Right-sided vagus nerve stimulation for drug-resistant epilepsy: A systematic review of the literature and perspectives.

BACKGROUND: Right-sided vagus nerve stimulation (RS-VNS) is indicated when the procedure was deemed not technically feasible or too risky on the indicated left side. OBJECTIVE: The present study aims to systematically review the literature on RS-VNS, assessing its effectiveness and safety. METHODS: A systematic review following PRISMA guidelines was conducted: Pubmed/MEDLINE, The Cochrane Library, Scopus, Embase and Web of science databases were searched from inception to August 13th,2023. Gray literature was searched in two libraries. Eligible studies included all studies reporting, at least, one single case of RS-VNS in patients for the treatment of drug-resistant epilepsy. RESULTS: Out of 2333 initial results, 415 studies were screened by abstract. Only four were included in the final analysis comprising seven patients with RS-VNS for a drug-resistant epilepsy. One patient experienced nocturnal asymptomatic bradycardia whereas the other six patients did not display any cardiac symptom. RS-VNS was discontinued in one case due to exercise-induced airway disease exacerbation. Decrease of epileptic seizure frequency after RS-VNS ranged from 25 % to 100 % in six cases. In the remaining case, VNS effectiveness was unclear. In one case, RS-VNS was more efficient than left-sided VNS (69 % vs 50 %, respectively) whereas in another case, RS-VNS was less efficient (50 % vs 95 %, respectively). CONCLUSION: Literature on the present topic is limited. In six out of seven patients, RS-VNS for drug-resistant epilepsy displayed reasonable effectiveness with a low complication rate. Further research, including prospective studies, is necessary to assess safety and effectiveness of RS-VNS for drug-resistant epilepsy patients.

Complications of Intracranial Multimodal Monitoring for Neurocritical Care: A Systematic Review and Meta-Analysis.

Intracranial multimodal monitoring (iMMM) is increasingly used for neurocritical care. However, concerns arise regarding iMMM invasiveness considering limited evidence in its clinical significance and safety profile. We conducted a synthesis of evidence regarding complications associated with iMMM to delineate its safety profile. We performed a systematic review and meta-analysis (PROSPERO Registration Number: CRD42021225951) according to the Preferred Reporting Items for Systematic Review and Meta-Analysis and Peer Review of Electronic Search Strategies guidelines to retrieve evidence from studies reporting iMMM use in humans that mention related complications. We assessed risk of bias using the Newcastle-Ottawa Scale and funnel plots. The primary outcomes were iMMM complications. The secondary outcomes were putative risk factors. Of the 366 screened articles, 60 met the initial criteria and were further assessed by full-text reading. We included 22 studies involving 1206 patients and 1434 iMMM placements. Most investigators used a bolt system (85.9%) and a three-lumen device (68.8%), mainly inserting iMMM into the most injured hemisphere (77.9%). A total of 54 postoperative intracranial hemorrhages (pooled rate of 4%; 95% confidence interval [CI] 0-10%; I2 86%, p < 0.01 [random-effects model]) was reported, along with 46 misplacements (pooled rate of 6%; 95% CI 1-12%; I2 78%, p < 0.01) and 16 central nervous system infections (pooled rate of 0.43%; 95% CI 0-2%; I2 64%, p < 0.01). We found 6 system breakings, 18 intracranial bone fragments, and 5 cases of pneumocephalus. Currently, iMMM systems present a similar safety profile as intracranial devices commonly used in neurocritical care. Long-term outcomes of prospective studies will complete the benefit-risk assessment of iMMM in neurocritical care. Consensus-based reporting guidelines on iMMM use are needed to bolster future collaborative efforts.

