The "state of the art" of intraoperative neurophysiological monitoring: An Italian neurosurgical survey.

Introduction: Intraoperative Neurophysiological Monitoring (IOM) is widely used in neurosurgery but specific guidelines are lacking. Therefore, we can assume differences in IOM application between Neurosurgical centers. Research question: The section of Functional Neurosurgery of the Italian Society of Neurosurgery realized a survey aiming to obtain general data on the current practice of IOM in Italy. Materials and methods: A 22-item questionnaire was designed focusing on: volume procedures, indications, awake surgery, experience, organization and equipe. The questionnaire has been sent to Italian Neurosurgery centers. Results: A total of 54 centers completed the survey. The annual volume of surgeries range from 300 to 2000, and IOM is used in 10-20% of the procedures. In 46% of the cases is a neurologist or a neurophysiologist who performs IOM. For supra-tentorial pathology, almost all perform MEPs (94%) SSEPs (89%), direct cortical stimulation (85%). All centers perform IOM in spinal surgery and 95% in posterior fossa surgery. Among the 50% that perform peripheral nerve surgery, all use IOM. Awake surgery is performed by 70% of centers. The neurosurgeon is the only responsible for IOM in 35% of centers. In 83% of cases IOM implementation is adequate to the request. Discussion and conclusions: The Italian Neurosurgical centers perform IOM with high level of specialization, but differences exist in organization, techniques, and expertise. Our survey provides a snapshot of the state of the art in Italy and it could be a starting point to implement a consensus on the practice of IOM.

Predominant cardiac sympathetic modulation during wake and sleep in patients with Rett syndrome.

BACKGROUND: Rett syndrome (RTT) is a rare neurological disorder primarily associated with mutations in the methyl-CpG-binding protein 2 (MECP2) gene. The syndrome is characterized by cognitive, social, and physical impairments, as well as sleep disorders and epilepsy. Notably, dysfunction of the autonomic nervous system is a key feature of the syndrome. Although Heart Rate Variability (HRV) has been used to investigate autonomic nervous system dysfunction in RTT during wakefulness, there is still a significant lack of information regarding the same during sleep. Therefore, our aim was to investigate cardiovascular autonomic modulation during sleep in subjects with RTT compared to an age-matched healthy control group (HC). METHOD: A complete overnight polysomnographic (PSG) recording was obtained from 11 patients with Rett syndrome (all females, 10 ± 4 years old) and 11 HC (all females, 11 ± 4 years old; p = 0.48). Electrocardiogram and breathing data were extracted from PSG and divided into wake, non-REM, and REM sleep stages. Cardiac autonomic control was assessed using symbolic non-linear heart rate variability analysis. The symbolic analysis identified three patterns: 0 V% (sympathetic), 2UV%, and 2LV% (vagal). RESULTS: The 0 V% was higher in the RTT group than in the HC group during wake, non-REM, and REM stages (p < 0.01), while the 2LV and 2UV% were lower during wake and sleep stages (p < 0.01). However, the 0 V% increased similarly from the wake to the REM stage in both RTT and HC groups. CONCLUSIONS: Therefore, the sympatho-vagal balance shifted towards sympathetic predominance and vagal withdrawal during wake and sleep in RTT, although cardiac autonomic dynamics were preserved during sleep.

Bleeding and thrombotic events and intensity of heparin therapy in the two first waves of COVID-19.

A systemic inflammatory response occurs during SARS-CoV2 infection and is associated with hypercoagulability and thrombotic events. From March 2020 in our hospital different dosages of low-molecular weight heparin (LMWH) were introduced according to the level of patient care intensity. Because bleeding episodes occurred in hospitalized COVID-19 patients on heparin, the dosage of LMWH at the end of first wave was tailored on the severity of COVID-19. The aim of this study is to describe bleeding and thrombotic events in patients hospitalized with SARS-CoV2 infection on LMWH therapy in the two waves of COVID-19 and analyze the factors associated with these events. Among 1143 patients enrolled in the COVID-19 Network registry, 912 were included in the analysis, 537 of them admitted during the first wave and 375 during the second. Bleeding events were 30 (3.3%): 22 (2.4%) major and 8 (0.9%) non-major. Arterial and venous thrombotic events were 6 (0.7%) and 24 (2.6%). The incidence of venous thrombotic events was higher in the first than in the second wave (0.29% [95% CI 0.20-0.45] events/day vs. 0.05% [95% CI 0.02-0.16]), with a 71% risk reduction (95% CI 22%-94%). The incidence of bleeding was 0.33% (95% CI 0.22-0.50) vs 0.14% events/day (95% CI 0.07-0.28), with no statistical between-wave difference (HR 0.41 95% CI 0.16-1.08). After adjusting for the competing risks of death and comorbidities, patients in the second wave had lower odds to have thrombotic events than in the first wave (0.24 HR [95% C.I. 0.07-0.89]). In this retrospective study on COVID-19 we found a low rate of hemorrhagic and thrombotic events, that may be explained by the absence in the case material of patients admitted to intensive care unit.

