bluuebunny/crossref_metadata_2025 huggingface dataset:
An Elevated Hemidiaphragm 3 Months After Internal Jugular Vein Hemodialysis Catheter Placement
Authors: Rodby Roger A. , Mir Sevgi , Serdaroglu Erkin
Published: May 2003

ABSTRACT Phrenic nerve palsy following central venous catheterization is a rare complication and is not well recognized. We present a 33 months old girl who has renal failure secondary to nephrotic syndrome. A left internal jugular catheter was placed using the Seldinger technique after a single injection of 2 ml prilocaine hydrochloride for local anesthesia and a single internal jugular vein cannulation. Subsequent chest roentgenograms confirmed proper catheter and diaphragm position. Three months after catheter placement, decreased breath sounds on the left side of the chest were noted. Left phrenic nerve palsy was demonstrated with fluoroscopy and electromyography with external diaphragmatic elecrodes. The nerve damage was delayed after catheter placement, it seems unlikely that it was related to direct nerve trauma from the cannulation needle, local anesthetic infiltration of the nerve, or subsequent hematoma formation in this case. The phrenic nerve is in close proximity to both the catheter and the vein in which the catheter rests, an inflammatory reaction related to the catheter has been suggested as the cause for the nerve damage.
The Use of Apheresis in Immune Renal Disorders
Authors: Kaplan Andre A.
Published: May 2003

Abstract:  Rapidly progressive glomerulonephritis (RPGN) is often associated with the presence of auto‐antibodies. Included in this group are the glomerulonephritides associated with anti‐GBM antibody (Goodpasture's syndrome), IgA mesangial deposition (the renal component of Henoch‐Schönlein purpura), lupus erythematosus, cryoglobulinemia and the antineutrophil cytoplasmic antibody (ANCA)‐associated pauci‐immune group. In each of these cases, apheresis may provide a therapeutically useful option. Apheresis has also been found useful in certain types of antibody‐mediated transplant rejection and in lowering the levels of preformed cytotoxic antibodies which may preclude transplantation. Finally, there are renal diseases in which the immune component is less clearly involved with pathogenesis but for which apheresis may offer a clear benefit, such as in the renal failure associated with ‘cast nephropathy’ (multiple myeloma) or the recurrence of FSGS (focal segmental glomerulosclerosis) in transplanted kidneys. It is the purpose of this paper to review the evidence supporting the use of apheresis in immune‐related diseases.
Leukocytapheresis for Rheumatic Disease
Authors: Hidaka Toshihiko , Suzuki Kimihiro
Published: May 2003

Abstract:  Leukocytapheresis (LCAP) is an apheresis technique for depleting pathogenic leukocytes from the circulating blood to improve the condition of the patient. LCAP sensu lato has been applied for the treatment of various rheumatic diseases; other treatments include thoracic duct drainage, photopheresis, centrifugal LCAP, granulocytapheresis (GCAP) and filtration LCAP. Among these modalities, GCAP and filtration LCAP are most commonly used in Japan for two reasons; the equipment and procedure are simple and practical and adverse events are rare and minor. In this article, LCAP, in particular filtration LCAP, for the treatment of rheumatic diseases is reviewed.
The Role of Plasmapheresis in the Treatment of Severe Central Nervous System Neuropsychiatric Systemic Lupus Erythematosus
Authors: Neuwelt C. Michael
Published: May 2003

Abstract:  Twenty‐six patients, who received plasmapheresis (PP) either alone or synchronized with cyclophosphamide (IV‐CYC/PP), are retrospectively reviewed from Medline searches and personal experience from 1976 to 2002. Patients with central nervous system neuropsychiatric systemic lupus erythematosus (CNS‐NPSLE) were evaluated according to the American College of Rheumatology (ACR) case definitions of 1999. Eleven of the patients were under the age of 21 years (range 7–21 years), highlighting the need for an aggressive treatment option for young patients who are refractory to other treatments. After treatment with PP or IV‐CYC/PP, 74% of patients improved, 13% stabilized, and 13% progressed. Major side‐effects occurred from central line placement rather than immunomodulation from PP itself. Step‐down therapies are needed to supplement IV‐CYC/PP once improvement has reached a plateau. Newer combinations of PP and intravenous immunoglobulin (IVIg), human stem cell transplant (HSCT) and rituximab (RTX) should be considered in the future. In the absence of randomized controlled trials (RCT), experienced clinicians must weigh risk, benefit, and cost profiles in considering the treatment of severe CNS‐NPSLE with PP.
Access in Therapeutic Apheresis
Authors: Stegmayr Bernd , Wikdahl Ann Marie
Published: May 2003

Abstract:  Various modes may be used to perform apheresis, such as plasma exchange, plasmapheresis, immunoadsorption, and blood perfusion. The vascular access used for acute procedures may be sufficiently supplied by two peripheral veins or catheters placed in the femoral vein or the right internal jugular vein. For chronic treatment it might be necessary to place an arteriovenous fistula or graft. The risks involved when using the various accesses is discussed, as is the insertion technique of the femoral vein catheter. The insertion of catheters into larger vessels is preferably controlled by ultrasound guidance. The incidence of adverse events due to access problems is about 0.4%. Once in every 1000 planned procedures, a problem with the access will cause an interruption of apheresis. Other complications that may occur are infections and thrombosis. Long‐term use of particularly subclavian vein catheters more frequently results in stenosis than the use of other accesses. The placement of a femoral vein catheter is facilitated by outward rotation of the leg. In addition, other practical suggestions are given.
Basic Steps for Increasing the Rate of Autogenic Vascular Accesses for Hemodialysis
Authors: Salgado Octavio J.
Published: May 2003