The Impact of Invasive Brain Oxygen Pressure Guided Therapy on the Outcome of Patients with Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Traumatic brain injury (TBI) is a major public health burden, causing death and disability worldwide. Intracranial hypertension and brain hypoxia are the main mechanisms of secondary brain injury. As such, management strategies guided by intracranial pressure (ICP) and brain oxygen (PbtO2) monitoring could improve the prognosis of these patients. Our objective was to summarize the current evidence regarding the impact of PbtO2-guided therapy on the outcome of patients with TBI. We performed a systematic search of PubMed, Scopus, and the Cochrane library databases, following the protocol registered in PROSPERO. Only studies comparing PbtO2/ICP-guided therapy with ICP-guided therapy were selected. Primary outcome was neurological outcome at 3 and 6 months assessed by using the Glasgow Outcome Scale; secondary outcomes included hospital and long-term mortality, burden of intracranial hypertension, and brain tissue hypoxia. Out of 6254 retrieved studies, 15 studies (n = 37,245 patients, of who 2184 received PbtO2-guided therapy) were included in the final analysis. When compared with ICP-guided therapy, the use of combined PbO2/ICP-guided therapy was associated with a higher probability of favorable neurological outcome (odds ratio 2.21 [95% confidence interval 1.72-2.84]) and of hospital survival (odds ratio 1.15 [95% confidence interval 1.04-1.28]). The heterogeneity (I2) of the studies in each analysis was below 40%. However, the quality of evidence was overall low to moderate. In this meta-analysis, PbtO2-guided therapy was associated with reduced mortality and more favorable neurological outcome in patients with TBI. The low-quality evidence underlines the need for the results from ongoing phase III randomized trials.

Brain Tissue Oxygenation-Guided Therapy and Outcome in Traumatic Brain Injury: A Single-Center Matched Cohort Study.

Brain tissue oxygenation (PbtO2)-guided therapy can improve the neurological outcome of traumatic brain injury (TBI) patients. With several Phase-III ongoing studies, most of the existing evidence is based on before-after cohort studies and a phase-II randomized trial. The aim of this study was to assess the effectiveness of PbtO2-guided therapy in a single-center cohort. We performed a retrospective analysis of consecutive severe TBI patients admitted to our center who received either intracranial pressure (ICP) guided therapy (from January 2012 to February 2016) or ICP/PbtO2-guided therapy (February 2017 to December 2019). A genetic matching was performed based on covariates including demographics, comorbidities, and severity scores on admission. Intracranial hypertension (IH) was defined as ICP > 20 mmHg for at least 5 min. Brain hypoxia (BH) was defined as PbtO2 < 20 mmHg for at least 10 min. IH and BH were targeted by specific interventions. Mann−Whitney U and Fisher's exact tests were used to assess differences between groups. A total of 35 patients were matched in both groups: significant differences in the occurrence of IH (ICP 85.7% vs. ICP/PbtO2 45.7%, p < 0.01), ICU length of stay [6 (3−13) vs. 16 (9−25) days, p < 0.01] and Glasgow Coma Scale at ICU discharge [10 (5−14) vs. 13 (11−15), p = 0.036] were found. No significant differences in ICU mortality and Glasgow Outcome Scales at 3 months were observed. This study suggests that the role of ICP/PbtO2-guided therapy should await further confirmation in well-conducted large phase III studies.

Synthetic MRI for stroke: a qualitative and quantitative pilot study.

Synthetic MR provides qualitative and quantitative multi-parametric data about tissue properties in a single acquisition. Its use in stroke imaging is not yet established. We compared synthetic and conventional image quality and studied synthetic relaxometry of acute and chronic ischemic lesions to investigate its interest for stroke imaging. We prospectively acquired synthetic and conventional brain MR of 43 consecutive adult patients with suspected stroke. We studied a total of 136 lesions, of which 46 DWI-positive with restricted ADC (DWI + /rADC), 90 white matter T2/FLAIR hyperintensities (WMH) showing no diffusion restriction, and 430 normal brain regions (NBR). We assessed image quality for lesion definition according to a 3-level score by two readers of different experiences. We compared relaxometry of lesions and regions of interest. Synthetic images were superior to their paired conventional images for lesion definition except for sFLAIR (sT1 or sPSIR vs. cT1 and sT2 vs. cT2 for DWI + /rADC and WMH definition; p values < .001) with substantial to almost perfect inter-rater reliability (κ ranging from 0.711 to 0.932, p values < .001). We found significant differences in relaxometry between lesions and NBR and between acute and chronic lesions (T1, T2, and PD of DWI + /rADC or WMH vs. mirror NBR; p values < .001; T1 and PD of DWI + /rADC vs. WMH; p values of 0.034 and 0.008). Synthetic MR may contribute to stroke imaging by fast generating accessible weighted images for visual inspection derived from rapidly acquired relaxometry data. Moreover, this synthetic relaxometry could differentiate acute and chronic ischemic lesions.

External hydrocephalus associated with dural sigmoid sinus arteriovenous fistula: a case report.

