bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Unsuccessful Testing During the Intracarotid Amobarbital Procedure in Preadolescent Children
Authors: Hamer Hajo M. , Wyllie Elaine , Stanford Lisa , Mascha Edward , Kotagal Prakash , Wolgamuth Barbara
Published: August 2005

Summary: Purpose: Identification of risk factors for unsuccessful testing during intracarotid amobarbital procedure (IAP) in preadolescent children.

Methods: A pediatric IAP protocol was attempted in 42 candidates for epilepsy surgery (5–12 years old; mean, 10 years) based on the ability to pass a practice test. Language dominance was defined by marked asymmetry until first verbal response and paraphasic errors. Intact hemispheric memory was defined by recall of 60% of test items. The odds ratios of baseline variables (age at IAP, Full‐Scale IQ, side of disease, age at seizure onset, amobarbital dose) were calculated for various IAP outcomes.

Results: IAPs were accomplished in 40 children. Language dominance was established in 25 (62.5%) of 40 patients: all 21 focal resection candidates were left language dominant; four hemispherectomy candidates had intact language after injection of the damaged hemisphere. In 12 (30%) of 40 patients, language testing failed because of agitation or obtundation. Compared with the 21 children with language dominance established by bilateral IAP, these 12 children had lower mean Full‐Scale IQ (66.4 vs. 87.9; p = 0.014), and more frequently, the epileptogenic lesion in the left hemisphere (presumed dominant by right‐handedness; 78 vs. 33%; p = 0.04). Excluding hemispherectomy candidates (intentionally only one injection), memory testing could not be completed in 13 (36%) of 36 children because of obtundation or agitation. These children were significantly younger than the 23 (64%) of 36 with successful bilateral memory testing (mean age, 107.6 vs. 128.7 months; p = 0.006). The eight (25%) of 32 children with failing retention scores after ipsilateral injection had lower Full‐Scale IQ than did the 24 (75%) patients who passed (mean, 59.6 vs. 81.7 months; p = 0.03).

Conclusions: The IAP successfully established hemispheric language dominance and memory representation for just under two thirds of the preselected preadolescent children. Risk factors for unsuccessful testing included low Full‐Scale IQ (especially <80), young age (especially <10 years), and seizures arising from the left hemisphere presumed dominant by right‐handedness.
Acute Single Photon Emission Computed Tomographic Study of Vagus Nerve Stimulation in Refractory Epilepsy
Authors: Vonck K. , Boon P. , Van Laere K. , D'Havé M. , Vandekerckhove T. , O'Connor S. , Brans B. , Dierckx R. , De Reuck J.
Published: August 2005

Summary: Purpose: Left‐sided vagus nerve stimulation (VNS) is an efficacious treatment for patients with refractory epilepsy. The precise mechanism of action remains to be elucidated. Only limited data on VNS‐induced changes in regional cerebral blood flow (rCBF) are available. The aim of this study was to investigate rCBF changes during initial VNS with single‐photon emission computed tomography (SPECT).

Methods: In 12 patients (8 women, 4 men) with mean age of 32 years and mean duration of epilepsy of 19 years, VNS‐induced rCBF changes were studied by means of a 99mTc‐ethyl cysteinate dimer activation study with a single‐day split‐dose protocol before and immediately after initial stimulation. Images were acquired on a triple‐head camera with fan‐beam collimators and were reconstructed with scatter and attenuation correction. After coregistration to a standardized template, both a semiquantitative analysis using predefined volumes‐of‐interest (VOIs) as well as voxel‐by‐voxel analysis of the intra‐subject activation were performed. During follow‐up, efficacy of VNS in terms of seizure‐frequency reduction was studied.

Results: The semiquantitative analysis, with reference to the total counts in all VOIs, revealed a significant decrease of activity in the left thalamus immediately after the initial stimulation train. These results agreed with voxel‐by‐voxel analysis. In our study ipsilateral thalamic hypoperfusion was the most significant finding. Mean frequency of complex partial seizures was reduced from 30 per month before implantation to six per month after implantation.

Conclusions: VNS induces rCBF changes immediately after initial stimulation that can be studied with SPECT. VNS‐induced changes in the thalamus may play an important role in suppression of seizures. However, no significant relation between the level of hypoperfusion and subsequent clinical efficacy was found.
Effect of Long‐Term Vigabatrin Administration on the Immature Rat Brain
Authors: Qiao M. , Malisza K. L. , Del Bigio M. R. , Kozlowski P. , Seshia S. S. , Tuor U. I.
Published: August 2005

Summary: Purpose: To determine whether the neuropathologic changes produced by vigabatrin (VGB; γ‐vinyl GABA) administration in the developing rat brain are reversible.

Methods: We injected rats daily with VGB (25–40 mg/kg/day, s.c.) from age 12 days for 2 weeks followed by 2 weeks of a drug‐free period. Behavioral testing, magnetic resonance (MR) imaging, biochemical assays, and histologic technique were used to assess the adverse effect of VGB in developing brain and its reversibility.

Results: At the end of 2 weeks' VGB administration: (a) there was a hyperactivity and a shortened latency to escape out of cool water; (b) white matter appeared hyperintense in T2 and diffusion‐weighted MR images with 4–15% increases in T2; (c) microvacuolation, TUNEL‐positive nuclei, and swollen axons were observed in the corpus callosum; (d) myelin staining indicated a reduction in myelination, as did the reduction in activities of myelin and oligodendrocyte‐associated enzymes and the decrease in myelin basic protein on Western blots. Two weeks after stopping VGB administration: (a) MR images were normal, and microvacuolation was no longer in the white matter; (b) reduction in myelination reversed partially; (c) the T2 relaxation time remained elevated in the hypothalamus; and (d) the behavioral response remained abnormal.

