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Biomedical subjects

James W Wheless

Publications and source records attributed to James W Wheless.

At least 19 recordsLinked to original sources

Vigabatrin.

Refractory epilepsies such as infantile spasms (IS) and complex partial seizures (CPS) can have a severe negative impact on the neurological integrity and quality of life of affected patients, in addition to drastically increasing their risk of premature mortality. Early identification of potentially effective pharmacotherapy agents is important. Vigabatrin has been shown to be a generally well tolerated and effective antiepileptic drug (AED) in a wide variety of seizure types affecting both children and adults, particularly those with IS and CPS. A bilateral, concentric constriction of the peripheral visual field characterizes the visual field defect (VFD) associated with vigabatrin, well characterized by numerous studies. This peripheral VFD presents in 30-50% of patients with exposure of several years; however, most of these patients are asymptomatic. In well-controlled studies, the earliest onset in patients with CPS is 11 months and at 5 months in infants, with average onsets being more than 5 years and 1 year, respectively. Patients with a peripheral VFD retain an average 65 degrees of lateral vision (normal, 90 degrees). The fact that many patients never develop the vigabatrin-related peripheral VFD, despite long-term exposure at high doses, may support the hypothesis that the injury is an idiosyncratic adverse drug reaction (as opposed to a strict dose- or duration-dependent toxicity). Effective testing methods are available to aid in the early detection and management of the peripheral VFD. This article discusses issues of importance to clinical decision-making in the use of vigabatrin to assist the physician and patient in assessing the benefits of vigabatrin therapy and understanding the potential risks of the VFD and uncontrolled seizures.

Animals↗

Intractable epilepsy: A survey of patients and caregivers.

The social and health consequences associated with epilepsy are often magnified among patients with refractory epilepsy. Despite recent advances in the treatment of seizure disorders, many people with epilepsy continue to suffer from uncontrolled seizures and adverse side effects from medical therapy. This survey is the first to focus solely on the experiences, attitudes, and quality of life of a refractory epilepsy population, both those with the condition and their caregivers. To participate in this survey, respondents had to currently be experiencing seizures or troubling treatment side effects and had to have tried at least two different epilepsy medications. These survey data represent three groups of participants (n = 903): those with epilepsy who self-reported on their condition (Group 1, n = 503), the caregivers of those with refractory epilepsy (Group 2, n = 200), and those with epilepsy who had their condition reported on by a caregiver (Group 3, n = 200). This survey revealed that the negative consequences associated with epilepsy tend to be greater among those experiencing treatment side effects and a greater number of seizures. Physicians must take into account medication side effects and quality-of-life issues when treating patients with epilepsy.

Adolescent↗

Childhood mesial temporal sclerosis.

The prevalence and clinical characteristics of mesial temporal sclerosis have not been well studied in children. All brain magnetic resonance imaging (MRI) reports of children less than 14 years of age were reviewed from two tertiary institutions. A 52-month period from one institution and a 37-month period from the other were reviewed. All reports of definite or possible mesial temporal sclerosis were noted. These patients' MRIs were then reviewed to confirm the MRI diagnostic criteria of mesial temporal sclerosis. The charts of the patients who satisfied these criteria were reviewed in detail. Three thousand one hundred brain MRI reports were reviewed. Twenty-six reports of mesial temporal sclerosis were found. Twenty-four of the 26 films satisfied the criteria of mesial temporal sclerosis by MRI after the films were reviewed. The prevalence among all pediatric brain MRI studies was 0.77%. All patients had presented with seizures, that is, there were no "incidental" findings of mesial temporal sclerosis. Four patients had a history of febrile seizures. Mesial temporal sclerosis is an uncommon finding in children, but when it occurs, it is always associated with epilepsy. Asymptomatic mesial temporal sclerosis or mesial temporal sclerosis not associated with a seizure disorder did not occur in our series. Febrile seizures can occur in association with mesial temporal sclerosis presenting in childhood.

Brain Diseases↗

Frequency of panic symptoms in psychogenic nonepileptic seizures.

