Biomedical subjects

Prasanna Jayakar

Publications and source records attributed to Prasanna Jayakar.

17 recordsLinked to original sources

PubMed2007

Signature of mitochondria of steroidal hormones-dependent normal and cancer cells: potential molecular targets for cancer therapy.

The cross-talk between the cell nucleus and mitochondria appears to control hormone-induced signaling involved in the apoptosis, proliferation, and differentiation of both normal and malignant cells. Evaluation of the defects in genetics and physiology of human endocrine diseases, such as cancer, may manifest as a result of mitochondrial physiologic and metabolic compensation of genetic defects. Steroidal agents control biogenesis and maintenance of mitochondria through the crosstalk between nuclear and mitochondrial genomes. The regulation of mitochondrial transcription by steroidal hormones, presumably occurring through pathways similar to those that take place in the nucleus, opens a new way to better understand steroid hormone and vitamin action at the cellular level. In addition to the steroid hormone receptors, estrogen generated mitochondrial oxidants together with an estrogen-driven increase in epithelial cell proliferation have been shown to participate in the initiation and promotion of the neoplastic lesions in estrogen-sensitive tissues. Mitochondria generation of ROS appears to transduce signals to the nucleus for the activation of transcription factors involved in the cell cycle progression of estrogen-dependent cancer cells. Therefore, an in-depth analysis of such redox regulatory mechanisms is pertinent to the development of novel drugs and gene therapy strategies for the treatment of steroid hormone-dependent diseases related to mitochondrial disorders including cancer.

Estrogen Receptor Modulators↗

PubMed2006

Orbitofrontal seizures presenting with ictal visual hallucinations and interictal psychosis.

Hallucinations are commonly believed to reflect temporal lobe dysfunction. This report presents the clinical, electroencephalographic, and neuroimaging findings in an 8-year-old male who experienced the acute onset of ictal auditory and visual hallucinations associated with epileptic activation of the right orbitofrontal region. Right frontal lobe surgery resulted in seizure freedom and disappearance of his psychotic symptoms. Histologic tissue examination revealed non-balloon cell Taylor type cortical dysplasia.

Child↗

PubMed2006

Proposed criteria for referral and evaluation of children for epilepsy surgery: recommendations of the Subcommission for Pediatric Epilepsy Surgery.

The Commission on Neurosurgery of the International League Against Epilepsy (ILAE) formed the Pediatric Epilepsy Surgery Subcommission in 1998 and charged it with formulating guidelines and recommendations for epilepsy surgery in childhood. Also endorsed by the Commission on Paediatrics, the following document is the consensus agreement after a meeting of 32 individuals from 12 countries in 2003. The panel agreed that insufficient class 1 evidence exists to recommend practice guidelines at this time. Instead, the panel generated criteria concerning the unique features of pediatric epilepsy patients to justify dedicated resources for specialty pediatric surgical centers, suggested guidelines for physicians for when to refer children with refractory epilepsy, and recommendations on presurgical evaluation and postoperative assessments. The panel also outlined areas of agreement and disagreement on which future research and consensus meetings should focus attention to generate practice guidelines and criteria for pediatric epilepsy surgery centers.

Child↗

PubMed2005

Integrated study of topographical functional maps based on an auditory comprehension paradigm using an eigensystem study and spectrum analysis.

This study integrates a spectral analysis of key frequency bands (Alpha, Beta, Delta, and Theta) with an eigensystem-based study in order to validate brain functional mappings associated with the characterization effects of an Auditory/Comprehension paradigm. This numerical characterization supported by topographic functional maps brings added insight in the involvement of the Wernicke and Broca's brain areas to language comprehension. A thorough examination of EEG recordings through the eigensystem reveals that eigenvectors associated with the largest eigenvalues produce an interesting activity pattern located in the frontal area of the brain directly attributable to those characteristic behaviors found in the Alpha, Beta, Delta, and Theta frequency bands. An evaluation of spectral arrays is performed using topographic maps of the induced brain activities during both listening and answering phases. This evaluation is then augmented with quantifying measures using the eigensystem study while results are validated through integration of EEG activity and eigensystem modalities. Such a representation can provide insightful information on how different patients react during an auditory and response phases, and in the ability to detect the presence of potential neurological disorders by assessing similar/dissimilar behaviors with respects to all former patients already included in the database. The algorithm as developed in this study could be extended in its application to other brain functional mapping tasks given its simple but effective practical mathematical foundation.

