Patient perception and satisfaction in awake burr hole trepanation under local anesthesia for evacuation of chronic subdural hematoma.

Evacuation of chronic subdural hematoma (CSDH) will be one of the most common neurosurgical procedures in the future in the increasingly aging societies. Performing cranial surgery on awake patients may place a psychological burden on them. Aim of this study was to evaluate the psychological distress of patients during awake CSDH relief. Patients with awake evacuation of CSDH via burr hole trepanation were included in our monocentric prospective study. Patient perception and satisfaction were measured using standardized surveys 3-5 days and 6 months after surgery. Among other questionnaires, the Hospital Anxiety and Depression and the Impact of Event Scale, were used to quantify patients' stress. A total of 50 patients (mean age 72.9 years (range 51 - 92)) were included. During surgery, 28 patients reported pain (mean 4.1 (SD 3.3)). Postoperatively, 26 patients experienced pain (mean 2.7 (SD 2.6)). Patients' satisfaction with intraoperative communication was reported with a mean of 8.3 (SD 2.1). There was a significant negative correlation between intraoperatively perceived pain and satisfaction with intraoperative communication (p = 0.023). Good intraoperative communication during evacuation of CSDH in awake patients is associated with positive patient perception and correlates with pain reduction.

Diesterified derivatives of 5-iodo-2'-deoxyuridine as cerebral tumor tracers.

With the aim to develop beneficial tracers for cerebral tumors, we tested two novel 5-iodo-2'-deoxyuridine (IUdR) derivatives, diesterified at the deoxyribose residue. The substances were designed to enhance the uptake into brain tumor tissue and to prolong the availability in the organism. We synthesized carrier added 5-[125I]iodo-3',5'-di-O-acetyl-2'-deoxyuridine (Ac2[125I]IUdR), 5-[125I]iodo-3',5'-di-O-pivaloyl-2'-deoxyuridine (Piv2[125I]IUdR) and their respective precursor molecules for the first time. HPLC was used for purification and to determine the specific activities. The iodonucleoside tracer were tested for their stability against human thymidine phosphorylase. DNA integration of each tracer was determined in 2 glioma cell lines (Gl261, CRL2397) and in PC12 cells in vitro. In mice, we measured the relative biodistribution and the tracer uptake in grafted brain tumors. Ac2[125I]IUdR, Piv2[125I]IUdR and [125I]IUdR (control) were prepared with labeling yields of 31-47% and radiochemical purities of >99% (HPLC). Both diesterified iodonucleoside tracers showed a nearly 100% resistance against degradation by thymidine phosphorylase. Ac2[125I]IUdR and Piv2[125I]IUdR were specifically integrated into the DNA of all tested tumor cell lines but to a less extend than the control [125I]IUdR. In mice, 24 h after i.p. injection, brain radioactivity uptakes were in the following order Piv2[125I]IUdR>Ac2[125I]IUdR>[125I]IUdR. For Ac2[125I]IUdR we detected lower amounts of radioactivities in the thyroid and stomach, suggesting a higher stability toward deiodination. In mice bearing unilateral graft-induced brain tumors, the uptake ratios of tumor-bearing to healthy hemisphere were 51, 68 and 6 for [125I]IUdR, Ac2[125I]IUdR and Piv2[125I]IUdR, respectively. Esterifications of both deoxyribosyl hydroxyl groups of the tumor tracer IUdR lead to advantageous properties regarding uptake into brain tumor tissue and metabolic stability.

Adult neurogenesis and Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder characterized by a progressive neuronal loss affecting preferentially the dopaminergic neurons of the nigrostriatal projection. Transplantation of fetal dopaminergic precursor cells has provided the proof of principle that a cell replacement therapy can ameliorate clinical symptoms in affected patients. Recent years have provided evidence for the existence of neural stem cells with the potential to produce new neurons, particularly of a dopaminergic phenotype, in the adult mammalian brain. Such stem cells have been identified in so called neurogenic brain areas, where neurogenesis is constitutively ongoing, but also in primarily non-neurogenic areas, such as the midbrain and the striatum, where neurogenesis does not occur under normal physiological conditions. We review here presently published evidence to evaluate the concept that endogenous neural stem cells may have the potential to be instrumentalized for a non-invasive cell replacement therapy with autologous neurons to repair the damaged nigrostriatal dopaminergic projection in Parkinson's disease.

Dopaminergic substantia nigra neurons project topographically organized to the subventricular zone and stimulate precursor cell proliferation in aged primates.

The subventricular zone of the adult primate brain contains neural stem cells that can produce new neurons. Endogenous neurogenesis might therefore be used to replace lost neurons in neurodegenerative diseases. This would require, however, a precise understanding of the molecular regulation of stem cell proliferation and differentiation in vivo. Several regulatory factors, including dopamine, have been identified in rodents, but none in primates. We have, therefore, studied the origin and function of the dopaminergic innervation of the subventricular zone in nonhuman primates. Tracing experiments in three macaques revealed a topographically organized projection from the substantia nigra pars compacta (SNpc), but not the adjacent retrorubral field, to the subventricular zone: the anteromedial SNpc projects to the anteroventral subventricular zone, the posterolateral SNpc to the posterodorsal subventricular zone. Double immunolabeling for tyrosine hydroxylase and BrdU (5-bromo-2'deoxyuridine) incorporated into the DNA of proliferating cells showed that dopaminergic fibers approach proliferating cells in the subventricular zone. We investigated the effect of this nigro-subventricular projection on cell proliferation in six aged macaques, because the rate of neurogenesis differs between young adult and aged primates and because neurodegenerative diseases mainly affect aged humans. Three macaques were treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to decrease dopaminergic innervation of the subventricular zone. A significant decrease in the number of PCNA+ (proliferating cell nuclear antigen-positive) proliferating cells (-44%) and PSA-NCAM(+) (polysialylated neural cell adhesion molecule-positive) neuroblasts (-59%) was found in the denervated regions of the subventricular zone, suggesting that an intact dopaminergic nigro-subventricular innervation is crucial for sustained neurogenesis in aged primates.