Ivabradine restores tonic cardiovascular autonomic control and reduces tachycardia, hypertension and left ventricular inflammation in post-weaning protein malnourished rats.

Malnutrition results in autonomic imbalance and heart hypertrophy. Overexpression of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in the left ventricles (LV) is linked to hypertrophied hearts and abnormal myocardium automaticity. Given that ivabradine (IVA) has emerging pleiotropic effects, in addition to the widely known bradycardic response, this study evaluated if IVA treatment could repair the autonomic control and cardiac damages in malnourished rats. AIM: Assess the impact of IVA on tonic cardiovascular autonomic control and its relationship with hemodynamics regulation, LV inflammation, and HCN gene expression in post-weaning protein malnutrition condition. MAIN METHODS: After weaning, male rats were divided into control (CG; 22 % protein) and malnourished (MG; 6 % protein) groups. At 35 days, groups were subdivided into CG-PBS, CG-IVA, MG-PBS and MG-IVA (PBS 1 ml/kg or IVA 1 mg/kg) received during 8 days. We performed jugular vein cannulation and electrode implant for drug delivery and ECG registration to assess tonic cardiovascular autonomic control; femoral cannulation for blood pressure (BP) and heart rate (HR) assessment; and LV collection to evaluate ventricular remodeling and HCN gene expression investigation. KEY FINDINGS: Malnutrition induced BP and HR increases, sympathetic system dominance, and LV remodeling without affecting HCN gene expression. IVA reversed the cardiovascular autonomic imbalance; prevented hypertension and tachycardia; and inhibited the LV inflammatory process and fiber thickening caused by malnutrition. SIGNIFICANCE: Our findings suggest that ivabradine protects against malnutrition-mediated cardiovascular damage. Moreover, our results propose these effects were not attributed to HCN expression changes, but rather to IVA pleiotropic effects on autonomic control and inflammation.

Clinical research on extreme longevity: The FACET experience.

People with extreme longevity represent a unique model to study the biology of aging. Unfortunately, their inclusion in research projects is challenging with the consequent lack of evidence and the need to rely on small convenience samples. Given the growing global aging population, especially in the segment of the oldest old (i.e., aged 90 and older), research in this population has become crucial. Furthermore, by studying the characteristics of extremely longeval persons, it might be possible to 1) better understand the mechanisms of aging, and 2) identify endogenous or exogenous factors contributing to a long life. The design and implementation of research activities in the oldest people need special consideration and a pragmatic approach. Possible implementable solutions and suggestions are provided from experience gained during the conduction of the FAtigue in CEnTenarians (FACET) study.

Predictive value of intraoperative vagus nerve corticobulbar motor evoked potentials to assess the risk of dysphagia in fourth ventricle surgery.

OBJECTIVE: Dysphagia is a significant complication in fourth ventricle surgery. Corticobulbar motor evoked potentials (CB-MEPs) of the lower cranial nerves may provide real-time information possibly correlating with postoperative swallowing dysfunction, and the vagus nerves may prove ideal for this purpose. However, the literature is heterogeneous, non-systematic, and inconclusive on this topic. The object of this retrospective study was to evaluate the correlation between CB-MEPs of the vagus nerve and postoperative worsening or new-onset swallowing deficits in intraaxial fourth ventricle surgery. METHODS: In 21 consecutive patients undergoing surgery for fourth ventricle intraaxial tumors between February 2018 and October 2022, endotracheal tubes with two applied electrodes contacting the vocal cords were used to record vagus nerve MEPs including values at baseline, the end of surgery, and the minimum value during the operation. From the mean value of right and left vagus nerve MEP amplitudes, the minimum-to-baseline amplitude ratio (MBR) and final-to-baseline amplitude ratio (FBR) were calculated. These indexes were correlated with postoperative swallowing function. RESULTS: Given their clinical significance, receiver operating characteristic curves were obtained to evaluate the performance of these indexes in predicting postoperative swallowing function. The area under the curve (AUC) was 0.850 (p < 0.001) and the best cutoff for FBR was 67.55% for the worsening of swallowing in the postoperative period. The AUC was 0.750 (p = 0.026) and the best cutoff was 46.37% in MBR for the absence of a swallowing disorder at the late follow-up. CONCLUSIONS: This study confirmed that vagus nerve MEPs are reliable predictors of postoperative swallowing function in fourth ventricle surgery and can be feasibly used as an intraoperative monitoring technique.