Abstract:  The number of patients on chronic hemodialysis (HD) is steadily increasing worldwide. The creation of a well‐functioning vascular access represents a critical aspect in their management. Autogenous arteriovenous fistulas (AVF) are considered the first choice vascular access in terms of lower morbidity and costs, and higher survival rates when compared with grafts. However, creating AVF at high rates is a complex task that requires a multidisciplinary approach, which includes nephrologists, access surgeons, dialysis nurses and radiologists. In the present work we review concisely the basic steps, for preserving all potential autogenic sites at both upper extremities for future AVF creation and, for prolonging the length of AVF survival. We feel that a more proactive involvement of nephrologists in the basic steps for AVF creation would substantially contribute to increase AVF rates among HD patients.
Long‐term Catheters for Apheresis and Dialysis with Surface Treatment with Infection Resistance and Low Thrombogenicity
Authors: Bambauer Rolf , Mestres Pedro , Schiel Ralf , Bambauer Silke , Sioshansi Piran , Latza Reinhard
Published: May 2003

Abstract:  Infection, thrombosis, and stenosis are among the most frequent complications associated with blood‐contacting catheters. These problems are usually related to surface properties of the base catheter material. Surface treatment processes, such as ion implantation and ion beam assisted deposition (IBAD) and microdomain structured surfaces, can be used to mitigate such complications. This study evaluated silver coated and implanted large bore catheters used for extracorporeal detoxification. In a 186 patient prospective study, 225 large bore catheters were inserted into the internal jugular or subclavian veins. Eighty‐five surface‐treated catheters (Spi‐Argent, Spire Corporation, Bedford, MA, USA ) and 28 catheters with surface treatment (Spi‐Silicone, Spire Corporation) were inserted in 90 patients. One hundred and twelve untreated catheters placed in 96 patients served as controls. After removal, the catheters were cultured for bacterial colonization using standard microbiologic assays. They also were examined using a scanning electron microscope (SEM). Bacterial colonization was observed in 8% of the treated catheter compared with 46.4% of untreated catheters. The SEM investigations showed all treated catheters to possess low thrombogenicity. Catheters with microdomain structured surfaces showed same results in preliminary observation. The surface treatments of the large bore catheters can be used to improve thrombus and infection resistance of blood contacting catheters.
A Possible Role for Gap Junctions in Generation of Very Fast EEG Oscillations Preceding the Onset of, and Perhaps Initiating, Seizures
Authors: Traub Roger D. , Whittington Miles A. , Buhl Eberhard H. , LeBeau Fiona E. N. , Bibbig Andrea , Boyd Stewart , Cross Helen , Baldeweg Torsten
Published: May 2003

Purpose: We propose an experimentally and clinically testable hypothesis, concerning the origin of very fast (>∼70 Hz) EEG oscillations that sometimes precede the onset of focal seizures. These oscillations are important, as they may play a causal role in the initiation of seizures.

Methods: Subdural EEG recordings were obtained from children with focal cortical dysplasias and intractable seizures. Intra‐ and extracellular recordings were performed in rat hippocampal slices, with induction of population activity, as follows: (a) bath‐applied tetramethylamine (an intracellular alkalinizing agent, that opens gap junctions); (b) bath‐applied carbachol, a cholinergic agonist; and (c) focal pressure ejection of hypertonic K+ solution. Detailed network simulations were performed, the better to understand the cellular mechanisms underlying oscillations. A major feature of the simulations was inclusion of axon‐axon gap junctions between principal neurons, as supported by recent experimental data.

Results: Very fast oscillations were found in children before seizure onset, but also superimposed on bursts during the seizure, and on interictal bursts. In slice experiments, very fast oscillations had previously been seen on interictal‐like bursts; we now show such oscillations before, between, and after epileptiform bursts. Very fast oscillations were also seen superimposed on gamma (30–70 Hz) oscillations induced by carbachol or hypertonic K+, and in the latter case, very fast oscillations became continuous when chemical synapses were blocked. Simulations replicate these data, when axonal gap junctions are included.

Conclusions: Electrical coupling between principal neurons, perhaps via axonal gap junctions, could underlie very fast population oscillations, in seizure‐prone brain, but possibly also in normal brain. The anticonvulsant potential of gapjunction blockers such as carbenoxolone, now in clinical use for treatment of ulcer disease, should be considered.
An Animal Model of Nonconvulsive Status Epilepticus: A Contribution to Clinical Controversies
Authors: Kršek Pavel , Mikulecká Anna , Druga Rastislav , Hliňák Zdeněk , Kubová Hana , Mareš Pavel
Published: May 2003

Purpose: To characterize electroencephalographic and behavioral effects as well as electrophysiologic and morphologic consequences of a subconvulsive dose of pilocarpine in lithium chloride—pretreated rats.

Methods: Pilocarpine (15 mg/kg) was administered intraperitoneally to adult rats pretreated with lithium chloride (3 mEq/kg, i.p.). Behavior was observed for 2 h and videotaped in three consecutive sessions. At the same time, EEG was recorded from the sensorimotor cortex and the dorsal hippocampus. Threshold intensities of currents necessary to elicit hippocampal afterdischarges were determined 24 h and 1 week after the pilocarpine administration. The brains were histologically examined 1 week after pilocarpine administration using Nissl stain.