This study investigates the frequency of symptoms of panic attack in a sample of adults (n = 18) and adolescents (n = 21) who were evaluated for intractable seizure disorder and diagnosed with psychogenic nonepileptic seizures (PNES). Medical records were retrospectively reviewed for symptoms associated with their typical seizure events as documented by the attending epileptologist. Adolescents, as a group, reported significantly more symptoms of panic attack than adults. Three adolescents met the full criteria for a panic attack, while no adults met these criteria. In addition, while numerous adults endorsed no panic symptoms associated with their PNES episodes, all adolescents endorsed at least one symptom. Implications of results are discussed in terms of the diagnosis and treatment of PNES in the different age groups.

Adolescent↗

Toward the substitution of invasive electroencephalography in epilepsy surgery.

The authors compared the localization accuracy of interictal magnetoencephalography (MEG) with ictal and interictal invasive video electroencephalography (VEEG) in identifying the epileptogenic zone in epilepsy surgery candidates. Forty-one patients, 29 with temporal lobe epilepsy (TLE) and 12 with extratemporal lobe epilepsy (ETLE), participated. Only patients with interictal changes during the MEG recordings were included. A comparison of the accuracy of invasive VEEG and MEG seizure zone identification was based on the degree of overlap between the location of the actual surgical resection and the zone identified by each method, and the success of surgery in reducing seizure activity. No statistical differences were observed between the accuracy of invasive VEEG and MEG in determining the location of the seizure zone across TLE and ETLE cases. Invasive VEEG and MEG localization judgments were correct in 54% and 56% of the cases, respectively. Separate group analyses suggested that MEG may be less beneficial relative to invasive VEEG in ETLE than TLE cases. MEG is of statistically equivalent accuracy to invasive VEEG, despite the fact that its use has not reached optimal conditions. The authors predict the replacement of the more invasive procedure with MEG in the near future for TLE cases, subsequent to the optimization of the conditions under which preoperative MEG is performed.

Adolescent↗

Atypical language representation in patients with chronic seizure disorder and achievement deficits with magnetoencephalography.

PURPOSE: To characterize the relation between hemispheric asymmetries in language-specific brain activity and reading/spelling achievement by using magnetoencephalography (MEG). METHODS: Patients (n = 83) with medically intractable complex partial seizures of either left- or right-hemisphere origin were classified as having reading and/or spelling deficits (RS) or as not impaired (NI) by using standard achievement tests. All patients had undergone noninvasive functional mapping of receptive language cortex by using MEG as part of a preoperative seizure surgery evaluation. RESULTS: RS patients with left-hemisphere seizure onset exhibited relatively greater activation and earlier onset of late, language-specific MEG activity in posterior temporal and inferior parietal areas of the right as compared with the left hemisphere than did NI patients. These findings also were evident on an individual basis and were independent of global intellectual abilities. CONCLUSIONS: Reading and spelling achievement deficits in patients with complex partial seizures of left-hemisphere origin are associated with atypical language organization, possibly secondary to reorganization of language function to right-hemisphere areas that are not as efficient as homotopic areas in the left hemisphere in supporting reading and spelling functions.

Achievement↗

Treatment of pediatric epilepsy: expert opinion, 2005.

