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Biomedical subjects

H T Chugani

Publications and source records attributed to H T Chugani.

At least 91 records · Page 5Linked to original sources
PubMed1995

Infantile spasms.

The recent intense focus of attention on further characterization and management of infantile spasms is due, in part, to the resistant nature of these seizures and the frequently poor cognitive outcome, even when the seizures are controlled. Technological advances have increased our ability to diagnose specific brain disorders associated with infantile spasms, and have led to new therapeutic approaches. Most infantile spasms previously classified as cryptogenic have now been shown to be associated with various types of brain malformations and can, therefore, be reclassified as symptomatic. Infantile spasms are probably initiated by cortical epileptic discharges which propagate to the brainstem and other subcortical areas. When the epileptogenic cortex is unilateral in an infant with resistant spasms, resective surgery may be considered. For most infants, however, surgery is not a viable option, and the search for the most effective and least toxic anticonvulsant continues.

Anticonvulsants↗
PubMed1995

Asymmetric and asynchronous infantile spasms.

Infantile spasms most commonly show symmetric behavioral and electroencephalogram (EEG) manifestations. Asymmetric and asynchronous behavioral spasms occur occasionally, but their relationship to ictal EEG and to other localizing studies has not received much attention. We reviewed 75 consecutive video-EEG recordings, done at UCLA from 1982 to 1992, that contained infantile spasms; 8,680 spasms were scored for behavioral and EEG asymmetry and asynchrony. Of the recorded spasms, 25% were asymmetric and 7% were asynchronous. Most asymmetric of asynchronous spasms were associated with an ictal EEG discharge that was contralateral to the behaviorally more involved side. In 12 of the 60 patients (20%), more than half of the recorded spasms were asymmetric of asynchronous. Baseline EEG, magnetic resonance imaging, positron emission tomography, and neurological examination revealed structural and functional brain abnormalities that involved the contralateral central region significantly more often in the children with > 50% spasm asymmetry or asynchrony than in the other children. Partial seizures with lateralized motor behavior also occurred frequently in these children. The findings suggest that asymmetric and asynchronous spasms are generated by a cortical epileptogenic region that involves the primary sensorimotor area. The combination of asymmetric and asynchronous infantile spasms, partial motor seizures involving the same side of the body, and pathology in the contralateral central region may represent a unique subset of symptomatic localization-related infantile epilepsy.

Cerebral Cortex↗
PubMed1995

Landau-Kleffner syndrome with continuous spikes and waves during slow-wave sleep.

The Landau-Kleffner syndrome is sometimes associated with continuous spike-waves during slow-wave sleep. The clinical significance of this association is unclear. In order to investigate differences in glucose metabolic patterns between awake and sleep states in two children with Landau-Kleffner syndrome and continuous spike-waves during slow-wave sleep, fluorodeoxyglucose positron-emission tomographic (PET) studies were performed in each state. In the first patient, the awake interictal PET study revealed moderate hypometabolism in the thalamus and frontal and temporal cortex and mild hypometabolism in the parietal and anterior cingulate cortex bilaterally. Occipital cortex was severely hypometabolic bilaterally. In a repeat PET study performed during sleep in which continuous spike-waves during slow-wave sleep were present, the only difference noted compared to the awake study was a marked bilateral increase in temporal cortex metabolism. The awake interictal PET in the second child was normal, except for mildly increased relative glucose metabolism in the left inferior temporal cortex. The sleep PET study with continuous spike-waves during slow-wave sleep in this child showed hypermetabolism in both temporal lobes; however, this was more pronounced, with a wider distribution in the left temporal cortex. In normal subjects, PET studies performed during awake and sleep states have not revealed such differences. Whether the temporal lobes are involved in the generation of continuous spike-waves during slow-wave sleep remains to be confirmed in a larger group of patients. The first child was treated surgically with multiple subpial transection, following which continuous spike-waves during slow-wave sleep disappeared and language function improved.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1995

Positron emission tomography in pediatric epilepsy.

PET is an additional tool in the armamentarium to provide improved care to children and infants with epilepsy. It provides important lateralizing information noninvasively, thus avoiding the need for depth or subdural electrodes in most instances. It can be invaluable when CT and MR imaging do not show a structural lesion. When it corresponds to an EEG focus of epileptogenicity, intraoperative electrocorticography may be used to delineate further the extent of surgical resection, often with impressive reduction in the seizure frequency postoperatively. As PET technology continues to improve, the clinical role of PET in the future will undoubtedly continue to grow.

Adolescent↗
PubMed1994

Metabolic recovery in caudate nucleus of children following cerebral hemispherectomy.

