bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the Cause of Localisation‐Related Epilepsy Influence the Response to Antiepileptic Drug Treatment?
Authors: Stephen Linda J. , Kwan Patrick , Brodie Martin J.
Published: March 2003

Summary: Purpose: We investigated the response to antiepileptic drug (AED) therapy in patients with localisation‐related epilepsy associated with different underlying causes.

Methods: Five hundred and fifty adolescent and adult patients who had partial epilepsy treated with AEDs and who had undergone magnetic resonance imaging of brain were followed up prospectively from 1984 at a single centre. More than 70% were newly diagnosed. None had had epilepsy surgery.

Results: Three hundred and twelve (57%) patients had been seizure free at their last clinic visit for at least a year. Patients with mesial temporal sclerosis (MTS; n = 73, 42% seizure free) were less likely to be controlled (p < 0.01) than were those with arteriovenous malformation (AVM; n = 14, 78%), cerebral infarction (n = 46, 67%), primary tumour (n = 35, 63%), cortical gliosis (n = 81, 57%), cerebral atrophy (n = 49, 55%), and cortical dysplasia (CD; n = 63, 54%). Among the seizure‐free patients, those with MTS were more likely to require more than one AED compared with those with other aetiologies (48 vs. 35%; p < 0.05). There was no difference in outcome between patients with symptomatic and cryptogenic epilepsy (n = 361, 58% vs. n = 189, 56% seizure free, respectively). Patients with MTS, CD, and cryptogenic epilepsy were more likely (p = 0.02) to have a family history of epilepsy than were the other groups. MTS patients also had a higher incidence of febrile convulsions (p < 0.001).

Conclusions: The majority of patients with focal‐onset epilepsy became seizure free on AED treatment. MTS‐related seizures had the worst prognosis. Although many patients with this pathology may benefit from epilepsy surgery, a considerable number will be controlled with AED therapy.
Operative Results without Invasive Monitoring in Patients with Frontal Lobe Epileptogenic Lesions
Authors: Mariottini A. , Lombroso C. T. , DeGirolami U. , Fois A. , Buoni S. , DiTroia A. M. , Farnetani M. A. , Palma L. , Zalaffi A. , Black P. McL.
Published: March 2003

Summary:  Purpose: To further explore the still controversial issues regarding whether all or most candidates for epilepsy surgery should be investigated preoperatively with invasive long‐term video‐EEG monitoring techniques (ILTVE).

Methods: We studied five patients with intractable seizures since early childhood using the same protocol: clinical evaluation, magnetic resonance imaging (MRI) with fluid‐attenuated inversion recovery (FLAIR) sequences, long‐term video‐EEG (LTVE) monitoring with scalp electroencephalogram (EEG), interictal single photon emission computed tomography (SPECT), positron emission tomography (PET), and neuropsychological testing. The patients' seizures had clinical features suggesting a frontal lobe (FL) origin. MRI scans revealed focal cortical dysplasia (CD) in four patients and a probable gliotic lesion in the fifth. The findings in both PET and SPECT images were congruent with those of the MRI. Scalp LTVE failed to localize the ictal onset, although the data exhibited features suggestive of both CDs and FL seizures. On the basis of these results, surgery was performed with intraoperative corticography, and the cortical area exhibiting the greatest degree of spiking was ablated.

Results: Histopathologic study of four of the resected specimens confirmed the presence of CD, whereas in the fifth, there were features consistent with a remote encephaloclastic lesion. There were no postoperative deficits. Seizures in three of the patients were completely controlled at 2–3.5 years of follow‐up; a fourth patient is still having a few seizures, which have required reinstitution of pharmacotherapy, and the fifth has obtained 70% control. All patients have had significant improvement in psychosocial measures. For comparison, five patients with generally similar clinical and neuroradiologic features to the previous group underwent preoperative ILTVE monitoring. The surgical outcomes between the two groups have not differed significantly.

Conclusions: We conclude that patients with FL epilepsies may be able to undergo successful surgery without preoperative ILTVE monitoring, provided there is high concordance between neuroimaging tests (MRI, SPECT, PET) and the seizure phenotypes, even when routine EEGs and scalp LVTE fail to localize ictal onset unambiguously. The surgical outcomes of these patients generally paralleled those of the other subjects who also had FL epilepsy but who were operated on only after standard ILTVE monitoring.
Generalized Convulsions After Consuming a Large Amount of Gingko Nuts
Authors: Miwa Hideto , Iijima Makiko , Tanaka Shigeki , Mizuno Yoshikuni
Published: March 2003

Summary: We report a 36‐year‐old woman, without any past or family histories of epilepsy, who presented frequent vomiting and generalized convulsions. About 4 h before the convulsion, she had consumed ∼70–80 gingko nuts, seeds of Gingko biloba, in an attempt to improve her health. It is important to know that convulsion may be induced if a large amount of gingko nuts is consumed. The neurotoxicity of gingko nuts, particularly their convulsion‐inducing effect, should be recognized.
Association of Fear Auras with Mood and Anxiety Disorders After Temporal Lobectomy
Authors: Kohler Christian G. , Carran Melissa A. , Bilker Warren , O'Connor Michael J. , Sperling Michael R.
Published: March 2003

Summary:  Purpose: Epilepsy has been associated with increased occurrence of behavioral disorders. Auras reflect abnormal stimulation of brain areas in close proximity to regions from which clinical seizures originate. The purpose of our study was to investigate whether fear auras are associated with a higher rate of mood and anxiety disorders before and 1 year after temporal lobectomy.

