bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification in Patient Urine Samples of Felbamate and Three Metabolites: Acid Carbamate and Two Mercapturic Acids
Authors: Thompson Charles D. , Barthen Mary T. , Hopper Darrin W. , Miller Thomas A. , Quigg Mark , Hudspeth Candice , Montouris Georgia , Marsh LaDonna , Perhach James L. , Sofia R. Duane , Macdonald Timothy L. 
Published: August 2005

Summary: Purpose: Previously we proposed and provided evidence for the metabolic pathway of felbamate (FBM), which leads to the reactive metabolite, 3‐carbamoyl‐2‐phenylpropionaldehyde. This aldehyde carbamate was suggested to be the reactive intermediate in the oxidation of 2‐phenyl‐1,3‐propanediol monocarbamate to the major human metabolite 3‐carbamoyl‐2‐phenylpropionic acid. In addition, the aldehyde carbamate was found to undergo spontaneous elimination to 2‐phenylpropenal, commonly known as atropaldehyde. Moreover, atropaldehyde was proposed to play a role in the development of toxicity during FBM therapy. Evidence for atropaldehyde formation in vivo was reported with the identification of modified N‐acetyl‐cysteine conjugates of atropaldehyde in both human and rat urine after FBM administration. Identification of the atropaldehyde‐derived mercapturic acids in urine after FBM administration is consistent with the hypothesis that atropaldehyde is formed in vivo and that it reacts with thiol nucleophiles. Based on the hypothesis that the potential for toxicity will correlate to the amount of atropaldehyde formed, we sought to develop an analytic method that would quantify the amount of relevant metabolites excreted in patient urine. Methods: We summarize the results of an LC/MS method used to quantify FBM, 3‐carbamoyl‐2‐phenylpropionic acid and two atropaldehyde‐derived mercapturic acids in the patient population. Results: Analysis was performed on 31 patients undergoing FBM therapy. The absolute quantities of FBM and three metabolites were measured. Conclusions: This method demonstrated sufficient precision for the identification of patients exhibiting “abnormal” levels of atropaldehyde conjugates and may hold potential for patient monitoring.
Topiramate Pharmacokinetics in Infants
Authors: Glauser Tracy A. , Miles Michael V. , Tang Peter , Clark Peggy , McGee Kathy , Doose Dennis R. 
Published: August 2005

Summary: Purpose: This study's goal was to provide preliminary data on the pharmacokinetics of topiramate (TPM) in a cohort of infants (younger than 4 years) participating in an open‐label trial of TPM in refractory infantile spasms. Methods: The pharmacokinetics of TPM were assessed in infants receiving a stable TPM dose for >7 days during the extension phase of this trial. Blood samples were drawn just before and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 h after the morning TPM dose. TPM plasma concentrations were determined by fluorescence polarization immunoassay. The noncompartmental analysis module of WinNonlin was used to calculate individual patient pharmacokinetics profiles. Results: Five infants (ages, 23.5–29.5 months) formed the study cohort. These infants had been given TPM for a median of 9 months (range, 6–11 months) and were currently receiving between 11 and 38.5 mg/kg/day TPM. One was receiving TPM monotherapy, whereas four were taking concomitant antiepileptic medications (AEDs; n = 2, enzyme‐inducing agents; n = 2, non‐enzyme‐inducing drugs). TPM pharmacokinetics in infants appears to be linear. In this cohort, mean TPM plasma clearance (CL/F, 66.6 ± 27.4 ml/h/kg) was slightly higher than that reported for children and adolescents and therefore substantially higher than that reported for adults. TPM CL/F was higher and the calculated half‐life shorter in the infants receiving concomitant enzyme‐inducing AEDs. Conclusions: Based on this small cohort of patients, it appears that infants may require significantly larger TPM doses, based on weight, than children, adolescents, or adults. Titration to effect and not absolute TPM dose should guide therapy in this age group.
Regional Cerebral Blood Flow During Temporal Lobe Seizures Associated with Ictal Vomiting: An Ictal SPECT Study in Two Patients
Authors: Baumgartner Christoph , Olbrich Achim , Lindinger Gerald , Pataraia Ekaterina , Gröppel Gudrun , Bacher Johanna , Aull Susanne , Serles Wolfgang , Hoffmann Martha , Leutmezer Fritz , Czech Thomas , Prayer Daniela , Pietrzyk Uwe , Asenbaum Susanne , Podreka Ivo 
Published: August 2005

