bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frovatriptan: A Review of Drug‐Drug Interactions
Authors: Buchan P. , Wade A. , Ward C. , Oliver S.D. , Mfpm  , Stewart A.J. , Freestone S. 
Published: March 2003

Objective.—To investigate the potential for interactions involving drugs likely to be coadministered with frovatriptan.Background.—Frovatriptan is a new 5‐hydroxytryptamine (5‐HT)1B/1D agonist. Preclinical data suggest that the pharmacokinetic and pharmacological profile of frovatriptan may differ from that of the currently available triptans.Methods.—The potential for interactions between frovatriptan and other drugs was investigated using in vitro methods, studies in healthy volunteers, and retrospective analysis of data from phase I trials.Results.—In vitro, frovatriptan was principally metabolized by cytochrome P‐450 (CYP) 1A2 but was found not to be an inhibitor or inducer of this or other CYP isoenzymes. Frovatriptan was only a weak inhibitor of monoamine oxidase at very high concentrations in vitro and was not a substrate for this enzyme (unlike some other triptans). Coadministration with moclobemide, at doses known to inhibit monoamine oxidase‐A, did not affect the pharmacokinetics of frovatriptan. Binding to plasma proteins was low (15%), and binding to erythrocytes was moderate (60%) and unlikely to be a source of interaction with other drugs. The pharmacokinetics of frovatriptan were not affected by moderate alcohol intake. There were slight increases in area under the curve and maximum concentration on concomitant administration with the combined oral contraceptives, propranolol, and fluvoxamine; and slight decreases in these parameters on concomitant administration with ergotamine and in tobacco smokers; these findings were considered to have no clinical significance in view of frovatriptan's large therapeutic index (well tolerated at doses ranging from 2.5 to 40 mg). These effects can be attributed primarily to modification of CYP1A2 activity but their impact is limited, probably due to frovatriptan also undergoing renal clearance and the likely role of blood cell binding in controlling the amount of unbound drug available for elimination.Conclusions.—Because it has no inhibitory or inducing effect on CYP isoenzymes and is only slightly bound to plasma proteins, it is unlikely that frovatriptan will alter the pharmacokinetics of concomitantly administered drugs. Frovatriptan, therefore, appears to have a low risk of interaction with other drugs, and adjustments of dose are unlikely to be required when it is coadministered with other agents.
Spectrum of Clinical and Histopathologic Responses to Intracranial Electrodes: From Multifocal Aseptic Meningitis to Multifocal Hypersensitivity‐type Meningovasculitis
Authors: Stephan Christina L. , Kepes John J. , SantaCruz Karen , Wilkinson Steven B. , Fegley Barbara , Osorio Ivan 
Published: March 2003

Summary:  Purpose: We sought to characterize and compare the histopathologic and clinical changes elicited by subdural and depth electrodes in subjects undergoing epilepsy surgery evaluation.Methods: A retrospective review of clinical records, imaging and histopathologic studies of epilepsy surgery cases requiring subdural strips and depth electrodes for localization of epileptogenic tissue was performed between 1993 and1999. Forty‐nine subjects had a combination of subdural and depth, whereas 10 had depth electrodes only. Histopathologic changes were classified as mild, moderate, or severe based on the density, extent, and composition of the inflammatory infiltrate.Results: Subdural electrodes induced a clinical picture of transient aseptic meningitis; histopathologically, the infiltrates were moderate in degree in the majority (73%) and severe in the remainder (27%), with T cells and eosinophils infiltrating the cortex and arteriolar walls (hypersensitivity‐type response). Depth electrodes alone caused minimal or no symptoms of meningeal irritation; the cellular response elicited by these electrodes was mild in five and moderate in the remaining five cases; severe inflammation was not observed in this group. Although the proportion of small clinically silent hematomas was larger in cases with depth (five of 59) compared with subdural electrodes (one of 49), microhemorrhages were considerably more numerous with subdural than with depth electrodes.Conclusions: These results suggest that the spectrum of brain responses to foreign bodies is wide, ranging from self‐limited physiologic to hypersensitivity‐type reactions of varying severity. Subdural strips elicited more intense inflammation than did depth electrodes. The histopathologic extent of the reaction to either type of electrodes could not be precisely defined because of the retrospective nature of this study. History of allergy to latex or previous craniotomies are probable risk factors for the hypersensitivity‐type reaction. Surgical outcome, excellent in the majority, was independent of the severity or type of inflammation, and there have not been neurologic or systemic sequelae.
Transient Dystonias in Three Patients Treated with Tiagabine
Authors: Wolańczyk Tomasz , Grabowska–Grzyb Ałbena 
Published: March 2003

