bluuebunny/crossref_metadata_2025 huggingface dataset:
Target‐specific Catecholamine Elevation Induced by Anticonvulsant Thalamic Deep Brain Stimulation
Authors: Ziai Wendy C. , Sherman David L. , Bhardwaj Anish , Zhang Ning , Keyl Penelope M. , Mirski Marek A.
Published: June 2005

Summary:  Purpose: Anterior thalamic nucleus (AN) deep brain stimulation (DBS) is effective in raising EEG and clonic seizure threshold in experimental models. Little is known about the specific properties of DBS that afford its anticonvulsant effect. We sought to test the hypothesis that experimental seizures and the anticonvulsant action of AN DBS alter the underlying regional neurochemistry of AN, specifically with facilitation of the serotonergic system to local electrical stimulation.

Methods: Halothane‐anesthetized adult Sprague–Dawley male rats underwent stereotactically guided bilateral placement of bipolar stimulating steel electrodes and dialysis probes–guide cannulae in AN and posterior thalamus (PT), and placement of four epidural EEG screw electrodes 48 h before experiments. Both stimulated (AN DBS) and nonstimulated (NO DBS) animals (n = 7 per group) were infused with i.v. pentylenetetrazol (PTZ, 5.5 mg/kg/min). Simultaneous thalamic and cortical EEG were recorded, and microdialysis samples were collected from AN and PT in 20‐min epochs. AN stimulation was delivered (150 μA; 0.1‐ms pulse duration) 40 min before and continued during PTZ infusion.

Results: Bilateral AN stimulation delayed the onset of EEG seizures compared with controls: 82 ± 8 vs. 58 ± 5 min (p = 0.02). PTZ infusion alone, or together with stimulation, resulted in a steady increase in norepinephrine (NE), but not dopamine, at AN and PT sites (p < 0.001). Although extracellular serotonin was measured at very low levels, the metabolite, 5‐hydroxyindoleacetic acid (5‐HIAA) increased selectively in AN after stimulation and during preconvulsant infusion of PTZ (p < 0.001), returning to baseline after the first generalized seizure.

Conclusions: These data suggest that PTZ and DBS together enhance the nonselective release of NE in thalamic nuclei while specifically stimulating AN‐localized serotonin. Low serotonin levels at baseline and during STIM alone or PTZ infusion may indicate efficient reuptake systems for serotonin, with 5‐HIAA serving as a surrogate marker for serotonergic activity. Modulation of the AN‐specific serotonergic activity may be critical in altering PTZ seizure threshold and be an important neurotransmitter system underlying the efficacy of AN DBS.
Gender Differences in Epilepsy
Authors: Christensen Jakob , Kjeldsen Marianne Juel , Andersen Henning , Friis Mogens Laue , Sidenius Per
Published: June 2005

Summary:  Purpose: The aim of this study was to look at gender differences in unselected populations of patients with epilepsy classified according to the 1989 International League Against Epilepsy (ILAE) criteria.

Methods: Data were obtained from two sources: (a) the EpiBase database at the outpatient clinic at the Department of Neurology, Aarhus University Hospital, Denmark, confined to adults with epilepsy (n = 2,170), and (b) the Danish Twin Registry (n = 318).

Results: In localization‐related epilepsy, no overall gender difference was found in either the EpiBase population (n = 1,511; w = 750 (50%), m = 761 (50%); p = 0.80) or in the twin population (n = 172; w = 86 (50%), m = 86 (50%); p = 1.00). However, in the EpiBase population, localization‐related symptomatic epilepsies were more frequent in men (n = 939; w = 426 (45%), m = 513 (55%); p = 0.005); and cryptogenic localization‐related epilepsies were more frequent in women (n = 572; w = 324 (57%), m = 248 (43%); p = 0.002). In generalized epilepsy, more women than men were diagnosed in both populations [EpiBase: n = 480, w = 280 (58%), m = 200 (42%); p < 0.001; twin population: n = 105, w = 63 (60%), m = 42 (40%); p = 0.05]. The difference was confined to idiopathic generalized epilepsy [EpiBase: n = 437, w = 259 (59%), m = 178 (41%); p < 0.001; twin population: n = 94, w = 60 (64%), m = 34 (36%); p = 0.01].

Conclusions: More women than men were diagnosed with idiopathic generalized epilepsy in two epilepsy populations. Overall, no gender difference was found in localization‐related epilepsy, but localization‐related symptomatic epilepsies were more frequent in men, and cryptogenic localization‐related epilepsies were more frequent in women The results suggest a gender susceptibility to the development of specific epilepsy subtypes.
Vigabatrin in Low Doses Selectively Suppresses the Clonic Component of Audiogenically Kindled Seizures in Rats
Authors: Vinogradova Ludmilla V. , Kuznetsova Galina D. , Shatskova Alla B. , Van Rijn Clementina M.
Published: June 2005

Summary:  Purpose: The effect of systemic administration of the γ‐aminobutyric acid (GABA)‐transaminase inhibitor vigabatrin (VGB) on different components of convulsions was tested in the model of audiogenically kindled seizures, which consist of brainstem (running, tonus) and forebrain (clonus) elements.

Methods: Audiogenically susceptible rats of Krushinsky‐Molodkina (KM), Wistar, and WAG/Rij strains received repeated sound stimulation (60 dB, 10–80 kHz) until kindled audiogenic seizures were reliably elicited. Kindled audiogenic seizures consisted of running, tonic, and generalized clonic phases in KM rats (severe audiogenic seizures) and of running and Racine stage 5 facial/forelimb clonus in Wistar and WAG/Rij rats (moderate seizures). Vehicle, 100, or 200 mg/kg of VGB was intraperitoneally injected 2, 4 and 24 h before the induction of kindled audiogenic seizures.

