R), and unilateral discharges on left side (UD-L). We used equivalent current dipole (ECD) modelling to analyse the cortical sources of interictal spikes. Both BSDs and UDs were found in Patients 1-4, whereas only UDs were identified in Patients 5 and 6. The ECDs of interictal spikes were located in rolandic regions, 10-20mm anterior and lateral to hand somatosensory cortices. Multi-dipole analysis of BSDs showed two ECDs in homotopic motor areas of the hemispheres. During BSDs, the right-sided activation preceded the left-sided activation by 15-21milliseconds in Patients 1 and 2. In Patients 3 and 4, the activation occurred 17-20milliseconds earlier in the left than the right hemisphere. Within the same hemisphere, the sources of BSDs and UDs were located in similar areas. In conclusion, our results imply the cortical epileptogenicity in bilateral perirolandic areas in BREC. The sequential activation during BSDs in both hemispheres suggest the existence of synaptic connections, possibly via the corpus callosum, between bilateral irritative foci.



Seizure. 2003 Oct;12(7):502-507.

Understanding the information needs of women with epilepsy at different lifestages: results of the 'Ideal World' survey.


Department of Neurosciences, York District Hospital, Wigginton Road, YO31 7HE, York, UK

            The impact of some commonly prescribed anti-epilepsy drugs (AEDs) on female health is well documented. Yet many women continue to experience side effects such as menstrual irregularities, interactions with hormonal contraception/HRT and teratogenicity [Seizure 8 (1999) 201] through lack of awareness or opportunity to discuss problems with a health professional on a regular basis.The 'Ideal World' survey aimed to:assess quality of current treatment information provision to women with epilepsy at different life stages (childbearing age, pre-conception/pregnancy, menopause);identify information needs and wants with a view to ensuring that all women with epilepsy are counselled appropriately, in a timely manner and able to make informed choices about their treatment.The survey content was developed with a steering group of epilepsy specialists during 2001 (see 'ACKNOWLEDGEMENTS') and mailed to Epilepsy Action (formerly the British Epilepsy Association) UK female membership aged 19+ (approximately 12000) during the period of January 2002. A sample of 2000 randomly selected responses was analysed by the Planning Shop International.The survey shows that women are not receiving important information about their condition and possible adverse effects of treatment, which could have profound implications for their health and the health of their unborn child. One third (33%) of women of childbearing age were not considering having children because of their epilepsy.Women with epilepsy need regular review and should receive appropriate information about the impact of their treatment in a timely manner.




Volume 44 Issue s10 Page 27  - October 2003

Prevention of Epilepsy After Head Trauma: Do We Need New Drugs or a New Approach?

Larry S. Benardo: lbenardo@downstate.edu

            Summary: Annually in the U.S. about 500,000 head injuries are severe enough to require hospitalization. Past studies of severe head trauma estimate the risk of late seizures, which are synonymous with epilepsy, to be from 26 to 53%. Furthermore, head trauma accounts for 5% of all epilepsy cases and 20% of symptomatic epilepsy. Although potentially preventable, no effective prophylaxis for posttraumatic epilepsy currently exists. Prior attempts to prevent posttraumatic epileptogenesis used various anticonvulsants, usually given many hours after injury. Generally these studies showed these agents suppressed seizures in the first week after trauma, but had no effect on the incidence of late posttraumatic seizures. Brain trauma engages a rapid excitotoxic process triggered by glutamate release, similar to that seen with ischemia. For ischemic cell damage early and rapid delivery of agents has been a key to rescuing or protecting neurons. Yet, no study has addressed whether the rapidity of drug delivery is critical in the prophylaxis of late seizures. Perhaps excitotoxicity proximate to the brain injury also leads to the neurological deficits seen after severe trauma, initiating and promoting epileptogenesis, and that disrupting this process may prevent epilepsy. While experimental models of epileptogenesis have shown that GABAergic drugs, including valproate (VPA), may be antiepileptogenic, the timing of treatment with putative prophylactic drugs has not been studied. Recent laboratory work explored this issue using an in vitro model of posttraumatic epileptogenesis. The data suggest that a limited time domain exists for VPA to intervene in the epileptogenic process, requiring the earliest possible intervention. We contend that protection from posttraumatic epileptogenesis can be conferred only if agents are given soon after trauma. A pilot study is proposed to begin to translate these findings to explore the feasibility of early VPA delivery to severe head trauma patients admitted to Kings County Hospital Center in Brooklyn, NY, a Level 1 trauma center.



