The impact of subthalamic deep-brain stimulation in restoring motor symmetry in Parkinson's disease patients: a prospective study.

BACKGROUND AND OBJECTIVES: The impact of subthalamic deep-brain stimulation (STN-DBS) on motor asymmetry and its influence on both motor and non-motor outcomes remain unclear. The present study aims at assessing the role of STN-DBS on motor asymmetry and how its modulation translates into benefits in motor function, activities of daily living (ADLs) and quality of life (QoL). METHODS: Postoperative motor asymmetry has been assessed on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson's Disease cohort. Asymmetry was evaluated at both baseline (pre-DBS) and 1 year after STN-DBS. A patient was considered asymmetric when the right-to-left MDS-UPDRS part III difference was ≥ 5. In parallel, analyses have been carried out using the absolute right-to-left difference. The proportion of asymmetric patients at baseline was compared to that in the post-surgery evaluation across different medication/stimulation conditions. RESULTS: 537 PD patients have been included. The proportion of asymmetric patients was significantly reduced after both STN-DBS and medication administration (asymmetric patients: 50% in pre-DBS MedOFF, 35% in MedOFF/StimON, 26% in MedON/StimOFF, and 12% in MedON/StimON state). Older patients at surgery and with higher baseline UPDRS II scores were significantly less likely to benefit from STN-DBS at the level of motor asymmetry. No significant correlation between motor asymmetry and ADLs (UPDRS II) or overall QoL (PDQ-39) score was observed. Asymmetric patients had significantly higher mobility, communication, and daily living PDQ-39 sub-scores. CONCLUSIONS: Both STN-DBS and levodopa lead to a reduction in motor asymmetry. Motor symmetry is associated with improvements in certain QoL sub-scores.

Determining Prior Authorization Approval for Lumbar Stenosis Surgery With Machine Learning.

STUDY DESIGN: Medical vignettes. OBJECTIVES: Lumbar spinal stenosis (LSS) is a degenerative condition with a high prevalence in the elderly population, that is associated with a significant economic burden and often requires spinal surgery. Prior authorization of surgical candidates is required before patients can be covered by a health plan and must be approved by medical directors (MDs), which is often subjective and clinician specific. In this study, we hypothesized that the prediction accuracy of machine learning (ML) methods regarding surgical candidates is comparable to that of a panel of MDs. METHODS: Based on patient demographic factors, previous therapeutic history, symptoms and physical examinations and imaging findings, we propose an ML which computes the probability of spinal surgical recommendations for LSS. The model implements a random forest model trained from medical vignette data reviewed by MDs. Sets of 400 and 100 medical vignettes reviewed by MDs were used for training and testing. RESULTS: The predictive accuracy of the machine learning model was with a root mean square error (RMSE) between model predictions and ground truth of .1123, while the average RMSE between individual MD's recommendations and ground truth was .2661. For binary classification, the AUROC and Cohen's kappa were .959 and .801, while the corresponding average metrics based on individual MD's recommendations were .844 and .564, respectively. CONCLUSIONS: Our results suggest that ML can be used to automate prior authorization approval of surgery for LSS with performance comparable to a panel of MDs.

Reproducibility of volume analysis of dynamic susceptibility contrast perfusion-weighted imaging in untreated glioblastomas.

PURPOSE: Despite a high variability, the hotspot method is widely used to calculate the cerebral blood volume (CBV) of glioblastomas on DSC-MRI. Our aim was to investigate inter- and intra-observer reproducibility of parameters calculated with the hotspot or a volume method and that of an original parameter assessing the fraction of pixels in the tumour volume displaying rCBV > 2: %rCBV > 2. METHODS: Twenty-seven consecutive patients with untreated glioblastoma (age: 63, women: 11) were retrospectively included. Three observers calculated the maximum tumour CBV value (rCBVmax) normalized with a reference ROI in the contralateral white matter (CBVWM) with (i) the hotspot method and (ii) with a volume method following tumour segmentation on 3D contrast-enhanced T1-WI. From this volume method, %rCBV > 2 was also assessed. After 8-12 weeks, one observer repeated all delineations. Intraclass (ICC) and Lin's (LCC) correlation coefficients were used to determine reproducibility. RESULTS: Inter-observer reproducibility of rCBVmax was fair with the hotspot and good with the volume method (ICC = 0.46 vs 0.65, p > 0.05). For CBVWM, it was fair with the hotspot and excellent with the volume method (0.53 vs 0.84, p < 0.05). Reproducibility of one pairwise combination of observers was significantly better for both rCBVmax and CBVWM (LCC = 0.33 vs 0.75; 0.52 vs 0.89, p < 0.05). %rCBV > 2 showed excellent inter- and intra-observer reproducibility (ICC = 0.94 and 0.91). CONCLUSION: Calculated in glioblastomas with a volume method, rCBVmax and CBVWM yielded good to excellent reproducibility but only fair with the hotspot method. Overall, the volume analysis offers a highly reproducible parameter, %rCBV > 2, that could be promising during the follow-up of such heterogeneous tumours.

