The impact of white matter lesions on the cognitive outcome of subthalamic nucleus deep brain stimulation in Parkinson's disease.

OBJECTIVES: White Matter lesions (WML) are a risk factor for cognitive impairment in Parkinson's disease. There is no clear evidence of reduced general cognitive function after DBS. However, a subgroup of patients develops dementia rapidly after DBS despite careful patient selection processes. The aim of this study was to evaluate the load of WML as a possible risk factor for cognitive decline following STN DBS. PATIENTS AND METHODS: 40 PD-patients receiving bilateral STN-DBS were followed at least three years after surgery to detect dementia. All patients underwent comprehensive neuropsychological assessment and MRI before surgery. The extent of WML was assessed using an automated approach. WML volume was correlated to the onset of dementia and the decline of a cognitive composite score retrospectively. RESULTS: Patients with a rapid onset of dementia within one, respective three following DBS showed significant higher WML volumes compared to cognitive normal and MCI patients (55.8cm3±18.836 vs. 9.3cm3±12.2; p=0.002). The same significant association was found in a multivariable model, including the covariables age, gender and PD disease duration (p=0.01). WML volume was associated to the rate of decline in cognitive composite score within three years after DBS surgery (p=0.006; R2=0.40) after correction for age. CONCLUSIONS: Damaged white matter may lead to a reduced compensation of disconnections in cognitive circuits caused by the implantation of the DBS electrodes or by chronic stimulation. The role of WML as a prognostic factor for the cognitive outcome after DBS may be underestimated. The WML burden should be taken seriously in preoperative risk stratification.

Anesthesiologic regimen and intraoperative delirium in deep brain stimulation surgery for Parkinson's disease.

BACKGROUND: In many centers the standard anesthesiological care for deep brain stimulation (DBS) surgery in Parkinson's disease patients is an asleep-awake-asleep procedure. However, sedative drugs and anesthetics can compromise ventilation and hemodynamic stability during the operation and some patients develop a delirious mental state after the initial asleep phase. Further, these drugs interfere with the patient's alertness and cooperativeness, the quality of microelectrode recordings, and the recognition of undesired stimulation effects. In this study, we correlated the incidence of intraoperative delirium with the amount of anesthetics used intraoperatively. METHODS: The anesthesiologic approach is based on continuous presence and care, avoidance of negative suggestions, use of positive suggestions, and utilization of the patient's own resources. Clinical data from the operations were analyzed retrospectively, the occurrence of intraoperative delirium was extracted from patients' charts. The last 16 patients undergoing the standard conscious sedation procedure (group I) were compared to the first 22 (group II) psychologically-guided patients. RESULTS: The median amount of propofol decreased from 146 mg (group I) to 0mg (group II), remifentanyl from 0.70 mg to 0.00 mg, respectively (P<0.001 for propofol and remifentanyl). Using the new procedure, 12 of 22 patients (55%) in group II required no anesthetics. Intraoperative delirium was significantly less frequent in group II (P=0.03). CONCLUSIONS: The occurrence of intraoperative delirium correlates with the amount of intraoperative sedative and anesthetic drugs. Sedation and powerful analgesia are not prerequisites for patients' comfort during awake-DBS-surgery.

Outcome-related co-factors in 105 cases of vertebral osteomyelitis in a tertiary care hospital.