Results: Pilocarpine induced time‐limited nonconvulsive status epilepticus (NCSE). Epileptic EEG activity concurrent with prominent behavioral features was observed both in the neocortex and, predominantly, in the hippocampus. No changes in afterdischarge thresholds were observed in the dorsal hippocampus 24 h and 1 week after NCSE. One week after NCSE, seizure‐related brain damage was found mainly in the motor neocortical fields.

Conclusions: Pilocarpine‐induced NCSE in rats strongly resembles a short‐term human complex partial status epilepticus. Our animal model is suitable for studying the possible adverse effects of prolonged nonconvulsive seizures.
Altered Activities of Rat Brain Metabolic Enzymes in Electroconvulsive Shock—Induced Seizures
Authors: Erakovićl V. , Župan G. , Varljen J. , Laginja J. , Simonić A.
Published: May 2003

Purpose: Electroconvulsive shock (ECS) induces generalized seizure activity and provides an excellent experimental model for studying the effects of global electrical stimulation on various biochemical parameters. The aim of this work was to investigate the influence of a single or repeated ECS‐induced seizures on rat brain metabolism.

Methods: Experiments were carried out on female Hannover—Wistar rats divided into four groups: (a) the control group, which was intact; (b) the 1ECS group, which was killed 2 h after single ECS; (c) the 5ECS group with 24 h rest, which was killed 24 h after the fifth daily ECS; and (d) the 10ECS group with 48 h rest, which was given ECS every 48 h and killed 24 h after the tenth ECS. Activities of glutamate dehydrogenase (GLDH), aspartate‐aminotransferase (AST), alanine‐aminotransferase (ALT), γ‐glutamyltransferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and creatine kinase (CK) in the frontal cortex, cerebellum, hippocampus, and pons/medulla regions were determined.

Results: Increased AST, ALP, LDH, and CK activities were detected in all examined regions of the 1ECS and 5ECS groups. ALT activity was increased in both these groups, except in the hippocampus of the 5ECS group, where increased GGT activity was detected. In the hippocampus of 1ECS group, GLDH activity was decreased. Increased hippocampal AST and cortical CK activities, together with increased LDH activities in the cortex, cerebellum, and pons/medulla, were found.

Conclusions: ECS treatment induces region‐specific changes in metabolic activity. Neither a 24‐h nor a 48‐h rest period between two ECSs was sufficient for complete brain recovery, although most of the observed increased enzyme activities present in 1ECS and 5ECS were not present in 10ECS.
Contribution of the MHC Class II Antigens to the Etiology of Infantile Spasm in Mexican Mestizos
Authors: Suastegui Roberto A. , de La Rosa Gabriela , Carranza Juan M. , Gonzalez‐Astiazaran Adalberto , Gorodezky Clara
Published: May 2003

Purpose:Infantile spasms (ISs) are age‐dependant epileptic seizures, which may be flexor, extensor, lightning or nods, or mixed. The aim of this study was the analysis of genetic factors within the human leukocyte antigen (HLA) complex associated with ISs.

Methods:Sixty‐five patients diagnosed according to the established international criteria were compared with 229 healthy individuals; all of them were Mexican Mestizos. Five families were also analyzed (seven affected and five healthy sibs); HLA class I and class II antigens were typed using the standard microlymphocytotoxicity methods.

Results:The findings showed female gender preference (2:1). Two thirds were symptomatic, and prevalent seizures were of mixed type (67%). A strong association with HLA‐DR17 was detected in the IS group (pc <0.01; OR = 3.6; EF = 0.20). DR17 was also found increased in the symptomatic patients (p = 0.009; OR = 3.16) and in those with other types of seizures (p = 0.001; OR = 2.0). Conversely, HLA‐DQ6 was significantly decreased (pc <0.002; PF = 0.37) in the total and in the symptomatic groups (p <0.01). Haplotype linkage was not confirmed in the families; however, those with more than one affected sib shared at least one haplotype.

Conclusions:These findings suggest the contribution of DR locus to the susceptibility and the participation of DQ region in the resistance to IS. Severity seems also to be influenced by HLA‐DR17, and therefore class II typing may be a helpful tool for disease prognosis.
Multiple Subpial Transections: The Yale Experience
Authors: Mulligan Lisa P. , Spencer Dennis D. , Spencer Susan S.
Published: May 2003

Purpose: Although resection of an epileptogenic region is the mainstay of epilepsy surgery, epileptogenic areas in functionally critical cortex cannot be approached in that manner. Multiple subpial transection (MST) was developed to treat those refractory seizures without causing unacceptable neurologic deficit. We review our experience with this technique.

Methods: Twelve patients who underwent MST with or without resection between 1990 and 1998 were retrospectively reviewed with regard to seizure and neurologic outcome, and predictive factors.

Results: Five (42%) of 12 patients obtained a significant improvement in seizure frequency, and two other patients had a marked decrease in the severity of their seizures. Resection with MST reduced seizure frequency more, but this was not a significant difference. No predictive factors for outcome were identified. Only one patient sustained any persistent neurologic deficit.

Conclusions: In selected patients, MST may be a viable alternative when the epileptogenic focus lies in unresectable cortex. A multicenter study with appreciable patient numbers will be necessary to define predictive factors for success.
The Effect of Lamotrigine on Epileptiform Discharges in Young Patients with Drug‐Resistant Epilepsy
Authors: Eriksson A‐S. , Knutsson E. , Nergårdh A.
Published: May 2003

Purpose: In a double‐blind crossover study with lamotrigine (LTG), we investigated a possible relationship between the clinical responses and changes of the amount of epileptiform activity in EEG.