Conclusions: Long‐term VGB administration to young rats causes brain injury, which recovers partially on its cessation. The observed cell death, disrupted myelination, and alterations in behavior indicate a need for further safety assessment in infants and children.
Spatial Extent of Neuronal Metabolic Dysfunction Measured by Proton MR Spectroscopic Imaging in Patients with Localization‐Related Epilepsy
Authors: Li L. M. , Cendes F. , Andermann F. , Dubeau F. , Arnold D. L.
Published: August 2005

Summary: Purpose: To assess the spatial extent of the decrease in the neuronal marker N‐acetyl‐aspartate (NAA) relative to creatine (Cr) in patients with localization‐related epilepsy, and to assess clinical differences between patients with and without widespread NAA/Cr reduction.

Methods: We studied 51 patients with localization‐related epilepsy. Patients were divided into three groups according to the EEG investigation: (a) temporal lobe epilepsy (TLE, n = 21), (b) extratemporal lobe epilepsy (extra‐TLE, n = 20), and (c) multilobar epilepsy (patients with a wider epileptogenic zone, n = 10). We acquired proton magnetic resonance (MR) spectrocopic imaging (1H‐MRSI) of temporal and frontocentroparietal regions in separate examinations for both patients and controls. NAA/Cr values 2 standard deviations below the mean of normal controls were considered abnormal.

Results: Twenty‐three (45%) patients including 12 with TLE had normal MR imaging including volumetric studies of the hippocampus. Forty‐nine (96%) patients had low NAA/Cr, indicating neuronal dysfunction in either temporal and/or extra‐temporal 1H‐MRSIs; 38% of patients with TLE and 50% of patients with extra‐TLE also had NAA/Cr reduction outside the clinical and EEG‐defined primary epileptogenic area. The NAA/Cr reduction was more often widespread in the multilobar group [six (60%) of 10] than in temporal or extratemporal groups [five (31%) of 16]. Nonparametric tests of (a) seizure duration, (b) seizure frequency, and (c) lifetime estimated seizures showed no statistically significant difference (p > 0.05) for TLE and extra‐TLE patients with or without NAA/Cr reduction outside the seizure focus.

Conclusions: Of patients with localization‐related epilepsy, 40–50% have neuronal metabolic dysfunction that extends beyond the epileptogenic zone defined by clinical‐EEG and/or the structural abnormality defined by MRI.
Cortical Excitability in Cryptogenic Localization‐Related Epilepsy: Interictal Transcranial Magnetic Stimulation Studies
Authors: Cantello R. , Civardi C. , Cavalli A. , Varrasi C. , Tarletti R. , Monaco F. , Migliaretti G.
Published: August 2005

Summary: Purpose: To assess whether single‐ and paired‐pulse transcranial magnetic stimulation (TMS) can measure the interictal brain excitability of medicated patients with cryptogenic localization related epilepsy (CLE). Changes in the balance between excitation and inhibition are the core phenomena in focal epileptogenesis. TMS can assess this balance in the primary motor cortex.

Methods: We selected 18 patients with CLE and similar clinical features in whom we located the epileptogenic area reliably, with 11 age‐ and sex‐matched healthy controls. For both motor cortices, we determined the threshold to TMS, the duration of the cortical silent period, and the corticocortical inhibition and facilitation curve.

Results: TMS was safe. The more antiepileptic drugs (AEDs) taken by the patients, the higher their threshold to TMS. The silent period duration failed to show significant changes. On paired TMS, a cluster analysis identified a homogeneous subgroup of patients (n = 7) who showed a significantly defective corticocortical inhibition and excess facilitation. With respect to the epileptogenic area, the phenomenon was bilateral in four of these patients, ipsilateral in two, and contralateral in one. The phenomenon was independent of AEDs and many other clinical variables. However, this patient group had a higher seizure frequency and a higher proportion of electroencephalograms (EEGs) showing interictal generalized epileptic discharges than the rest of the patients.

Conclusion: Paired TMS provided a valuable pathophysiologic insight into the interictal excitatory state of the cortex in CLE. This method can potentially supply useful prognostic clinical information.
Markedly Elevated Nitrate/Nitrite Levels in the Cerebrospinal Fluid of Children with Progressive Encephalopathy with Edema, Hypsarrhythmia, and Optic Atrophy (PEHO Syndrome)
Authors: Vanhatalo Sampsa , Riikonen Raili
Published: August 2005

Summary: Purpose: To compare the levels of brain nitric oxide production in patients with PEHO or PEHO‐like syndrome and in controls with other neurologic disease.

Methods: Nitric oxide metabolites, nitrates, and nitrites (NNx), were measured in the cerebrospinal fluid (CSF) of children with PEHO syndrome or PEHO‐like syndrome, and in controls with other neurologic diseases.

Results: The NNx levels were markedly higher in both PEHO (mean, 48 μM; p < 0.001) and PEHO‐like (22 μM; p < 0.003) patients as compared with the controls (6 μM), but did not correlate with age or with brain atrophy or CSF levels of insulin‐like growth factor‐1 (IGF‐1).