Acoustic Stimulation↗

PubMed2005

Near-infrared spectroscopy to define cognitive frontal lobe functions.

Near-infrared spectroscopy (NIRS) monitors changes in the regional cerebral oxygenation (rSO) and has been used to study cerebral physiologic functions in normal states and during epileptic seizures. Yet, the limitations and pitfalls of the technique are not fully understood. The authors evaluated NIRS changes over the frontal lobes during language tasks known to be associated with the integrity of the dominant frontal lobe in 17 normal adults (handedness: 14 right, 3 left). Recording protocol involved a baseline (3 minutes) with the subject relaxed and thinking of a blue sky and a second baseline during voluntary mouth movements mimicking speech. Two standardized neuropsychological word-generation tasks (controlled word-association tests: CFL and Animals) were then administered (4 minutes total) followed again by the two baseline procedures. Mouth movement without verbalization increased rSO values in excess of 2 SD of baseline fluctuations in 70% of the subjects. A t-test comparison of these baseline measurements was statistically significant (P < 0.0001). A general linear model repeated-measures procedure was then used to statistically examine NIRS increments during the cognitive tasks above and beyond the contribution produced by mouth movements during the second baseline. Compared to the second baseline, rSO further increased significantly during the word generation tasks (left frontal F value = 21.4, P < 0.0001; right frontal F value = 15.2, P < 0.001), confirming the utility of the technique. There was no apparent difference related to handedness. These findings corroborate the usefulness of NIRS to demonstrate focal cerebral activation during an "executive" language task. However, interpretation of changes can be confounded by extracerebral factors such as mouth movement, a finding of particular relevance in NIRS clinical applications.

Adult↗

PubMed2005

Surgery for epilepsy due to cortical malformations: ten-year follow-up.

Children with malformations of cortical development represent a significant proportion of pediatric epilepsy surgery candidates. From a cohort of 40 children operated on between 1980 and 1992 with malformation of cortical development, 38 were alive and had data 10 years after surgery. Age at surgery ranged from 6 months to 18 years (mean, 9.6 years). Thirty-six had partial seizures, and two had infantile spasms; 20 were nonlesional. Pathologic diagnoses were cortical dysplasia (n = 31) and developmental tumor (n = 7). At 10-year follow-up, 15 (40%) were seizure free, 10 (26%) had >90% seizure reduction, and 13 (34%) were improved or unchanged. Children seizure free at two-year follow-up were likely to remain seizure free. Ten-year seizure freedom was 72% in children with developmental tumors and 32% in the cortical dysplasia group. Complete resection was statistically significant for favorable outcome, and no patient with an incomplete resection was seizure free.

Adolescent↗

PubMed2005

Seizure disorders: functional MR imaging for diagnostic evaluation and surgical treatment--prospective study.

PURPOSE: To prospectively evaluate effect of functional magnetic resonance (MR) imaging on diagnostic work-up and treatment planning in patients with seizure disorders who are candidates for surgical treatment. MATERIALS AND METHODS: Institutional review board approval was obtained; informed consent was obtained either from the patient or the parent or guardian in all patients. This study was conducted with Health Insurance Portability and Accountability Act compliance. Sixty consecutively enrolled patients (33 males, 27 females; mean age, 15.8 years +/- 8.7 [standard deviation]; range, 6.8-44.2 years) were prospectively examined. Forty-five (75%) patients were right handed, nine (15%) were left handed, and six (10%) had indeterminate hand dominance. Prospective questionnaires were used to evaluate diagnostic work-up, counseling, and treatment plans of the seizure team before and after functional MR imaging. Confidence level scales were used to determine effect of functional MR imaging on diagnostic and therapeutic thinking. Paired t test and 95% confidence interval analyses were performed. RESULTS: In 53 patients, language mapping was performed; in 33, motor mapping; and in seven, visual mapping. The study revealed change in anatomic location or lateralization of language-receptive (Wernicke) (28% of patients) and language-expressive (Broca) (21% of patients) areas. Statistically significant increases were found in confidence levels after functional MR imaging in regard to motor and visual cortical function evaluation. In 35 (58%) of 60 patients, the seizure team thought that functional MR imaging results altered patient and family counseling. In 38 (63%) of 60 patients, functional MR imaging results helped to avoid further studies, including Wada test. In 31 (52%) and 25 (42%) of 60 patients, intraoperative mapping and surgical plans, respectively, were altered because of functional MR imaging results. In five (8%) patients, two-stage surgery with extra-operative direct electrical stimulation mapping was averted, and resection was accomplished in one stage. In four (7%) patients, extent of surgical resection was altered because eloquent areas were identified close to seizure focus. CONCLUSION: Functional MR imaging results influenced diagnostic and therapeutic decision making of the seizure team; results indicated language dominance changed, confidence level in identification of critical brain function areas increased, patient and family counseling were altered, and intraoperative mapping and surgical approach were altered.

