bluuebunny/crossref_metadata_2025 huggingface dataset:
Voltage‐Activated Calcium Channels: Targets of Antiepileptic Drug Therapy?
Authors: Stefani Alessandro , Spadoni †Francesca , Bernardi Giorgio
Published: August 2005

Summary: Voltage‐gated calcium currents play important roles in controlling neuronal excitability. They also contribute to the epileptogenic discharge, including seizure maintenance and propagation. In the past decade, selective calcium channel blockers have been synthesized, aiding in the analysis of calcium charinel subtypes by patch‐clamp recordings. It is still a matter of debate whether whether any of the currently available antiepileptic drugs (AEDs) inhibit these conductances as part of their mechanism of action. We tested oxcarbazepine, lamotrigine, and felbamate and found that they consistently inhibited voltage‐activated calcium currents in cortical and striatal neurons at clinically relevant concentrations. Low micro‐molar concentrations of GP 47779 (the active metabolite of oxcarbazepine) and lamotrigine reduced calcium conductances involved in the regulation of transmitter release. In contrast, felbamate blocked nifedipine‐sensitive conductances at concentrations significantly lower than those required to modify N‐methyl‐d‐aspartate (NMDA) responses or sodium currents. Aside from contributing to AED efficacy, this mechanism of action may have profound implications for preventing fast‐developing cellular damage related to ischemic and traumatic brain injuries. Moreover, the effects of AEDs on voltage‐gated calcium signals may lead to new therapeutic strategies for the treatment of neurodegenerative disorders.
Dissociation in Epilepsy and Conversion Nonepileptic Seizures
Authors: Alper Kenneth , Devinsky Orrin , Perrine Kenneth , Luciano Daniel , Vazquez Blanca , Pacia Steven , Rhee Eun
Published: August 2005

Summary: Purpose: We examined the dimensionality of the item content of the Dissociative Experiences Scale (DES) in relation to the clinical diagnosis of conversion nonepileptic seizures (C‐NES) versus complex partial epilepsy (CPE).

Methods: The DES was administered to a sex‐ and agematched sample of 132 patients with C‐NES and 169 with CPE and was factor analyzed with principal components analysis (PCA) with varimax rotation.

Results: The mean total DES score was 15.1 in the C‐NES group and 12.7 in the CPE group (p = 0.079). The factors obtained by PCA differentiated the CPE and C‐NES groups more strongly than did the total DES score. The factor accounting for the most variance, interpreted as “depersonalizationderealization,” was significantly greater in C‐NES than CPE (p = 0.005). An “absorption‐imaginative involvement” factor, which included some of the clinical features of posttraumatic stress disorder was elevated only in subjects reporting histories of childhood abuse (p = 0.001) regardless of the diagnosis of CPE or C‐NES. An “amnestic” factor appearing to represent memory problems related to neurologic impairment showed a trend toward elevation in CPE (p = 0.056) and may have confounded the CPE versus C‐NES distinction using total DES scores.

Conclusions: The DES has separate underlying dimensions that appear to relate distinctively to depersonalization and derealization, childhood trauma, and neurologic impairment. The heterogeneous item content of the DES is a potential confound that should be appreciated when this instrument is used to study dissociation in neuropsychiatric populations.
The Relation Between Quantitative MRI Measures of Hippocampal Structure and the Intracarotid Amobarbital Test
Authors: Baxendale S. A. , Van Paesschen W. , Thompson P. J. , Duncan J. S. , Shorvon S. D. , Connelly A.
Published: August 2005

Summary: Purpose: The increasing sophistication of quantitative magnetic resonance imaging (MRI) techniques has generated hopes that they may eventually supersede the intracarotid amobarbital procedure (IAP) in the presurgical screening for bilateral abnormalities in prospective candidates for temporal lobe epilepsy surgery. As the first step toward this aim, the purpose of this study was to examine the relationship between these measures of structural and functional integrity.

Methods: We examined the relation between memory performance and pasdfail rates on the IAP and two MRI measures of hippocampal integrity: hippocampal volumes, adjusted for intracranial volume (HCvol) and hippocampal T2 relaxometry (HCT2), in 48 patients with medically intractable temporal lobe epilepsy, who underwent the IAP as part of their presurgical evaluation for temporal lobectomy.

Results: The unilateral memory scores from the IAP were not significantly correlated with the corresponding HCvol or HCT2 measures in the right‐ and left‐temporal‐lobe groups. However, the MRI measures of hippocampal asymmetry (right minus left HCvol right minus left HCT2) were significantly correlated with our measure of functional asymmetry, the right minus left hemisphere memory score from the IAP, supporting the role of the IAP in lateralising temporal lobe dysfunction. Forty‐six patients with unilateral hippocampal sclerosis and concordant EEG studies passed the IAP. Two patients failed the memory component of the IAP. In both cases, other presurgical investigations suggested bilateral abnormalities.

Conclusions: We conclude that patients with unilateral hippocampal sclerosis, established by a rigorous quantitative MRI protocol, and concordant ictal and interictal EEG findings may not be at risk for postoperative amnesia, despite baseline neuropsychological deficits suggestive of bilateral disturbance.
Widespread Cerebral Structural Changes in Two Patients with Gelastic Seizures and Hypothalamic Hamartomata
Authors: Sisodiya S. M. , Free S. L. , Stevens J. M. , Fish D. R. , Shorvon S. D.
Published: August 2005

Summary: Purpose: We tested the hypothesis that widespread extralesional abnormalities of cerebral structure exist in association with apparently isolated hypothalamic hamartomata, providing a structural basis for the poor response of seizures to removal of the hamartoma or other apparently focal epilepto‐genic zones present.