Methods and Principles of the Intraoperative Neurophysiologic Monitoring in Neurosurgery.

Intraoperative neurophysiologic monitoring (IONM) is an innovation introduced in neurosurgery in the past decades. It aims to support and guide the neurosurgeon to obtain the best surgical result possible, preventing the occurrence of neurological deficits. The somatosensory evoked potentials (SSEP) assess the integrity of the sensory pathways monitoring the dorsal column-medial lemniscus pathway during spine and cerebral surgery. Motor evoked potentials (MEPs) provide information on the integrity of the motor pathway monitoring the efferent motor pathways from the motor cortex to the muscle through corticospinal (or corticobulbar) tracts. Free-running EMG is the standard technique to monitor peripheral nerves, roots, or cranial motor nerves during surgery. Intraoperative EMG signals are activated during cranial motor nerves damaging or after an irritative stimulus. The duration, morphology, and persistence of EMG reflects the severity of neural injury. Nerve mapping consists of recording muscle activations given by direct nerve stimulation. This technique makes use of a stimulation probe available to the neurosurgeon which allows administering current directly to the nervous tissue (nerves, roots, etc.). Intraoperative neurophysiological monitoring (IONM) represents the standard of care during many procedures, including spinal, intracranial, and vascular surgeries, where there is a risk of neurological damage. Close communication and collaboration between the surgical team, neurophysiologist, and anesthesiologist is mandatory to obtain high-quality neuromonitoring, thus preventing neurologic injuries and gaining the best surgical "safe" results.

Percutaneous Balloon Compression for Trigeminal Neuralgia. A Comparative Study Between the Fluoroscope Guided and Neuronavigated Technique.

Percutaneous balloon compression (PBC) is a safe and effective procedure in the treatment of trigeminal neuralgia (TN) due to its simplicity, low cost and the possibility of being repeated in case of pain recurrence. Foramen ovale (FO) cannulation is accomplished with the assistance of intraoperative C-arm fluoroscopy. Recently, several authors have reported successful application of intraoperative CT navigation as well. The reported advantages of CT navigation are linked to better spatial orientation and the low rate of attempts for FO cannulation. However, these advantages should be considered in the face of concerns regarding increased radiation dose to the patient and its possible adverse effects. Here we compared the fluoroscopic guided and neuronavigated PBC techniques in terms of efficacy and radiological exposure. We retrospectively analyzed 37 patients suffering for TN and submitted to PBC. We observed a significant improvement of pain at 1 month FU compared with the pre-operative in both groups (p < 0.0001 and p < 0.0001, respectively). A significant increase in radiation exposure was found in the neuronavigated group compared with the fluoroscopy group (p < 0.0001). We suggest the use of neuronavigated PBC only in selected cases, such as patients with multiple previous operations, in whom a difficult access can be pre-operatively hypothesized.

Spinal Cord High-Frequency Stimulation. The Current Experience and Future Directions.

Spinal cord stimulation (SCS) is a neuromodulation technology that has emerged as a valid treatment for chronic intractable neuropathic pain. After conventional tonic SCS, new waveforms of stimulation, like high frequency (HF), have proved that they can provide safe and effective pain relief. In addition, SCS is now being utilized more broadly as a potential treatment for a range of indications, including motor disorders and spasticity. Our study presents a retrospective analysis of 20 patients with heterogenous aetiologies of neuropathic pain treated with HF stimulation, after a standardized protocol in a temporary trial. We observed a significant improvement in pain relief according to comparisons of numerical rating scale (NRS) scores before the procedure, after the clinical trial and at latest follow-up. Two unusual clinical cases were also reported, and the pertinent literature was discussed.

