Bilateral Simultaneous Magnetic Resonance-Guided Focused Ultrasound Pallidotomy for Life-Threatening Status Dystonicus.

BACKGROUND: Invasive treatments like radiofrequency stereotactic lesioning or deep brain stimulation of the globus pallidus internus can resolve drug-resistant status dystonicus (SD). However, these open procedures are not always feasible in patients with SD. OBJECTIVE: The aim was to report the safety and efficacy of simultaneous asleep bilateral transcranial magnetic resonance-guided focused ultrasound (MRgFUS) pallidotomy for life-threatening SD. METHODS: We performed bilateral simultaneous MRgFUS pallidotomy under general anesthesia in 2 young patients with pantothenate kinase-associated neurodegeneration and GNAO1 encephalopathy. Both patients had medically refractory SD and severe comorbidities contraindicating open surgery. RESULTS: SD resolved at 4 and 12 days after MRgFUS, respectively. Adverse events (intraoperative hypothermia and postoperative facial paralysis) were mild and transient. CONCLUSION: Bilateral simultaneous MRgFUS pallidotomy under general anesthesia is safe and may be a valid alternative therapeutic option for fragile patients. Further studies are needed to assess long-term efficacy of the procedure. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Focused ultrasound therapy in movement disorders: management roadmap toward optimal pathway organization.

MRI-guided focused ultrasound (MRgFUS) lesioning is an innovative, safe and effective treatment which provides an innovative development in the field of minimally invasive stereotactic neurosurgery. Based on the application of focused ultrasound energy under full MR planning and thermal imaging control, unilateral lesioning of the thalamus, subthalamic nucleus, and globus pallidus is indicated for the treatment of movement disorders, including essential tremor, Parkinson's disease, and dystonia. We started to apply this technique in February 2019 for the treatment of patients with movement disorders. The authors developed a diagnostic therapeutic care pathway, which is herewith proposed and applied as an explication of standard clinical practice in use. The project was the result of the application of different methods such as Health Technology Assessment (HTA), Strengths, Weaknesses, Opportunities and Threats analysis (SWOT) and Demin -Plan, Do, Check, Act (PDCA) cycle. The aim of this project was to standardize the MRgFUS diagnostic-therapeutic pathway (DTP), describe its application and the appropriateness of different phases (patient selection, intervention phase and follow-up). Here, we described in detail our experience in the DTP application from 2019 up to now in 610 patients with movement disorders.

A Benefit/Risk Assessment of Intrathecal Ziconotide in Chronic Pain: A Narrative Review.

BACKGROUND: Ziconotide is an intrathecal drug administered for the treatment of chronic pain. The current literature lacks an exhaustive benefit/risk assessment on this drug. We herein focus on Ziconotide's pharmacology and clinical applications. METHODS: Literature research was conducted to identify studies on Ziconotide administration for the treatment of chronic pain, published between January 1990 and March 2023 and located via PubMed, Embase, Medline, Cinahl, and Web of Science, using the following keywords: Ziconotide, Omega conotoxin, Prialt, SNX-111, intrathecal therapy, and neuropathic pain. Only publications written in English were selected. RESULTS: Among the 86 selected studies, we found 4 Randomized Controlled Trials (RCTs) and 3 prospective long-term studies concerning the intrathecal use of Ziconotide as a monotherapy in chronic pain. Other studies described the intrathecal infusion of Ziconotide combined with other drugs. Overall, Ziconotide has been proved to have strong efficacy for relieving chronic pain, although patients with co-morbid psychiatric disorders require a careful monitoring when treated with Ziconotide. CONCLUSIONS: Overall, the use of Ziconotide, as a monotherapy or in conjunction with other therapies for the treatment of chronic pain, was reported to be efficacious. Overall, its use in patients with chronic pain refractory to other pharmacologic agents outweighs the possible adverse consequences, thus resulting in a favorable benefit/risk assessment.