Personality Related to Quality-of-Life Improvement After Deep Brain Stimulation in Parkinson's Disease (PSYCHO-STIM II).

BACKGROUND: Deep brain stimulation of the sub-thalamic nucleus (DBS-STN) reduces symptoms in Parkinson's disease (PD) patients with motor fluctuations. However, some patients may not feel ameliorated afterwards, despite an objective motor improvement. It is thus important to find new predictors of patients' quality of life (QoL) amelioration after DBS-STN. We hypothesized that personality dimensions might affect QoL after DBS-STN. OBJECTIVE: To evaluate associations between personality dimensions and QoL improvement one year after DBS-STN. METHODS: DBS-STN-PD patients (n = 303) having answered the "Temperament and Character Inventory" (TCI) before surgery and the PDQ-39 before and one year after surgery were included, from the cohort study PREDI-STIM. Linear regression models were used to evaluate associations between TCI dimensions and change in PDQ-39 scores after DBS-STN. RESULTS: Novelty Seeking and Cooperativeness scores before surgery were positively associated with PDQ-39 scores improvement after DBS-STN (FDR-adjusted p < 0.01). Moreover, paradoxically unimproved patients with deterioration of their PDQ-39 scores after DBS-STN despite improvement of their MDS-UPDRS-IV scores had lower Cooperativeness scores, while paradoxically improved patients with amelioration of their PDQ-39 scores despite deterioration of their MDS-UPDRS-IV scores had higher Reward Dependence scores. CONCLUSION: Some presurgical personality dimensions were significantly associated with QoL amelioration and discrepancy between motor state and QoL changes after DBS-STN in PD. Educational programs before DBS-STN should take in account patient personality dimensions to better deal with their expectations.

Clinical long-term consequences of thoraco-lumbar spine fracture and osteosynthesis.

OBJECT: Although traumatic spine fractures can be treated by osteosynthesis, their long-term clinical, social, and familial consequences are less known. The aim of this study was to assess these global consequences to a very long-term (at least more than 12 years after the fracture). METHODS: Two groups, one composed of 30 patients operated for a thoracolumbar fracture by posterior fixation and one with 30 controls (who never had a spinal fracture) matched for age, sex, job and time of follow-up were studied. Patients and control subjects had to answer to 3 questionnaires: one about clinical, familial, and socio-professional changes, and 2 back pain (Dallas and Eifel) scales. RESULTS: The mean patient follow-up was 14.5 years (from 12 to 18 years, sd 2.3) - control subjects, 15 years. The majority (56%) of the fractures occurred at T12/L1 level. At last follow-up, the chronic low back pain concerned 20 (66,7%) patients versus 11 (36.7%) control subjects (p=0.03); more patients (13 patients - 43.3%) consumed analgesics than control (5 persons - 16.6%) subjects (p=0.04). A large majority (13 patients, 57%) had sick leaves that exceeded 6 months. The loss of wage due to traumatism or chronic low back pain was also significant (p=0.002) between patients and matched controls over the period. At follow-up, the mean Eifel score for the whole patients' cohort was significaty superior compared to control group (4.7 [sd 3.75] vs. 2.6 [sd 4.2], p=0.008). Dallas score was superior in the patient's group for the daily, work-leisure activities and sociability aspect (p<0.05). CONCLUSION: Chronic back pain, long sick leaves, changes in professional and familial life, the very long-term postoperative outcome of patients could be more difficult than expected in a majority of patients operated for thoracolumbar fracture. In order to facilitate the back to work and reduce these long-term consequences, we propose that guidelines about job resume in traumatic spinal fractures should be established along with early occupational medicine consultations. LEVEL OF EVIDENCE: III; retrospective case control study.

