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Biomedical subjects

W H Theodore

Publications and source records attributed to W H Theodore.

At least 127 records · Page 7Linked to original sources
PubMed1984

Disposition of mephenytoin and its metabolite, nirvanol, in epileptic patients.

We investigated the conversion of mephenytoin to nirvanol in five patients with uncontrolled complex partial seizures. After a 50-mg single oral dose, mean peak mephenytoin level was 0.48 microgram/ml and nirvanol 0.37 microgram/ml. After 400 mg, peak mephenytoin level was 3.9 micrograms/ml and nirvanol 2.5 micrograms/ml. On 400 mg daily, mephenytoin reached a mean steady-state level of 1.5 micrograms/ml. Nirvanol mean steady-state level was 18 micrograms/ml. Mean plasma half-life was 17 hours for mephenytoin and 114 hours for nirvanol. Two patients had reduced seizures during mephenytoin therapy and one a transient increase during drug withdrawal. No toxicity was seen, but mephenytoin was not more effective than phenytoin.

Adolescent↗
PubMed1983

EEG, transmission computed tomography, and positron emission tomography with fluorodeoxyglucose 18F. Their use in adults with gliomas.

We evaluated the relationship between findings from EEG, transmission computed tomography (CT), and positron emission tomography in 23 adults with gliomas. The cortical metabolic rate was suppressed in patients with and without focal slowing. Focal delta activity was not related to involvement of gray or white matter. Rhythmic delta activity and focal attenuation of background amplitude on EEG, however, were correlated with involvement of the thalamus.

Adult↗
PubMed1983

Familial spastic paraplegia, mental retardation, and precocious puberty.

Two brothers had progressive spastic paraplegia and precocious puberty develop due to Leydig's cell hyperplasia when they were 2 years old. Both later had moderate mental retardation. Family members displayed brisk lower-extremity reflexes and dysarthria in a pedigree that suggested autosomal dominant inheritance with variable expression. Precocious puberty has been associated with other neurologic syndromes. Its occurrence in two brothers with spastic paraplegia has not, to our knowledge, been previously reported.

Adult↗
PubMed1983

Removal of sedative-hypnotic antiepileptic drugs from the regimens of patients with intractable epilepsy.

Sedative-hypnotic antiepileptic drugs have potentially toxic effects, but their removal is often thought to be difficult and dangerous. We completely withdrew all barbiturates and benzodiazepines from 78 patients with intractable epilepsy (48 inpatients and 30 outpatients). Initially, 19 patients had plasma levels of sedative drugs above the therapeutic range; 28 were taking more than one of these drugs. Dosages of nonsedative antiepileptic drugs were adjusted to provide optimal seizure control. After 6 months of outpatient follow-up, 69 patients remained on a nonsedative regimen: 35 (51%) showed improvement in both drug toxicity and seizure control, 13 (19%) in toxicity alone, 8 (12%) in seizure control alone; 12 (16%) were unchanged, and 1 was worse. Of 9 patients restarted on sedative antiepileptic drugs by their private physicians, 4 had more toxic symptoms than at discharge, 1 had more frequent seizures, 3 were unchanged, and 1, who had had a temporal lobectomy after drug withdrawal, had less frequent seizures. Sedative drugs are not necessary for optimal seizure control, even in intractable epilepsy, and they may be safely withdrawn.

Adolescent↗
PubMed1983

[18F]fluorodeoxyglucose positron emission tomography in refractory complex partial seizures.

Positron emission tomography with simultaneous electroencephalographic monitoring was performed with [18F]fluorodeoxyglucose in 20 patients with complex partial seizures who had normal computed tomographic scans. Seven patients had only unilateral epileptiform discharges on the electroencephalogram, 3 had predominantly unilateral discharges, and 10 had nonlocalized epileptiform abnormalities. Positron emission tomography showed a hypometabolic lesion in 16 of the 20 patients. Pathological changes in the hypometabolic region were found in postoperative specimens in 4 of 5 patients studied. Positron emission tomography was unaffected by the seizure frequency, state of alertness, or number of spike discharges during the scan. There was a tendency for patients to have higher overall metabolic rates when taking less medication. Seizures occurring during [18F]fluorodeoxyglucose uptake in 3 patients produced a hypermetabolic area at the interictal hypometabolic focus. Positron emission tomography sometimes showed more widespread hypometabolism than suspected on the basis of the scalp-recorded electroencephalogram. The frontal lobe showed a greater degree of hypometabolism than the temporal lobe in 3 patients. Focal lesions may be identified by positron emission tomography even if the electroencephalographic abnormality is not well localized.

Adult↗
PubMed1983

EEG and evoked potentials in precocious puberty.

We recorded brain stem auditory evoked potentials, pattern reversal visual evoked potentials and electroencephalograms in 19 children, 2-8 years old. Sixteen had precocious puberty and three had precocious adrenarche. Two of the children with precocious puberty had hypothalamic hamartomas, one had an optic glioma, and one had a history of hydrocephalus. The EEG was abnormal in 7 patients: three had diffuse slowing, and four showed possible paroxysmal features. BAEPs and VEPs were normal in all patients. This study showed no abnormalities in two conduction pathways of the central nervous system and no evidence of a deleterious effect of hormonal aberrations in patients with precocious puberty. Abnormal EEG in these patients is more likely to reflect occult diencephalic disease than widespread neurophysiological dysfunction.