Conclusions: Our findings suggest that in PEHO syndrome, production of nitric oxide is markedly increased, suggesting that nitric oxide is involved in the pathologic phenomena (i.e., seizures and neurodegeneration) of the disease.
Lateralization of Temporal Lobe Epilepsy (TLE) and Discrimination of TLE from Extra‐TLE Using Pattern Analysis of Magnetic Resonance Spectroscopic and Volumetric Data
Authors: Li Li Min , Caramanos Zografos , Cendes Fernando , Andermann Frederick , Antel Samson B. , Dubeau François , Arnold Douglas L.
Published: August 2005

Summary: Purpose: To examine whether or not pattern analysis of magnetic resonance volumetric (MRVol) and proton magnetic resonance spectroscopic imaging (1H‐MRSI) data would enable (a) the accurate lateralization of temporal lobe epilepsy (TLE) and (b) the discrimination of TLE from extra‐temporal epilepsy (E‐TLE).

Methods: For lateralization analysis, we used data from 150 nonforeign tissue lesional TLE patients [88 left‐sided (L‐TLE), 46 right‐sided (R‐TLE), and 16 bilateral (Bi‐TLE)]. For the discrimination of TLE from E‐TLE, we used data from 174 patients (145 with unilateral TLE, 14 with unilateral E‐TLE, and 15 with widespread epileptogenic zones involving both the TL and extra‐TL regions—multilobar epilepsy). A series of “leave‐one‐out” cross‐validated linear discriminant analyses were performed using the MRVol and 1H‐MRSI data sets to lateralize TLE and discriminate it from E‐TLE.

Results: Lateralization: The leave‐one‐out linear discriminant analyses were able to correctly lateralize (with a posterior probability >0.50) 120 (90%) of the 134 L‐TLE and R‐TLE patients. Imposing higher posterior probability (>0.95) increased accuracy of lateralization to 98%, with only two discordant cases who underwent surgery on the side of electroencephalogram, and both had bad outcome. Discrimination: the leave‐one‐out linear discriminant analyses were able to correctly classify (with a posterior probability >0.50) 142 (89%) of the 159 TLE and E‐TLE patients. Accuracy increased slightly as higher posterior probability cutoffs were imposed, with fewer patients being classified.

Conclusions: Pattern analysis of 1H‐MRSI and MRVol data can accurately lateralize TLE. Discriminating TLE from E‐TLE was less accurate, probably due to the presence of temporal lobe damage in some patients with E‐TLE reflecting dual pathology.
Rectal Absorption of Lamotrigine Compressed Tablets
Authors: Birnbaum Angela K. , Kriel Robert L. , Burkhardt R. Todd , Remmel Rory P.
Published: August 2005

Summary: Purpose: Interruption of oral drug administration poses a significant clinical problem for antiepileptic drugs that have no parenteral formulation. If a drug is absorbed rectally, rectal administration can be a useful alternative when the oral route of administration is not possible. The purpose of this study was to compare the single‐dose pharmacokinetics of la‐motrigine (LTG) compressed tablets after rectal and oral administration in healthy volunteers.

Methods: A single LTG compressed tablet (100 mg) was administered orally and rectally to 12 volunteers in this single‐dose, two‐period, crossover study with a 2‐week washout between doses. For rectal administration, tablets were crushed and suspended in 10 mL of water. Plasma samples were collected from 0 to 120 hr after each dose and analyzed for LTG by an HPLC method developed for this investigation.

Results: LTG plasma concentrations were lower after rectal administration versus oral administration. The average area under the curve was 28.90 ± 9.5 μg/mL/hr after rectal administration and 51.71 ± 19.2 μg/mL/hr after oral administration. The average maximum LTG concentration was 0.53 ± 0.14 μg/mL after rectal administration and 1.45 ± 0.35 μg/mL after oral administration. The relative bioavailability for LTG compressed tablets was 0.63 ± 0.33 for rectal administration. There were no drug‐related rashes or serious side effects.

Conclusions: LTG suspension prepared from LTG compressed tablets is absorbed rectally, although not to the same extent or rate as when given orally.
Tonsillar Pain Mimicking Glossopharyngeal Neuralgia as a Complication of Vagus Nerve Stimulation: Case Report
Authors: Duhaime Ann‐Christine , Melamed Susan , Clancy Robert R.
Published: August 2005

Summary: An adolescent girl presented with severe, lancinating tonsillar pain exacerbated by swallowing 6 weeks after initiation of left vagus nerve stimulation for intractable epilepsy. Her symptoms mimicked those seen in glossopharyngeal neuralgia and were relieved by temporary cessation of stimulation. Gradual reinstitution of therapy with alteration in stimulus parameters resulted in improved seizure control as well as cessation of pain symptoms. Direct stimulation of the vagus nerve may result in vagoglossopharyngeal neuralgia, which, in this case, was amenable to stimulus modification.
Valproic Acid‐Induced Hyperammonemic Encephalopathy with Triphasic Waves
Authors: Kifune Akira , Kubota Fumio , Shibata Nobuyoshi , Akata Takushirou , Kikuchi Senichirou
Published: August 2005

Summary: Purpose: To examine a patient with valproic acid (VPA)‐induced hyperammonemic encephalopathy accompanied by triphasic waves.

Methods: A 61‐year‐old male patient with epilepsy experienced disturbance of consciousness after VPA dose was increased because of poor seizure control. The electroencephalogram (EEG) taken on admission revealed triphasic waves and high‐amplitude δ‐activity with frontal predominance. Although serum hepatic enzymes, such as AST and ALT, were normal, serum ammonium level was high at 96 μg/dl (normal range, 3–47 μg/dl). Serum amino acid analysis showed multiple minor abnormalities. Administration of VPA was discontinued immediately after admission, while other anticonvulsants were continued.