External hydrocephalus (EH) is a recognised sub-type of hydrocephalus associated with macrocephaly in infancy. EH is characterised by the enlargement of subarachnoid spaces (so-called subarachnomegaly) with a normal ventricular system on brain imaging. EH is traditionally considered benign and self-limiting, yet its pathophysiology remains puzzling. Mounting evidence for an association between EH and hydrovenous disorders reshapes our understanding of this condition and its management. To our knowledge, we report the first association between EH and dural arteriovenous fistula (dAVF) in a 17-months-old boy. As dAVF may be a life-threatening condition, early diagnosis and optimal treatment are critical. This case epitomises the intricacies of EH's aetiology and associated conditions requiring careful management. Therefore, we recommend considering MR angiography in EH's workup and long-term follow-up. Our experience supports the ongoing reconsideration of EH's presumed benignity.

Fibrin-coated collagen fleece versus absorbable dural sealant for sellar closure after transsphenoidal pituitary surgery: a comparative study.

Various surgical methods to prevent postoperative cerebrospinal fluid (CSF) leaks during transsphenoidal surgery have been reported. However, comparative studies are scarce. We aimed to compare the efficacy of a fibrin-coated collagen fleece (TachoSil) versus a dural sealant (DuraSeal) to prevent postoperative CSF leakage. We perform a retrospective study comparing two methods of sellar closure during endoscopic endonasal transsphenoidal surgery (EETS) for pituitary adenoma resection: TachoSil patching versus DuraSeal packing. Data concerning diagnosis, reconstruction technique, and surgical outcomes were analyzed. The primary endpoint was postoperative CSF leak rate. We reviewed 198 consecutive patients who underwent 219 EETS for pituitary adenoma from February 2007 and July 2018. Intraoperative CSF leak occurred in 47 cases (21.5%). A total of 33 postoperative CSF leaks were observed (15.1%). A reduction of postoperative CSF leaks in the TachoSil application group compared to the conventional technique using Duraseal was observed (7.7% and 18.2%, respectively; p = 0.062; Pearson exact test) although non-statistically significant. Two patients required lumbar drainage, and no revision repair was necessary to treat postoperative CSF rhinorrhea in Tachosil group. Fibrin-coated collagen fleece patching may be a valuable method to prevent postoperative cerebrospinal fluid (CSF) leaks during EETS for pituitary adenoma resection.

Posterior quadrant disconnection for refractory epilepsy: how I do it.

BACKGROUND: Posterior quadrant disconnection (PQD) is intended to interrupt the propagation of intractable unilateral temporo-parieto-occipital epilepsy. METHOD: An enhanced operative video presents the illustrative case of a total PQD indicated for a 15-year-old boy with Sturge-Weber syndrome suffering from seizure recurrence after a partial PQD. We describe the surgical procedure with emphasis on relevant anatomy and multimodal intraoperative guidance in three steps: (i) parieto-occipital disconnection, (ii) posterior callosotomy, and (iii) temporal disconnection/resection. Pearls and pitfalls of surgical management are discussed. CONCLUSION: PQD is a less invasive surgical option to typical hemispherotomy and hemispherectomy for selected indications of posterior multilobar epilepsy.

Complete Corpus Callosotomy for Refractory Epilepsy in Children.

Corpus callosotomy is an interhemispheric disconnection by callosal commissural fiber ablation. Its rationale is the disruption of ictal spread to prevent seizure generalization. The objective pursued is alleviation of intractable, debilitating, and injurious manifestations of generalized epilepsy.1 Eight decades of experience support this procedure's safety and effectiveness for appropriately selected patients with drug-resistant epilepsy not amenable to optimal resection; particularly, favorable outcomes for tonic or atonic seizures with drop attacks have been reported.2,3 Children may benefit more than adults from callosotomy for improved daily function, psychosocial adjustment, and family satisfaction.4 A meta-analysis found a better seizure reduction from total than partial callosotomy (88.2% vs. 58.6% of worthwhile reduction) comprising drop-attacks (77.8% vs. 45.4%) with an increased but transient (i.e., resolution within 6 weeks) risk of significant disconnection syndromes (12.5% vs. none).5 Here, we present the illustrative case of a 4-year-old boy with Lennox-Gastaut syndrome who underwent open single-stage complete callosotomy. Video 1 shows the microscope-assisted interhemispheric approach aided by stereotactic navigation. We showcase critical steps such as dissection of cingulate gyri and anterior and then posterior callosotomy while highlighting crucial anatomic landmarks. This procedure may be accessible for epilepsy surgeons worldwide in resource-constrained environments6 while serving as a basis for promising high-technology development (e.g., endoscopic, radiosurgical, laser interstitial thermal therapy, or magnetic resonance-guided focused ultrasound callosotomies). In this video article, we aim to provide a streamlined and stepwise approach to this rare but important epilepsy surgery.