Results: At both doses, VGB did not change the seizure latency and the duration of running and tonic convulsions, but suppressed clonic ones in all rat strains. In KM rats, the mean duration of posttonic clonus was significantly reduced at 24 h after 100 mg/kg and from 4 h after 200 mg/kg. In Wistar and WAG/Rij rats, the mean duration of facial/forelimb clonus was reduced from 4 and 2 h after 100‐ and 200‐mg/kg administration, respectively; 24 h after the high‐dose injection, clonus was completely blocked in all rats of both strains. No difference in efficacy of VGB between Wistar and WAG/Rij rats was observed.

Conclusions: VGB more effectively suppresses clonic convulsions than running and tonic ones in audiogenically kindled rats. It is supposed that this selective anticonvulsive effect of VGB results from different sensitivities of forebrain and brainstem epileptic networks to the presumed GABA enhancement.
Drug Resistance in Epilepsy: Putative Neurobiologic and Clinical Mechanisms
Authors: Schmidt Dieter , Löscher Wolfgang
Published: June 2005

Summary:  Drug‐resistant epilepsy with uncontrolled severe seizures despite state‐of‐the‐art medical treatment continues to be a major clinical problem for up to one in three patients with epilepsy. Although drug resistance may emerge or remit in the course of epilepsy or its treatment, in most patients, drug resistance seems to be continuous and to occur de novo. Unfortunately, current antiepileptic drugs (AEDs) do not seem to prevent or to reverse drug resistance in most patients, but add‐on therapy with novel AEDs is able to exert a modest seizure reduction in as many as 50% of patients in short‐term clinical trials, and a few become seizure free during the trial. It is not known why and how epilepsy becomes drug resistant, while other patients with seemingly identical seizure types can achieve seizure control with medication. Several putative mechanisms underlying drug resistance in epilepsy have been identified in recent years. Based on experimental and clinical studies, two major neurobiologic theories have been put forward: (a) removal of AEDs from the epileptogenic tissue through excessive expression of multidrug transporters, and (b) reduced drug‐target sensitivity in epileptogenic brain tissue. On the clinical side, genetic and clinical features and structural brain lesions have been associated with drug resistance in epilepsy. In this article, we review the laboratory and clinical evidence to date supporting the drug‐transport and the drug‐target hypotheses and provide directions for future research, to define more clearly the role of these hypotheses in the clinical spectrum of drug‐resistant epilepsy.
Epilepsies after Pocket Monster Seizures
Authors: Okumura Akihisa , Watanabe Kazuyoshi , Negoro Tamiko , Ishikawa Tatsuya , Ishiguro Yoshiko , Takenaka Junko , Takada Hiroyuki
Published: June 2005

Summary:  Background: We conducted a 5‐year follow‐up study in patients with a seizure induced by animated cartoon “Pocket Monster.”

 Methods: A recurrence of seizures was observed in 25 of 91 patients with a Pocket Monster seizure. The patients were divided into two groups: Epilepsy group of 12 patients with a history of epilepsy and Nonepilepsy group of 13 patients without a history of epilepsy.

Results: Age below 12 years and generalized seizures were more often in Nonepilepsy group than in Epilepsy group. Seizure recurrence was earlier in Epilepsy group than in Nonepilepsy group. Photoparoxysmal response was relatively infrequent in Epilepsy group. The majority of patients were classified into idiopathic generalized epilepsies in Nonepilepsy group, whereas most patients were categorized into localization‐related epilepsies in Epilepsy group.

Conclusions: Epilepsies after Pocket Monster seizures were different according to the presence or absence of a history of epilepsy. These results will be useful in order to determine the treatment of a patient with a visually induced seizure.
Hippocampal Malformations Do Not Necessarily Evolve into Hippocampal Sclerosis
Authors: Sen Arjune , Thom Maria , Martinian Lillian , Dawodu Stephen , Sisodiya Sanjay M.
Published: June 2005

Summary: Purpose:Hippocampal malformations have been proposed to underlie or evolve into hippocampal sclerosis, a common cause of refractory partial epilepsy. We report two patients with chronic epilepsy and developmental abnormalities of the hippocampus and cortex. We seek to address, in patients with recurrent convulsive seizures over many decades, whether hippocampal malformations necessarily progress to hippocampal sclerosis.

Methods:The first patient died at age 76 years and had experienced convulsive seizures for 43 years. The second patient, aged 64 years at death, had experienced convulsive seizures for 49 years. The brains were processed routinely. Immunohistochemistry for dynorphin and neuropeptide Y was performed.

Results:The first case exhibited bilateral perisylvian polymicrogyria. Both hippocampi demonstrated abnormal convolution in the CA1 subfield and subiculum. In the second case, periventricular heterotopia was found in the wall of the right lateral ventricle. The right hippocampus was abnormally oriented with excessive convolutions of the pyramidal cell layer between CA1 and the subiculum. In neither patient did the hippocampi exhibit neuronal loss. Furthermore, dynorphin immunohistochemistry revealed no reactivity in the molecular layers, and staining with neuropeptide Y confirmed normal numbers of hilar interneurons.

Conclusions:These two cases demonstrate histologically that, even in long‐standing epilepsy, malformations of the hippocampus do not necessarily develop into hippocampal sclerosis.
The Neuropsychological and Language Profile of Children with Benign Rolandic Epilepsy
Authors: Northcott Ellen , Connolly Anne M. , Berroya Anna , Sabaz Mark , McIntyre Jenny , Christie Jane , Taylor Alan , Batchelor Jennifer , Bleasel Andrew F. , Lawson John A. , Bye Ann M. E.
Published: June 2005

Summary:  Purpose: Benign rolandic epilepsy (BRE) has an excellent prognosis for seizures, but recent research has raised concerns using cognition as an outcome measure. Methodologic problems related to recruitment bias and assessment processes are evident in previous studies. With well‐defined criteria for inclusion and comprehensive assessment, the aim of this study was to define the cognitive profile of children with BRE and to assess the effect of interictal EEG activity.

