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Biomedical subjects

J W Wheless

Publications and source records attributed to J W Wheless.

At least 37 records · Page 2Linked to original sources
PubMed2000

Genetic and neuroradiological heterogeneity of double cortex syndrome.

Mutations in the X-linked doublecortin gene appear in many sporadic cases of double cortex (DC; also known as subcortical band heterotopia), a neuronal migration disorder causing epilepsy and mental retardation. The purpose of this study was to examine why a significant percentage of sporadic DC patients had been found not to harbor doublecortin mutations and to determine whether clinical features or magnetic resonance imaging scan appearance could distinguish between patients with and without doublecortin mutations. Magnetic resonance imaging scan analysis differentiated patients into the following four groups: anterior biased/global DC with doublecortin mutation (16 of 30; 53%), anterior biased/global DC without mutation (8 of 30; 27%), posterior biased DC without mutation (3 of 30; 10%), and limited/unilateral DC without mutation (3 of 30; 10%). The presence of these atypical phenotypes suggests that other genetic loci or mosaicism at the doublecortin locus may be responsible for this diversity of DC cases.

Adolescent↗
PubMed1999

Language dominance determined by magnetic source imaging: a comparison with the Wada procedure.

OBJECTIVE: To evaluate the validity of data derived from magnetic source imaging (MSI) regarding cerebral dominance for language in patients with intractable seizure disorder. METHOD: The authors performed functional imaging of the receptive language cortex using a whole-head neuromagnetometer in 26 consecutive epilepsy patients who also underwent the intracarotid amobarbital (Wada) procedure. During MSI recordings, patients engaged in a word recognition task. This task was shown previously to activate language areas in normal adults as well as in patients who undergo intraoperative language mapping, allowing confirmation of MSI findings. Language laterality indices were formed for both the Wada and the MSI procedures. In addition, clinical judgments regarding cerebral dominance for language were made using the two methods by independent raters. RESULTS: Cluster analysis indicated excellent agreement between the quantitative MSI and Wada indices. Rater judgments showed almost complete agreement as well. CONCLUSION: MSI is a promising method for determining cerebral dominance for language.

Adolescent↗
PubMed1999

Physiology of perception: cortical stimulation and recording in humans.

OBJECTIVES: 1) To determine the effect of stimulus train duration (TD) on sensory perception using direct stimulation of somatosensory and visual cortices. 2) To investigate the occurrence of evoked potentials in response to stimulation that is subthreshold for perception. BACKGROUND: Studies of the mechanisms of conscious perception using direct cortical stimulation and recording techniques are rare. The clinical necessity to implant subdural electrode grids in epilepsy patients undergoing evaluation for surgery offers an opportunity to examine the role of stimulus parameters and evoked potentials in conscious perception. METHODS: Subjects included epilepsy patients with grids over somatosensory or occipital cortex. Single pulses (100 microseconds) and stimulus trains were applied to electrodes, and thresholds for perception were found. Evoked potentials were recorded in response to peripheral stimulation at intensities at, above, and below sensory threshold. RESULTS: During cortical stimulation, sensory threshold changed little for stimulus trains of 250 milliseconds and longer, but increased sharply as TD decreased below this level. Primary evoked activity was recorded in response to peripheral stimulations that were subthreshold for conscious perception. CONCLUSIONS: The results confirm a previous report of the effects of stimulus TD on sensory threshold. However, no motor responses occurred following somatosensory stimulation with short trains, as previously reported. The TD threshold pattern was similar in visual cortex. In agreement with the previous report, early components of the primary evoked response were not correlated with conscious sensory awareness.

Adolescent↗
PubMed1999

Atypical temporal lobe language representation: MEG and intraoperative stimulation mapping correlation.

Functional brain imaging techniques hold many promises as the methods of choice for identifying areas involved in the execution of language functions. The success of any of these techniques in fulfilling this goal depends upon their ability to produce maps of activated areas that overlap with those obtained through standard invasive procedures such as electrocortical stimulation. This need is particularly acute in cases where active areas are found outside of traditionally defined language areas. In the present report we present two patients who underwent mapping of receptive language areas preoperatively through magnetoencephalography (MEG) and intraoperatively through electrocortical stimulation. Language areas identified by both methods were located in temporoparietal regions as well as in less traditional regions (anterior portion of the superior temporal gyrus and basal temporal cortex). Importantly there was a perfect overlap between the two sets of maps. This clearly demonstrates the validity of MEG-derived maps for identifying cortical areas critically involved in receptive language functions.

Adult↗
PubMed1999

Magnetic resonance angiography of primary varicella vasculitis: report of two cases.

