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.

The Optimal Targeting for Focused Ultrasound Thalamotomy Differs between Dystonic and Essential Tremor: A 12-Month Prospective Pilot Study.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is increasingly used to treat drug-resistant essential tremor (ET). Data on MRgFUS thalamotomy in dystonic tremor (DT) are anecdotal. OBJECTIVES: To investigate efficacy, safety, and differences in target coordinates of MRgFUS thalamotomy in DT versus ET. METHODS: Ten patients with DT and 35 with ET who consecutively underwent MRgFUS thalamotomy were followed for 12 months. Although in both groups the initial surgical planning coordinates corresponded to the ventralis intermediate (Vim), the final target could be modified intraoperatively based on clinical response. RESULTS: Tremor significantly improved in both groups. The thalamic lesion was significantly more anterior in DT than ET. Considering both ET and DT groups, the more anterior the lesion, the lower the odds ratio for adverse events. CONCLUSIONS: MRgFUS thalamotomy is safe and effective in DT and ET. Compared to classical Vim coordinates used for ET, more anterior targeting should be considered for DT.

Virtual hospital and artificial intelligence: a first step towards the application of an innovative health system for the care of rare cerebrovascular diseases.

The development of virtual care options, including virtual hospital platforms, is rapidly changing the healthcare, mostly in the pandemic period, due to difficulties in in-person consultations. For this purpose, in 2020, a neurological Virtual Hospital (NOVHO) pilot study has been implemented, in order to experiment a multidisciplinary second opinion evaluation system for neurological diseases. Cerebrovascular diseases represent a preponderant part of neurological disorders. However, more than 30% of strokes remain of undetermined source, and rare CVD (rCVD) are often misdiagnosed. The lack of data on phenotype and clinical course of rCVD patients makes the diagnosis and the development of therapies challenging. Since the diagnosis and care of rCVDs require adequate expertise and instrumental tools, their management is mostly allocated to a few experienced hospitals, making difficult equity in access to care. Therefore, strategies for virtual consultations are increasingly applied with some advantage for patient management also in peripheral areas. Moreover, health data are becoming increasingly complex and require new technologies to be managed. The use of Artificial Intelligence is beginning to be applied to the healthcare system and together with the Internet of Things will enable the creation of virtual models with predictive abilities, bringing healthcare one step closer to personalized medicine. Herein, we will report on the preliminary results of the NOVHO project and present the methodology of a new project aimed at developing an innovative multidisciplinary and multicentre virtual care model, specific for rCVD (NOVHO-rCVD), which combines the virtual hospital approach and the deep-learning machine system.

Fibrocartilaginous embolism: a rare cause leading to spinal cord infarction?

PURPOSE: Fibrocartilaginous nucleus pulposus components herniation and embolism rarely causes acute ischaemic events involving the spinal cord. Few reports have suggested this as a mechanism leading to anterior spinal artery syndrome. The purpose of this study was to evaluate the topography and pattern of this rare myelopathy by MRI. METHODS: A retrospective observational case series of patients, admitted to our Institute between 2008 and 2021, with a diagnosis of fibrocartilaginous embolism based on typical clinical and radiological features. RESULTS: Five patients were identified (2 men and 3 women; range 13-38 years). No one had pre-existing vascular risk factors. All referred potential precipitating event in the 24 h prior to symptom onset. MRI findings showed increased signal intensity of the spinal cord on T2-weighted images in all cases and degenerative disc changes opposite to it in four of them. The outcome was poor: three showed only partial sensitivity and motor improvement (mRs 4, 3, and 2, respectively); one completely recovered except for isolated hand paresis (mRs 1); and one remained severely neurologically affected (mRs 5). CONCLUSIONS: Fibrocartilaginous embolism must be a differential diagnosis in case of otherwise unexplained spinal cord infarction in adult and paediatric low risk population. Neuroradiological findings such as abnormal spinal cord signal intensity and degenerative disc changes can aid in early diagnosis of this rare myelopathy. The prevalent myelopathy location was thoracic. All signal alterations were detected in the anterior region of the spinal cord in the territories of the anterior spinal artery.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy May Spare Dopaminergic Therapy in Early-Stage Tremor-Dominant Parkinson's Disease: A Pilot Study.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is a safe and effective procedure for drug-resistant tremor in Parkinson's disease (PD). OBJECTIVE: The aim of this study was to demonstrate that MRgFUS ventralis intermedius thalamotomy in early-stage tremor-dominant PD may prevent an increase in dopaminergic medication 6 months after treatment compared with matched PD control subjects on standard medical therapy. METHODS: We prospectively enrolled patients with early-stage PD who underwent MRgFUS ventralis intermedius thalamotomy (PD-FUS) and patients treated with oral dopaminergic therapy (PD-ODT) with a 1:2 ratio. We collected demographic and clinical data at baseline and 6 and 12 months after thalamotomy. RESULTS: We included 10 patients in the PD-FUS group and 20 patients in the PD-ODT group. We found a significant increase in total levodopa equivalent daily dose and levodopa plus monoamine oxidase B inhibitors dose in the PD-ODT group 6 months after thalamotomy. CONCLUSIONS: In early-stage tremor-dominant PD, MRgFUS thalamotomy may be useful to reduce tremor and avoid the need to increase dopaminergic medications. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Endovascular treatment of acute ischemic stroke due to tandem lesions of the anterior cerebral circulation: a multicentric Italian observational study.

