SARS-CoV2 evokes structural brain changes resulting in declined executive function.

BACKGROUND: Several research has underlined the multi-system character of COVID-19. Though effects on the Central Nervous System are mainly discussed as disease-specific affections due to the virus' neurotropism, no comprehensive disease model of COVID-19 exists on a neurofunctional base by now. We aimed to investigate neuroplastic grey- and white matter changes related to COVID-19 and to link these changes to neurocognitive testings leading towards a multi-dimensional disease model. METHODS: Groups of acutely ill COVID-19 patients (n = 16), recovered COVID-19 patients (n = 21) and healthy controls (n = 13) were prospectively included into this study. MR-imaging included T1-weighted sequences for analysis of grey matter using voxel-based morphometry and diffusion-weighted sequences to investigate white matter tracts using probabilistic tractography. Comprehensive neurocognitive testing for verbal and non-verbal domains was performed. RESULTS: Alterations strongly focused on grey matter of the frontal-basal ganglia-thalamus network and temporal areas, as well as fiber tracts connecting these areas. In acute COVID-19 patients, a decline of grey matter volume was found with an accompanying diminution of white matter tracts. A decline in executive function and especially verbal fluency was found in acute patients, partially persisting in recovered. CONCLUSION: Changes in gray matter volume and white matter tracts included mainly areas involved in networks of executive control and language. Deeper understanding of these alterations is necessary especially with respect to long-term impairments, often referred to as 'Post-COVID'.

Amelioration of Parkinsonian tremor evoked by DBS: which role play cerebello-(sub)thalamic fiber tracts?

BACKGROUND: Current pathophysiological models of Parkinson's disease (PD) assume a malfunctioning network being adjusted by the DBS signal. As various authors showed a main involvement of the cerebellum within this network, cerebello-cerebral fiber tracts are gaining special interest regarding the mediation of DBS effects. OBJECTIVES: The crossing and non-decussating fibers of the dentato-rubro-thalamic tract (c-DRTT/nd-DRTT) and the subthalamo-ponto-cerebellar tract (SPCT) are thought to build up an integrated network enabling a bidimensional communication between the cerebellum and the basal ganglia. The aim of this study was to investigate the influence of these tracts on clinical control of Parkinsonian tremor evoked by DBS. METHODS: We analyzed 120 electrode contacts from a cohort of 14 patients with tremor-dominant or equivalence-type PD having received bilateral STN-DBS. Probabilistic tractography was performed to depict the c-DRTT, nd-DRTT, and SPCT. Distance maps were calculated for the tracts and correlated to clinical tremor control for each electrode pole. RESULTS: A significant difference between "effective" and "less-effective" contacts was only found for the c-DRTT (p = 0.039), but not for the SPCT, nor the nd-DRTT. In logistic and linear regressions, significant results were also found for the c-DRTT only (pmodel logistic = 0.035, ptract logistic = 0,044; plinear = 0.027). CONCLUSIONS: We found a significant correlation between the distance of the DBS electrode pole to the c-DRTT and the clinical efficacy regarding tremor reduction. The c-DRTT might therefore play a major role in the mechanisms of alleviation of Parkinsonian tremor and could eventually serve as a possible DBS target for tremor-dominant PD in future.

Deep brain stimulation for treatment resistant obsessive compulsive disorder; an observational study with ten patients under real-life conditions.