Methods: High‐resolution magnetic resonance imaging (MRI) brain scans of 2 patients with hypothalamic hamartomata were quantified by determination of regional distribution and symmetry of distribution of cortical gray matter and subcortical matter volumes. The results were compared with normal ranges for the distribution of such tissues in 33 controls.

Results: Both patients had abnormalities of distribution of gray and subcortical matter, whereas control subjects did not. These abnormalities were beyond the hamartoma itself, in areas of cerebrum that on visual inspection alone appeared completely normal.

Conclusions: Extralesional abnormalities of cerebral structure are present in the cerebrum of patients with hypothalamic hamartoma, as in most patients with other dysgeneses. These abnormalities may explain the poor outcome of epilepsy surgery in patients with this form of dysgenesis. These preliminary findings require further investigation.
Cyclic Alternating Pattern as a Provocative Factor in Nocturnal Paroxysmal Dystonia
Authors: Terzano Mario Giovanni , Monge‐Straws Marie‐France , Mikol Francois , Spaggiari Maria Cristina , Parrino Liborio
Published: August 2005

Summary: Purpose: We made a polygraphic study of 6 patients with nocturnal paroxysmal dystonia (NPD) in which the cyclic alternating pattern (CAP) parameters were compared with those of a group of age‐ and sex‐matched controls.

Methods: All patients met the requirements for NPD diagnosis, characterized by generalized stereotyped movements (dystonic‐dyskinetic), with a 1‐min centered duration but with no clear evidence of epileptic abnormalities in the waking EEG and during nocturnal recordings.

Results: Besides the major events, the NPD polysomnograms also showed shorter, repeated episodes of shorter duration (generally <20 s) consisting of abrupt movements involving one or more body segments. Overall, the motor events in patients with NPD were closely related to periods of unstable non‐REM (NREM) sleep, as evidenced by the sequences of CAP, and began during an A phase. According to the conventional scoring parameters, NPD and controls differed only in sleep latency (+14 min in the NPD patients: p < 0.04). However, the architecture of sleep in the group with NPD was characterized by prolonged and irregular NREMREM cycles. In addition, the NPD recordings showed significantly higher values of CAP rate (p < 0.0001). When major motor attacks were suppressed by medication, sleep was characterized by a decrease in the excessive amounts of CAP rate and by a more regular architecture.

Conclusions: The modulatory role of CAP on nocturnal motor events is reported.
Initial Human Experience with Ganaxolone, a Neuroactive Steroid with Antiepileptic Activity
Authors: Monaghan Edward P. , Navalta Laura A. , Shum Linyee , Ashbrook Donald W. , Lee David A.
Published: August 2005

Summary: Purpose: Studies were conducted to establish the safety, tolerability, and pharmacokinetics of the antiepileptic drug (AED) ganaxolone. Ganaxolone belongs to a novel class of neuroactive steroids called epalons, which specifically modulate the γ‐aminobutyric acid type A (GABAA) receptor in the central nervous system (CNS). Chemically related to progesterone but devoid of any hormonal activity, the epalons have potent antiepileptic, anxiolytic, sedative, and hypnotic activities in animals.

Methods: Ninety‐six healthy male and female volunteers received ganaxolone in a variety of formulations, doses, and dosing regimens. The pharmacokinetics of ganaxolone were systematically characterized, and adverse events associated with drug use were documented.

Results: Ganaxolone was well tolerated after single doses (≥1,500 mg) and after multiple doses (≥300 mg b.i.d for 10 days). Steady‐state plasma levels (trough) occurred after ˜7 days of dosing, with mean steady‐state plasma concentrations (Cmax) in multiple dose studies of between 32 ng/ml (50‐mg doses) and 376 ng/ml (500‐mg doses). No serious or lifethreatening adverse events attributed to the drug were observed. The majority of adverse events reported were mild (82%) to moderate (14%) and were limited to headache, dizziness, somnolence, gastrointestinal disturbances, and malaise.

Conclusions: Ganaxolone alone or formulated with pharmaceutical‐grade excipients is rapidly absorbed from the gastrointestinal tract after oral administration in doses ranging from 50 to 1,500 mg. Pharmacokinetic analysis revealed a linear and proportional increase in the area under the curve (AUC) and Cmax values with increasing dose within the expected therapeutic dose range. Safety and tolerability in the clinical program were unremarkable.
Intraventricular Interferon‐α Stops Seizures in Rasmussen's Encephalitis: A Case Report
Authors: Dabbagh Omar , Gascon Generoso , Crowell Janice , Bamoggadam Fawzia
Published: August 2005

Summary: A 3.5‐year‐old girl had epilepsia partialis continua of the right side. Clinical and laboratory findings were consistent with Rasmussen's encephalitis. Treatment with high‐dose methylprednisolone led to temporary control of seizures, but for 2 years, the seizures remained refractory to phenobarbital, phenytoin, lorazepam, carbamazepine, valproic acid, vigaba‐trin, gabapentin, and lamotrigine. A 6‐week course, and later a 6‐month course, of intraventricular interferon‐α almost totally suppressed the seizures. Although moderately hemiparetic, the child has reasonable neurologic function with mild speech delay. She is receiving her third course of treatment, and seizures remain completely controlled.
Landau‐Kleffner Syndrome: Consistent Response to Repeated Intravenous γ‐Globulin Doses: A Case Report
Authors: Fayad Michel N. , Choueiri Roula , Mikati Mohamad
Published: August 2005

Summary: Purpose: Although several treatments have been tried for Landau‐Kleffner syndrome (LKS) too many patients are refractory to known therapies. We report an 8–year‐old girl who failed other therapies but who had a consistent response after treatment with intravenous (i.v.) γ‐globulin.