Multimodal management of surgery- and radiation-refractory meningiomas: an analysis of the French national tumor board meeting on meningiomas cohort.

PURPOSE: Meningiomas represent the most frequent tumor of the central nervous system in adults. While most meningiomas are efficiently treated by surgery and radiotherapy/radiosurgery, there is a small portion of radiation- and surgery-refractory tumors for which there is no clear recommendation for optimal management. The French National Tumor Board Meeting on Meningiomas (NTBM) offers a glimpse on the current management of such patients. METHODS: We retrospectively reviewed the charts of patients presented to the multidisciplinary Meeting between 2016 and 2019. We selected patients with a progressive disease after at least two treatments, including surgery and radiotherapy. RESULTS: In this multicentric cohort of 86 cases, patients harbored 17 (19.8%) WHO Grade I, 48 (55.8%) WHO Grade II and 21 (24.4%) WHO Grade III tumors. The median number of treatments received before inclusion was 3 (range: 2 - 11). Following the Board Meeting, 32 patients (37.2%) received chemotherapy, 11 (12.8%) surgery, 17 (19.8%) radiotherapy, 14 (16.3%) watchful observation and 12 (13.9%) palliative care. After a mean follow-up of 13 months post-inclusion, 32 patients (37.2%) had died from their disease. The mean progression free survival was 27 months after radiotherapy, 10 months after surgery, 8.5 months after chemotherapy (Bevacizumab: 9 months - Octreotide/Everolimus: 8 months). CONCLUSIONS: Surgery- and radiation-refractory meningiomas represent a heterogeneous group of tumors with a majority of WHO Grade II cases. If re-irradiation and redo-surgery are not possible, bevacizumab and octreotide-everolimus appear as a valuable option in heavily pre-treated patients considering the current EANO guidelines.

Iron distribution in the lentiform nucleus: A post-mortem MRI and histology study.

Iron plays an important role in many neurobiological processes, especially in the basal ganglia, the brain structures with the highest concentration. Composed of the pallidum and putamen, the lentiform nucleus plays a key role in the basal ganglia circuitry. With MRI advances, iron-based sequences such as R2* and quantitative susceptibility mapping (QSM) are now available for detecting and quantifying iron in different brain structures. Since their validation using classic iron detection techniques (histology or physical techniques), these sequences have attracted growing clinical attention, especially in the field of extrapyramidal syndromes that particularly affect the basal nuclei. Accurate mapping of iron in these nuclei and their connections is needed to gain a better understanding of this specific anatomy, before considering its involvement in the physiopathological processes. We performed R2* and QSM along with Perls histology, to gain new insights into the distribution of iron in the lentiform nucleus and its surrounding structures, based on four specimens obtained from voluntary donors. We found that iron is preferentially distributed in the anterior part of the globus pallidus externus and the posterior part of the putamen. The lateral wall of the putamen is iron-poor, compared with the lateral medullary lamina and intraputaminal fibers. The relevance of perivascular iron concentration, along with pallido- and putaminofugal iron-rich fibers, is discussed.

Surgical Site Infections after glioblastoma surgery: results of a multicentric retrospective study.

BACKGROUND: The effects of surgical site infections (SSI) after glioblastoma surgery on patient outcomes are understudied. The aim of this retrospective multicenter study was to evaluate the impact of SSI on the survival of glioblastoma patients. METHODS: Data from SSI cases after glioblastoma surgeries between 2009 and 2016 were collected from 14 French neurosurgical centers. Collected data included patient demographics, previous medical history, risk factors, details of the surgical procedure, radiotherapy/chemotherapy, infection characteristics, and infection management. Similar data were collected from gender- and age-paired control individuals. RESULTS: We used the medical records of 77 SSI patients and 58 control individuals. 13 were excluded. Our analyses included data from 64 SSI cases and 58 non-infected glioblastoma patients. Infections occurred after surgery for primary tumors in 38 cases (group I) and after surgery for a recurrent tumor in 26 cases (group II). Median survival was 381, 633, and 547 days in patients of group I, group II, and the control group, respectively. Patients in group I had significantly shorter survival compared to the other two groups (p < 0.05). The one-year survival rate of patients who developed infections after surgery for primary tumors was 50%. Additionally, we found that SSIs led to postoperative treatment discontinuation in 30% of the patients. DISCUSSION: Our findings highlighted the severity of SSIs after glioblastoma surgery, as they significantly affect patient survival. The establishment of preventive measures, as well as guidelines for the management of SSIs, is of high clinical importance.

