Search PubMed⌕ Search

Biomedical subjects

H T Chugani

Publications and source records attributed to H T Chugani.

At least 55 records · Page 3Linked to original sources
PubMed1999

Basic mechanisms of childhood epilepsies: studies with positron emission tomography.

Although functional imaging with positron emission tomography (PET) and single-photon emission computed tomography are useful in the clinical evaluation of intractable epilepsy, these techniques have not been widely applied to understanding the basic mechanisms of the epilepsies. Among patients with infantile spasms, PET studies with 2-deoxy-2[18F]fluoro-D-glucose (FDG) suggest that the spasms are the result of secondary generalization from cortical foci and that maturational factors result in the recruitment of basal ganglia and brainstem serotonin mechanisms that lead to secondary generalization and the unique semiology of the spasms. Attempts to develop an animal model of infantile spasms have not been successful. Glucose utilization studies in the Lennox-Gastaut syndrome also indicate cortical lesions and further suggest that the electroencephalographic pattern of 1 to 2.5 Hz spike-wave activity (slow spike-wave pattern) is an interictal phenomenon. There is a remarkable consistency between 14C-2-deoxyglucose autoradiographic findings and PET observations of glucose utilization performed for patients in the ictal, interictal, and postictal states. Although three patterns of ictal glucose hypermetabolism have been described, hypermetabolism also can be seen in the postictal and interictal clinical states and in various animal models. Preliminary studies of benzodiazepine receptor binding with PET have found that the cortical epileptic region of decreased binding is smaller than the region of hypometabolism on glucose utilization studies, but detailed electrophysiologic comparisons have not been made. Development of new PET methods for the study of presynaptic and postsynaptic neurotransmitter functions will offer unique opportunities in the study of epileptic mechanisms.

Anticonvulsants↗
PubMed1999

[11C]flumazenil PET: activity images versus parametric images for the detection of neocortical epileptic foci.

UNLABELLED: [11C]flumazenil (FMZ) imaged with PET allows the computation of parametric images of both tracer influx (K1) and volume of distribution (VD). The VD images, which allow visualization of a quantitative measure of benzodiazepine receptor binding, are reported to have high sensitivity and specificity for the delineation of epileptic foci. However, the clinical feasibility of this method is compromised by the necessity of arterial blood sampling. We therefore compared the performance of parametric VD images against simple FMZ activity images for the detection of neocortical epileptic foci. METHODS: FMZ PET data from 7 children with extratemporal lobe epilepsy (mean age [+/- SD] 9.8+/-4.4 y) and 6 healthy adult volunteers (mean age [+/- SD] 40+/-8 y) were analyzed using a semiautomated analysis algorithm. FMZ activity images and parametric VD images were analyzed for asymmetry with cutoff thresholds of 8%, 10% and 12%. RESULTS: The time frame between 10 and 20 min after injection represented overall the best agreement between FMZ activity and VD images independent of the threshold. The normal asymmetry in VD images was determined as 6.4%+/-1.4% and was significantly higher in the FMZ activity images (7.6%+/-1.4%, P = 0.001). Increasing the cutoff threshold resulted in a significant decrease in the area defined as abnormal in both the VD and the FMZ activity images. Abnormalities defined in FMZ activity images identified additional brain regions as abnormal at the 8% threshold, but there was good agreement with VD images at the 10% asymmetry threshold. In those regions where abnormalities in VD and FMZ activity images were not matched, the asymmetry indices obtained from K1 images were significantly higher than those derived from the VD images (P = 0.01). CONCLUSION: Differences between VD and activity images above the 8% threshold are mainly due to K1. Abnormalities defined in FMZ activity images using a threshold of 10% agree well with those obtained from parametric VD images, indicating that activity images obtained from the time frame of 10-20 min are essentially equivalent to VD images with regard to detection of regions of abnormality for seizure focus localization.

Adult↗
PubMed1998

Task-related activations in heterotopic brain malformations: a PET study.

