Motor performance after posteroventral pallidotomy and VIM-thalamotomy in Parkinson's disease: a 1-year follow-up study.
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Twenty-three patients with Parkinson's disease underwent stereotactic surgery. To study the long-term motor performance, the patients were evaluated at the pre-operative period and at the 1st, 3rd, 6th, and 12th post-operative months, with the following scales: Unified Parkinson's Disease Rating Scale (UPDRS) motor score and Larsen's Scale for Dyskinesias. The patients under levodopa therapy were assessed both in "on" and "off" periods. Fourteen unilateral ventrolateral thalamotomies (VLT), 4 unilateral posteroventral pallidotomies (PVP), 2 bilateral PVP, and 3 VLT with contralateral PVP were performed. The motor improvement was significant and long-lasting in the "off" period, except for 2 patients. The "on" period quality improved, mainly due to the control of dyskinesias. The improvement of dyskinesias was long-lasting for the majority of the patients. There was no significant decrease in the levodopa dose. Three patients showed permanent complications, but none was severe. (+info)
Spectral integration in the inferior colliculus of the mustached bat.
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Acoustic behaviors including orientation and social communication depend on neural integration of information across the sound spectrum. In many species, spectral integration is performed by combination-sensitive neurons, responding best when distinct spectral elements in sounds are combined. These are generally considered a feature of information processing in the auditory forebrain. In the mustached bat's inferior colliculus (IC), they are common in frequency representations associated with sonar signals but have not been reported elsewhere in this bat's IC or the IC of other species. We examined the presence of combination-sensitive neurons in frequency representations of the mustached bat's IC not associated with biosonar. Seventy-five single-unit responses were recorded with the best frequencies in 10-23 or 32-47 kHz bands. Twenty-six displayed single excitatory tuning curves in one band with no additional responsiveness to a second signal in another band. The remaining 49 responded to sounds in both 10-23 and 32-47 kHz bands, but response types varied. Sounds in the higher band were usually excitatory, whereas sounds in the lower band either facilitated or inhibited responses to the higher frequency signal. Interactions were usually strongest when the higher and lower frequency stimuli were presented simultaneously, but the strength of interactions varied. Over one-third of the neurons formed a distinct subset; they responded most sensitively to bandpass noise, and all were combination sensitive. We suggest that these combination-sensitive interactions are activated by elements of mustached bat social vocalizations. If so, neuronal integration characterizing analysis of social vocalizations in many species occurs in the IC. (+info)
Three-dimensional stereotactic surface projection analysis of macaque brain PET: development and initial applications.
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To characterize better the local brain functions of conscious rhesus macaques, we developed automated image analysis techniques for monkey PET images, examined the cerebral glucose metabolism of monkeys, and compared it with that of humans. METHODS: Glucose metabolic PET images from 11 monkeys were obtained using a high-resolution animal PET scanner after intravenous administration of FDG. T1-weighted MR images were obtained from 6 of the monkeys. Referencing a bicommissural stereotactic macaque brain atlas, we created a PET brain template using coregistered MR images. Each individual PET image set was transformed to the PET template through an automated affine transformation, followed by nonlinear warping along the directions of the major neuronal fiber bundles in the brain. For minimization of residual anatomic variability, metabolic activities were extracted using 3-dimensional stereotactic surface projections. The effects of anatomic standardization were evaluated using MR images. Patterns of cerebral glucose metabolism of young versus aged monkeys were examined. The metabolic activities of aged monkeys were compared with those of elderly healthy human volunteers that had been analyzed similarly. RESULTS: Anatomic standardization reduced individuals' anatomic variability as evidenced by a reduction in the number of MR pixels with higher SDs calculated across monkeys. Coefficient-of-variation maps of conscious monkeys revealed that the greatest metabolic variances were near the central sulci and occipital cortices. Age-associated glucose metabolic reductions were most pronounced in the occipital lobe, caudate nucleus, and temporal lobe. Compared with human brains, the monkey frontal lobe and posterior cingulate gyrus had significantly less metabolic activity and the supramarginal gyrus and vermis had significantly more metabolic activity. CONCLUSION: The proposed method permits pixel-by-pixel characterization of the metabolic activities of rhesus macaque brains in the stereotactic coordinate system. Greater metabolic variances in the central sulcus region and occipital lobe suggest potential difficulties in controlling sensory input and motor output or planning in conscious monkey experiments. The analyses revealed age-related metabolic reductions in monkeys and marked differences in metabolic patterns between aged monkey brains and aged human brains. The proposed brain-mapping technique enables reproducible and observer-independent analyses and will serve as an important investigative tool for primate brain imaging research. (+info)
O6-benzylguanine potentiates the antitumor effect of locally delivered carmustine against an intracranial rat glioma.
