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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. [ABSTRACT FROM AUTHOR]

Background: The evidence in the effectiveness of deep brain stimulation in children with medication‐refractory non‐degenerative monogenic dystonia is heterogeneous and long‐term results are sparse. Objectives: The objective is to describe long‐term outcomes in a single‐center cohort and compare our results with a meta‐analysis cohort form literature. Methods: We performed a retrospective single‐center cohort study including consecutive pediatric patients with non‐degenerative genetic or idiopathic dystonia treated with globus pallidus internus deep brain stimulation at our center and a systematic review and individual‐patient data meta‐analysis with the same inclusion criteria. The primary outcome was the change from baseline in the Burke‐Fahn‐Marsden Dystonia Rating Scale‐movement (BFMDRS‐M) score. Results: The clinical cohort included 25 patients with a mean study follow‐up of 11.4 years. The meta‐analysis cohort included 224 patients with a mean follow‐up of 3 years. Overall, the BFMDRS‐M mean improvements at 1 year and at last follow‐up were 41% and 33% in the clinical cohort and 58.9% and 57.2% in the meta‐analysis cohort, respectively. TOR1A‐dystonia showed the greatest and most stable BFMDRS‐M improvement in both cohorts at 1 year and at last follow‐up (76.3% and 74.3% in the clinical cohort; 69.6% and 67.3% in the meta‐analysis cohort), followed by SGCE‐dystonia (63% and 63.9% in the meta‐analysis cohort). THAP1‐dystonia (70.1% and 29.8% in the clinical cohort; 52.3% and 42.0% in the meta‐analysis cohort) and KMT2B‐dystonia (33.3% and 41.3% in the clinical cohort; 38.0% and 26.7% in the meta‐analysis cohort) showed a less pronounced or sustained response. Conclusion: Globus pallidus deep brain stimulation long‐term treatment seems effective with a possible gene‐specific differential effect. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and purpose: Iatrogenic cerebral amyloid angiopathy (iCAA) is a specific type of cerebral amyloid angiopathy which is becoming increasingly diagnosed. It has been hypothesized that iCAA might arise as a late consequence of past neurosurgical interventions involving dural patch grafts. Positron emission tomography (PET) scans with amyloid tracers and the assay of beta‐amyloid levels in cerebrospinal fluid (CSF) are auxiliary criteria, however, definite diagnosis remains histopathologically determined. Methods: Case report. Results: We present a 48‐year‐old patient who suffered multiple lobar cerebral haemorrhages from the age of 47. The patient had undergone surgery for remolval of hemangioblastoma with lyophilized dural graft at the age of 11, in 1987. Brain MRI, amiloid PET and CSF analysis led to a diagnosis of probable iCAA. Conclusion: It is necessary to increase the awareness of iCAA, in order to avoid overlooking the potential causal involvement of surgical procedures which took place far back in time. Moreover, the diagnostic relevance of amyloid PET and beta‐amyloid levels in CSF must be emphasised. [ABSTRACT FROM AUTHOR]

Objectives: Cerebral amyloid angiopathy (CAA)-related features on neuroimaging often coexist with signs of arteriolosclerosis-small vessel disease on neuroimaging in people with intracranial hemorrhage (ICH). This study aimed at defining the value of amyloid pathology detected by 18F flutemetamol PET in reclassification and stratification of risk of bleeding in people with mixed CAA-arteriolosclerosis features., Methods: We included consecutive patients admitted to 2 institutions (2018-2023) with spontaneous symptomatic ICH, subarachnoid hemorrhage (SAH), transient focal neurologic episodes (TFNE), or cognitive impairment and MRI showing CAA hallmarks. All patients underwent brain magnetic resonance imaging (MRI) with susceptibility weighted imaging and 18F flutemetamol PET imaging and were followed up for at least 1 year. We compared cases with CAA and arteriolosclerosis + CAA features and defined long-term outcomes (composite outcome including death, ICH, ischemic stroke, SAH, TFNE) depending on PET status (CAA/amyloid pathology vs arteriolosclerosis-predominant groups)., Results: Among 47 patients, according to PET and MRI imaging, 38 patients were reclassified in the CAA/amyloid pathology group and 9 in the arteriolosclerosis-predominant group, with similar cardiovascular risk factors but a significantly higher lobar microbleed burden for the former group. The CAA/amyloid pathology group had higher rates of composite outcome (43.9 vs 11.1 events per 100 patient-year; p = 0.039) and ICH (36.5 vs 5.6 events per 100 patient-years; p = 0.04) compared with the arteriolosclerosis-predominant group., Discussion: 18F Flutemetamol PET imaging can help in reclassification of mixed arteriolosclerosis + CAA into CAA/amyloid pathology and arteriolosclerosis-predominant, with implications on long-term risk of recurrent events., Classification of Evidence: This study provides Class IV evidence that 18F flutemetamol PET can distinguish between CAA + arteriolosclerosis and arteriolosclerosis-predominant pathology.