Two patients with onset of hemiparesis 3 weeks following primary varicella infection demonstrated contralateral temporal lobe and basal ganglia infarctions on magnetic resonance imaging. In both cases, magnetic resonance angiography (MRA) was performed and demonstrated flow abnormalities ipsilateral to the infarcts. Digital subtraction angiography was performed in one case; however, the findings were significantly less conspicuous than those of the MRA. MRA proved to be sensitive to the diagnosis of varicella-induced vasculitis in two consecutive cases and provided a noninvasive means of following the progression of the disease process in response to therapy.

Arteritis↗
PubMed1999

Characterization of mutations in the gene doublecortin in patients with double cortex syndrome.

Mutations in the X-linked gene doublecortin, which encodes a protein with no dear structural homologues, are found in pedigrees in which affected females show "double cortex" syndrome (DC; also known as subcortical band heterotopia or laminar heterotopia) and affected males show X-linked lissencephaly. Mutations in doublecortin also cause sporadic DC in females. To determine the incidence of doublecortin mutations in DC, we investigated a cohort of eight pedigrees and 47 sporadic patients with DC for mutations in the doublecortin open reading frame as assessed by single-stranded conformational polymorphism analysis. Mutations were identified in each of the eight DC pedigrees (100%), and in 18 of the 47 sporadic DC patients (38%). Identified mutations were of two types, protein truncation mutations and single amino acid substitution mutations. However, pedigrees with DC displayed almost exclusively single amino acid substitution mutations, suggesting that patients with these mutations may have less of a reproductive disadvantage versus those patients with protein truncation mutations. Single amino acid substitution mutations were tightly clustered in two regions of the open reading frame, suggesting that these two regions are critical for the function of the Doublecortin protein.

Brain Diseases↗
PubMed1999

Safety of rapid intravenous infusion of valproate loading doses in epilepsy patients.

IV valproate may be given to patients requiring rapid elevation of serum valproate or for patients unable to take oral medication. Previously we established the loading dose of IV valproate needed to achieve serum concentrations of > 100 ug/ml. This study evaluated the safety of rapid infusion of valproate to achieve high therapeutic levels. Twenty-four infusions of IV valproate were carried out electively in twenty-one patients with epilepsy (ages 2-54 years). The dose ranged from 21-28 mg/kg (mean 24.2 mg/kg). Target infusion rates were 3 or 6 mg/kg per min, yielding an infusion duration of 4.17 or 8.34 min. ECG was monitored; blood pressure was measured before and after infusion. Post infusion serum valproate concentrations were 64-204.1 ug/ml (mean 132.6). There were no significant changes in blood pressure and no ECG abnormalities observed. Transient pain occurred at the site of injection in five patients, associated with redness in two. This appeared to related to the concentration of valproic acid in the infusion fluid. We conclude that a loading dose of IV valproate can be administered safely and rapidly. This finding enables further studies evaluating IV valproate as a non-sedative anticonvulsant in the management of status epilepticus.

Adolescent↗
PubMed1999

A comparison of magnetoencephalography, MRI, and V-EEG in patients evaluated for epilepsy surgery.

PURPOSE: To determine the efficacy and relative contribution of several diagnostic methods [ictal and interictal scalp and intracranial EEG, magnetic resonance imaging (MRI), and magnetoencephalography (MEG)] in identifying the epileptogenic zone for resection. METHODS: This was a prospective study using a masked comparison-to-criterion standard. Fifty-eight consecutive patients with refractory partial epilepsy from two university comprehensive epilepsy programs were studied. Patients who were evaluated for and underwent epilepsy surgery were recruited. The main outcome measure was the efficacy of each diagnostic method to identify the resected epileptogenic zone, when referenced to surgical outcome. RESULTS: MEG (52%) was second only to ictal intracranial V-EEG in predicting the epileptogenic zone for the entire group of patients who had an excellent surgical outcome (seizure free or rare seizure). In a subanalysis, for patients who had temporal lobe surgery, this same relation was seen (MEG, 57%, ictal intracranial V-EEG, 62%). With extratemporal resection, ictal (81%) and interictal (75%) intracranial EEG were superior to MEG (44%) in predicting the surgery site in those patients with an excellent outcome. Finally, for all patients who had a good surgical outcome, MEG (52%) was better than ictal (33%) or interictal (45%) scalp VEEG in predicting the site of surgery. CONCLUSIONS: These results indicate that MEG is a very promising diagnostic method and raise the possibility that it may obviate the need for invasive EEG in some cases or reduce the length of scalp EEG evaluation in others.

Adolescent↗
PubMed1999

New formulations of drugs in epilepsy.