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Local delivery of carmustine (BCNU) via biodegradable polymers prolongs survival against experimental brain tumors and in human clinical trials. O6-benzylguanine (O6-BG), a potent inhibitor of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase (AGT), has been shown to reduce nitrosourea resistance and, thus, enhance the efficacy of systemic BCNU therapy in a variety of tumor models. In this report, we demonstrate that O6-BG can potentiate the activity of BCNU delivered intracranially via polymers in rats challenged with a lethal brain tumor. Fischer 344 rats received a lethal intracranial challenge of 100,000 F98 glioma cells (F98 cells have significant AGT activity, 328 fmol/mg protein). Five days later, animals receiving an i.p. injection of O6-BG (50 mg/kg) 2 h prior to BCNU polymer (3.8% BCNU by weight) implantation had significantly improved survival (n = 7; median survival, 34 days) over animals receiving either O6-BG alone (n = 7; median survival, 22 days; P = 0.0002) or BCNU polymer alone (n = 8; median survival, 25 days; P = 0.0001). Median survival for the control group (n = 8) was 23.5 days. Moreover, there was no physical, behavioral, or pathological evidence of treatment-related toxicity. These findings suggest that O6-BG can potentiate the effects of interstitially delivered BCNU and, for tumors expressing significant AGT, may be necessary for the BCNU to provide a meaningful therapeutic benefit. Given the clinical use of BCNU polymers against malignant gliomas, concurrent treatment with O6-BG may provide an important addition to our therapeutic armamentarium. (+info)
Functional cranial neuronavigation. Direct integration of fMRI and PET data.
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OBJECTIVE: We report our first experiences with the direct integration of fMRI data into cranial neuronavigation. METHOD: For navigation we used the MKM system and thin-sliced T1 contrast enhanced images. As a first step 21 patients had fMRI for localization of the precentral gyrus, 2 patients for Broca area detection. By anatomical correlation, these functional data were indirectly compared to the intraoperative findings using cortical SSEP (n=20) or cortical stimulation (n=3). Encouraged by these preliminary results, we started the direct integration of fMRI into neuronavigation in June 1999, followed by PET in January 2000, enabling us to compare functional images with intraoperative findings directly. fMRI and PET data were integrated by landmark matching referring on skin fiducials. Meanwhile, fMRI data of 8 patients (6 motorcortex, 2 Broca) and PET images of 1 patient were directly integrated into neuronavigation. Six out of 8 patients had additional cortical monitoring, 2/8 were exclusively operated on by functional neuronavigation. RESULTS: Using indirect comparison between fMRI and intraoperative findings we observed a good correlation in every case for the motorcortex, but only in 1/2 for the speech area. In all 6 direct integrated fMRI cases, these findings corresponded well to the conventional ones. Both patients with sole functional navigation did not have any postoperative neurological deficit. The inaccuracy of the fMRI ifT1 matching was 2. 7 mm (sigma=0.9 mm) and 1.3 mm (sigma=0.4 mm) of the subsequent referenciation of the navigation. The tumor delinement shown by 11C-methionine PET could be proven by intraoperative biopsy outside its indicated tumor margin. The inaccuracy of the PET matching was 0. 8 mm. CONCLUSION: Functional neuronavigation enables to visualize and preserve relevant brain areas. Other functional areas like short-term memory, which solely can be detected by fMRI might also be monitored in the future. The integration of PET data expect to gain a better differentiation of tumor and edema. (+info)
Experience with the advanced breast biopsy instrumentation system.