Positron emission tomography (PET) studies have shown normal or elevated levels of glucose metabolism in neuronal heterotopia, raising the issue of potential participation of heterotopic neurons in cognitive processing. We studied three patients with heterotopic malformations, using [(15)O]water PET and experimental conditions selected according to the location of the malformations. Task performance was associated with blood flow increases of > 17% within the heterotopia in each patient. In two, these occurred in left frontal heterotopia during sentence generation. In the third patient, activations for facial and visuospatial discrimination and picture naming were found in a right posterior heterotopion. Our findings may reflect participation of heterotopia in cognitive function and suggest that heterotopic neurons synapse with neurons in other brain regions.

Adolescent↗
PubMed1998

Differences in D2 dopamine receptor binding in the neostriatum between cats hemidecorticated neonatally or in adulthood.

In order to study differences in response to neocortical injury sustained at different ages at the neurotransmitter level, we examined the density in D2 dopamine receptors in the neostriatum of cats hemidecorticated neonatally (N = 4) or in adulthood (N = 4), as well as in intact brains (N = 6). Receptor densities were measured using quantitative autoradiography and [3H]-spiperone binding in 12 regions of the neostriatum and nucleus accumbens septi. We found that the anterior lateral caudate nucleus on both sides of the brain contained a higher D2 receptor density in neonatal-lesioned as compared to adult-lesioned brains. Ipsilateral to the lesion, the increase was 101% (P < 0.05) and contralaterally it amounted to 77% (P < 0.05). Moreover, this region of the ipsilateral caudate nucleus of neonatal-lesioned cats tended to be more densely labeled than that of intact brain by 58% (P < 0.1). D2 receptor densities in adult-lesioned cats did not differ from that of intact controls. Comparison of these data with those of a former morphological study using the same animals suggested that this bilateral elevation of D2 receptor density in neonatally lesioned brains represents a higher mean density of binding sites per neuron. The elevation in the neonatal-lesioned cats might be a response of the striatum to neuroplastic changes in the striatal neuropil, including the corticostriatal afferents, since such changes are different in neonatal- as compared to adult-lesioned cats.

Aging↗
PubMed1998

Impairment of dentato-thalamo-cortical pathway in autistic men: language activation data from positron emission tomography.

Recent evidence suggests disturbances of serotonin synthesis affecting the dentato-thalamo-cortical pathway in autistic boys. We studied possible effects of such disturbances on brain activations for language in autistic adults. Four autistic and five normal men were studied while listening to, repeating, and generating sentences, using [15(O)]-water positron emission tomography (PET). Activation in the right dentate nucleus and in the left frontal area 46 was reduced during verbal auditory and expressive language and enhanced during motor speech functions in the autism as compared to the control group. The thalamus showed group differences concordant with area 46 for expressive language. The results may indicate atypical functional specialization of the dentato-thalamo-cortical pathway and are compatible with a model of region-specific biochemical disturbances in the developing autistic brain.

Adolescent↗
PubMed1998

Differential patterns of language and motor reorganization following early left hemisphere lesion: a PET study.

OBJECTIVE: There is extensive evidence for post-lesional plasticity in the language and motor domains. We examined possible domain-specific differences in reorganizational patterns, hypothesizing that interhemispheric reorganization would be predominantly homotopic for language, but predominantly nonhomotopic for motor control. DESIGN: Using oxygen 15-water positron emission tomography, regional cerebral blood flow was studied during rest, listening to sentences, repetition of sentences, and finger tapping of the right hand. Task-specific primary, secondary, and tertiary regions of interest were defined according to the degree of regional involvement in language/motor functions as documented in previous studies. Regional activations were compared within and across functional domains. PATIENTS: Nine patients (aged 4-20 years) with unilateral left hemisphere lesion involving both the primary motor and perisylvian language cortices were studied. Two samples of healthy adults were included for additional comparisons. MAIN OUTCOME MEASURE: Hemispheric asymmetry of blood flow changes within regions of interest. RESULTS: As predicted, rightward asymmetry of activations in primary and secondary regions was stronger for language than for movement, but the expected inverse difference for tertiary regions (greater rightward asymmetry of motor activations) was not found. Within-domain comparisons showed that for listening to sentences, rightward asymmetry was strongest in primary and weakest in tertiary regions, whereas the inverse differences were found for movement. CONCLUSION: The findings suggest a greater potential for homotopic interhemispheric reorganization in the language than in the motor domain. Interhemispheric motor reorganization was generally limited.