Results: The patient's condition was improved on the fourth day of admission. An EEG, serum ammonium level, and amino acid profile were normal on the eighth day. Based on VPA administration, serum ammonium levels, and results of amino acid analysis, this patient had VPA‐induced hyperammonemic encephalopathy.

Conclusions: Our case indicates that caution is required if triphasic waves appear in VPA‐induced hyperammonemic encephalopathy.
Status Epilepticus–Induced Neuronal Loss in Humans Without Systemic Complications or Epilepsy
Authors: Fujikawa Denson G. , Itabashi Hideo H. , Wu Aiguo , Shinmei Steve S.
Published: August 2005

Summary: Purpose: To determine the regional distribution of neuronal damage caused strictly by status epilepticus (SE) without systemic complications, underlying brain pathology, or a history of preexisting epilepsy.

Methods: The medical records and electroencephalograms (EEGs) of three deceased patients who developed SE in the hospital were reviewed. Their brains were formalin‐fixed, and 17 brain regions were selected, embedded in paraffin, and sectioned. Alternate sections were stained with either hematoxylin and eosin and cresyl violet to determine the extent of neuronal loss and gliosis or glial fibrillary astrocytic protein to confirm the extent of astrocytic proliferation.

Results: The three patients died 11 to 27 days after the onset of focal motor SE; none had hypotension, hypoxemia, hypoglycemia, or significant hyperthermia. Two patients had no prior seizures and no underlying brain pathology. The third patient, who had leptomeningeal carcinomatosis, had one seizure 2 months before the onset of SE. The duration of SE was 8.8 hours to 3 days. EEGs showed unilateral temporal lobe sharp‐wave discharges in one patient and independent temporal lobe sharp‐wave discharges bilaterally in the other two patients. In addition to widespread neuronal loss and reactive gliosis in the hippocampus, amygdala, dorsomedial thalamic nucleus, and Purkinje cell layer of the cerebellum, we report for the first time periamygdaloid (piriform) and entorhinal cortical damage occurring acutely after SE in humans.

Conclusions: In the absence of systemic complications or preexisting epilepsy, SE produces neuronal loss in a distribution similar to that from domoic acid‐induced SE in humans and from kainic acid‐ and pilocarpine‐induced SE in rats.
Prevalence, Knowledge, Attitude, and Practice of Epilepsy in Kerala, South India
Authors: Radhakrishnan K. , Pandian J. D. , Santhoshkumar T. , Thomas S. V. , Deetha T. D. , Sarma P. S. , Jayachandran D. , Mohamed E.
Published: August 2005

Summary: Purpose: To ascertain the prevalence and pattern of epilepsy and to characterize and quantify knowledge, attitude, and practice (KAP) toward epilepsy among the people of the state of Kerala, which is distinguished from the rest of India by a high level of literacy and health awareness of its population.

Methods: We conducted a door‐to‐door survey covering the entire population of 238,102 people residing in 43,681 households in a semiurban area of central Kerala. The screening questionnaire administered by medical social workers had a sensitivity of 100% for identifying persons with epilepsy. Neurologists examined all the individuals suspected of having epilepsy. We evaluated KAP toward epilepsy among 1,118 subjects (439 males and 679 females; mean age, 33.3 years; age range, 15–85 years) from households without epilepsy in the study area.

Results: Through a three‐phased survey, we ascertained 1,175 cases (616 males and 559 females) with active epilepsy, providing a crude point prevalence ratio of 4.9 cases per 1,000 people and an age‐adjusted prevalence ratio of 4.7 cases per 1,000 population. The highest age‐specific prevalence rate of 6.5 per 1,000 occurred in the 10‐ to 19‐year‐old age group. Sex‐specific prevalence rates did not significantly differ. The proportion of generalized and localization‐related epilepsies was 58.8% and 30.6%, respectively. Ninety‐nine percent of the KAP respondents had read or heard about epilepsy. Thirty‐one percent and 27% thought epilepsy was a hereditary disorder and a form of insanity, respectively. About 40% of the respondents felt that individuals with epilepsy could not be properly educated or employed. Eleven percent would object to their children having contact with epileptic children.

Conclusions: The prevalence and pattern of epilepsy in central Kerala, South India, do not differ from that of developed countries. Although the awareness of epilepsy among the people of Kerala was comparable to that of developed countries, the attitudes were much more negative. The need for educating the people of Kerala on epilepsy and for incorporating an adequate knowledge of epilepsy in the school curricula cannot be overemphasized.
Autonomic Seizures Versus Syncope in 18q‐ Deletion Syndrome: A Case Report
Authors: Sturm Kerstin , Knake Susanne , Schomburg Ulrich , Wakat Jörg‐P. , Hamer Hajo M. , Fritz Barbara , Oertel Wolfgang H. , Rosenow Felix
Published: August 2005

Summary: Purpose: The 18q‐ deletion syndrome (18qDS) is frequently associated with cardiac anomalies. Patients with this syndrome may also have epilepsy, which presents certain diagnostic difficulties. This case report aims to illustrate these diagnostic problems, document the usefulness of heart rate‐based seizure detection algorithms in this setting, and define the epilepsy syndrome associated with 18qDS.

Methods: Closed‐circuit video electroencephalogram (EEG) monitoring using a heart rate–based seizure detection software was used to identify the event in question and to establish the diagnosis of epilepsy. Chromosomal analysis and magnetic resonance imaging (MRI) were used to further define the epilepsy syndrome.