BACKGROUND: Childhood epilepsies are a heterogeneous group of conditions that differ in diagnostic criteria and management and have dramatically different outcomes. Despite increasing data on treatment of epilepsy, research findings on childhood epilepsy are more limited and many clinical questions remain unanswered, so that clinicians must often rely on clinical judgment. In such clinical situations, expert opinion can be especially helpful. METHODS: A survey on pediatric epilepsy and seizures (33 questions and 645 treatment options) was sent to 41 U.S. physicians specializing in pediatric epilepsy, 39 (95%) of whom completed it. In some questions, the experts were asked to recommend overall treatment approaches for specific syndromes (the order in which they would use certain strategies). Most of the questions asked the experts to rate options using a modified version of the RAND 9-point scale for medical appropriateness. Consensus was defined as a non-random distribution of scores by chi-square test, with ratings used to assign a categorical rank (first line/usually appropriate, second line/equivocal, and third line/usually not appropriate) to each option. RESULTS: Valproate was treatment of choice for symptomatic myoclonic and generalized tonic-clonic seizures except in the very young, with lamotrigine and topiramate also first line (usually appropriate). Zonisamide was first line only if the child also has myoclonic seizures. For initial monotherapy for complex partial seizures, oxcarbazepine and carbamazepine were treatments of choice, with lamotrigine and levetiracetam also first line. As initial therapy for infantile spasms caused by tuberous sclerosis, viagabatrin was treatment of choice, with adrenocorticotropic hormone (ACTH) also first line. As initial therapy for infantile spasms that are symptomatic in etiology, ACTH was treatment of choice, with topiramate also first line. As initial therapy for Lennox-Gastaut syndrome, valproate was treatment of choice, with topiramate and lamotrigine also first line. For acute treatment of a prolonged febrile seizure or cluster of seizures, rectal diazepam was treatment of choice. For benign childhood epilepsy with centro-temporal spikes, oxcarbazepine and carbamazepine were treatments of choice, with gabapentin, lamotrigine, and levetiracetam also first line. For childhood absence epilepsy, ethosuximide was treatment of choice, with valproate and lamotrigine also first line. For juvenile absence epilepsy, valproate and lamotrigine were treatments of choice. For juvenile myoclonic epilepsy in adolescent males, valproate and lamotrigine were treatments of choice, with topiramate also first line; for juvenile myoclonic epilepsy in adolescent females, lamotrigine was treatment of choice, with topiramate and valproate other first-line options. As initial therapy for neonatal status epilepticus, intravenous phenobarbital was treatment of choice, with intravenous lorazepam or fosphenytoin also first line. As initial therapy for all types of pediatric status epilepticus, lorazepam was treatment of choice, with intravenous diazepam also first line. For generalized tonic-clonic status epilepticus, rectal diazepam and fosphenytoin were also first line; for complex partial status epilepticus, fosphenytoin was also first line; and for absence status epilepticus, intravenous valproate was also first line. CONCLUSION: The expert panel reached consensus on many treatment options. Within the limits of expert opinion and with the understanding that new research data may take precedence, the experts' recommendations provide helpful guidance in situations where the medical literature is scant or lacking. The information in this report should be evaluated in conjunction with evidence-based findings.

Adolescent↗

Integrating sensory and motor mapping in a comprehensive MEG protocol: clinical validity and replicability.

Considerable evidence supports the idea of magnetoencephalography (MEG) being a valuable noninvasive tool for presurgical mapping of sensory and motor functions. In this study, we test the validity and replicability of a new experimental paradigm for simultaneous sensory and motor mapping using MEG recordings. This comprehensive sensorimotor protocol (CSSMP), where external mechanic stimulation serves as a cue for voluntary movements, allows the recording of sensory and motor cortical responses during a single activation task. The stability and replicability of MEG-derived recordings during this paradigm were tested in a group of eight neurologically normal volunteers and six patients with perirolandic lesions. We found that a common sensorimotor cortical network, engaging sensory (S1, S2) and motor (M1) areas, was reliably activated in all subjects and patients and that the results remained exceptionally stable over time. Additionally, the clinical validity of the MEG-derived maps of activation was tested through intraoperative electrocortical stimulation mapping in the group of patients. The MEG-derived anatomical maps for specific sensory (S1) and motor (M1) responses were verified, by direct cortical mapping, and confirmed with the patient's surgical outcome. The results of this validation study show that the so-called CSSMP is a reliable and reproducible method for assessing simultaneously sensory and motor areas. This method minimizes methodological problems and improves our knowledge of the spatiotemporal organization of the sensorimotor cortical network and helps to optimize the surgical management of patients with perirolandic lesions.

Adult↗

Magnetic resonance imaging detection of mesial temporal sclerosis in children.

The objective of this study was to investigate the prevalence and clinical characteristics of mesial temporal sclerosis as diagnosed by brain magnetic resonance imaging in children. A total of 390 consecutive brain magnetic resonance imaging studies in children were reviewed for evidence of mesial temporal sclerosis. Subsequently, the magnetic resonance imaging scans and charts of patients with mesial temporal sclerosis were reviewed and their clinical details were evaluated. The magnetic resonance imaging studies had been performed for multiple indications, including seizures, headache, and developmental problems. In children, the prevalence of mesial temporal sclerosis among all brain magnetic resonance imaging studies was 3.1% (12 of 390 studies) and 12.1% (12 of 99 studies) among all brain magnetic resonance imaging studies performed for seizures. These children all presented with a history of seizure disorder, often had other medical problems, and histopathology (when available) nearly always (5 of 6 patients) confirmed their magnetic resonance imaging diagnosis of mesial temporal sclerosis. The prevalence of mesial temporal sclerosis is low among all pediatric patients who had magnetic resonance imaging brain studies. All our mesial temporal sclerosis patients had clinical seizures; i.e., it was never an "incidental finding". Children with mesial temporal sclerosis often had comorbid conditions, and the diagnosis of mesial temporal sclerosis made by magnetic resonance imaging was accurate when compared with the available histopathology.

Child↗

Magnetoencephalography (MEG) and magnetic source imaging (MSI).

BACKGROUND: Real-time, direct assessment of brain electrophysiology is critical for noninvasive functional mapping and for the identification of paroxysmal epileptiform abnormalities in the evaluation of patients for epilepsy surgery. Historically, electroencephalography (EEG) and evoked potentials (EPs) have performed these functions. However, both often required direct intracranial recording for precise localization. Magnetoencephalography (MEG) takes advantage of the fact that neuromagnetic signals penetrate the skull and scalp without distortion. The magnetic source image (MSI) is created when the MEG data is superimposed on a magnetic resonance image (MRI). REVIEW SUMMARY: MEG performs noninvasive functional imaging by recording the magnetic flux on the head surface associated with electrical currents in activated sets of neurons. MEG has rapidly evolved in the last 2 decades because of the introduction of whole head systems and advances in computer technology. MEG is now the imaging modality of choice where a precise and high degree of localization is required. MEG can be used to localize the primary sensory cortices (visual, auditory, or somatosensory), areas involved with receptive language function, the irritative zone in epilepsy patients, and identify children with anomalous language development. This article reviews the basis of MEG, the instrumentation used, the clinical applications and current limits of the technology. CONCLUSION: MEG studies can now be performed on a routine basis as a clinical tool. MEG is now indicated for: 1) localization of the irritative zone in lesional and nonlesional epilepsy surgery patients, 2) functional mapping of eloquent cortex, and 3) assessment of normal and abnormal language development. In the future MEG may help the understanding of normal development and reorganization after brain injury. The neurologist can use MEG data to complement structural and metabolic imaging techniques.

Brain Mapping↗

Nonpharmacologic treatment of the catastrophic epilepsies of childhood.

The catastrophic epilepsy syndromes of childhood are initially treated with a pharmacologic intervention in most cases. However, due to the poor response patients often have to pharmacologic interventions, nonpharmacologic treatment options are an important part of a comprehensive treatment plan for this group of children. Additionally, nonpharmacologic therapy may offer a method to minimize associated morbidity and mortality. This article discusses the use of epilepsy surgery, the ketogenic diet, and vagus nerve stimulation in the treatment of patients with infantile spasms, Lennox-Gastaut syndrome, and progressive myoclonic epilepsy. Efficacy of the nonpharmacologic treatment options, as measured by reduction in seizure frequency, as well as by developmental progress or behavioral improvement, varies according to the specific catastrophic epilepsy disorder and the treatment option.

Brain↗

Choosing antiepileptic drugs for developmentally normal children with specific epilepsy syndromes and behavioral disorders.

Antiepileptic drugs are often used for the treatment of both epilepsy and a wide range of behavioral and psychiatric disorders. The treatment of patients with epilepsy has been the proving ground for antiepileptic drugs, not only with respect to their efficacy in the treatment of seizures but also for clarifying their dose-related and idiosyncratic adverse events. This information has been useful in treating patients with behavioral and psychiatric disorders. Indeed, the number of prescriptions written for many antiepileptic drugs for nonepileptic uses far exceeds those written for the same drugs for epilepsy. Because patients with chronic epilepsy have a higher incidence of axis I psychiatric disorders, physicians can choose an antiepileptic drug to treat both the epilepsy and psychiatric comorbidity in selected patients. Guided by the principles of evidence-based medicine as outlined by the American Academy of Neurology and the American Academy of Pediatrics, this article reviews the application of antiepileptic drugs for epilepsy and behavioral and psychiatric disorders in children.

Anticonvulsants↗

Topiramate, carbamazepine, and valproate monotherapy: double-blind comparison in children with newly diagnosed epilepsy.