Adolescent↗
PubMed1998

Objective method for localization of cortical asymmetries using positron emission tomography to aid surgical resection of epileptic foci.

We designed a semiautomated method for the objective detection of abnormal regions of tracer accumulation in the brain. The purpose of the present study was to examine the diagnostic performance of this method by applying it to patients with clinically intractable epilepsy of unilateral origin; they underwent [F-18] deoxyglucose positron emission tomography (PET) prior to surgical resection of epileptic foci. A semiautomated method for assessment of asymmetries in the brain cortex was developed that compares activity concentrations in homotopic cortical areas. When these differences exceeded a predefined threshold, the areas with lower activity were marked and 3-dimensional surface rendered images were created to guide placement of intracranial electrodes (ECoG) followed by surgical resection. The normal amount of asymmetry between small (0.5-0.7 cm2) homotopic cortical regions was determined as 5.9 +/- 4.0% (mean +/- SD). The false-positive fraction was determined for cutoff thresholds of 1 SD (10%), 1.5 SD (12%), and 2 SD (15%) outside the mean and was found to be 89, 44, and 0%, respectively. The obtained sensitivity-specificity pairs for correct localization of epileptogenic lobes based on the ECoG results were best for the 15% threshold (80/94%, accuracy 0.90). This objective PET method allows the accurate determination of cortical asymmetries, and it proved to be highly efficient in guiding epilepsy surgery.

Adolescent↗
PubMed1998

Human brain serotonin synthesis capacity measured in vivo with alpha-[C-11]methyl-L-tryptophan.

Local cerebral serotonin synthesis capacity was measured with alpha-[C-11]methyl-L-tryptophan ([C-11]AMT) in normal adult human brain (n = 10; five males, five females; age range, 18-38 years, mean 28.3 years) by using positron emission tomography (PET). [C-11]AMT is an analog of tryptophan, the precursor for serotonin synthesis, and is converted to alpha-[C-11]methyl-serotonin ([C-11]AM-5HT), which is trapped in serotonergic neurons because [C-11]AM-5HT is not degraded by monoamine oxidase. Kinetic analysis of [C-11] activity in brain after injection of [C-11]AMT confirmed the presence of a compartment with unidirectional uptake that represented approximately 40% of the activity in the brain at 50 min after tracer administration. The undirectional rate constant K, which represents the uptake of [C-11]AMT from the plasma to brain tissue followed by the synthesis and physiologic trapping of [C-11]AM-5HT, was calculated using the Patlak graphic approach on a pixel-by-pixel basis, thus creating parametric images. The rank order of K values for different brain regions corresponded well to the regional concentrations of serotonin in human brain (P < .0001). High serotonin synthesis capacity values were measured in putamen, caudate, thalamus, and hippocampus. Among cortical regions, the highest values were measured in the rectal gyrus of the inferior frontal lobe, followed by transverse temporal gyrus; anterior and posterior cingulate gyrus; middle, superior, and inferior temporal gyri; parietal cortex; occipital cortex, in descending order. Values in women were 10-20% higher (P < .05, MANOVA) throughout the brain than those measured in men. Differences in the serotonin synthesis capacity between men and women measured in this study may reflect gender differences of importance to both normal and pathologic behavior. This study demonstrates the suitability of [C-11]AMT as a tracer for PET scanning of serotonin synthesis capacity in human brain and provides normal adult values for future comparison with patient groups.