Posterior Hypothalamic Region Deep Brain Stimulation for the Treatment of Aggression Disorders in Patients with Intellectual Disability: A Systematic Review.

INTRODUCTION: Aggressive disorders, in patients with intellectual disability, are satisfactorily managed with an educational, psychological, and pharmacological approach. Posterior hypothalamic region deep brain stimulation emerged in the last two decades as a promising treatment for patients with severe aggressive disorders. However, limited experiences are reported in the literature. METHODS: A systematic review was performed following PRISMA guidelines and recommendations by querying PubMed and Embase on August 24th, 2022, with the ensuing string parameters: ([deep brain stimulation] OR [DBS]) AND ([aggressiv*] OR disruptive). Cochrane Library, DynaMed, and ClinicalTrials.gov were consulted using the combination of keywords "deep brain stimulation" and "aggressive" or "aggression". The clinical outcome at the last follow-up and the rate of complications were considered primary and secondary outcomes of interest. RESULTS: The initial search identified 1,080 records, but only 10 studies met the inclusion criteria and were considered. The analysis of clinical outcome and complications was therefore performed on a total of 60 patients. Quality of all selected studies was classified as high, but one. Mean Overt Aggression Scale (OAS) improvement was 68%, while Inventory for Client Agency Planning (ICAP) improvement ranged between 38.3% and 80%. Complications occurred in 4 patients (6.7%). CONCLUSION: Posterior hypothalamic region deep brain stimulation may be considered a valuable option for patients with severe aggression disorders and ID. This review can represent a mainstay for those who will be engaged in the surgical treatment of these patients.

Microvascular decompression for trigeminal neuralgia: a single-center experience with 516 cases, including 32 patients with multiple sclerosis.

BACKGROUND AND OBJECTIVES: To evaluate the effectiveness and long-term pain relief of microvascular decompression (MVD) for "typical" trigeminal neuralgia (TN), including patients affected by multiple sclerosis (MS). METHODS: Between January 2011 and December 2022, 516 consecutive patients presenting with trigeminal neuralgia and a diagnosed neurovascular conflict at MRI underwent microvascular decompression surgery in our neurosurgery department. Ten surgeons with different ages and experiences performed the surgical procedures. Pain improvement, re-operation rate, and complication rates were retrospectively collected and analyzed. RESULTS: 516 patients were included (214 males 302 females, ranging from 12 to 87 years), including 32 patients with multiple sclerosis. Neurovascular compression was found in all cases during surgery. Barrow Neurological Institute pain intensity scale with a score of I was achieved in 404 patients (78,29%), a score II or III was obtained in 100 cases (19,37%) and a score of IV and V in 12 patients (2,32%). In the multiple sclerosis subset of patients, a BNI score of I was achieved in 21/32 (65.62%). The pain recurrence rate of our series was 15.11%. The follow-up for all patients was at least of 13 months, with a mean follow-up of 41.93 months (± 17.75 months, range 13-91 months). Neither intraoperative mortality nor major intra-operative complications occurred in the analyzed series. The re-operation rate was 12.98%. Thermorhizotomy, percutaneous balloon compression, cyber-knife radiosurgery, or new MVD were the surgical techniques utilized for re-operations. CONCLUSIONS: MVD may be considered an effective and safe surgical technique for TN, and in patients affected by multiple sclerosis, it may be proposed even if a less favorable outcome has to be expected with respect to classic TN patients. Larger studies focusing on the relation of multiple sclerosis with neurovascular compression are required.

3D4K exoscope in epilepsy surgery: a seminal experience.

