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Biomedical subjects

W H Theodore

Publications and source records attributed to W H Theodore.

At least 109 records · Page 6Linked to original sources

Cerebrospinal fluid pleocytosis following simple, complex partial, and generalized tonic-clonic seizures.

We observed postictal pleocytosis in 7 of 62 cerebrospinal fluid specimens obtained from 27 patients with epilepsy. Each patient had a known seizure disorder; none had any other cause for the pleocytosis. The maximum number of leukocytes was 12/mm3; the maximum number of erythrocytes was 190/mm3. Postictal pleocytosis was more common in samples obtained within 12 hours of the last seizure. Although previous studies have emphasized that pleocytosis is more common after repetitive generalized tonic-clonic seizures, we found increased leukocyte counts in cerebrospinal fluid after single simple, complex partial, or generalized tonic-clonic seizures.

Adolescent↗

Antiepileptic drugs and cerebral glucose metabolism.

Using PET with [18-F]-2-deoxyglucose (FDG), we studied the effects of antiepileptic drugs on cerebral glucose metabolism. Serial scans were performed before and after the test drug was added to or removed from the patient's regimen. At least 3 weeks elapsed after achieving steady-state plasma levels when drugs were added, or after plasma levels were undetectable when drugs were tapered, before repeat scans were obtained. Only a single drug was changed between scans. In the phenobarbital (PB) study, the "on-drug" scan was performed first in each case. In this instance, a mean of 14 weeks elapsed between the time blood levels were undetectable and repeat scanning in order to avoid the possibility of withdrawal effects. Scanning in each group was performed 30 min after injection of 5 mCi of FDG, with EEG monitoring to exclude ictal activity. Regional glucose metabolic rates were calculated in 8 to 20 regions of interest. PB reduced LCMRglu in seven of eight regions studied, with a mean reduction over all regions of 37 +/- 3%. Phenytoin (PHT) reduced LCMRglu in only two of 10 regions (mean = 13%). We studied the effect of PHT on cerebellar metabolism in 42 patients using unpaired scans. Cerebellar LCMRglu was lower when patients were taking PHT at the time of scan, as well as in those who were taking PHT for 5 years or more, but the differences were not significant. There was a weak inverse correlation between PHT serum level and cerebellar LCMRglu in patients taking the drug at the time of scan (r = -0.36; 0.05 less than p less than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Anticonvulsants↗

Patterns of cerebral glucose metabolism in patients with partial seizures.

We analyzed local cerebral metabolic rates of glucose (LCMRglu) in 20 regions from 22 patients with complex partial seizures, who were taking neither phenytoin nor phenobarbital and who had normal CTs. Results were compared with data from 19 normal controls. Ten patients had left temporal, eight right temporal, and four bitemporal or generalized EEG discharges. There were no significant differences between patient and control values in any of 20 regions of interest. LCMRglu was depressed at the site of the epileptic focus: L/R ratio was 0.85 +/- 0.12 (p less than 0.003 compared with control), 0.92 +/- 0.08 (p less than 0.05), and 0.84 +/- 0.1 (p less than 0.001), respectively, in mesial, superior, and inferior temporal regions for patients with left temporal foci; 1.7 +/- 0.96 (p less than 0.04), 1.1 +/- 0.1 (NS), and 1.15 +/- 0.04 (p less than 0.001) for patients with right temporal foci. Patients with left temporal EEG foci had significantly lower values than patients with right temporal foci in left superior frontal and thalamic as well as left temporal regions, while patients with right-sided EEG foci had depressed LCMRglu (compared with patients with left temporal EEG foci) restricted to right mesial temporal lobe. The patients with left temporal foci tended to have longer seizure histories (22.7 +/- 5.4 versus 11 +/- 5.6 years; p less than 0.001). There was an inverse correlation between length of seizure history and mean LCMRglu (r = 0.38; 0.1 greater than p greater than 0.05). Our study suggests that LCMRglu is not depressed in regions beyond the epileptic focus when patients are not taking drugs known to decrease cerebral glucose metabolism.

Brain↗

Clinical and electroencephalographic features of simple partial seizures.

The clinical and electroencephalographic features of 87 simple partial seizures in 14 patients were studied with video-EEG telemetry. The patients were able to respond to verbal stimuli during all seizures and, later, could clearly recall ictal events. To determine whether the EEG changes in simple partial seizures could be reliably observed, a reader blindly reviewed four EEGs of equal duration for each seizure. These EEGs consisted of one ictal and three nonictal recordings obtained at predetermined times before the seizure. There were 27 motor seizures (mean duration, 86 seconds; range, 2 to 250 seconds), all involving clonic movements of the head and/or upper extremities; 8 (30%) of these had a sensory component (pain in 6, paresthesia in 2). An EEG change, usually localized spikes or sharp waves over the contralateral or both rolandic regions, was identifiable in nine (33%) of the motor seizures. The 60 nonmotor seizures (mean duration, 63 seconds; range, 8 to 375 seconds) involved a variety of symptoms, including somatosensory/special sensory (3 seizures), autonomic (26 seizures), cognitive (1 seizure), affective (14 seizures), and mixed, or more than one category of nonmotor symptoms (16 seizures). In only nine (15%) of the nonmotor seizures was there an ictal EEG change, usually localized spikes or paroxysmal theta activity over the temporal region. Overall, among the 87 simple partial seizures, only 18 (21%) revealed ictal EEG changes. Thus, a normal EEG is common during simple partial seizures and does not exclude the diagnosis.