Adolescent↗
PubMed1998

Imaging epileptogenic tubers in children with tuberous sclerosis complex using alpha-[11C]methyl-L-tryptophan positron emission tomography.

Several reports have indicated that cortical resection is effective in alleviating intractable epilepsy in children with tuberous sclerosis complex (TSC). Because of the multitude of cortical lesions, however, identifying the epileptogenic tuber(s) is difficult and often requires invasive intracranial electroencephalographic (EEG) monitoring. As increased concentrations of serotonin and serotonin-immunoreactive processes have been reported in resected human epileptic cortex, we used alpha-[11C]methyl-L-tryptophan ([11C]AMT) positron emission tomography (PET) to test the hypothesis that serotonin synthesis is increased interictally in epileptogenic tubers in patients with TSC. Nine children with TSC and epilepsy, aged 1 to 9 years (mean, 4 years 1 month), were studied. All children underwent scalp video-EEG monitoring, PET scans of glucose metabolism and serotonin synthesis, and EEG monitoring during both PET studies. [11C]AMT scans were coregistered with magnetic resonance imaging and with glucose metabolism scans. Whereas glucose metabolism PET showed multifocal cortical hypometabolism corresponding to the locations of tubers in all 9 children, [11C]AMT uptake was increased in one tuber (n=3), two tubers (n=3), three tubers (n=1), and four tubers (n=1) in 8 of the 9 children. All other tubers showed decreased [11C]AMT uptake. Ictal EEG data available in 8 children showed seizure onset corresponding to foci of increased [11C]AMT uptake in 4 children (including 2 with intracranial EEG recordings). In 2 children, ictal EEG was nonlocalizing, and in 1 child there was discordance between the region of increased [11C]AMT uptake and the region of ictal onset on EEG. The only child whose [11C]AMT scan showed no regions of increased uptake had a left frontal seizure focus on EEG; however, at the time of his [11C]AMT PET scan, his seizures had come under control. [11C]AMT PET may be a powerful tool in differentiating between epileptogenic and nonepileptogenic tubers in patients with TSC.

Brain↗
PubMed1998

Brain organization of language after early unilateral lesion: a PET study.

Neuropsychological studies suggest that good long-term language outcome is possible following extensive early left-hemisphere damage. We explored the brain organization for language in children with early unilateral lesion, using [15O]-water PET. In 12 patients with left lesion (LL) and 9 patients with right lesion (RL), cerebral blood flow changes during listening to sentences and repetition were studied. A rightward shift of language activations in the LL group was found in perisylvian areas and multiple other, mostly temporo-parietal, regions. The hypothesis of intrahemispheric reorganization in the LL group found only limited support. The number of activated regions was overall greater in the RL group. Unexpected findings included a stronger subcortical and cerebellar language involvement in the RL group. We suggest that (a) early left lesion is associated with enhanced language participation of the right hemisphere in and beyond the classical language areas, and (b) postlesional effects are in part additive (recruitment of noncanonical areas), in part subtractive (functional depression in areas normally involved in language).

Adolescent↗
PubMed1998

Motor organization after early middle cerebral artery stroke: a PET study.

The brain organization for movement in a 20-year-old man with a history of intrauterine or perinatal right middle cerebral artery stroke was studied. [(15)O]-water positron emission tomography demonstrated a normal pattern of activation during finger movement in the right hand. Movement of the hemiparetic left hand was associated with activation in the supplementary motor area bilaterally and in the left premotor cortex. Blood flow increase was observed in the right temporal lobe adjacent to an extensive area of encephalomalacia, suggesting atypical motor function in the temporal lobe.

Adult↗
PubMed1998

Brain organization of motor and language functions following hemispherectomy: a [(15)O]-water positron emission tomography study.