Summary: Purpose: Ictal vomiting represents a rare clinical manifestation during seizures originating from the temporal lobes of the nondominant hemisphere. The precise anatomic structures responsible for generation of ictal vomiting remain to be clarified. Ictal single photon emission computed tomography (SPECT), which allows one to visualize the three‐dimensional dynamic changes of regional cerebral blood flow (rCBF) associated with the ongoing epileptic activity, should be useful to study the brain areas activated during ictal vomiting. Methods: We performed ictal Tc‐HMPAO SPECT scans in two patients with mesial temporal lobe epilepsy (MTLE) whose seizures were characterized by ictal retching and vomiting. MTLE was documented by typical clinical seizure semiology, interictal and ictal EEG findings, hippocampal atrophy on magnetic resonance imaging (MRI) scan, and a seizure‐free outcome after selective amydalohippocampectomy. In both patients, seizures originated in the nondominant temporal lobe. We obtained accurate anatomic reference of rCBF changes visible on SPECT by a special coregistration technique of MRI and SPECT. We used ictal SPECT studies in 10 patients with MTLE who had seizures without ictal vomiting as controls. Results: In the two patients with ictal vomiting, we found a significant hyperperfusion of the nondominant temporal lobe (inferior, medial, and lateral superior) and of the occipital region on ictal SPECT. In patients without ictal vomiting, on the contrary, these brain regions never were hyperperfused simultaneously. Conclusions: Ictal SPECT provides further evidence that activation of a complex cortical network, including the medial and lateral superior aspects of the temporal lobe, and maybe the occipital lobes, is responsible for the generation of ictal vomiting.
A Beneficial Effect on Mood in Partial Epilepsy Patients Treated with Gabapentin
Authors: Harden Cynthia L. , Lazar Lorraine M. , Pick Lawrence H. , Nikolov Blagovest , Goldstein Martin A. , Carson Deborah , Ravdin Lisa D. , Kocsis James H. , Labar Douglas R. 
Published: August 2005

Summary: Purpose: Antiepileptic drugs (AEDs) are frequently used for their beneficial psychoactive effects on affective disorders. We sought to demonstrate a psychoactive effect of gabapentin (GBP) when used as add‐on AED therapy. Methods: Forty adult patients with partial epilepsy were studied in a prospective, non‐randomized fashion with interviewer‐rated and self‐rated scales of mood and anxiety: the Cornell Dysthymia Rating Scale (CDRS), Beck Depression Inventory (BDI), and Hamilton Depression (Ham‐D) and Anxiety (Ham‐A) Scales. After completion of baseline mood and anxiety scales (time 1), 20 of the 40 patients were prescribed add‐on GBP (treated group). The remaining 20 patients served as a control group. Both groups were similar in age and sex distribution. Follow‐up mood and anxiety scales were performed in all patients ∼3 months later (time 2). The average GBP dose at time 2 was 1,615 mg/day. All patients were taking stable doses of one to four AEDs at baseline and throughout the study. Seizure frequency was monitored throughout. Statistical significance was assessed by analysis of variance (ANOVA) by using a two‐factor repeated‐measures model. Results: The GBP‐treated group had a significant decrease in CDRS score over time compared with the control group (p = 0.04). No significant differences between the control and the treated groups were found for any of the remaining mood scales (BDI, p = 0.58; Ham‐D, p = 0.59; Ham‐A, p = 0.93). There was no significant difference or change in seizure frequency between groups. Conclusions: GBP treatment is associated with mood improvement as measured by the CDRS. This improvement was not accounted for by seizure improvement.
Gabapentin as Add‐On Therapy in Children with Refractory Partial Seizures: A 12‐Week, Multicentre, Double‐Blind, Placebo‐Controlled Study
Authors: Appleton Richard , Fichtner Klaus , LaMoreaux Linda , Alexander Jeannine , Halsall Gwyneth , Murray Guta , Garofalo Elizabeth ,   Gabapentin Paediatric Study Group
Published: August 2005

