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Biomedical subjects

W H Theodore

Publications and source records attributed to W H Theodore.

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

Functional anatomy of cognitive development: fMRI of verbal fluency in children and adults.

OBJECTIVE: To identify age-dependent activation patterns of verbal fluency with functional MRI (fMRI). BACKGROUND: Few fMRI language studies have been performed in children, and none provide comparison data to adult studies. Normative data are important for interpretation of similar studies in patients with epilepsy. METHODS: A total of 10 normal children (5 boys, 5 girls; mean age, 10.7 years; range, 8.1 to 13.1 years) and 10 normal adults (5 men, 5 women; mean age, 28.7 years; range, 19.3 to 48 years) were studied on a 1.5-T Signa MRI scanner using BOLD echo planar imaging of the frontal lobes with a verbal fluency paradigm, covert word generation to letters. Studies were analyzed with a cross-correlation algorithm (r = 0.7). A region-of-interest analysis was used to determine the extent, magnitude, and laterality of brain activation. RESULTS: Children and adults activated similar regions, predominantly in left inferior frontal cortex (Broca's area) and left middle frontal gyrus (dorsolateral prefrontal cortex). Children had, on average, 60% greater extent of activation than adults, with a trend for greater magnitude of activation. Children also had significantly more right hemisphere and inferior frontal gyrus activation than adults. CONCLUSIONS: In a test of verbal fluency, children tended to activate cortex more widely than adults, but activation patterns for fluency appear to be established by middle childhood. Thus, functional MRI using verbal fluency paradigms may be applied to pediatric patient populations for determining language dominance in anterior brain regions. The greater activation found in children, including the right inferior frontal gyrus, may reflect developmental plasticity for the ongoing organization of neural networks, which underlie language capacity.

Adolescent↗
PubMed2000

Postoperative changes in cerebral metabolism in temporal lobe epilepsy.

BACKGROUND: Fludeoxyglucose F 18 positron emission tomography ((18)F-FDG-PET) can detect focal metabolic abnormalities ipsilateral to the seizure focus in 80% of patients with temporal lobe epilepsy (TLE). Regions outside the epileptogenic zone can also be affected. We hypothesized that these remote regions might show altered metabolism, tending to return toward normal values, after surgery. DESIGN: Interictal preoperative and postoperative (18)F-FDG-PET metabolism were compared in patients with refractory TLE. Based on pathological findings, disease was classified in the following 3 groups: mesial temporal sclerosis, mass lesions, and no pathological diagnosis. Quantitative PET data analysis was performed using the region-of-interest template previously described. Global normalization was used to adjust for the effect of antiepileptic medication changes. Data were analyzed by Wilcoxon signed rank test and analysis of variance. SETTING: The Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health. PATIENTS: Twenty-two patients with refractory TLE. RESULTS: Preoperatively, in all groups, cerebral metabolic rate for glucose was decreased ipsilateral to the resection site in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, in all groups, cerebral metabolic rate for glucose increased in ipsilateral inferior frontal area and thalamus. In the mesial temporal sclerosis group, we found a statistically significant increase in the contralateral thalamus. CONCLUSION: Temporal lobe epilepsy is associated with extensive preoperative decreased metabolism in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, we found increased IF and thalamic metabolism. Seizures may have a reversible effect on brain areas connected with, but remote from, the epileptogenic cortex. Arch Neurol. 2000;57:1447-1452

Adult↗
PubMed2000

Relationship of seizure frequency to hippocampus volume and metabolism in temporal lobe epilepsy.

PURPOSE: To examine the relationship between frequency of complex partial (CPS) and secondarily generalized tonic-clonic seizures (sGTCS) on hippocampal volume (HV) and temporal lobe metabolism. METHODS: We performed volumetric magnetic resonance imaging (MRI) and positron emission tomography with 18fluorodeoxyglucose (18FDG-PET) in 32 patients with epilepsy. Temporal lobe foci were localized by ictal video-EEG. RESULTS: We did not find any association between CPS frequency or lifetime number of sGTCS and HV or metabolism ipsilateral to electroencephalographic focus. CONCLUSION: The progress of metabolic or pathologic abnormalities of temporal lobe epilepsy may not be altered by adequate seizure control. The presence of an epileptic focus might be associated with progressive neuronal injury even in clinically well-controlled patients.