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OBJECTIVES: To report early experience with the advanced breast biopsy instrumentation (ABBI) system and to compare the results with those of other published studies. DESIGN: A nonrandomized case series. SETTING: An outpatient breast diagnostic centre at a large urban community hospital. PATIENTS: Thirty-four women; 27 had suspicious calcifications, 2 had a nonpalpable mass and 5 had both. INTERVENTION: The ABBI procedure to excise a breast lesion or obtain a representative sample for histologic examination. MAIN OUTCOME MEASURES: Success of the procedure with respect to diagnosis, sample quality, technical problems, margins of tumour free tissue and patient satisfaction. RESULTS: Malignant tissue was diagnosed in 7 women (21%) and atypical ductal hyperplasia in 2 (6%). In all cancers, the obtained samples had malignant cells present at the margins or less than 1 mm away. Technical problems were encountered in 32% of cases. Manual extraction of the specimen was required in 21% of cases. CONCLUSIONS: The preliminary data correlate well with those of other published results. Although it is possible that a small number of cases and a relatively high proportion of technical difficulties may represent a normal learning curve, there is a definite need for improvement of some ABBI components. ABBI does not appear to provide adequate margins of uninvolved tissue in patients with cancer and thus should not be used with curative intent. ABBI provides excellent quality samples for pathological study and good patient satisfaction. There are not yet enough data for meaningful comparison of ABBI with stereotactic core biopsy and excisional biopsy with needle localization. (+info)
Stereotactic single-dose radiation therapy of liver tumors: results of a phase I/II trial.
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PURPOSE: To investigate the feasibility and the clinical response of a stereotactic single-dose radiation treatment for liver tumors. PATIENTS AND METHODS: Between April 1997 and September 1999, a stereotactic single-dose radiation treatment of 60 liver tumors (four primary tumors, 56 metastases) in 37 patients was performed. Patients were positioned in an individually shaped vacuum pillow. The applied dose was escalated from 14 to 26 Gy (reference point), with the 80% isodose surrounding the planning target volume. Median tumor size was 10 cm(3) (range, 1 to 132 cm(3)). The morbidity, clinical outcome, laboratory findings, and response as seen on computed tomography (CT) scan were evaluated. RESULTS: Follow-up data could be obtained from 55 treated tumors (35 patients). The median follow-up period was 5.7 months (range, 1.0 to 26.1 months; mean, 9.5 months). The treatment was well tolerated by all patients. There were no major side effects. Fifty-four (98%) of 55 tumors were locally controlled after 6 weeks at the initial follow-up based on the CT findings (22 cases of stable disease, 28 partial responses, and four complete responses). After a dose-escalating and learning phase, the actuarial local tumor control rate was 81% at 18 months after therapy. A total of 12 local failures were observed during follow-up. So far, the longest local tumor control is 26.1 months. CONCLUSION: Stereotactic single-dose radiation therapy is a feasible method for the treatment of singular inoperable liver metastases with the potential of a high local tumor control rate and low morbidity. (+info)
The protective effect of ceramide in immature rat brain hypoxia-ischemia involves up-regulation of bcl-2 and reduction of TUNEL-positive cells.
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Preconditioning brain with tumor necrosis factor alpha (TNF-alpha) can induce tolerance to experimental hypoxia and stroke and ceramide is a downstream messenger in the TNF-alpha signaling pathway. A hypoxic-ischemic (HI) insult in the immature rat injures brain primarily through apoptosis. Apoptosis is regulated by Bcl-2 family proteins. The authors explored whether ceramide protects against HI in the immature rat, and whether Bcl-2 family protein expression is involved. Hypoxia-ischemia was produced in seven-day-old rats by ligating the right carotid artery, followed by 2 hours of 8% oxygen exposure. Thirty minutes after HI, C2-ceramide (150 microg/kg) was injected intraventricularly. Infarct volume was measured 5 days later. C2-ceramide reduced HI-induced brain damage by 45% to 65% compared with HI/dimethyl sulfoxide (DMSO) (vehicle control) or HI only groups. In separate experiments, brains of sham-operated control and HI only animals and animals subjected to HI plus C2-ceramide or DMSO infusion were sampled 6 hours, 24 hours, and 5 days after treatments and analyzed for Bcl-2, Bcl-xl, and Bax expression (Western blotting), and apoptosis (TUNEL assay). Augmented Bcl-2 and Bcl-xl levels in the C2-ceramide treated group were associated with a significant decrease in TUNEL-positive cells. The results support a protective role for ceramide in neonatal HI. (+info)