BACKGROUND AND OBJECTIVES: To report the progressive introduction of the exoscope (EX) from surface lesionectomy to antero-mesial temporal lobectomy (AMTL) in an epilepsy surgery practice. METHODS: We describe a population of ten consecutive patients undergoing EX surgery, with a minimum follow-up of 6 months, that was compared to a similar population of patients referred to operative microscopic surgery (OM). RESULTS: All surgeries were performed with the use of EX or OM alone. Transient neurological complications for surgery in eloquent regions were recorded in one patient for each population. Nine and seven patients undergoing, respectively, EX and OM surgery resulted in Engel class Ia (90% vs. 70%). The mean duration of EX and OM surgery resulted in 265.5 and 237.9 min, respectively, with a mean of 308.3 and 253.3 min for AMTL cases, respectively. CONCLUSIONS: This preliminary study revealed that ORBEYE EX can be safe and effective in different types of epilepsy surgeries. The transition from OM to EX is fast, even though it is slower for the more challenging mesial temporal structure removal. Ergonomic and operative team interaction is improved by the use of EX. Our data need to be confirmed by larger studies.

Incidence and management of idiopathic peri-lead edema (IPLE) following deep brain stimulation (DBS) surgery: Case series and review of the literature.

OBJECTIVE: Idiopathic peri-lead edema (IPLE) is being increasingly described as a potential complication occurring after DBS surgery. Its incidence and relationship to post-operative symptoms, though, are still poorly defined and its understanding and management yet limited. METHODS: We reviewed delayed (≥ 72 h) post-operative CT imaging of patients who underwent DBS surgery at our Institution. A comparison of clinical and laboratory findings was carried out between patients with IPLE and controls. RESULTS: 61 patients, accounting for 115 electrodes, were included. Incidence of IPLE was 37.7 % per patient and 29.5 % per electrode. Patients with IPLE were significantly older than controls (52.82 ± 15.65 years vs 44.73 ± 18.82 years, p = 0.04). There was no difference in incidence of new-onset neurological symptoms between patients with IPLE and controls. Longer operative time (180.65 ± 34.30 min vs 158.34 ± 49.28 min, p = 0.06) and a greater number of MERs per electrode were associated with IPLE (3.37 ± 1.21 vs 3.00 ± 1.63, p = 0.089), though these comparisons did not meet the statistical significance. None of the patients with IPLE underwent hardware removal, with IPLE vanishing spontaneously over months. CONCLUSIONS: IPLE is an underestimated, benign event that may occur after DBS surgery. Age, longer operative time and MER use may represent risk factors for IPLE formation, but further studies are needed. The presence of post-operative neurological symptoms and fever was not associated with IPLE presence, highlighting its benign nature and suggesting that empiric treatment may not be always justified.

Left Mesial Temporooccipital PLNTY: Supracerebellar Transtentorial Approach in Epilepsy Surgery.

The supracerebellar transtentorial approach for the resection of brain lesion at the level of the mesial temporooccipital region is underused in the field of epilepsy surgery, despite the theoretical advantage of sparing normal brain structures, in particular in the dominant hemisphere for language. Hereby we present the case of a patient with a low-grade epilepsy associated tumor, presenting with weekly drug-resistant focal seizures, treated by a supracerebellar transtentorial lesionectomy. Surgery was uneventful and the histopathology revealed a pleomorphic low-grade neuroepithelial tumor of the young patient. At the 6-month follow-up, the patient did not present neurologic deficits and she never presented with seizures after surgery, so antiepileptic drug tapering started. The integration of supracerebellar transtentorial approach in the "armory" of the epilepsy neurosurgeon requires a dedicated expertise and an anesthesiologic setting used to manage the semisitting position; on the other hand, it could provide a relevant option to provide safe and complete lesionectomy in the mesial temporooccipital region, together with the more classical sublobar and transcerebral approaches (Video 1).

Vanishing contrast-enhancing peri-lead oedema following deep brain stimulation surgery: A case report.

Idiopathic peri-lead oedema (IPLE) after deep brain stimulation (DBS) surgery is still a poorly understood phenomenon. It is usually asymptomatic and does not present contrast enhancement at the post-operative Magnetic Resonance Imaging (MRI). Here we present the rare case of contrast-enhancing IPLE occurring in a completely asymptomatic patient vanishing spontaneously at the radiological follow-up at one month. The radiological picture raised the concerns of peri-lead abscess, but the absence of clinical and laboratory signs of infection and the benefit of DBS over the patient's dystonic symptoms prompted a more conservative approach. To our knowledge, this is the first reported case of asymptomatic contrast-enhancing IPLE conservatively managed.