Methods: Twelve patients, aged 4–21 years, with generalized drug‐resistant epilepsy who had responded to LTG, completed the study. Twenty‐four‐hour video‐EEGs were taken during control, placebo, and drug phases. The amounts of epileptiform discharges were estimated and compared with the clinical effects.

Results: The duration of periods of repeated epileptiform discharges was significantly reduced during the LTG phase compared with the placebo phase (n = 12, p = 0.04). Ten patients showed a reduction of the amount of epileptiform discharges in the LTG phase by a mean of 81% (range, 17–100%). Periods of repeated epileptiform discharges with duration longer than 30 s were significantly reduced in length (p = 0.03) and number (p = 0.04) during the LTG phase compared with the placebo phase. Shorter periods of epileptiform discharges and the numbers of single epileptiform discharges were not affected. In five patients there was a seizure reduction (≥50%) concomitant with the reduction of epileptiform discharges in the EEG. The behavior improved during LTG treatment in all patients. The patients became more alert, and their concentration and performance improved, according to their parents and the medical personnel.

Conclusions: LTG in dosages of 1–8 mg/kg body weight was found to depress relatively long episodes of interictal, repetitive, epileptiform activity in young patients with drug‐resistant epilepsy, whereas short episodes were not affected. It depressed seizures in about half of the patients studied but gave improvements of behavior in all patients.
Adverse Event Monitoring in Lamotrigine Patients: A Pharmacoepidemiologic Study in the United Kingdom
Authors: Wong Ian C. K. , Mawer George E. , Sander Josemir W. A. S.
Published: May 2003

Purpose: This postmarketing surveillance study of lamotrigine (LTG) was performed to provide complementary data to large‐scale Prescription—Event Monitoring study with a retrospective case records survey in five tertiary referral epilepsy centres in the United Kingdom.

Methods: Adverse events were recorded and compared with those of two other new antiepileptic drugs (AEDs), gabapentin (GBP) and vigabatrin (VGB). All deaths were followed up and standardised mortality ratios (SMRs) were calculated. Serious adverse events were assessed individually.

Results: A total of 2,701 patients was identified as being exposed to LTG and/or the comparators. It was necessary to exclude 1,326 patients because LTG and/or comparators had been commenced outside the study centres. The adverse events with LTG reported by this study were similar to those reported in the literature. Skin rash was the major adverse event. Life‐threatening hepatic failure, acute exacerbation of ulcerative colitis, disseminated intravascular coagulation, and renal failure were reported. No death could be directly attributed to the use of LTG. The SMR was slightly higher than that reported in the literature; this probably reflects severity of epilepsy in the study population.

Conclusions: The safety profile of LTG was similar to that in the large‐scale Prescription‐Event Monitoring study and generally acceptable. Life‐threatening adverse reactions were rare.
Fosphenytoin: Pharmacokinetics and Tolerance of Intramuscular Loading Doses
Authors: Pryor Flavia M. , Gidal Barry , Ramsay R. Eugene , DeToledo John , Morgan Robert O.
Published: May 2003

Purpose: Fosphenytoin (FPHT; Cerebyx) is well absorbed when given intramuscularly (IM). All prior pharmacokinetic studies had the first plasma sample obtained 30 min after IM administration. The objectives of this study were to determine the rate and extent of FPHT absorption and to evaluate the tolerability of IM FPHT compared with IM saline.

Methods: This was an open‐label, double‐blinded study in which patients received 10 mg/kg dose of IM FPHT in one gluteus and IM saline in the other gluteus. Half the patients received saline injection of equal volume to FPHT (up to 19.5 mL); the other half received 2 mL of saline. Neurologic examination, vital signs, PHT blood samples, injection site examination, and subjective pain scores at injection site were obtained before and at timed intervals for 6 h.

Results: Total PHT serum concentrations 10 μg/mL were obtained in 5 min in 14.3% of patients and in 26.3% after 10 min. More than half the patients had therapeutic serum concentrations at 30 min; 45.8% of patients reported no pain at either the FPHT or saline injection site. No significant difference in pain was noted between FPHT and saline injection sites at 60 min and thereafter. Early decrease in blood pressure occurred but was not clinically significant. Classic PHT‐induced central nervous system (CNS) side effects were evident in one third of patients within 1 h after injection.

Conclusions: (a) IM FPHT is rapidly absorbed (therapeutic levels achieved as early as 5–20 min). (b) IM FPHT is well tolerated by most patients irrespective of injection volume.
Distribution of Valproate to Subdural Cerebrospinal Fluid, Subcutaneous Extracellular Fluid, and Plasma in Humans: A Microdialysis Study
Authors: Lindberger Martin , Tomson Torbjörn , Wallstedt Lars , Ståhle Lars
Published: May 2003