Methods: Twenty‐two patients with fear auras were compared with matched groups with other auras and no auras. Neurologic and neuropsychological evaluations before, 1–2 months after, and 1 year after temporal lobectomy were reviewed for mood and anxiety disorders and psychotropic medication treatment. A logistic regression model examined effects of patient group and psychiatric status on postoperative psychiatric status.

Results: The majority of patients in the three groups experienced mood and anxiety disorders before surgery. Mood and anxiety disorders declined in the control, but not in the fear aura group after surgery. Presence of auras at 1 year after surgery was not related to psychiatric outcome. Postoperative mood and anxiety disorders were more common in patients with persistence of seizures and in those in the fear group who were seizure free. The minority of patients in all groups underwent psychotropic treatment before surgery, but the majority with fear auras underwent treatment after surgery.

Conclusions: Postoperative mood and anxiety disorders were more common in fear aura patients after temporal lobectomy, in particular, if seizure free. Possible mechanisms include the role of the amygdala in fear conditioning, the concepts of forced normalization, and kindling.
Sodium Methohexital (Brevital) as an Anesthetic in the Wada Test
Authors: Buchtel Henry A. , Passaro Erasmo A. , Selwa Linda M. , Deveikis John , Gomez‐Hassan Diana
Published: March 2003

Summary:  Purposes: We report our experience with sodium methohexital (Brevital) as an anesthetic used in the Wada test for language and memory in 86 epilepsy surgery patients (173 procedures).

Methods: The methods are compared with those of the more commonly used anesthetic sodium amobarbital (Amytal).

Results: Despite differences between the methohexital and amobarbital test protocols, the behavioral and neurologic effects of the two anesthetics are similar. Because of the brief duration of methohexital, two successive injections are made on each side rather than one, to lengthen the time available for testing both language and memory. Behavioral and EEG indices return to baseline more quickly and more completely with methohexital than with amobarbital, allowing several repetitions of the procedure without incremental drowsiness, and the total time taken for the procedure is less with methohexital than with amobarbital.

Conclusions: The results of language and memory testing in the Wada test are equivalent for amobarbital and methohexital, except that methohexital has a briefer duration of action and is associated with less sedation.
Magnetic Resonance Imaging in the Study of the Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Adult Rats
Authors: Roch Catherine , Leroy Claire , Nehlig Astrid , Namer Izzie J.
Published: March 2003

Summary:  Purpose: In temporal lobe epilepsy, it remains to be clarified whether hippocampal sclerosis is the cause or the consequence of epilepsy. We studied the temporal evolution of the lesions in the lithium–pilocarpine model of epilepsy in the rat with magnetic resonance imaging (MRI) to determine the progressive morphologic changes occurring before the appearance of chronic epilepsy.

Methods: MRI was performed on an MR scanner operating at 4.7 T. We followed the evolution of lesions using T2‐ and T1‐weighted sequences before and after the injection of gadolinium from 2 h to 9 weeks.

Results: At 2 h after status epilepticus (SE), a blood–brain barrier breakdown could be observed only in the thalamus; it had disappeared by 6 h. At 24 h after SE, edema was present in the amygdala and the piriform and entorhinal cortices together with extensive neuronal loss; it disappeared progressively over a 5‐day period. During the chronic phase, a cortical signal reappeared in all animals; this signal corresponded to gliosis, which appeared on glial fibrillary acidic protein (GFAP) immunohistochemically stained sections as hypertrophic astrocytes with thickened processes. In the hippocampus, the correlation between histopathology and T2‐weighted signal underscored the progressive constitution of atrophy and sclerosis, starting 2 days after SE.

Conclusions: These data show the reactivity of the cortex that characterizes the initial step leading to the development of epilepsy and the late gliosis that could result from the spontaneous seizures. Moreover, it appears that hippocampal sclerosis progressively worsened and could be both the cause and the consequence of epileptic activity.
Chronic Anterior Thalamus Stimulation for Intractable Epilepsy
Authors: Hodaie Mojgan , Wennberg Richard A. , Dostrovsky Jonathan O. , Lozano Andres M.
Published: March 2003

Summary:  Purpose: A significant number of patients with epilepsy remain poorly controlled despite antiepileptic medication (AED) treatment and are not eligible for resective surgery. Novel therapeutic methods are required to decrease seizure burden in this population. Several observations have indicated that the anterior thalamic region plays an important role in the maintenance and propagation of seizures. We investigated neuromodulation of the anterior thalamus by using deep‐brain stimulation (DBS) in patients with intractable seizures.

Methods: Five patients with medically refractory epilepsy underwent stereotactic placement of and received stimulation through bilateral DBS electrodes in the anterior thalamus.

Results: Treatment showed a statistically significant decrease in seizure frequency, with a mean reduction of 54% (mean follow‐up, 15 months). Two of the patients had a seizure reduction of ≥75%. No adverse effects were observed after DBS electrode insertion or stimulation. Unexpectedly, the observed benefits did not differ between stimulation‐on and stimulation‐off periods.

Conclusions: DBS of the anterior thalamus is a safe procedure and possibly effective in patients with medically resistant seizures.
Interictal and Ictal EEG Activity in the Basal Ganglia: An SEEG Study in Patients with Temporal Lobe Epilepsy
Authors: Rektor Ivan , Kuba Robert , Brázdil Milan
Published: March 2003

Summary:  Purpose: The interictal and ictal EEG activity in the basal ganglia in patients with temporal lobe epilepsy were studied during invasive EEG monitoring.

Methods: Eight epilepsy surgery candidates, each with a proven mesiotemporal seizure‐onset zone, participated in the study. We used two invasive EEG methods to determine the seizure‐onset zone. In both methods, diagonal electrodes were targeted into the amygdalohippocampal complex via a frontal approach and were passed through the basal ganglia with several leads. We analyzed 16 partial epileptic seizures, four of which became secondarily generalized.