Summary: Purpose: To evaluate the efficacy and safety of gabapentin (Neurontin; GBP) as add‐on therapy for refractory partial seizures in paediatric patients aged 3–12 years. Methods: After a 6‐week baseline period, 247 patients (54 centres) entered a 12‐week double‐blind phase and were randomized to receive either GBP (t.i.d., titrated to 23‐35 mg/kg/day) or placebo. Seizure activity and type were recorded daily. Efficacy variables included Response Ratio (RRatio), responder rate, and percentage change in frequency (PCH) for all partial seizures; PCH and RRatio for individual types of partial seizures; and investigator and parent/guardian global assessments of seizure frequency and patient well‐being. Results: RRatio for all partial seizures was significantly lower (better) for GBP‐treated patients (p = 0.0407). Responder rate favored GBP, but the difference between treatment groups was not statistically significant. Median PCH for all partial seizures for the GBP treatment group (‐17.0%) was better than that for the placebo group (‐6.5%). Median PCH for specific seizure types showed GBP to be most effective in controlling complex partial seizures (‐35%) and secondarily generalized seizures (‐28%) when compared with placebo (‐12%, +13%, respectively). A greater percentage of GBP‐treated patients exhibited improvement according to investigator and parent/guardian global assessments, with a statistically significant difference observed in the parent/guardian global assessment of seizure‐frequency reduction (p = 0.046). Three GBP patients and one placebo patient were seizure free during the double‐blind treatment period. GBP was well tolerated. Conclusions: GBP was effective and well tolerated as an add‐on therapy for partial seizures in paediatric patients with previously drug‐resistant seizures.
Wallerian Degeneration in the Optic Radiation After Temporal Lobectomy Demonstrated In Vivo with Diffusion Tensor Imaging
Authors: Wieshmann U. C. , Symms M. R. , Clark C. A. , Lemieux L. , Franconi F. , Parker G. J. M. , Barker G. J. , Shorvon S. D. 
Published: August 2005

Summary: Purpose: Diffusion tensor imaging allows the quantitative assessment of the microstructural organization of tracts in vivo (MR tractography). We used the new technique of MR tractography to demonstrate the effects of temporal lobectomy on the optic radiation. Methods: Spatially normalised maps encoding magnitude of the bias (anisotropy) of diffusion of three patients with temporal lobe resections were compared with spatially normalised diffusion maps of 22 control subjects. All three patients were operated on for the treatment of medically intractable temporal lobe epilepsy and had a normal neurologic examination before surgery. One patient had an amygdalocorticectomy. Two patients had standard en bloc resections, one of whom developed a homonymous hemianopia after surgery. Results: In the patient with hemianopia, a significant reduction of diffusion anisotropy (greater than mean ± 2 SD) consistent with wallerian degeneration was demonstrated in the optic radiation on the side of the temporal lobectomy, extending from the temporal to the occipital lobe. In the other patient with standard en bloc resection but clinically no hemianopia, the optic radiation was only marginally affected. In the third patient (amygdalocorticectomy), the diffusion anisotropy was within the normal range in the expected position of the optic radiation. Conclusions: Our findings show that MR tractography may be a useful tool to demonstrate wallerian degeneration in the optic radiation after temporal lobectomy in patients with hemianopia. This is the first time that this new method has been applied in postoperative imaging; it enables us to visualise the morphologic correlate of dysfunctional pathways after epilepsy surgery in vivo. The potential for using MR tractography to study other aspects of epilepsy is discussed.
The Depiction of Seizures in Film
Authors: Kerson Jennie F. , Kerson Toba Schwaber , Kerson Lawrence A. 
Published: August 2005

Summary: Purpose: The purpose was to describe the depiction of epilepsy in English language film. Methods: The list of films, developed by consulting several databases, film scholars, and neurologists, includes every film suggested by any source. By using the saturation techniques of grounded theory, names of films were sought until no new names were received. All films were reviewed by an experienced board‐certified neurologist. Results: Seizures were depicted in 20 films. Generally, seizures are used in film to develop narrative or enrich character. They serve four functions: (a) a principal character has epilepsy; thus the condition is critical to character and narrative; (b) a seizure is used to drive the narrative; (c) a seizure is used to enrich a minor role; and (d) a seizure is feigned to distract attention from another activity. Conclusions: Conclusions can be drawn in four areas: character, accuracy of depiction, roles and responses of onlookers, and the place of epilepsy in the films: (a) Epilepsy is one dimension linked with other aspects of an individual to enrich character; (b) Seizures are depicted fairly accurately, but their frequent representation as uncontrollable and violent is exaggerated and out of date; (c) In the films, the onlookers' responses range from fear to taking correct measures; and (d) The presence of epilepsy is never arbitrary, but the function varies. Overall, the view of epilepsy conveyed in film continues to be distorted, sensationalized, and presented in the most frightening ways.
Chronic Epileptogenic Cellular Alterations in the Limbic System After Status Epilepticus
Authors: Coulter Douglas A. 
Published: August 2005