Summary:  Purpose: Tiagabine (TGB) is a new antiepileptic drug (AED) with γ‐aminobutyric acid (GABA)ergic mechanism of action. GABAergic compounds may influence the extrapyramidal system, probably via modulation of dopaminergic nigrostriatal neurons. A well‐known side effect of TGB is probably dose‐related extrapyramidal tremor. To our knowledge, acute dystonias associated with TGB treatment have yet to be described.Methods: Three patients with transient acute dystonic reactions while taking TGB as add‐on therapy with carbamazepine (CBZ) are presented. The focal limb dystonia in one case, an oromandibular dystonia in second, and writer's cramp in third one were observed.Results: In all cases dystonic movements resolved spontaneously without discontinuation of TGB therapy and without any concomitant treatment.Conclusions: Tiagabine may cause various mild extrapyramidal side effects. All three cases reported were diagnosed with transient possibly drug‐related dystonia after increase in TGB dose. It remain unclear whether dystonic movements are specific for patients treated with TGB/CBZ bitherapy.
Carnitine Levels and the Ketogenic Diet
Authors: Berry‐Kravis Elizabeth , Booth Gayle , Sanchez Ana Carolina , Woodbury‐Kolb Jean 
Published: March 2003

Summary: Purpose:To determine the long‐term effect of the ketogenic diet (KD) on carnitine levels and whether carnitine depletion is a significant cause of clinical complications during KD initiation or treatment.Methods:Carnitine levels at 0, 1, 6, 12, and 24 months of diet treatment, carnitine antiepileptic drug (AED) history, lowest blood glucose and time to achieve ketosis during diet initiation, and diet complications were analyzed for 38 consecutive patients who initiated the KD from May 1997 to March 2000. Carnitine levels at follow‐up were analyzed for eight patients started on the diet before to May 1997.Results:Total carnitine (TC) at diet initiation correlated negatively with the number of AEDs at diet initiation but not with number of past AEDs, lowest blood glucose, or time to ketosis. TC decreased in the first months of diet treatment and then stabilized or increased slightly with long term treatment. Only 19% of patients were supplemented with carnitine for low TC. No patient showed clinical signs of carnitine deficiency.Conclusions:Multiple AED exposure lowers TC, but actual TC deficiency in patients initiating the KD is not common, and TC levels do not appear to predict hypoglycemia or problems achieving ketosis. Mild carnitine depletion may occur early in KD treatment and occasionally TC decreases out of the normal range, without clinical symptoms. TC stabilizes or increases back toward baseline with long‐term treatment, and most patients do not require carnitine supplementation.
Alfentanil‐Induced Epileptiform Activity: A Simultaneous Surface and Depth Electroencephalographic Study in Complex Partial Epilepsy
Authors: Ross J. , Kearse L. A. , Barlow M. K. , Houghton K. J. , Cosgrove G. R. 
Published: March 2003

Summary:  Purpose: Alfentanil is a high potency mu opiate receptor agonist commonly used during presurgical induction of anesthesia. This and other opiate receptor agonists have demonstrated proconvulsant effects in animals, but these properties have been less consistently demonstrated in humans. Most human scalp EEG studies have failed to demonstrate induction of epileptiform activity with these agents, which is inconsistent with findings using intracranial EEG. Simultaneous scalp and depth EEG recordings have yet to be performed in this setting. The relationship between opiate dose and proconvulsant activity is unclear.Methods: Simultaneous scalp and depth electrode recordings were performed on five patients with complex partial epilepsy (CPE) who underwent alfentanil anesthesia induction before depth electrode removal. Consecutive equal bolus doses of alfentanil were administered to each patient according to strict time intervals so as to assess their correlation with any induced epileptiform activity.Results: Epileptiform activity was induced by alfentanil in three of five patients. Two of these patients had electrographic seizures. Epileptiform activity was only detected from the depth electrodes, occurring within 2 min of the first bolus dose in all three cases. Further increase or spread of epileptiform activity did not occur despite cumulative bolus doses of alfentanil.Conclusions: Alfentanil is proconvulsant in patients with CPE. Induced seizures may be subclinical and lack a scalp EEG correlate. There is a complex dose–response relationship. Alfentanil induction of anesthesia should be approached with caution in patients with CPE.
Impaired Motor Function in Patients with Psychogenic Pseudoseizures
Authors: Sackellares Dalma Kalogjera , Sackellares J. Chris 
Published: March 2003