Atlantoaxial Anterior Transarticular Screw Fixation: Indications and Surgical Technique.

Posterior atlantoaxial screw fixation is a widely adopted therapeutic option for C1-C2 instability secondary to fractures or dislocation, degenerative diseases, or tumors at this level. Anterior transarticular screw fixation (ATSF) is an effective alternative to the posterior approaches, presenting several advantages despite being scarcely known and rarely chosen.In this chapter, we describe the ATSF step by step, illustrating its variations reported in literature, and we critically analyze the several advantages and contraindications of this technique. Moreover, we provide a list of tips and tricks on the surgical procedure, including critical operating room settings-the result of more than 10 years of experience in the field by a senior author.ATSF is a valid strategy for the treatment of different diseases occurring at the level of the atlantoaxial complex that needs consideration. Given the significant learning curve of this strategy, some hints may be essential to begin introducing this technique in the personal armamentarium of a spine surgeon so that they can perform ATSF safely and effectively.

Spinal Epidural Atypical Meningioma: Case Report and Review of the Literature.

Spinal atypical meningiomas are rare, and those whose main extension is in the epidural space are anecdotal. Here, we report a case of a young woman presenting with sensory disturbances and a radiological diagnosis of a dorsal epidural sleeve-like mass. The surgical resection of the lesion allowed the decompression of the spinal cord and led to the histopathological diagnosis of atypical meningioma. At the 3-month follow-up, her neurological recovery was complete. Because of the gross total removal of the lesion, adjuvant radiotherapy was not performed: At the 2-year follow-up, no recurrence of disease was detected. A comprehensive literature review was performed, and just two more case reports on epidural atypical meningiomas were found in the English literature. Through this case report and literature review, we described a rare manifestation of spinal meningioma that entered into a differential diagnosis for extradural spinal lesions, such as secondary malignancies.

Toward the End of the Funnel: The Ventriculus Terminalis-The State of Art of an Ancient Entity with a Recent History.

PURPOSE: The ventriculus terminalis (VT), also called the fifth ventricle, is a small cavity containing cerebrospinal fluid (CSF) that is in the conus medullaris in continuity with the central canal of the spinal cord. In adults, persistent VT is a very rare entity, and the diagnosis is incidental in most cases. Rarely, VT may become symptomatic for still-uncertain reasons but most often for its cystic dilatation. The management of these selected cases is still controversial and sometimes associated with unsatisfactory outcomes. METHODS: We performed a critical review of the existing literature on the management of symptomatic VT in adults. The etiology, pathophysiology, and treatment of VT are presented and discussed, focusing on the best timing for surgery. RESULTS: Conservative management, marsupialization, or the placement of a T drain have been reported. The existing classifications describe the most correct approach for each clinical presentation, but scarce importance has been given to the delay from symptoms' onset to surgical treatment. CONCLUSION: Although different cases have been described in the literature, this rare pathology remains unknown to most neurosurgeons.

Does Laminectomy Affect Spino-Pelvic Balance in Lumbar Spinal Stenosis? A Study Based on the EOS X-Ray Imaging System.

PURPOSE: Lumbar spinal stenosis (LSS) is a degenerative disorder causing the forward bending of the trunk and pelvic retroversion with the consequent loss of lumbar lordosis; surgical treatment is intended to enlarge the canal and foramina and decompress the nerve roots. The purpose of our study is to determine whether and to what extent facet-sparing laminectomy affects the spino-pelvic balance. METHODS: The spino-pelvic balance of 26 patients was analysed before and after surgery through the EOS X-ray Imaging System. The following parameters were considered: thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS). Clinical data were expressed in numeric values according to the Oswestry Disability Index (ODI), the visual analogue scale (VAS) and the modified Japanese Orthopaedic Association (mJOA) scoring system. RESULTS: Significant SS decreases and PT increases were noticed after surgery, without modification in LL, axial vertebral rotation (AVR) and the general alignment. Pain and disability had a significant improvement, as represented by a decrease in scores on the VAS and ODI scales and an increase in scores on the mJOA functional scale. CONCLUSION: The most important parameter seems to be a congruence between pelvic and spinal parameters, which achieves an economic posture with the physiologic position of the axis of gravity. According to the literature, a standard sagittal balance (SB) has not been defined.