Summary:Status epilepticus (SE) is associated with both acute and permanent pathological sequellae. One common long term consequence of SE is the subsequent development of a chronic epileptic condition, with seizures frequently originating from and involving the limbic system. Following SE, many studies have demonstrated selective loss of neurons within the hilar region of the dentate gyrus, CA1 and CA3 pyramidal neurons. Selective loss of distinct subpopulations of interneurons throughout the hippocampus is also frequently evident, although interneurons as a whole are selectively spared relative to principal cells. Accompanying this loss of neurons are circuit rearrangements, the most widely studied being the sprouting of dentate granule cell (DGC) axons back onto the inner molecular layer of the dentate gyrus, termed mossy fiber sprouting. Less studied are the receptor properties of the surviving neurons within the epileptic hippocampus following SE. DGCs in epileptic animals exhibit marked alterations in the functional and pharmacological properties of γ‐aminobutyric acid (GABA) receptors. DGCs have a significantly elevated density of GABAA receptors in chronically epileptic animals. In addition, the pharmacological properties of GABAA receptors in post‐SE epileptic animals are quite different compared to controls. In particular, GABAA receptors in DGCs from epileptic animals show an enhanced sensitivity to blockade by zinc, and a markedly altered sensitivity to modulation by benzodiazepines. These pharmacological differences may be due to a decreased expression of α1 subunits of the GABAA receptor relative to other α subunits in DGCs of post‐SE epileptic animals. These GABAA receptor alterations precede the onset of spontaneous seizures in post‐SE DGCs, and so are temporally positioned to contribute to the process of epileptogenesis in the limbic system. The presence of zinc sensitive GABA receptors combined with the presence of zinc‐containing “sprouted” mossy fiber terminals innervating the proximal dendrites of DGCs in the post‐SE epileptic hippocampus prompted the development of the hypothesis that repetitive activation of the DG in the epileptic brain could result in the release of zine. This zinc in turn may diffuse to and block “epileptic” zinc‐sensitive GABAA receptors in DGCs, leading to a catastrophic failure of inhibition and concomitant enhanced seizure propensity in the post‐SE epileptic limbic system.
Depression in Epilepsy: Etiology, Phenomenology, and Treatment
Authors: Lambert Michelle V. , Robertson Mary M. 
Published: August 2005

Summary:A history of depression or depressive symptomatology has been reported in up to two‐thirds of patients with medically intractable epilepsy, whereas community studies have demonstrated affective disorder only in a quarter of these patients. Depression has been reported peri‐ and interictally. However, differentiation may be difficult in patients with frequent seizures. Most authors have found no correlation between depression and epilepsy variables. However, complex partial seizures, especially of temporal lobe origin, appear to be etio‐logic factors, particularly in men with left‐sided foci. Depression is also more common in patients treated with polytherapy especially with barbiturates, phenytoin, and vigabatrin. Depression has also been described de novo after temporal lobectomy. Psychosocial factors also play a part, but underlying risk factors (e.g., genetic, endocrine and metabolic) may explain the increased rates of depression in people with epilepsy compared to those with other neurologic and chronic medical conditions. The depression appears to be endogenous. Patients tend to exhibit fewer neurotic traits and more psychotic symptoms such as paranoia, delusions, and persecutory auditory hallucinations. Treatment approaches include psychotherapy, rationalization of antiepileptic drug medication, antidepressant treatment, and ECT. The tricyclic and related antidepressants appear to be epileptogenic, especially in people at high risk (personal or family history of seizures, abnormal pretreatment EEG, brain damage, alcohol or substance abuse/withdrawal and concurrent use of CNS‐active medication). Seizures tend to occur early in treatment or after dose increments, especially if rapidly titrated. There is little evidence that the newer antidepressants, e.g., selective serotonin reuptake inhibitors, moclobemide, venlafaxine, or nefazodone are more epileptogenic than placebo.
Interactions Between Anticonvulsant and Psychoactive Drugs
Authors: Monaco Francesco , Cicolin Alessandro 
Published: August 2005