PURPOSE: Acute ischemic stroke (AIS) due to tandem lesions (TLs) of extracranial Internal Carotid Artery and Anterior Cerebral Circulation are challenging for endovascular treatment (EVT). This study aims to evaluate feasibility, safety and efficacy of EVT for TLs' AIS, with or without emergent carotid artery stenting (eCAS), in a real-life scenario. METHODS: Retrospective review of prospectively collected non-randomized thrombectomy databases from five stroke centers between 2015 and 2019. Consecutive patients with TLs' AIS were selected. Clinical, neuroimage and procedure features, as well as antiplatelet therapy regimen, were evaluated. Primary outcome was 90-day mRS ≤ 2. Secondary outcomes included: mTICI score 2b-3, extracranial recanalization, procedural complications, symptomatic intracerebral hemorrhage (SICH) and 90-day mortality. RESULTS: Two hundred twenty-seven patients were enrolled (67.8% males; mean age 65.9 ± 12.9 years). We obtained mTICI 2b-3 in 77.1%, extracranial recanalization in 86.8%, 90-day mRS (available in 201/227 cases) ≤ 2 in 49.8%. Procedural complications occurred in 16.7%, SICH in 9.7%; 90-day mortality rate (available in 201/227 cases) was 14.4%. The strongest predictors of good clinical outcome were young age (p < 0.0001), low baseline NIHSS (p = 0.008), high baseline ASPECTS (p < 0.0001), good collateral flow (p = 0.013) and extracranial recanalization (p = 0.001). The most significant predictors of SICH were low baseline ASPECTS (p < 0.0001), occurrence of complications (p < 0.0001) and eCAS (p = 0.002). CONCLUSION: In our real-life series, the EVT for TLs' AIS was feasible, safe and effective in improving 90-day functional outcome with acceptable morbi-mortality rates. ECAS increased the risk of SICH, independently from the antiplatelet therapy regimen.

Direct thrombectomy for stroke in the presence of absolute exclusion criteria for thrombolysis.

BACKGROUND: Intravenous thrombolysis (IVT)-ineligible patients undergoing direct thrombectomy tended to have poorer functional outcome as compared with IVT-eligible patients undergoing bridging therapy. We aimed to assess radiological and functional outcomes in large vessel occlusion-related stroke patients receiving direct thrombectomy in the presence of absolute exclusion criteria for IVT vs relative exclusion criteria for IVT and vs non-exclusion criteria for IVT. METHODS: A cohort study on prospectively collected data from 2282 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke cohort for treatment with direct thrombectomy (n = 486, absolute exclusion criteria for IVT alone; n = 384, absolute in combination with relative exclusion criteria for IVT; n = 777, relative exclusion criteria for IVT alone; n = 635, non-exclusion criteria for IVT). RESULTS: After adjustment for unbalanced variables (model 1), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.595, 95% CI 1.042-2.440) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.235, 95% CI 1.014-1.504). After adjustment for predefined variables (model 2: age, sex, pre-stroke mRS ≤ 1, NIHSS, occlusion in the anterior circulation, onset-to-groin time, and procedure time), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.235, 95% CI 1.014-1.504) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.246, 95% CI 1.039-1.495). No significant difference was found between the groups as regards any type of intracerebral hemorrhage and parenchymal hematoma within 24 h, successful and complete recanalization after procedure, and modified Rankin Scale score 0-2 at 3 months. After adjustment for predefined variables of model 2, ORs for death were higher in the presence of recent administration of IV heparin (OR: 2.077), platelet count < 100,000/mm3 (OR: 4.798), bacterial endocarditis (OR: 15.069), neoplasm with increased hemorrhagic risk (OR: 6.046), and severe liver disease (OR: 6.124). CONCLUSIONS: Radiological outcomes were similar after direct thrombectomy in patients with absolute, relative, and non- exclusion criteria for IVT, while an increase of fatal outcome was observed in the presence of some absolute exclusion criterion for IVT.