Results: No epileptic interictal or ictal discharges were noticed in the basal ganglia. The interictal activity in the basal ganglia was a mixture of low‐voltage beta activity and medium‐voltage alpha–theta activity. When the ictal paroxysmal activity remained localized to the seizure‐onset zone, the activity of the basal ganglia did not change. The spread of epileptic activity to other cortical structures was associated with the basal ganglia EEG slowing to a theta–delta range of 3–7 Hz. This slowing was dependent on the spread of ictal discharge within the ipsilateral temporal lobe (related to the investigated basal ganglia structures); alternatively, the slowing occurred in association with the regional spread of ictal activity from the mesiotemporal region to the temporal neocortex contralaterally to the investigated basal ganglia. Secondary generalization was associated with a further slowing of basal ganglia activity.

Conclusions: The basal ganglia do not generate specific epileptic EEG activity. Despite the absence of spikes, the basal ganglia participate in changing or reflect changes in the distribution of the ictal epileptic activity.
Randomized Double‐blind Parallel‐group Study Comparing Cognitive Effects of a Low‐dose Lamotrigine with Valproate and Placebo in Healthy Volunteers
Authors: Aldenkamp A. P. , Arends J. , Bootsma H. P. R. , Diepman L. , Hulsman J. , Lambrechts D. , Leenen L. , Majoie M. , Schellekens A. , De Vocht J.
Published: March 2003

Summary:  Purpose: This study aimed at investigating the cognitive and mood effects of lamotrigine (LTG) versus valproate (VPA) and placebo (PBO).

Methods: By studying the effects in healthy volunteers, it is possible to separate the genuine effects of LTG from the cognitive improvements, caused by better seizure control. The study used a pretest–posttest comparison of 50 mg LTG, 900 mg VPA, or PBO in a double‐blind single‐dummy parallel‐group design with 30 healthy volunteers. Study duration was 12 days (with a last control on day 13). Outcome measures included cognitive tests (FePsy neuropsychological test battery), mood scales (ASL; mood‐rating scale), and a scale for subjective complaints (ABNAS Neurotoxicity scale). Total sleep time was controlled with actigraphic recordings. The results were analyzed by comparing the change over time (pretest with posttest) for the three treatments with Student's t tests.

Results: Cognitive tests: significant differences between the treatments were found for measurements of cognitive activation (i.e., three of the four simple reaction‐time measurements showed statistically significant differences in change between PBO and LTG in favor of LTG (p = 0.03; 0.03; 0.04); two of four tests showed statistically significant differences in change between LTG and VPA, both in favor of LTG (p = 0.03; 0.05). Subjective complaints: the ABNAS‐neurotoxicity scale reveals a significant reduction of drug‐related cognitive complaints for the subjects taking LTG, relative to VPA (p = 0.02). Mood rating: significant changes were found on the scale assessing “tiredness,” showing increased tiredness/sedation for VPA relative to PBO (p = 0.02) and on the “timid scale” for LTG reporting “being more at ease” compared with both PBO and VPA (p = 0.02; 0.02). The general direction of change for the mood scales was toward “activation” for LTG (five of six scales improved), whereas for VPA, the reverse effect was found (four of six scales showed a change in the direction of “tiredness/sedation”).

Conclusions: Short‐term treatment in normal volunteers with a low dose of LTG resulted in improved cognitive activation on simple reaction‐time measurements, a more positive subjective report about the impact of drug treatment relative to VPA, and mood changes concurring with the activating effect demonstrated by the cognitive tests.
Mutational Analysis of Nicotinic Acetylcholine Receptor β2 Subunit Gene (CHRNB2) in a Representative Cohort of Italian Probands Affected by Autosomal Dominant Nocturnal Frontal Lobe Epilepsy
Authors: Duga Stefano , Asselta Rosanna , Bonati Maria Teresa , Malcovati Massimo , Dalprà Leda , Oldani Alessandro , Zucconi Marco , Ferini‐Strambi Luigi , Tenchini Maria Luisa
Published: March 2003

Summary: Twenty‐four autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) probands were analyzed for the presence of V287L and V287M mutations in the CHRNB2 gene, which have been recently associated with the disease. In all patients, the involvement of the two additional loci reported as being associated with ADNFLE (CHRNA4 gene and chromosome 15q24 region) had been previously excluded. Mutational screening was performed by sequencing a polymerase chain reaction–amplified CHRNB2 DNA fragment, spanning the whole exon 5, which contains the V287L and V287M mutations and codes for ∼65% of the mature protein. In none of the patients were mutations in the analyzed region of CHRNB2 found. These data, obtained in the largest ADNFLE cohort so far analyzed, demonstrate the rarity of the identified CHRNB2 mutations in ADNFLE patients.
Voltage‐gated Sodium Channels in Epilepsy
Authors: Köhling Rüdiger
Published: March 2003

Summary: Animal experiments, and particularly functional investigations on human chronically epileptic tissue as well as genetic studies in epilepsy patients and their families strongly suggest that some forms of epilepsy may share a pathogenetic mechanism: an alteration of voltage‐gated sodium channels. This review summarizes recent data on changes of sodium channel expression, molecular structure and function associated with epilepsy, as well as on the interaction of new and established antiepileptic drugs with sodium currents. Although it remains to be determined precisely how and to what extent altered sodium‐channel functions play a role in different epilepsy syndromes, future promising therapy approaches may include drugs modulating sodium currents, and particularly substances changing their inactivation characteristics.
Tactile‐evoked Rolandic Discharges: A Benign Finding?
Authors: Langill Lisa , Wong Peter K. H.
Published: March 2003

Summary:  Purpose: This retrospective study was undertaken to determine if patients having tactile‐evoked rolandic discharges were a more “benign” patient population than those with spontaneously occurring nontactile rolandic discharges and to determine whether the presence of tactile‐evoked rolandic discharges was a marker for the future development of epilepsy, as previously reported.