Adult↗
PubMed1999

The effect of vigabatrin (gamma-vinyl GABA) on cerebral blood flow and metabolism.

OBJECTIVE: To investigate the effect of vigabatrin (VGB; gamma-vinyl gamma-aminobutyric acid [GABA]), a selective irreversible GABA-transaminase inhibitor, on cerebral metabolic rate for glucose (CMRGlc) and cerebral blood flow (CBF) measured with 18F-fluorodeoxyglucose (FDG) PET and 15O water PET. BACKGROUND: Antiepileptic drugs (AEDs) reduce CMRGlc to varying degrees. Phenobarbital causes a mean decrease of 30 to 40%. Phenytoin, carbamazepine (CBZ), and valproate (VPA) cause milder reductions in CMRGlc. The combination of VPA with CBZ results in a greater decrease than either drug alone. The effect of novel AEDs on both CBF and CMRGlc has not been studied extensively. METHODS: Fourteen patients with refractory complex partial seizures on CBZ monotherapy for 4 weeks were included in the study. All patients had baseline 18F-FDG and 15O water PET studies followed by double-blind randomization to placebo (PLC) or VGB while on continuous CBZ treatment. PET scans were repeated after an interval of 2 months on target dose of VGB (50 mg/kg) or PLC. Quantitative PET data analysis was performed using a region of interest template. Significance was tested with the Wilcoxon rank sum test. RESULTS: No statistically significant difference in age, duration of epilepsy, or CBZ levels was observed in the two patient groups. VGB reduced global CMRGlc by 8.1+/-6.5% and global CBF by 13.1+/-10.4%. The change in CMRGlc was different in patients taking VGB compared with those on PLC (p < 0.04). VGB patients showed regional decreases in both CMRGlc and CBF, particularly in temporal lobes. CSF total GABA increased in the VGB patient group (1.48+/-1.06 versus 4.03+/-4.19 nm/mL). The increase differed from the PLC group (p < 0.03). We found a strong relation between decreased total CSF GABA and increased CMRGlc in the VGB patient group (R2 = 0.82, p < 0.01). CONCLUSIONS: Vigabatrin (VGB) causes mild reductions in both cerebral blood flow (CBF) and cerebral metabolic rate for glucose (CMRGlc) in contrast to other drugs such as barbiturates, which are direct agonists at the gamma-aminobutyric acid-benzodiazepine receptor complex. Conventional AEDs depress CBF and CMRGlc to a greater degree than does VGB. The relatively mild reduction could be due to pre- as well as postsynaptic effects or a use-dependent mechanism.

Adult↗
PubMed1999

Hippocampal atrophy, epilepsy duration, and febrile seizures in patients with partial seizures.

BACKGROUND: Previous studies have suggested a variety of factors that may be associated with the presence of hippocampal formation (HF) atrophy in patients with complex partial seizures (CPS), including a history of complex or prolonged febrile seizures (FS), age at seizure onset, and epilepsy duration. OBJECTIVE: To determine whether epilepsy duration is related to HF atrophy. METHODS: We performed MRIs on 35 patients with uncontrolled CPS who had temporal lobe ictal onset on video-EEG. None had evidence for an alien tissue lesion or extra-hippocampal seizure onset. All had a history of secondary generalization. Brain structures were drawn on consecutive images and pixel points summed from successive pictures to calculate volumes. RESULTS: Nine patients with a history of complex or prolonged FS had smaller ipsilateral HF volume and ipsilateral/contralateral ratio than did patients without a history of FS. Epilepsy duration had a significant relation to ipsilateral HF volume and ipsilateral/contralateral ratio. In a multivariate analysis, the effect of duration, but not age at onset or scan, was significant. Patients with a history of FS did not have earlier age at epilepsy onset or longer duration. CONCLUSIONS: A history of FS predicted the severity of HF atrophy in our patients. Age at onset or study was not a significant factor. Epilepsy duration, however, did have a significant effect, suggesting that, after an initial insult, progressive HF damage may occur in patients with persistent seizures.