Summary:  Purpose: To evaluate motor speed and grip strength in patients with well‐documented psychogenic pseudoseizures.Methods: We analyzed manual motor speed and grip strength in a group of 40 patients with confirmed psychogenic pseudoseizures (without evidence of concomitant epilepsy) and a group of 40 normal controls matched for handedness and gender, and of comparable age. The two groups were compared with respect to manual motor performance with the dominant hand, nondominant hand, and asymmetry between the dominant and nondominant hands. For the patient sample, we reviewed the neurologic history.Results: Patients with pseudoseizures performed more poorly than controls with both dominant and nondominant hands. In addition, pseudoseizure patients failed to demonstrate the dominant‐hand advantage observed in the normal control subjects on both tasks. The patient group had a high incidence of head trauma and other antecedent neurologic risk factors, and the proportion of left‐handers was 3 times higher than expected.Conclusions: Bilaterally reduced motor speed and grip strength, reduced intermanual performance asymmetry, the high percentage of left‐handers, and historical evidence of antecedent insults to the brain indicate that frontal lobe impairment may be common in patients with psychogenic pseudoseizures.
Vagus Nerve Stimulation in Children with Refractory Seizures Associated with Lennox–Gastaut Syndrome
Authors: Frost Michael , Gates John , Helmers Sandra L. , Wheless James W. , Levisohn Paul , Tardo Carmelo , Conry Joan A. 
Published: March 2003

Summary:  Purpose: Vagus nerve stimulation (VNS) is approved for use for refractory partial seizures. Nevertheless, information regarding VNS therapy for special populations, including Lennox–Gastaut syndrome (LGS) is limited. We discuss the effectiveness, tolerability, and safety of VNS therapy in patients with LGS.Methods: A six‐center, retrospective study evaluated the effectiveness of VNS therapy in patients with LGS at 3 and 6 months and compared preimplant and postimplant seizure frequency. Adverse effects and quality of life (QOL) were included as secondary measures.Results: Fifty patients, median age 13 years, with medically refractory epilepsy, were implanted. Median age at onset of seizures was 1.4 years, and a median of nine anticonvulsants (AEDs) had been tried before implantation. Data‐collection forms were designed for retrospectively gathering data on each patient's preimplant history, seizures, implants, device settings, QOL, and adverse events. Median reductions in total seizures were 42% at 1 month, 58.2% at 3 months, and 57.9% at 6 months. The most common adverse events reported were voice alteration and coughing during stimulation. Other uncommon adverse events included increased drooling and behavioral changes. Investigators noted that QOL had improved for some patients in the study.Conclusions: VNS is an effective treatment for medically refractory epilepsy in LGS. This treatment is well tolerated, safe, and may improve QOL.
Levetiracetam Psychosis in Children with Epilepsy
Authors: Kossoff Eric H. , Bergey Gregory K. , Freeman John M. , Vining Eileen P. G. 
Published: March 2003

Summary: Purpose:Levetiracetam is a new anticonvulsant (AED) with a novel mechanism of action. Although it is generally well tolerated with a good cognitive profile, irritability and hostility have been reported in some adults taking levetiracetam. Observations in children are limited; levetiracetam is not yet approved by the Food and Drug Administration for use in children.Methods:In four young patients, acute psychosis developed within days to months of initiation of levetiracetam for seizures.Results:A 5‐year‐old girl began having visual hallucinations of spiders in her room 14 days after starting levetiracetam. A 13‐year‐old boy began having auditory hallucinations, insomnia, and screaming behavior 3 months after initiation of levetiracetam. A 16‐year‐old girl became acutely agitated, hyperreligious, and had persecutory delusions within 7 days of starting levetiracetam. A 17‐year‐old girl had auditory hallucinations telling her to sing and yell after 30 days of taking the drug. All four children had dramatic improvement within days of either discontinuing or decreasing the dose of levetiracetam. The three adolescents had historical findings consistent with mild behavioral problems before initiating levetiracetam, and all four patients had prior cognitive deficits.Conclusions:Reversible treatment‐emergent psychosis associated with levetiracetam therapy was observed in four children and adolescents. Whether rapid initiation or prior neurobehavioral problems predispose to this side effect is not established.
Induction of Hypersensitivity to a Previously Tolerated Antiepileptic Drug by a Second Antiepileptic Drug
Authors: Klassen B. D. , Sadler R. M. 
Published: March 2003