Methods: During this 8‐year study, 304 patients were seen with rolandic discharges. These patients all had tactile stimulation of their hands and/or feet. They formed two groups: patients with spontaneous rolandic discharges that could not be evoked by tactile stimulation (NT) and patients with spontaneous rolandic discharges that could be enhanced with tactile stimulation (TE). Over a 14‐month period, every patient had tactile stimulation of both hands and both feet, resulting in a third group of patients having rolandic discharges seen only with tapping (TO).

Results: Tactile‐enhanced discharges constituted 38.2% of all rolandic discharges. Patients with TE and TO discharges had a higher incidence of normal development and intelligence, normal neurologic examinations, and a lower incidence of seizures and focal or generalized background abnormalities on their EEGs. Only one patient with normal background and no coexisting epileptiform abnormalities had partial motor seizures with corresponding contralateral central discharges. Only two patients who had no seizures at the time of their first EEG subsequently went on to develop seizures. Neither fit the pattern of the seizure disorder described in the literature.

Conclusions: It is hypothesized that tactile‐evoked rolandic discharges are a benign, age‐related phenomenon, which do not represent a marker for the future development of epilepsy and are not the interictal electrographic correlate to an already existing seizure disorder.
Cardiac Asystole in Epilepsy: Clinical and Neurophysiologic Features
Authors: Rocamora R. , Kurthen M. , Lickfett L. , Von Oertzen J. , Elger C. E.
Published: March 2003

Summary:  Purpose: Cardiac asystole provoked by epileptic seizures is a rare but important complication in epilepsy and is supposed to be relevant to the pathogenesis of sudden unexplained death in epilepsy (SUDEP). We sought to determine the frequency of this complication in a population of patients with medically intractable epilepsy and to analyze the correlation between EEG, electrocardiogram (ECG), and clinical features obtained from long‐term video‐EEG monitoring.

Methods: Retrospective analysis of the clinical records of hospitalized patients from May 1992 to June 2001 who underwent long‐term video‐/EEG monitoring.

Results: Of a total of 1,244 patients, five patients had cardiac asystole in the course of ictal events. In these patients, 11 asystolic events, between 4 and 60 s long in a total of 19 seizures, were registered. All seizures had a focal origin with simple partial seizures (n = 13), complex partial seizures (n = 4), and secondarily generalized seizures (n = 2). One patient showed the longest asystole ever reported (60 s) because of a seizure. Cardiac asystole occurred in two patients with left‐sided temporal lobe epilepsy (TLE) and in three patients with frontal lobe epilepsy (FLE; two left‐sided, one bifrontal). Two patients reported previous cardiac disease, but only one had a pathologic ECG by the time of admission. Two patients had a simultaneous central ictal apnea during the asystole. None of the patients had ongoing deficits due to the asystole.

Conclusions: These findings confirm that seizure‐induced asystole is a rare complication. The event appeared only in focal epilepsies (frontal and temporal) with a lateralization to the left side. A newly diagnosed or known cardiac disorder could be a risk factor for ictal asystole. Abnormally long postictal periods with altered consciousness might point to reduced cerebral perfusion during the event because of ictal asystole. Central ictal apnea could be a frequent associated phenomenon.
Ih Blockers Have a Potential of Antiepileptic Effects
Authors: Kitayama Masaomi , Miyata Harue , Yano Michiko , Saito Nobuko , Matsuda Yoshiki , Yamauchi Toshio , Kogure Shinichi
Published: March 2003

Summary:  Purpose: The h current (Ih) is an inwardly mixed cationic conductance activated by membrane hyperpolarization and distributed predominantly in the apical dendrites of hippocampal pyramidal neurons. To verify a hypothesis that an anomalous hyperpolarization generates an abnormal excitation by way of Ih channels, we examined the effects of Ih blockers (CsCl and ZD7288) on electrically induced paroxysmal discharges (PADs).

Methods: Fifty‐three adult male rabbits were used. We measured the PAD threshold elicited by stimulation to the apical dendritic layer of the hippocampal CA1 region before and after injecting 50 μl of each Ih blocker or saline extracellularly into the same region.

Results: In Ih blocker injection groups (n = 26), we obtained a significant increase in PAD threshold (1 mM CsCl: 163%, p < 0.01; 10 mM CsCl: 265%, p < 0.01; 100 mM CsCl: 199%, p < 0.01; 100 μM ZD7288: 192%, p < 0.05; 1 mM ZD7288: 246%, p < 0.05). Conversely, we did not obtain the increase in PAD threshold in a saline injection group (n = 10, 107%). The magnitude as well as duration of the effect had a tendency to depend on concentration of Ih blockers, although a saturated or declining tendency was observed with the 100 mM CsCl injection.

Conclusions: We concluded that Ih channels might contribute to hippocampal epileptiform discharges in vivo. Our hypothesis for epileptogenesis demonstrated in the present experiment offers an idea to develop a new type of antiepileptic drug based on Ih blockers for the treatment of epileptic disorders refractory to current medications.
EEG in Adult‐onset Idiopathic Generalized Epilepsy
Authors: Yenjun Suthida , Harvey A. Simon , Marini Carla , Newton Mark R. , King Mark A. , Berkovic Samuel F.
Published: March 2003

Summary:  Purpose: It remains controversial whether adult‐onset idiopathic generalized epilepsy (IGE) is a distinct syndrome or a continuum among IGE syndromes. EEG is the only known biologic marker of IGE and helps differentiate many of its classic subsyndromes. In this study, we looked for the differences in the EEG findings of IGE of classic adolescent onset versus adult onset that may suggest syndromic heterogeneity.