Methods: We monitored the girl from the age of 6 years, when she presented with a 6–month history of loss of language with normal hearing, normal brain magnetic resonance imaging (MRI), increased cerebrospinal fluid (CSF) IgG index, and an EEG showing almost continuous, predominantly left‐sided spike‐ and slow‐wave complexes. She had no clinical seizures and did not respond to consecutive trials of valproate (VPA), clonazepam (CZP), prednisone, and carbamazepine (CBZ). She received three courses of intravenous (i.v.) γ‐globulin; after each course, clinical and electrographic improvement lasted a few months. After each of the initial two eourses, clinical improvement lasted 3–4 months but was followed by recurrence of the spikes on the EEG and by speech deterioration.

Results: However, her last remission has been continuous for the past 16 months. Her CSF IgG index became normal after the first i.v. γ‐globulin infusion.

Conclusions: Based on our experience with this patient and on other investigators' experience, we believe that further research into immunologic mechanisms and therapies of this syndrome are warranted.
Left Hemispheric Dominance of Epileptiform Discharges
Authors: Dean Andy C. , Solomon Gail , Harden Cynthia , Papakostas George , Labar Douglas R.
Published: August 2005

Summary: Purpose: We reviewed 1,360 EEG reports for all patients studied in two different neurophysiology laboratories during 1 calendar year to determine whether epileptiform discharges have a hemispheric dominance.

Methods: Both inpatients and outpatients, with or without epilepsy, were included.

Results: Ninety‐four records (6.9%) demonstrated generalized epileptiform activity. Of 95 EEG reports indicating spikes solely from one hemisphere, spikes arose from the left in 61 and from the right in 34. Among 50 other records with bilateral independent spikes with lateralization, 40 were left hemisphere‘dominant and 10 were right hemisphere dominant.

Conclusions: These findings raise the possibility that the left cerebral hemisphere may generate focal epilepsy more frequently than the right.
Cyclosporin A and Brain Excitability Studied In Vitro
Authors: Taubøll Erik , Gerdts Remo , Gjerstad Leif
Published: August 2005

Summary: Purpose: Seizures are frequently observed after organ transplantations. This has been attributed to a direct effect of cyclosporin A (CsA) on the brain, although other mechanisms may also be of importance. The aim of this study was to investigate possible acute and direct effects of CsA on neuronal excitability.

Methods: Female rat hippocampal slices were perfused with CsA solutions containing 400 (n = 4), 1,000 (n = 4), 2,000 (n = 6), 8,000 (n = 8) μg/L CsA or control (n = 8) for 30 min, or penicillin, 2,000 IE/ml (n = 7). Actual concentrations of CsA were measured in the perfusate drawn from the slice chamber. To study CsA accumulation in the slices, uptake of radioactive CsA was measured in 12 living and 11 dead slices.

Results: Despite a significant accumulation of CsA in the living neuronal slices, no effects were observed on prevolley, field excitatory postsynaptic potential (EPSP), or population spike amplitude. Penicillin, however, led to epileptiform activity within 10 min in all cases. Concentrations of CsA in the perfusate from the slice chamber were about half the calculated levels, demonstrating that the slices had been exposed to actual CsA concentrations in the range of ε200–4,000 μg/L CsA.

Conclusions: Our results demonstrate a lack of acute effects of CsA on neuronal excitability within clinically relevant concentrations despite an active accumulation of the drug in the slices. Long‐term effects on brain tissue, indirect metabolic effects, or synergistic effects may be responsible for the neurotoxicity of the drug.
Complications of the Ketogenic Diet
Authors: Ballaban‐Gil Karen , Callahan C. , O'Dell C. , Pappo M. , Moshé S. , Shinnar S.
Published: August 2005

Summary: Purpose: The ketogenic diet has been successfully used in treatment of pediatric epilepsy for >70 years. Few serious complications caused by the diet have been reported. We report complications that have been experienced by children receiving the ketogenic diet.

Methods: In a 22‐month period, we treated 52 children with the classic ketogenic diet and monitored them in a prospective manner.

Results: Five children (10%) experienced serious adverse events (AE) after initiation of the diet. Four patients (80%) were treated with valproate (VPA) in addition to the diet, as compared with 25 (53%) of the other 47 children. Two patients developed severe hypoproteinemia within 4 weeks of initiation of the diet, and 1 of them also developed lipemia and hemolytic anemia. A third child developed Fanconi's renal tubular acidosis within 1 month of diet initiation. Two other children manifested marked increases in liver function tests, 1 during the initiation phase and the other 13 months later.

Conclusions: Clinicians who wish to use the ketogenic diet must be aware of the potential of serious AE and possible interactions of the diet with VPA.
Neuropsychological Effect of Temporal Lobe Resection in Preadolescent Children with Epilepsy
Authors: Szabó C. Akos , Wyllie Elaine , Stanford Lisa D. , Geckler Cheri , Kotagal Prakash , Comair Youssef G. , Thornton Allen E.
Published: August 2005

Summary: Purpose: Numerous studies have demonstrated changes in cognitive, memory, and language functioning in adults and adolescents after temporal lobectomy, yet little information is available regarding neuropsychological outcome in preadolescent children.

