Long-Term Results of Cortical Motor Stimulation for Neuropathic Peripheral and Central Pain: Real-World Evidence From Two Independent Centers.

BACKGROUND AND OBJECTIVES: Cortical motor stimulation (CMS) is used to modulate neuropathic pain. The literature supports its use; however, short follow-up studies might overestimate its real effect. This study brings real-world evidence from two independent centers about CMS methodology and its long-term outcomes. METHODS: Patients with chronic refractory neuropathic pain were implanted with CMS. The International Classification of Headache Disorders 3rd Edition was used to classify craniofacial pain and the Douleur Neuropathique en 4 Questions Scale score to explore its neuropathic nature. Demographics and clinical and surgical data were collected. Pain intensity at 6, 12, and 24 months and last follow-up was registered. Numeric rating scale reduction of ≥50% was considered a good response. The Clinical Global Impression of Change scale was used to report patient satisfaction. RESULTS: Twelve males (38.7%) and 19 females (61.3%) with a mean age of 55.8 years (±11.9) were analyzed. Nineteen (61.5%) were diagnosed from painful trigeminal neuropathy (PTN), and seven (22.5%) from central poststroke pain. The mean follow-up was 51 months (±23). At 6 months, 42% (13/31) of the patients were responders, all of them being PTN (13/19; 68.4%). At last follow-up, only 35% (11/31) remained responders (11/19 PTN; 58%). At last follow-up, the global Numeric rating scale reduction was 34% ( P = .0001). The Clinical Global Impression of Change scale punctuated 2.39 (±0.94) after 3 months from the surgery and 2.95 (±1.32) at last follow-up ( P = .0079). Signs of suspicious placebo effect were appreciated in around 40% of the nonresponders. CONCLUSION: CMS might show long-term efficacy for neuropathic pain syndromes, with the effect on PTN being more robust in the long term. Multicentric clinical trials are needed to confirm the efficacy of this therapy for this and other conditions.

Cognitive phenotyping of GBA1-Parkinson's disease: A study on deep brain stimulation outcomes.

BACKGROUND: Heterozygous variants in the glucocerebrosidase (GBA1) gene are the most common genetic risk factor for Parkinson's Disease (PD). GBA1-PD patients exhibit earlier disease onset, severe motor impairment, and heightened cognitive decline. Deep Brain Stimulation (DBS) offers motor improvement for PD patients, but its cognitive effects, particularly in GBA1-PD, are debated. METHODS: This study involved 96 PD patients who underwent subthalamic nucleus DBS at Hospital de la Santa Creu i Sant Pau between 2004 and 2023. Clinical and neuropsychological assessments were conducted pre- and post-surgery, focusing on Mattis Dementia Rating Scale (MDRS) and Frontal Systems Behavior Scale (FrSBe). Patients were categorized into GBA1-PD and non-GBA1-PD groups, with non-GBA1-PD further divided into cognitive fast-progressors and slow-progressors. RESULTS: GBA1 variants were present in 13.5 % of patients. GBA1-PD patients showed greater cognitive decline over time, particularly in attention, conceptualization, and memory, compared to non-GBA1-PD. Non-GBA1-PD fast-progressors exhibited significant cognitive deterioration in initiation and conceptualization within the first year post-DBS. Motor outcomes improved similarly across all groups, but slow-progressors showed a greater reduction in Levodopa Equivalent Daily Dose (LEDD). CONCLUSIONS: GBA1-PD patients experience more rapid cognitive decline, particularly in posterior-cortical and fronto-striatal functions. Additionally, a subset of non-GBA1-PD patients shows significant early cognitive decline post-DBS, especially in executive functions. Baseline MDRS scores do not predict cognitive outcomes, highlighting the need for further research to refine prognostic tools. Despite cognitive challenges, GBA1-PD patients benefit from DBS in terms of motor outcomes, underscoring the importance of individualized assessments for DBS suitability, regardless of genetic status.