Indications, Techniques, and Outcomes of Robot-Assisted Insular Stereo-Electro-Encephalography: A Review.

Stereo-electro-encephalography (SEEG) is an invasive, surgical, and electrophysiological method for three-dimensional registration and mapping of seizure activity in drug-resistant epilepsy. It allows the accurate analysis of spatio-temporal seizure activity by multiple intraparenchymal depth electrodes. The technique requires rigorous non-invasive pre-SEEG evaluation (clinical, video-EEG, and neuroimaging investigations) in order to plan the insertion of the SEEG electrodes with minimal risk and maximal recording accuracy. The resulting recordings are used to precisely define the surgical limits of resection of the epileptogenic zone in relation to adjacent eloquent structures. Since the initial description of the technique by Talairach and Bancaud in the 1950's, several techniques of electrode insertion have been used with accuracy and relatively few complications. In the last decade, robot-assisted surgery has emerged as a safe, accurate, and time-saving electrode insertion technique due to its unparalleled potential for orthogonal and oblique insertion trajectories, guided by rigorous computer-assisted planning. SEEG exploration of the insular cortex remains difficult due to its anatomical location, hidden by the temporal and frontoparietal opercula. Furthermore, the close vicinity of Sylvian vessels makes surgical electrode insertion challenging. Some epilepsy surgery teams remain cautious about insular exploration due to the potential of neurovascular injury. However, several authors have published encouraging results regarding the technique's accuracy and safety in both children and adults. We will review the indications, techniques, and outcomes of insular SEEG exploration with emphasis on robot-assisted implantation.

Modern Brainstem MRI Techniques for the Diagnosis of Parkinson's Disease and Parkinsonisms.

The brainstem is the earliest vulnerable structure in many neurodegenerative diseases like in Multiple System Atrophy (MSA) or Parkinson's disease (PD). Up-to-now, MRI studies have mainly focused on whole-brain data acquisition. Due to its spatial localization, size, and tissue characteristics, brainstem poses particular challenges for MRI. We provide a brief overview on recent advances in brainstem-related MRI markers in Parkinson's disease and Parkinsonism's. Several MRI techniques investigating brainstem, mainly the midbrain, showed to be able to discriminate PD patients from controls or to discriminate PD patients from atypical parkinsonism patients: iron-sensitive MRI, nigrosome imaging, neuromelanin-sensitive MRI, diffusion tensor imaging and advanced diffusion imaging. A standardized multimodal brainstem-dedicated MRI approach at high resolution able to quantify microstructural modification in brainstem nuclei would be a promising tool to detect early changes in parkinsonian syndromes.

Glioblastoma survival is better analyzed on preradiotherapy MRI than on postoperative MRI residual volumes: A retrospective observational study.

OBJECTIVES: Establishing an overall survival prognosis for resected glioblastoma during routine postoperative management remains a challenge. The aim of our single-center study was to assess the usefulness of basing survival analyses on preradiotherapy MRI (PRMR) rather than on postoperative MRI (POMR). PATIENTS AND METHODS: A retrospective review was undertaken of 75 patients with glioblastoma treated at our institute. We collected overall survival and MRI volumetric data. We analyzed two types of volumetric data: residual tumor volume and extent of resection. Overall survival rates were compared according to these two types of volumetric data, calculated on either POMR or PRMR and according to the presence or absence of residual enhancement. RESULTS: Analysis of volumetric data revealed progression of some residual tumors between POMR and PRMR. Kaplan-Meier analysis of the correlations between extent of resection, residual tumor volume, and overall survival revealed significant differences between POMR and PRMR data. Both MRI scans indicated a difference between the complete resection subgroup and the incomplete resection subgroup, as median overall survival was longer in patients with complete resection. However, differences were significant for PRMR (25.3 vs. 15.5, p =  0.012), but not for POMR (21.3 vs. 15.8 months, p =  0.145). With a residual tumor volume cut-off value of 3 cm3, Kaplan-Meier survival analysis revealed non-significant differences on POMR (p =  0.323) compared with PRMR (p =  0.007). CONCLUSION: Survival in patients with resected glioblastoma was more accurately predicted by volumetric data acquired with PRMR. Differences in predicted survival between the POMR and PRMR groups can be attributed to changes in tumor behavior before adjuvant therapy.