Methods: Patients (n = 42) were recruited from six EEG laboratories. The EEG features analyzed were spike frequency, trains, and laterality. Comprehensive neuropsychological and language assessments were conducted. Group means on cognitive measures were compared with normative means. Tests were correlated with EEG features.

Results: The study demonstrated that children with BRE have normal intelligence and language ability. However, a specific pattern of difficulties in memory and phonologic awareness was found. Furthermore, a large proportion of children had disproportionate scores in these areas compared with intellectual and language ability. EEG features were minimally associated with cognitive difficulties, and no correlation was found with memory indices and tests of phonologic awareness.

Conclusions: Some children with BRE have specific difficulties in memory and phonologic processing skills, not explained by interictal activity. We recommend that pediatricians ask about academic performance specifically in areas of prereading, reading, spelling, and memory. If difficulties are suspected, assessment targeting phonologic awareness and memory are recommended, as they may not be reflected in overall intellectual and language ability. Difficulties in phonologic awareness affect literacy, and memory problems affect academic performance.
Nonfebrile Illness Seizures: A Unique Seizure Category?
Authors: Zerr Danielle M. , Blume Heidi K. , Berg Anne T. , Del Beccaro Mark A. , Gospe Sidney M. , Allpress Amanda L. , Christakis Dimitri A.
Published: June 2005

Summary:  Purpose. To describe the clinical characteristics of children with a first‐time nonfebrile seizure in the setting of mild illness and to test the hypothesis that these seizures are associated with illness characterized by diarrhea.

Methods. This retrospective cohort study was performed in a pediatric emergency department. Patients ages 6 months to 6 years who were evaluated with first‐time seizures were eligible for inclusion. Subjects were divided into three groups on the basis of symptoms accompanying their seizure: febrile (temperature, >38.0°C with seizure), unprovoked (no symptoms of illness), and nonfebrile illness (no fever at the time of seizure, but other symptoms of illness present).

Results. Of the 323 children with first‐time seizures, 247 (76%) had febrile seizure, 37 (12%) had unprovoked seizures, and 39 (12%) had nonfebrile illness seizures. Children with nonfebrile illness seizures were more likely than children with febrile seizures to have diarrheal illnesses accompanying their seizure (44 vs. 16%; p = 0.001). Frequency of cough, rhinorrhea, and rash did not differ significantly between children with febrile and nonfebrile illness seizures. Diagnostic testing for infectious etiologies was not performed frequently in either group.

Conclusions. Nonfebrile illness seizures may represent a distinct group of seizures with unique epidemiology. Further study to define this seizure group better is warranted.
Anticonvulsant Properties of the Novel Nootropic Agent Nefiracetam in Seizure Models of Mice and Rats
Authors: Kitano Yutaka , Komiyama Chika , Makino Mitsuhiro , Takasuna Kiyoshi , Takazawa Akira , Sakurada Shinobu
Published: June 2005

Summary: Purpose:Nefiracetam (NEF) is a novel pyrrolidone‐type nootropic agent, and it has been reported to possess various pharmacologic effects as well as cognition‐enhancing effects. The present study focused on the anticonvulsant effect of NEF and its potential for antiepileptic therapy.

Methods:The anticonvulsant properties of NEF were investigated in experimental seizure models of mice and rats, compared with levetiracetam (LEV) and other standard antiepileptic drugs [AEDs; zonisamide (ZNS), phenytoin (PHT), carbamazepine (CBZ), valproic acid (VPA), diazepam (DZP), and ethosuximide (ESM)]. With reference to standard programs for evaluating potential AEDs, the study included the traditional maximal electroshock seizure and subcutaneous chemoconvulsant (pentylenetetrazole, bicuculline, picrotoxin, strychnine, orN‐methyl‐d‐aspartate) seizure tests and two threshold models (the increasing‐current electroshock seizure test and intravenous pentylenetetrazole seizure threshold test). Neurotoxic activities were examined with the rotarod test and traction test.

Results:NEF inhibited electroshock‐induced seizures at nontoxic doses, whereas it had no effect on seizures chemically induced by pentylenetetrazole, bicuculline, picrotoxin, strychnine, orN‐methyl‐d‐aspartate. The anticonvulsant spectrum of NEF paralleled that of ZNS, PHT, and CBZ. The anticonvulsant efficacy of NEF was comparable with that of ZNS and less potent than that of PHT, CBZ, and DZP. However, the safety margin of NEF was superior to that of ZNS, CBZ, VPA, and DZP. LEV showed only slight anticonvulsant effects in threshold models, and it was not effective in conventional screening models.

Conclusions:These results suggest that NEF has distinct anticonvulsant spectrum and mechanisms from those of LEV. NEF is an orally active and safe AED, and it possesses a potential for antiepileptic therapy.
Localization of Breast Cancer Resistance Protein (BCRP) in Microvessel Endothelium of Human Control and Epileptic Brain
Authors: Aronica Eleonora , Gorter Jan A. , Redeker Sandra , Van Vliet Erwin A. , Ramkema Marja , Scheffer George L. , Scheper Rik J. , Van Der Valk Paul , Leenstra Sieger , Baayen Johannes C. , Spliet Wim G. M. , Troost Dirk
Published: June 2005

Summary:  Purpose: Breast cancer resistance protein (BCRP) is a half adenosine triphosphate (ATP)‐binding cassette (ABC) transporter expressed on cellular membranes and included in the group of multidrug resistant (MDR)‐related proteins. Recently, upregulation of different MDR proteins has been shown in human epilepsy‐associated conditions. This study investigated the expression and cellular distribution of BCRP in human control and epileptic brain, including a large number of both neoplastic and nonneoplastic specimens from patients with chronic pharmacoresistant epilepsy.

Methods: Several epileptogenic pathologies, such as hippocampal sclerosis (HS), focal cortical dysplasia (FCD), dysembryoplastic neuroepithelial tumor, oligodendroglioma astrocytoma, and glioblastoma multiforme were studied by using Western blot and immunocytochemistry.

Results: With Western blot, we could demonstrate the presence of BCRP in both normal and epileptic human brain tissue. In contrast to P‐glycoprotein (P‐gp) and multidrug resistance–associated protein (MRP) 2, BCRP expression levels did not change in tissue from patients with HS, compared with control hippocampus. No BCRP immunoreactivity was observed in glial or neuronal cells, including reactive astrocytes and dysplastic neurons in FCD. BCRP expression was, however, increased in tumor brain tissue. Immunocytochemistry demonstrated that BCRP was exclusively located in blood vessels and was highly expressed at the luminal cell surface and in newly formed tumor capillaries. This localization closely resembles that of P‐gp. The higher expression observed in astrocytomas by Western blot analysis was related to the higher vascular density within the tumor tissue.

Conclusions: These results indicate a constitutive expression of BCRP in human endothelial cells, representing an important barrier against drug access to the brain. In particular, the strong BCRP expression in the microvasculature of epileptogenic brain tumors could critically influence the bioavailability of drugs within the tumor and contribute to pharmacoresistance.
Successful Initiation of Combined Therapy with Valproate Sodium Injection and Divalproex Sodium Extended‐release Tablets in the Epilepsy Monitoring Unit
Authors: Boggs Jane G. , Preis Keith
Published: June 2005

Summary:  Purpose: Patients in epilepsy monitoring units (EMUs) often require aggressive initiation or reinitiation of therapy before discharge. We developed a simple dosing scheme using valproate sodium injection (VPA‐IV) and divalproex sodium extended‐release (VPA‐ER) tablets to minimize the time required for initiation of therapy, without increasing the likelihood of seizures and adverse effects.

Methods: We identified 42 patients in the EMU, naïve to VPA‐IV and VPA‐ER, for whom one of the discharge AEDs included divalproex sodium. On the day of discharge, patients were loaded with 20 mg/kg VPA‐IV at 6 mg/kg/min, followed by ∼20 mg/kg VPA‐ER within 1 h. The discharge daily dose of VPA‐ER was identical to the dose given after the IV load. We assessed tolerability and seizure occurrence during infusion, at 1 h, 4 h, and 1 week after discharge.

Results: All patients tolerated the VPA‐IV dose followed by VPA‐ER. Four patients reported mild nausea, and two patients reported mild dizziness within 4 h. No seizures or significant changes in heart rate or blood pressure occurred within 4 h, and all patients were discharged the same day. All patients denied systemic complaints at 1 week, and five had seizures during the week after discharge. All patients had improved seizure frequencies at the end of the first week.

Conclusions: VPA‐IV is well tolerated and convenient for rapid loading in the EMU. When promptly followed by VPA‐ER, seizure control remains excellent.
Partial Seizure Provoked by Hyperbaric Oxygen Therapy: Possible Mechanisms and Implications
Authors: Doherty Michael J. , Hampson Neil B.
Published: June 2005

Summary:  Hyperbaric oxygen treatment (HBO2) is used commonly for treatment of bone and soft‐tissue radiation necrosis. It may be a potential therapy for radiation necrosis seen after brain irradiation. HBO2 risks include generalized tonic–clonic convulsions. We report a patient after resection of anaplastic astrocytoma and 5,580 cGy of total external‐beam radiation treatments with brain radiation necrosis who underwent HBO2 therapy and developed a partial seizure during treatment. Mechanisms and implications are discussed.
Brain Perfusion Assessed by 99mTc‐ECD SPECT Imaging in Pediatric Patients with Neurally Mediated Reflex Syncope
Authors: İLGIN N. , OLGUNTURK† R. , KULA† S. , TURAN† L. , TUNAOĞLU† S. , TEMIZ H. , GOKCORA N. , GÜCÜYENER† K.
Published: June 2005

Background: The involvement of cardiogenic and neurogenic mechanisms in neurally mediated reflex syncope is well documented. In our previous studies in patients with neurally mediated reflex syncope, we have found evidence for differential regulation of the noradrenergic receptors in tilt‐positive and tilt‐negative patients. The present work concentrates on the observations of differences in regional brain perfusion using brain SPECT via injecting the patient at the completion of the tilt test.

Methods and Results: The following study was designed to assess the reduction and regional differences in cerebral blood flow by means of SPECT using technetium‐99m labeled V‐oxo‐1,2‐N1ethylenedylbisl‐cysteine diethylester (ECD) in patients with an injection during tilt testing. Twenty patients with NMS were included in the study with a mean age of 12.2 years (age range; 8–16 years). HUT was positive in 10 patients and negative in 10 patients. When tilt (+) and tilt (−) were evaluated together, regional cortical/cerebellum ratios were ranging from 0.85 to 1.25 in different cortical areas with highest variability of perfusion index in left frontoparietal cortex. The lowest perfusion index values were observed in the left anterior frontal region followed by the left prefrontal‐frontoparietal‐anterior, parietal‐orbito frontal, and anterior temporal regions where perfusion is predominantly supplied via the anterior and middle cerebral arteries, while these differences did not reach statistical significance in a single dominant region compared to the other regions examined using ANOVA (P > 0.05) with this sample size.
Decreases in [99mTc]ECD uptake were more widespread regionally on the left hemisphere than were decreases in right side of the brain. However when tilt– and tilt+ groups were compared, perfusion was significantly lower in the right periinsular posterior parietal and temporal regions (P < 0.05) in tilt + group.

Conclusion: These tilt induced regional differences in brain perfusion suggest the distinct roles of middle cerebral artery dominant territory‐related vasodepressor compensation mechanisms in neurally mediated reflex syncope phenomena where cerebral lateralization of cardiac control and insular ischemia may play an important role.
Effect of Inter‐electrode Distance on Bipolar Intramural Radiofrequency Ablation
Authors: KOVOOR PRAMESH , DALY MICHAEL , POULIOPOULOS JIM , DEWSNAP M. BARBARA , EIPPER VICKI , ROSS DAVID L.
Published: June 2005

Objectives: We aimed at evaluating bipolar radiofrequency ablation by correlating inter‐electrode distance (ILD) with lesion dimensions and continuity.

Background: Previous reports indicated that bipolar radiofrequency (RF) current applied to two adjacent sites in vitro, synergistically increased lesion sizes greater than that observed for unipolar RF current delivery using the same electrodes.

Methods: Ablations were performed intramurally to ensure that each electrode surface (radius = 0.4 mm, area = 3.52 mm2) provided consistent contact with the myocardium. Ninety‐six ablations were performed in four greyhounds using bipolar ablation needles with ILDs of 1, 2, 3, and 4 mm. An epicardial approach was used to ensure accurate positioning of the needles within the myocardium. Lesions were created using temperature‐controlled RF delivery for a duration of 60 seconds to achieve 90°C at the electrode proximal to the needle base. Lesion dimensions were determined histologically.

Results: Increasing the ILD, decreased lesion width (P = 0.003) but increased lesion depth (P = 0.001). Lesions remained continuous with ILDs of 1–3 mm but became discontinuous at 4 mm. Energy requirements during ablation increased with increasing ILDs.

Conclusion: Using the above parameters (electrode radius, RF power delivery, time) during bipolar ablation, lesion continuity was critically dependent on the ILD. The maximum ILD threshold to create contiguous overlapping lesions was 3 mm. Lesions of greater width were created using shorter ILDs. Clinically, greater control over lesion dimensions can be obtained by manipulating the ILD distance.
Cross‐Ventricular Pacemaker‐Mediated Tachycardia by Myopotential Induction during Biventricular Pacing
Authors: GUENOUN MAXIME , HERO MARC , ROUX OLIVIER , MAINARDIS MARC
Published: June 2005

Background: Patients in permanent atrial fibrillation treated for heart failure and ventricular asynchrony can be implanted with conventional dual chamber pacemakers (DDD) pacemakers used in the biventricular mode. The left ventricular lead is connected to the atrial channel.

Case Report: We report the case of a patient who developed ventriculo‐ventricular pacemaker‐mediated tachycardia (PMT) induced by myopotential sensing in the atrial channel, inhibiting left ventricular pacing.

Conclusion: In the absence of specifically designed pacemakers, the use of DDD pacemakers in the biventricular mode requires certain precautions, such as anti‐PMT mode activation, disabling automatic sensitivity, and lengthening the postventricular atrial refractory period (PVARP), or mode switch to DVIR.
Pacing‐Induced Electrophysiological Remodeling in Hypertrophic Obstructive Cardiomyopathy—Observations on Cardiac Memory
Authors: NOWINSKI KAROLINA , WECKE LILIANE , GADLER FREDRIK , LINDE CECILIA , BERGFELDT LENNART
Published: June 2005

Background: Hypertrophic cardiomyopathy carries an increased risk for sudden cardiac death. While pacing therapy reduces the left ventricular outflow tract gradient and improves symptoms in a subgroup of hypertrophic obstructive cardiomyopathy (HOCM) patients, its electrophysiological consequences are unknown and were therefore assessed in this prospective study.

Methods and Results: Fifteen consecutive HOCM patients were studied and compared with 14 patients without HOCM paced because of sinus bradycardia. ECG intervals were measured before pacemaker implantation and after ≥3 months of DDD pacing in HOCM patients and ≥5 weeks in controls. Both groups showed similar ECG signs of cardiac memory development. In HOCM patients, with baseline QTc 447 ± 33 ms, cardiac memory development was not associated with any significant changes in ECG intervals. In contrast, baseline repolarization in control patients was significantly prolonged by 6% (QTc 429 ± 33 vs 454 ± 46 ms; P < 0.05). Furthermore, in HOCM patients repolarization was 7% shorter during DDD pacing compared to sinus rhythm (JTc 329 ± 25 vs 353 ± 21 ms; P < 0.05), despite a significantly prolonged ventricular activation time (QRS duration 155 ± 16 vs 91 ± 9 ms; P < 0.01).

Conclusions: Importantly, the development of cardiac memory‐induced different repolarization responses depending on baseline structure and electrophysiology. In HOCM patients repolarization was shorter during right ventricular apical pacing than during normal activation despite prolonged activation time.
Reduction of Right Ventricular Pacing in Patients with Sinus Node Dysfunction Using an Enhanced Search AV Algorithm
Authors: MELZER CHRISTOPH , SOWELAM SAMEH , SHELDON TODD J. , BONDKE H.J. , BAUMANN GERT , COMBS BILL , THERES HEINZ
Published: June 2005

Background: Dual chamber pacing typically results in a high percentage of ventricular pacing. A number of studies have been conducted suggesting detrimental effects of ventricular desynchronization produced by long‐term RV pacing. Pacemaker algorithms that extend the AV interval to uncover intrinsic AV conduction have been utilized to reduce ventricular pacing. These algorithms are often limited to AV intervals below 250 ms limiting the ventricular pacing reduction. We hypothesized that by allowing AV intervals to extend beyond 300 ms, a marked reduction in RV pacing can be achieved.

