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Background: The efficacy and safety of intracerebral gene therapy for brain disorders like Parkinson's disease depends on the appropriate distribution of gene expression., Objectives: To assess whether the distribution of gene expression is affected by vector titer and protein type., Methods: Four adult macaque monkeys seronegative for adeno-associated virus 5 (AAV5) received a 30-µl inoculation of a high- or a low-titer suspension of AAV5 encoding glial cell line-derived neurotrophic factor (GDNF) or green fluorescent protein (GFP) in the right and left ventral postcommissural putamen. The inoculations were conducted using convection-enhanced delivery and intraoperative MRI (IMRI)., Results: IMRI confirmed targeting and infusion cloud irradiation from the catheter tip into the surrounding area. A postmortem analysis 6 weeks after surgery revealed GFP and GDNF expression ipsilateral to the injection site that had a titer-dependent distribution. GFP and GDNF expression was also observed in fibers in the substantia nigra (SN) pars reticulata (pr), demonstrating anterograde transport. Few GFP-positive neurons were present in the SN pars compacta (pc), possibly by direct retrograde transport of the vector. GDNF was present in many neurons of the SNpc and SNpr., Conclusions: After controlling for target and infusate volume, the intracerebral distribution of the gene product was affected by the vector titer and product biology.

Transplantation of autologous sympathetic ganglion was performed in 35 patients with Parkinson's disease. Approximately half the patients showed improvement of parkinsonian symptoms over the 3 years following transplantation. The patients showed amelioration of bradykinesia and gait disturbance, but tremor and muscle rigidity were not improved by transplantation. The other half of the patients did not show amelioration after transplantation. No serious complications were encountered, though mild ptosis was observed in all patients. The mechanism of improvement of symptoms might be the release of dopamine from the grafted sympathetic ganglion. Transplantation of autologous sympathetic ganglion can be a therapeutic modality for Parkinson's disease.

Patients with idiopathic Parkinson's disease who had become refractory to medical treatment underwent unilateral stereotactic transplantation of mesencephalic tissue obtained from 7- to 9-week-old postconception fetuses. Small pieces of tissue, less than 1 mm, were deposited in 9 sites in the putamen and 3 in the caudate. Patients were 4 men and 3 women and aged from 42 to 59 years (mean 50). Symptom durations were from 9 to 21 years (mean 14). The examinations were done at 3- to 4-month intervals pre- and postoperatively. Patients were examined for a minimum of 1 year postoperatively. The examinations consisted of neurological and general physical examinations, UCLA Parkinson's Disability Scale, Hoehn and Yahr rating and United Parkinson's Disease Rating Scale (PDRS), all in both 'on' and 'off' states. Video recordings and timed tests of a number of motor tests were performed. Patients also completed 7 consecutive days of hourly self-assessments prior to each visit. Fluorodopa PET scans were obtained pre- and 6 and 15 months postoperatively. The operations took place from mid-July 1992 to January 1993. Postoperative states have been free of complications. All have been on immunosuppressants. Levodopa was transiently decreased in the postoperative period, but raised to approximately the preoperative level thereafter. In late March 1993, 3 patients appeared to show modest improvement in the UCLA and UPDRS scales and in the patients' self-assessments.

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.

Central nervous system transplantation currently is being investigated in numerous centers throughout the world. The concept of restoring lost neurological function by grafting neuronal or neuronal-like tissue into the CNS has the potential for revolutionizing the treatment of numerous neurological disorders. Parkinson's disease is the subject of the majority of CNS transplantation studies although the first human studies were disappointing. However, further refinements of technique and patient selection, and animal research using a newly developed primate model of parkinsonism, led to promising results reported from several centers. Despite this, numerous fundamental issues have yet to be resolved: (1) age of patient? (2) degree of disability of patient? (3) use of fetal or adrenal tissue? (4) caudate or putamen placement? and (5) open or stereotactic surgery? This report reviews the clinically significant results of nonhuman primate research and clinical studies, and addresses these unresolved issues.

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.