Background: Heterozygous mutations in the GBA gene, encoding the lysosomal enzyme β-glucocerebrosidase (GCase), are the most frequent genetic risk factor for Parkinson's disease (PD). GBA -related PD (GBA-PD) patients have higher risk of dementia and reduced survival than non-carriers. Preclinical studies and one open-label trial in humans demonstrated that the chaperone ambroxol (ABX) increases GCase levels and modulates α-synuclein levels in the blood and cerebrospinal fluid (CSF)., Methods and Analysis: In this multicentre, double-blind, placebo-controlled, phase II clinical trial, we randomise patients with GBA-PD in a 1:1 ratio to either oral ABX 1.2 g/day or placebo. The duration of treatment is 52 weeks. Each participant is assessed at baseline and weeks 12, 26, 38, 52 and 78. Changes in the Montreal Cognitive Assessment score and the frequency of mild cognitive impairment and dementia between baseline and weeks 52 are the primary outcome measures. Secondary outcome measures include changes in validated scales/questionnaires assessing motor and non-motor symptoms. Neuroimaging features and CSF neurodegeneration markers are used as surrogate markers of disease progression. GCase activity, ABX and α-synuclein levels are also analysed in blood and CSF. A repeated-measures analysis of variance will be used for elaborating results. The primary analysis will be by intention to treat., Ethics and Dissemination: The study and protocols have been approved by the ethics committee of centres. The study is conducted according to good clinical practice and the Declaration of Helsinki. The trial findings will be published in peer-reviewed journals and presented at conferences., Trial Registration Numbers: NCT05287503, EudraCT 2021-004565-13., Competing Interests: Competing interests: RC has received speaking honoraria from Zambon Italia; Zambon SAU; Bial Italia Srl; advisory board fees from Bial; research support from the Italian Ministry of Health; he is Editor-in-Chief of the neuromuscular and movement disorders section of Brain Sciences (MDPI); Associate Editor of Parkinsonism and Related Disorders (Elsevier) and Frontiers in Ageing Neuroscience., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cerebral metastasis (CM) is the most common malignancy affecting the brain. Individualized treatment of CM still represents a challenge for neuro-oncological teams: in patient eligible for surgery, complete tumor removal is the most relevant predictor of overall survival (OS) and neurological outcome. The development of surgical microscopes harboring specific filter able to elicit the fluorescent response from sodium fluorescein (SF) has facilitated fluorescein-guided microsurgery and the identification of pathological tumor tissue, especially at the tumor margins. In this study, we analyzed the effect of SF on the visualization and resection of a large monoinstitutional cohort of CM., Methods: Surgical database of FLUOCERTUM study (Besta Institute, Milan, Italy) was retrospectively reviewed to find CM surgically removed with a fluorescein-guided technique from March 2016 to December 2022. SF was intravenously injected (5 mg/kg) immediately after induction of general anesthesia. Tumors were removed using a microsurgical technique with the YELLOW560 filter (Carl Zeiss Meditec, Oberkochen, Germany). In the most recent cases, biopsies at the tumor margins were performed to evaluate the ability of fluorescein to discriminate between fluorescent and nonfluorescent tissue at the lesion borders., Results: Seventy-nine patients were included; most of them showed a bright, diffuse fluorescent staining that markedly enhanced tumor visibility; 11 melanomas presented a specific faint enhancement of the black pigmented central nodule with high fluorescence at tumor boundaries. Only in a minimal percentage of cases (N.=4-5.1%), fluorescein enhancement was tenuous, thus not providing a significant help during tumor resection. Altogether, in more than 90% of cases, SF was considered useful in the identification of tumoral tissue and in achieving a high rate of CM resection; thus, gross total resection was achieved in 96.2% (N.=76) of patients and in no case the detection of tumor remnants was an unexpected event. The resulted sensitivity and specificity of fluorescein in identifying tumor tissue at the tumor margin was 88.9% with a predictive positive value of 88.9%. No adverse event was registered during the postoperative course., Conclusions: The use of SF is a valuable method for safe fluorescence-guided tumor resection. Our data showed a positive effect of fluorescein-guided surgery on intraoperative visualization during resection of CM, suggesting a role in improving the extent of resection of these lesions.

Disorders of consciousness (DOC) raise profound scientific, clinical, ethical, and philosophical issues. Growing knowledge on fundamental principles of brain organization in healthy individuals offers new opportunities for a better understanding of residual brain function in DOCs. We here discuss new perspectives derived from a recently proposed scheme of brain organization underlying consciousness in healthy individuals. In this scheme, thalamo-cortical networks can be divided into two, often antagonistic, global systems: (i) a system of externally oriented, sensory-motor networks (the "extrinsic" system); and (ii) a system of inward-oriented networks (the "intrinsic" or default system). According to this framework, four distinct mental states would be possible that could be relevant for understanding DOCs. In normal healthy volunteers and locked-in syndrome patients, a state of high functionality of both the extrinsic and intrinsic or default systems is expected--associated with full awareness of environment and self. In this case, mental imagery tasks combined with fMRI can be used to detect covert awareness in patients that are unable to communicate. According to the framework, two complementary states of system imbalance are also possible, in which one system is in a hyperfunctional state, while the other is hypoactive. Extrinsic system hyperfunction is expected to lead to a state of total sensory-motor "absorption" or "lost self." In contrast, intrinsic or default system hyperfunction is expected to lead to a state of complete detachment from the external world. A state where both extrinsic and intrinsic systems are hypofunctional is predicted to lead to markedly impaired consciousness as seen in DOCs. Finally, we review the potential use of ultra-slow fluctuations in BOLD signal as a tool for assessing the functional integrity of extrinsic and intrinsic systems during "resting state" fMRI acquisitions. In particular, we discuss the potential provided by assessment of these slow spontaneous BOLD fluctuations as a novel tool in assessing the cognitive state and chances of recovery from brain pathologies underlying DOCs.