Navigated intraoperative ultrasound in neuro-oncology: volumetric accuracy and correlation with high-field MRI.

OBJECTIVE: The use of intraoperative techniques to detect residual tumors has recently become increasingly important. Intraoperative MRI has long been considered the gold standard; however, it is not widely used because of high equipment costs and long acquisition times. Consequently, real-time intraoperative ultrasound (ioUS), which is much less expensive than MRI, has gained popularity. The aim of the present study was to evaluate the capacity of ioUS to accurately determine the primary tumor volume and detect residual tumors. METHODS: A prospective study of adult patients who underwent surgery for intra-axial brain tumors between November 2017 and October 2020 was performed. Navigated intraoperative ultrasound (nioUS) of the brain was used to guide tumor resection and to detect the presence of residual disease. Both convex (5-8 MHz) and linear array (6-13 MHz) probes were used. Tumor volume and residual disease were measured with nioUS and compared with MR images. A linear regression model based on a machine learning pipeline and a Bland-Altman analysis were used to assess the accuracy of nioUS versus MRI. RESULTS: Eighty patients (35 females and 45 males) were included. The mean age was 58 years (range 25-80 years). A total of 88 lesions were evaluated; there were 64 (73%) gliomas, 19 (21.6%) metastases, and 5 (5.7%) other tumors, mostly located in the frontal (41%) and temporal (27%) lobes. Most of the tumors (75%) were perfectly visible on ioUS (grade 3, Mair grading system), except for those located in the insular lobe (grade 2). The regression model showed a nearly perfect correlation (R2 = 0.97, p < 0.001) between preoperative tumor volumes from both MRI and nioUS. Ultrasonographic visibility significantly influenced this correlation, which was stronger for highly visible (grade 3) tumors (p = 0.01). For residual tumors, the correlation between postoperative MRI and nioUS was weaker (R2 = 0.78, p < 0.001) but statistically significant. The Bland-Altman analysis showed minimal bias between the two techniques for pre- and postoperative scenarios, with statistically significant results for the preoperative concordance. CONCLUSIONS: The authors' findings show that most brain tumors are well delineated by nioUS and almost perfectly correlated with MRI-based measurements both pre- and postoperatively. These data support the hypothesis that nioUS is a reliable intraoperative technique that can be used for real-time monitoring of brain tumor resections and to perform volumetric analysis of residual disease.

Long-term outcomes of deep brain stimulation for treatment-resistant schizophrenia: Exploring potential targets.

BACKGROUND: Schizophrenia is a complex and disabling disorder. Around 30% of patients have treatment-resistant schizophrenia (TRS). OBJECTIVE: This study summarizes the outcomes after three years follow-up of the first series of patients with TRS treated with deep brain stimulation (DBS) and discuss surgical, clinical and imaging analysis. METHODS: Eight patients with TRS treated with DBS in the nucleus accumbens (NAcc) or the subgenual cingulate gyrus (SCG) were included. Symptoms were rated with the PANSS scale and normalized using the illness density index (IDI). A reduction in IDI-PANSS of ≥25% compared to baseline was the criterion of good response. The volume of activated tissue was calculated to perform a connectomic analysis for each patient. An estimation of the tracts and cortical areas modulated was generated. RESULTS: Five women and three men were analyzed. After 3 years' follow-up, positive symptoms improved in 50% of the SCG group and 75% of the NAcc group (p = 0.06), and general symptoms improved in 25% and 50% respectively (p = 0.06). The SCG group showed activation of the cingulate bundle and modulation of orbitofrontal and frontomesial regions; in contrast, the NAcc group showed activation of the ventral tegmental area projections pathway and modulation of regions associated with the "default mode network" (precuneus) and Brodmann areas 19 and 20. CONCLUSIONS: These results showed a trend toward improvement for positive and general symptoms in patients with TRS treated with DBS. The connectomic analysis will help us understand the interaction of this treatment with the disease to pursue future trial designs.