Methods: We studied pre‐and postoperative neuropsychological test results from 14 children who underwent temporal lobe resection for intractable epilepsy at age 7–12 years (mean 9.4 years).

Results: Thirteen patients (93%) had no seizures or less than one seizure a year at follow‐up 23‐48 months (mean 34 months) after operation. Postoperative neuropsychological testing was performed 6–9 months (mean 7 months) after surgery in 13 patients and 36 months after the first operation in 1 patient who underwent two‐stage resection of a tumor. Verbal, Performance, and Full Scale IQ were initially in the low‐average range, with no significant change across the pre‐and postoperative evaluations. Immediate verbal memory performance decreased significantly in children who initially performed above the median preoperatively and tended to decrease in children who had left rather than right temporal lobe resection. Significant postoperative decreases in delayed memory scores were independent of preoperative ability or side of resection.

Conclusions: Our small study suggests vulnerability to postoperative decline in immediate verbal memory scores in preadolescent children who have higher baseline immediate memory function or undergo left rather than right temporal lobe resection, similar to that observed in adolescents in adults. The entire group exhibited a statistically significant decrease in delayed verbal memory. Study of larger series of patients will be important to clarify further the short‐and long‐term risks and benefits of temporal lobe resection in childhood.
When Should Induction Protocols Be Used in the Diagnostic Evaluation of Patients with Paroxysmal Events?
Authors: Parra Jaime , Kanner Andrés M. , Iriarte Jorge , Gil‐Nagel Antonio
Published: August 2005

Summary: Purpose: To determine the timing of spontaneous psychogenic nonepileptic events (PNEE) during video‐EEG telemetry (VEEG), and the need to use induction protocols (IP).

Methods: We studied 100 consecutive patients (75 females, 25 males) admitted to our inpatient VEEG unit from July 1994 to June 1996 for differential diagnosis of paroxysmal events. We recorded the time to the first diagnostic spontaneous event, identified by the patient or a family member as typical. Episodes were classified as PNEE, physiologic nonepileptic events (PhysNEE), and epileptic seizures (ES).

Results: The mean duration of VEEG was 74 ± SD 54.1 h. In 82 patients, a diagnostic event occurred spontaneously. The first event was an ES in 22 patients, a PNEE in 53, and a PhysNEE in 7. The time to first diagnostic event was significantly shorter for PNEE than for ES [15.0 ± SD 16.3 h (range 5 min to 58 h) vs. 28.6 ± SD 34.0 h (range 1–110 h) F= 15.621, p <0.00011. In the first 24 h, 77.4% of the patients with PNEE had an event. By 48 h, all but 2 (96.2%) had had diagnostic events. After the first 58 h of monitoring, all patients with PNEE experienced a spontaneous diagnostic event.

Conclusion: Spontaneous events can be expected to occur within 48 h in most patients with PNEE. Therefore, if IP are to be used as a diagnostic tool, we suggest that they be withheld during the initial 48 h of VEEG monitoring.
Positive and Negative Psychotropic Effects of Lamotrigine in Patients with Epilepsy and Mental Retardation
Authors: Ettinger Alan B. , Weisbrot Deborah M. , Saracco Jennifer , Dhoon Aliasgar , Kanner Andres , Devinsky Yorrin
Published: August 2005

Summary: Purpose: To describe significant positive or negative psychotropic effects of lamotrigine (LTG) observed in epilepsy patients with mental retardation (MR).

Methods: Seven mentally retarded epilepsy patients, [5 with Lennox‐Gastaut syndrome (LGS)] who experienced significant behavioral improvements or worsening after addition of LTG to their medication regimen were studied.

Results: LTG produced behavioral improvements in 4 patients. Patient 1, a 14‐year‐old girl, had LTG added to valproate (VPA) and thioridazine, resulting in diminished lethargy, less hyperactivity, and more appropriate speech. In a 17‐year‐old boy (patient 2) LTG added to VPA, phenytoin (PHT), and gabapentin (GBP) lessened irritability and hyperactivity. In patient 3, a 41‐year‐old woman, LTG added to PHT, VPA, and carbamazepine (CBZ) diminished lethargy and enhanced her social interactions. In patient 4, a 27‐year‐old man, LTG monotherapy diminished irritability and hyperactivity. Adverse behavioral effects were noted in 3 patients. In patient 5, a 43‐ year‐old man, LTG added to PHT, phenobarbital (PB), lorazepam, sertraline, and thioridazine produced irritability, hyperactivity, and poor cooperation. In patient 6, a 29‐year‐old woman, LTG added to VPA produced frequent screaming, temper tantrums, increased rocking movements, and hyperactivity. In patient 7, a 29‐year‐old man, LTG added to VPA and PHT resulted in severe exacerbation of baseline behaviors, including self‐injurious activity, temper tantrums, and failure to obey simple instructions.

Conclusions: In some patients with epilepsy and MR, LTG has significant positive or negative effects on behavior.
Brain Thyrotropin‐Releasing Hormone Content Varies Through Amygdaloid Kindling Development According to Afterdischarge Frequency and Propagation
Authors: de Gortari P. , Joseph‐Bravo P. , Monroy‐Ruiz J. , Martínez A. , Cisneros M. , Guardiola A. Fernández
Published: August 2005

Summary: Purpose: Thyrotropin‐releasing hormone (TRH), present in extra hypothalamic brain areas, has been proposed to have neuromodulatory functions and to be susceptible to change by electrical stimulation paradigms. We measured TRH concentrations of several brain areas during kindling development before its establishment and determined whether the changes detected in TRH levels were related to the behavioral stages of kindling, the number of stimulations required to reach these stages and, with the electrophysiological parameters characteristic of this paradigm (amygdaloid afterdischarge (AD) frequency, duration, and propagation).

