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PubMed2002

The effect of age on rate of functional recovery after intracarotid amobarbital injection.

PURPOSE: The duration of the drug effect during the intracarotid amobarbital procedure (IAP) is an important factor when considering the prioritization of behavioral testing during the IAP. Previous studies of thiopental, a barbiturate similar to sodium amobarbital, found that age and gender significantly affect the dose required to induce anesthesia, such that younger patients require higher dosage. METHODS: A total of 55 patients who underwent the IAP procedure at Johns Hopkins Hospital were included in the study (110 hemispheric injections). The patient group included 30 female and 25 male patients, ranging in age from 11 to 50 years. To determine if a higher dose of sodium amobarbital was needed for younger patients during the IAP, we analyzed the time to return to preinjection EEG baseline status and time to return to 5/5 strength as a function of patient age and gender. RESULTS: We found that younger patients (11-20 years old) returned to preinjection baseline EEG status and full (5/5) strength faster than older patients. No gender difference was found. CONCLUSIONS: The sodium amobarbital effect during IAP dissipates faster in young patients. Consideration of this difference in rate of recovery in 11-to 20-year-old patients has important clinical implications in terms of prioritizing behavioral testing.

Adolescent↗
PubMed2005

Language and arithmetic--a study using the intracarotid amobarbital procedure.

The intracarotid amobarbital procedure is used as a standard procedure in presurgical evaluation to assess hemispheric lateralization of language and memory, but has not been applied to investigate numerical processing. Patients with medically intractable epilepsy (n=20) were consecutively recruited during a presurgical evaluation programme. All 14 patients with left-lateralized language showed better arithmetic performance with the left hemisphere (intracarotid amobarbital procedure right), while five out of six patients with bilateral or right-hemispheric language representation showed better performance with the right hemisphere (intracarotid amobarbital procedure left). Furthermore, in patients with left-lateralized language, an interaction between intracarotid amobarbital procedure and type of arithmetic operation was found. The study suggests a close association between language lateralization and hemispheric specialization for arithmetic processing.

Adult↗
PubMed1999

Evaluation of functional changes in the medial temporal region during intracarotid amobarbital procedure by use of SPECT.

PURPOSE: Because the main blood supply to the medial temporal region is through the posterior cerebral artery, the validity of the intracarotid amobarbital procedure (IAP) is still debated. To verify clinical validity of the IAP, we investigated changes in neuronal function in the medial temporal region during IAP. METHODS: Brain single photon emission computed tomography (SPECT) was performed during IAP (IAP-SPECT) in 22 patients with temporal lobe epilepsy (TLE), and regional cerebral blood flow (rCBF) in the medial and lateral temporal regions of interest (ROIs) was measured quantitatively. To determine the distribution of sodium amobarbital, in another 20 patients with TLE, SPECT images were obtained after intracarotid injection of 99mTc-HMPAO mixed with sodium amobarbital. RESULTS: Mean rCBF was 89.2% in the medial temporal region and 81.6% in the lateral temporal region: in the former region, it was significantly lower than that shown by the results of interictal SPECT (99.1%; p < 0.001). In a few patients, however, rCBF did not decrease in the medial temporal region. In only 25% of patients, the medial temporal region was visualized in SPECT images obtained after intracarotid injection of 99mTc-HMPAO. CONCLUSIONS: The results in this study demonstrate that IAP is valid because the medial temporal region is inactivated in spite of infrequent delivery of sodium amobarbital. We assume that intratemporal diaschisis is operating for the inactivation of neuronal function. IAP-SPECT with intratemporal ROIs may be useful for monitoring changes in neuronal function in the medial temporal region during IAP.

Adolescent↗
PubMed2001

Language dominance in children as determined by magnetic source imaging and the intracarotid amobarbital procedure: a comparison.