Adolescent↗

PubMed2004

Interictal spike detection using the Walsh transform.

The objective of this study was to evaluate the feasibility of using the Walsh transformation to detect interictal spikes in electroencephalogram (EEG) data. Walsh operators were designed to formulate characteristics drawn from experimental observation, as provided by medical experts. The merits of the algorithm are: 1) in decorrelating the data to form an orthogonal basis and 2) simplicity of implementation. EEG recordings were obtained at a sampling frequency of 500 Hz using standard 10-20 electrode placements. Independent sets of EEG data recorded on 18 patients with focal epilepsy were used to train and test the algorithm. Twenty to thirty minutes of recordings were obtained with each subject awake, supine, and at rest. Spikes were annotated independently by two EEG experts. On evaluation, the algorithm identified 110 out of 139 spikes identified by either expert (True Positives = 79%) and missed 29 spikes (False Negatives = 21%). Evaluation of the algorithm revealed a Precision (Positive Predictive Value) of 85% and a Sensitivity of 79%. The encouraging preliminary results support its further development for prolonged EEG recordings in ambulatory subjects. With these results, the false detection (FD) rate is estimated at 7.2 FD per hour of continuous EEG recording.

Action Potentials↗

PubMed2004

A new mathematical approach based on orthogonal operators for the detection of interictal spikes in epileptogenic data.

This study focuses on the design of orthogonal operators based on unique Electroencephalograph (EEG) signal decompositions in order to detect interictal spikes that characterize epileptic seizures in EEG data. The merits of the algorithm are: (a) in elaborating a unique analysis scheme that scrutinizes EEG data through orthogonal operators designed to extract features that best characterize spikes in epileptogenic EEG data; and (b) in establishing mathematical derivations that provide quantitative measures through the designed operators, and characterize and locate the event of an interictal spike. The uniqueness of this algorithm is in its good performance and simplicity of implementation. Clinical experiments involved 31 patients with focal epilepsy. EEG data collected from 10 of these patients were used initially in a training phase to ascertain the reliability of the observable and formulated features that were used in the spike detection process. Spikes were annotated independently by three EEG experts. On evaluation of the algorithm using the 21 remaining patients in the testing phase revealed a Precision (Positive Predictive Value) of 92% and a Sensitivity of 82%. Based on the 20 to 30-minute epochs of continuous EEG recording per subject, the false detection (FD) rate is estimated at 1.8 FD per hour of recorded EEG. These are good results that support further development of this algorithm for EEG diagnosis.

Action Potentials↗

PubMed2004

An optimization approach to recognition of epileptogenic data using neural networks with simplified input layers.

This study introduces a simplified approach for the implementation of artificial neural networks (ANN) for the recognition of epileptic data in electroencephalograph (EEG) recordings. The training set construction is based on a trend-adaptive polygon which simplifies the search process as it reduces the size of the training set. This data reduction, at a sampling rate of 200 Hz, yielded a reduction ratio of 34% as a minimum to an 81% in the best case scenario. With a higher sampling rate of 500 Hz, a reduction ratio of 73% as a minimum to an impressive 92% in the best case scenario was achieved. The outcome is thus a computationally attractive classifier with a simpler design implementation and with higher prospects for accurate diagnosis. The algorithm was trained and tested with EEG data from four epileptic patients using the k-fold cross-validation technique.