Methods: Male Wistar rats were implanted stereotaxically with indwelling bipolar electrodes in the basolateral nucleus of the amygdala and with two stainless‐steel electrodes epidurally in frontal cortex. Amygdaloid kindling was induced by daily electrical stimulation; AD frequency and duration were recorded and analyzed throughout the development of kindling. TRH was extracted from several regions and quantified by radioimmunoassay (RIA).

Results: Modifications in TRH concentrations were detected, depending on the region assayed, from stage II of kindling. A positive correlation was noted between the levels of TRH and the frequency and propagation of AD, but not with the number of stimulations. The rate of change in TRH concentration in relation to AD frequency or duration was highest in frontal cortex followed by hippocampus and amygdala.

Conclusions: A graded response was noted in the increase in TRH concentration dependent on the increase of AD frequency and propagation. The rate of response correlated with the region's epileptogenic susceptibility.
Antiepileptic Drugs as a Cause of Worsening Seizures
Authors: Perucca E. , Gram L. , Avanzini G. , Dulac O.
Published: August 2005

Summary: Purpose: Although the paradoxical ability of anti‐epileptic drugs (AEDs) to increase seizure activity has been recognized for decades, the underlying mechanisms are poorly understood and few systematic studies have addressed this problem. This article is intended to provide a critical review of available literature on this topic.

Methods: Information was collected by means of computerized literature searches, screening of journals and textbooks, and consultation with colleagues. Mechanisms which potentially might precipitate underlying drug‐induced exacerbation of seizures were considered based on available pharmacologic and clinical knowledge.

Results: The reviewed information suggests that a paradoxical increase in seizure frequency may occur as a result of at least two separate mechanisms. The first appears to involve a nonspecific manifestation of drug intoxication; seizure‐worsening in this context is usually reversible by dosage reduction or elimination of unnecessary polypharmacy. Conversely, the other mechanism may involve a distinct adverse primary action of the drug in specific seizure types or in syndromic forms. Carabamazepine, in particular, has been reported to precipitate or exacerbate a variety of seizures, most notably absence, atonic, or myoclonic seizures in patients with generalized epilepsies characterized by bursts of diffuse and bilaterally synchronous spike‐and‐wave EEG activity. Phenytoin and vigabatrin also have been implicated in worsening of seizures, particularly generalized seizures, whereas gabapentin has been associated repeatedly with precipitation of myoclonic jerks. Benzodiazepines occasionally have been reported to precipitate tonic seizures, especially when given intravenously to control other seizure types in patients with Lennox‐Gastaut syndrome. Seizure deterioration has been reported also with other drugs; though in most cases evidence is still insufficient for meaningful conclusions to be drawn.

Conclusions: Drug‐induced exacerbation of seizures is a serious and common clinical problem that is often unrecognized or overlooked by the treating physician. Its occurrence appears to be related to three possible causes: an incorrect diagnosis of seizure type or syndromic form, lack of knowledge about certain drugs that are contraindicated in specific types of epilepsies, or to prescription of excessive drug dosages and drug combinations. Further studies are required to evaluate the prevalence of this phenomenon of drug‐induced exacerbation of seizures, to investigate its mechanisms in greater detail and to characterize additional prognostic factors that may be used for early identification of patients at risk.
Treatment of Refractory Status Epilepticus with Propofol: Clinical and Pharmacokinetic Findings
Authors: Stecker Mark M. , Kramer Thomas H. , Raps Eric C. , O'Meeghan Rosemary , Dulaney Eugene , Skaar Debra J.
Published: August 2005

Summary: Purpose: We compared propofol with high‐dose barbiturates in the treatment of refractory status epilepticus (RSE) and propose a protocol for the administration of propofol in RSE in adults, correlating propofol's effect with plasma levels.

Methods: Sixteen patients with RSE were included; 8 were treated primarily with high‐dose barbiturates and 8 were treated primarily with propofol.

Results: Both groups of patients had multiple medical problems and a subsequent high mortality. A smaller but not statistically significant fraction of patients had their seizures controlled with propofol (63%) than with high‐dose barbiturate therapy (82%). The time from initiation of high‐dose barbiturate therapy to attainment of control of RSE was longer (123 min) than the time to attainment of seizure control in the group receiving propofol (2.6 min, p = 0.002). Plasma concentrations of propofol associated with control of SE were 14 μM ± 4 (2.5 μg/ml). Recurrent seizures were common when propofol infusions were suddenly discontinued but not when the infusions were gradually tapered.

Conclusions: If used appropriately, propofol infusions can effectively and quickly terminate many but not all episodes of RSE. Propofol is a promising agent for use in treating RSE, but more studies are required to determine its true value in comparison with other agents.
Reversible Pseudoatrophy of the Brain and Mental Deterioration Associated with Valproate Treatment
Authors: Guerrini Renzo , Belmonte Anna , Canapicchi Raffaello , Casalini Claudia , Perucca Emilio
Published: August 2005

Summary: Purpose: To describe an 11‐year‐old girl with symptomatic localization‐related epilepsy and normal intelligence who developed reversible mental deterioration and pseudoatrophic brain changes while receiving valproate (VPA).