Women have a greater cardiac vagal withdrawal to heat stress compared to men.

The heated environment shifts the sympatho-vagal balance toward sympathetic predominance and vagal withdrawal. Women's heart is more reliant on vagal autonomic control, while men's heart is more dependent on sympathetic control. However, sex differences in cardiovascular autonomic responses to heat stress remain unknown. We aimed to investigate the cardiovascular autonomic regulation under heat stress between sexes. Thirty-two young participants (27 ± 4 years old; 16 women) were enrolled in a single visit, resting for 30min at baseline (thermal reference condition TC; ∼24°C) and 30min under a heated environment (HOT; ∼38°C). Blood pressure (BP), skin temperature, electrocardiogram, and respiratory oscillations were continuously recorded. The heart rate variability (HRV) was assessed by spectral analysis (low-frequency [LFnu; sympathetic and vagal] and high-frequency [HFnu; vagal]), and symbolic analysis (0 V% [sympathetic] and 2UV%, and 2LV% [vagal]). The spontaneous baroreflex sensitivity (BRS) was calculated by the gain between BP and R-R within the LF band (αLF). The estimated maximal aerobic capacity and body surface area were employed as covariates in sex comparisons. The effects of HOT were the following: 1) Women have a greater cardiac vagal withdrawal to heat stress compared to men; 2) Sex differences on cardiac autonomic response to heat stress exist after controlling for the effect of estimated physical fitness and body surface area. Therefore, heat stress provokes a higher vagal withdrawal to the heart in women compared to men. It could be attributed to sex per se since significant differences between men and women were not modified after covariate analysis.

Reactome pathway analysis from whole-blood transcriptome reveals unique characteristics of systemic sclerosis patients at the preclinical stage.

Objective: This study aims to characterize differential expressed pathways (DEP) in subjects with preclinical systemic sclerosis (PreSSc) characterized uniquely by Raynaud phenomenon, specific autoantibodies, and/or capillaroscopy positive for scleroderma pattern. Methods: Whole-blood samples from 33 PreSSc with clinical prospective data (baseline and after 4 years of follow-up) and 16 matched healthy controls (HC) were analyzed for global gene expression transcriptome analysis via RNA sequencing. Functional Analysis of Individual Microarray Expression method annotated Reactome individualized pathways. ANOVA analysis identified DEP whose predictive capability were tested in logistic regression models after extensive internal validation. Results: At 4 years, 42.4% subjects progressed (evolving PreSSc), while the others kept stable PreSSc clinical features (stable PreSSc). At baseline, out of 831 pathways, 541 DEP were significant at a false discovery rate <0.05, differentiating PreSSc versus HC with an AUROC = 0.792 ± 0.242 in regression models. Four clinical groups were identified via unsupervised clustering (HC, HC and PreSSc with HC-like features, PreSSc and HC with PreSSc-like features, and PreSSc). Biological signatures changed with disease progression while remaining unchanged in stable subjects. The magnitude of change was related to the baseline cluster, yet no DEP at baseline was predictive of progression. Disease progression was mostly related to changes in signal transduction pathways especially linked to calcium-related events and inositol 1,4,5-triphosphate metabolism. Conclusion: PreSSc had distinguished Reactome pathway signatures compared to HC. Progression to definite SSc was characterized by a shift in biological fingertips. Calcium-related events promoting endothelial damage and vasculopathy may be relevant to disease progression.

The role of artificial intelligence in the management of trigeminal neuralgia.

Trigeminal neuralgia (TN) is the most frequent facial pain. It is difficult to treat pharmacologically and a significant amount of patients can become drug-resistant requiring surgical intervention. From an etiologically point of view TN can be distinguished in a classic form, usually due to a neurovascular conflict, a secondary form (for example related to multiple sclerosis or a cerebello-pontine angle tumor) and an idiopathic form in which no anatomical cause is identifiable. Despite numerous efforts to treat TN, many patients experience recurrence after multiple operations. This fact reflects our incomplete understanding of TN pathogenesis. Artificial intelligence (AI) uses computer technology to develop systems for extension of human intelligence. In the last few years, it has been a widespread of AI in different areas of medicine to implement diagnostic accuracy, treatment selection and even drug production. The aim of this mini-review is to provide an up to date of the state-of-art of AI applications in TN diagnosis and management.