Delayed intracranial hemorrhage of patients with mild traumatic brain injury under antithrombotics on routine repeat CT scan: a systematic review and meta-analysis.

BACKGROUND: Patients on antithrombotics experiencing mild traumatic brain injury (mTBI) may benefit from a routine repeat CT scan to detect delayed intracranial hemorrhage (dICH). OBJECTIVES: The primary outcome was the incidence of dICH on routine repeat CT scans of mTBI patients on antithrombotics within an intra-hospital observation period of up to 48 hours. The secondary outcomes were potential risk factors, readmissions, neurosurgical interventions, and mortality. METHODS: A systematic review and a meta-analysis of single proportions were performed according to the PRISMA and PRESS guidelines. The risk of bias was assessed using Newcastle-Ottawa Scale. RESULTS: Eighteen studies with 4613 patients were included. The pooled incidence of dICH was 2% [95% CI 1-2%] with similar rates between different antithrombotic regimens, even in combination. Of the 67 patients with dICH reported (1.45%), eleven required surgery (0.24%), while six died (0.13%). Loss of consciousness was a risk factor of dICH (risk ratio 3.04 [95%CI 0.96; 9.58]). A total of 48 patients were reported for readmission without associated death or surgical intervention. CONCLUSION: The contribution of this routine repeat CT scan should be questioned due to the low incidence, the limited clinical significance, and the unsubstantiated clinical benefit of early or systematic detection of dICH.

Single-stage resection of bottom-of-a-sulcus dysplasia involving eloquent cortex using navigated transcranial magnetic stimulation and intraoperative modalities.

BACKGROUND: Focal cortical dysplasia (FCD) is a common etiology of refractory epilepsy, particularly in children. Surgical management is potentially curative, but poses the challenge of distinguishing the border between ictogenic regions of dysplasia and functionally critical brain tissue. Bottom-of-a-sulcus dysplasia (BOSD) amplifies this challenge, due to difficulties in physiologic mapping of the deep tissue. METHODS: We report a one-stage resection of a dysplasia-associated seizure focus abutting and involving the hand and face primary motor cortex. In doing so, we describe our surgical planning integrating neuronavigated transcranial magnetic stimulation (nTMS) for functional motor mapping, combined with intraoperative ultrasonography, intracranial electroencephalography, and magnetic resonance imaging (MRI). A 5-year-old girl with intractable focal epilepsy was referred to our comprehensive epilepsy program. Despite attentive pharmacotherapy, she experienced status epilepticus and up to 70 seizures per day, accompanied by multiple side effects from her antiseizure medication. A right frontal BOSD in close proximity to the hand motor area of the precentral gyrus was identified on MRI. Postoperatively, she is seizure-free for over 1 year with no hand deficit. CONCLUSION: Although technically complex, single-stage resection taking advantage of comprehensive surgical planning with optimized fusion of functional mapping and intraoperative modalities merits consideration given the invasiveness of a two-stage approach for limited added value. Integrated pre-surgical nTMS allowed for mapping of eloquent cortex without invasive electrocortical stimulation.

Dabrafenib monotherapy for a recurrent BRAFV600E-mutated TTF-1-positive posterior pituitary tumor.

Posterior pituitary tumors (PPT) expressing thyroid transcription factor-1 (TTF-1) are extremely rare low-grade neoplasms. The recent discovery of BRAF mutations in these tumors offers a potential alternative treatment using targeted therapies. We present the case of a 57-year-old female with recurrent BRAFV600E-mutated TTF-1-positive PPT treated with a BRAF inhibitor monotherapy (dabrafenib) leading to tumor regression. After 18 months of uninterrupted treatment, ongoing radiological tumor regression was observed and the patient remained asymptomatic without any significant adverse event. BRAF inhibitor is potentially a valuable treatment option for recurrent TTF-1-positive PPT with BRAF mutation.

Safety profile of an intracranial multimodal monitoring bolt system for neurocritical care: a single-center experience.