Kim, Hongkeun; Yi, Sangdoe ; Son, Eun Ik ; Kim, Jieun

Differential Effects of Left Versus Right Mesial Temporal Lobe Epilepsy on Wechsler Intelligence Factors.

Neuropsychology. 17(4):556-565, October 2003.

            This study investigates the effects of left versus right mesial temporal lobe epilepsy (MTLE) on Wechsler intelligence factors. In the left MTLE group, the Verbal Comprehension (VC) factor score was significantly lower than the Perceptual Organization (PO) factor score, whereas in the right MTLE group, the PO factor score was significantly lower than the VC factor score. The VC factor score was significantly lower for the left than the right MTLE group, whereas the PO factor score was significantly lower for the right than the left MTLE group. Thus, left versus right MTLE was associated with relative deficits in verbal versus nonverbal intelligence, respectively. These findings indicate that lateralized cognitive deficits in unilateral MTLE patients are not limited to the learning-memory domain but include more global intelligence functions.



Epilepsia  Volume 44 Issue s10 Page 11  - October 2003

Epidemiology of Posttraumatic Epilepsy: A Critical Review

Lauren C. Frey; laurencfrey@hotmail.com

            Summary: Problem: Traumatic brain injury (TBI) is a major cause of epilepsy. We need to understand its frequency and its contribution to the total spectrum of the convulsive disorders.

Methods: A review of selected articles dealing with epilepsy after brain trauma was undertaken.

Results: The number of epidemiologic studies of posttraumatic seizures has increased substantially over the past 40-50 years, offering steadily increasing knowledge of the frequency, natural history, and risk factors of this well-recognized complication of TBI. In general, the incidence of posttraumatic seizures varies with the time period after injury and population age range under study, as well as the spectrum of severity of the inciting injuries, and has been reported to be anywhere from 4 to 53%. As high as 86% of patients with one seizure after TBI will have a second in the next 2 years. Longer-term remission rates of 25-40% have been reported. Significant risk factors for the development of seizures in the first week after injury include acute intracerebral hematoma (especially subdural hematoma), younger age, increased injury severity, and chronic alcoholism. Significant risk factors for the development of seizures >1 week after TBI include seizures within the first week, acute intra-cerebral hematoma (especially subdural hematoma), brain contusion, increased injury severity, and age >65 years at the time of injury.

Conclusions: Epilepsy is a frequent consequence of brain injury in both civilian and military populations. We understand some factors associated with its development, but there remain many unanswered questions.



Epilepsia   Volume 44 Issue s10 Page 18  - October 2003

Risk Factors for Posttraumatic Seizures in Adults

Nancy R. Temkin; temkin@u.washington.edu

            Summary: Purpose: Traumatic brain injury has long been known to be a cause of epilepsy. Most information on risk factors for developing posttraumatic seizures is from before computed tomography (CT) scanning became universal. This article looks at factors about the injury or individual that put people at especially high risk of developing posttraumatic seizures.

Methods: We considered 783 cases at high risk of developing seizures, followed up for 2 years as part of seizure prophylaxis studies. Cumulative incidence of seizures in subgroups and standardized incidence ratios were used to identify factors related to unprovoked seizure risk.

Results: Subgroups with significantly elevated risk include those with evacuation of a subdural hematoma; surgery for an intracerebral hematoma; Glasgow Coma Scale in the severe range of 3 to 8; early seizures, especially delayed early seizures; time to following commands of a week or more; depressed skull fracture that was not surgically elevated; dural penetration by injury; at least one nonreactive pupil; and parietal lesions on CT scan.

Conclusions: Both the risk factors and the time course of the risk are important for designing seizure-prophylaxis studies and, if an effective prophylactic regimen is identified, for deciding on appropriate candidates for prophylaxis.