Methods: Seventy‐six patients (47 adolescent‐onset IGE, 29 adult‐onset IGE) with a clinical and EEG diagnosis of IGE were included. We defined IGE with age at onset of 11–20 years as adolescent‐onset IGE and age at onset of 20 years or after as adult‐onset IGE. Patients with first‐decade onset of seizures, delayed EEGs, and no EEG available for review were excluded. The first EEG was performed within 24 h of the seizure, and if negative, a sleep‐deprived EEG was done. All EEGs were reviewed in detail with respect to the background activity and the generalized spike–wave (GSW) characteristic.

Results: EEGs (87; 56 adolescent‐onset IGE, 31 adult‐onset IGE) were systematically reviewed. Background was normal in all patients. The morphology, amplitude, duration, frequency, occurrence, or activation of the GSW pattern did not differ between these two groups.

Conclusions: No differences of EEG features were found between the classic adolescent‐onset and the adult‐onset IGE. This supports the hypothesis that they share common biologic determinants and exist along a life‐long age spectrum of classic IGE.
Interlaboratory Variability in the Quantification of New Generation Antiepileptic Drugs Based on External Quality Assessment Data
Authors: Williams John , Bialer Meir , Johannessen Svein I. , Krämer Günther , Levy René , Mattson Richard H. , Perucca Emilio , Patsalos Philip N. , Wilson John F.
Published: March 2003

Summary:  Purpose: To assess interlaboratory variability in the determination of serum levels of new antiepileptic drugs (AEDs).

Methods: Lyophilised serum samples containing clinically relevant concentrations of felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), the monohydroxy derivative of oxcarbazepine (OCBZ; MHD), tiagabine (TGB), topiramate (TPM), and vigabatrin (VGB) were distributed monthly among 70 laboratories participating in the international Heathcontrol External Quality Assessment Scheme (EQAS). Assay results returned over a 15‐month period were evaluated for precision and accuracy.

Results: The most frequently measured compound was LTG (65), followed by MHD (39), GBP (19), TPM (18), VGB (15), FBM (16), and TGB (8). High‐performance liquid chromatography was the most commonly used assay technique for all drugs except for TPM, for which two thirds of laboratories used a commercial immunoassay. For all assay methods combined, precision was <11% for MHD, FBM, TPM, and LTG, close to 15% for GBP and VGB, and as high as 54% for TGB (p < 0.001). Mean accuracy values were <10% for all drugs other than TGB, for which measured values were on average 13.9% higher than spiked values, with a high variability around the mean (45%). No differences in precision and accuracy were found between methods, except for TPM, for which gas chromatography showed poorer accuracy compared with immunoassay and gas chromatography–mass spectrometry.

Conclusions: With the notable exception of TGB, interlaboratory variability in the determination of new AEDs was comparable to that reported with older‐generation agents. Poor assay performance is related more to individual operators than to the intrinsic characteristics of the method applied. Participation in an EQAS scheme is recommended to ensure adequate control of assay variability in therapeutic drug monitoring.
Antiepileptic Actions of Neuropeptide Y in the Mouse Hippocampus Require Y5 Receptors
Authors: Baraban Scott C.
Published: March 2003

Summary:  Purpose: Recent evidence suggests an antiepileptic role for neuropeptide Y (NPY) in the central nervous system. The precise receptor subtypes mediating the inhibitory actions of NPY in the hippocampal formation, however, remain unclear. In vitro studies suggest a role for Y2 receptors in modulating excitatory hippocampal synaptic transmission and epileptiform discharge. In vivo studies implicate Y5 receptors. Here we used pharmacologic tools and Y5‐receptor knockout mice to examine the role of Y5 receptors in mediating the antiexcitatory and antiepileptic actions of NPY in the hippocampal formation.

Methods: Hippocampal slices were obtained from age‐matched wild‐type (WT; 129 s3/svimj) and Y5‐receptor knockout (Y5R KO) mice generated on the same background strain. Extracellular or whole‐cell voltage‐clamp recordings were obtained in area CA3 pyramidale. Evoked population spikes or excitatory postsynaptic currents were monitored during bath application of NPY, NPY13‐36, or human pancreatic polypeptide (hPP). In some slices, zero‐magnesium cerebrospinal fluid (CSF) was used to evoke spontaneous epileptiform discharges.

Results: NPY and NPY agonists with preference for either Y2 (NPY13‐36) or Y5 (hPP) receptor subtypes caused a significant reduction in population spike and excitatory postsynaptic current (EPSC) amplitudes in slices from WT mice. NPY (and NPY agonists) also suppressed zero‐magnesium epileptiform burst discharge in slices from WT mice. In contrast, bath application of NPY, NPY13‐36, or hPP had no effect in slices from Y5R KO mice.

Conclusions: NPY modulates excitatory synaptic transmission and inhibits limbic seizure activity in the mouse hippocampus. The antiepileptic actions of NPY, in the mouse, appear to require activation of hippocampal Y5 receptors.
Progesterone Reduces Pentylenetetrazol‐Induced Ictal Activity of Wild‐Type Mice But Not Those Deficient in Type I 5α‐Reductase
Authors: Frye Cheryl A. , Rhodes Madeline E. , Walf Alicia , Harney Jacob
Published: March 2003

Summary:  Purpose: To investigate the importance of progesterone (P4) metabolism by the 5α‐reductase type I enzyme in mitigating P4 antiseizure effects.