In 3 children who had undergone cerebral hemispherectomy (hemidecortication) between the ages of 1 year 5 months and 4 years for the alleviation of intractable epilepsy, cerebral glucose utilization was studied serially with positron emission tomography. Three to 7 months after hemispherectomy, glucose utilization in the caudate nuclei on the side of hemispherectomy had decreased to below preoperative values, presumably due to total deprivation of ipsilateral cortical input. One to 2.5 years after surgery, complete restoration of glucose metabolic activity to preoperative levels was seen in 2 patients and partial recovery was seen in 1 patient. These alterations of cerebral glucose utilization are believed to reflect microscopic anatomical reorganizational changes (e.g., collateral sprouting) that have been documented following similar lesions in several animal models. Our findings suggest that positron emission tomography may provide a sensitive measure of developmental brain plasticity in vivo.

Brain↗
PubMed1994

Copper deficiency secondary to a copper transport defect: a new copper metabolic disturbance.

We describe a 21-year-old man who developed copper deficiency manifested as a demyelinating neuropathy, chronic intestinal pseudo-obstruction, osteoporosis, testicular failure, retinal degeneration, and cardiomyopathy with a tortuous aorta. His serum copper was low and did not increase despite administration of large doses of intravenous copper sulfate. The ceruloplasmin level as measured by an antibody technique was normal, yet ceruloplasmin (Cp) oxidase activity was very low. The Cp amino acid sequence was normal. This suggests that the copper deficiency was caused by a defect in hepatic processing of copper for incorporation into Cp.

Adult↗
PubMed1994

Cerebral hemidecortication alters expression of transforming growth factor alpha mRNA in the neostriatum of developing rats.

Transforming growth factor alpha (TGF alpha) is a mitogenic polypeptide which acts at the epidermal growth factor receptor to produce its biologic effects. Recent studies have demonstrated that TGF alpha may act as a neurotrophic factor. Cerebral hemispherectomy (hemidecortication) is performed on some children with intractable epilepsy. Prior studies have demonstrated improved functional recovery in both children and animals when the surgery is performed at a very early age. In order to test whether TGF alpha may be involved in the functional recovery of the neostriatum following cerebral hemidecortication, we performed in situ hybridization for TGF alpha mRNA on brains of rats which underwent hemispherectomy at postnatal day (P) 6 or P12 or in adulthood, and sacrificed one, 7, or 30 days following surgery. Normal striatal expression in control animals was very high at P6 and then decreased throughout development. In animals undergoing lesion at earlier ages (P6 and P12), TGF alpha mRNA expression was first depressed in the ipsilateral neostriatum one day after surgery and then elevated to supranormal levels 7 and 30 days after surgery. Maximal decreases (40% below contralateral neostriatum) were seen in animals lesioned at P12 and sacrificed the next day. Maximal elevations (60% greater than opposite neostriatum) were seen in animals operated on at P6 and sacrificed 30 days post surgery. Expression in the adult animal was only mildly affected, with a 20% increase found in the ipsilateral caudate 7 days after the lesion, but no significant changes after one or 30 days survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Corpus callosum agenesis and epilepsy: PET findings.

Positron emission tomography (PET) with 2-deoxy-2[18F]fluoro-D-glucose (FDG) was used to study 9 children who demonstrated complete or partial agenesis of the corpus callosum (ACC) on magnetic resonance imaging (MRI). Of the 7 patients with epilepsy, FDG-PET clearly localized areas of cortical metabolic abnormality in 6 patients; in 5 of these, localization of the metabolic abnormalities on PET corresponded to electroencephalographic localization of epileptogenicity. MRI documented focal cortical abnormalities in only 2 of the 7 children with epilepsy. In 1 patient, the abnormality observed on MRI was confined to a frontal lobe, whereas the FDG-PET study revealed hypometabolism of the entire hemisphere. One patient with infantile spasms exhibited bilateral multifocal epileptiform discharges on electroencephalography, whereas both the PET and MRI revealed only left hemispheral cortical abnormalities. Another patient with infantile spasms had prominent brainstem glucose metabolic activity on FDG-PET in the absence of any MRI or PET cortical abnormality. Two children underwent surgery because of refractory seizures; the resected cortical tissue in both patients consisted of cortical microdysgenesis. Seizure control improved significantly in both patients. FDG-PET studies in the 2 highest functioning patients (i.e., only minor learning disabilities and no epilepsy) did not reveal any focal cortical hypometabolism; therefore, there appears to be an association between the presence of focal metabolic abnormalities on PET and the presence of seizures in ACC patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Agenesis of Corpus Callosum↗
PubMed1994

Chronic pretreatment with naloxone modifies benzodiazepine receptor binding in amygdaloid kindled rats.