Minimally Invasive Carpal Tunnel Release: A Technical Note and a 20-Year Retrospective Series.

Introduction The surgical treatment of carpal tunnel syndrome (CTS) has been enriched, during the last years, by different minimally invasive techniques to decompress the median nerve at the wrist as the endoscopic approaches or modified open technique. However, controversy remains about their safety and complication rate. We present the results of our minimally-invasive technique to median nerve release at the wrist. We will discuss the instrumental preoperative assessment, surgical steps, post-operative management, and complications. Methods We retrospectively reviewed clinical and neurophysiological data of all patients admitted at our institution between January 2001 and December 2020 for CTS surgery. The technique, performed under local anesthesia, is based on a single, small, linear transverse incision proximal to the wrist fold. After unsharpened dissection of subcutaneous tissues, a grooved guide is inserted in a slightly medial direction towards the fourth finger; this strategy prevents possible damages of nerve branches that could originate at this level. A second small incision over the guide's tip allows a wide corridor in the context of the ligament. The carpalotome is then inserted into the guide; the two minor wounds are closed with 5-0 prolene sutures. The final result is a wide release of the nerve. Results A total of 1568 operations on 1371 patients were performed using the described technique at our institution. The patients' cohort showed a higher prevalence of women (68%), with a mean age of 56.4 years (range 24-88 years). Paresthesia and numbness of the first three fingers were the most frequent signs and symptoms. All patients were submitted to a preoperative electrophysiological evaluation, which revealed the typical signs of CTS in most patients. The US evaluation of the median nerve at the wrist was a more recent introduction, dating from 2018. In 47 patients, despite an electromyography (EMG) not showing marked neurophysiological signs of severe CTS, the ultrasonographic evaluation was strongly consistent with the clinical diagnosis. In such patients, carpal tunnel release determined the resolution of symptoms. In 99.8% of total cases, we obtained a complete symptoms remission, with the disappearance of acroparesthesia and numbness. Conclusion The use of this technique has become widespread at our institution due to fewer local complications, a very low rate of recurrence, faster functional recovery, and reduced surgical time if compared to traditional open surgery and to endoscopic release too.

Assessing the role of sodium fluorescein in peripheral nerve sheath tumors and mimicking lesions surgery: An update after 142 cases.

Objective: Peripheral nerve sheath tumors (PNST) include mainly schwannomas and neurofibromas. Surgical resection represents the mainstay of treatment but due to their pathogenesis, distinguishing between intact functional nerve and the fibers from whence the PNST arose may not always be easy to perform, constituting the most relevant risk factor in determining a worsening in neurological condition. The introduction of intraoperative tools to better visualize these tumors could help achieve a gross-total resection. In this study, we analyzed the effect of sodium fluorescein (SF) on the visualization and resection of a large cohort of PNST. Methods: Between September 2018 and December 2021, 142 consecutive patients harboring a suspected PNST underwent fluorescein-guided surgery at the Department of Neurosurgery of the Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. All patients presented with a different degree of contrast enhancement at preoperative MRI. SF was intravenously injected after intubation at 1 mg/kg. Intraoperative fluorescein characteristics and postoperative neurological and radiological outcomes were collected, analyzed, and retrospectively compared with a historical series. Results: 142 patients were included (42 syndromic and 100 sporadic); schwannoma was the predominant histology, followed by neurofibroma (17 neurofibroma e 12 plexiform neurofibroma) and MPNST. Bright fluorescence was present in all cases of schwannomas and neurofibromas, although with a less homogeneous pattern, whereas it was significantly less evident for malignant PNST; perineurioma and hybrid nerve sheath tumors were characterized by a faint fluorescence enhancement. The surgical resection rate in the general population and even among the subgroups was about 66.7%; from the comparative analysis, we found a consistently higher rate of complete tumor removal in plexiform neurofibromas, 66% in the "fluorescent" group vs 44% in the "historical" group (p-value < 0.05). The rate of complications and mean surgical time were superimposable among the two populations. Conclusions: SF is a valuable method for safe fluorescence-guided PNST and mimicking lesions resection. Our data showed a positive effect of fluorescein-guided surgery in increasing the rate of surgical resection of plexiform neurofibromas, suggesting a possible role in improving the functional and oncological outcome of these lesions.