In a novel double-blind trial, topiramate was compared with the investigator's choice of carbamazepine or valproate as first-line therapy in patients as young as 6 years of age with newly diagnosed epilepsy. Among 613 patients enrolled in the trial, 119 (19%) were children or adolescents (6-16 years of age). No differences between fixed doses of topiramate (100 and 200 mg/day) and carbamazepine (600 mg/day) or valproate (1250 mg/day) were observed in efficacy measures: time to exit, time to first seizure, and the proportion of patients who were seizure free during the last 6 months of treatment. Topiramate 100 mg/day (2.0 mg/kg/day in this study population) was associated with the fewest discontinuations owing to side effects. Based on efficacy and tolerability, the recommended target dose for topiramate as first-line therapy in children and adolescents is 100 mg/day.

Adolescent↗

Vagus nerve stimulation therapy.

Until recently, antiepileptic drugs and traditional epilepsy surgery were the two primary treatment options available to patients with epilepsy. Drug therapy, however, does not always control seizures and can be associated with negative side effects. Additionally, only a minority of patients are candidates for epilepsy surgery. Vagus nerve stimulation (VNS) therapy, approved by the US FDA in 1997, is now a treatment option that is effective in reducing seizure frequency and severity as well as improving patient quality of life without the pharmacological side effects associated with traditional antiepileptic drugs. Provided here is an overview of VNS therapy and the VNS therapy system, including the history of vagal nerve stimulation, patient selection guidelines and new indications currently under investigation for this novel therapy.

Clinical Trials as Topic↗

Successful neurosurgical treatment of childhood complex partial status epilepticus with focal resection.

The treatment of complex partial status epilepticus continues to be controversial, especially with regard to the intensity of the treatment. Medical therapy and drug-induced coma are sometimes required. Rarely this may not be effective. A healthy 4-year old girl was first seen in complex partial status epilepticus. She had a 1-year history of cryptogenic partial-onset seizures. Detailed magnetic resonance imaging (MRI) studies were normal. Her course was refractory to multiple medical therapies and multiple subpial transection (MST). An urgent epilepsy surgery evaluation resulted in a focal cortical resection being performed over the right mesial parietal region with resultant seizure freedom and no significant neurologic deficit 2 years later. This patient illustrates the need to consider occult focal cortical dysplasia as a cause of nonconvulsive status epilepticus (NCSE) in children, and if it is not responsive to medical management, the utility of performing an urgent epilepsy surgery evaluation.

Brain Mapping↗

The ketogenic diet: adolescents can do it, too.

PURPOSE: To determine both the efficacy of and compliance with the ketogenic diet in the adolescent population. METHODS: A retrospective study of 45 patients, aged 12-19 years, consecutively enrolled in a ketogenic diet program from 1994 to 2002, was performed. Thirty-seven patients were from The Johns Hopkins Medical Institutions; eight were from The University of Texas at Houston. Charts were reviewed, and patients were contacted by telephone. RESULTS: Six months after diet initiation, 28 (62%) of 45 remained on the ketogenic diet, with six (21%) of 28 having 50-90% seizure reduction, and eight (29%) of 28 having >90%. At 12 months, 20 (44%) of 45 remained on the diet, with seven (35%) of 20 having 50-90% seizure reduction and six (30%) of 20 achieving >90% efficacy. Only 22% discontinued the diet for perceived restrictiveness. The mean diet duration was 1.2 years. Patients with multiple seizure types did best, whereas gender, prior seizure frequency, diet ratio, and age did not influence outcome. Patients dependent on parents for daily care were more likely to remain on the diet at 6 months, but had less efficacy. Weight loss (60%) and menstrual dysfunction (45% of female subjects) were the most commonly reported side effects. CONCLUSIONS: The ketogenic diet is as well tolerated and efficacious for adolescents with epilepsy as for the general childhood population.

Adolescent↗

Acute management of seizures in the syndromes of idiopathic generalized epilepsies.

Three of the seizure types (myoclonic, absence, and generalized tonic-clonic) and syndromes associated with idiopathic generalized or genetic epilepsies can present an acute status epilepticus picture that requires acute therapy. These are not the usual seizures observed in status epilepticus because most of these patients have secondary generalized or symptomatic generalized convulsive seizures. In this review, I discuss the unique presentation and treatment options for the acute management of seizures in the syndromes of idiopathic generalized epilepsy (IGE), with special emphasis on the seizures of status epilepticus, which persist over time or occur in a series without recovery of consciousness.

Acute Disease↗