Results: We report on a patient with an atrial septal defect, enlargement of the right heart, and incomplete right bundle branch block, who developed episodes of tachycardia, loss of consciousness, and pallor, for which he was amnesic. Chromosomal analysis demonstrated karyotype 46, XY, del(18)(q21.3). ish del(18)(wcp18+, D18Z1+) with a loss of the gene for myelin basic protein. MRI revealed multifocal dysmyelination. Video‐EEG monitoring using an electrocardiogram (ECG)‐triggered seizure detection software proved to be indispensable in detecting an autonomic seizure and establishing the correct diagnosis; the procedure also allowed for the definition of the epilepsy syndrome. The patient was treated with carbamazepine and remained seizure‐free.

Conclusions: Video‐EEG monitoring using a heart rate‐based seizure detection software can be helpful in diagnostically differentiating autonomic seizures from syncope. Dysmyelination due to loss of the myelin basic protein gene on 18q and cortical dysgenesis may be of pathogenic relevance.
Community Leader Education to Increase Epilepsy Attendance at Clinics in Epworth, Zimbabwe
Authors: Ball D. E. , Mielke J. , Adamolekun B. , Mundanda T. , McLean J.
Published: August 2005

Summary: Objective: To determine whether educating community leaders about epilepsy would lead to an increase in epilepsy cases being diagnosed and treated at primary health centers.

Methods: This was a single‐arm cohort study performed in Epworth, a periurban township outside Harare, Zimbabwe. The subjects were Epworth community leaders (Local Board members, teachers, nurses, police officers, traditional healers, prophets). Educational workshops were given on epilepsy, its cause, and its management, and the number of new epilepsy cases on local primary health clinic registers 6 months after the workshops was measured.

Results: Six new cases were recorded, all among patients previously diagnosed with epilepsy. This was a significant increase (p = 0.02) compared with the null hypothesis.

Conclusion: Although there was a significant increase in new cases, these did not represent newly diagnosed patients. Significant prejudice within the community may still prevent identified patients with epilepsy from seeking treatment. Alternative methods must be sought to increase the awareness of epilepsy within low‐income communities and to reach “hidden” people with epilepsy.
Patient‐Based Assessments of Quality of Life in Newly Diagnosed Epilepsy Patients: Validation of the NEWQOL
Authors: Abetz Linda , Jacoby Ann , Baker Gus A. , McNulty Pauline
Published: August 2005

Summary:Purpose: In epilepsy, patient‐based assessments are increasingly used as outcome measures in clinical trials of novel therapies alongside the traditional clinical measures of efficacy. The objective of this study was to validate psychometrically a quality of life (QOL) measure developed for use with recently diagnosed epilepsy patients.

Methods: The NEWQOL (Quality of Life in Newly Diagnosed Epilepsy Instrument) is a 93‐item self‐administered battery designed to assess QOL in patients with new‐onset epilepsy. NEWQOL consists of eight multi‐item scales (13 subscales) measuring several health parameters: Anxiety, Depression, Social Activities, Symptoms, Locus of Control/Mastery, Neuropsychological Problems (includes the following subscales: Fatigue, Memory, Concentration, Motor Skills, and Reading), Social Stigma, Worry, Work Limitations, and several single‐item measures (General Health, Number of Seizures, Social Limitations, Social Support, Self Concept, Ambition Limitations, Health Transition, and General Limitations). The NEWQOL was collected at baseline and 1 week post‐baseline from 108 patients in the U.K. and U.S.

Results: All of the multi‐item scales had high item discriminant validity, good test‐retest reliability, and acceptable levels of internal consistency reliability; all but the Reading and Stigma subscales had negligible floor and ceiling effects. General linear models were used to examine the known groups validity of NEWQOL. Significant differences were observed in the Worry, Symptoms, Summary Neuropsychological Scales, and all Neuropsychological subscales (Memory, Fatigue, Concentration, Motor Skills, and Reading), indicating poorer functioning in the more frequent or severe seizure groups.

Conclusions: Results from this study offer supportive evidence that NEWQOL has good validity and reliability and can discriminate between patient groups, particularly in relation to symptoms and psychological problems. We conclude that NEWQOL represents a useful measure for future studies in this patient population.
A Population‐Based Study on Epilepsy in Mentally Retarded Children
Authors: Airaksinen Eila M. , Matilainen Riitta , Mononen Tarja , Mustonen Kirsi , Partanen Juhani , Jokela Veikko , Halonen Pirjo
Published: August 2005

Summary: Purpose: This study presents data on cumulative risk of seizures, cause, comorbidity, and remission of epilepsy among mentally retarded (MR) children followed until the age of 22 years.

Methods: A total of 151 MR children were identified at the age of 8 or 9 years by screening four birth cohorts of 12,882 children born from 1969 to 1972 in the Finnish province of Kuopio. Information about epilepsy was gathered longitudinally when children were 9 to 10, 17, and 22 years old. The guidelines for epidemiological studies on epilepsy proposed by the International League Against Epilepsy were followed.

Results: By the age of 10 years, 29 of the 151 MR children (19%) had epilepsy. The cumulative risk for epilepsy at 22 years was 21%. The probability of developing epilepsy was increased fivefold in severely MR children compared with mildly MR children, i.e., in 27 of the 77 severely MR children (35%) versus 5 of the 74 mildly MR children (7%). Postnatal causes of mental retardation or association with cerebral palsy increased the risk for epilepsy, especially in the mildly MR children. When these risk factors were not present, the mildly MR children exhibited only a 3% risk for epilepsy, whereas the respective risk was about 10‐fold in severe mental retardation. The cumulative probability of epilepsy being in remission for 5 years by the age of 22 was 32%.