BACKGROUND: Intracranial multimodality monitoring (iMMM) is increasingly used in acute brain-injured patients; however, safety and reliability remain major concerns to its routine implementation. METHODS: We performed a retrospective study including all patients undergoing iMMM at a single European center between July 2016 and January 2020. Brain tissue oxygenation probe (PbtO2), alone or in combination with a microdialysis catheter and/or an 8-contact depth EEG electrode, was inserted using a triple-lumen bolt system and targeting normal-appearing at-risk brain area on the injured side, whenever possible. Surgical complications, adverse events, and technical malfunctions, directly associated with iMMM, were collected. A blinded imaging review was performed by an independent radiologist. RESULTS: One hundred thirteen patients with 123 iMMM insertions were included for a median monitoring time of 9 [3-14] days. Of those, 93 (76%) patients had only PbtO2 probe insertion and 30 (24%) had also microdialysis and/or iEEG monitoring. SAH was the most frequent indication for iMMM (n = 60, 53%). At least one complication was observed in 67/123 (54%) iMMM placement, corresponding to 58/113 (51%) patients. Misplacement was observed in 16/123 (13%), resulting in a total of 6/16 (38%) malfunctioning PbtO2 catheters. Intracranial hemorrhage was observed in 14 iMMM placements (11%), of which one required surgical drainage. Five placements were complicated by pneumocephalus and 4 with bone fragments; none of these requires additional surgery. No CNS infection related to iMMM was observed. Seven (6%) probes were accidentally dislodged and 2 probes (2%) were accidentally broken. Ten PbtO2 probes (8%) presented a technical malfunction after a median of 9 [ranges: 2-24] days after initiation of monitoring and 4 of them were replaced. CONCLUSIONS: In this study, a high occurrence of complications related to iMMM was observed, although most of them did not require specific interventions and did not result in malfunctioning monitoring.

Brain tissue oxygenation guided therapy and outcome in non-traumatic subarachnoid hemorrhage.

Brain hypoxia can occur after non-traumatic subarachnoid hemorrhage (SAH), even when levels of intracranial pressure (ICP) remain normal. Brain tissue oxygenation (PbtO2) can be measured as a part of a neurological multimodal neuromonitoring. Low PbtO2 has been associated with poor neurologic recovery. There is scarce data on the impact of PbtO2 guided-therapy on patients' outcome. This single-center cohort study (June 2014-March 2020) included all patients admitted to the ICU after SAH who required multimodal monitoring. Patients with imminent brain death were excluded. Our primary goal was to assess the impact of PbtO2-guided therapy on neurological outcome. Secondary outcome included the association of brain hypoxia with outcome. Of the 163 patients that underwent ICP monitoring, 62 were monitored with PbtO2 and 54 (87%) had at least one episode of brain hypoxia. In patients that required treatment based on neuromonitoring strategies, PbtO2-guided therapy (OR 0.33 [CI 95% 0.12-0.89]) compared to ICP-guided therapy had a protective effect on neurological outcome at 6 months. In this cohort of SAH patients, PbtO2-guided therapy might be associated with improved long-term neurological outcome, only when compared to ICP-guided therapy.

COVID-19 Impact on Neurosurgical Practice: Lockdown Attitude and Experience of a European Academic Center.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented challenge. Different models of reorganization have been described aiming to preserve resources and ensure optimal medical care. Limited clinical neurosurgical experience with patients with COVID-19 has been reported. We share organizational experience, attitudes, and preliminary data of patients treated at our institution. METHODS: Institutional guidelines and patient workflow are described and visualized. A cohort of all neurosurgical patients managed during the lockdown period is presented and analyzed, assessing suspected nosocomial infection risk factors. A comparative surgical subcohort from the previous year was used to investigate the impact on surgical activity. RESULTS: A total of 176 patients were admitted in 66 days, 20 of whom tested positive for COVID-19. Patients initially admitted to the neurosurgical ward were less likely to be suspected for a COVID-19 infection compared with patients admitted for critical emergencies, particularly with neurovascular and stroke-related diseases. The mortality of patients with COVID-19 was remarkably high (45%), and even higher in patients who underwent surgical intervention (77%). In addition to the expected decrease in surgical activity (-53%), a decrease in traumatic emergencies was noted. CONCLUSIONS: By applying infection prevention and resource-sparing logistics measures shared by the international medical community, we were able to maintain essential neurosurgical care in a pandemic with controlled nosocomial infection risk. Special consideration should be given to medical management and surgical indications in patients infected with severe acute respiratory syndrome coronavirus 2, because they seem to show a problematic hemostatic profile that might result in an unfavorable clinical and surgical outcome.