Introduction: Obsessive-compulsive disorder (OCD) affects 2-3% of the global population, causing distress in many functioning levels. Standard treatments only lead to a partial recovery, and about 10% of the patients remain treatment-resistant. Deep brain stimulation offers a treatment option for severe, therapy-refractory OCD, with a reported response of about 60%. We report a comprehensive clinical, demographic, and treatment data for patients who were treated with DBS in our institution. Methods: We offered DBS to patients with severe chronic treatment resistant OCD. Severity was defined as marked impairment in functioning and treatment resistance was defined as non-response to adequate trials of medications and psychotherapy. Between 2020 and 2022, 11 patients were implanted bilaterally in the bed nucleus of stria terminalis (BNST). Patients were evaluated with YBOCS, MADRS, GAF, CGI, and WHOQOL-BREF. We performed the ratings at baseline (before surgery), after implantation before the start of the stimulation, after reaching satisfactory stimulation parameters, and at follow-up visits 3, 6, 9, and 12 months after optimized stimulation. Results: One patient has retracted his consent to publish the results of his treatment, thus we are reporting the results of 10 patients (5 males, 5 females, mean age: 37 years). Out of our 10 patients, 6 have shown a clear response indicated by a YBOCS-reduction between 42 and 100 percent at last follow-up. One further patient experienced a subjectively dramatic effect on OCD symptoms, but opted afterwards to stop the stimulation. The other 3 patients showed a slight, non-significant improvement of YBOCS between 8.8 and 21.9%. The overall mean YBOCS decreased from 28.3 at baseline to 13.3 (53% reduction) at the last follow-up. The improvement of the OCD symptoms was also accompanied by an improvement of depressive symptoms, global functioning, and quality of life. Conclusion: Our results suggest that BNST-DBS can be effective for treatment-resistant OCD patients, as indicated by a reduction in symptoms and an overall improvement in functioning. Despite the need for additional research to define the patients' selection criteria, the most appropriate anatomical target, and the most effective stimulation parameters, improved patient access for this therapy should be established.

Factors influencing the reliability of intraoperative testing in deep brain stimulation for Parkinson's disease.

BACKGROUND: Several meta-analyses comparing the outcome of awake versus asleep deep brain stimulation procedures could not reveal significant differences concerning the postoperative improvement of motor symptoms. Only rarely information on the procedural details is provided for awake operations and how often somnolence and disorientation occurred, which might hamper the reliability of intraoperative clinical testing. The aim of our study was to investigate possible influencing factors on the occurrence of somnolence and disorientation in awake DBS procedures. METHODS: We retrospectively analyzed 122 patients with Parkinson's disease having received implantation of a DBS system at our centre. Correlation analyses were performed for the duration of disease prior to surgery, number of microelectrode trajectories, AC-PC-coordinates of the planned target, UPDRS-scores, intraoperative application of sedative drugs, duration of the surgical procedure, perioperative application of apomorphine, and the preoperative L-DOPA equivalence dosage with the occurrence of intraoperative somnolence and disorientation. RESULTS: Patients with intraoperative somnolence were significantly older (p=0.039). Increased duration of the DBS procedure (p=0.020), delayed start of the surgery (p=0.049), higher number of MER trajectories (p=0.041), and the patients' % UPDRS improvement (p=0.046) also correlated with the incidence of intraoperative somnolence. We identified the main contributing factor to intraoperative somnolence as the use of sedative drugs applied during skin incision and burr hole trepanation (p=0.019). Perioperatively applied apomorphine could reduce the occurrence of somnolent phases during the operation (p=0.026). CONCLUSION: Several influencing factors were found to seemingly increase the risk of intraoperative somnolence and disorientation, while the use of sedative drugs seems to be the main contributing factor. We argue that awake DBS procedures should omit the use of sedatives for best clinical outcome. When reporting on awake DBS surgery these factors should be considered and adjusted for, to permit reliable interpretation and comparison of DBS study results.

Analysis of Functional Neuroplastic Changes in the Cortical Language System in Relation to Different Growth Patterns of Glioblastoma.

The interpretation of fMRI data in glioblastoma (GB) is challenging as these tumors exhibit specific hemodynamic processes which, together with malignancy, tumor volume and proximity to eloquent cortex areas, may lead to misinterpretations of fMRI signals. The aim of this study was to investigate if different radiologically defined GB tumor growth patterns may also influence the fMRI signal, activation pattern and functional connectivity differently. Sixty-four patients with left-hemispheric glioblastoma were included and stratified according to their radiologically defined tumor growth pattern into groups with a uniform (U-TGP) or diffuse tumor growth pattern (D-TGP). Task-based fMRI data were analyzed using SPM12 with the marsbar, LI and CONN toolboxes. The percent signal change and the laterality index were analyzed, as well as functional connectivity between 23 selected ROIs. Comparisons of both patient groups showed only minor non-significant differences, indicating that the tumor growth pattern is not a relevant influencing factor for fMRI signal. In addition to these results, signal reductions were found in areas that were not affected by the tumor underlining that a GB is not a localized but rather a systemic disease affecting the entire brain.

