Can intraoperative clinical testing predict the effects of the permanent DBS electrode in the subthalamic nucleus?

Background and Objectives: Intraoperative test stimulation is established to optimize target localization in STN DBS, but requires a time-consuming awake surgery in off-medication state. The aim of this study was to evaluate whether stimulation-induced effects of the permanent electrode are predictable by intraoperative test stimulation. Methods: 59 PD-patients receiving bilateral STN-DBS were clinically examined with stepwise increasing monopolar stimulation during surgery and DBS programming at matched stimulation depths. Thresholds of therapeutic effects on rigidity, tremor, akinesia as well as threshold and categories of side effects as dysarthria, paraesthesia, oculomotor dysfunction, autonomic and capsular effects were obtained from standardized examination protocols retrospectively. Results: The central trajectory was chosen in 48.3% for implantation of the final electrode. Postoperative stimulation via the permanent electrode caused any category of side effect at a significantly lower threshold than predicted during intraoperative test stimulation (p<0,001); whereas sufficient therapeutic effects were achieved at significantly higher thresholds. The category of side effects differed frequently in individual patients, only 33.5% of intraoperative side effects were reproducible in their category with permanent stimulation. Conclusions: Stimulation-induced therapeutic and side effects do not seem to be reliably predictable by intraoperative test stimulation concerning their thresholds and even their categories. Hence intraoperative testing may lead to an overestimation of the therapeutic window

Benefit of ELISpot in early diagnosis of tuberculous meningoencephalitis: Case report and literature review

Tuberculous meningitis and meningoencephalitis are rare and dangerous complications of infections with mycobacteria-complex. Usually these are complications of systemic florid infection with Mycobacterium (M.) tuberculosis. They are most often seen in immune compromised patients. The confirmation of diagnosis can be elaborate and delayed due to long-term culture requirements for M. tuberculosis. We present a female patient, without history of immunosuppression, who was diagnosed with tuberculous meningoencephalitis using ELISpot to detect immune reactivity against mycobacterial antigens with lymphocytes from cerebrospinal fluid (CSF). ELISpot with CSF derived lymphocytes seems to be an appropriate method to diagnose tuberculous meningitis and meningoencephalitis and to make therapeutic decisions easier and earlier in atypical cases of infection with M. tuberculosis

Educational attainment and motor burden in advanced Parkinson's disease – The emerging role of education in motor reserve

Objective: To explore the relationship of motor burden and educational attainment in patients with advanced stage PD. Materials and methods: We included 102 consecutive patients who underwent a complete evaluation for DBS surgery, including detailed neuropsychological testing and UPDRSIII in a standardized Levodopa challenge. Years of education (YoE) were calculated as the highest grade attained in secondary school plus years for post-secondary training. Results: The OFF medication UPDRS-III score was associated with YoE (p = 0.006; t = -2.82) and age (p = 0.007; t = -2.75) in our multivariable linear regression model even while including disease duration (p = 0.8; t = 0.21), presence of mild cognitive impairment (MCI) (p = 0.9; t = 0.16) or current IQ (p = 0.2; t = 1.25) as additional covariables. In a subgroup of 60 patients two years after DBS, the ON/ON UPDRS score was associated with YoE (p = 0.01; t = -2.42) and diagnosis of PD dementia (p = 0.05, t = 1.95), while age (p = 0.08, t = 1.75), disease duration (p = 0.6 t = 0.48) and LEDD (p = 0.3; t = 1.05) showed no significant association to ON/ON UPDRS score. Conclusions: We found an inverse correlation between years of education and lower (better) UPDRS-III motor score after adjusting for important covariables. Education may lead to an increased ability to compensate disturbances in basal ganglia circuits affecting not only for cognitive, but also for motor aspects of PD. Thus, educational attainment may play an important role in the concept of motor reserve

Saccadic Impairments in Patients with the Norrbottnian Form of Gaucher’s Disease Type 3