The Lipid Asset Is Unbalanced in Peripheral Nerve Sheath Tumors.

Peripheral nerve sheath tumors (PNSTs) include schwannomas, neurofibromas (NFs), and plexiform neurofibromas (PNFs), among others. While they are benign tumors, according to their biological behavior, some have the potential for malignant degeneration, mainly PNFs. The specific factors contributing to the more aggressive behavior of some PNSTs compared to others are not precisely known. Considering that lipid homeostasis plays a crucial role in fibrotic/inflammatory processes and in several cancers, we hypothesized that the lipid asset was also unbalanced in this group of nerve tumors. Through untargeted lipidomics, NFs presented a significant increase in ceramide, phosphatidylcholine, and Vitamin A ester. PNFs displayed a marked decrease in 34 out of 50 lipid class analyzed. An increased level of ether- and oxidized-triacylglycerols was observed; phosphatidylcholines were reduced. After sphingolipidomic analysis, we observed six sphingolipid classes. Ceramide and dihydroceramides were statistically increased in NFs. All the glycosylated species appeared reduced in NFs, but increased in PNFs. Our findings suggested that different subtypes of PNSTs presented a specific modulation in the lipidic profile. The untargeted and targeted lipidomic approaches, which were not applied until now, contribute to better clarifying bioactive lipid roles in PNS natural history to highlight disease molecular features and pathogenesis.

Intraoperative compound muscle action potentials (CMAPs) amplitude changes after decompression and neurolysis of peripheral nerves in upper limbs neuropathies: electrophysiologial considerations and relation with clinical outcome.

BACKGROUND: Decompression and, when necessary, neurolysis in entrapment neuropathies of upper limbs are effective and safe procedures, but their correlation with the variation of compound muscle action potentials (CMAPs) is still unclear, based in particular on experimental models. In addition, there are few data regarding the efficacy of intraoperative neurophysiologic monitoring (IOM) to predict clinical early and late outcome after surgery in term of pain control and sensitive/motor recovery. We report about the association between the intraoperative anatomical and neurophysiological findings and the mid- and long-term postoperative clinical course in a surgical series. METHODS: We retrospectively reviewed clinical data of 24 patients among 68 admitted at our Institution for upper limb neuropathies from September 2012 to May 2015. All patients completed two preoperative questionnaires for assessing the level of disability (DASH) and of pain/discomfort (NRS). CMAPs' amplitudes were intraoperatively detected, before and after decompression and neurolysis and the variations were then related to clinical outcome, evaluated through DASH and NRS questionnaires at 6-, 9- and 12-months follow-up. RESULTS: A statistically significant difference was noted in CMAPs amplitudes before and after decompression (P<0.01). In two patients, this variation was so satisficing to determinate the end of procedure, without the need to perform neurolysis. Major correlations between the variation of CMAPs amplitude after surgery and change of DASH and NRS scores at follow-up were found. CONCLUSIONS: Variations of CMAPs amplitude provide real-time information on nerves function and may be helpful in predicting mid- and long-term postoperative outcome regarding pain relief and neurological functions.

Contrast-Enhanced Ultrasound Assisted Surgery of Intramedullary Spinal Cord Tumors: Analysis of Technical Benefits and Intra-operative Microbubble Distribution Characteristics.