PURPOSE: Vertebral osteomyelitis (VO) is an infection of the vertebral body and the adjacent disc space. The aim of our study was to identify outcome-related co-factors of patients with VO treated in the last decade. METHODS AND RESULTS: We retrospectively identified 105 patients with VO (mean age 66.1 years) who had been treated at our institution from 2004 to 2011. The median time of hospitalization at our institution was 31.5 days, and 44 patients required intensive medical care. Back pain and fever were documented in 66.7 and 33.3 % of cases, respectively. The radiologic diagnosis of VO was made in 94.8 % of all obtained magnetic resonance imaging scans and in 66.2 % of all computed tomography (CT) scans. Biopsies were taken in 71 patients, and the causative organisms were identified in 56.2 % of patients, with Staphylococcus aureus being the predominant pathogen. Fifty-six patients underwent surgical treatment. During hospitalization, infectious complications were observed in 63 patients (60.0 %). The most common complications were psoas, paravertebral and epidural abscesses. Patients with S. aureus infections had a significantly higher rate of infectious complications than those without (76.5 vs. 40.3 %, respectively), and were more frequently treated in intensive care units (58.8 vs. 34.7 %, respectively). Overall in-hospital mortality rate was 12.4 %. Elevated C-reactive protein levels at admission, advanced age and a Charlson Comorbidity Index of ≥2 were associated with higher mortality. CONCLUSIONS: Magnetic resonance imaging currently is the imaging procedure of choice for the radiologic diagnosis of VO. Mortality is attributable in part to co-morbidities. However, infections with S. aureus are frequent in this patient population and are associated with a higher rate of complications and a trend towards higher mortality.

Improving the spatial accuracy in functional magnetic resonance imaging (fMRI) based on the blood oxygenation level dependent (BOLD) effect: benefits from parallel imaging and a 32-channel head array coil at 1.5 Tesla.

Geometric distortions and low spatial resolution are current limitations in functional magnetic resonance imaging (fMRI). The aim of this study was to evaluate if application of parallel imaging or significant reduction of voxel size in combination with a new 32-channel head array coil can reduce those drawbacks at 1.5 T for a simple hand motor task. Therefore, maximum t-values (tmax) in different regions of activation, time-dependent signal-to-noise ratios (SNR(t)) as well as distortions within the precentral gyrus were evaluated. Comparing fMRI with and without parallel imaging in 17 healthy subjects revealed significantly reduced geometric distortions in anterior-posterior direction. Using parallel imaging, tmax only showed a mild reduction (7-11%) although SNR(t) was significantly diminished (25%). In 7 healthy subjects high-resolution (2 x 2 x 2 mm3) fMRI was compared with standard fMRI (3 x 3 x 3 mm3) in a 32-channel coil and with high-resolution fMRI in a 12-channel coil. The new coil yielded a clear improvement for tmax (21-32%) and SNR(t) (51%) in comparison with the 12-channel coil. Geometric distortions were smaller due to the smaller voxel size. Therefore, the reduction in tmax (8-16%) and SNR(t) (52%) in the high-resolution experiment seems to be tolerable with this coil. In conclusion, parallel imaging is an alternative to reduce geometric distortions in fMRI at 1.5 T. Using a 32-channel coil, reduction of the voxel size might be the preferable way to improve spatial accuracy.

Adult neurogenesis in serotonin transporter deficient mice.

Serotonin (5-HT) is a regulator of morphogenetic activities during early brain development and neurogenesis, including cell proliferation, migration, differentiation, and synaptogenesis. The 5-HT transporter (5-HTT, SLC6A4) mediates high-affinity reuptake of 5-HT into presynaptic terminals and thereby fine-tunes serotonergic neurotransmission. Inactivation of the 5-HTT gene in mice reduces 5-HT clearance resulting in persistently increased concentrations of synaptic 5-HT. In the present study, we investigated the effects of elevated 5-HT levels on adult neurogenesis in the hippocampus of 5-HTT deficient mice, including stem cell proliferation, survival, and differentiation. Using an in vivo approach, we showed an increase in proliferative capacity of hippocampal adult neural stem cells in aged 5-HTT knockout mice (approximately 14.5 months) compared to wildtype controls. In contrast, in vivo and additional in vitro analyses of younger adult 5-HTT knockout mice (approximately 7 weeks and approximately 3.0 months) did not reveal significant changes in proliferation of neural stem cells or survival of newborn cells. We showed that the cellular fate of newly generated cells in 5-HTT knockout mice is not different with respect to the total number and percentage of neurons or glial cells from wildtype controls. Our findings indicate that elevated synaptic 5-HT concentration throughout early development and later life of 5-HTT deficient mice does not induce adult neurogenesis in adult mice, but that elevated 5-HT levels in aged mice influence stem cell proliferation.