We sought to study the time course of the distribution of valproate (VPA) to subdural cerebrospinal fluid (CSF) in relation to subcutaneous extracellular fluid (ECF) and plasma after a single oral dose and to study the distribution to these three compartments under steady‐state conditions. Microdialysis was used to estimate unbound VPA concentrations in subdural CSF and subcutaneous ECF, and blood samples were drawn for estimation of total and unbound VPA plasma concentrations in four patients with drug‐resistant partial epilepsy undergoing presurgical evaluation with subdural EEG monitoring. Three patients were given a single oral dose of VPA, and one patient was receiving regular VPA treatment. VPA was analyzed by gas chromatography with flame ionization detection. The distribution of VPA to subdural CSF was rapid (Tmax, 3.5 h in two patients and 5.5 h in one patient) and subject to a minor delay in all three patients compared with that in the subcutaneous tissue ECF (Tmax, 2.5 h in all three patients), which in turn exhibited no evidence of a distribution delay compared with plasma. Subdural CSF levels of VPA were slightly lower than subcutaneous ECF levels (mean ratio, 0.78) and unbound plasma levels (mean ratio, 0.91). VPA rapidly enters the subdural CSF in unbound concentrations marginally lower than those obtained in subcutaneous ECF and plasma. These findings provide a pharmacokinetic rationale for acute administration of VPA. The good correlation between VPA concentrations in subcutaneous ECF and subdural CSF indicates that estimation of unbound VPA concentrations in subcutaneous tissue using microdialysis sampling has the potential to be useful for monitoring purposes.
Epileptic Seizures in Behçet Disease
Authors: Aykutlu Ebru , Baykan Betül , Serdaroǧlu Piraye , Gökyiǧit Aysen , Akman‐Demir Gülsen
Published: May 2003

Summary:  Purpose: To outline the clinical characteristics of seizures in our large series of Behçet disease (BD) patients with neurologic involvement.

Methods: All files of 223 patients with neuro‐BD were evaluated retrospectively, and the group with clearly documented seizures was included in the current study. Clinical characteristics, EEG, neuroimaging and cerebrospinal fluid findings were reevaluated, and the seizures were classified according to the new proposed criteria of the International League Against Epilepsy. On excluding the patients in whom the seizures were due to possible seizure‐provoking factors, the seizures that appeared during a neurologic exacerbation were noted.

Results: Seizures were seen in 10 (4.48%) of 223 patients. There were one female and nine male patients. In five of the patients, seizures occurred during neurologic exacerbation. Therefore, the actual prevalence of seizures due to BD in our group is 2.2%. In the remaining five patients, the seizures were not related to neurologic BD attacks, but probably were due to some seizure‐provoking factors. The predominating seizure type was generalized tonic–clonic convulsions accompanied by focal motor seizures. It is notable that four patients died 1–5 years after the onset of the seizures.

Conclusions: Our study showed that seizures are rare in BD. As the seizures due to some interventions and drugs are as frequent as neuro‐BD–related seizures, seizure‐provoking factors must be considered before attributing them to the pathogenetic mechanism of BD. The occurrence of seizures seems to be associated with a high mortality rate.
Increased Plasma Levels of Pro‐ and Anti‐inflammatory Cytokines in Patients with Febrile Seizures
Authors: Virta Miia , Hurme Mikko , Helminen Merja
Published: May 2003

Summary:  Purpose: Pro‐ and antiinflammatory cytokines regulate the febrile response during infection. Febrile seizures (FSs) conversely are associated with rapid onset of high fever. Activation of the cytokine network has been shown in previous studies of FSs and cytokines. In this study, the association between cytokines and FSs was further investigated.

Methods: Interleukin‐1β (IL‐1β), interleukin‐1 receptor antagonist (IL‐1RA), interleukin‐6 (IL‐6), interleukin‐10, and tumor necrosis factor‐α plasma levels were measured with enzyme‐linked immunosorbent assay in 55 children with FSs and in 20 age‐matched febrile controls immediately on arrival at the hospital. Cerebrospinal fluid cytokine levels also were measured in 16 FS children.

Results: The plasma IL‐1RA/IL‐1β ratio (mean, 2,133 vs. 119; median, 790 vs. 105; p < 0.0001) and plasma IL‐6 (mean, 41.7 pg/ml vs. 16.1 pg/ml; median, 19.6 pg/ml vs. 10.5 pg/ml; p = 0.005) were significantly higher in FS patients compared with control children. Logistic regression analysis was used to find the most significant predisposing factors for FSs. In this analysis, the high plasma IL‐1RA/IL‐1β ratio was the most significant factor connected to FSs (OR, 41.5; 95% CI, 4.9–352.8), but high plasma IL‐6 also was significantly associated with FSs (OR, 5.3; 95% CI, 1.4–20.3).

Conclusions: Present results support the hypothesis that the cytokine network is activated and could have a role in the pathogenesis of FS.
Reflex Seizures Induced by Defecation, with an Ictal EEG Focus in the Left Frontotemporal Region
Authors: Harbord Michael G. , Mitchell Carmel
Published: May 2003

Summary: We report a 9‐year‐old boy with seizures induced by defecation. The episodes occurred 1–2 min after passing a bowel action and consisted of initial staring, gagging, and drooling followed by a secondarily generalized tonic–clonic seizure. The interictal EEGs were normal, but an ictal EEG with concurrent video monitoring demonstrated a polyspike wave discharge in the left frontotemporal region. There was no evidence of syncope, and the seizures did not occur while straining to empty his bowels or immediately on standing afterward. His magnetic resonance imaging scan was normal. This is the first reported case in which ictal EEG monitoring has demonstrated reflex seizures induced by defecation.
Focal Cooling Suppresses Spontaneous Epileptiform Activity without Changing the Cortical Motor Threshold
Authors: Karkar Kameel M. , Garcia Paul A. , Bateman Lisa M. , Smyth Matthew D. , Barbaro Nicholas M. , Berger Mitchel
Published: May 2003

Summary:  Purpose: Focal cerebral cooling has been shown to reduce epileptiform activity in animals. There are, however, few reports of this phenomenon in humans.

Methods: Electrocorticography was performed before resection of a right frontal tumor in a patient with partial seizures. Cold saline was applied to the interictal spike focus, and its effect on the epileptiform discharges was observed.