Methods: A total of 30 patients (17 men, mean age 71 ± 9) with standard Brady indications, and implanted with a Medtronic Kappa 700 pacemaker, were randomized to 2‐week treatments with default Search AV (KSAV) parameters or Enhanced Search AV (ESAV) parameters. The Enhanced Search AV algorithm included the capability for continuous adjustment of AV delays and the ability to auto disable in patients with persistent AV block.

Results: Among patients with intact AV conduction, percent VP was greater in KSAV versus ESAV (70 ± 40% vs 19 ± 28%, P < 0.001). In patients with persistent AV block, the algorithm suspended appropriately and there was no significant change in the percent VP between both arms of the study. In 18/22 patients, percent VP was reduced below 40%.

Conclusions: Substantial reduction in ventricular pacing can be achieved by allowing the AV interval parameters to extend beyond 300 ms using the ESAV algorithm. In patients with AV block, ESAV suspended and patients were paced at their nominal settings.
Characteristics Associated with Low Treatment Satisfaction in Patients with Implanted Cardioverter Defibrillators: Results from the LICAD Study
Authors: LADWIG KARL‐HEINZ , DEISENHOFER ISABELLE , SIMON HEIDI , SCHMITT CLAUS , BAUMERT JENS J.
Published: June 2005

The evaluation of low treatment satisfaction (LTS) with an implanted cardioverter defibrillator (ICD) remains a neglected area of clinical research. However, a trustful attitude toward an ICD is crucial. Within the scope of ICD health technology assessment, we searched for predictors of LTS. Of 195 ICD patients enrolled (mean 59.8 years, standard deviation 12.6), 163 (83.6%) were men and 26 (16.4%) were women. We measured anxiety, helplessness, and depression with standardized instruments and LTS with 11 dichotomous items concerning a mistrustful attitude, a negative body image, and low appraisal. A total of 47 (24.1%) patients were considered as LTS patients. Multivariate logistic regression was used for assessment of LTS. Adjusted for age and survey, LTS was significantly more prevalent in depressed, anxious, and phobic patients. Multivariate logistic regression including medical and psychological covariates revealed the experience of ≥5 shocks with an odds ratio (OR) of 10.17 (95% CI 3.57–29.00, P ≤ 0.001), being employed with an OR of 8.07 (95% CI 2.39–27.19, P ≤ 0.001), and feelings of helplessness (OR 4.61, 95% CI 1.79–11.90, P ≤ 0.002) as the most important predictors for LTS. Women had a slightly not significant effect on LTS. Age, educational status, and depression were not significant. LTS patients required more support for living with the ICD (P ≤ 0.001). Thus, LTS serves as surrogate measure for deteriorated psychic health. Clinicians should be advised to identify LTS patients and to consider psychotherapeutic counseling for them.
Radiofrequency Catheter Ablation Therapy of Swallowing‐Induced Atrioventricular Nodal Reentrant Tachycardia: Report of Two Cases
Authors: SATISH ORUGANTI SAI , YEH SAN‐JOU , YEH KUAN‐HUNG , WEN MING‐SHIEN , WANG CHUN‐CHIEH , CHOU CHUNG‐CHUAN , WU DELON
Published: June 2005

We describe two patients who presented with a history of recurrent palpitations on swallowing of solid food. The event‐recorder and Holter monitoring documented episodic supraventricular tachycardia (SVT) initiated by atrial premature contractions (APCs). During electrophysiological study (EPS), swallowing of solid food consistently induced APCs and their activation sequence, morphology of P wave were suggestive of their right atrial origin in them. Drug challenge did not affect the APC onset during the swallowing. During EPS, slow‐fast variety of atrioventricular nodal reentrant tachycardia (AVNRT) was induced and successful radiofrequency (RF) catheter ablation of slow pathway resulted in total relief of their symptoms.
Development of Implantable Devices for Continuous Ambulatory Monitoring of Central Hemodynamic Values in Heart Failure Patients
Authors: BENNETT TOM , KJELLSTROM BARBRO , TAEPKE ROBERT , RYDEN LARS ,   for the Implantable Hemodynamic Monitor Investigators
Published: June 2005

Background: Care and management of patients with congestive heart failure (CHF) is a major health‐care challenge. The value of acute hemodynamic data in assessing heart failure has been questioned in some studies, while more intensive hemodynamic monitoring has been reported to improve patient care in others. A series of patient studies are reported here that were conducted to identify device requirements and verify the feasibility of continuous hemodynamic monitoring in CHF patients and devices for remote transfer and use of these data.

Methods and Results: The results of four separate studies in 68 CHF patients who received systems for chronic hemodynamic monitoring between 1992 and the present are reviewed. One early study was with five patients followed for 7–16 months and another study was with nine patients followed for 4–22 months. A third study included 21 patients followed up to 39 months, and the fourth study included 32 patients implanted in 1998–99 with many of them still in follow‐up. These studies support the technical feasibility of implanted devices and the external instrumentation required to transfer and manage the collected data. They also support the long‐term stability and accuracy of these systems. Three additional acute studies conducted with 30 patients and chronic data from 53 of the 68 patients with the implanted systems are presented that support the feature included in the newer monitors – the ability to reliably estimate pulmonary artery diastolic pressures from the right ventricular pressure signal.