Adolescent↗

Cerebral glucose metabolism in the Lennox-Gastaut syndrome.

We used positron emission tomography with fluorine 18-labeled 2-deoxyglucose to study cerebral glucose metabolism in 10 patients with Lennox-Gastaut syndrome who had normal neuroradiological studies. The scans showed decreased metabolic rates relative both to those in the caudate nucleus and to normal control values in 3 patients whose seizures began before the age of 1, as well as in a patient with hyperprolinemia. No patient had a region of persistent focal hypometabolism. Metabolic rates increased in parallel with increased electroencephalographic discharges in 1 patient; 3 patients had lower metabolic rates when the electroencephalogram showed epileptiform discharges and while the patients were taking barbiturates.

Adolescent↗

Localization of magnetic interictal discharges in temporal lobe epilepsy.

Three young adults with intractable complex partial seizures were studied by electroencephalography, magnetoencephalography, and electrocorticography. Interictal electroencephalographic (EEG) spikes for each patient were grouped according to their morphological characteristics and distribution across channels. Mapping of simultaneously recorded magnetoencephalographic signals produced dipolar patterns from which the three-dimensional locations of equivalent current dipoles were calculated, whereas the mapping of EEG spikes showed single regions of electronegativity. The magnetic spikes were localized to the anterotemporal lobe, and the EEG spikes were localized somewhat anterior or posterior to the magnetic spikes. The magnetoencephalographic findings corresponded well with intraoperative electrocorticographic and depth-electrode findings of discharging areas located over the lateral temporal lobe and on the basal and mesial surfaces of the temporal cortex.

Adult↗

Seizures during barbiturate withdrawal: relation to blood level.

We studied 21 patients with complex partial seizures during phenobarbital (PB) or primidone withdrawal. Blood levels were measured daily, and seizure frequency was monitored by nursing staff and EEG-video telemetry. Patients were monitored for one week of baseline and for five weeks after PB tapering was initiated (withdrawal). Most were observed for at least one week after levels were undetectable. When ranked seizure counts were averaged, there was a tendency for seizure rates to be highest as PB levels passed through the range 15 to 20 mg/l, compared with rates at higher or lower PB levels. There was little or no relation between the rate of PB withdrawal, other drug therapy, or initial PB level and the ratio of highest seizure frequency to mean seizure frequency. Patients withdrawing from PB may be most likely to experience an increase in seizure frequency when their PB blood level falls below 20 mg/l.

Humans↗

Effect of phenytoin on human cerebral glucose metabolism.

We used serial positron emission tomography scans with [18F]2-deoxyglucose to study the effect of phenytoin on human cerebral glucose metabolism in 10 patients with seizure disorders. Local CMRglu for each patient was measured in 10 regions of interest. EEGs were performed during each procedure to match scans for state of consciousness and exclude data from scans with ictal activity. Serial scans without a drug change were performed in six control patients. Metabolic rates were significantly lower in two cortical regions while patients were taking phenytoin. No significant changes on repeat scan were seen in the control population. Measured across all regions of interest, metabolic rates were 13% higher when patients were off phenytoin (p less than 0.02).

Adult↗

Barbiturates reduce human cerebral glucose metabolism.

We studied the effect of barbiturates on local cerebral glucose metabolism by performing positron emission scans before and after withdrawal of phenobarbital or primidone. The postwithdrawal scan showed a significant increase (mean, 37%) in seven of eight cortical regions tested. Patients who had serial scans without a drug change showed a nonsignificant tendency for metabolic rates to go down on the second scan (mean decrease, 7%). Addition or deletion of a single drug other than barbiturate did not change metabolic rates on repeat scans. The depression in cerebral glucose metabolic rate due to phenobarbital, if confirmed, may have bearing on the adverse neuropsychological effects of the drug.

Adult↗

Neuroimaging in refractory partial seizures: comparison of PET, CT, and MRI.

We compared the results of x-ray CT, magnetic resonance imaging (MRI), and positron emission tomography (PET) using 18F 2-deoxyglucose in 36 patients with partial seizures. Seventeen patients had localized epileptic discharges on surface EEG. MRI showed an abnormality in 9, CT in 4, and PET in 13 of 14 patients who had the test. Nineteen patients had nonlocalizing EEG discharges. MRI showed an abnormality in 11, CT in 10, and PET in 8 of 12. MRI is more sensitive than CT in detecting structural lesions underlying PET hypometabolism.