Methods: Ovariectomized, female homozygous and heterozygous 5α‐reductase type I knockout mice (n = 23) and their wild‐type siblings (n = 31) were administered P4 (1.0 mg), and their pentylenetetrazol (PTZ)‐induced ictal behaviors were compared with those of vehicle‐administered mice (n = 49).

Results: Mice deficient in the 5α‐reductase type I enzyme administered P4, or vehicle‐administered control mice, had significantly shorter latencies and increased incidence of PTZ‐induced hindlimb extension and death than did wild‐type mice administered P4.

Conclusions: These data suggest that P4's metabolism by the 5α‐reductase type I enzyme may mitigate some of P4's antiseizure effects in the PTZ‐induced seizure model.
Electrophysiologic Abnormalities of the Hippocampus in the Pilocarpine/Cycloheximide Model of Chronic Spontaneous Seizures
Authors: Longo Beatriz M. , Sanabria Emilio R. G. , Gabriel Siegrun , Mello Luiz E. A. M.
Published: March 2003

Summary:  Purpose: Mossy fiber sprouting (MFS) and synaptic reorganization in the dentate gyrus (DG) is considered one of the physiopathologic mechanisms in temporal lobe epilepsy. Supragranular MFS can be blocked by cycloheximide (CHX) without interfering with the genesis of spontaneous recurrent seizures. The aim of this study was to investigate electrophysiologic properties of the hippocampus in the CHX/pilocarpine (CHX/PILO) model as compared with the conventional PILO model.

Methods: In vitro electrophysiology was performed 2 months after status epilepticus (SE) induction using extracellular recordings in hippocampal slices from PILO (n = 8) and CHX/PILO animals (n = 10). Field potential responses were evoked in the CA1 and DG regions during perfusion with normal artificial cerebrospinal fluid (aCSF) and aCSF containing 3.5, 5, or 8 mM K+ without or with bicuculline added. Neo‐Timm staining was used for the assessment of supragranular MFS.

Results: Evoked potentials in PILO‐ and CHX/PILO‐treated rats displayed small‐amplitude polyspiking activity (epileptiform responses) in CA1 and an apparently normal isolated population spike in DG. More important, PILO and CHX/PILO animals did not differ regarding electrophysiologic abnormalities, even under high K+ or high K+/bicuculline. Analysis of the neo‐Timm staining revealed strong supragranular MFS in PILO‐injected rats and significantly less staining in CHX/PILO rats. Thus, occurrence of abnormal stimulus responses and high K+‐ or high K+/bicuculline‐induced epileptiform activities did not depend on the degree of MFS.

Conclusions: We therefore suggest that other mechanisms such as anomalous intrinsic bursting and disinhibition rather than MFS might account for the increased hippocampal hyperexcitability in this model.
Behavior and Physiology of Mice Lacking the GABAA‐Receptor δ Subunit
Authors: Spigelman Igor , Li Zhiwei , Banerjee Pradeep K. , Mihalek Robert M. , Homanics Gregg E. , Olsen Richard W.
Published: March 2003

Summary:  Purpose: Mice with a targeted disruption of the γ‐aminobutyric acid (A) receptor (GABAAR) δ subunit exhibited spontaneous seizures and a strikingly selective attenuation of responses to neuroactive steroids, but not to other neuromodulators. This study further characterized the behavior and physiology of the δ mutants.

Methods: Seizure susceptibility to pentylenetetrazol (PTZ) injection, intracellular recordings, and whole‐cell patch recordings in dentate granule neurons was determined.

Results: Susceptibility to PTZ‐induced convulsive seizures was significantly higher in −/− versus +/+ mice. In intracellular recordings, the evoked inhibitory postsynaptic potentials (IPSPs) had much faster decay τ in −/− mutants (25 ± 3.5 ms) compared with +/+ controls (51 ± 5.2 ms). In whole‐cell patch recordings, the decay τ of pharmacologically isolated miniature spontaneous GABAAR‐mediated synaptic currents (mIPSCs) from −/− mice was only slightly, but significantly faster (5.7 ± 0.13 ms; n = 18) than that of +/+ controls (6.8 ± 0.32 ms; n = 20). Furthermore, mIPSC prolongation by bath application of alphaxalone (10 μM), was much smaller in −/− mice (52 ± 12%; n = 3) compared with +/+ littermates (192 ± 14%; n = 3).

Conclusions: Faster decay of evoked IPSPs and mIPSCs is consistent with altered GABAAR subunit composition in the δ mutants, but suggests predominant extrasynaptic δ subunit location in the dentate gyrus of normal mice. Faster‐decaying IPSPs likely contribute to the proepileptic phenotype of the δ mutants. Reduced neurosteroid sensitivity might also contribute to seizure susceptibility. It remains to be determined whether δ subunit–containing GABAARs represent the actual target of neurosteroids or whether the behavioral and physiologic sensitivity to neurosteroids is indirectly altered in the δ−/− mice.
The Global Burden of Epilepsy
Authors: Leonardi Matilde , Ustun T. Bedirhan
Published: March 2003