Action Potentials↗

PubMed2004

An integrated auditory-comprehension process augmented through topographical maps and a new eigensystem study.

The algorithm developed in this study integrates a frequency analysis of key frequency bands (Alpha, Beta, Delta, and Theta) with the principal component analysis (PCA) in order to validate brain functional mappings associated with the characterization effects of an Auditory/Comprehension task. This study provides added insight to earlier findings involving the Wernicke and Broca's brain areas in relation to language comprehension. A thorough examination of the electroencephalograph (EEG) recordings through the PCA reveals that eigenvectors associated with the largest eigenvalues produce an interesting activity pattern directly attributable to those characteristic behaviors found in the Alpha, Beta, Delta, and Theta frequency bands. The clinical EEG data involved 9 patients at Miami Children's Hospital using the Electrical Source Imaging system with 256 electrodes. An evaluation of spectral arrays is performed using topographic maps of the induced brain activities during both listening and answering phases. This evaluation is then augmented with quantifying measures using the PCA while results are validated through integration of EEG and PCA modalities. Such a representation allows us to bring new insight out on how different patients react under different circumstances, and be able to detect consequently the presence of potential neurological disorders by assessing similar/dissimilar behaviors with respects to all former patients already included in the database. The good results obtained are foreseen to extend the algorithm's application to other brain functional mapping tasks.

Algorithms↗

PubMed2003

Occult spinal dysraphism: evidence-based diagnosis and treatment.

This article reviews the scientific evidence behind the diagnostic tools available for the appropriate workup and management of patients with occult spinal dysraphism (OSD). The diagnostic tools include the use of detailed history and physical examination, plain films, ultrasound, MR imaging, and neurophysiologic tests. In addition, the article discusses the epidemiology of the most common causes of OSD in children, which will allow physicians caring for children to develop a pretest probability of disease and make a more educated decision as to when additional diagnostic testing is required.

Evidence-Based Medicine↗

PubMed2003

3-d source localization of epileptic foci integrating EEG and MRI data.

This study evaluates the utility of 3-D localization of interictal spike activity on the electroencephalographs (EEG) superimposed on magnetic resonance imagery (MRI) in a pediatric population with extra-temporal lesional epileptic foci. 3-D software programming based on the CURRY platform (a multimodal neuro-imaging software) was adapted for analyzing scalp EEG data and reconstructing superimposed images in 10 children who underwent extensive pre-surgical evaluation for intractable partial seizures. The results of 3-D spike source localization were assessed in relationship to focal lesions evident on the patient's MRI scans. Calculated spike sources were closest to the lesions during intervals corresponding to the spike peaks. The information was useful in surgical planning in six children that underwent successful resections.

Action Potentials↗

PubMed2002

False lateralization of language cortex on functional MRI after a cluster of focal seizures.

fMRI can define language cortex but its limitations are not yet fully understood. This article describes a child in whom fMRI falsely lateralized language cortex when performed after a cluster of left temporal lobe seizures. Multiple language tasks revealed no activation over the left temporal lobe despite a normal neurologic exam at the time of the study. A second fMRI performed 2 weeks later activated sites predominantly over the left, which were confirmed by extra-operative functional language mapping. fMRI may be unhelpful after frequent seizures.

Adolescent↗

PubMed2002

The use of stereotactic radiosurgery to treat intractable childhood partial epilepsy.