This study evaluated the validity of data derived from magnetic source imaging regarding hemispheric dominance for language in children and adolescents with intractable seizure disorder by comparison with results of the intracarotid amobarbital procedure. Functional imaging of the receptive language cortex using a whole-head neuromagnetometer was performed in 19 consecutive epilepsy patients, ages 8 to 18 years, who also underwent the intracarotid amobarbital procedure. During magnetic source imaging recordings, patients engaged in a continuous recognition memory task for words in visual and auditory modalities. This task has previously been shown to be valid for the purpose of lateralization and localization of language cortex in adult epilepsy patients who undergo the intracarotid amobarbital procedure and intraoperative language mapping allowing confirmation of magnetic source imaging findings. Results indicated that language laterality indices formed for the intracarotid amobarbital procedure and magnetic source imaging procedures were highly correlated (R = .87). In addition, clinical judgments regarding cerebral dominance for language made by independent raters using the two methods were in excellent agreement. We conclude that magnetic source imaging is a promising method for determination of cerebral dominance for language in children and adults.

Adolescent↗
PubMed1985

Amobarbital interactions with 25-hydroxycholecalciferol: effects on the extraction, quantification, and competitive protein binding in vitro.

Amobarbital has been found to coelute with 25-hydroxycholecalciferol (25OHD3) on a normal phase high performance liquid chromatographic system and cause subsequent interference in the UV detection and plasma transport competitive protein binding assay for this vitamin D metabolite. Concentrations of 25OHD3 were overestimated by 95% in the presence of 0.4 mg amobarbital in the competitive protein binding assay; as little as 0.1 mg amobarbital caused a 22% overestimation in the concentration of 25OHD3 in the assay. Separation of 25OHD3 from amobarbital on a reverse phase high performance liquid chromatographic system allowed for proper quantification without interference. Because of the similarity of chemical structures, other barbital-based compounds may cause similar interactions with 25OHD3 or other vitamin D metabolites as well.

Amobarbital↗
PubMed1990

The intracarotid amobarbital procedure as a predictor of memory failure following unilateral temporal lobectomy.

We investigated the efficacy of the intracarotid amobarbital procedure to accurately predict post-temporal lobectomy anterograde amnesia. We presented items at 2 separate times during amobarbital assessment; both early and late item recall were decreased during the injection contralateral to seizure onset indicating sensitivity to bilateral temporal lobe dysfunction. Ten patients for whom follow-up neuropsychological assessment was available failed either the early or late item recognition portions of their amobarbital evaluation ipsilateral to seizure onset, but had hippocampus included in the temporal lobectomy by virtue of satisfactory performance on other tests of hippocampal function. None of these 10 patients displayed postoperative anterograde amnesia, although there was a reduction in material-specific memory in some patients. These results indicate that relying solely on amobarbital memory testing to assess the functional ability of the contralateral temporal lobe to sustain global memory prior to temporal lobectomy may needlessly exclude patients from a viable therapeutic option.

Amnesia↗
PubMed2002

Tailored cognitive testing with provocative amobarbital injection preceding AVM embolization.

BACKGROUND AND PURPOSE: Transarterial embolization of cerebral arteriovenous malformations (AVMs) has been associated with postprocedural neurologic complications in 7-39% of patients. We sought to determine whether a method of targeted neurologic and cognitive testing during AVM embolization reduces the incidence of focal cognitive and other neurologic deficits associated with the procedure. METHODS: A cognitive neurologist extensively examined 12 patients prior to AVM embolization. In each patient, a battery of tests tailored to their specific abilities was developed by using stimuli selected from standard and experimental cognitive tests to probe specific brain regions related to the location of the AVM. In each feeder vessel to be embolized, a 50-mg bolus of sodium amobarbital was superselectively administered through a microcatheter; this was followed immediately by neurologic and cognitive testing with the tailored battery. After testing, the position of the microcatheter tip was checked with fluoroscopy. If the provocative test results were negative, the evaluated feeder was embolized with N-butyl cyanoacrylate glue. RESULTS: Although results with 27 of 29 provocative amobarbital injections were negative, results with two injections in two different individuals revealed cognitive deficits during tailored provocative testing. In both, the evoked deficits resolved with dissipation of the amobarbital effect; the feeder vessels were not embolized. Neurologic and cognitive evaluation after each of 27 embolizations revealed no major or minor deficits. CONCLUSION: In our experience, provocative amobarbital testing prior to AVM embolization was helpful in identifying vascular territories where embolization may lead to neurologic and cognitive deficits.

Adult↗
PubMed1989

Memory following intracarotid amobarbital injection contralateral to hippocampal damage.