Brain Diseases↗
PubMed1983

Intractable seizures: long-term follow-up after prolonged inpatient treatment in an epilepsy unit.

Seventy-four patients with intractable seizures were followed up 6 to 57 months (mean 25 months) after intensive monitoring. At discharge from the hospital, 59% of the patients had at least a 50% reduction in seizure frequency and 63% had decreased antiepileptic drug toxicity. The findings at follow-up compared with those at admission showed reduced seizure frequency in 55% of the patients, diminished medication toxicity in 54%, and improved social adjustment in 38%. A change in the seizure diagnosis was the best predictor of a favorable outcome. Patients with impaired mental status were not less likely to improve. The relationship between seizure type and outcome was not significant, although patients with complex partial seizures tended to be less likely to improve. Intensive monitoring can lead to significant long-lasting improvement of patients with severe epilepsy.

Adolescent↗
PubMed1983

Complex partial seizures: clinical characteristics and differential diagnosis.

Videotape analysis of 163 complex partial seizures in 40 patients showed that the mean duration of the attack was 128 seconds. Automatisms occurred in 159 seizures (97%) and involved more than the face and arms in 132 (80%). Most automatisms were simple, stereotypic, or aimless movements. Postural tone increased in 24 seizures and decreased in 62. Clonic movements of the eyelids occurred in 19 attacks, and clonic movements of the extremities in 4. Only nine patients reported auras. Distinct ictal and postictal phases could be distinguished in 132 seizures (80%); in these, the mean ictal duration was 54 seconds and the mean postictal duration 89 seconds. Videotape analysis provides objective criteria by which complex partial seizures may be differentiated from other seizure types.

Adolescent↗
PubMed1983

Nonsedative regimens in the treatment of epilepsy.

Trends in the diagnosis of epilepsy have continued to focus on the fundamental cause of the seizures, as well as the seizure type. It is the latter that determines symptomatic therapy. New drugs have improved the lives of many epileptic patients, and emphasis on nonsedative medications, both new and old, is now possible and desirable in most patients. Finally, new and better drugs are needed for the many severely affected epileptic patients who are not helped by the currently available antiepileptic drugs.

Carbamazepine↗
PubMed1982

Phenytoin: an inhibitor and inducer of primidone metabolism in an epileptic patient.

The interaction between primidone and phenytoin was studied in an epileptic patient treated with primidone only and primidone plus phenytoin for 3 months. Plasma and urine levels of drugs and metabolites were monitored daily by GC and GC-MS. The addition of phenytoin to the regimen increased steady-state plasma levels of phenobarbitone and phenylethylmalonamide (PEMA), metabolites of primidone, and decreased levels of primidone and unconjugated p-hydroxyphenobarbitone (p-OHPB), a metabolite of phenobarbitone. After withdrawal of phenytoin, plasma phenobarbitone and primidone levels slowly returned to previous steady-state levels, PEMA rapidly decreased to lower levels than before, and p-OHPB levels rose rapidly. Urinary excretion of primidone and its metabolites paralleled the changes in their plasma levels after the addition of phenytoin but the percentage of unconjugated p-OHPB in urine was unchanged during the course of the study. In conclusion phenytoin initially induces the conversion of primidone to PEMA and phenobarbitone, although each to a different extent, but it appears to inhibit the hydroxylation of phenobarbitone. Thus, two apparently contradictory phenomena seem to be involved in the primidone-phenytoin interaction. The net effect is an enhanced increase in plasma phenobarbitone levels.

Adult↗
PubMed1981

Meningeal carcinomatosis.

We reviewed 33 cases of meningeal carcinomatosis seen at the Mount Sinai Hospital, New York, from 1970 through 1979. The major sources of meningeal disease were carcinoma of the breast (21 cases), carcinoma of the lung (five), and malignant melanoma (five). Seventy-eight percent of the patients had widespread metastases at the time of neurologic diagnosis. A combination of radiotherapy and intrathecal administration of methotrexate was the most successful treatment, and 14 of 22 treated patients showed at least symptomatic improvement; however, mean survival in the most improved group was still less than six months.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Cerebral activation during speech discrimination in temporal lobe epilepsy.

Eight patients with uncontrolled complex partial seizures underwent positron emission tomography with 18-fluoro-2-deoxyglucose both at rest and during an auditory order discrimination task using speech syllables. Eight age-matched controls were scanned under identical conditions; an additional 18 normal subjects were scanned only at rest. No consistent task-related changes were seen in control subjects. For the 3 patients with left temporal epileptogenic foci, left inferior temporal lobe hypometabolism was more evident during the activated than during the resting scan. Activation procedures may augment the diagnostic yield of metabolic scanning in epilepsy.

Adult↗
PubMedDate not supplied

MR imaging and positron emission tomography of cortical heterotopia.

