Biomedical subjects

Patrick B Senatus

Publications and source records attributed to Patrick B Senatus.

5 recordsLinked to original sources

PubMed2006

A technique for minimally altering anatomically based subthalamic electrode targeting by microelectrode recording.

OBJECT: Implantation of a subthalamic nucleus (STN) deep brain stimulation (DBS) electrode is increasingly recognized as an effective treatment for advanced Parkinson disease (PD). Despite widespread use of microelectrode recording (MER) to delineate the boundaries of the STN prior to stimulator implantation, it remains unclear to what extent MER improves the clinical efficacy of this procedure. In this report, the authors analyze a series of patients who were treated at one surgical center to determine to what degree final electrode placement was altered, based on readings obtained with MER, from the calculated anatomical target. METHODS: Subthalamic DBS devices were placed bilaterally in nine patients with advanced PD. Frame-based volumetric magnetic resonance images were acquired and then transferred to a stereotactic workstation to determine the anterior and posterior commissure coordinates and plane. The initial anatomical target was 4 mm anterior, 4 mm deep, and 12 mm lateral to the midcommissural point. The MERs defined the STN boundaries along one or more parallel tracks, refining the final electrode placement by comparison of results with illustrations in a stereotactic atlas. In eight of 18 electrodes, the MER results did not prompt an alteration in the anatomically derived target. In another eight placements, MER altered the target by less than 1 mm and two of 18 electrode positions differed by less than 2 mm. The anterior-posterior difference was 0.53 +/- 0.65 mm, whereas the medial-lateral direction differed by 0.25 +/- 0.43 mm. The ventral boundary of the STN defined by MER was 2 +/- 0.72 mm below the calculated target (all values are the means +/- standard deviation). All patients attained clinical improvement, similar to previous reports. CONCLUSIONS: In this series of patients, microelectrode mapping of the STN altered the anatomically based target only slightly. Because it is not clear whether such minor adjustments improve clinical efficacy, a prospective clinical comparison of MER-refined and anatomical targeting may be warranted.

Brain Mapping↗

PubMed2006

Restoration of p53 function for selective Fas-mediated apoptosis in human and rat glioma cells in vitro and in vivo by a p53 COOH-terminal peptide.

We have shown that a COOH-terminal peptide of p53 (amino acids 361-382, p53p), linked to the truncated homeobox domain of Antennapedia (Ant) as a carrier for transduction, induced rapid apoptosis in human premalignant and malignant cell lines. Here, we report that human and rat glioma lines containing endogenous mutant p53 or wild-type (WT) p53 were induced into apoptosis by exposure to this peptide called p53p-Ant. The peptide was comparatively nontoxic to proliferating nonmalignant human and rat glial cell lines containing WT p53 and proliferating normal human peripheral marrow blood stem cells. Degree of sensitivity to the peptide correlated directly with the level of endogenous p53 expression and mutant p53 conformation. Apoptosis induction by p53p-Ant was quantitated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and Annexin V staining in human glioma cells in vitro and in a syngeneic orthotopic 9L glioma rat model using convection-enhanced delivery in vivo. The mechanism of cell death by this peptide was solely through the Fas extrinsic apoptotic pathway. p53p-Ant induced a 3-fold increase in extracellular membrane Fas expression in glioma cells but no significant increase in nonmalignant glial cells. These data suggest that p53 function for inducing Fas-mediated apoptosis in gliomas, which express sufficient quantities of endogenous mutant or WT p53, may be restored or activated, respectively, by a cell-permeable peptide derived from the p53 COOH-terminal regulatory domain (p53p-Ant). p53p-Ant may serve as a prototypic model for the development of new anticancer agents with unique selectivity for glioma cancer cells and it can be successfully delivered in vivo into a brain tumor by a convection-enhanced delivery system, which circumvents the blood-brain barrier.

Amino Acid Sequence↗

PubMed2005

Subthalamic stimulation for Parkinson disease: determination of electrode location necessary for clinical efficacy.