We examined the relationship between memory performance and hippocampal damage in temporal lobe epileptics undergoing the intracarotid amobarbital sodium procedure (IAP). Overall memory performance in the course of IAP was correlated with seizure lateralization. The hemisphere of seizure focus had impaired IAP memory in 63% (19/30) of the patients. The IAP memory performance following perfusion of the hemisphere contralateral to severe hippocampal lesions was impaired in five of six patients. These patients also exhibited hypometabolism of the impaired temporal lobe as determined independently by positron emission tomography. The single patient with a severely damaged hippocampus who did not demonstrate IAP memory impairment with contralateral hemisphere injection did not exhibit perfusion of the ipsilateral posterior cerebral artery with amobarbital. Memory performance following intracarotid amobarbital injection contralateral to a less severely damaged hippocampus was impaired in 14 of 24 patients and was not related to extent of hippocampal damage, temporal lobe hypometabolism of labeled glucose, perfusion of the ipsilateral posterior cerebral artery, hemispheric language dominance, or order of injection. These results indicate that impaired memory performance during IAP may reflect severe hippocampal damage and/or epileptogenic abnormality.

Adult↗
PubMed1991

The neural substrate of memory impairment demonstrated by the intracarotid amobarbital procedure.

The intracarotid amobarbital sodium (Amytal) procedure (IAP) was performed for 46 patients with temporal lobe epilepsy (21 with left seizure foci; 25 with right seizure foci). After anteromedial temporal lobectomy, neuronal densities were established for hippocampal subfields CA1, CA2, and CA3; the hilum; and the dentate granule cell layer. Intracarotid amobarbital procedure memory results were related to CA3 neuronal loss only. Patients who did not demonstrate memory after injection contralateral to the seizure focus had significantly fewer cells in CA3 than patients who did. Additionally, a significant correlation was observed between the intracarotid amobarbital procedure memory examination raw score after injection contralateral to the seizure focus and CA3 cell density. Using chi 2 analysis, significant differences were documented in the frequency with which memory was demonstrated after injection contralateral to the seizure focus for groups of patients classified by degree of CA3 neuronal loss. This finding supports prior research showing subfield specificity in some memory processes.

Adolescent↗
PubMed1991

Dominant-side intracarotid amobarbital spares comprehension of word meaning.

Abolition of speech production after intracarotid amobarbital injection is generally considered evidence for language laterality. However, complex auditory comprehension may be preserved after injection of the dominant (left) side. The possibility that this sparing may be due to the intracarotid amobarbital injection not adequately deactivating some of the areas responsible for speech comprehension in the posterior part of the hemisphere was tested with a task known to be critically dependent on the left posterotemporal-inferoparietal region, one assessing visuo-verbal semantic relatedness. Even when the intracarotid injection of the left side produced marked deficits of speech production, comprehension of semantic relations was still intact in eight of 15 patients. Ten of these 15 patients also received right carotid injections, none of which affected comprehension of semantic relatedness. These data indicate that the intracarotid amobarbital injection cannot always specify the laterality of all language functions, an important concern when considering surgical procedures in the dominant posterotemporal-inferoparietal region.

Adolescent↗
PubMed1997

Dichotic-listening performance and intracarotid injections of amobarbital in children and adolescents. Preoperative and postoperative comparisons.

BACKGROUND: Dichotic listening (DL) to consonant-vowel syllables is frequently used in clinical and experimental studies of brain laterality. However, the paradigm of consonant-vowel syllables has not been thoroughly validated through a comparison with injections of amobarbital sodium (Amytal). OBJECTIVE: To validate the DL test for hemisphere dominance preoperatively vs postoperatively with the results from intracarotid injections of amobarbital (i.e., the Wada test) in epileptic children and adolescents. DESIGN AND MAIN OUTCOME MEASURES: Patients were tested with DL preoperatively and at 6-month follow-up. Correct reports in the DL tests were entered in a stepwise discriminant analysis for calculation of correct classification of hemisphere dominance with the results from the injections of amobarbital as the grouping variable. Correct reports from the right and left ears on the consonant-vowel DL test were compared preoperatively and postoperatively, separated for the subjects with regard to language dominance in the left and right hemispheres. SETTING: The Department of Pediatrics, Ostra Hospital, University of Göteborg, Göteborg, Sweden. PATIENTS: Thirteen children and adolescents between the ages of 10 and 19 years, who were surgically treated for resistant epilepsy, were included in the study. The operated area corresponded with morphological changes and functional dysfunctions according to findings from computed tomography, magnetic resonance imaging, single photon emission computed tomography, and electroencephalography. RESULTS: The results of the Wada tests revealed that 10 subjects had left hemisphere language dominance, with 3 subjects having right hemisphere language dominance. All 3 subjects with right hemisphere language dominance showed a left ear advantage on the DL test preoperatively and postoperatively, with 8 and 7 of the 10 subjects with left hemisphere dominance showing a right ear advantage, preoperatively and postoperatively, respectively. However, according to discriminant analysis, knowledge of the DL performance led to a correct classification according to the Wada test results in 12 (92%) of the 13 subjects. CONCLUSIONS: A quantitative classification procedure like discriminant analysis may be more sensitive when predicting hemisphere speech dominance from DL data than a qualitative procedure based on the ear advantage dichotomy. The ear advantage dichotomy may actually introduce arbitrary left-right categories that do not correspond to the actual clustering of the data.