Adolescent↗

Neuroimaging.

The role of neuroimaging procedures, including new techniques, such as positron emission tomography and magnetic resonance imaging in the evaluation of seizures, is discussed.

Aged↗

The clinical value of free phenytoin levels.

The relationship between total and free phenytoin levels and drug toxicity was studied in 80 patients. Twenty-four were taking phenytoin alone. Drug toxicity was assessed by a "blind" rater using an eight-point standardized scoring system. The mean free phenytoin fraction was 0.076 in patients taking phenytoin alone or phenytoin and carbamazepine and 0.11 in patients taking valproic acid (p less than 0.001). The free fraction did not change with the total level over the range tested (6.7 to 39.9 micrograms/ml total phenytoin). There was a strong correlation between free and total levels (r = 0.84). Both free (r = 0.59) and total (r = 0.49) phenytoin levels were positively correlated with the toxicity score. Only total phenytoin levels showed a weak positive correlation with decreasing seizure frequency. Our results suggest that routine free phenytoin level monitoring is not necessary in most clinical situations.

Adolescent↗

Positron emission tomography in generalized seizures.

We used 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to study nine patients with clinical absence or generalized seizures. One patient had only absence seizures, two had only generalized tonic-clonic seizures, and six had both seizure types. Interictal scans in eight failed to reveal focal or lateralized hypometabolism. No apparent abnormalities were noted. Two patients had PET scans after isotope injection during hyperventilation-induced generalized spike-wave discharges. Diffusely increased metabolic rates were found in one compared with an interictal scan, and in another compared with control values. Another patient had FDG injected during absence status: EEG showed generalized spike-wave discharges (during which she was unresponsive) intermixed with slow activity accompanied by confusion. Metabolic rates were decreased, compared with the interictal scan, throughout both cortical and subcortical structures. Interictal PET did not detect specific anatomic regions responsible for absence seizure onset in any patient, but the results of the ictal scans did suggest that pathophysiologic differences exist between absence status and single absence attacks.

Adult↗

The role of positron emission tomography in the evaluation of seizure disorders.

We studied patients with partial and primary generalized seizures using fluorine-18-labeled 2-fluorodeoxyglucose and positron emission tomography. Interictal studies of patients with partial seizures showed regions of focal or lateralized hypometabolism in 15 of 17 patients with unilateral electroencephalographic foci. Several patients had more than one hypometabolic region. In 1 patient PET hypometabolism was contralateral to the electroencephalographic epileptic focus. Six of 10 patients without definite electroencephalographic foci also showed unilateral PET hypometabolic regions. PET during complex partial seizures in 3 patients showed hypermetabolism at the site of the hypometabolic focus. A postictal scan in 1 patient showed extension of interictal temporal hypometabolism to the frontal lobe as well. Interictal scans in 8 patients with primary generalized seizures did not reveal any hypometabolic regions. One patient scanned during an attack of absence status epilepticus showed a slight decrease in metabolic rate compared to the interictal scan. Temporal lobectomy has been performed in 6 patients with focal PET hypometabolism. PET may obviate the need for depth electrode study in some patients with intractable partial seizures.

Electroencephalography↗

Phenytoin: the pseudosteady-state phenomenon.

After reaching an apparent steady state, plasma phenytoin (PHT) levels may then undergo inexplicable changes, a phenomenon called " pseudosteady state". We evaluated 13 pseudosteady -state periods in 10 inpatients with complex partial seizures. Eleven of the periods occurred after a change in PHT dosage and two after drug withdrawal. The pseudosteady -state period began 2 to 12 days (means = 5.7 days) after dosage change and lasted 5 to 10 days (means = 6.3 days), during which plasma PHT levels were stable (+/- 5%). Plasma PHT levels thereafter fluctuated spontaneously by greater than 25% for 5 to 22 days (means = 10.8 days). A final steady-state level was reached 13 to 31 days (means = 21.4 days) after the first dosage change. Falling plasma PHT levels increased seizure frequency in two patients, and a level of 52 micrograms/ml led to medication toxicity in another.

Adult↗

Serial EEG in intractable epilepsy.

We compared serial EEGs performed at admission, discharge, and follow-up (mean, 25 months) to clinical outcome in 70 patients with intractable epilepsy. The diagnosis in each case was confirmed by intensive monitoring. EEG features evaluated were background slowing, focal slowing, and focal, bilateral, or generalized epileptiform discharges. Clinical measures were seizure frequency and medication toxicity. No statistically significant correlations were found between improvement in any EEG feature and any clinical measure. EEG did not predict which patients would benefit from intensive monitoring. Serial EEGs may be of little value in assessing the results of treatment in patients with severe epilepsy.

Adolescent↗