The capacity of the developing brain for compensatory reorganization after early hemispherectomy has been previously shown in neurobehavioral studies, above all with regard to language recovery. The present study examines the organization of motor and language areas by means of [(15)O]-water positron emission tomography (PET) in a 6-year-old boy who underwent right functional hemispherectomy at age 3 years. The results suggest that compensatory allocation for movement of the weak hand primarily involves the premotor, inferior frontal, and insular cortices, and the supplementary motor area in the retained hemisphere, as well as the bilateral cerebellum. Receptive language and prosodic functions primarily activated the left perisylvian cortices. However, language and motor activations were also seen in cortical and subcortical remains on the hemispherectomized side suggesting incomplete disconnection by functional hemispherectomy.

Brain↗
PubMed1998

Alternating hemiplegia of childhood: insights into its pathophysiology.

Alternating hemiplegia of childhood is a rare disorder characterized by episodic paroxysmal attacks of neurologic dysfunction and has historically been thought to represent a migraine equivalent, an unusual form of epilepsy, or a movement disorder. Medical treatment with a variety of anticonvulsants and migraine agents is largely unsuccessful, and progressive mental deterioration is universally expected. Despite extensive laboratory studies, the pathophysiologic basis of this condition has thus far eluded identification. Recently, an international workshop was held to generate testable hypotheses regarding the pathophysiology of alternating hemiplegia of childhood. This paper summarizes the major proceedings of that workshop, and hopes to stimulate further interest in elucidating the molecular and cellular mechanisms underlying this unusual disorder.

Brain↗
PubMed1998

Proton magnetic resonance spectroscopy in children with Sturge-Weber syndrome.

Quantitative proton magnetic resonance spectroscopy was performed on six children with Sturge-Weber syndrome following gadolinium enhanced magnetic resonance imaging (MRI). MRI revealed only unilateral involvement in all cases. The mean concentration (mmol/kg wet weight) of the neuronal marker N-acetyl-aspartate was significantly reduced by 37% in the ipsilateral gadolinium enhanced volume of interest compared to a similarly placed contralateral volume of interest (5.39 +/- 1.70 [SD] vs 8.50 +/- 1.14, P < .005, two-tailed paired Student's t-test). Decreased N-acetyl-aspartate in the ipsilateral volume of interest was observed in all patients studied. No significant differences were found in the concentrations of creatine/phosphocreatine or choline compounds between the ipsilateral and contralateral volumes of interest. These findings give possible new insight into the pathophysiology of this disease and suggest that quantitative proton magnetic resonance spectroscopy may be useful for the early characterization and monitoring of neuronal dysfunction or loss in infants and children with Sturge-Weber syndrome.

Adolescent↗
PubMed1998

Developmental changes of cortical and cerebellar motor control: a clinical positron emission tomography study with children and adults.

Functional neuroimaging data regarding the development of motor organization in normal children and adolescents are virtually unavailable because of ethical concerns. As an alternative approach, we studied child and adult lesion patients, focusing on movement of the hand ipsilateral to the lesion and on brain activations in the contralesional hemisphere. [15O]-water positron emission tomography was performed during rest and sequential finger-thumb tapping in 10 children (aged 6 to 14 years) and 15 adults (aged 18 to 74 years) with unilateral lesion. We expected more distinct activation/deactivation patterns during movement in adults than in children. While there were no group differences in activation of primary and secondary motor cortices, deactivations in nonmotor cortex were significantly more pronounced in adults than in children. This indirectly supports our hypothesis of developmental focalization of cerebral motor control. Activations in the cerebellum and vermis were significantly stronger in the adults than in the children, possibly reflecting normal developmental patterns.

Adolescent↗
PubMed1998

Biological basis of emotions: brain systems and brain development.

Functional neuroimaging techniques such as positron emission tomography have made it possible to investigate brain metabolism noninvasively during development. Studies have revealed a dynamic period of metabolic maturation and neuronal growth corresponding to the processes of synaptic proliferation and pruning of unused pathways. This physiologic plasticity is believed to be the biological basis for a critical period of learning and emotional development.

Adolescent↗