Epilepsia  Volume 44 Issue s10 Page 21  - October 2003


Overview of Studies to Prevent Posttraumatic Epilepsy

Ettore Beghi; beghi@marionegri.it

            Summary: Purpose: Prevention of posttraumatic epilepsy (PTE) is of primary importance to reduce the degree of functional morbidity following traumatic brain injury (TBI). However, the effects of antiepileptic drugs (AEDs) in patients with TBI must be assessed separately in terms of prevention and control of provoked seizures (which include immediate and early posttraumatic seizures) and prevention of subsequent unprovoked seizures (late posttraumatic seizures or PTE).

Methods: Potential mechanisms for prevention of epileptogenesis as well as reports and systematic reviews were evaluated to determine strategies and results of attempts to reduce or prevent the development of epilepsy following TBI.

Results: In observational studies, after a period ranging from 6 months to 13 years, the proportion of cases developing seizures was 0-10% in patients receiving treatment compared to 2-50% in those who were left untreated. In randomized clinical trials, the difference between active treatment [phenytoin (PHT), phenobarbital, or carbamazepine (CBZ)] and placebo was less remarkable after a follow-up ranging from 3 to 60 months and was virtually lacking for the prevention of PTE. In a Cochrane systematic review of 890 patients from 10 RCTs assessing PHT or CBZ, the pooled relative risk (RR) for prevention of early seizures was 0.33 (95% CI 0.21-0.52). By contrast, the RR for prevention of late seizures was 1.28 (95% CI 0.90-1.81). Mortality and neurological disability were similar in the two treatment groups. The use of PHT was followed by an increased (nonsignificant) risk of skin rashes. In addition, cognitive performance was significantly affected by PHT in severely injured patients at 1 month and treatment withdrawal was followed by improvement in cognitive function.

Conclusions: The failure to influence the risk of PTE in studies of patients with TBI are similar to findings of meta-analysis of randomized clinical trials on seizure prevention in other conditions, such as febrile seizures, cerebral malaria, craniotomy, and excessive alcohol intake. For these reasons, the prophylactic use of AEDs should be short-lasting and limited to the prevention of immediate and early seizures. Chronic treatment should be considered only after a diagnosis of PTE.



Annual Review of Neuroscience

Jul 2003, Vol. 26, pp. 599-625


Jeffrey L. NoebelsDepartment of Neurology, Baylor Coll of Med: jnoebels@bcm.tmc.edu

            Mutations in over 70 genes now define biological pathways leading to epilepsy, an episodic dysrhythmia of the cerebral cortex marked by abnormal network synchronization. Some of the inherited errors destabilize neuronal signaling by inflicting primary disorders of membrane excitability and synaptic transmission, whereas others do so indirectly by perturbing critical control points that balance the developmental assembly of inhibitory and excitatory circuits. The genetic diversity is now sufficient to discern short- and long-range functional convergence of epileptogenic molecular pathways, reducing the broad spectrum of primary molecular defects to a few common processes regulating cortical synchronization. Synaptic inhibition appears to be the most frequent target; however, each gene mutation retains unique phenotypic features. This review selects exemplary members of several gene families to illustrate principal categories of the disease and trace the biological pathways to epileptogenesis in the developing brain.



Epilepsia, Volume 44 Issue s10 Page 2  - October 2003

The Epidemiology of Traumatic Brain Injury: A Review

John Bruns, Jr., and W. Allen Hauser; wahauser@optonline.net

            Summary: Purpose: Traumatic brain injury (TBI) not only has considerable morbidity and mortality, but it is a major cause of epilepsy. We wish to determine the frequency of TBI, special groups at risk for TBI, and mortality from TBI.

Methods: We reviewed studies of TBI that are either population based or derived from definable catchment areas that allow determination of incidence, identification of risk groups, and mortality. We review methodology used in epidemiologic studies of TBI and try to distinguish this data from that of head injury not necessarily affecting the brain. We report epidemiologic characteristics of TBI, including incidence, differences by age, gender, race and ethnic group, and geographic variation, and mortality.