Adolescent↗
PubMed2000

Determination of amobarbital and secobarbital in plasma samples using micellar liquid chromatography.

A new liquid chromatographic procedure for the determination of amobarbital and secobarbital in plasma samples is proposed. The method uses a Spherisorb octadecylsilane ODS-2 C(18) analytical column, a guard column of similar characteristics and 0.04 M CTAB solution buffered at pH 7.5 containing 3% 1-propanol as micellar mobile phase. The UV detection was carried out at 250 nm. Butabarbital was used as internal standard. Plasma samples preparation only required adequate dilution with the mobile phase before injection into the chromatographic system. The limits of detection were 0.2 and 0.4 mg/L for amobarbital and secobarbital, respectively. The proposed method allows the determination of amobarbital and secobarbital in plasma at therapeutic levels.

Amobarbital↗
PubMed1988

Brain injury, handedness, and speech lateralization in a series of amobarbital studies.

Data on handedness and speech lateralization in patients selected for amobarbital studies have frequently been extrapolated to the normal population, despite the high frequency of brain injuries which might alter lateralization in these patients. To achieve a better definition of the relationships between brain injury, handedness, and speech lateralization, we reviewed the records of 237 consecutive patients who underwent amobarbital testing. Brain injuries sufficient to cause right hemiparesis were strongly associated with left handedness and atypical (right hemisphere or bilateral) speech representation. Among nonhemiparetic patients, abnormal extratemporal radiological findings were associated with an increased incidence of left handedness and atypical speech lateralization. It was not possible to demonstrate any alteration in handedness or speech representation resulting from abnormalities restricted to the temporal lobes, although such alterations could not be excluded. Handedness and speech lateralization established using amobarbital studies in neurosurgical patients may not be representative of the normal population.

Adolescent↗
PubMed1976

Genetic study of amobarbital elimination based on its kinetics in twins.

Following the intravenous administration of 125 mg amobarbital sodium in 7 pairs of dizygotic and 7 pairs of monozygotic twins, the time-course of plasma concentrations was observed. The number of detectable compartments varied from subject to subject but was consistently 1 or 2 or 3 within a given individual. The terminal slope of the semilogarithmic concentration-time plot (corresponding to biologic half-life of 22.8 hr) did not represent the elimination rate constant even in persons with apparently single-compartmental characteristics. The redistribution of amobarbital was rapid in comparison with its elimination. The rate of the latter (characterized by kel = 0.051 hr-1, plasma clearance = 37.7 ml/min) could be closely identified with the rate of metabolism. The twin data showed that genetic control was exerted on kinetic parameters characterizing the rate of amobarbital elimination and, therfore, the rate of its metabolism. Correlation analysis suggested that this control was independent of size factors, which were themselves substantially heritable. The genetic analysis of twin data included, in addition to intracelass correlations and Holzinger's H factors, newly developed lower (and upper) bounds of the broad-sense heritability. In pharmacogenetic studies, assessment of model-independent kinetic parameters, such as plasma clearance with or without adjustment for body weight, is recommended.

Administration, Oral↗
PubMed1978

Effect of human growth hormone on amobarbital metabolism in children.