Methods: Assessment of mental function using Wechsler Intelligence Scale for Children‐III (WISC) and Raven's Progressive Matrices (PM), EEG recordings while awake and asleep, and brain magnetic resonance imaging (MRI), were performed at the beginning of VPA therapy, after 2 years and 8 months of treatment and following VPA discontinuation.

Results: After 2 years and 6 months on VPA (≤26 mg/kg/day) the girl insidiously developed mental deterioration (loss of 18 IQ points and drop in age‐adjusted PM score from the 95th to the 50th percentile) associated with MRI‐documented pseudoatrophy of the brain. Onset of severe cognitive impairment coincided with serum VPA concentrations near 100 μg/ml. There were no other manifestations of drug toxicity or hyperammonemia. Background EEG activity was normal. Reduction of VPA dosage and subsequent discontinuation 4 months later resulted in disappearance of clinical symptoms with a 20‐point improvement at IQ testing and recovery of previous PM score. Repeat MRI showed disappearance of pseudoatrophic changes.

Conclusions: The striking cognitive improvement and reversal of pseudoatrophic brain changes following VPA discontinuation strongly suggest a drug‐induced condition. Based on this and previous reports, the syndrome of VPA‐associated mental deterioration and pseudoatrophy of the brain appears to encompass different but possibly related clinical entities, which include parkinsonism with cognitive deterioration, mental deterioration with signs of VPA‐toxicity, and isolated mental deterioration, as seen in our patient. A drug‐induced effect should be considered whenever cognitive deterioration and imaging findings of brain atrophy occur in VPA‐treated patients.
The Syndromic Classification of the International League Against Epilepsy: A Hospital‐Based Study from South India
Authors: Murthy J. M. K. , Yangala Ravi , Srinivas Mantha
Published: August 2005

Summary: Purpose: To determine the distribution of various epilepsies and epileptic syndromes in the epileptic population treated in a university hospital in a developing country.

Methods: Data concerning 2,531 patients with epilepsy seen between January 1989 and June 1994 were analyzed using the international League Against Epilepsy (ILAE) classification.

Results: Of 2,531 cases, 48% fell into ILAE categories 1.3, 3.2, or 4.1 (cryptogenic, without unequivocal generalized or focal seizures; or situation‐related seizures, respectively). Localization‐related epilepsies (LREs) and epileptic syndromes (1.1, 1.2, 1.3) were found in 1,591 (62.9%) patients; of these patients, symptomatic localization‐related epilepsies totaled 62.7%, and idiopathic localization‐related epilepsies accounted for only 0.7%. Juvenile myoclonic epilepsy was the most common type of idiopathic generalized epilepsy (IGE), comprising 4.9% of the total study population and 7.7% of patients registered in the epilepsy clinic. A combination of childhood and juvenile absence epilepsies were found in only 0.4% of the total study population.

Single computed tomography (CT) enhancing lesion (SCTEL) and focal cerebral calcification (FCC) accounted for 22% of the etiologic factors for localization‐related epilepsies. Neurologic deficits were found in 9.5% of patients with SCTEL; none were found with FCC. None of the patients with these lesions had any history of antecedent events that suggested CNS involvement. In patients with localization‐related epilepsies with unremarkable clinical data, the proportion of CT scans showing SCTELs was 39 (95% confidence interval [CI], 0.35–0.43) and 0.18 (95% CI, 15–0.21) for FCCs. The proportion for both lesions together was 0.57 (95% CI, 0.53–0.61). Seizures did not recur once the lesion resolved in patients with SCTELs. In patients with FCCs, seizure remission was 71.5% (95% CI, 53.7–85.4) at 3 years.

Conclusions: This study illustrates the rarity in one patient population of some of the syndromes and categories described in the ILAE classification. Childhood and juvenile absence epilepsies together formed a small proportion. SCTEL and FCC were important etiologic factors for localization related epilepsies. The epilepsy associated with SCTEL was a form of benign epilepsy; epilepsy associated with FCC had remission rates similar to other remote symptomatic epilepsies. Without neuroimaging evidence, these 2 lesions would have been missed and the patients might have been grouped under cryptogenic localization related epilepsy. For this reason, we emphasize the need for neuroimaging in patients with localization related epilepsies with unremarkable clinical findings, before classification into the cryptogenic category. In the absence of neuroimaging, such patients should be classified as “probably cryptogenic.”
Seizures with Fever After Unprovoked Seizures: An Analysis in Children Followed from the Time of a First Febrile Seizure
Authors: Berg Anne T. , Darefsky Amy S. , Holford Theodore R. , Shinnar Shlomo
Published: August 2005

Summary: Purpose: To determine how the onset of unprovoked seizures influences recurrence of seizures with fever in children followed from the time of a first febrile seizure.

Methods: In a prospective cohort of children (n = 428) identified at the time of a first febrile seizure, predictors of a second seizure with fever were identified. The occurrence of a first unprovoked seizure was treated as a time‐dependent covariate in a Cox regression model rather than as a censoring point as it traditionally has been in the past.

Results: One hundred forty‐three (33.4%) children had further seizures. Seven had further seizures with fever only after onset of unprovoked seizures. After adjustment was made for the four previously described predictors of recurrent febrile seizures (age at onset, family history, height of fever, and duration of fever), the onset of unprovoked seizures was associated with a rate ratio of 3.47 (p = 0.0015), indicating a large increase in the risk of further seizures with fever after onset of unprovoked seizures.

Conclusions: Young children who develop unprovoked seizures after a febrile seizure are at substantial risk for further seizures with fever. This may represent part of the spectrum of benign febrile seizures or it may represent the so‐called “epilepsy triggered by fever” spectrum. It affects only a small proportion of children with febrile seizures; however, in some children, it may be useful information to consider when making treatment decisions.
Selection of Phenytoin Responders and Nonresponders in Male and Female Amygdala‐Kindled Sprague–Dawley Rats
Authors: Löscher Wolfgang , Cramer Sybille , Ebert Ulrich
Published: August 2005

Summary: Purpose: We recently described that, by repeated testing of the anticonvulsant phenytoin (PHT), it is possible to select responders and nonresponders from large populations of amygdala‐kindled Wistar rats. Whereas responders show marked and reproducible increases of focal seizure threshold (afterdischarge threshold; ADT) on repeated testing of PHT, 75 mg/kg i.p., nonresponders do not show any significant ADT increase after this dose, thus allowing use of these subgroups in the search for mechanisms of pharmacoresistance in temporal lobe epilepsy. In this study, we examined whether PHT responders and nonresponders can also be selected from large groups of kindled rats of the Sprague‐Dawley strain.

Methods: Male and female Sprague‐Dawley rats were amygdala kindled, followed by once weekly i.p. testing of PHT.

Results: In contrast to recent experiments in Wistar rats, 75 mg/kg PHT did not induce significant ADT increases in Sprague‐Dawley rats, indicating strain differences in response to this drug after kindling. When the dose was lowered to 50 or 25 mg/kg, significant and reproducible ADT increases were obtained in Sprague‐Dawley rats of both genders. Therefore these doses were used for selection of responders and nonresponders in a total of 42 rats. Almost 50% of the rats were PHT responders, responders, whereas no rat was a nonresponder when tested in up to six subsequent drug trials. Many rats were variable responders (i.e., showed ADT increases in some but not all trials), which was not due to low or variable drug absorption after i.p. injection.

Conclusions: The data indicate that, in contrast to Wistar rats, Sprague‐Dawley rats are not suited for selection of PHT nonresponders, but rather are quite responsive to this drug. A further difference to the Wistar strain is the truncated dose‐response with loss of anticonvulsant efficacy at 75 mg/kg in kindled Sprague‐Dawley rats, which may, at least in part, explain the inconsistent results reported on the anticonvulsant efficacy of PHT in this strain in the literature. The lack of anticonvulsant activity after administration of 75 mg/kg may be a result of kindling, because administration of this dose before kindling causes a significant ADT increase in this strain. This kindling‐induced alteration of the anticonvulsant activity of PHT is a phenomenon that contrasts Sprague‐Dawley with Wistar rats and deserves further investigation.
Hemicranial Volume Deficits in Patients with Temporal Lobe Epilepsy With and Without Hippocampal Sclerosis
Authors: Briellmann Regula S. , Jackson Graeme D. , Kalnins Renate , Berkovic Samuel F.
Published: August 2005

Summary: Purpose: In patients with refractory temporal lobe epilepsy, studies have suggested volume deficits measured by MRI of brain structures outside the epileptogenic hippocampus. Hippocampal sclerosis (HS) is a frequent, but not obligate, finding in such patients. The present study examines the influence of the presence of HS on quantitative magnetic resonance imaging (MRI) measurements.

Methods: We analyzed 47 patients and 30 controls by quantitative MRI, including intracranial volume (ICV), hemicranial volume, hippocampal volume (HCV), and T2relaxometry. MRI results were compared with histological findings in the resected temporal lobe.

Results: Histology documented HS in 35 patients (HS group) and other findings in 12 patients (no‐HS group). In both groups, the hemicranial volume ipsilateral to the epileptogenic focus was significantly smaller than on the contralateral side (p <0.004). The HCV on both sides was smaller in the HS group compared with patients without HS (p ≥ 0.004). Unilateral hippocampal atrophy and increased T, value were found in 71% of patients with HS, and bilaterally normal HCV and T, value were found in 67% of patients without HS.

Conclusions: The smaller hemicranial volume on the focus side, irrespective of the presence or absence of HS suggests a different pathogenic mechanism for the additional hemicranial volume deficit, compared to HS itself. The contralateral HCV deficit depends on the presence of HS, indicating a pathogenic connection between damage to both hippocampi.
l‐Carnitine Supplementation in Childhood Epilepsy: Current Perspectives
Authors: De Vivo Darryl C. , Bohan Timothy P. , Coulter David L. , Dreifuss Fritz E. , Greenwood Robert S. , Nordli Douglas R. , Shields W. Donald , Stafstrom Carl E. , Tein Ingrid
Published: August 2005

Summary: In November 1996, a panel of pediatric neurologists met to update the consensus statement issued in 1989 by a panel of neurologists and metabolic experts on L‐carnitine supplementation in childhood epilepsy. The panelists agreed that intravenous L‐carnitine supplementation is clearly indicated for valproate (VPA)‐induced hepatotoxicity, overdose, and other acute metabolic crises associated with carnitine deficiency. Oral supplementation is clearly indicated for the primary plasmalemmal carnitine transporter defect. The panelists concurred that oral L‐carnitine supplementation is strongly suggested for the following groups as well: patients with certain secondary carnitine‐deficiency syndromes, symptomatic VPA‐associated hyperammonemia, multiple risk factors for VPA hepatotoxicity, or renal‐associated syndromes; infants and young children taking VPA; patients with epilepsy using the ketogenic diet who have hypocarnitinemia; patients receiving dialysis; and premature infants who are receiving total parenteral nutrition. The panel recommended an oral L‐carnitine dosage of 100 mg/kg/day, up to a maximum of 2 g/day. Intravenous supplementation for medical emergency situations usually exceeds this recommended dosage.
The Relationship Between Sleep and Epilepsy in Frontal and Temporal Lobe Epilepsies: Practical and Physiopathologic Considerations
Authors: Crespel Arielle , Baldy‐Moulinier Michel , Coubes Philippe
Published: August 2005

Summary: Purpose: The influence of sleep on the incidence of seizures and the reciprocal effects of epilepsy on sleep were analyzed in 30 patients with intractable partial seizures, all candidates for surgery.