Long-Term Results of Deep Brain Stimulation for Treatment-Resistant Depression: Outcome Analysis and Correlation With Lead Position and Electrical Parameters.

BACKGROUND: Long-term efficacy and mechanisms of action of deep brain stimulation (DBS) for treatment-resistant depression (TRD) are under investigation. OBJECTIVE: To compare long-term outcomes with active electrode's coordinates and its electrical parameters in patients with TRD treated with DBS in the subgenual cingulate gyrus (SCG-DBS). METHODS: Seventeen patients with TRD underwent SCG-DBS. Demographic and baseline characteristics were recorded. The 17-item Hamilton Depression Rating Scale was used to measure the response to the therapy. The anterior commissure-posterior commissure coordinates of the active contacts and the total electrical energy delivered were calculated and correlated with clinical outcomes. Patient-specific tractographic analysis was performed to identify the modulated pathways in responders. RESULTS: Twelve women (70.6%) and 5 men (29.4%) with a median age of 48 yr (34-70 years) were included. Along the 5-year follow-up, 3 main clinical trajectories were observed according to symptom's improvement: great responders (≥80%), medium responders (≥50%-79%), and poor responders (<50%). Active contacts' coordinates and total electrical energy delivered showed no correlation with clinical outcomes. Brodmann area 10 medial was the most frequently stimulated area and the forceps minor, the most frequently modulated tract. CONCLUSION: SCG-DBS for TRD is clearly effective in some patients. Active contacts' coordinates were highly variable within the region and, like electrical parameters, did not seem to correlate with clinical outcomes. In the current series, Brodmann area 10 medial and the forceps minor were the most frequently targeted area and modulated pathway, respectively.

Neuronavigated Ultrasound in Neuro-Oncology: A True Real-Time Intraoperative Image.

OBJECTIVE: Ultrasound is considered a real-time imaging method in neuro-oncology because of its highly rapid image acquisition time. However, to our knowledge, there are no studies that analyze the additional surgical time that it requires. METHODS: A prospective study of 100 patients who underwent intra-axial brain tumor resection with navigated intraoperative ultrasound. The primary outcomes were lesion visibility grade on ultrasound and concordance with preoperative magnetic resonance imaging (MRI) scan, intraoperative ultrasound usage time, and percentage of tumor resection on ultrasound and comparison with postoperative MRI scan. RESULTS: The breakdown of patients included the following: 53 high-grade gliomas, 26 metastases, 14 low-grade gliomas, and 7 others. Ninety-six percent of lesions were clearly visualized. The tumor border was clearly delimited in 71%. Concordance with preoperative MRI scan was 78% (P < 0.001). The mean time ± SD for sterile covering of the probe was 2.16 ± 0.5 minutes, and the mean image acquisition time was 2.49 ± 1.26 minutes. Insular tumor location, low-grade glioma, awake surgery, and recurrent tumor were statistically associated with an increased ultrasound usage time. Ultrasound had a sensitivity of 94.4% and a specificity of 100% for residual tumor detection. CONCLUSIONS: Neuronavigated ultrasound can be considered a truly real-time intraoperative imaging method because it does not increase surgical time significantly and provides optimal visualization of intra-axial brain lesions and residual tumor.

Intracavernous Branches of the Internal Carotid Artery Through an Endoscopic Endonasal Approach: Anatomical Study and Review of the Literature.

