Ultra-early navigated transcranial magnetic stimulation for perioperative stroke: anatomo-functional report.

Navigated repetitive transmagnetic stimulation is a non-invasive and safe brain activity modulation technique. When combined with the classical rehabilitation process in stroke patients it has the potential to enhance the overall neurologic recovery. We present a case of a peri-operative stroke, treated with ultra-early low frequency navigated repetitive transmagnetic stimulation over the contralesional hemisphere. The patient received low frequency navigated repetitive transmagnetic stimulation within 12 hours of stroke onset for seven consecutive days and a significant improvement in his right sided weakness was noticed and he was discharge with normal power. This was accompanied by an increase in the number of positive responses evoked by navigated repetitive transmagnetic stimulation and a decrease of the resting motor thresholds at a cortical level. Subcortically, a decrease in the radial, axial, and mean diffusivity were recorded in the ipsilateral corticospinal tract and an increase in fractional anisotropy, axial diffusivity, and mean diffusivity was observed in the interhemispheric fibers of the corpus callosum responsible for the interhemispheric connectivity between motor areas. Our case demonstrates clearly that ultra-early low frequency navigated repetitive transmagnetic stimulation applied to the contralateral motor cortex can lead to significant clinical motor improvement in patients with subcortical stroke.

Impact of Preoperative Mapping and Intraoperative Neuromonitoring in Minimally Invasive Parafascicular Surgery for Deep-Seated Lesions.

BACKGROUND: Transsulcal tubular retractor-assisted minimally invasive parafascicular surgery changes the surgical strategy for deep-seated lesions by promoting a deficit-sparing approach. When integrated with preoperative brain mapping and intraoperative neuromonitoring (IONM), this approach may potentially improve patient outcomes. In this study, we assessed the impact of preoperative brain mapping and IONM in tubular retractor-assisted neuro-oncological surgery. METHODS: This retrospective single-center cohort study included patients who underwent transsulcal tubular retractor-assisted minimally invasive parafascicular surgery for resection of deep-seated brain tumors from 2016 to 2022. The cohort was divided into 3 groups: group 1, no preoperative mapping or IONM (17 patients); group 2, IONM only (25 patients); group 3, both preoperative mapping and IONM (38 patients). RESULTS: We analyzed 80 patients (33 males and 47 females) with a median age of 46.5 years (range: 1-81 years). There was no significant difference in mean tumor volume (26.2 cm3 [range 1.07-97.4 cm3]; P = 0.740) and mean preoperative depth of the tumor (31 mm [range 3-65 mm], P = 0.449) between the groups. A higher proportion of high-grade gliomas and metastases was present within group 3 (P = 0.003). IONM was related to fewer motor (P = 0.041) and language (P = 0.032) deficits at hospital discharge. Preoperative mapping and IONM were also related to shorter length of stay (P = 0.008). CONCLUSIONS: Preoperative and intraoperative brain mapping and monitoring enhance transsulcal tubular retractor-assisted minimally invasive parafascicular surgery in neuro-oncology. Patients had a reduced length of stay and prolonged overall survival. IONM alone reduces postoperative neurological deficit.

Cortical-Subcortical Functional Preservation and Rehabilitation in Neuro-Oncology: Tractography-MIPS-IONM-TMS Proof-of-Concept Study.

Surgical management of deep-seated brain tumors requires precise functional navigation and minimally invasive surgery. Preoperative mapping using navigated transcranial magnetic stimulation (nTMS), intraoperative neurophysiological monitoring (IONM), and minimally invasive parafascicular surgery (MIPS) act together in a functional-sparing approach. nTMS also provides a rehabilitation tool to maximize functional recovery. This is a single-center retrospective proof-of-concept cohort study between January 2022 and June 2023 of patients admitted for surgery with motor eloquent deep-seated brain tumors. The study enrolled seven adult patients, five females and two males, with a mean age of 56.28 years old. The lesions were located in the cingulate gyrus (three patients), the central core (two patients), and the basal ganglia (two patients). All patients had preoperative motor deficits. The most common histological diagnosis was metastasis (five patients). The MIPS approach to the mid-cingulate lesions involved a trajectory through the fronto-aslant tract (FAT) and the fronto-striatal tract (FST). No positive nTMS motor responses were resected as part of the outer corridor for MIPS. Direct cortical stimulation produced stable motor-evoked potentials during the surgeries with no warning signs. Gross total resection (GTR) was achieved in three patients and near-total resection (NTR) in four patients. Post-operatively, all patients had a deterioration of motor function with no ischemia in the postoperative imaging (cavity-to-CST distance 0-4 mm). After nTMS with low-frequency stimulation in the contralateral motor cortex, six patients recovered to their preoperative functional status and one patient improved to a better functional condition. A combined Tractography-MIPS-IONM-TMS approach provides a successful functional-sparing approach to deep-seated motor eloquent tumors and a rehabilitation framework for functional recovery after surgery.