The advent of numerous new treatment options in epilepsy therapy over the last decade is enabling a more flexible and individualized approach to patients with seizures. For some patients, these products offer added efficacy, reduction of troublesome side effects associated with standard anticonvulsants, and control over acute seizure exacerbations. This review profiles new formulations of anti-epileptic drugs. Tegretol-XR (TXR) and Carbatrol (CBTL), two extended-release preparations of carbamazepine (CBZ), which allow twice daily administration, minimising drug toxicity and improving efficacy. Topiramate sprinkles and lamotrigine chewable dispersible tablets allow easier administration in children. The rectal gel preparation of diazepam (Diastat) is useful for parents of patients with acute seizure exacerbations. Intravenous valproate (Depacon) and fosphenytoin (Cerebyx) provide parenteral treatment of acute seizures, without sedation or significant peripheral venous side effects. All of these new formulations expand treatment options for patients with epilepsy, who will benefit from them.

Anticonvulsants↗
PubMed1999

Magnetoencephalographic mapping of the language-specific cortex.

OBJECT: In this paper the authors introduce a novel use of magnetoencephalography (MEG) for noninvasive mapping of language-specific cortex in individual patients and in healthy volunteers. METHODS: The authors describe a series of six experiments in which normative MEG data were collected and the reliability, validity, and topographical accuracy of the data were assessed in patients who had also undergone the Wada procedure or language mapping through intraoperative cortical stimulation. CONCLUSIONS: Findings include: 1) receptive language-specific areas can be reliably activated by simple language tasks and this activation can be readily recorded in short MEG sessions; 2) MEG-derived maps of each individual are reliable because they remain stable over time and are independent of whether auditory or visual stimuli are used to activate the brain; and 3) these maps are also valid because they concur with results of the Wada procedure in assessing hemispheric dominance for language and with the results of cortical stimulation in identifying the precise topography of receptive language regions within the dominant hemisphere. Although the MEG mapping technique should be further refined, it has been shown to be efficacious by correctly identifying the language-dominant hemisphere and specific language-related regions within this hemisphere. Further development of the technique may render it a valuable adjunct for routine presurgical planning in many patients who harbor tumors or have epilepsy.

Acoustic Stimulation↗
PubMed1999

Localization of language-specific cortex by using magnetic source imaging and electrical stimulation mapping.

OBJECT: In this paper the authors demonstrate the concordance between magnetic source (MS) imaging and direct cortical stimulation for mapping receptive language cortex. METHODS: In 13 consecutive surgical patients, cortex specialized for receptive language functions was identified noninvasively by obtaining activation maps aided by MS imaging in the context of visual and auditory word-recognition tasks. Surgery was then performed for treatment of medically intractable seizure disorder (eight patients), and for resection of tumor (four), or angioma (one). Mapping of language areas with cortical stimulation was performed intraoperatively in 10 patients and extraoperatively in three. Cortical stimulation mapping verified the accuracy of the MS imaging-based localization in all cases. CONCLUSIONS: Information provided by MS imaging can be especially helpful in cases of atypical language representation, including bihemispheric representation, and location of language in areas other than those expected within the dominant hemisphere, such as the anterior portion of the superior temporal gyrus, the posteroinferior portion of the middle temporal gyrus, the basal temporal cortex, and the lateral temporooccipital cortex.

Acoustic Stimulation↗
PubMed1998

A multicenter study of the efficacy of the ketogenic diet.

OBJECTIVE: To determine the efficacy of the ketogenic diet in multiple centers. DESIGN: A prospective study of the change in frequency of seizures in 51 children with intractable seizures who were treated with the ketogenic diet. SETTING: Patients were enrolled from the clinical practices of 7 sites. The diet was initiated in-hospital and the patients were followed up for at least 6 months. PATIENTS: Fifty-one children, aged 1 to 8 years, with more than 10 seizures per week, whose electroencephalogram showed generalized epileptiform abnormalities or multifocal spikes, and who had failed results when taking at least 2 appropriate anti-epileptic drugs. INTERVENTION: The children were hospitalized, fasted, and a 4:1 ketogenic diet was initiated and maintained. MAIN OUTCOME MEASURES: Frequency of seizures was documented from parental calendars and efficacy was compared with prediet baseline after 3, 6, and 12 months. The children were categorized as free of seizures, greater than 90% reduction, 50% to 90% reduction, or lower than 50% reduction in frequency of seizures. RESULTS: Eighty-eight percent of all children initiating the diet remained on it at 3 months, 69% remained on it at 6 months, and 47% remained on it at 1 year. Three months after initiating the diet, frequency of seizures was decreased to greater than 50% in 54%. At 6 months, 28 (55%) of the 51 initiating the diet had at least a 50% decrease from baseline, and at 1 year, 40% of those starting the diet had a greater than 50% decrease in seizures. Five patients (10%) were free of seizures at 1 year. Age, sex, principal seizure type, and electroencephalogram were not statistically related to outcome. CONCLUSION: The ketogenic diet is effective in substantially decreasing difficult-to-control seizures and can successfully be administered in a wide variety of settings.

Child↗
PubMed1998

Pediatric use of intravenous and intramuscular phenytoin: lessons learned.