Adult↗
PubMed1999

(15)O water positron emission tomography in language localization: a study comparing positron emission tomography visual and computerized region of interest analysis with the Wada test.

We compared (15)O water positron emission tomography (PET) auditory and visual confrontational naming activation with an intracarotid amobarbital (Amytal) injection procedure (IAP) for language lateralization in 12 patients with intractable epilepsy. PET scans were evaluated by three raters experienced in functional imaging as well as by a region of interest (ROI) approach. Compared with IAP, raters' positive predictive value for language lateralization ranged from 88 to 91%. ROI analysis had a positive predictive value of 80%. Six patients had surgery; 1 with right-sided IAP language dominance but left-sided PET activation had dysphasia for 6 months after left temporal lobectomy.

Adolescent↗
PubMed1999

Repetitive transcranial magnetic stimulation of the dominant hemisphere can disrupt visual naming in temporal lobe epilepsy patients.

We used repetitive transcranial magnetic stimulation (rTMS) to study visual naming in 14 patients with temporal lobe epilepsy. Ten had left hemisphere language by Wada testing and all experienced speech arrest with rTMS of the motor speech area in the left frontal lobe. One left-hander had speech arrest with stimulation of sites on both sides. Subjects were asked to name pictures or read words presented on a computer monitor. rTMS was delivered on half of the trials. Stimulation sites were the motor speech area in the left frontal lobe, the mirror site on the right, and the left and right mid superior and posterior temporal lobes. rTMS at left hemisphere sites caused more naming errors than did right hemisphere rTMS. All individual subjects, except two who had temporal lobe resections and the one with bilateral speech arrest, produced more naming errors with rTMS of left hemisphere sites. There was no significant effect on word reading. rTMS at the left hemisphere and right frontal sites produced reductions in reaction time for picture naming, but not for word reading. This was observed for both correct and incorrect responses. This study shows that left hemisphere rTMS can disrupt visual naming selectively.

Adult↗
PubMed1999

The efficacy of felbamate as add-on therapy to valproic acid in the Lennox-Gastaut syndrome.

We studied the efficacy of felbamate (FBM) in combination with valproic acid (VPA) in 13 patients with the Lennox-Gastaut syndrome and evaluated the contribution of each drug. Following stabilization on VPA monotherapy, FBM or placebo titration was performed for two observation periods lasting 7 weeks with a washout period between them. 6-h video-electroencephalography was recorded following each observation period. In addition to examining the effects of the drugs with parental reports and video-EEG, we compared video-EEG data with families' seizure reports. Based on parental counts for the 7-week observation periods, patients had 40% fewer drop attacks (p < 0.03, Wilcoxon rank sum test) and 60% fewer total seizures (p < 0.02) on VPA and FBM. VPA level rose by 12.7% when FBM was added (p < 0.01). When the effect of FBM was factored out, VPA had a significant effect on drop attack frequency, although not total number of seizures. FBM's therapeutic effect on drop attacks is due in part to increased VPA levels, although the combination may be synergistic for the effect on total seizure number.

Adolescent↗
PubMed1999

Positive and negative psychiatric effects of antiepileptic drugs in patients with seizure disorders.