Results: Application of cold saline to the spike focus resulted in a transient, complete cessation of spiking. This effect was reproduced with a second application of cold saline. The motor threshold for electrical stimulation remained unchanged during the application of saline.

Conclusions: In this patient with tumor‐related epilepsy, focal cooling of the cortex reproducibly abolished interictal epileptiform discharges without changing the motor threshold to electrical stimulation.
A Sheep Model for the Study of Focal Epilepsy with Concurrent Intracranial EEG and Functional MRI
Authors: Opdam Helen I. , Federico Paolo , Jackson Graeme D. , Buchanan Joanne , Abbott David F. , Fabinyi Gavin C. A. , Syngeniotis Ari , Vosmansky Milosh , Archer John S. , Wellard R. Mark , Bellomo Rinaldo
Published: May 2003

Summary:  Purpose: We describe a sheep model of penicillin‐induced seizure activity using electroencephalography (EEG) and functional MRI (fMRI).

Methods: Ten adult sheep were used. Spikes and seizures were generated by instillation of 8,000–10,000 IU of penicillin into the right prefrontal cortex via a specially designed port. Bilateral intracranial EEG was acquired by using carbon fiber electrodes. Animals had behavioral characterization of their seizures and were then anesthetized for fMRI studies. Functional MRI was performed at 1.5 and 3 Tesla by measuring blood oxygen level–dependent (BOLD) weighted signal intensity at different times during the evolution of seizures.

Results: Behavioral seizures were associated with electrographic seizures. Intracranial EEG obtained in the MR scanner was of high quality. Focal spiking and seizures were seen in all animals and developed 11.3 ± 11.2 s and 17.3 ± 12.1 min after penicillin administration, respectively. An average of 13 ± 4.8 seizures were seen per animal, each lasting 27.3 ± 12.3 s. Functional MR images with little parenchymal artefact were obtained. Regional BOLD signal‐intensity changes were observed during seizures at the seizure focus and ipsilateral amygdala.

Conclusions: We have developed an animal model of partial epilepsy in which seizures can be reliably elicited with concurrent fMRI and intracranial EEG. During unilateral electrographic seizures, focal BOLD signal changes occurred at the seizure focus and ipsilateral amygdala, suggesting the presence of a cortico–subcortical loop. This observation illustrates the potential of the model for understanding seizure generation, spread, and possibly the consequences of repeated seizures on the brain.
Hypomotor Seizures in Infants and Children
Authors: Källén Kristina , Wyllie Elaine , Lüders Hans O. , Lachhwani Deepak , Kotagal Prakash
Published: May 2003

Summary:  Purpose: Hypomotor seizures (characterized by diminished behavioral activity with indeterminate level of consciousness) have been identified as an important seizure type in infants. Our goal was to investigate further the clinical and EEG features of hypomotor seizures.

Methods: We retrospectively reviewed 110 hypomotor seizures from 34 patients recorded with video‐EEG.

Results: Twenty‐seven (79%) patients were younger than 48 months, and seven (21%) were aged 4 to 15 years. Seventy‐one (64%) seizures had regional or lateralized EEG onset, arising predominantly from temporal or parietal lobe regions. The other 39 (35%) seizures had generalized onset, usually with abrupt onset of diffuse rhythmic high‐amplitude theta activity or diffuse electrodecrement and only rarely (two patients) with slow spike–wave complexes or 3‐Hz spike–wave complexes. Hypomotor seizures with generalized EEG onset were significantly shorter than those with regional or lateralized onset (p = 0.01, GEE model). Unsustained head or eye movements and subtle mouth automatisms were commonly seen in hypomotor seizures with either focal or generalized onset. Seventeen percent of hypomotor seizures with focal onset evolved to include version of head and eyes or jerking of one arm, whereas 2% of generalized hypomotor seizures evolved to a cluster of spasms.

Conclusions: Hypomotor seizures may be either focal or generalized. Regional EEG onsets were most often temporal or parietal, suggesting that focal hypomotor seizures may be a bland form of “complex partial” seizures with no or minimal automatisms, seen predominantly in infants. Generalized hypomotor seizures were rarely associated with an ictal pattern of generalized spike–wave complexes, suggesting a different mechanism from absence seizures seen later in life.
Memory Lateralization in Medial Temporal Lobe Epilepsy Assessed by Functional MRI
Authors: Golby Alexandra J. , Poldrack Russell A. , Illes Judy , Chen David , Desmond John E. , Gabrieli John D. E.
Published: May 2003

Summary:  Purpose: To determine the utility of functional magnetic resonance imaging (fMRI) in preoperative lateralization of memory function in patients with medial temporal lobe epilepsy (MTLE).

Methods: Nine patients with MTLE underwent standard preoperative assessment including video‐EEG and intracarotid amytal testing (IAT). fMRI was performed while subjects encoded four types of stimuli (patterns, faces, scenes, and words). Activation maps were created for each subject representing areas more active for novel than for repeated stimuli. Regions of interest were drawn around the MTL in individual subjects, suprathreshold voxels were counted, and an asymmetry index was calculated.

Results: In eight of nine subjects, lateralization of memory encoding by fMRI was concordant with that obtained from the IAT. Group‐level analysis demonstrated greater activation in the MTL contralateral to the seizure focus such that in the left MTLE group, verbal encoding engaged the right MTL, whereas in the right MTLE group, nonverbal encoding engaged the left MTL.