IgG4-related hypertrophic pachymeningitis with chronic subdural haematoma.

Hypertrophic pachymeningitis is a rare disorder of the dura mater of the spine or brain. It can be caused by inflammatory, infective or neoplastic conditions or can be idiopathic. We report a man with hypertrophic pachymeningitis and bilateral chronic subdural haematoma caused by IgG4-related disease. We highlight the diagnostic challenges and discuss possible underlying mechanisms of subdural haematoma formation in inflammatory conditions. Isolated IgG4-related hypertrophic pachymeningitis with chronic subdural haematoma is very rare; previously reported cases have suggested a possible predilection for men in their sixth decade, presenting with headache as the dominant symptom. Given the rarity and complexity of the condition, it should be managed in a multidisciplinary team setting.

MGMT Promoter Methylation: Prognostication beyond Treatment Response.

MGMT promoter methylation is related to the increased sensitivity of tumour tissue to chemotherapy with temozolomide (TMZ) and thus to improved patient survival. However, it is unclear how the extent of MGMT promoter methylation affects outcomes. In our study, a single-centre retrospective study, we explore the impact of MGMT promoter methylation in patients with glioblastoma who were operated upon with 5-ALA. Demographic, clinical and histology data, and survival rates were assessed. A total of 69 patients formed the study group (mean age 53.75 ± 15.51 years old). Positive 5-ALA fluorescence was noted in 79.41%. A higher percentage of MGMT promoter methylation was related to lower preoperative tumour volume (p = 0.003), a lower likelihood of 5-ALA positive fluorescence (p = 0.041) and a larger extent of resection EoR (p = 0.041). A higher MGMT promoter methylation rate was also related to improved progression-free survival (PFS) and overall survival (OS) (p = 0.008 and p = 0.006, respectively), even when adjusted for the extent of resection (p = 0.034 and p = 0.042, respectively). A higher number of adjuvant chemotherapy cycles was also related to longer PFS and OS (p = 0.049 and p = 0.030, respectively). Therefore, this study suggests MGMT promoter methylation should be considered as a continuous variable. It is a prognostic factor that goes beyond sensitivity to chemotherapy treatment, as a higher percentage of methylation is related not only to increased EoR and increased PFS and OS, but also to lower tumour volume at presentation and a lower likelihood of 5-ALA fluorescence intraoperatively.

Prognostic Factors for Surgically Managed Spontaneous Spinal Epidural Hematoma: A Single-Center Case Series of 18 Patients.

BACKGROUND: Spontaneous spinal epidural hematoma (SSEH) is a rare pathology, which carries a significant morbidity. OBJECTIVE: To review our institutional experience of surgically managed patients with SSEH, seeking to better understand clinical prognostic factors related to postoperative outcomes and thereby improve counseling of patients before treatment. METHODS: All patients who underwent surgical management of SSEH between September 2011 and 2021. Baseline and postoperative clinical and radiological characteristics are presented, including the American Spinal Injury Association grade (ASIA). Statistical analyses were performed using Stata 13.1. RESULTS: Eighteen patients were identified in total (11 male patients and 7 female patients) with a median age of 59.5 (range 3-83) years. The most common spinal region affected was cervicothoracic (33.3%). Limb weakness (94.4%) and urinary dysfunction (83.3%) represented the most common presenting symptoms. Preoperatively, the presence of spinal cord edema on imaging was associated with worse preoperative Medical Research Council (MRC) grade ( P = .033), female sex was associated with preserved saddle sensation ( P = .04), and patients receiving antiplatelet medication were associated with a higher risk of preoperative axial back pain ( P = .005). Higher postoperative MRC grade was associated with higher preoperative ASIA ( P = .012) and MRC grade ( P = .005), and preservation of saddle sensation ( P = .018). Postoperative improvements in axial back pain were associated with higher preoperative ASIA grade ( P = .035) and anticoagulation treatment ( P = .029). CONCLUSION: Neurosurgical intervention for SSEH yields positive outcomes and benefits patients. Patients with higher preoperative ASIA, MRC grade, and those presenting with preserved saddle sensation may experience further improved clinical outcomes after intervention.