OBJECT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) performed using intraoperative microelectrode recording (MER) to adjust electrode placement has become a widely used treatment for patients with advanced Parkinson disease (PD). Few studies have been conducted to examine the location of implanted electrodes relative to the intended target, and even fewer have been undertaken to investigate the degree to which variations in the location of these electrodes impacts their clinical efficacy. This study was performed to examine these issues. METHODS: The authors located 52 bilaterally implanted DBS electrode tips on postoperative magnetic resonance (MR) images obtained in 26 consecutive patients. Postoperative and preoperative planning MR images were merged to determine the DBS electrode tip coordinates relative to the midcommissural point. Surgical records listed the intended target coordinates for each DBS electrode tip. Clinical outcome assessment included the Unified PD Rating Scale (UPDRS) motor score at 1 year, standardized questionnaires, and routine follow-up visits. The mean difference between electrode tip location and intended target for all 52 electrodes was less than 2 mm in all axes. Only one electrode was farther than 3 mm from the intended target, and this was the only electrode that had to be replaced due to lack of clinical efficacy (lack of tremor suppression); its reimplantation 4 mm more medially provided excellent tremor control. High correlation coefficients indicate that the MR imaging analysis accurately determined the anatomical location of the electrode tips. Blinded videotape reviews of UPDRS motor scores comparing effects of stimulation in patients who were "on" and "off" medication identified subgroups in whom there was minimal and maximal stimulation response. Patients in these subgroups had no differences between the MR imaging-determined actual electrode tip location and its intended location. Similarly, improvements of dyskinesias and severity of symptoms encountered during the wearing-off period for the drug did not correlate with variations of electrode tip location. CONCLUSIONS: The findings in this study lead the authors to suggest that a DBS electrode placed anywhere within a 6-mm-diameter cylinder centered at the presumed middle of the STN (based on stereotactic atlas coordinates) provides similar clinical efficacy. Future studies may be warranted to evaluate prospectively the degree to which MER modification of the anatomically and/or image-determined target improves clinical efficacy of DBS electrodes.

Adult↗

PubMed2005

The transformation of pediatric gliomatosis cerebri to cerebellar glioblastoma multiforme presenting as supra- and infratentorial acute disseminated encephalomyelitis. Case report.

Cerebellar glioblastoma multiforme (GBM) is a rare entity in adults and an extremely rare entity in children. Approximately 30 cases have been reported in the literature. The authors report the case of a histologically confirmed cerebellar GBM presenting initially as supra- and infratentorial gliomatosis cerebri. Acute disseminated encephalomyelitis had been diagnosed in the patient and that diagnosis remained until near the end of his treatment. This case underscores the need for recognizing the clinical presentation of gliomatosis cerebri and multifocal GBM in the pediatric subpopulation thought to harbor demyelinating disease.

Cerebellar Neoplasms↗

PubMed2004

Implantation of bilateral deep brain stimulators in patients with Parkinson disease and preexisting cardiac pacemakers. Report of two cases.

Deep brain stimulation (DBS) has become an important modality in the treatment of refractory Parkinson disease (PD). In patients with comorbid arrhythmias requiring cardiac pacemakers, DBS therapy is complicated by concerns over a possible electrical interaction between the devices (or with device programming) and the inability to use magnetic resonance imaging guidance for implantation. The authors report two cases of PD in which patients with preexisting cardiac pacemakers underwent successful implantation of bilateral DBS electrodes in the subthalamic nucleus (STN). Each patient underwent computerized tomography-guided stereotactic frame-based placement of DBS electrodes with microelectrode recording. Both extension wires were passed from the right side of the head and neck (contralateral to the pacemaker) to place the cranial pulse generators subcutaneously in the left and right abdomen. The cranial pulse generators were placed farther than 6 in from the cardiac pacemaker and from each other to decrease the chance of interference between the devices during telemetry reprogramming. Postoperative management involved brain stimulator programming sessions with simultaneous cardiological monitoring of pacemaker function and cardiac rhythm. No interference was noted at any time, and proper pacemaker function was maintained throughout the follow-up period. With bilateral STN stimulation, both patients experienced a dramatic improvement in their PD symptoms, including elimination of dyskinesias, reduction of "off" severity, and increase of "on" duration. With some modifications of implantation strategy, two patients with cardiac pacemakers were successfully treated with bilateral DBS STN therapy for refractory PD. To our knowledge, this is the first report on patients with cardiac pacemakers undergoing brain stimulator implantation.

Aged↗