Summary: We briefly describe the Global Burden of Diseases (GBD) study, its goals, and some of its outcomes as related to neurologic and psychiatric disorders. The summary measure of population health DALYs (Disability Adjusted Life Years) are described, as well as the implications for neuropsychiatric disorders of changing health indicators and the move from mortality toward disability indicators. The pressing need for new measures for health is answered by the new WHO Classification of Functioning Disability and Health, ICF, and a brief summary of its basic principles is provided. Although a better understanding of the physical, social, and economic burden of epilepsy has moved this disorder higher on the world's agenda, epilepsy still has problems to be recognized as a public health priority. The implications of a shift toward considering the disability of epilepsy, as outlined in the the WHO World Health Report 2001, are important. The burden of epilepsy is high and, for the year 2000, accounts for ∼0.5% of the whole burden of diseases in the world.
Clues to the Genetic Influences of Drug Responsiveness in Epilepsy
Authors: Ramachandran V. , Shorvon Simon D.
Published: March 2003

Summary: Despite the introduction of newer antiepileptic drugs (AEDs), nonresponsiveness to AEDs remains a common problem in epilepsy clinics. There may be important genetic determinants for responsiveness, and this discussion focused on some potential areas: drug transporters; drug‐metabolizing enzymes, and ion channels. We review the literature and speculate the contribution of each of these factors in management of patients with epilepsy in the future.
Perspectives from a Developed Nation
Authors: Redhead Keith
Published: March 2003

Summary: Epilepsy is the most common serious neurologic disorder, affecting 350,000 people in the United Kingdom. There are five neurologists per 1,000,000 population, which is better than in India but much lower than in other developed nations. Thus, a patient's day‐to‐day prescribing, supervision, and support depends on primary care. In the U.K., patients are entitled to register with a genereal practitioner (GP), who has an average of 1,841 patients. Seventy‐eight percent of patients will consult their GP annually. Patients in the U.K. find that GPs are accessible and have good communication skills. There is, however, inadequate time in short consultations to provide the quality of care suggested by the latest review of services for patients with epilepsy (CSAG). This is further complicated by the heterogeneous and stigmatising nature of the condition. An improvement in the process of care in the primary‐care setting can result from three important strategies: appropriately trained practice nurses running practice nurse‐led clinics; structured management of care, possible because of the unique system of registration, which facilitates audit, prescription monitoring, and recall; and, finally, improved teamwork and communication based on protocols locally agreed upon between primary and secondary care. The future will tell whether these initiatives will improve the outcomes of care.
The Prospective Role of Transesophageal Echocardiography in the Diagnosis and Management of Patients with Suspected Infective Endocarditis
Authors: Harris Kevin M. , Li Dean Y. , L'Ecuyer Paul , Moon Karl E.T. , German Matt , Fraser Victoria , Barzilai Benico
Published: March 2003

Study Objectives: Transesophageal echocardiography (TEE) has a high sensitivity for the diagnosis of infective endocarditis (IE), but the prospective role of TEE when added to a careful clinical examination has not been well‐studied. Design: We compared the results of TEE to a clinical evaluation by an infectious disease specialist in 43 consecutive patients in whom TEE was ordered to rule out IE. Prior to TEE, the patients were classified on clinical grounds as to their likelihood of IE using a modification of the von Reyn criteria. Changes in management occurring as a result of TEE also were evaluated. Measurements and Results: TEE was positive in 11 patients, negative in 29, and indeterminate in 3. TEE was positive in 6 (46%) of 13 high probability patients, 2 (67%) of medium probability patients, and 3 (11%) of 27 low probability patients. A change in management based on TEE occurred in 4 (31%) patients with high probability, in no patients with medium probability, and in 1 (4%) patient with low probability. Conclusions: TEE confirms IE in patients with high probability of IE and often leads to a management change. However, TEE is unlikely to establish the diagnosis or change management in patients with low probability. (ECHOCARDIOGRAPHY, Volume 20, January 2003)
Endocarditis Abscess of the Aortic Annulus Involving the Left Ventricular Inferior Wall and Causing a Moderate Aortic Systolic Obstruction:
Authors: Iarussi Diana , Martino Vincenzo , Pergola Valeria , Renzo Giuseppe , Tripodi Maria Francoise , Utili Riccardo , Calabrò Raffaele
Published: March 2003

Abscesses are an important and potentially devastating complication of aortic valve endocarditis. The extension of the infectious process from the aortic valve to surrounding tissue can occur in different directions. This case report describes a 28‐year‐old man in whom the abscess of the aortic annulus was very large, causing a moderate aortic systolic obstruction, and also involved the left ventricular inferior wall. The diagnosis was provided by a combination of TTE and TEE examination and was confirmed by cardiac surgery. (ECHOCARDIOGRAPHY, Volume 20, January 2003)
Die Bedeutung des Helicobacter – auch jenseits des Magens
Authors: Ferenci P.
Published: March 2003

Die Entdeckung der Rolle des Helicobacter (H.) pylori als Verursacher des Ulcus pepticum war ein Meilenstein in der Gastroenterologie. Neben der Ulkuskrankheit könnte H. pylori auch bei anderen internen Erkrankungen wie der koronaren Herzkrankheit, der rheumatoiden Arthritis, der hepatischen Enzephalopathie und beim Sjoegren‐Syndrom eine Rolle spielen. Alle diese möglichen Assoziationen sind widersprüchlich und bedürfen weiterer Studien. Andere Helicobacterstämme (H. bilis, H. hepaticus, H. rappani, H. pullorum) werden als Erreger chronischer Leber‐ und Gallenwegserkrankungen sowie von Durchfallserkrankungen diskutiert. Besonders die mögliche Rolle dieser Keime für die Krebsentstehung ist hochinteressant und Gegenstand intensiver Forschungsarbeit.
Die Diagnose der Helicobacter pylori‐Infektion
Authors: Hirschl A. M.
Published: March 2003