Summary: Purpose:To describe the induction of hypersensitivity to one antiepileptic drug (AED) by a second AED.Methods:Case report and review of the relevant literature.Results:A patient is reported who was treated with phenytoin (PHT) for 6 months without adverse effect, but developed a hypersensitivity reaction with rash, fever, elevated liver enzymes, lymphadenopathy, and colitis 6 weeks after the introduction of carbamazepine (CBZ). PHT and CBZ were discontinued. Seizures continued despite treatment with valproic acid and clobazam. A decision was made to cautiously reintroduce PHT. Diffuse skin rash and pharyngitis appeared after two doses of PHT.Conclusions:The AED hypersensitivity syndrome has been thought to occur as a consequence of preexisting pharmacogenetic and immunologic abnormalities. Our case demonstrates induction of hypersensitivity to an AED that had been formerly well tolerated, after a hypersensitivity reaction to another AED. This is distinct from simple cross‐reactivity between one or more drugs. Such induction of hypersensitivity with AEDs has not been previously described.
Functional MRI of Language Processing: Dependence on Input Modality and Temporal Lobe Epilepsy
Authors: Carpentier A. , Pugh K. R. , Westerveld M. , Studholme C. , Skrinjar O. , Thompson J. L. , Spencer D. D. , Constable R. T. 
Published: March 2003

Summary:  Purpose: Functional magnetic resonance imaging (MRI) using two language‐comprehension tasks was evaluated to determine its ability to lateralize language processing and identify regions that must be spared in surgery.Methods: Two parallel cognitive language tasks, one using auditory input and the other visual input, were tested in a group of control subjects and in temporal lobe epilepsy patients who were candidates for surgical intervention. The patient studies provide an opportunity to compare functional MRI language localization with that obtained using Wada testing and electrocorticography. All of the patients in this study underwent all three procedures and a battery of neuropsychological testing. Such studies provide an opportunity not only to validate the fMRI findings but also, by comparing the patient results with those obtained in control subjects, to provide insight into the impact of a pathology such as epilepsy on cortical organization or functional patterns of activation.Results: The results reveal both modality‐dependent and modality‐independent language‐processing patterns for visual versus auditory task presentation. The visual language task activated distinct sites in Broca's area, BA (Brodmann area) 44 that were not activated in the auditory language task. The auditory language task strongly activated contralateral right BA22‐21 area (homologous to Wernicke's area on the left). Language lateralization scores were significantly stronger for visual than for auditory task presentation. The conjunction of activation from the two different input modalities (modality‐independent areas) likely highlights regions that perform more abstract computations (e.g., syntactic or pragmatic processing) in language processing. Modality‐specific areas (e.g., right Wernicke, left fusiform gyrus, Broca BA44, supramarginal gyrus), appear to cope with the computations relevant to making contact with these more abstract dimensions. Patients showed recruitment of contralateral homologous language areas (p < 0.005) that was significantly above that found in a normal control group. Extra‐ and intraoperative cortical stimulations were concordant with the fMRI data in eight of 10 cases. The fMRI lateralization scores were also consistent with the Wada testing in 8/10 patients.Conclusions: The fMRI results demonstrate that the epileptic brain may be a progressive model for cortical plasticity.
Myoclonus in Epilepsy Patients with Anticonvulsive Add‐On Therapy with Pregabalin
Authors: Huppertz Hans‐Jürgen , Feuerstein Thomas J. , Schulze‐Bonhage Andreas 
Published: March 2003

