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Intracerebral cell transplantation is being pursued as a treatment for many neurological diseases, and effective cell delivery is critical for clinical success. To facilitate intracerebral cell transplantation at the scale and complexity of the human brain, we developed a platform technology that enables radially branched deployment (RBD) of cells to multiple target locations at variable radial distances and depths along the initial brain penetration tract with real-time interventional magnetic resonance image (iMRI) guidance. iMRI-guided RBD functioned as an "add-on" to standard neurosurgical and imaging workflows, and procedures were performed in a commonly available clinical MRI scanner. Multiple deposits of super paramagnetic iron oxide beads were safely delivered to the striatum of live swine, and distribution to the entire putamen was achieved via a single cannula insertion in human cadaveric heads. Human embryonic stem cell-derived dopaminergic neurons were biocompatible with the iMRI-guided RBD platform and successfully delivered with iMRI guidance into the swine striatum. Thus, iMRI-guided RBD overcomes some of the technical limitations inherent to the use of straight cannulas and standard stereotactic targeting. This platform technology could have a major impact on the clinical translation of a wide range of cell therapeutics for the treatment of many neurological diseases.

Object: The aim of this study was to estimate the impact of stereotactic pallidal surgery on the binding potential of dopamine D2 receptors in patients with advanced Parkinson disease (PD)., Methods: Six patients with advanced PD (three men and three women; mean age 56.7 +/- 9.8 years, Hoehn and Yahr stage 3.3 +/- 1.1/3.9 +/- 1.2 [on/off scores], mean +/- standard deviation) underwent stereotactic pallidal surgery. One underwent right posteroventral pallidotomy (PVP), one received left PVP, three were treated with deep brain stimulation (DBS) of the left globus pallidus internus (GPi), and one with bilateral DBS of the GPi. The binding potential of the dopamine D2 receptors of these patients was determined before and after surgery by using positron emission tomography scanning with 11C-nemonapride and it was compared with the value in eight healthy volunteers. The authors also examined whether changes in the D2 receptor binding potential were correlated with the clinical outcome. The clinical symptoms, especially those in the off state, were significantly improved after surgery. Preoperatively, the D2 receptor binding potential in the putamen was elevated by 27% (p < 0.01) and that in the thalamus was 29% lower than that in controls (p < 0.01). The D2 receptor binding potential in the putamen and thalamus returned to control levels after surgery. The preoperative level of the D2 receptor binding potential in the anterior cingulate cortex was comparable to that of controls, but it declined significantly after surgery, whereas the D2 receptor binding potential in other regions of both hemispheres showed no significant changes after surgery. Although the D2 receptor binding potential did not correlate with the Hoehn and Yahr stage, the Schwab and England score, or the Unified PD Rating Scale (UPDRS) score, a positive correlation was seen between the percent improvement rate of the total UPDRS score in the off state and the percentage change of the D2 receptor binding potential in the putamen (r = 0.773, p = 0.0417 according to the Pearson linear correlation)., Conclusions: The altered dopamine D2 receptor binding potential in the putamen might play a crucial role in clinical improvement after PVP or DBS of the GPi in advanced PD.

The authors present a simple, reliable, and safe system for performing neural transplantation in the human brain. The device consists of a transplantation cannula and microinjector system that has been specifically designed to reduce implantation-related trauma and to maximize the number of graft deposits per injection. The system was evaluated first in an experimental rat model of Parkinson's disease (PD). Animals in which transplantation with this system had been performed showed excellent graft survival with minimal trauma to the brain. Following this experimental stage, the cannula and microinjector system were used in eight patients with PD enrolled in the Halifax Neural Transplantation Program who received bilateral putaminal transplants of fetal ventral mesencephalic tissue. A total of 16 transplantation operations and 64 trajectories were performed in the eight patients, and there were no intraoperative or perioperative complications. Magnetic resonance imaging studies obtained 24 hours after surgery revealed no evidence of tissue damage or hemorrhage. Transplant survival was confirmed by fluorodopa positron emission tomography scans obtained 6 and 12 months after surgery. As neural transplantation procedures for the treatment of neurological conditions evolve, the ability to deliver viable grafts safely will become critically important. The device presented here has proved to be of value in maximizing the number of graft deposits while minimizing implantation-related trauma to the host brain.

The authors have studied the indications and limitations for computerized tomography (CT)-guided stereotaxic surgery (CTGS Surgery) of hypertensive intracerebral haematomas (ICH), based on the analysis of 158 patients in our institutions. Of 158 patients, 120 had putaminal haemorrhage, 21 thalamic, 14 subcortical and 3 in other locations. The patients ranged in age from 37 to 82 years (average 60). Haematoma volume ranged from 8 to 140 ml (average 43). Eleven patients in the series worsened postoperatively because of rebleeding in 6 cases, cerebral infarction in 2, and unknown causes in the remaining 3 cases. Seven of the 11 patients pre-operatively had untreated hypertension and 3 had mild liver dysfunction without major haemorrhagic tendency. Most postoperative complications were seen in older patients and in those with severe neurological deficit or chronic disease. All these cases ended in poor outcome. From our study, we propose three indications for CTGS Surgery: absolute, aggressive and passive indications. The absolute indication is applied to those who would have been operated on by conventional open surgery. The aggressive indication is for those with mild neurological deficit so that early rehabilitation can be started to regain higher cerebral function. The passive indication is for elderly patients and those with severe neurological deficit or chronic disease. This indication must be decided carefully because poor outcome is likely.

We report our preliminary results related to CT-guided stereotactic transplantation of foetal ventral mesencephalic cell suspension into the striatum of five patients with idiopathic Parkinson's disease. The mean age was 51 years, the evolution time of the disease ranged from 7 to 14 years, and all of them had motor complications associated with chronic L-dopa therapy. The patients were evaluated according to the Core Assessment Program for Intracerebral Transplantations (CAPIT) for one year before and three months after surgery. The postoperative clinical assessment demonstrated significant improvement of neurological symptoms and reduction of daily L-dopa dosage.

Autograft of adrenal medullary tissue into the striatum was performed stereotactically in 5 patients with severe Parkinson's disease. Two patients had suffered from side effects of L-dopa, and 3 were severely disabled without L-dopa preoperatively. After surgery, the dosage of L-dopa could be reduced in 1, and L-dopa could be withdrawn in 4 patients. The results of adrenal medullary tissue transplantation in Parkinson's disease are analyzed.

Adrenal to striatum transplants may be effective, but many technical issues are still debated. A procedure whereby a number of grafts were stereotactically placed at the putamen and caudatum is reported. It enables grafting deep nuclei, such as the putamen, the most denervated structure in Parkinson's disease, and allows a widespread spatial distribution of multiple grafts within these huge targets, conceivably enhancing the local release of neurotransmitters at the site or in the vicinity of the denervated receptors. It also enables the use of a sizeable volume of tissue, presumably a crucial but as yet unknown factor. Although preliminary, the present data seem to warrant further clinical trials.

During the last 3 years, 46 cases of hypertensive intracerebral hemorrhage were treated by CT-guided stereotactic surgery. Our present report is concerned with the evaluation of this procedure in the treatment of hypertensive intracerebral hematoma, in terms of the rate of aspirated hematoma and follow-up study of patients. It is difficult to draw any definite conclusion about the operative indications. CT-guided stereotactic aspiration, however, can be evaluated as a less invasive and more definitive treatment of intracerebral hematoma in the basal ganglia and thalamus.

Changes in cerebral blood flow (CBF) after CT guided stereotactic aspiration of putaminal haematoma were investigated in 13 patients with Xe-133 inhalation and single photon emission computed tomography. The interval from onset to operation ranged from 13 to 82 days (mean 30 days). The mean estimated haematoma volume ranged from 20 to 50 ml (mean 31.9 ml). The percentage of haematoma aspirated ranged from 75 to 98% (mean 86.8%). Postoperative CBF in two thirds of the patients was improved even though all cases were operated on in the subacute stage. Both the mean hemispheric and regional CBF in the anterior territory of the middle cerebral artery and in the region of the thalamus and basal ganglia in the affected hemisphere were increased postoperatively. Also in the nonaffected hemisphere, regional CBF in the region of the thalamus and basal ganglia was improved.

In computed tomography (CT)-controlled stereotactic surgery, the coordinate system of the CT scanner is applied to determine the target depth and direction as well as for readjustment of final probe direction. This method can be used for all types of stereotactic surgery for the brain.

Believing that improved therapeutic results in cases of intracerebral hematoma might be obtained by minimal invasion of the brain, we used computed tomographic-guided stereotactic aspiration in 175 of 241 patients with putaminal hemorrhage. These patients, who were treated 6 or more hours after onset, had hematomas larger than 8 ml and were unable to raise an arm and/or leg on the affected side. Craniotomy was performed in 15 other patients, most of whom were brought to the hospital with large hematomas within 6 hours of onset. The remaining patients either had mild deficits of consciousness (33 patients) or severe deficits and/or were elderly (18 patients) and were treated conservatively. Thirteen patients (7.4%) showed rebleeding after stereotactic aspiration (6 instances of major and 7 instances of minor rebleeding). Craniotomy and removal of the hematoma were required in three of these patients. Aspiration should be avoided in patients who have a tendency for bleeding, even if mild, because rebleeding occurred in 6 of 23 such patients (26%) in these study. The consciousness level improved in 66 patients (38%), was unchanged in 103 patients (59%), and was worse in 6 patients (3%) 1 week postoperatively. Motor function of the arm improved in 55 patients (31%) and was worse in 23 patients (14%). Six months after surgery, the results for the 175 patients who underwent stereotactic aspiration were: 19% excellent, 32% good, 35% fair, 7% poor, 6% dead, and 1% unknown. For the entire series of 241 patients, the results were: 24% excellent, 26% good, 31% fair, 7% poor, 11% dead, and 1% unknown.(ABSTRACT TRUNCATED AT 250 WORDS)