Results: Population-based studies in the United States suggest that the incidence of TBI is between 180 and 250 per 100,000 population per year. Incidence may be higher in Europe and South Africa. There are groups at high risk for TBI. This includes males and individuals living in regions characterized by socioeconomic deprivation. There are selective age groups at risk for TBI. This includes the very young, adolescents and young adults, and the elderly. Mortality varies by severity but is high in those with severe injury and in the elderly.

Conclusions: TBI is a major public health problem as well as a major cause of epilepsy. If primary prevention is to be undertaken, we must understand the epidemiology of the condition. The primary causes of TBI vary by age, socioeconomic factors, and geographic region, so any planned interventions must be tailored accordingly.



Nature Neuroscience

October 2003 Volume 6 Number 10 pp 1079 - 1085

In vitro formation of a secondary epileptogenic mirror focus by interhippocampal propagation of seizures

Ilgam Khalilov, Gregory L Holmes & Yehezkel Ben-Ari; ben-ari@inmed.univ-mrs.fr

            We have determined whether seizures generate an epileptogenic focus in distal structures using an in vitro preparation composed of three independent chambers that accommodate two intact hippocampi and their connecting commissures. This enabled us to apply a convulsive agent to one hippocampus, allow the propagation of a given number of seizures to the other side and block the connections reversibly by applying tetrodotoxin (TTX) to the commissural chamber. The propagation of seizures from the kainate-treated side to the naive side transformed the latter into an independent epileptogenic focus that was capable of generating spontaneous and evoked seizures. The induction mechanism required activation of NMDA receptors and the epileptogenic transformation was associated with long-term alterations in GABAergic synapses, which became excitatory because of a shift in the chloride reversal potential, ECl. These data indicate that the excitatory actions of GABA may be a fundamental property of epileptogenic structures.



Journal of Neurology, Neurosurgery and Psychiatry, Sept 2003 v74 i9 p1240(5)

Contralateral medial temporal lobe damage in right but not left temporal lobe epilepsy: a [sup.1]H magnetic resonance spectroscopy study.

F Zubler; M Seeck; T Landis; F Henry; F Lazeyras.

            Background: Proton magnetic resonance spectroscopy (MRS) of the hippocampus is useful in lateralising the epileptic focus in temporal lobe epilepsy for subsequent surgical resection. Previous studies have reported abnormal contralateral MRS values in up to 50% of the patients.  Objective: To identify the contributing factors to contralateral damage, as determined by MRS, and its extension in patients with temporal lobe epilepsy.  Methods: Single voxel MRS was carried out in the hippocampus and lateral temporal neocortex of both hemispheres in 13 patients with left temporal lobe epilepsy (LTLE) and 16 patients with right temporal lobe epilepsy (RTLE). All patients had mesial temporal lobe epilepsy with hippocampal sclerosis. Controls were 21 healthy volunteers of comparable age.  Results: Consistent with previous studies, the NAA/(Cho+Cr) ratio was abnormally low in the hippocampus ipsilateral to the focus (p < 0.0001), and there were lower values in both patient groups in the ipsilateral temporal neocortex (p < 0.0001). Patients with RTLE had left hippocampal MRS anomalies (p = 0.0018), whereas the right hippocampus seemed to be undamaged in LTLE patients. Conclusions: Unilateral mesial temporal lobe epilepsy is associated with widespread metabolic abnormalities which involve contralateral mesial and neocortical temporal lobe structures. These abnormalities appear to be more pronounced in patients with RTLE.



Journal of Neurology, Neurosurgery and Psychiatry, Sept 2003 v74 i9 p1245(5)

Amygdala volumetry in "imaging-negative" temporal lobe epilepsy.

SPC Bower; SJ Vogrin; K Morris; I Cox; M Murphy; CJ Kilpatrick; MJ Cook.