Summary:  Purpose: To report on the occurrence of myoclonus in patients receiving pregabalin (PGB) for the treatment of focal epilepsy.Methods: Clinic records of 19 patients who were consecutively enrolled at a tertial referral epilepsy center in a randomized, double‐blind and/or open add‐on study with PGB were reviewed.Results: In four patients treated with PGB, focal myoclonus newly developed. The side effect appeared with PGB doses of 50–600 mg/day; the intensity showed some dose dependency. All patients had medically refractory focal epilepsy and received other antiepileptic drugs (AEDs) besides the study medication. One patient showed focal myoclonic jerks of the left arm, whereas the other patients developed multifocal myoclonus. Polygraphic studies including electromyogram (EMG)‐triggered back‐averaging of the EEG in the patient with the highest frequency of myoclonic jerks showed no visible correlate of the myoclonus. In this patient, frequency and intensity of myoclonic jerks significantly decreased after dose reduction of PGB. In the other cases, myoclonus was only subtle and did not significantly interfere with daily activities, so that a dose reduction of PGB was not considered necessary.Conclusions: These data indicate a relatively high incidence (four of 19) of myoclonus associated with PGB therapy. The rate seems to be at least as high as reported in patients receiving the structurally similar anticonvulsant gabapentin.
Effect of Vagal Nerve Stimulation on Interictal Epileptiform Discharges: A Scalp EEG Study
Authors: Kuba Robert , Guzaninová Markéta , Brázdil Milan , Novák Zdenĕk , Chrastina Jan , Rektor Ivan 
Published: March 2003

Summary:  Purpose: To investigate the effects of acute vagal nerve stimulation (VNS) on interictal epileptiform discharges (IEDs).Methods: Fifteen epilepsy patients, all of whom had been treated with VNS for ≥6 months, entered the study. In each subject, the absolute number of IEDs was counted at the baseline period (BP), the stimulation period (SP), six interstimulation periods (IPs), and the prestimulation period (PP), by using an original paradigm. The number of IEDs at the BP and the PP was compared with the number of IEDs at the SP and IPs. The results were correlated with other variables (the duration of VNS, the value of the output current, the duration of epilepsy, the type of epilepsy, the effect of VNS, and the effect of extrastimulation).Results: We observed a significantly higher reduction in the number of IEDs in the SP and all the IPs as compared with the BP. We noticed a significantly higher reduction in the number of IEDs in the SP and in the first IP as compared with the PP. The reduction of IEDs was greater in patients who responded to VNS (>50% reduction of all seizures) and in patients who responded positively to magnetic extrastimulation. There were no other significant results in the reduction of IEDs when comparing other variables.Conclusions: Short‐term VNS reduces IEDs significantly. The reduction is most prominent during the SP (i.e., when the pulse generator is active). The value of reduction of IEDs is higher in patients who respond to VNS and in patients with positive experiences with magnetic extrastimulation. These results can be useful in predicting the effect of VNS.
Reduced Extrahippocampal NAA in Mesial Temporal Lobe Epilepsy
Authors: Mueller Susanne G. , Suhy Joyce , Laxer Kenneth D. , Flenniken Derek L. , Axelrad Jana , Capizzano Andres A. , Weiner Michael W. 
Published: March 2003

Summary:  Purpose: Structural and metabolic abnormalities in the hippocampal region in medial temporal lobe epilepsy (mTLE) are well described; less is known about extrahippocampal changes. This study was designed to characterize extrahippocampal metabolic abnormalities in mTLE with magnetic resonance spectroscopy in combination with tissue segmentation and volumetry of gray and white matter.Methods: Multislice magnetic resonance spectroscopic imaging (1H‐MRSI) in combination with tissue segmentation was performed on 16 patients with mTLE and 12 age‐matched healthy volunteers. The data were analyzed by using a regression‐analysis model that estimated the metabolite concentrations in 100% cortical gray and 100% white matter in the frontal lobe and nonfrontal brain. The segmented image was used to calculate the fraction of gray and white matter in these regions.Results: mTLE had significantly lower N‐acetyl aspartate (NAA) in ipsi‐ and contralateral frontal gray (p = 0.03) and in ipsi‐ and contralateral nonfrontal white matter (p = 0.008) compared with controls. Although there were no associated volumetric deficits in frontal gray and white matter, ipsilateral nonfrontal gray matter (p = 0.003) was significantly smaller than that in controls.Conclusions: mTLE is associated with extrahippocampal metabolic abnormalities and volumetric deficits, but these do not necessarily affect the same regions.