Machine learning assisted DSC-MRI radiomics as a tool for glioma classification by grade and mutation status.

BACKGROUND: Combining MRI techniques with machine learning methodology is rapidly gaining attention as a promising method for staging of brain gliomas. This study assesses the diagnostic value of such a framework applied to dynamic susceptibility contrast (DSC)-MRI in classifying treatment-naïve gliomas from a multi-center patients into WHO grades II-IV and across their isocitrate dehydrogenase (IDH) mutation status. METHODS: Three hundred thirty-three patients from 6 tertiary centres, diagnosed histologically and molecularly with primary gliomas (IDH-mutant = 151 or IDH-wildtype = 182) were retrospectively identified. Raw DSC-MRI data was post-processed for normalised leakage-corrected relative cerebral blood volume (rCBV) maps. Shape, intensity distribution (histogram) and rotational invariant Haralick texture features over the tumour mask were extracted. Differences in extracted features across glioma grades and mutation status were tested using the Wilcoxon two-sample test. A random-forest algorithm was employed (2-fold cross-validation, 250 repeats) to predict grades or mutation status using the extracted features. RESULTS: Shape, distribution and texture features showed significant differences across mutation status. WHO grade II-III differentiation was mostly driven by shape features while texture and intensity feature were more relevant for the III-IV separation. Increased number of features became significant when differentiating grades further apart from one another. Gliomas were correctly stratified by mutation status in 71% and by grade in 53% of the cases (87% of the gliomas grades predicted with distance less than 1). CONCLUSIONS: Despite large heterogeneity in the multi-center dataset, machine learning assisted DSC-MRI radiomics hold potential to address the inherent variability and presents a promising approach for non-invasive glioma molecular subtyping and grading.

General Anesthesia Versus Conscious Sedation and Local Anesthesia During Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: As numerous questions remain about the best anesthetic strategy during thrombectomy, we assessed functional and radiological outcomes in stroke patients treated with thrombectomy in presence of general anesthesia (GA) versus conscious sedation (CS) and local anesthesia (LA). METHODS: We conducted a cohort study on prospectively collected data from 4429 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. RESULTS: GA was used in 2013 patients, CS in 1285 patients, and LA in 1131 patients. The rates of 3-month modified Rankin Scale score of 0-1 were 32.7%, 33.7%, and 38.1% in the GA, CS, and LA groups: GA versus CS: odds ratios after adjustment for unbalanced variables (adjusted odds ratio [aOR]), 0.811 (95% CI, 0.602-1.091); and GA versus LA: aOR, 0.714 (95% CI, 0.515-0.990). The rates of modified Rankin Scale score of 0-2 were 42.5%, 46.6%, and 52.4% in the GA, CS, and LA groups: GA versus CS: aOR, 0.902 (95% CI, 0.689-1.180); and GA versus LA: aOR, 0.769 (95% CI, 0.566-0.998). The rates of 3-month death were 21.5%, 19.7%, and 14.8% in the GA, CS, and LA groups: GA versus CS: aOR, 0.872 (95% CI, 0.644-1.181); and GA versus LA: aOR, 1.235 (95% CI, 0.844-1.807). The rates of parenchymal hematoma were 9%, 12.6%, and 11.3% in the GA, CS, and LA groups: GA versus CS: aOR, 0.380 (95% CI, 0.262-0.551); and GA versus LA: aOR, 0.532 (95% CI, 0.337-0.838). After model of adjustment for predefined variables (age, sex, thrombolysis, National Institutes of Health Stroke Scale, onset-to-groin time, anterior large vessel occlusion, procedure time, prestroke modified Rankin Scale score of <1, antiplatelet, and anticoagulant), differences were found also between GA versus CS as regards modified Rankin Scale score of 0-2 (aOR, 0.659 [95% CI, 0.538-0.807]) and GA versus LA as regards death (aOR, 1.413 [95% CI, 1.095-1.823]). CONCLUSIONS: GA during thrombectomy was associated with worse 3-month functional outcomes, especially when compared with LA. The inclusion of an LA arm in future randomized clinical trials of anesthesia strategy is recommended.