BackgroundChronic neuronopathic Gaucher’s disease type 3 (GD3) is relatively frequent in northern Sweden. Besides multiple other neurological symptoms, horizontal gaze palsy or oculomotor apraxia is common in GD3.ObjectiveTo characterize the saccades in patients with Norrbottnian GD3 with respect to their neurological and cognitive status using a computer-based eye-tracking technique.MethodsHorizontal and vertical reflexive saccades as well as antisaccades of nine GD3 patients [4M/5F; 41.1 ± 11.0 years; modified severity scoring tool (mSST): 9.3 ± 5.4; Montreal Cognitive Assessment (MoCA): 24.0 ± 4.2] and age-matched controls were analyzed using EyeBrain T2, a head-mounted binocular eye tracker. Systematic clinical assessment included the mSST, a valid tool for monitoring the neurological progression in GD3 and MoCA.ResultsIn Norrbottnian GD3 patients, gain, peak, and average velocity (107.5°/s ± 41.8 vs. 283.9°/s ± 17.0; p = 0.0009) of horizontal saccades were reduced compared to healthy controls (HCs). Regarding vertical saccades, only the average velocity of downward saccades was decreased (128.6°/s ± 63.4 vs. 244.1°/s ± 50.8; p = 0.004). Vertical and horizontal saccadic latencies were increased (294.3 ms ± 37.0 vs. 236.5 ms ± 22.4; p = 0.005) and the latency of horizontal reflexive saccades was correlated with the mSST score (R2 = 0.80; p = 0.003). The latency of antisaccades showed association to MoCA score (R2 = 0.70; p = 0.009). GD3 patients made more errors in the antisaccade task (41.5 ± 27.6% vs. 5.2 ± 5.8%; p = 0.005), and the error rate tended to correlate with the cognitive function measured in MoCA score (p = 0.06).ConclusionThe mean age of 41 years of our GD3 cohort reflects the increased life expectancy of patients in the Norrbottnian area compared to other GD3 cohorts. Marked impairment of horizontal saccades was evident in all patients, whereas vertical saccades showed distinct impairment of downward velocity. Latency of reflexive saccades was associated with the severity of neurological symptoms. Increased latency and error rate in the antisaccade task were linked to cognitive impairment. The assessment of saccades provides markers for neurological and neuropsychological involvement in Norrbottnian GD3

Intraoperative clinical testing overestimates the therapeutic window of the permanent DBS electrode in the subthalamic nucleus

Intraoperative test stimulation is established to optimize target localization in STN DBS, but requires a time-consuming awake surgery in off-medication state. The aim of this study was to compare the thresholds of stimulation-induced effects of test stimulation and the permanent electrode. Fifty-nine PD patients receiving bilateral STN DBS were clinically examined with stepwise increasing monopolar stimulation during surgery and DBS programming at matched stimulation depths. Thresholds of therapeutic and side effects were obtained from standardized examination protocols. Postoperative stimulation via the permanent electrode caused side effects at a significantly lower threshold than predicted during intraoperative test stimulation (P < 0.001); whereas sufficient therapeutic effects were achieved at significantly higher thresholds (P < 0.001). Intraoperative testing may lead to an overestimation of the therapeutic window. The two different electrodes lead to distinct spreading of the electric field in the STN and surrounding tissues that causes different volume of tissue activated (VTA). Clinicians involved in DBS surgery and programming should be aware of the differences in both stimulation settings, concerning electrodes geometry, stimulation modes as well as the impact of time. Therapeutic and side effects of permanent stimulation are not predictable by intraoperative test stimulation. Test stimulation may be an orientating test for very low thresholds of side effects instead

Winters are changing: snow effects on Arctic and alpine tundra ecosystems

Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions and moisture availability during winter. It also affects the growing season’s start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover’s role for vegetation, plant-animal interactions, permafrost conditions, microbial processes and biogeochemical cycling. We also compare studies of natural snow gradients with snow manipulation studies, altering snow depth and duration, to assess time scale difference of these approaches. The number of studies on snow in tundra ecosystems has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. In specific, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by manipulative studies (average 7.9 days advance, 5.5 days delay) were substantially lower than those observed over spatial gradients (mean range of 56 days) or due to interannual variation (mean range of 32 days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates

Winters are changing: snow effects on Arctic and alpine tundra ecosystems

Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions, and moisture availability during winter. It also affects the growing season’s start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover’s role for vegetation, plant-animal interactions, permafrost conditions, microbial processes, and biogeochemical cycling. We also compare studies of natural snow gradients with snow experimental manipulation studies to assess time scale difference of these approaches. The number of tundra snow studies has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. Specifically, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by snow addition and snow removal manipulations (average 7.9&nbsp;days advance and 5.5&nbsp;days delay, respectively) were substantially lower than the temporal variation over natural spatial gradients within a given year (mean range 56&nbsp;days) or among years (mean range 32&nbsp;days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates

Winters are changing:snow effects on Arctic and alpine tundra ecosystems

Abstract Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions, and moisture availability during winter. It also affects the growing season’s start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover’s role for vegetation, plant-animal interactions, permafrost conditions, microbial processes, and biogeochemical cycling. We also compare studies of natural snow gradients with snow experimental manipulation studies to assess time scale difference of these approaches. The number of tundra snow studies has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. Specifically, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by snow addition and snow removal manipulations (average 7.9 days advance and 5.5 days delay, respectively) were substantially lower than the temporal variation over natural spatial gradients within a given year (mean range 56 days) or among years (mean range 32 days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates