Gender gap in deep brain stimulation for Parkinson's disease: preliminary results of a retrospective study.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment of PD for both women and men. However, discussions have been reported about the impact of STN-DBS surgery in PD. The aim of our study is to identify differences between men and women in terms of pre- and post-DBS symptoms and try to explain the possible causes. In the current study, we evaluated the gender impact on STN-DBS in PD at the Department of Neurosurgery of University of Naples "Federico II" from 2013 to 2021. Motor and non-motor symptoms were evaluated. To compare the data before and after surgery and between the genders, Wilcoxon-Mann-Whitney tests were performed. A total of 43 patients with PD were included; of them, 17 (39%) were female. Baseline evaluation revealed no gender differences in the age of onset (p = 0.87). Not significant differences were noted in the Unified Parkinson's Disease Rating Scale (UPDRS) pre-surgery score, but if we consider UPDRS subscores of motor examination, significant clinical improvement was reported in both male and female in terms of UPDRS pre- and post-surgery (p < 0.001). STN-DBS is a highly effective treatment for motor and non-motor symptoms of PD for both women and men but our study hints towards gender-specific outcomes in motor domains. Improving our knowledge in this field can allow us to implement strategies to identify new directions in the development of an adequate treatment of PD in terms of surgical intervention and in consideration of the gender.

Posterolateral approaches to the thoracic spine for calcific disc herniation: is wider exposure always better?

OBJECTIVE: To compare the costotransversectomy (CTV) and transpedicular (TP) approaches versus the transfacet (TF) approach for the surgical treatment of calcific thoracic spine herniations (cTDH), in terms of surgical and clinical outcomes. BACKGROUND: Surgical approaches for cTDH are debated. Anterior approaches are recommended, while posterolateral approaches are preferred for non-calcific, paramedian, and lateral hernias. Currently, there is limited evidence about the superiority of a more invasive surgical approach, such as CTV or TP, over TF, a relatively less invasive approach, in terms of neurological outcome, pain, and surgical complications, for the treatment of cTDH. METHODS: A retrospective, observational, monocentric study was conducted on patients who underwent posterolateral thoracic approaches for symptomatic cTDH, between 2010 and 2023, at our institute. Three groups were drafted, based on the surgical approach used: TF, TP, and CTV. All procedures were assisted by intraoperative CT scan, spinal neuronavigation, and intraoperative neuromonitoring. Analyzed factors include duration of surgery, amount of bone removal, intraoperative blood loss, CSF leak, need of instrumentation for iatrogenic instability, degree of disc herniation removal, myelopathy recovery. Afterwards, a statistical analysis was performed to investigate the bony resection of the superior posterior edge of the vertebral soma. The primary outcome was the partial or total herniation removal. RESULTS: This study consecutively enrolled 65 patients who underwent posterolateral thoracic surgery for cTDH. The TF approach taking the least, and the CTV the longest time (p < 0.01). No statistical difference was observed between the three mentioned approaches, in terms of intraoperative blood loss, dural leakage, post-resection instrumentation, total herniation removal, or myelopathy recovery. An additional somatic bony resection was successful in achieving total herniation removal (p < 0.01), and the extent of bony resection was directly proportional to the extent of hernia removal (p < 0.01). CONCLUSIONS: No statistically significant differences were highlighted between the TP, TF, and CTV regarding the extent of cTDH removal, the postoperative complications, and the neurological improvement. The described somatic bone resection achieved significant total herniation removal and was directly proportional to the preop against postop anteroposterior diameter difference.

Impact of deep brain stimulation therapy on the vertebral sagittal balance in Parkinson's disease patients.

Parkinson's disease (PD) is characterized by cardinal motor signs: 4-6 Hz resting tremor, rigidity, and bradykinesia. In addition, 3-18% of PD patients have camptocormia, an abnormal forward flexion of the thoracolumbar spine, which may have a negative impact on patients' quality of life. Different possible treatments have been suggested for such a condition, but no one is resolutive. This study aims to define the possible impact of DBS, with selective targeting on the dorsal-lateral region of the STN, on the sagittal balance of patients affected by PD. Among all patients that have undergone DBS procedures in our institution, we selected eight subjects, four females and four males, with selective targeting on the dorsal-lateral region of the subthalamic nucleus (STN) because of camptocormia and other severe postural changes. Radiological assessments of spinal balance parameters before surgery and at 6 and 12 months postoperatively were carried out. Comparison of preoperative and postoperative spine X-ray data showed a statistically significant improvement in dorsal kyphosis angle (D-Cobb) 12 months after the operation. Deep brain stimulation with selective targeting of the dorsal lateral part of the STN may induce changes of the posture in patients with Parkinson's disease 12 months after the operation, which appears to improve in this small sample size, but larger observational and controlled trials would be required to confirm this observation.

Bio-inspired microneedle design for efficient drug/vaccine coating.

Biomimetics is the interdisciplinary scientific field focused on the study and imitation of biological systems, with the aim of solving complex technological problems. In this paper, we present a new bio-inspired design for microneedles (MNs) and MN arrays, intended for rapidly coating the MNs with drug/vaccine. The biomimetic approach consists in ornamenting the lateral sides of pyramidal MNs with structures inspired by the external scent efferent systems of some European true bugs, which facilitate a directional liquid transport. To realize these MNs, two-photon polymerization (TPP) technique was used. Liquid coating capabilities of structured and non-structured MNs were compared. Moreover, both in-vivo and ex-vivo skin tests were performed to prove that MNs pierce the skin. We show that the arrays of MNs can be accurately replicated using a micro-moulding technique. We believe this design will be beneficial for the process of drug/vaccine loading onto the needles' surfaces, by making it more efficient and by reducing the drug/vaccine wastage during MN coating process.

Analysis of a Low-Cost EEG Monitoring System and Dry Electrodes toward Clinical Use in the Neonatal ICU.

Electroencephalography (EEG) is an important clinical tool for monitoring neurological health. However, the required equipment, expertise, and patient preparation inhibits its use outside of tertiary care. Non-experts struggle to obtain high-quality EEG due to its low amplitude and artefact susceptibility. Wet electrodes are currently used, which require abrasive/conductive gels to reduce skin-electrode impedance. Advances in dry electrodes, which do not require gels, have simplified this process. However, the assessment of dry electrodes on neonates is limited due to health and safety barriers. This study presents a simulation framework for assessing the quality of EEG systems using a neonatal EEG database, without the use of human participants. The framework is used to evaluate a low-cost EEG acquisition system and compare performance of wet and dry (Micro Transdermal Interface Platforms (MicroTIPs), g.tec-g.SAHARA) electrodes using accurately acquired impedance models. A separate experiment assessing the electrodes on adult participants was conducted to verify the simulation framework's efficacy. Dry electrodes have higher impedance than wet electrodes, causing a reduction in signal quality. However, MicroTIPs perform comparably to wet electrodes at the frontal region and g.tec-g.SAHARA performs well at the occipital region. Using the simulation framework, a 25dB signal-to-noise ratio (SNR) was obtained for the low-cost EEG system. The tests on adults closely matched the simulated results.

Hollow silicon microneedles, fabricated using combined wet and dry etching techniques, for transdermal delivery and diagnostics.

Microneedle-based technologies are the subject of intense research and commercial interest for applications in transdermal delivery and diagnostics, primarily because of their minimally invasive and painless nature, which in turn could lead to increased patient compliance and self-administration. In this paper, a process for the fabrication of arrays of hollow silicon microneedles is described. This method uses just two bulk silicon etches - a front-side wet etch to define the 500 µm tall octagonal needle structure itself, and a rear-side dry etch to create a 50 µm diameter bore through the needle. This reduces the number of etches and process complexity over the approaches described elsewhere. Ex-vivo human skin and a customised applicator were used to demonstrate biomechanical reliability and the feasibility of using these microneedles for both transdermal delivery and diagnostics. Microneedle arrays show no damage even when applied to skin up to 40 times, are capable of delivering several mL of fluid at flowrates of 30 µL/min, and of withdrawing 1 µL of interstitial fluid using capillary action.

Design, Fabrication and Performance Assessment of Flexible, Microneedle-Based Electrodes For ECG Signal Monitoring.

Microneedle-based electrodes have attracted significant attention for the monitoring of physiological signals, including ECG, EMG, and E OG, as they have the potential to eliminate the skin preparation and stability issues associated with conventional wet gel electrodes. This paper describes the development of a polymeric flexible microneedle electrode (FMNE) that does not require skin abrasion and can be used for long-term ECG monitoring. Fabricated using a combination of epoxy resin microneedles bonded to a flexible substrate, the performance of the FMNE was compared to that of a conventional wet-gel electrode by simultaneously capturing the ECG signal using both electrodes, and estimating the signal-to-noise ratio (SNR) of each. Results show that the flexible electrode can acquire ECG signals in which all the characteristic components of the wave are visible, and that are comparable in quality to those obtained using commercial wet electrodes. Bland-Altman plots were drawn to validate the performance of FMNE, and show that the mean difference ± standard deviation in SNR obtained using wet electrodes and FMNE was [Formula: see text]. Clinical Relevance- These microneedle-based 'dry electrodes' could be used in long-term monitoring of biopotential activity.

Exploration of Microneedle-assisted skin delivery of cyanocobalamin formulated in ultraflexible lipid vesicles.

Vitamin B12 (cyanocobalamin) deficiency is a widespread condition because of its different aetiologies, like malabsorption syndrome or lifestyles as strict veganism that is increasing its incidence and prevalence in developed countries. It has important haematological consequences that require pharmacological treatment. Current therapy consists of oral or parenteral supplements of cyanocobalamin; however, the oral route is discarded for malabsorption syndrome patients and the parenteral route is not well accepted generally. Topical treatments have been suggested as an alternative, but the molecular weight and hydrophilicity of cyanocobalamin limits its diffusion through the skin. Lipid vesicles can allow the transdermal absorption of molecules > 500 Da. The aim of this work was to use different ultraflexible lipid vesicles (transfersomes and ethosomes) to enhance cyanocobalamin transdermal delivery. Vesicles were characterized and lyophilised for long-term stability. The ability to deliver cyanocobalamin through the skin was assessed in vitro using full-thickness porcine skin in Franz diffusion cells. As expected, the best transdermal fluxes were provided by ultraflexible vesicles, in comparison to a drug solution. Moreover, the pre-treatment of the skin with a solid microneedle array boosts the amount of drug that could potentially reach the systemic circulation.

Development and Characterization of Passivation Methods for Microneedle-based Biosensors.

Microneedles (MN) are short, sharp structures that have the ability to painlessly pierce the stratum corneum, the outermost layer of the skin, and interface with the dermal interstitial fluid that lies beneath. Because the interstitial fluid is rich in biomarkers, microneedle-based biosensors have the potential to be used in a wide range of diagnostic applications. To act as an electrochemical sensor, the tip or the body of the MN must be functionalized, while the substrate areas are generally passivated to block any unwanted background interference that may occur outside of the skin. This work presents four different passivation techniques, based on the application of SiO2, polymethyl methacrylate (PMMA), an adhesive film, and varnish to the substrate areas. Optical, SEM and electrochemical measurements were performed to quantitatively assess the performance of each film. The data shows that whilst manual application of varnish provided the highest level of electrical isolation, the spin-coating of a 5 µm thick layer of PMMA is likely to provide the best combination of performance and manufacturability. Clinical Relevance- Substrate passivation techniques will improve the performance of microneedle-based non-invasive continuous monitoring systems.

Midline Skull Base Meningiomas: Transcranial and Endonasal Perspectives.

Skull base meningiomas have always represented a challenge for neurosurgeons. Despite their histological nature, they may be associated with unfavorable outcomes due to their deep-seated location and the surrounding neurovascular structures. The state of the art of skull base meningiomas accounts for both transcranial, or high, and endonasal, or low, routes. A comprehensive review of the pertinent literature was performed to address the surgical strategies and outcomes of skull base meningioma patients treated through a transcranial approach, an endoscopic endonasal approach (EEA), or both. Three databases (PubMed, Ovid Medline, and Ovid Embase) have been searched. The review of the literature provided 328 papers reporting the surgical, oncological, and clinical results of different approaches for the treatment of skull base meningiomas. The most suitable surgical corridors for olfactory groove, tuberculum sellae, clival and petroclival and cavernous sinus meningiomas have been analyzed. The EEA was proven to be associated with a lower extent of resection rates and better clinical outcomes compared with transcranial corridors, offering the possibility of achieving the so-called maximal safe resection.

System Level Framework for Assessing the Accuracy of Neonatal EEG Acquisition.

Significant research has been conducted in recent years to design low-cost alternatives to the current EEG monitoring systems used in healthcare facilities. Testing such systems on a vulnerable population such as newborns is complicated due to ethical and regulatory considerations that slow down the technical development. This paper presents and validates a method for quantifying the accuracy of neonatal EEG acquisition systems and electrode technologies via clinical data simulations that do not require neonatal participants. The proposed method uses an extensive neonatal EEG database to simulate analogue signals, which are subsequently passed through electrical models of the skin-electrode interface, which are developed using wet and dry EEG electrode designs. The signal losses in the system are quantified at each stage of the acquisition process for electrode and acquisition board losses. SNR, correlation and noise values were calculated. The results verify that low-cost EEG acquisition systems are capable of obtaining clinical grade EEG. Although dry electrodes result in a significant increase in the skin-electrode impedance, accurate EEG recordings are still achievable.

Universal Applicator for Digitally-Controlled Pressing Force and Impact Velocity Insertion of Microneedles into Skin.

Microneedle technologies have been developed for dermal drug and vaccine delivery, including hollow-, solid-, coated-, and dissolving microneedles. Microneedles have been made in many different geometries and of many different materials, all of which may influence their skin-penetrating ability. To ensure reproducible and effective drug and vaccine delivery via microneedles, the optimal insertion parameters should be known. Therefore, a digitally-controlled microneedle applicator was developed to insert microneedles into the skin via impact insertion (velocity) or via pressing force insertion. Six microneedle arrays with different geometries and/or materials were applied onto ex vivo human skin with varying velocities or pressing forces. Penetration efficiency and delivered antigen dose into the skin after application of microneedles were determined. In general, microneedles pierced the skin more efficiently when applied by impact application as compared to application via pressing force. However, the angle of application of the applicator on the skin can affect the velocity of the impact, influencing the penetration efficiency of microneedles. Regarding the antigen delivery into the skin, the delivered dose was increasing by increasing the velocity or pressure, and thus, increasing the penetration efficiency. These data demonstrate that an applicator is an important tool to determine optimal application conditions with ex vivo human skin.