PURPOSE: Although conventional surgery is presently used to treat seizures of temporolimbic and neocortical origin, deep-seated lesions are often associated with morbidity. Stereotactic radiosurgery is a noninvasive procedure that effectively treats patients with vascular malformations and brain tumors, but its efficacy for epileptogenic foci is limited, especially in children. METHODS: Between 1995 and 1999, four candidates who had medically uncontrolled seizures and localized seizure foci were selected for stereotactic radiosurgery, with a mean age of 9.75 years at the time of surgery (range, 4-17 years). Seizure foci were identified on the basis of ictal and interictal video-EEG. Magnetic resonance (MR) images were obtained before and after surgery. Ictal single-photon emission computed tomography (SPECT) was performed by using stabilized hexamethyl-propyleneamine oxime (HMPAO; 300 microcuries/kg) with early injection after electrographic ictal onset. The clinical features of the patients are given. All radiosurgical procedures were performed with the gamma knife unit with the Leksell stereotactic frame, stereotactic MRI imaging, and the Gamma Plan workstation. Seizure outcome was scored according to Engel's classification. RESULTS: Two patients had hypothalamic hamartoma (HH), and two had neocortical epilepsy. At mean follow-up of 39.2 months (range, 26-69 months), two patients were seizure free, one with a HH and one with a suggestive developmental tumor in the insular cortex by MRI findings. The other patient with HH had 90% reduction of seizures. One patient with a widespread seizure focus that involved the motor strip was unimproved. The two patients with HH also exhibited markedly improved neurobehavioral status after surgery. There were no significant complications of radiosurgical therapy. CONCLUSIONS: Our findings suggest that gamma knife surgery is a potentially valuable treatment modality for children with medically intractable epilepsy due to a well-localized seizure focus that is difficult to excise by conventional techniques or for whom they are deemed unsuitable. More widespread application in childhood epilepsy should be investigated in larger series.

Adolescent↗

PubMedDate not supplied

Detection of interictal spikes and artifactual data through orthogonal transformations.

This study introduces an integrated algorithm based on the Walsh transform to detect interictal spikes and artifactual data in epileptic patients using recorded EEG data. The algorithm proposes a unique mathematical use of Walsh-transformed EEG signals to identify those criteria that best define the morphologic characteristics of interictal spikes. EEG recordings were accomplished using the 10-20 system interfaced with the Electrical Source Imaging System with 256 channels (ESI-256) for enhanced preprocessing and on-line monitoring and visualization. The merits of the algorithm are: (1) its computational simplicity; (2) its integrated design that identifies and localizes interictal spikes while automatically removing or discarding the presence of different artifacts such as electromyography, electrocardiography, and eye blinks; and (3) its potential implication to other types of EEG analysis, given the mathematical basis of this algorithm, which can be patterned or generalized to other brain dysfunctions. The mathematics that were applied here assumed a dual role, that of transforming EEG signals into mutually independent bases and in ascertaining quantitative measures for those morphologic characteristics deemed important in the identification process of interictal spikes. Clinical experiments involved 31 patients with focal epilepsy. EEG data collected from 10 of these patients were used initially in a training phase to ascertain the reliability of the observable and formulated features that were used in the spike detection process. Three EEG experts annotated spikes independently. On evaluation of the algorithm using the 21 remaining patients in the testing phase revealed a precision (positive predictive value) of 92% and a sensitivity of 82%. Based on the 20- to 30-minute epochs of continuous EEG recording per subject, the false detection rate is estimated at 1.8 per hour of continuous EEG. These are positive results that support further development of this algorithm for prolonged EEG recordings on ambulatory subjects and to serve as a support mechanism to the decisions made by EEG experts.

Action Potentials↗

PubMedDate not supplied

Subdural EEG patterns in children with taylor-type cortical dysplasia: comparison with nondysplastic lesions.

The authors compared interictal and ictal abnormalities from chronic intracranial recordings in children with Taylor-type cortical dysplasia (TTCD) and nondysplastic lesions. Interictal epileptiform discharges and ictal patterns were retrospectively analyzed in 13 children with TTCD and 12 children with nondysplastic lesions (tumor, 4; gliosis, 8). Features analyzed and compared between groups included the morphologic and temporal characteristics and field distribution of ictal and interictal patterns and rapidity of ictal propagation. The frequency of runs of interictal continuous epileptiform discharges (CEDs) or bursts of fast activity did not differ significantly between dysplastic and nondysplastic tissue. Fast frequencies characterized the majority of seizure onsets (49/67) in dysplastic patients and repetitive spikes were more frequent at seizure onset (31/56) in nondysplastic patients (P < 0.002). Field of ictal onset was limited to adjacent cortex and independent of histology. The interval between seizure onset and spread to adjacent or nonadjacent cortex was significantly shorter in dysplastic than nondysplastic patients. Interictal EEG patterns are not specific markers of dysplastic cortex but the morphology of ictal onset differs significantly with dysplastic cortex showing significantly more rapid propagation than nondysplastic cortex. These findings suggest that markers other than CEDs physiologically characterize dysplastic cortex and that children with TTCD exhibit more widespread excitability of neural pathways.

Brain Diseases↗