Matching ex vivo MRI With Iron Histology: Pearls and Pitfalls.

Iron levels in the brain can be estimated using newly developed specific magnetic resonance imaging (MRI) sequences. This technique has several applications, especially in neurodegenerative disorders like Alzheimer's disease or Parkinson's disease. Coupling ex vivo MRI with histology allows neuroscientists to better understand what they see in the images. Iron is one of the most extensively studied elements, both by MRI and using histological or physical techniques. Researchers were initially only able to make visual comparisons between MRI images and different types of iron staining, but the emergence of specific MRI sequences like R2* or quantitative susceptibility mapping meant that quantification became possible, requiring correlations with physical techniques. Today, with advances in MRI and image post-processing, it is possible to look for MRI/histology correlations by matching the two sorts of images. For the result to be acceptable, the choice of methodology is crucial, as there are hidden pitfalls every step of the way. In order to review the advantages and limitations of ex vivo MRI correlation with iron-based histology, we reviewed all the relevant articles dealing with the topic in humans. We provide separate assessments of qualitative and quantitative studies, and after summarizing the significant results, we emphasize all the pitfalls that may be encountered.

Substantia nigra locations of iron-content, free-water and mean diffusivity abnormalities in moderate stage Parkinson's disease.

BACKGROUND: Prior work demonstrated that free water in the posterior substantia nigra (SN) was elevated in Parkinson's disease (PD) compared to healthy controls (HC) across single- and multi-site cohorts, and increased over 1 year in Parkinson's disease but not in relation with the iron deposition in SN with the relaxometry T2*. OBJECTIVES: The main objective of the present study was to evaluate changes in the SN using relaxometry T2*, single- and bi-tensor models of diffusion magnetic resonance imaging between PD patients and HC. METHODS: 39 subjects participated in this study, including 21 HCs and 18 PD patients, in moderate stage (7 years), whose data were collected at two visits separated by approximately 2 years, underwent 3-T MRI comprising: T2*-weighted, T1-weighted and diffusion tensor imaging (DTI) scans. Relaxometry T2*, bi-tensor free water (FW), free-water-corrected fractional anisotropy, free-water-corrected mean diffusivity, single-tensor fractional anisotropy, and single-tensor mean diffusivity were computed for the anterior, posterior and whole substantia nigra. RESULTS: In the anterior SN, relaxometry T2* values were greater for PD patients than HCs. In the posterior SN, free water, single- and bi-tensor mean diffusivity values were greater for PD patients than HCs. No significant change were found over time in FW/MD/R2* maps for PD patients with moderate stage. CONCLUSION: The specific increase of R2* in the anterior SN concomitant with the specific increase of FW in posterior SN suggests a complementary aspect of the two parameters and, perhaps, different underlying pathophysiological processes.

Impact on survival of early tumor growth between surgery and radiotherapy in patients with de novo glioblastoma.

PURPOSE: Systematic pre-radiotherapy MRI in patients with newly resected glioblastoma (OMS 2016) sometimes reveals tumor growth in the period between surgery and radiotherapy. We evaluated the relation between early tumor growth and overall survival (OS) with the aim of finding predictors of regrowth. METHODS: Seventy-five patients from 25 to 84 years old (Median age 62 years) with preoperative, immediate postoperative, and preradiotherapy MRI were included. Volumetric measurements were made on each of the three MRI scans and clinical and molecular parameters were collected for each case. RESULTS: Fifty-four patients (72%) had an early regrowth with a median contrast enhancement volume of 3.61 cm3-range 0.12-71.93 cm3. The median OS was 24 months in patients with no early tumor growth and 17.1 months in those with early tumor regrowth (p = 0.0024). In the population with initial complete resection (27 patients), the median OS was 25.3 months (19 patients) in those with no early tumor growth between surgery and radiotherapy compared to 16.3 months (8 patients) in those with tumor regrowth. In multivariate analysis, the initial extent of resection (p < 0.001) and the delay between postoperative MRI and preradiotherapy MRI (p < 0.001) were significant independent prognostic factors of regrowth and of poorer outcome. CONCLUSIONS: We demonstrated that, in addition to the well known issue of incomplete resection, longer delays between surgery and adjuvant treatment is an independent factors of tumor regrowth and a risk factor of poorer outcomes for the patients. To overcome the delay factor, we suggest shortening the usual time between surgery and radiotherapy.