Conclusions: Development of implantable technology to measure several hemodynamic variables in ambulatory CHF patients is feasible. External instrumentation needed to remotely acquire data from the implanted devices has been verified. The potential to eliminate the uncertainties associated with the use of acute, invasive hemodynamics and the ability to evaluate long‐term ambulatory hemodynamic patterns is provided. These findings set the stage for determining the potential clinical value of these systems in impacting the care of chronic CHF patients.
Right Atrial Tachycardia in a Patient with Severe Atrial Conduction Disturbances and an Anatomically Normal Heart
Authors: NOVAK PAUL G. , MACLE LAURENT , THIBAULT BERNARD , GUERRA PETER G.
Published: June 2005

We describe a case of abnormal right atrial (RA) conduction in a patient with atrial tachycardia (AT) but no history of structural heart disease or cardiac surgery. Following ablation of AT, the patient experienced typical atrial flutter (AFL) and a postcardioversion ECG suggestive of low atrial rhythm. Repeat EPS and three‐dimensional electroanatomic activation mapping showed unusual RA activation during SR. This case illustrates the possibility that abnormal intraatrial conduction may lead to unusual patterns of activation in the RA which can serve as a necessary substrate for the initiation and maintenance of macro‐reentry circuits.
Left Ventricular Lead Performance in Cardiac Resynchronization Therapy: Impact of Lead Localization and Complications
Authors: ALBERTSEN ANDI EIE , NIELSEN JENS COSEDIS , PEDERSEN ANDERS KIRSTEIN , HANSEN PETER STEEN , JENSEN HENRIK KJÆRULF , MORTENSEN PETER THOMAS
Published: June 2005

Introduction: Cardiac resynchronization therapy (CRT) using left ventricular (LV) pacing from the coronary sinus tributary is increasingly and frequently used in patients with severe congestive heart failure. The present study investigates LV lead performance in different anatomic locations.

Methods: The LV pacing site was defined by bi‐plane fluoroscopy. In the left anterior oblique view, the coronary sinus is encircling the mitral ring with the tributaries radiating out like the hands of a watch. Using this clockwise method, Group A had an LV pacing site before 3 o'clock and Group B at or after 3 o'clock. In right anterior oblique view, the LV was divided into three segments: basal, mid‐ventricular, and apical.

Results: LV lead implantation was successful in all of 120 consecutive patients. Mean follow‐up was 16.7 months. Implantation time decreased from mean 190 to 80 minutes during the period (P = 0.01). The mean LV lead stimulation threshold increased initially and stabilized afterwards. The threshold measured at last follow‐up was higher than at implantation (2.3 vs 2.7 μJ, P = 0.04). Useful venograms were obtained in 94 patients. No significant difference in thresholds was observed between Groups A and B. Phrenic nerve stimulation was most commonly seen in Group B (8/70 vs 1/24, P = 0.001).

Conclusion: Implantation of an LV lead for CRT is possible in patients with congestive heart failure and associated with an acceptable low complication rate. LV lead implantation is associated with a learning curve. At mid‐term follow‐up, LV lead performance is stable and unrelated to the LV implantation site.
Electrogram Configuration and Detection of Supraventricular Tachycardias by a Morphology Discrimination Algorithm in Single Chamber ICDs
Authors: LÜTHJE L. , VOLLMANN D. , ROSENFELD M. , UNTERBERG‐BUCHWALD C.
Published: June 2005

Background: Inappropriate ICD therapy for supraventricular tachycardia (SVT) remains a significant problem. A morphology‐based algorithm (Wavelet™) compares baseline and tachycardia electrograms (EGM). For this analysis different EGM sources can be programmed. This study evaluates the performance of Wavelet using two different EGM configurations (SVC‐Can and RV‐Can) for the detection of exercise‐induced SVT.

Methods: Patients with a Medtronic model 7230 single chamber ICD and a dual coil lead were included. For each EGM source (SVC‐Can or RV‐Can), a baseline EGM template was acquired and the morphology similarity to this template (match percentage) was evaluated for 10–15 beats at different heart rates during exercise testing. The lower VT detection limit was programmed to 600 ms (therapies off).

Results: A total of 28 patients (66.9 ± 4.7 years, 93% men) and 5,824 intracardiac QRS complexes were analyzed. With the RV‐Can source, a consistently high similarity to the baseline EGM template was observed (≤100 bpm: 90.90 ± 0.56%; >100 bpm: 90.24 ± 0.55%, P > 0.05). In contrast, SVC‐Can was associated with a lower match percentage at baseline and a significant decrease at higher heart rates (≤100 bpm: 77.91 ± 2.65%; >100 bpm: 59.05 ± 5.65%, P < 0.005). Accordingly, the specificity for appropriate detection of exercise‐induced SVT was higher with RV‐Can (21/21 episodes) than with SVC‐Can (8/18 episodes, specificity 100% vs 44%; P < 0.0001).

Conclusion: The RV‐Can configuration appears to be superior to SVC‐Can as EGM source for appropriate SVT detection with the Wavelet algorithm.
Pregnancy in Postural Orthostatic Tachycardia Syndrome
Authors: GLATTER KATHRYN A. , TUTEJA DIPIKA , CHIAMVIMONVAT NIPAVAN , HAMDAN MOHAMED , PARK JEANNY K.
Published: June 2005

Introduction: Postural orthostatic tachycardia syndrome (POTS) is a rare disease characterized by syncope, sinus tachycardia, and orthostasis due to autonomic dysfunction.

Methods and Results: Two women aged 26 and 24 years with severe POTS became pregnant. Both women experienced hyperemesis gravidarum with subsequent marked improvement in their POTS symptoms until 6 months gestation, when their syncope and sinus tachycardia caused clinical decompensation. Both patients delivered healthy babies at 37 weeks by elective cesarian section.