Intra-operative contrast-enhanced ultrasound (CEUS) is a relatively standardized procedure in brain neurosurgery, but it is still underused in spinal cord and intramedullary tumor evaluation. We reviewed and analyzed the intra-operative data from a surgical series of patients harboring intramedullary spinal cord tumors who underwent surgery under CEUS guidance. CEUS was performed in 12 patients (age range: 13-55 y); all lesions had ill-defined boundaries or peritumoral cysts at preliminary intra-operative B-mode ultrasound. CEUS highlighted the tumors in all cases. The contrast agent's spinal distribution revealed different phases (arterial, peak, washout), as observed in the brain, but these appeared to be slower and less intense. In our experience, intra-operative CEUS allows surgeons to assess spinal cord perfusion and highlight intramedullary tumors in real time. As for other imaging modalities, ultrasound contrast agents add valuable information over baseline imaging, and their use should be fostered to better understand microbubble distribution dynamics.

The effect of ozone injection within a common peroneal nerve schwannoma: A mistreatment due to a misdiagnosis.

BACKGROUND: Peripheral schwannomas can be misdiagnosed or mistreated as they can mimic other subcutaneous lesions, leading to wrong diagnosis and, therefore, to improper treatment. CASE DESCRIPTION: A 23-years-old male presented a painful growing nodule at the left popliteal fossa, with distally irradiated pain. A first magnetic resonance imaging depicted a heterogeneous lesion between common peroneal and sural nerves but, surprisingly, the patient was submitted to perilesional injection of ozone-oxygen mixture, causing the onset of intense neuropathic pain. A second MRI showed a morphological change of tumor characteristics. He finally underwent surgery but, intraoperatively, inter-fascicular fibrous adherences were noticed, making the tumor removal more difficult and riskier. The histopathological diagnosis was of schwannoma with areas of foreign body reaction. CONCLUSION: The injection of ozone or other substances within a subcutaneous swelling should be avoided, before a complete imaging assessment; because of such swelling could be a peripheral nerve schwannoma. The correct assessment of a lesion of the limbs determining radiating pain should be carefully demanded to a thorough history, clinical examination, and appropriate imaging technique. To avoid incorrect management, the treatment of such tumors should be performed in the first place by dedicated equips with proven expertise in this field.

High-Definition 4K 3D Exoscope (ORBEYETM) in Peripheral Nerve Sheath Tumor Surgery: A Preliminary, Explorative, Pilot Study.

BACKGROUND: Surgery for peripheral nerve sheath tumors aims to preserve functional fascicles achieving gross-total resection. Increasing the visualization of anatomic details helps to identify the different layers and the tumor-nerve interface. The traditional microscope can present some limitations in this type of surgery, such as its physical obstruction. OBJECTIVE: To present a proof-of-concept study about exoscope-guided surgery for schwannomas of the lower limbs, to analyze the advantages and disadvantages of the 4K, high-quality, 3-dimensional (3D) imaging. METHODS: We analyzed 2 consecutive surgical cases of suspected schwannomas of the lower limbs using the ORBEYE™ exoscope (Olympus). A standard operative microscope was also available in the operating room. All procedures were performed with neurophysiological monitoring, to identify functioning nerves and to localize the tumor capsule safest entry point. The cases are reported according to the PROCESS guidelines. RESULTS: In both cases, we achieved a gross total resection of the schwannomas; the exoscope provided an excellent view of the anatomic details at tumor-nerve interface, as visible in intraoperative images and in the 3D-4K video supporting these findings. The surgeon's position was comfortable in both cases, although if the co-surgeon positioned himself in front of the first surgeon, the comfort was slightly reduced. The 4K monitor allowed a realistic, nontiring 3D vision for all the team. CONCLUSION: The ORBEYETM, after an adequate learning curve, can represent a feasible and comfortable instrument for nerve tumor surgery, which is usually performed in a single horizontal plane. Further and wider clinical series are necessary to confirm this first impression.