Male Sprague-Dawley rats received either naloxone (75 micrograms/h) or saline (0.5 microliter/h) s.c. for 14 days delivered with osmotic minipumps. Two days after termination of either treatment, daily amygdala kindling stimulation was applied until the animals experienced stage V kindled seizures. Benzodiazepine (BDZ) binding sites were labeled with [3H]flunitrazepam (2 nM), and changes in specific brain areas were determined by in vitro quantitative autoradiography. Twenty-four hours after the last electrical stimulation, the saline pretreated fully kindled rats showed enhanced BDZ receptor binding in dentate gyrus, and decreased binding in cingulate cortex ipsilateral to the stimulation compared to saline controls. Twenty-eight days after the last stage V kindled seizure, the significant alterations were no longer evident. In agreement with a previous study, we found that naloxone pretreated amygdala kindled rats showed stage V kindled seizures followed by intervals of 3-5 days in which the same electrical stimulation failed to induce any behavioral and EEG alterations. In comparison with the saline pretreated kindled and saline control groups, the naloxone pretreated kindled rats had significantly higher BDZ binding in different cortical areas, amygdala complex, hippocampus, substantia nigra and periaqueductal gray, 24 h after the last electrical stimulation. The present study indicates that previous chronic exposure to naloxone increases BDZ receptor binding in kindled rats, and suggests that this effect may be associated with the enhanced seizure suppression observed in these animals.

Amygdala↗
PubMed1994

Spielmeyer-Vogt (Batten, Spielmeyer-Sjögren) disease. Distinctive patterns of cerebral glucose utilization.

We have studied seven patients with Spielmeyer-Vogt disease (SV), aged 11-29 years, using PET and 2-deoxy-2[18F]fluoro-D-glucose. Five patients showed a distinctive age-related progression with decreased metabolic activity starting in the calcarine area and spreading rostrally to the entire cortex, leaving normal uptake only in the basal ganglia and brainstem of the oldest patients. Calcarine hypometabolism was mild in the youngest patient. All patients, including the youngest when the study was repeated 2 years later, had significantly decreased calcarine metabolic activity (P = 0.002). Two patients had PET patterns markedly different from the five others, with significantly decreased metabolic activity in most brain areas. Both patients may represent a new SV variant. An adult pathological control with congenital amaurosis showed normal cerebral metabolic activity in all areas. Two patients had older sisters, one now deceased, the other not available for study, who presented a rapid regression associated with epilepsy. Phenytoin and carbamazepine probably caused increased seizure activity and faster regression. The younger siblings treated with phenobarbital monotherapy had few seizures and maintained motor functions 5-8 years longer compared with their respective sisters. While the clinical course made obvious that some areas, such as the macula, are damaged before others, the progression from the calcarine area to the more anterior regions (but sparing the basal ganglia) provides unexpected insights into selective vulnerability of neurons that will allow a more precise way of monitoring individual patients.

Adolescent↗
PubMed1994

The role of PET in childhood epilepsy.

Functional brain imaging with positron emission tomography (PET) has led to significant advances in the diagnosis and management of various forms of childhood epilepsy. Interictal PET in temporal lobe epilepsy typically shows decreased glucose utilization (hypometabolism) in one or both temporal lobes. Children with early-onset refractory extratemporal lobe epilepsy who do not manifest structural abnormalities on magnetic resonance imaging often show single or multiple cortical foci of hypometabolism indicating underlying microdysgenesis that corresponds to the area of epileptogenicity. The findings of focal cortical metabolic lesions and metabolic activation of subcortical structures (brain stem and lenticular nuclei) in patients with infantile spasms have allowed many infants with intractable spasms to be treated surgically with cortical resection, and have altered our concepts regarding the pathophysiology of these seizures. New observations in Lennox-Gastaut syndrome, Sturge-Weber syndrome, tuberous sclerosis, hemimegalencephaly, Landau-Kleffner syndrome, and other pediatric epilepsy syndromes have been documented with PET and have improved our understanding of these disorders. Recent PET studies of several neurotransmitter receptors in adult epileptic patients suggest that this approach holds great promise in the study of childhood epilepsy. The current guidelines indicating which patients with epilepsy should be referred for a PET study are outlined.

Blood Glucose↗
PubMed1993

Benzodiazepine receptor binding following chronic treatment with naloxone, morphine and met-enkephalin in normal rats.