Summary:This review considers the relevance of pharmaco‐kinetic interactions between antiepileptic drugs (AEDs) and psychoactive drugs in the treatment of mood disorders in patients with epilepsy. The determination of plasma levels of some of these drugs (mainly the AEDs) has enabled clinicians to evaluate the kinetic modifications during the course of such combined therapies and to adjusting the dosages in cases of subtherapeutic or toxic levels. In general, phenobarbital, phenytoin, and carbamazepine stimulate the catabolic degradation of tricyclic antidepressants (TCAs), and TCAs have an inhibitory effect on the elimination of AEDs. The newer antidepressants that selectively inhibit the reuptake of serotonin (SSRIs), although in different fashions for the different substances (fluoxetine, fluvoxamine, paroxetine) may cause an increase of plasma AED levels through inhibition of the isoenzyme P450 2D6. Similarly, antipsychotics (APs) are more rapidly metabolized when AEDs are co‐administered, whereas AED metabolism is scarcely influenced by AP. Finally, plasma levels of tranquilizers are lowered by AED co‐therapy. As the concomitant administration of AED and psychoactive drugs becomes increasingly used for treatment of mood disorders in patients with or without epilepsy, therapeutic drug monitoring may be useful in designing correct and rational therapy.
Photosensitive Epilepsy Studied by Functional Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy
Authors: Chiappa Keith H. , Hill Rosamund A. , Huang‐Hellinger Frank , Jenkins Bruce G. 
Published: August 2005

Summary:Purpose: To study metabolic and hemodynamic correlates of photic stimulation‐triggered discharges.Methods: Simultaneous EEG, functional MRI (fMRI) and magnetic resonance spectroscopy (MRS) were performed in nine patients with photosensitive epilepsy and in 12 normal subjects.Results: Prominent visual cortex activation was seen in all normal subjects and patients, and no fMRI‐registered hemodynamic abnormalities were correlated with the brief photoparoxysmal spike‐wave activity evoked in the photosensitive patients. However, irrespective of the presence of a spike‐wave response to the photic stimulation, the photosensitive patients showed four findings not seen in the normal subjects: (a) slightly, but significantly, elevated lactate levels in the occipital cortex in the resting state; (b) an increased area of visual cortical activation with photic stimulation; (c) simultaneous with the occipital cortex stimulus‐induced increased fMRI signal, there were noncontiguous areas of signal attenuation most prominent in perirolandic regions; and (d) a marked decrement (undershoot) of fMRI signal intensity immediately after the photic stimulation in the occipital cortex and in the region of the posterior cingulate gyrus.Conclusions: These findings suggest abnormal interictal metabolism and increased vascular reactivity in the photosensitive patients.
Mechanisms of Video‐Game Epilepsy
Authors: Fylan F. , Harding G. F. A. , Edson A. S. , Webb R. M. 
Published: August 2005

Summary:Purpose: We aimed to elucidate the mechanisms underlying video‐game epilepsy by comparing the flicker‐ and spatial‐frequency ranges over which photic and pattern stimulation elicited photoparoxysmal responses in two different populations: (a) 25 patients with a history of seizures experienced while playing video games; and (b) 25 age‐ and medication‐matched controls with a history of photosensitive epilepsy, but no history of video‐game seizures.Methods: Abnormality ranges were determined by measuring photoparoxysmal EEG abnormalities as a function of the flicker frequency of patterned and diffuse intermittent photic stimulation (IPS) and the spatial frequency of patterns on a raster display.Results: There was no significant difference between the groups in respect of the abnormality ranges elicited by patterned or diffuse IPS or by spatial patterns. When the groups were compared at one specific IPS frequency (‐50 Hz), however, the flicker frequency of European television displays, the video‐game patients were significantly more likely to be sensitive.Conclusions: The results suggest that video‐game seizures are a manifestation of photosensitive epilepsy. The increased sensitivity of video‐game patients to IPS at 50 Hz indicates that display flicker may underlie video‐game seizures. The similarity in photic‐ and pattern‐stimulation ranges over which abnormalities are elicited in video‐game patients and controls suggests that all patients with photosensitive epilepsy may be predisposed toward video‐game‐induced seizures. Photosensitivity screening should therefore include assessment by using both IPS at 50 Hz and patterns displayed on a television or monitor with a 50‐Hz frame rate.