Effectiveness and safety of intracranial events associated with the use of direct oral anticoagulants for atrial fibrillation: A systematic review and meta-analysis of 92 studies.

AIMS: Observational studies have investigated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) used in nonvalvular atrial fibrillation. We performed a systematic review and meta-analysis assessing the risk of ischaemic stroke, thromboembolism (TE) and intracranial haemorrhage (ICH) associated with the use of DOACs and VKAs. METHODS: Medline and Embase were systematically searched until April 2021. Observational studies were gathered and hazard ratios (HRs) with 95% confidence intervals (CI) were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, exposure to VKA, age and sex were performed. A random-effects model was used. RESULTS: We included 92 studies and performed 107 comparisons. Apixaban was associated with lower risk of stroke (HR: 0.82, 95% CI: 0.68-0.99) compared to dabigatran. Rivaroxaban was associated with lower risk of stroke (HR: 0.90, 95% CI: 0.83-0.98) compared to VKA. Dabigatran (HR: 0.85, 95% CI: 0.80-0.91), rivaroxaban (HR: 0.83, 95% CI: 0.77-0.89) and apixaban (HR: 0.75, 95% CI: 0.65-0.86) were associated with lower risk for TE/stroke compared to VKA. Apixaban (HR: 1.32, 95% CI: 1.03-1.68) and rivaroxaban (HR: 1.58, 95% CI: 1.31-1.89) were associated with higher risk of ICH compared to dabigatran. Dabigatran (HR: 0.48, 95% CI: 0.44-0.52), apixaban (HR: 0.60, 95% CI: 0.49-0.73) and rivaroxaban (HR: 0.73, 95% CI: 0.65-0.81) were associated with lower risk of ICH compared to VKA. CONCLUSION: Our study demonstrated significant differences in the risk of ischaemic stroke, TE/stroke and ICH associated with individual DOACs compared to both other DOACs and VKA.

Prognostic factors for surgically managed intramedullary spinal cord tumours: a single-centre case series.

PURPOSE: Intramedullary spinal cord tumours (IMSCTs) are comparatively rare neoplasms. We present a single-centre clinical case series of adult patients with surgically managed IMSCTs. METHODS: We performed a retrospective analysis of electronic patient records in the time period spanning July 2010 to July 2021. All adult patients that had undergone surgical management for IMSCTs were eligible for inclusion. Baseline and post-operative clinical and radiological characteristics, along with follow-up data, were assessed. We also performed a literature review with a focus on surgical outcomes for IMSCTs. RESULTS: Sixty-six patients matched our selection criteria, with a median age of 42 years (range 23-85). Thirty-four ependymomas, 17 haemangioblastomas, 12 astrocytomas, 2 lymphomas and 1 teratoma were included. Statistical analysis yielded several significant findings: IMSCTs spanning a greater number of vertebral levels are significantly associated with poor McCormick outcomes (p = 0.03), presence of gait disturbance before surgery is significantly associated with poor outcome for both post-operative McCormick and Nurick scores (p = 0.007), and radicular pain present pre-operatively is significantly associated with a good post-operative McCormick score (p = 0.045). Haemangioblastomas are significantly more likely to have a clear intra-operative dissection plane compared to ependymomas and astrocytomas (p = 0.009). However, astrocytomas have a significantly higher prevalence of good McCormick outcomes compared to ependymomas and haemangioblastomas (p = 0.03). CONCLUSION: Histological diagnosis, cranio-caudal extent of the tumour and the presence or absence of baseline deficits-such as gait impairment and radicular pain-are significant in determining neurological outcomes after surgery for IMSCTs.

Dabigatran, rivaroxaban, and apixaban are superior to warfarin in Asian patients with non-valvular atrial fibrillation: An updated meta-analysis.