OBJECTIVE: The endoscopic endonasal transcavernous (EET) approach is an increasingly popular approach for the cavernous sinus and surrounding structure lesions as well as a surgical corridor to pre-mesencephalic cisterns. This endoscopic study describes the main intracavernous branches of the internal carotid artery, providing nuances to improve the safety of this approach. MATERIAL AND METHODS: Forty-six fresh cavernous sinus (23 heads) were injected with colored silicon and studied via an EET approach; 6 were excluded due to insufficient injection. The internal carotid artery, the meningohyphophyseal trunk (MHT) and its branches, and the inferolateral trunk were dissected, and branching patterns identified and classified. RESULTS: The MHT was identified in 82.5% of cases. Two main MHT types were identified: complete, with 3 main branches, and incomplete, with fewer than 3. The main branches encountered were the inferior hypophyseal artery, present in 92.5% of cases, the dorsal meningeal artery (DMA), present in 87.5%, and the tentorial artery, present in 87.5%. The DMA was classified as prominent medial (48.6%), prominent lateral (20%), or bifurcation type (25.7%). Complete and incomplete MHT were further classified as complete MHT (A, B, and C) and incomplete MHT (A, B, C, and D) according to the combination of the different DMA types with other branches. The inferolateral trunk was a branch of the MHT in 7% of cases. CONCLUSIONS: The MHT is a highly prevalent intracavernous branch, with 7 identifiable patterns based on DMA morphology and branch combination. This knowledge could guide surgeons in performing a safer EET approach.

Occipital nerve stimulation and deep brain stimulation for refractory cluster headache: a prospective analysis of efficacy over time.

OBJECTIVE: Occipital nerve stimulation (ONS) and deep brain stimulation (DBS) are widely used surgical treatments for chronic refractory cluster headache (CH). However, there is little literature regarding long-term follow-up of these treatments. METHODS: The authors describe two prospective cohorts of patients with refractory CH treated with ONS and DBS and compare preoperative to postoperative status at 6 and 12 months after the surgery and at final follow-up. Efficacy analysis using objective and subjective variables is reported, as well as medication reduction and complications. RESULTS: The ONS group consisted of 13 men and 4 women, with a median age of 44 years (range 31-61 years). The median number of attacks per week (NAw) before surgery was 28 (range 7-70), and the median follow-up duration was 48 months. The DBS group comprised 5 men and 2 women, with a median age of 50 years (range 29-64 years). The median NAw before surgery was 56 (range 14-140), and the median follow-up was 36 months. The NAw and visual analog scale score were significantly reduced for the ONS and DBS groups after surgery. However, while all the patients from the DBS group were considered responders at final follow-up, with more than 85% being satisfied with the treatment, approximately 29% of initial responders to ONS became resistant by the final follow-up (p = 0.0253). CONCLUSIONS: ONS is initially effective as a treatment for refractory CH, although a trend toward loss of efficacy was observed. No clear predictors of good clinical response were found in the present study. Conversely, DBS appears to be effective and provide a more stable clinical response over time with an acceptable rate of surgical complications.

Intraoperative Use and Benefits of Tractography in Awake Surgery Patients.

OBJECTIVE: The present study analyzed the benefits of the use of tractography in the preoperative and intraoperative scenarios. METHODS: We present a prospective cohort study with 2 groups of patients who had undergone awake surgery for brain tumor resection. A control group for which no intraoperative navigated diffusion tensor imaging (DTI) was used (non-DTI group) and the case group (DTI group). The operative time, complete tumor resection, and neurological postoperative deficits were measured as primary outcomes. A secondary analysis was performed to determine the power of preoperative DTI to predict for complete tumor resection. RESULTS: A total of 37 patients were included, 18 in the non-DTI group and 19 in the DTI group. No differences were found between the 2 groups for sex, mean age, tumor histological findings, and preoperative mean tumor volume. The awake surgical time in the non-DTI group was 119.8 ± 31.1 minutes and 93.6 ± 12.2 minutes in the DTI group (P = 0.007). A trend was found toward complete tumor resection in the DTI group (P = 0.09). The sensitivity and specificity for predicting complete tumor resection were 88% and 62.5% for the non-DTI group and 100% and 80% for the DTI group, respectively. The area under the receiver operating characteristic curve was 0.720 in the non-DTI group and 0.966 in the DTI group (P = 0.041). CONCLUSIONS: Intraoperative navigated tractography shortened the time of awake neuro-oncological surgery and might provide help in performing complete tumor resection. Also, tractography used in the preoperative planning could be a useful tool for better prediction of complete tumor resection.