Conclusion: In long‐term follow‐up, both women reported improvement in their prepartum symptoms. We describe the first report, to our knowledge, of two successful pregnancy outcomes in severe POTS, including the first report of midodrine use in pregnant women.
Utilization of Intracardiac Echocardiography to Access the Coronary Sinus for Left Ventricular Lead Placement
Authors: SHALABY ALAA A.
Published: June 2005

This is a presentation of a case series of 10 consecutive patients undergoing implantation of cardiac resynchronization therapy defibrillator (CRT‐D). Intracardiac echocardiography (ICE) is utilized to gain access to the coronary sinus. The method used is detailed with a brief discussion of observations gained from this early experience.
Remote Catheter Ablation of Parahisian Accessory Pathways Using a Novel Magnetic Navigation System—A Report of Two Cases
Authors: ERNST SABINE , HACHIYA HITOSHI , CHUN JULIAN K.R. , OUYANG FEIFAN
Published: June 2005

Introduction: Ablation of anteroseptal (parahisian) pathways may be difficult using conventional catheters.

Methods and Results: Two patients (51 and 20 years old) underwent ablation of a parahisian accessory pathway using the magnetic navigation system Niobe® (Stereotaxis, Inc.), which consists of two external permanent magnets (0.08 Tesla) that steer a small magnet embedded in the tip of the ablation catheter. A motor drive allows the advancement or retraction of the catheter. From the control room, the ablation was performed using a single radiofrequency current application (fluoroscopy 3.2 and 6.0 minutes, respectively).

Conclusions: The Niobe magnetic navigation system was successfully used to perform completely remote controlled mapping and ablation of parahisian accessory pathways.
Embolic Events and Char Formation During Pulmonary Vein Isolation in Patients with Atrial Fibrillation: Impact of Different Anticoagulation Regimens and Importance of Intracardiac Echo Imaging
Authors: WAZNI OUSSAMA M. , ROSSILLO ANTONIO , MARROUCHE NASSIR F. , SAAD EDUARDO B. , MARTIN DAVID O. , BHARGAVA MANDEEP , BASH DIANNA , BEHEIRY SALWA , WEXMAN MARK , POTENZA DOMENICO , PISANO ENNIO , FANELLI RAFFAELE , BONSO ALDO , THEMISTOCLAKIS SAKIS , ERCIYES DEMET , SALIBA WALID I. , SCHWEIKERT ROBERT A. , BRACHMANN JOHANNES , RAVIELE ANTONIO , NATALE ANDREA
Published: June 2005

Thromboembolic events are important complications of pulmonary vein isolation (PVI) procedures, occurring in up to 2.8% of patients. In this study, we report the incidence of char formation and embolic events with different anticoagulation protocols prospectively changed to reduce such complication.

Methods: A total of 785 patients (mean age: 54 years, 83.5% male) underwent catheter‐based PVI for treatment of drug refractory, symptomatic atrial fibrillation (AF). PVI was performed utilizing different strategies including radiofrequency (RF) using temperature control energy delivery and RF using intracardiac echocardiography (ICE)‐guided power titration. Patients were divided based on the anticoagulation protocol into three groups: in group 1 (194 patients), activation coagulation time (ACT) was maintained between 250 and 300 seconds; in group 2 (180 patients), ACT was maintained between 300 and 350 seconds plus the IV infusion of eptifibatide (135 μg/kg bolus + 0.5 μg/kg/min); and in group 3 (411 patients), ACT was maintained between 350 and 400 seconds.

Results: Char formation was detected in 69 patients of group 1, 5 of group 2, and 8 of group 3. An embolic event was observed in 7 patients of group 1, 3 of group 2, and 2 of group 3 (P = 0.01; group 1 vs group 3). Higher degree of anticoagulation with heparin was associated with a reduced incidence of embolic events even after removing the patients undergoing ICE‐guided ablation (P = 0.04).

Conclusion: More aggressive anticoagulation with heparin reduced periprocedural embolic events. The use of platelet inhibition does not have incremental beneficial effect. None of the anticoagulation protocol abolished char formation.
Quantitative Assessment of Microvolt T‐Wave Alternans in Patients with Congestive Heart Failure
Authors: KLINGENHEBEN THOMAS , PTASZYNSKI PAWEL , HOHNLOSER STEFAN H.
Published: June 2005

Introduction: T‐wave alternans has been shown to be linked to the genesis of ventricular tachyarrhythmias. Currently, only qualitative assessment of microvolt T‐wave alternans (MTWA) is recommended in clinical practise. Whether quantitave assessment of MTWA yields complementary information is unknown.

Methods and Results: Noninvasive MTWA determination was performed in 204 consecutive patients with ischemic or nonischemic cardiomyopathy. Of those, 100 tested MTWA positive. In these recordings, MTWA magnitude was quantitatively assessed (alternans voltage, Valt). Patients were followed for a mean of 17 months. Ventricular tachyarrhythmic events constituted the study endpoint. Patients with nonischemic cardiomyopathy had a higher Valt than patients with ischemic cardiomyopathy (10.3 ± 9.2 [median 7.2] vs 6.2 ± 3.2 [median 4.6]μV; P = 0.007). The number of MTWA‐positive ECG leads was also higher in patients nonischemic cardiomyopathy (7.3 ± 2.4 [median 8] vs 6.0 ± 2.5 [median 6]; P = 0.016). Patients who suffered an arrhythmic event during follow‐up had higher MTWA voltages (10.8 ± 10.0 [median 8.8] vs 7.4 ± 5.7 [median 6.4]μV; P = 0.05) a higher number of MTWA‐positive ECG leads (7.6 ± 2.4 [median 8] vs 6.4 ± 2.5 [median 6]; P = 0.05) compared to patients with an uncomplicated course.

Conclusion: Patients with nonischemic cardiomyopathy and patients with tachyarrhythmic complications have more extensive MTWA possibly reflecting more extensive myocardial damage and a higher arrhythmia propensity.