Methods: The patients were classified into two groups of 15 patients according to the documented site of the epileptogenic zone: frontal lobe epilepsy (FLE) and medial temporal lobe epilepsy (TLE). Frequency and waking‐sleep distribution of seizures were evaluated by continuous video‐EEG monitoring for 5 days, under defined antiepileptic drug (AED), sleep, and sleep deprivation regimens. Sleep organization was analyzed by polysomnography prior to the presurgical protocol.

Results: Significant differences were found between the two groups in sleeping‐waking distribution of seizures under varied conditions, and in the quality of sleep organization. In FLE patients, seizures most often occurred during sleep, although sleep organization was normal. In TLE patients, most seizures occurred while patients were awake, and sleep organization was characterized by a low efficiency index. The difference in seizure distribution between FLE and TLE persisted under all conditions investigated, i.e., after AED discontinuation and sleep deprivation.

Conclusions: Sleep recording may be useful for diagnosis of FLE, and monitoring after sleep deprivation for that of TLE. We speculate that sleep‐related seizures in FLE may depend on interaction between frontal lobe areas with the thalamus cortical synchronization system and the acetylcholine regulatory system of waking.
Occipital Lobe Seizures as the Major Clinical Manifestation of Reversible Posterior Leukoencephalopathy Syndrome: Magnetic Resonance Imaging Findings
Authors: Bakshi Rohit , Bates Vernice E. , Mechtler Laszlo L. , Kinkel Peter R. , Kinkel William R.
Published: August 2005

Summary: Purpose: Reversible posterior leukoencephalopathy syndrome (RPLS) is an increasingly recognized brain disorder most commonly associated with malignant hypertension, toxemia of pregnancy, or the use of immunosuppressive agents. When associated with acute hypertension, RPLS typically occurs concurrently with the fulminant clinical syndrome of hypertensive encephalopathy. We describe occipital lobe seizures, in the setting of only moderate elevations of blood pressure, as the major clinical manifestation of RPLS.

Methods: Two patients from the Dent Neurologic Institute are presented with clinical and magnetic resonance imaging(MRI) correlation.

Results: New onset secondarily generalized occipital seizures were noted, with MRI findings consistent with RPLS. Both of the patients had chronic renal failure and a moderate acute exacerbation of chronic hypertension. Other features of hypertensive encephalopathy were lacking, such as headache, nausea, papilledema, and an altered sensorium. Magnetic resonance imaging (MRI) showed edematous lesions primarily involving the posterior supratentorial white matter and corticomedullary junction, consistent with RPLS. With lowered blood pressure, the MRI lesions resolved and the patients became seizure‐free without requiring chronic anticonvulsant therapy.

Conclusions: Occipital seizures may represent the only major neurologic manifestation of RPLS due to acute hypertension, especially in patients with renal failure. Other evidence of hypertensive encephalopathy, such as cerebral signs and symptoms, need not be present. Blood pressure elevations may be only moderate. Early recognition of this readily treatable cause of occipital seizures may obviate the need for extensive, invasive investigations. Despite the impressive lesions on MRI, prompt treatment of this disorder carries a favorable prognosis.
Celiac Disease, Bilateral Occipital Calcifications and Intractable Epilepsy: Mechanisms of Seizure Origin
Authors: Bernasconi Andrea , Bernasconi Neda , Andermann Frederick , Dubeau François , Guberman Alan , Gobbi Giuseppe , Olivier André
Published: August 2005

Summary: Purpose: To elucidate the mechanisms of seizure origin in patients with celiac disease and bilateral occipital calcifications (CEBOC). Individuals with CEBOC frequently present with occipital lobe seizures, but additional lesions and additional attack patterns may occur.

Methods: We studied two men and one woman who had CEBOC. Villous atrophy was revealed in the two patients who underwent duodenal biopsy. All had a comprehensive presurgical evaluation, including prolonged video‐EEG recordings. Two had magnetic resonance imaging (MRI) with volumetric study of mesial temporal structures (MRIV). One patient had undergone stereotactic intracranial depth electrode studies (SEEG).

Results: All patients presented with intractable complex partial seizures. Two had partial simple seizures with visual aura. Neurologic examination was normal; one was of normal intelligence, and two were mildly retarded. Neuroimaging studies showed that each had bilateral occipital calcifications as well as epileptiform abnormalities over temporal lobes. In one, MRI showed an additional right frontal lesion, but SEEG demonstrated right occipital lobe seizure origin with anterior spread; this male patient later underwent a right occipital lobe resection. Another with a history of prolonged febrile convulsions had bilateral hippocampal and amygdalar atrophy demonstrated by MRIV.

Conclusions: In one patient, SEEG confirmed that seizures originated in the occipital lobe. The presence of dual pathology was demonstrated in another, raising the possibility of both occipital and temporal seizure onset. The presence of extraoccipital lesions or of mesial temporal atrophy requires SEEG for clarification of seizure onset. In the absence of confounding factors and when laterality can be demonstrated, surgical treatment may be considered.