Für die Diagnose der Infektion mit H. pylori stehen, wie für kaum eine andere bakterielle Infektion, eine Vielzahl sowohl invasiver als auch nicht‐invasiver Testverfahren zur Verfügung. Zu den bewährten Tests, die in vielen Studien eine einheitlich hohe Aussagekraft gezeigt haben, zählen der Biopsie‐Ureasetest, Histologie, Kultur und der 13C‐Atemtest. Zu den wichtigsten neuen Testansätzen gehören molekularmikrobiologische Verfahren, die u. a. die Möglichkeit der raschen Bestimmung von Virulenzfaktoren und Resistenzgenen eröffnen, sowie der Antigennachweis im Stuhl. Letztgenanntem Nachweisverfahren dürfte, nach Klärung einiger offener Fragen, in Zukunft große Bedeutung zukommen. Die Verfügbarkeit von Atemtests und Antigennachweis schränkt die Notwendigkeit des Einsatzes serologischer Tests ein, zumal die Mehrzahl der verfügbaren Schnelltests nicht ausreichend verläßlich ist. Gut definierte Indikationen zur Behandlung der Infektion mit H. pylori sind eine wesentliche Voraussetzung für einen vernünftigen Einsatz des diagnostischen Repertoirs.
Morbus Basedow: Klinik und Behandlungsergebnisse
Authors: Crivellaro C. , Oberhofer R. , Leimgruber K. , Amor H.
Published: March 2003

Zusammenfassung: Die Diagnose des Morbus Basedow wurde durch geeignete Untersuchungen erleichtert und beschleunigt, die Therapie durch die kombinierte Behandlung mit antithyreoidalen Medikamenten, Operation und Radiojodtherapie verbessert. Retrospektiv wurden aus dem Krankenkollektiv unserer Schilddrüsenambulanz 278 Patienten mit M. Basedow der Jahre 1992 – 1999 untersucht: Es sollten die wichtigsten subjektiven Beschwerden („Leitsymptome”), welche zum Arztbesuch führten, den objektiven klinischen Symptomen bei Krankheitsbeginn gegenübergestellt und die geeigneten diagnostischen Kriterien aufgezeigt werden. Therapiebeginn, Dosis der Medikamente, Behandlungsdauer und Therapieerfolge wurden kritisch bewertet, besonders im Hinblick auf Remissionsrate und ‐dauer, Rezidivhäufigkeit und Erfolg der ergänzenden ablativen Behandlungsmöglichkeiten. Die rein medikamentöse Therapie führte bei insgesamt 156 Patienten zur anhaltenden Remission (bei 113 in der 1. und 43 in der 2. „Runde”), die Chirurgie war bei 46 und die Radiojodbehandlung bei 40 Patienten erfolgreich. Eine kausale Therapie des M. Basedow ist bisher nicht möglich, aber die sequenzielle Anwendung von medikamentöser Therapie, Operation und Radiojodbehandlung führte bei insgesamt 242 Patienten zu einer dauerhaften Remission.
The Influence of New Scientific Information  on the Treatment of Elderly Patients in General Practice
Authors: Kubešová H. , Holik J. , Bogrova I.
Published: March 2003

Summary: It has been proven that with an increasing number of diseases elderly patients are treated by an increasing number of drugs despite the fact that treatment of elderly persons should be as simple as possible. Simpler dosage of (fewer?) drugs may contribute to a good cooperation on the part of patients, as well as to a lower incidence of undesirable effects and drug interactions. Sticking to established medication schemes is another feature observed in practice, which interferes with the introduction of novelties. The aim of this study was to investigate the actual situation of medication of elderly patients treat­ed by general practitioners in this country.  Between 1996 and 1998, a random group of 1481 patients aged older than 75 was studied in cooperation with general practitioners. A detailed history was obtained and physical examination was performed, signs of depression were assessed, Barthel  's test of everyday activities, and IADL (activities of daily living) and MMSE (Mini Mental State Examination) tests were applied. A unified “Protocol on Examination” was used in which three questions were concerned with medication – the kinds of drugs taken by the patient, their names and dosage, and whether any hypnotics were taken.  The five most frequently prescribed groups include vasodilators (62 % patients), cardiotonics (39 %), analgetics (41 %) and Ca‐antagonists (25 %). The dynamics of the prescription were remarkable – a significant decrease of the use of analgetics and cardiotonics was observed in comparison with a significant increase in the use of ACE inhibitors. The number of drugs administered is as follows: while only 1.3 % patients took no drugs, 1.6 % patients took more than 13 drugs. 61 % patients rank among the categories taking 4 – 5 or 6 – 8 kinds of drugs. On the whole, general practitioners tend to prescribe medicaments in doses one tablet per day.  Conclusions: The results suggest that, even nowadays, elderly patients are treated with a rather high number of medicaments. In contrast, the dosage of one tablet a day decreases the total number of the tablets taken. A significant influence of new ­scientific information was visible in the prescription habits of general practitioners. Be that as it may, in elderly patients, the simplest possible medication should continue to be aimed at.
Bestrahlungsbehandlung der endokrinen Orbitopathie – State of the Art
Authors: Prettenhofer Ulrike , Ramschak‐Schwarzer Sigrid , Langmann Andrea , Mayer R. , Schedlbauer P. , Hackl A.
Published: March 2003

Zusammenfassung: Seit mehreren Jahrzehnten stellt die endokrine Orbitopathie entweder als alleinige Behandlungsform oder in Kombination mit einer Kortisontherapie eine Indikation für die Strahlentherapie dar. Damit kann bei zirka zwei Drittel der Patienten eine Besserung der entzündlichen Schwellung des orbitalen Bindegewebes und der eingeschränkten Augenmuskelbeweglichkeit erzielt werden.