Conclusions: fMRI is a valid tool for assessing of memory lateralization in patients with MTLE and may therefore allow noninvasive preoperative evaluation of memory lateralization. FMRI revealed that memory encoding may be reorganized to the contralateral MTL in patients with MTLE.
Optimizing Parameters for Terminating Cortical Afterdischarges with Pulse Stimulation
Authors: Motamedi Gholam K. , Lesser Ronald P. , Miglioretti Diana L. , Mizuno‐Matsumoto Yuko , Gordon Barry , Webber William R. S. , Jackson Darryl C. , Sepkuty Jehuda P. , Crone Nathan E.
Published: May 2003

Summary:  Purpose: We previously reported that brief pulses of electrical stimulation (BPSs) can terminate afterdischarges (ADs) during cortical stimulation. We investigated conditions under which BPS is more likely to suppress ADs.

Methods: We analyzed parameters altering BPS effectiveness on 200 ADs in seven patients with implanted subdural electrodes.

Results: The odds of BPSs stopping ADs was 8.6 times greater at primary sites (directly stimulated electrodes) than at secondary sites (adjacent electrodes) (p = 0.016). BPS applied within 4.5 s after onset of AD had 2 times greater odds of stopping ADs (p = 0.014). BPS applied when AD voltage was negative was 1.9 times more likely to stop ADs (p = 0.012). ADs with rhythmic pattern responded best (p < 0.0001). BPS stopped 100% of ADs not starting immediately after localization stimulus (LS) versus 29% of those starting immediately (p < 0.0001).

Conclusions: BPS is more likely to terminate ADs at primary electrodes, if given early, if applied to the negative peak of the AD waveform, if AD has a rhythmic pattern, and if AD did not start immediately after LS.
Is There an Association between Maternal Carbamazepine Use during Pregnancy and Eye Malformations in the Child?
Authors: Kroes Hester Y. , Reefhuis Jennita , Cornel Martina C.
Published: May 2003

Summary:  Purpose: To check for an association between carbamazepine (CBZ) use by the mother during pregnancy and congenital eye malformations (i.e., anophthalmia, microphthalmia, and coloboma) in the child, as suggested by Sutcliffe et al. (1998), who reported four cases.

Methods: We checked all the cases with these eye malformations for CBZ use by the mother in the EUROCAT Northern Netherlands dataset, which registers infants with congenital malformations and records possible teratogenic exposures (including medication taken by the mother). We also reviewed 13 studies in the literature.

Results: The EUROCAT dataset recorded 77 cases of anophthalmia, microphthalmia, or coloboma, but none with prenatal exposure to CBZ. Prenatal CBZ exposure was recorded in seven other cases without congenital eye malformation. Large studies in the literature on the teratogenic effects of CBZ (and other antiepileptic drugs), including data from the MADRE database, revealed no association between these congenital eye malformations and prenatal CBZ exposure. One case reported bilateral anophthalmia and other congenital anomalies after prenatal exposure to CBZ in combination with vigabatrin and dexamethasone.

Conclusions: Our data do not support Sutcliffe's suggestion that prenatal CBZ exposure may result in congenital eye malformations. However, despite the large population represented, both the low birth prevalence of these congenital eye malformations and the low prevalence of CBZ exposure during pregnancy make it difficult to exclude an increased relative risk. The many large prospective and retrospective studies in the literature seem to agree with our findings, although there is still uncertainty about the teratogenic effect of CBZ in polytherapy.
Frequency and Significance of Acute Postoperative Seizures Following Epilepsy Surgery in Children and Adolescents
Authors: Park Kristen , Buchhalter Jeffrey , McClelland Robyn , Raffel Corey
Published: May 2003

Summary:  Purpose: To determine the frequency and prognostic features of acute postoperative seizures (APOSs), within the first postoperative week, in a group of children undergoing surgery for the treatment of medically refractory epilepsy.

Methods: Patients younger than 18 years who underwent surgery for the relief of medically intractable epilepsy at the Mayo Clinic between 1985 and 1998 with a minimum of 12 months of follow‐up were eligible. A retrospective chart review was conducted to abstract information regarding demographics, epilepsy history, and preoperative, intraoperative, and postoperative risk factors, APOSs, and outcome. A multivariate analysis was conducted to control for confounding variables.

Results: The study group was composed of 148 patients (mean age at surgery, 13 years; range, 5 months to 18 years). Twenty‐five percent of patients experienced APOSs. Risk factors associated with a statistically significant (p < 0.05) greater likelihood of experiencing APOS were non–complex partial seizure type, extratemporal surgery, postoperative fever, non–temporal lobe epilepsy, and postoperative interictal epileptiform activity. At last follow‐up, patients who did not experience APOSs had a significantly greater chance of being seizure free (80 vs. 51%; p < 0.001). With a multivariate analysis, APOS was found to be an independent predictor of outcome.

Conclusions: This study indicates that APOSs are predictive of a less favorable outcome in the pediatric postsurgical patient; however, 51% remained seizure free at last follow‐up. Finally, the effects of APOSs on outcome were shown to be stable over a 12‐month follow‐up period.
Seizure Suppression by Adenosine‐releasing Cells Is Independent of Seizure Frequency
Authors: Boison Detlev , Huber Alexander , Padrun Vivianne , Déglon Nicole , Aebischer Patrick , Möhler Hanns
Published: May 2003

Summary:  Purpose: Intraventricular cellular delivery of adenosine was recently shown to be transiently efficient in the suppression of seizure activity in the rat kindling model of epilepsy. We tested whether the suppression of seizures by adenosine‐releasing grafts was independent of seizure frequency.