Heterotopia of the gray matter is a developmental malformation in which ectopic cortex is found in the white matter of the brain. A case of a 33-year-old man with cortical heterotopia who had a lifelong history of seizures and psychomotor retardation is reported, including the results of cerebral CT, magnetic resonance imaging, and positron emission tomography using 18F-2-deoxyglucose.

Adult↗
PubMedDate not supplied

Complex partial seizures: cerebral structure and cerebral function.

We studied the relationships between cerebral structure and function in 10 patients with complex partial seizures who had major cerebral lesions, including porencephalic cysts, tuberose sclerosis, agenesis of the corpus callosum, and cerebral hemiatrophy. Evaluation included computed tomography (CT) and magnetic resonance imaging (MRI) scanning, EEG, and positron emission tomography (PET) using [18F]-2-deoxyglucose. Surface EEG usually showed widespread, bilateral epileptiform discharges even if pathology was clearly restricted to one hemisphere. In several cases, interictal PET hypometabolism was more widespread than structural changes seen on CT and MRI, extending to involve the ipsilateral temporal lobe in patients with extratemporal lesions. This study shows that patterns of metabolic and electrophysiologic dysfunction may not be predicted by structural lesions in patients with partial seizure disorders.

Agenesis of Corpus Callosum↗
PubMedDate not supplied

Complex partial seizures: cerebellar metabolism.

We used positron emission tomography (PET) with [18F]2-deoxyglucose to study cerebellar glucose metabolism (LCMRglu) and the effect of phenytoin (PHT) in 42 patients with complex partial seizures (CPS), and 12 normal controls. Mean +/- SD patient LCMRglu was 6.9 +/- 1.8 mg glucose/100 g/min (left = right), significantly lower than control values of 8.5 +/- 1.8 (left, p less than 0.006), and 8.3 +/- 1.6 (right, p less than 0.02). Only four patients had cerebellar atrophy on CT/MRI; cerebellar LCMRglu in these was 5.5 +/- 1.5 (p = 0.054 vs. total patient sample). Patients with unilateral temporal hypometabolism or EEG foci did not have lateralized cerebellar hypometabolism. Patients receiving phenytoin (PHT) at the time of scan and patients with less than 5 years total PHT exposure had lower LCMRglu, but the differences were not significant. There were weak inverse correlations between PHT level and cerebellar LCMRglu in patients receiving PHT (r = -0.36; 0.05 less than p less than 0.1), as well as between length of illness and LCMRglu (r = -0.22; 0.05 less than p less than 0.1). Patients with complex partial seizures have cerebellar hypometabolism that is bilateral and due only in part to the effect of PHT.

Adult↗
PubMedDate not supplied

Felbamate: a clinical trial for complex partial seizures.

We performed a randomized, double-blind, three-period cross-over study of felbamate (FBM, 2-phenyl-1,3-propanediol dicarbamate: Carter-Wallace 554) in patients with complex partial seizures. Patients continued carbamazepine (CBZ) throughout the study and were observed in the hospital for the entire trial period. The entry criteria required at least six seizures in a 3-week baseline period (and no more than 1 week with a single seizure) with CBZ alone. Thirty subjects were randomized. Two left the study after randomization, 1 owing to seizure exacerbation, and 1 owing to hyponatremia, which may have been related to CBZ therapy. The daily dosage of 50 mg/kg (maximum 3,000 mg) FBM per day was well tolerated by all 28 patients who completed the study. Only mild adverse experience were observed during the trial. FBM reduced CBZ level (p less than 0.0001; 95% confidence interval -28%, -20%). There was no significant difference in seizure frequency between placebo and FBM periods (one-sided p = 0.172), but when a correction was made for the lower CBZ level noted during FBM periods, the data suggested a strong antiseizure effect of FBM.

Adult↗
PubMedDate not supplied

Effect of valproate on human cerebral glucose metabolism.

We studied the effects of valproate (VPA) on local cerebral glucose metabolism (LCMRglc) in eight patients with partial seizure disorders and two with primary generalized epilepsy. Each patient had two positron-emission tomography (PET) scans with 18F-2-deoxyglucose (FDG), with, and without, VPA (mean level 52 mg/dl, range 30-127 mg/dl). Patients continued carbamazepine (CBZ) for both scans: serum concentrations were not significantly changed by VPA (CBZ range 5.4-12 mg/dl). Seven patients had the "without-VPA" scan first. Mean interval between PET scans was 75 days. Global CMRglc was decreased by 22% by addition of VPA (7.2 +/- 1.8 mg/100 g/min without VPA, 5.6 +/- 1.1 g/min with VPA, p less than 0.05, corrected). Thirteen regions of interest (ROIs) were analyzed in each hemisphere in each PET scan. Metabolic rates were significantly lower in 15 of 26 ROIs with VPA (p less than 0.05, corrected). VPA depresses cerebral metabolism to a greater degree than do CBZ and phenytoin (PHT) but less than does phenobarbital (PB). The metabolic effect may be related to the mechanism of action and have neuropsychological implications.

Brain↗