BACKGROUND: Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation (AF) originated from western countries. AIM: To systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran, rivaroxaban, and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF. METHODS: Medline, Cochrane, and ClinicalTrial.gov databases were reviewed. A random-effect model meta-analysis was used and I-square was utilized to assess the heterogeneity. The primary outcome was ischemic stroke. The secondary outcomes were all-cause mortality, major bleeding, intracranial hemorrhage, and gastrointestinal bleeding. RESULTS: Twelve studies from East Asia or Southeast Asia and 441450 patients were included. Dabigatran, rivaroxaban, and apixaban were associated with a significant reduction in the incidence of ischemic stroke [hazard ratio (HR) = 0.78, 95% confidence interval (CI): 0.65-0.94; HR = 0.79, 95%CI: 0.74-0.85, HR = 0.70, 95%CI: 0.62-0.78; respectively], all-cause mortality (HR = 0.68, 95%CI: 0.56-0.83; HR = 0.66, 95%CI: 0.52-0.84; HR = 0.66, 95%CI: 0.49-0.90; respectively), and major bleeding (HR = 0.61, 95%CI: 0.54-0.69; HR = 0.70, 95%CI: 0.54-0.90; HR = 0.58, 95%CI: 0.43-0.78; respectively) compared to warfarin. CONCLUSION: Dabigatran, rivaroxaban, and apixaban appear to be superior to warfarin in both efficacy and safety in Asians with non-valvular AF.

Intranasal insulin in Alzheimer's dementia or mild cognitive impairment: a systematic review.

BACKGROUND AND AIMS: Due to common pathophysiological findings of Alzheimer's disease (AD) with diabetes mellitus (DM), insulin has been suggested as a possible treatment of AD or mild cognitive impairment (MCI). A safe alternative of IV insulin is intranasal (IN) insulin. The aim of this systematic review is to investigate the effects of IN insulin on cognitive function of patients with either AD or MCI. METHODS: A literature search of the electronic databases Medline, Scopus and CENTRAL was performed to identify RCTs investigating the effect of IN insulin administration on cognitive tasks, in patients with AD or MCI. RESULTS: Seven studies (293 patients) met our inclusion criteria. Most studies showed that verbal memory and especially story recall was improved after IN insulin administration. Sometimes the effect was restricted for apoe4 (-) patients. Intranasal insulin did not affect other cognitive functions. However, there were some positive results in functional status and daily activity. Data suggested that different insulin types and doses may have different effects on different apoe4 groups. In addition, the effects of treatment on Αß levels differed from study to study. Finally, IN insulin resulted in minor adverse effects. CONCLUSIONS: Intranasal insulin improved story recall performance of apoe4 (-) patients with AD or MCI. Other cognitive functions were not affected, but there were some positive results in functional status and daily activity. Since IN insulin is a safe intervention, future studies should be conducted with larger doses and after proper selection of patients and insulin types.

Atrial fibrillation and cognitive function in patients with heart failure: a systematic review and meta-analysis.

Cognitive impairment and dementia are established complications of heart failure (HF) in adult patients and impair medication adherence and self-care. Atrial fibrillation (AF) is suggested to play an independent role in the cognitive decline in patients with HF. The objective of this systematic review was to assess the effect of AF on cognitive function in these patients. Medline (PubMed), Scopus, and the CENTRAL databases were queried from their inception up to April 30, 2016. The search included primary research articles evaluating the effect of AF on cognition in HF patients. There were five eligible studies, including a total of 1670 patients with HF; of these, 449 (26.9%) had AF. Different AF types were studied, including persistent, paroxysmal, or permanent. Four cognitive tests were used to assess cognitive function (Mini-Mental State Examination, Short Portable Mental Status Questionnaire, Modified Mini-Mental Examination, and Montreal cognitive assessment tool). Using the inverse variance method and a random effects model, we observed that presence of AF was significantly associated with increased risk of cognitive impairment in HF patients (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.30-2.87), although with significant heterogeneity (I 2  = 39%). This heterogeneity can be attributed to the different populations and types of AF studied as well as to varying cognitive assessment methods. Concomitant AF may exacerbate cognitive dysfunction in HF patients. However, data are sparse and heterogeneous. Well-designed, prospective studies are needed to (a) establish a causative link and (b) identify the underlying mechanism in order to design appropriate interventions to attenuate risk of cognitive impairment in patients with HF.