Methods: Adenosine‐releasing cells were encapsulated and grafted into the lateral brain ventricle of rats kindled in the hippocampus. During 4 weeks after grafting, electric test stimulations were delivered at a frequency of either once a week or 3 times per week. Seizure activity was evaluated by visual scoring of seizure severity and by the recording of EEGs.

Results: Adenosine released from encapsulated cells exerted potent antiepileptic activity for ≥2 weeks. One week after grafting, treated rats displayed a complete protection from clonic seizures, and a protection from focal seizures was observed in the majority of animals. Seizure suppression was accompanied by a reduction of afterdischarges in EEG recordings. The protective efficacy of the grafted cells was the same irrespective of whether electrical test stimulations were delivered 1 or 3 times per week. Rats receiving control grafts continued to display full clonic convulsions.

Conclusions: This study demonstrated that the frequency of test stimulations did not influence the seizure‐suppressive potential of adenosine‐releasing grafts. Thus the local delivery of adenosine is likely to be effective in seizure control over a threefold range of seizure‐discharge frequency.
Epilepsy inThe Alienist and Neurologist, 1880–1920
Authors: Lipson Scott E. , Montes Jennifer A. , Devinsky Orrin
Published: May 2003

Summary: Purpose:To study the history of epilepsy from 1880 to 1920.

Methods:We reviewed all 40 volumes ofThe Alienist and Neurologistand identified articles concerning primarily epilepsy. We analyzed three of these articles in greater detail.

Results:The Alienist and Neurologistpublished “Original Contributions,”“Selections,” (abstracts from other journals written by the editorial board), “Editorials,” and (book) “Reviews.” Of 258 epilepsy articles, there were 40 Original Contributions, 164 Selections, 39 Editorials, and 15 Reviews. These articles included 71 on therapy (41 medication, 13 surgery, and 17 other therapies); 66 general discussions; 46 on etiology or symptoms; 34 case studies; 28 social/legal articles; and 13 autopsy or pathology articles.

Conclusions:Analysis ofThe Alienist and Neurologistprovides a unique and valuable perspective on the clinical practice and academic world of epileptology during the decades around the turn of the twentieth century.
Amygdaloid Kindling in Glutamate Transporter (GLAST) Knockout Mice
Authors: Tsuru Noriko , Ueda Yuto , Doi Taku
Published: May 2003

Summary:  Purpose: Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system. We previously reported abnormal glutamate release during seizures after kindling. GLAST and GLT‐1 are astrocytic glutamate transporters, highly concentrated in the cerebellum and the telencephalon, respectively. We have investigated whether stages of amygdala kindling in knockout (KO) mice deficient in GLAST are the same as those of wild mice.

Methods: Electrodes were implanted into the basolateral amygdala, bilaterally, in C57BL/6J mice and GLAST KO mice under anesthesia. Once‐daily stimulation was applied on one side through these electrodes, and bilateral EEG recordings were obtained.

Results: The behavioral manifestations of kindling in mice were (a) arrest of behavior, (b) head nodding, (c) forelimb clonus, (d) bilateral forelimb clonus with rearing, (e) tonic generalized convulsion with elevation of tail and falling with generalized tonic convulsion (GTC). Results of kindling: (a) Mutant mice kindled more slowly than wild‐type mice (more stimulations were required to reach each stage in mutants); (b) after kindling was completed, additional stimulations induced shorter afterdischarges (ADs) in mutants than in wild‐type mice; (c) Interictal epileptic spikes were more frequent in the mutants than in the wild‐type mice, both in the stimulated amygdala and in the contralateral amygdala.

Conclusions: GLAST KO mice, which are missing one type of astrocytic glutamate transporter, demonstrate kindling of an epileptic focus. However, the kindling is significantly slower in the GLAST mutant than in wild‐type mice. These findings suggest that glutamate transport by the astrocytic GLAST transporter may have a role in normal epileptogenesis.
Lack of an Effect of Topiramate on Lamotrigine Serum Concentrations
Authors: Berry David J. , Besag Frank M. C. , Pool Felicity , Natarajan Jaya , Doose Dennis
Published: May 2003

Summary:  Purpose: Pharmacokinetic interactions between the older antiepileptic drugs (AEDs) and topiramate (TPM) were assessed during the clinical development of this drug. Lamotrigine (LTG) has become established as an important new drug in treating a wide spectrum of seizure types, but there are no published data on whether LTG serum concentrations change when TPM is added to treatment.

Methods: Escalating doses of TPM were added to stable LTG treatment in 24 young patients (8–21 years) with epilepsy. Blood samples taken before the morning dose were collected for drug‐concentration measurement in all patients before starting treatment with TPM and after stabilisation at each dose escalation. Several patients had been maintained on unchanged therapy with drug‐concentration monitoring for many months before introducing TPM, and a sequence of baseline LTG serum concentrations were available on these patients.

Results: The mean of all baseline LTG concentrations for the group as a whole was 10.4 ± 4.4 mg/L compared with 9.7 ± 4.3 mg/L after addition of TPM. A comparison of last baseline LTG concentration with first test LTG concentration (i.e., after 2 weeks' TPM treatment) gave mean values of 10.7 ± 4.7 and 10.8 ± 4.6 mg/L, respectively. The mean LTG concentration for patients while taking their highest TPM dose was 9.5 ± 4.3 mg/L. The analysis‐of‐variance modeling for the effect of TPM on LTG concentration yielded a mean LTG concentration ratio (with TPM vs. without TPM) of 94.2%, with a 90% confidence interval of 89.5–99.1%.

Conclusions: TPM did not cause a significant change in LTG serum concentration in this group of patients.