Deane B. Jacques

Quantitative proton-decoupled 31P MRS and 1H MRS in the evaluation of Huntington's and Parkinson's diseases

Objective: To determine cerebral energy status in patients with Huntingtons disease(HD) and Parkinsons disease (PD). Methods: The study included 15 patients with DNA-proven, symptomatic HD and five patients with medically treated, idiopathic PD, all of whom were candidates for neurotransplant treatment, as well as 20 age-related normal subjects. Quantitative noninvasive, MRI-guided proton MRS was performed of single volumes in putamen of basal ganglia (BG), occipital gray matter, and posterior parietal white matter; in addition, quantitative phosphorus and proton-decoupled phosphorus MRS of superior biparietal white and gray matter was done. Outcome measures were quantitative metabolite ratios and millimolar concentrations of neuronal and glial markers, creatine (Cr) and adenosine triphosphate (ATP), and intracellular pH. Results: In volume-corrected control BG (10.46 ± 0.37 mM), [Cr] was 29%(p < 0.05) higher than in control gray matter (8.10 ± 1.04 mM). In HD and PD, energy metabolism was not abnormal in the four cerebral locations measured by MRS. No increase in cerebral lactate or decrease in phosphocreatine and ATP was detected. Small, systematic abnormalities in N-acetylaspartate (NAA, ddecreased), Cr (decreased), choline-containing compounds (Cho, increased), and myoinositol (mI, increased) were demonstrable in all patients individually and in summed spectra but were insufficient to make diagnosis possible in the individual patient. Conclusion: Previously described failure of global energy metabolism in HD was not confirmed. However, quantitative 1-hydrogen MRS and decoupled 31-phosphorus MRS are sensitive to ±10% alterations in key cerebral metabolites, and may be of value in noninvasive monitoring of appropriate therapies.

In vivo magnetic resonance spectroscopy of human fetal neural transplants.

To better define the survival and cellular composition of human fetal neurotransplants in vivo, we performed quantitative 1H MRS to determine the concentration of the neuronal amino acid [N‐acetylaspartate] within MRI‐visible grafts. In all, 71 grafts in 38 patients [24 Parkinsons disease (PD), 14 Huntingtons disease (HD)] were examined, as well as 24 untreated PD and HD patients and 13 age‐matched normal controls. MRI appearances of edema were present in three out of 71 grafts, the remainder being consistent with histologically identified viable neural transplant tissue. N‐acetylaspartate (NAA), creatine, choline, myoinositol and glutamine plus glutamate (Glx) were identified in all post‐transplant putamens, with abnormal metabolites, lactate and/or lipid detectable in only three patients. Of 71 grafts, 19 occupied more than 60% of the MRS‐examined volume (VOI) (mean 84.2 ± 3%; range 61–100%). In those, [NAA] was 8.50 ± 0.99 mM in eight PD spectra and 6.59 ± 0.81 mM in 11 HD spectra, and was not significantly different from controls. In contrast, transplanted fetal neurones contain less than 0.4 mM of the neuronal amino acid NAA. This suggests that established fetal neurotransplants in the human putamen of both PD and HD patients are populated by adult neurones, axons and dendrites. Copyright

Gamma Knife Thalamotomy for the Treatment of Persistent Pain

Twenty patients who suffered persistent intractable pain from a variety of disorders underwent medial thalamotomy with the Leksell Gamma Knife. The lesions were directed at the intralaminar nuclei, the lateral portion of the medial dorsal nucleus, the centromedian and the parafascicular nuclei. Lesions were made with radiation doses from 140 to 180 Gy using a 4-mm beam collimator helmet and either a single isocenter (1 patient), two isocenters (17 patients) or three isocenters (2 patients). Two thirds of the patients experienced either excellent or good pain relief in a follow-up period between 1 and 22 months. One patient showed temporary complications which resolved, and 2 other patients also suffered complications which currently are improving. One patient died due to radiation necrosis following a bilateral thalamotomy. Gamma Knife thalamotomy may offer a potentially safe and effective alternative for the treatment of certain difficult persistent pain problems.

Immunotherapy for recurrent malignant glioma: an interim report on survival

We present interim survivial data, for a group of 83 adult patients with recurrent malignant glioma treated by implanting stimulated autologous lymphocytes into the tumour bed following surgical debulking. The patients were treated 6 months or more prior to data analysis. Fifty-nine patients were male and 24 female. The mean age for the entire group was 48.4 years and the mean Karnofsky rating (KR) was 67.2. Eight of the patients had grade II tumours, 33 had grade III tumours and 42 had grade IV tumours. Statistical analysis focuses on tumour grade, KR and patient age, factors that have been shown to affect survival in previous studies. Multifactorial analyses are employed to identify interrelationships among factors related to survival. Seven patients (8%) did not respond to immunotherapy, 76 (92%) had a good initial response. Twenty-five patients (30.1%) are living and 18 (22%) have shown no evidence of recurrence. Results are evaluated in the light of those obtained in trials of other experimental therapies for recurrent malignant gliomas. It is concluded that the present protocol offers a safe and comparatively effective treatment option.

Outcomes and Complications of Fetal Tissue Transplantation in Parkinson’s Disease

This study was undertaken to investigate the outcomes, complication rates and risk factors of stereotactic intrastriatal neurotransplantation for Parkinson’s disease (PD). Bilateral stereotactic neurotransplantation was performed (as previously described) in 60 patients with idiopathic PD. Clinical outcome was evaluated using the Unified Parkinson’s Disease Rating Scale (UPDRS). The incidence of complication was evaluated by retrospective analysis of the clinical outcomes of the transplanted patients. Patients demonstrated significant improvement in UPDRS scores 12 months after transplantation. Nine patients experienced adverse effects after neurotransplantation, 3 requiring surgical intervention. Patients showed a significant overall improvement and no greater incidence of risk than that of other intracranial procedures.

Metabolic response of glioblastoma to adoptive immunotherapy: detection by phosphorus MR spectroscopy.

In a patient with cerebral glioblastoma, metabolic disturbances were detected within the tumor and in the surrounding brain. Within the volume occupied by the tumor, phosphocreatine (PCr)/adenosine triphosphate was reduced and inorganic phosphate/PCr elevated, indicative of tissue necrosis. Loss of total 31P signal was consistent with reduced metabolite content within the area of tumor defined by CT and magnetic resonance (MR). These studies were accomplished with 31P MR spectroscopy at 2 T, using a volume head coil and the technique of two-dimensional phase-encoding to map regional metabolism across the entire cerebral cortex in voxels of 30 cm3. Using the same method, only minor variations in 31P metabolism were noted in six normal controls. Treatment with locally placed Interleukin-2 activated lymphocytes resulted in changes in both MR and 31P MR spectroscopy in the region of the tumor.

Gamma Knife Radiosurgery for Metastatic Brain Tumors

Sixty-three patients with metastatic brain tumors have had stereotactic radiosurgery 90 times with the Leksell Gamma Knife over a 29-month period. Initially, a single treatment of 35 to 45 Gy was delivered to the enhanced CT margin. This dose was found to be inadequate for tumor control. We then raised the marginal dose to 50 to 55 Gy, but even this radiosurgical dose did not appear to control tumor growth. However, we have found that metastatic brain tumors can be controlled successfully using enhanced MR scans and a peripheral dose of 60 Gy or even 65 Gy adjacent to the enhanced margins of the metastatic brain tumors, especially melanomas.