Transnasal devascularisation of a sinonasal hypervascular tumour (glomangiopericytoma) with direct injection of liquid polymer agent (Squid®).

The technique of direct intratumoral injection of permanent liquid agents has evolved significantly over the past few decades. The percutaneous direct puncture technique is being utilised more and more for embolisation of head and neck hypervascular lesions. We describe a case treated via the direct percutaneous transnasal (TN) puncture technique for embolisation of a sinonasal hypervascular tumour, performed in a 21-year-old male patient. Due to extensive vascularisation of the tumour, preoperative embolisation was requested by our otolaryngologist team in order to minimise intraoperative bleeding and reduce surgical morbidity. A primary attempt at trans-arterial embolisation through selective ophthalmic artery catheterisation was unsuccessful due to unfavourable anatomy. An extensive devascularisation of the nasal fossa lesion was obtained using a single injection of low-density polymeric embolic agent (SQUID®). Post-operative eradication was uneventful. Final histopathology exam revealed vascular tumour consistent with a rare sinonasal glomangiopericytoma. To our knowledge, this is the first reported case of a rare sinonasal glomangiopericytoma treated by direct TN injection, utilising the liquid polymer agent SQUID®.

Primary versus secondary mechanical thrombectomy for anterior circulation stroke in children: An update.

This review of the literature on the use of mechanical thrombectomy (MT) in children with acute ischemic stroke from occlusion of the internal carotid artery and the proximal middle cerebral artery (MCA) compares the efficacy and safety of primary and secondary MT. We analyzed the data reported for 24 case reports from 20 relevant articles published up to 31 December 2016 and the data of a patient treated at our institution. Eighteen cases received primary MT and 7 received secondary MT. The proportions of complete MCA recanalization, small infarcts, and asymptomatic intracranial hemorrhage were similar in both MT groups (73% [11/15] vs. 67% [4/6], 58% [7/12] vs. 60% [3/5], and 15% [2/13] vs. 17% [1/6], respectively). The proportion of favorable neurological outcomes was higher for the primary MT group (69% [11/16] vs. 43% [3/7]). We found no substantial differences in efficacy and safety between primary and secondary MT for anterior circulation stroke in children.

Effects of Robot-Assisted Training for the Unaffected Arm in Patients with Hemiparetic Cerebral Palsy: A Proof-of-Concept Pilot Study.

On a voluntary basis, 10 adolescents with hemiparesis due to cerebral palsy and 11 neurologically healthy control subjects participated in this proof-of-concept pilot study. The aim was to examine the effects of robot-assisted training for the unaffected arm in patients with hemiparetic cerebral palsy. Baseline comparison between the unaffected arm of the hemiparetic patients with cerebral palsy and the dominant arm of healthy control subjects showed significant differences on the Jebsen-Taylor Hand Function test and action planning ability tests. Within-group comparison after ten 30-minute sessions (five days a week for two consecutive weeks) of robot-assisted training for the unaffected arm showed significant improvements in patients with cerebral palsy on the Jebsen-Taylor Hand Function test (performed at both hands) and action planning ability test (evaluated at the unaffected arm). Our findings are in line with previous evidences of action planning deficits at the unaffected arm in patients with hemiparetic cerebral palsy and support the hypothesis that robot-assisted training for the unaffected arm may be useful to improve manual dexterity and action planning in patients with hemiparesis due to cerebral palsy.