            Objective: Although amygdala abnormalities are sometimes suspected in "imaging-negative" patients with video EEG confirmed unilateral focal epilepsy suggestive of temporal lobe epilepsy (TLE), amygdala asymmetry is difficult to assess visually. This study examined a group of "imaging-negative" TLE patients, estimating amygdala volumes, to determine whether cryptic amygdala lesions might be detected.  Methods: Review of video EEG monitoring data yielded 11 patients with EEG lateralised TLE and normal structural imaging. Amygdala volumes were estimated in this group, in 77 patients with pathologically verified hippocampal sclerosis (HS), and in 77 controls.  Results: Seven of 11 "imaging-negative" cases had both significant amygdala asymmetry and amygdala enlargement, concordant with seizure lateralisation. Although significant amygdala asymmetry occurred in 35 of 77 HS patients, it was never attributable to an abnormally large ipsilateral amygdala. Compared with patients with HS, patients with amygdala enlargement were less likely to have suffered secondarily generalised seizures (p<0.05), and had an older age of seizure onset (p<0.01).  Conclusion: Abnormal amygdala enlargement is reported in seven cases of "imaging-negative" TLE. Such abnormalities are not observed in patients with HS. It is postulated that amygdala enlargement may be attributable to a developmental abnormality or low grade tumour. It is suggested that amygdala volumetry is indicated in the investigation and diagnosis of "imaging-negative" TLE.




Cochrane Database Syst Rev. 2003;4:CD002029.

Psychological treatments for epilepsy.

Ramaratnam S, Baker G, Goldstein L.

            BACKGROUND: Psychological interventions such as relaxation therapy, cognitive behaviour therapy, electroencephalogram (EEG) bio-feedback and educational interventions have been used alone or in combination in the treatment of epilepsy, to reduce the seizure frequency and improve the quality of life. OBJECTIVES: To assess whether the treatment of epilepsy with psychological methods is effective in reducing seizure frequency and/or leads to a better quality of life. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trial register (11 June 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library issue 2, 2003), MEDLINE (on 11 June 2003) and cross references from identified publications. SELECTION CRITERIA: Randomized or quasi-randomized studies assessing one or more types of psychological or behaviour modification techniques for people with epilepsy. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included reduction in seizure frequency and quality of life. MAIN RESULTS: We found three small trials (50 participants) of relaxation therapy. They were of poor methodological quality and a meta-analysis was therefore not undertaken. No study found a significant effect of relaxation therapy on seizure frequency. One trial found cognitive behavioural therapy to be effective in reducing depression, among people with epilepsy with a depressed affect, whilst another did not.One trial of group cognitive therapy found no significant effect on seizure frequency. Two trials of combined relaxation and behaviour therapy and one of EEG bio-feedback and four of educational interventions did not provide sufficient information to assess their effect on seizure frequency. Combined use of relaxation and behaviour modification was found beneficial for anxiety and adjustment in one study. In one study EEG bio-feedback was found to improve the cognitive and motor functions in individuals with greatest seizure reduction. Educational interventions were found to be beneficial in improving the knowledge and understanding of epilepsy, coping with epilepsy, compliance to medication and social competencies. REVIEWER'S CONCLUSIONS: In view of methodological deficiencies and limited number of individuals studied, we have found no reliable evidence to support the use of these treatments and further trials are needed.



J Neuropsychiatry Clin Neurosci 15:450-452, November 2003

Mesial Temporal Structures and Comorbid Anxiety in Refractory Partial Epilepsy

Parthasarathy Satishchandra, D.M., Ennapadam S. Krishnamoorthy, M.D., Ludger Tebartz van Elst, M.D., Louis Lemieux, Ph.D., Mathias Koepp, Ph.D., Richard J. Brown, Ph.D. and Michael R. Trimble, M.D.; m.trimble@ion.ucl.ac.uk (E-mail).

            We used quantitative magnetic resonance imaging (MRI) to examine the mesial temporal structures in subjects with refractory partial epilepsy and comorbid anxiety and found preservation with a right-sided preponderance. The findings indicate a role for this brain region in the genesis of anxiety.

            We have shown that the volume of the amygdala and hippocampus is preserved in subjects with refractory partial epilepsy and anxiety, in contrast to patients with epilepsy and no associated psychopathology. This is despite the significantly earlier seizure onset and longer duration of epilepsy in this group. Our findings are in line with recent literature linking these structures, the amygdala in particular, to generalized anxiety disorder11 and subjective anxiety in social phobia12 and are unlikely therefore to be specific to refractory epilepsy.


Epilepsia. 2004 Jan;45(1):64-70.
Depression and altered quality of life in women with epilepsy of childbearing age.
Beghi E, Roncolato M, Visona G.
Purpose: To calculate the prevalence of depression in a referral population of women of childbearing age, to define the factors associated with depression, and to assess health-related quality of life (HRQOL) in the same population. Methods: The 642 consecutive women with epilepsy aged 18-55 years were enrolled by 40 neurologists over an 8-month period and asked to give details on selected demographic and clinical features regarding the disease, any associated clinical condition, and any drug treatment. Depression was diagnosed by using the Hamilton depression scale and HRQOL was measured through the SF-36 form. Demographic, clinical, and therapeutic risk factors for depression were searched for within the study population. Results: Depression (any severity) was present at interview in 242 women, giving a prevalence rate of 37.7%[95% confidence interval (CI), 33.9-41.6]. Mild depression was reported by 18.5% of women, moderate depression by 8.6%, major depression by 10.3%, and severe depression by 0.3%. Factors found to be independently associated with depression (any severity) included treatment of associated conditions [relative risk (RR), 1.5; 95% CI, 1.2-1.8), concurrent disability (RR, 1.3; 95% CI, 1.0-1.6), seizures in the preceding 6 months (RR, 1.4; 95% CI, 1.1-1.7), and being unemployed or a housewife (RR, 1.3; 95% CI, 1.0-1.5). Factors associated with moderate to severe depression included treatment for associated conditions (RR, 2.0; 95% CI, 1.4-2.7), seizures in the preceding 6 months (RR, 1.7; 95% CI, 1.2-2.5), and being unemployed or a housewife (RR, 1.6; 95% CI, 1.1-2.2). Compared with normal women of similar age, patients with epilepsy tended to present lower scores for each HRQOL domain (mostly Role Physical, General Health, Social Functioning, and Role Emotional). However, when the analysis was limited to nondepressed women with epilepsy, any difference disappeared. Conclusions: Women with epilepsy of childbearing age are at high risk of depression. Factors associated with depression include lack of occupation, the presence of an underlying disabling condition (with treatment), and the severity of epilepsy. Compared with the general population, depressed women have greater impairment of HRQOL with epilepsy, which reflects the physical, social, and emotional implications of the disease.


Epilepsy Behav. 2003 Dec;4(6):674-9.

Antidepressive treatment in patients with temporal lobe epilepsy and major depression: a prospective study with three different antidepressants.

Kuhn KU, Quednow BB, Thiel M, Falkai P, Maier W, Elger CE.

            Major depression (MD) is underdiagnosed and undertreated in patients with temporal lobe epilepsy (TLE). Side effects of some antidepressants, like increased risk of seizures and drug-drug interactions with anticonvulsants, contribute to undertreatment of MD in patients with TLE. We analyzed post hoc the data from 2 years of treatment of inpatients with MD and TLE. Seventy-five patients received standard treatment with citalopram, mirtazapine, or reboxetine, respectively, at recommended dosage. Examinations were done with the Hamilton Rating Scale for Depression at admission and after 4 and 20-30 weeks. Plasma levels of anticonvulsants were examined at admission and discharge. Seizures were documented. The antidepressive treatment was efficacious in all antidepressant groups. No case of serious adverse event or drug interaction occurred. There was no increase in frequency or severity of seizures. At endpoint the dropout rate for mirtazapine was significantly higher than that for reboxetine or citalopram. Reboxetine showed a trend to be more efficacious than citalopram but not mirtazapine at Week 4.



Confirmatory Factor Analysis of the California Verbal Learning Test in Patients With Epilepsy: Relationship to Clinical and Neuropathological Markers of Temporal Lobe Epilepsy

James H. Baños, David L. Roth, Cheryl Palmer, Richard Morawetz, Robert Knowlton, Edward Faught, Ruben Kuzniecky, Erhan Bilir, and Roy C. Martin

Neuropsychology, 2004, Vol. 18, No. 1, 60–68, ©2004 American Psychological Association

            Latent constructs involved in California Verbal Learning Test (D. C. Delis, J. H. Kramer, E. Kaplan, & B. A. Ober, 1987) performance were examined using confirmatory factor analysis in 388 epilepsy surgery candidates. Eight factor models were compared. A single-factor model was examined, along with 7 models accommodating constructs of auditory attention, inaccurate recall, and delayed recall in different combinations. The retained model consisted of 3 correlated factors: Auditory Attention, Verbal Learning, and Inaccurate Recall. Validity of this factor structure was examined in a subsample of patients with left and right temporal lobe epilepsy. All 3 factors were related to seizure focus and magnetic resonance imaging hippocampal volume. Only Verbal Learning was related to hippocampal neuropathology, supporting the distinction between learning and attention in the factor structure.