Drug metabolism changes during the course of growth and development. Hormones mediate somatic growth and may mediate other developmental changes. To determine the effect of human growth hormone (hGH) on human drug metabolism, 6 hGH-deficient children were given single oral doses of amobarbital before and 6 wk after beginning hGH replacement therapy. Amobarbital was selected as a marker of hepatic microsomal oxidation. Half-lives rose from 13.89 +/- 2.78 hr to 22.75 +/- 3.97 hr, volume of distribution was unchanged, and clearance fell from 62.2 +/- 15.2 ml/kg/hr to 31.2 +/- 11.4 ml/kg/hr. Results indicate that hGH slows the metabolism of amobarbital, probably through an effect on the hepatic microsomal drug-oxidizing system.

Adolescent↗
PubMed1978

Distinctive patterns of amobarbital metabolites.

This paper establishes that the relative proportion of amobarbital metabolites in urine is highly variable from person to person and that observations of plasma half-life give no indication of this variability, but it shows that a valid estimate of a given person's metabolite pattern can be obtained by studying a single urine specimen in the postdistributive phase. The two metabolites which were measured in urine accounted on the average of 9 subjects for 80% +/- 3% of the dose with a range from 66% to 94%. The two metabolites were the well known 3'-hydroxyamobarbital (COH) as a product of side chain hydroxylation and N-beta-D-glucopyranosyl amobarbital (N-glu), a glucose conjugate which at some earlier time had been mistaken for an N-hydroxylation product. Among 129 volunteer subjects, the metabolite ratio N-glu/COH showed a median value of about 0.5 with a range from 0 to 2.8. A virtual absence of N-glu was observed in one of the 129 subjects and confirmed by a second administration of amobarbital 3 mo later. Of the 14 subjects with predominant N-glu excretion 4 were of Chinese origin, while there were 6 Chinese among the 115 other subjects (p less than 0.02).

Amobarbital↗
PubMed1979

A method for studying drug metabolism in populations: racial differences in amobarbital metabolism.

The two main metabolites of amobarbital excreted in urine are 3'-hydroxyamobarbital (C-OH) and 1-(beta-D-glucopyranosyl) amobarbital (N-glu). When testing the metabolite ratio in small single samples of urine, it was found that the urine in a Caucasian population contained about one-third glucose conjugation and two-thirds hydroxylation product, while an Oriental population excreted both metabolites in equal proportion. Attempts to learn the causes for the different metabolite ratios led to an investigation of metabolite concentrations in urine. The sums of the average urinary concentration of C-OH was greater in Caucasians than in Orientals, no matter how the data were expressed; the reverse was true for the N-glu metabolite. C-OH data was scattered more widely among Orientals than Caucasians; this might indicate bimodality of the distribution curves. There also was a trend toward more N-glu metabolite in urine of females than of males. Measuring the metabolite/creatinine ratios narrowed the distribution range of the data, particularly after correction for sex difference in creatinine, but population differences were not changed. Expected relationships between metabolite content of urine, sampling times, and plasma half-life (t1/2) were established by calculation. A Caucasian female with no capacity for N-glucosidation was found during the first part of this population survey. An Oriental male with only trace capacity for amobarbital hydroxylation was found in the second part.

Amobarbital↗
PubMed1997

Serial recovery of language during the intracarotid amobarbital procedure.

There is considerable variability among epilepsy centers in the methods and interpretations of the intracarotid amobarbital procedure. Prominent among these differences is the determination of language representation and assessment of language functions. Some centers rely on speech arrest following amobarbital injection as a marker for language representation, whereas other centers examine verbal output for the presence of aphasic errors. The present study assessed the pattern of language recovery following amobarbital injection in epilepsy patients who were candidates for temporal lobectomy. Language recovery from dominant hemisphere injection (left or right) followed a stereotypical progression, with 71.8% of patients showing return of vocalization followed by return of naming and comprehension. Repetition deficits with paraphasic errors persisted the longest (mean = 12'30"), with a conduction aphasia persisting after the acute global aphasia resolved. Although two patients interpreted as left hemisphere language dominant were mute following right hemisphere injection, all language functions were intact immediately upon resumption of vocalization and they showed no other signs of aphasia such as paraphasias or anomia. Possible explanations for serial language recovery and persistent conduction aphasia are discussed. These findings have significant implications for the determination of cerebral language dominance.

Adult↗