First developed in 1950, parenterally administered phenytoin offered substantial advantages over parenterally administered phenobarbital and paraldehyde, which were the treatments for status epilepticus until the 1960s. During the 1950s, clinical research established the pediatric dosage of parenteral phenytoin for the treatment of seizures, which was based on the adult dosage adjusted to each child's weight. Studies in the late 1970s and early 1980s established more appropriate dosing for neonates and children on a milligram-per-kilogram basis. Scientifically derived dosing guidelines have been available only for the past 12 years. Side effects associated with parenteral phenytoin, caused primarily by its high pH level and the propylene glycol content needed to increase its solubility, were frequently reported during the 1970s and 1980s, after 25 years of clinical use. Intravenous administration of phenytoin caused burning at the infusion site and was associated with severe local cutaneous reactions following infiltration into surrounding tissue, leading to a recommendation that intravenous phenytoin be avoided in young children and the elderly. The propylene glycol solvent was linked to seizures, arrhythmia, asystole, and hepatic and renal damage. When administered intramuscularly, phenytoin is poorly absorbed and can cause hemorrhagic necrosis of the soft tissues at the injection site. Many of these side effects can be avoided in children with the use of fosphenytoin.

Anticonvulsants↗
PubMed1998

Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial.

OBJECTIVE: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. BACKGROUND: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. METHODS: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. RESULTS: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. CONCLUSIONS: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

Adolescent↗
PubMed1997

Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome (LGS) is one of the intractable epilepsies of childhood that is associated with an epileptic encephalopathy. Although LGS has been accepted as a distinct epilepsy syndrome for the last 30 years, understanding of its pathogenesis is still incomplete. Because this heterogenous entity has many diverse etiologies, some with specific therapy, a complete evaluation is necessary. The natural history is well defined; most children with LGS will ultimately be mentally retarded, will continue to have seizures, and as adults will be dependent for their daily care. Therefore, their only hope is new therapies and advances in our understanding of the pathogenesis of LGS. Several new treatment options have emerged. For the first time in the last 20 years, we have several medications with documented efficacy. In addition, there are effective nonpharmacologic treatments. These treatments offer the potential for improved seizure control, which we hope will have impact and lessen the subsequent epileptic encephalopathy. Children with LGS require multidisciplinary assessment and treatment along with vigorous intervention aimed at minimizing their seizures to maximize their potential. Pediatric neurologists should be familiar with the treatments with proven efficacy, including new antiepileptic drugs, and should develop a rational plan of treatment for each child with LGS.

Adult↗
PubMed1997

Identification of side of seizure onset in temporal lobe epilepsy using memory tests in the context of reading deficits.

Sixty patients with temporal lobe epilepsy were classified into reading deficient (RD; n = 21) and non-reading deficient (non-RD; n = 39) groups. Selective deficits in verbal or nonverbal memory, consistent with side of seizure onset, were evident in the non-RD patients. Both verbal and nonverbal memory performance were reduced equivalently in individuals with RD, regardless of side of seizure onset. As a result, memory tests that were accurate in identifying side of seizure onset in the non-RD group were not as accurate in the RD group. When individual cases were classified using a clinically applicable decision rule, significantly more RD patients were either unclassifiable or incorrectly classified than were non-RD patients. Findings suggest that preoperative memory data obtained from individuals with epilepsy and evidence of RD may not be as valid an indicator of side of seizure onset as are those obtained from patients without RD.

Achievement↗
PubMed1997

Asymmetries in the effect of side of seizure onset on recognition memory following intracarotid amobarbital injection.

PURPOSE: To assess interhemispheric differences in recognition memory for objects during the intracarotid amobarbital sodium procedure (IAP). METHODS: The recognition memory for real objects of patients with either right (RTLE; n = 28) or left (LTLE; n = 22) temporal lobe epilepsy was assessed at baseline, and after left and right intracarotid amobarbital sodium injection. RESULTS: There were no differences between groups on baseline performance. Performance following injection ipsilateral to the side of seizure focus was relatively lower for the LTLE as compared with the RTLE group, but this difference did not reach statistical significance. However, performance following injection contralateral to the side of seizure focus was significantly lower for the RTLE as compared with the LTLE group. Within-group differences in performance after ipsilateral as compared with contralateral injection were significant for the RTLE but not the LTLE group. The difference in interhemispheric asymmetry in IAP memory performance between RTLE and LTLE groups was reflected in decreased ability to classify LTLE patients as compared with RTLE patients about side of seizure onset, using a clinically applicable decision rule. CONCLUSIONS: Recognition memory during the IAP for real objects, simultaneously named and presented visually during encoding, is mediated effectively by both the left and right hemisphere when there is no seizure focus present. However, memory appears to be more vulnerable to the presence of a seizure focus in the right as compared with the left hemisphere.

Adolescent↗