Conclusions: The cumulative risk of epilepsy varies according to the severity and the cause of the retardation as well as the presence of additional disabilities. The cumulative probability of epilepsy remission tended to increase with age.
Febrile Seizures: Treatment and Prognosis
Authors: Knudsen Finn Ursin
Published: August 2005

Summary: Recent epidemiologic data indicate that the vast majority of children with febrile seizures have a normal long‐term outcome. A precise knowledge of the short‐ and long‐term outcome with or without treatment, and short‐ and long‐term side effects is an important prerequisite for assessing the various treatment strategies. We focus on the impact of short‐term or prophylactic treatment on the short‐ and long‐term outcome of various types of febrile seizures. There is universal agreement that daily prophylaxis with antiepileptic agents should never be used routinely in simple febrile seizures, but only in highly selected cases, if at all. Intermittent diazepam (DZP) prophylaxis at times of fever may or may not reduce the recurrence rate, but it does not appear to improve the long‐term outcome as compared with short‐term seizure control. The treatment may be used to reduce the recurrence rate for a small arbitrarily defined group with multiple simple febrile seizures, complex febrile seizures, especially focal, prolonged or both, febrile status, and when parental anxiety is severe. However, there is no evidence that treatment of simple febrile seizures can prevent the rare cases of later epilepsy, and many children with complex febrile seizures have a benign long‐term outcome, even without treatment. Many prefer a “wait and see” policy. An attractive alternative is to treat new febrile seizures with rectal DZP in solution at seizure onset, given by the parents at home to prevent febrile status. Newer, less well documented short‐term strategies include nasal, oral, or rectal administration of other benzodiazepines. Short‐term seizure control of febrile status and careful parental counseling are the two most important targets of treatment.
Discriminating Between Epileptic and Nonepileptic Events: The Utility of Hypnotic Seizure Induction
Authors: Barry John J. , Atzman Orit , Morrell Martha J.
Published: August 2005

Summary: Purpose: To determine the validity of the Hypnotic Induction Profile (HIP) followed by seizure induction during continuous video‐electroencephalographic (EEG) monitoring to discriminate between epileptic (EE) and nonepileptic events (NEE).

Methods: Eighty‐two patients admitted to the Stanford Comprehensive Epilepsy Center for differential diagnosis of seizure‐like events were evaluated. Exclusion criteria included inability or refusal to complete the HIP, lack of a “typical”event, an IQ <70, present evidence of psychosis, or a physiological cause for NEE. Sixty‐nine patients met these criteria. While undergoing continuous video‐EEG monitoring, the patient completed an HIP, an inventory designed to measure the degree of hypnotizability. An attempt was then made to induce the patient's typical events under hypnosis by using a splitscreen technique. An event without an EEG correlate was thought to represent an NEE. A diagnosis of NEE was made independently by the neurology team and was compared with results obtained with the hypnotic evaluation.

Results: Results for patients with EE were compared with those with NEE and a group consisting of both EE/NEE. All patients with NEE were then contrasted with the EE group. HIP scores for the EE patients indicated lower hypnotizability than the NEE group and were statistically significant when NEE patients and those with NEE/EE were combined. The sensitivity of seizure induction in the diagnosis of NEE was 77%, with a specificity of 95%.

Conclusions: The HIP coupled with seizure induction is a useful technique to aid in the diagnosis of patients with NEE. It is sensitive and specific, and it may provide the patient with a useful behavioral tool to control NEEs. It may also furnish a conduit for long‐term treatment.
Is Epilepsy a Progressive Disease? The Neurobiological Consequences of Epilepsy
Authors: Cole Andrew J.
Published: August 2005

Summary: While primary, or idiopathic, epilepsies may exist, in the vast majority of cases epilepsy is a symptom of an underlying brain disease or injury. In these cases, it is difficult if not impossible to dissociate the consequences of epilepsy from the consequences of the underlying disease, the treatment of either the disease or the epilepsy, or the actual seizures themselves. Several cases of apparent complications of epilepsy are presented to illustrate the range of consequences encountered in clinical practice and the difficulty in assigning blame for progressive symptomatology in individual cases. Because of the difficulty in interpreting clinical material, many investigators have turned to epilepsy models in order to address the potential progressive consequences of recurrent seizures. The authors review experimental data, mainly from animal models, that illustrate short‐, medium‐, and long‐term morphological and biochemical changes in the brain occurring after seizures, and attempt to relate these observations to the human condition.
Psychiatric Comorbidity in Chronic Epilepsy: Identification, Consequences, and Treatment of Major Depression
Authors: Hermann Bruce P. , Seidenberg Michael , Bell Brian
Published: August 2005

Summary:The purpose of this article is to review the topic of interictal psychiatric comorbidity among adult patients with chronic epilepsy, focusing specifically on those studies that have used contemporary psychiatric nosology. Five specific issues are addressed: (a) the risk and predominant type(s) of psychiatric comorbidity in chronic epilepsy, (b) adequacy of recognition and treatment of psychiatric comorbidity, (c) the additional burdens that comorbid psychiatric disorders impose upon patients with chronic epilepsy, (d) the etiology of these disorders, and (e) strategies for treatment. Current appreciation for these issues in epilepsy is contrasted to related fields (e.g., primary care, psychiatry, and epidemiology), where considerable attention has been devoted to the identification, consequences, and treatment of psychiatric comorbidity. The issue of psychiatric comorbidity in epilepsy is reviewed with the aim of identifying a clinical and research agenda that will advance understanding of at least one important psychiatric condition associated with epilepsy—namely, major depression.
Presurgical Evaluation: Current Role of Invasive EEG
Authors: Zumsteg Dominik , Wieser Heinz Gregor
Published: August 2005