The effects of chronic administration of naloxone, morphine and met-enkephalin on benzodiazepine (BDZ) receptor binding in rat brain were determined 2 and 50 days after treatments were accomplished. Two days after naloxone treatment (75 micrograms/h s.c. for 14 days), enhanced BDZ receptor binding was observed in cingulate, frontal, piriform, entorhinal and sensorimotor cortices; amygdala complex, hippocampus, substantia nigra and central gray. Two days after morphine treatment (20 mg/kg i.p. daily for 6 days), increased BDZ receptor binding was detected in cingulate, frontal, piriform, entorhinal and sensorimotor cortices; amygdala complex, hippocampus and substantia nigra. Two days after met-enkephalin treatment (10 micrograms/h i.c.v. for 6 days) enhanced BDZ receptor binding was shown only in sensorimotor cortex. No significant changes were observed 50 days after the treatments were completed. These data indicate an important interaction between GABAergic and opioid peptide systems.

Animals↗
PubMed1993

Characterization of mu opioid receptor binding during amygdala kindling in rats and effects of chronic naloxone pretreatment: an autoradiographic study.

Using in vitro autoradiography, mu receptor binding in rat brain was characterized at different amygdala kindling stages and in amygdaloid kindled animals pretreated chronically with naloxone. Male Sprague-Dawley rats implanted with bipolar electrodes in the right amygdala received one of the following pretreatments s.c. for 14 days via osmotic minipumps: normal saline solution, 0.5 microliters/h, or naloxone HCl, 75 micrograms/h. Two days after treatments were accomplished animals were stimulated daily. Our data showed different patterns of mu receptor binding during the normal kindling process: during stage II-III, pronounced binding increase was detected in cingulate, temporal and entorhinal cortices, anterior amygdala, caudate putamen, thalamic nuclei, ventrolateral and dorsolateral portions of central gray, substantia nigra pars compacta and pars reticulata. Twenty-four hours after the last stage V kindled seizure, enhanced binding was observed in cingulate and frontoparietal cortices, anterior amygdala, caudate putamen and ventromedial thalamic nucleus. Twenty-eight days after the last stage V kindled seizure, binding augmentation was noticed in cingulate and frontoparietal cortices, whereas decreased binding was detected in amygdala complex, substantia nigra pars reticulata, piriform, perirhinal, parietal, temporal and entorhinal cortices. Mu receptor binding in kindled rats chronically pretreated with naloxone was significantly higher in several structures when compared with control and normal kindled groups. Our data indicate different regional selective patterns of mu receptor binding during amygdala kindling which may depend on epileptogenesis and long-term changes induced by this process. In addition, even higher mu receptor binding results from chronic naloxone administration prior to kindling.

Amygdala↗
PubMed1993

Hemispherectomy for intractable seizures: presurgical cerebral glucose metabolism and post-surgical non-verbal communication.

This study examined the presurgical 2-deoxy-2[18F]-fluoro-D-glucose positron emission tomography (PET) patterns of regional cerebral glucose metabolism in the non-resected hemisphere of 13 children who underwent hemispherectomy for early-onset intractable seizures. These patterns were compared with the rate of change in the children's non-verbal communication scores, measured before and after surgery. Irrespective of the side of surgery, the pre-operative glucose metabolism in the non-resected prefrontal cortex correlated significantly with the postoperative rate of change in the children's ability to focus the attention of an adult on an object or event (joint attention). These preliminary findings suggest that pre-operative PET patterns might be associated with certain aspects of the developmental outcome of children undergoing hemispherectomy.

Brain↗
PubMed1993

Positron emission tomography scanning: applications in newborns.

Positron emission tomography (PET) is an imaging technique that allows local chemical and physiologic functions in various body organs to be measured. Studies of local cerebral glucose metabolism in infants and children using PET have provided important information on human brain functional development and plasticity. In the neonate, PET studies have provided important clues into the pathophysiology of hypoxic-ischemic injury. Patterns of cerebral glucose utilization in various clinical subtypes of cerebral palsy associated with perinatal brain injury are discussed and contrasted to metabolic patterns seen in cerebral palsy without clear etiology. Expanding PET technology provides a new approach that holds great promise in the diagnosis and management of brain disorders affecting the neonate.

Adult↗
PubMed1993

Strategies for diagnosis and treatment of childhood epilepsy.

Recent developments in neuroimaging have advanced our capability to diagnose and perform presurgical evaluations in a large proportion of children without recourse to invasive monitoring techniques. Functional imaging is also providing us with novel insights into the mechanism of certain childhood epileptic syndromes. The role of anatomic (computed tomography, magnetic resonance imaging) and functional (single photon emission computed tomography, positron emission tomography) imaging modalities in the diagnosis and therapeutic decision making in major epileptic syndromes of childhood is reviewed.

Child↗