Mediation of Tremor Control by the Decussating and Nondecussating Part of the Dentato-Rubro-Thalamic Tract in Deep Brain Stimulation in Essential Tremor: Which Part Should Be Stimulated?

OBJECTIVES: The dentato-rubro-thalamic tract (DRTT) has been found to play a major role in the mechanisms of tremor alleviation by deep brain stimulation (DBS) in essential tremor (ET). Still, the influence of the two different parts of the DRTT, consisting of crossing and nondecussating fibers, is not yet clear with respect to tremor reduction. The aim of this study was to assess the influence of the crossing and the nondecussating part of the DRTT on tremor control in ET. MATERIALS AND METHODS: We investigated 80 electrode contacts in ten patients with ET who received bilateral DBS of the Nucleus ventralis intermedius of the thalamus (VIM). Preoperatively and with patients under general anesthesia, 3T magnetic resonance imaging scans were performed, including Diffusion Tensor Imaging scans with 64 gradient directions. We calculated the course of the two parts of the DRTT based on a workflow for probabilistic fiber tracking including protocols for correction of susceptibility- and eddy current-induced distortions. Distances of electrode contacts were correlated with clinical data from neurologic single pole testing. RESULTS: Voltage- and current-steered systems were analyzed separately. Regarding postural tremor, effective contacts showed significantly lower distances to both parts of the DRTT (crossing p < 0.001, nondecussating p < 0.05) in voltage-steered systems. Regarding intentional tremor, significant results were only found for the crossing part (p < 0.01). Regarding both tremor types, effective contacts were closer to the crossing part, unlike less effective contacts. Nonlinear regression analyses using a logistic model showed higher coefficients for the crossing part of the DRTT. Multivariate regression models including distances to both parts of the DRTT showed a significant influence of only the crossing part. Analysis of current-steered systems showed unstable data, probably because of the small number of analyzed patients. CONCLUSIONS: Our data suggest an involvement of both parts of the DRTT in tremor reduction, indicating mediation of DBS effects by both fiber bundles, although the crossing part showed stronger correlations with good clinical responses. Nevertheless, special attention should be paid to methodologic aspects when using probabilistic tractography for patient-specific targeting to avoid uncertain and inaccurate results.

Diffusion tensor imaging changes in patients with glioma-associated seizures.

INTRODUCTION: Structural white matter changes associated with certain epilepsy subtypes have been demonstrated using diffusion tensor imaging (DTI). This observational study aims to identify potential water diffusion abnormalities in glioma patients with associated seizures. METHODS: Two cohorts from two centers were analyzed independently: (A) Prospectively recruited patients diagnosed with glioma who received preoperative DTI to measure mean diffusivity (MD) and fractional anisotropy (FA) in regions-of-interest (ROIs) including the marginal tumor zone (TU), adjacent peritumoral white matter as well as distant ipsilateral and contralateral white matter and cortex. Data were compared between patients with and without seizures and tested for statistical significance. (B) A retrospective cohort using an alternative technical approach sampling ROIs in contrast enhancement, necrosis, non-enhancing tumor, marginal non-enhancing tumor zone, peritumoral tissue, edema and non-tumorous tissue. RESULTS: (A) The prospective study cohort consisted of 23 patients with 12 (52.2%) presenting with a history of seizures. There were no significant seizure-associated differences in MD or FA for non-tumor white matter or cortical areas. MD-TU was significantly lower in patients with seizures (p = 0.005). (B) In the retrospective cohort consisting of 46 patients with a seizure incidence of 50.0%, significantly decreased normalized values of MD were observed for non-enhancing tumor regions of non-glioblastoma multiforme (GBM) cases in patients with seizures (p = 0.022). CONCLUSION: DTI analyses in glioma patients demonstrated seizure-associated diffusion restrictions in certain tumor-related areas. No other structural abnormalities in adjacent or distant white matter or cortical regions were detected.