Summary: Our purpose was to review the current role of invasive and semi‐invasive EEG in the presurgical evaluation of candidates for epilepsy surgery. The use of stereotactically implanted intracranial depth (stereo‐EEG), subdural strip and grid, and foramen ovale electrodes, as well as intraoperative electrocorticography and electrical brain stimulation (“functional mapping”) at the Epilepsy Center University Hospital Zurich, from 1984 to 1998, is analyzed. Advantages and disadvantages of the various intracranial EEG techniques are critically discussed. Out of 422 selective amygdalohippocampectomies performed in Zurich, 54% had non‐invasive, 32% had semi‐invasive, and 14% had invasive presurgical EEG evaluation. Because patients currently referred to our center increasingly present with a complex history of disease, i.e., constitute so‐called “difficult cases”, there is trend to combine several invasive and semi‐invasive, pre‐ and intraoperative neurophysiological techniques.
Temporal Lobe Epilepsy: When Are Invasive Recordings Needed?
Authors: Diehl B. , Lüders H. O.
Published: August 2005

Summary: Temporal lobe epilepsy (TLE) is the most common type of medically intractable partial epilepsy amenable to surgery. In the majority of cases, the underlying pathology in temporal lobe epilepsy is mesial temporal sclerosis (MTS). Whereas historically invasive recordings were required for most epilepsy surgeries, indications have dramatically changed since the introduction of high‐resolution MRI, which uncovers structural lesions in a high percentage of cases. No invasive recordings are required to perform a temporal lobectomy in patients with intractable epilepsy who have structural imaging suggesting unilateral MTS and concordant interictal and ictal surface EEG recordings, functional imaging, and clinical findings. Invasive testing is needed if there is evidence of bitemporal MTS on structural imaging and/or electrophysiologically, and additional information from functional imaging, neuropsychology, and the intracarotid amobarbital (Wada) test also does not help to lateralize the epileptogenic zone. Depth electrodes can be particularly helpful in this setting. However, no surgery is indicated, even without invasive recordings, if bitemporal‐independent seizures are recorded by surface EEG and all additional testing is inconclusive. Other etiologies of TLE such as a tumor, vascular malformation, encephalomalacia, or congenital developmental abnormality account for about 30% of all patients who undergo epilepsy surgery. Epilepsy surgery is indicated after limited electrophysiologic investigations if neuroimaging and electrophysiology converge. However, approaches for resection in lesional temporal lobe epilepsy vary among centers. Completeness of resection is crucial and invasive recordings may be needed to guide the resection by mapping eloquent cortex and/or to determine the extent of the non‐MRI‐visible epileptogenic area. Specific approaches for the different pathologies are discussed because there is evidence that the relationship between the lesions visible on MRI and the epileptogenic zone varies among lesions of different pathologies, and therefore variable surgical strategies must be applied.
Association Between the Density of Mossy Fiber Sprouting and Seizure Frequency in Experimental and Human Temporal Lobe Epilepsy
Authors: Pitkänen Asla , Nissinen Jari , Lukasiuk Katarzyna , Jutila Leena , Paljärvi Leo , Salmenperä Tuuli , Karkola Kari , Vapalahti Matti , Ylinen Aarne
Published: August 2005

Summary: Purpose: If the sprouting of granule cell axons or mossy fibers in the dentate gyrus is critical for the generation of spontaneous seizures in temporal lobe epilepsy (TLE), one could hypothesize that epileptic animals or humans with increased sprouting would have more frequent seizures. This hypothesis was tested by analyzing the data gathered from experimental and human epilepsy.

Methods: In experiment I (rats with “newly diagnosed” TLE), self‐sustained status epilepticus was induced in rats by electrically stimulating the amygdala. Thereafter, the appearance of spontaneous seizures was monitored by continuous video‐electroencephalography (EEG) until the animal developed two spontaneous seizures and for 11 d thereafter. Rats were perfused for histology, and mossy fibers were stained using the Timm method. In experiment II (rats with “recently diagnosed” TLE), status epilepticus was induced in rats and the development of seizures was monitored by video‐EEG for 24 h/d every other day for 60 days. All animals were then perfused for histology. In experiment III (rats with “chronic” TLE), animals were monitored by video‐EEG for 24 h/d every other day for 6 months before histologic analysis. To assess mossy fiber sprouting in human TLE, hippocampal sections from 31 patients who had undergone surgery for drug‐refractory TLE were stained with an antibody raised against dynorphin.

Results and Conclusions: Our data indicate that the density of mossy fiber sprouting is not associated with the total number of lifetime seizures or the seizure frequency in experimental or human TLE.
Does Status Epilepticus Influence the Motor Development of Immature Rats?
Authors: Kubová Hana , Haugvicová Renata , Suchomelová Lucie , Mareš Pavel
Published: August 2005

Summary: Purpose: To study the effect of severe status epilepticus (SE) on the motor development of rats.

Methods: SE was induced in 12‐day‐old rats (P12 group) and 25‐day‐old rats (P25 group) using the lithium‐pilocarpine model. Seizures were interrupted after 2 hours by paraldehyde with an intraperitoneal dose of 0.3 or 0·6 mL/kg, respectively. Starting 3 days after SE, all animals were repeatedly exposed to a battery of motor and behavioral tests, including the bar‐holding test, rotarod test, and open field test.

Results: In P12 animals, motor impairment occurred 2 months after SE, when significantly worse performance in the rotarod test was found. No difference between controls and experimental rats was found in any other test used. In contrast, P25 animals were significantly poorer in the bar‐holding test from postnatal day 34 until adulthood. In open field study, P25 rats were found to be hyperactive during the whole period of testing, whereas P12 animals exhibited an initial period of hypoactivity (in the first test) that was replaced by hyperactivity that lasted until 2 months of age. In the last test performed at the age of 98 days, experimental P12 animals were again less active than age‐matched controls.

Conclusions: Animals of both age groups exhibited permanent changes of motor performance; however, both the pattern and the time course of these changes was related to age when SE was elicited.
Morphological Plasticity in an Infant Monkey Model of Temporal Lobe Epilepsy
Authors: Wenzel H. Jürgen , Born Donald E. , Dubach Mark F. , Gunderson Virginia M. , Maravilla Kenneth R. , Robbins Carol A. , Szot Partrizia , Zierath Danielle , Schwartzkroin Philip A.
Published: August 2005

Summary: Purpose/Methods: Seizures in early life are thought to contribute to the development of human temporal lobe epilepsy. To examine the consequences of early seizures, we elicited status epilepticus in immature, 5.5‐ to 7.0‐month‐old pigtailed macaques by unilateral microinfusion of bicuculline methiodide into the entorhinal cortex.

Results: This report focuses on neuropathological changes in the hippocampus. Bicuculline infusion consistently elicited limbic‐like seizures with prolonged, relatively localized electrographic activity. Magnetic resonance imaging revealed enhanced signal intensity in the ipsilateral hippocampus after seizures; in some cases, there was also progressive hippocampal atrophy. Histological changes were variable; in two of five monkeys, there was significant hippocampal neuron loss, gliosis, granule cell dispersion, and mossy fiber reorganization.

Conclusions: The histopathological findings and associated magnetic resonance imaging abnormalities after bicuculline‐induced status epilepticus in infant monkeys mimic common aspects of human temporal lobe epilepsy.
Brain Plasticity and Cellular Mechanisms of Epileptogenesis in Human and Experimental Cortical Dysplasia
Authors: Babb Thomas L. , Ying Zhong , Mikuni Nobuhiro , Nishiyama Kazuotoshi , Drazba Judy , Bingaman William , Wyllie Elaine , Wylie Christi J. , Yacubova Karina
Published: August 2005

Summary: Purpose: The cellular mechanisms that may contribute to epilepsy in resected human cortical dysplasia (CD) were compared with the in utero radiated rat CD model. In human and rat focal hippocampal epilepsy, postsynaptic N‐methyl‐d‐aspartate receptors are up‐regulated and presynaptic axon collaterals hyperinnervate them. We hypothesized that in both human and rat CD: (a) the N‐methyl‐d‐aspartate receptor subunits NR1 and NR2A/B would be increased and coassembled, and (b) aberrant axons would be in regions of CD.

Methods: Tests for presynaptic and postsynaptic changes in human and rat CD included the following: (a) cytology, (b) immunocytochemistry, (c) coimmunoprecipitation, (d) double‐labeled immunofluorescence, and (e) Timm histochemistry of hippocampal mossy fibers. Within‐patient comparisons were made between epileptic tissue, identified by subdural electro‐encephalographic seizure onsets, and nonepileptic tissue remote from the focus but within the therapeutic resection. Rats were radiated at embryonic day 17, and offspring were studied postnatally. Statistical comparisons were made against normal rats matched for age and tissue processing.

Results: In focal CD patients, NR2A/B subunits and their coassemblies with NR1 were increased significantly more than for the remote nonepileptic cortex. Confocal microscopy showed that NR1‐NR2A/B colabeled single dysplastic neurons in both human and rat. In CD rats, mossy fibers innervated the anomalously oriented hippocampal neurons.

Conclusions: Human epileptic CD exhibits a spectrum of abnormal cell orientations and laminations that must require plastic axodendritic changes during development. These altered circuits and receptors could account for the seizures and cognitive deficits found in patients with CD. The radiated rat CD model with cortical dyslaminations and NR2A/B subunit increases would allow the development and testing of drugs targeted at only the NR2A/B subunit or at decoupling the NR1‐NR2 coassembly, which could provide a specific antiepileptic drug for dysplastic circuits without inducing general depression of all brain neurons.
Hippocampal Neurons Express GABAAReceptor Insensitive to Diazepam in Hyperexcitable Conditions
Authors: Kapur Jaideep
Published: August 2005

Summary:Purpose: To define the properties of γ‐aminobutyric acid‐type A (GABAA) receptors expressed on dentate granule cells in neonatal rats and to define the impact of prolonged seizures on GABAAreceptors in 28‐ to 35‐day‐old rats.

Methods: Whole GABAAreceptor currents were recorded from acutely isolated dentate granule cells. Cells were isolated from 7‐ to 14‐day‐old rats for the first experiment. For the second experiment, cells were isolated from 28‐ to 35‐day‐old naive rats and rats that had undergone 45 minutes of status epilepticus. Modulation of GABAAreceptor currents by diazepam (DZP), zinc, and zolpidem was studied.

Results: In 7‐ to 14‐day‐old rats, dentate granule cells express DZP‐ and zolpidem‐insensitive, zinc‐sensitive GABAAreceptors. In 28‐ to 35‐day‐old rats, dentate granule cells express DZP‐sensitive GABAAreceptors. At the latter age, prolonged seizures render GABAAreceptors DZP‐insensitive.

Conclusion: Hippocampal dentate granule cells express DZP‐insensitive receptors in hyperexcitable states. These receptors are likely to contain α4 subunit.