Lateralization of Epileptic Foci by Neuropsychological Testingin Mesial Temporal Lobe Epilepsy

Hongkeun Kim, Sangdoe Yi and Eun Ik Son, Jieun Kim

Neuropsychology, 2004, Vol. 18, No. 1, 141–151, ©2004 American Psychological Association

            This study investigated the lateralizing value of neuropsychological testing in presurgical evaluation of mesial temporal lobe epilepsy (MTLE). This study differed from previous ones in that the cutoff values were determined to yield high positive predictive values (PPVs), multiple neuropsychological predictors were considered in combination, and patients with atypical language dominance or low intelligence were not excluded from the sample. The participants were 92 patients with MTLE (left, n = 47; right, n = 45) who showed good postoperative seizure control. With a stringent cutoff criterion, the multiple neuropsychological predictors considered in combination yielded a sensitivity of 15% and a PPV of 93%, and with a less stringent cutoff criterion, a sensitivity of 37% and a PPV of 83%.



A systematic review of the contribution of qualitative research to the study of quality of life in children and adolescents with epilepsy.

Mcewan, KJ, Espie, CA, Metcalfe, J

Seizure. 2004 Jan;13(1):3-14.

            A sizeable literature focusing on QOL in children and adolescents with epilepsy has been produced over the last few years. However, relatively little emphasis has been placed on defining these issues from direct exploration of children's and adolescents' views. Qualitative methodologies are proposed in this review as an appropriate means of eliciting such information.This review systematically investigated the extent to which studies of QOL in children and adolescents with epilepsy have used recognised qualitative methodology. Articles for inclusion were identified by searching the term 'epilepsy', combined with 'adolescent(s) and/or child(ren)' and 'psychosocial and/or quality of life'. Selected articles were reviewed and rated using CASP Guidelines for qualitative research by two independent raters.Seventeen studies were retrieved through literature search. Of these six used some form of qualitative methodology either individually or combined with quantitative methods. However, only one study met quality criteria for selection in this systematic review.A summary of both selected and excluded studies is presented and methodological limitations discussed. Recommendations for appropriate methodology for investigation of QOL issues in children and adolescents are given


***Non-Epiletic Seizures (NES), including Psychogenic Seizures


…many more coming…


Salmon, Peter DPhil; Al-Marzooqi, Suad M. PhD; Baker, Gus PhD; Reilly, James PhD

Childhood Family Dysfunction and Associated Abuse in Patients With Nonepileptic Seizures: Towards a Causal Model.[Article]

Psychosomatic Medicine. 65(4):695-700, July/August 2003.

            Objective: A history of childhood sexual abuse is thought to characterize patients with nonepileptic seizures (NES). We tested the hypotheses: 1) that history of sexual abuse is more prevalent in patients with NES than in controls with epilepsy; 2) that such abuse is associated with NES, not directly but because it is a marker of family dysfunction; and 3) that family dysfunction and abuse are, in turn, linked to NES because they increase a general tendency to somatize. Methods: We compared 81 patients with NES with 81 case-matched epilepsy patients, using questionnaires to elicit recollections of sexual, physical, and psychological abuse and family atmosphere and to quantify current somatization. Results: Although each form of abuse was more prevalent in NES patients, only child psychological abuse uniquely distinguished NES from epilepsy. However, its association with NES was explained by family dysfunction. A general tendency to somatize explained part of the relationship of abuse to NES. Conclusions: Abuse therefore seems to be a marker for aspects of family dysfunction that are associated with - and may therefore cause - somatization and, specifically, NES.

(***Problem: NES assumed homogenous, psychogenic, when it is not – hence, sample is diluted)