Antiepileptic drugs (AEDs) have various mechanisms of actions and therefore have diverse anticonvulsant, psychiatric, and adverse effect profiles. Two global categories of AEDs are identified on the basis of their predominant psychotropic profiles. One group has "sedating" effects in association with fatigue, cognitive slowing, and weight gain, as well as possible anxiolytic and antimanic effects. These actions may be related to a predominance of potentiation of gamma-aminobutyric acid (GABA) inhibitory neurotransmission induced by drugs such as barbiturates, benzodiazepines, valproate, gabapentin, tiagabine, and vigabatrin. The other group is associated with predominant attenuation of glutamate excitatory neurotransmission and has "activating" effects, with activation, weight loss, and possibly anxiogenic and antidepressant effects. This group includes agents such as felbamate and lamotrigine. Agents such as topiramate, with both GABAergic and antiglutamatergic actions, may have "mixed" profiles. Mechanisms of actions, activity in animal models of anxiety and depression, and clinical psychotropic effects of AEDs in psychiatric and epilepsy patients are reviewed in relationship to this proposed categorization. These considerations suggest the testable hypothesis that better psychiatric outcomes in seizure disorder patients could be achieved by treating patients with baseline "activated" profiles (insomnia, agitation, anxiety, racing thoughts, weight loss) with "sedating" predominantly GABAergic drugs, and conversely those with baseline "sedated" or anergic profiles (hypersomnia, fatigue, apathy, depression, sluggish cognition, weight gain) with "activating" predominantly antiglutamatergic agents. Systematic clinical investigation of more precise relationships of discrete mechanisms of actions to psychotropic profiles of AEDs is needed to assess the utility of this general proposition and define exceptions to this broad principle.

Anticonvulsants↗
PubMed1998

Regional cerebral blood flow during auditory responsive naming: evidence for cross-modality neural activation.

One issue of continuing debate in language research concerns whether the brain holds separate representations for semantic information through the auditory vs visual modalities. Regardless of whether we hear, see or read meaningful information, our brains automatically activate both auditory and visual semantic associations to the sensory input. The prominent models for how the brain makes these cross-modality associations holds that semantic information conveyed through either sensory input modality is represented in a shared semantic system comprising the traditionally identified language areas in the brain. A few recent case reports as well as activation imaging studies, have challenged this notion by demonstrating category-specific organization within the semantic system in spatially discrete brain regions. Neither view posits a role for primary sensory cortices in semantic processing. We obtained positron emission tomographic (PET) images while subjects performed an auditory responsive naming task, an auditory analog to visual object naming. Subjects heard and responded to descriptions of concrete objects while blindfolded to prevent visual stimulation. Our results showed that, in addition to traditional language centers, auditory language input produced reciprocal activation in primary and secondary visual brain regions, just as if the language stimuli had entered in the visual modality. These findings provide evidence for a distributed semantic system in which sensory-specific semantic modules are mutually interactive, operating directly onto early sensory processing centers.

Acoustic Stimulation↗
PubMed1998

Extratemporal atrophy in patients with complex partial seizures of left temporal origin.

Total cerebral, temporal lobe, hippocampal, caudate, and lenticular nuclei volumes were quantified from magnetic resonance images of 21 patients with left temporal lobe epilepsy and medically intractable complex partial seizures. These regional brain volumes were compared with the same measures in 19 controls. No significant differences in total cerebral, left temporal lobe, right temporal lobe, or total temporal lobe volumes were found. As expected, left hippocampal volumes were significantly smaller in the patients with epilepsy than in control subjects. The left hippocampus-to-right hippocampus volume ratio was significantly lower in patients than in control subjects. In addition to left hippocampal volumes, mean left thalamic, left caudate, and bilateral lenticular volumes were significantly smaller in the patients with epilepsy than in control subjects. The left-to-right thalamic volume ratio was also significantly lower in the patients with epilepsy compared with control subjects, but there were no significant group differences in caudate or lenticular ratios. These results show that medically intractable temporal lobe epilepsy is associated with volume loss in brain structures outside the presumably involved hippocampus. The pathophysiological significance of our findings is uncertain. They could be related to the underlying cause of the disorder. However, volume loss also may reflect damage due to involvement of these structures in recurrent seizure activity.

Adult↗