Essential tremor and parkinsonian tremor affect approximately 5–7% of individuals over the age of 65. Pharmacological therapies yield sustained clinical improvement in only about 50% of cases. For patients ineligible for deep brain stimulation, Gamma Knife thalamotomy (GKVIM) offers a non-invasive alternative, demonstrating a tremor reduction efficacy of 70–80%, typically with a latency of approximately 4.8 months. This study aimed to identify regional cerebral metabolic patterns predictive of clinical response to GKVIM using [¹8F]-FDG positron emission tomography (FDG-PET). Fifteen consecutive patients diagnosed with essential tremor (n=10) or parkinsonian tremor (n=5) underwent preoperative cerebral FDG-PET imaging within 24 hours prior to GKVIM at Erasme University Hospital between January 2020 and January 2023. All patients were clinically followed for a minimum of six months (mean follow-up: 9 ± 3 months) by experienced neurologists or neurosurgeons. Statistical Parametric Mapping (SPM) was used to compare metabolic patterns between treatment responders (n=11; 73%) and non-responders (n=4) to identify potential predictors of therapeutic response. As a secondary objective, metabolic differences between patients with essential tremor and healthy controls (n=54) were analyzed to explore neurobiological correlates of disease pathophysiology. Those analysis revealed that responders exhibited significant hypometabolism in the prefrontal cortex and supramarginal gyrus, alongside cerebellar hypermetabolism. In the secondary analysis, patients with essential tremor demonstrated distinct metabolic alterations, notably involving the inferior olivary nuclei. This study thus identifies specific regional cerebral metabolic patterns associated with favourable clinical response to Gamma Knife thalamotomy, suggesting potential neuroimaging biomarkers for patient selection. Moreover, the observed metabolic changes provide additional insight into the pathophysiological mechanisms underlying essential tremor.

Background Most patients with Fontan circulation struggle to increase cardiac output during exercise affecting aerobic capacity, response to training and quality of life. This poor cardiac performance affects their aerobic capacity, their response to training and their quality of life. We sought to identify the pre-Fontan and managerial factors that influence their exercise cardiac performance. Methods We retrospectively collected pre and post-Fontan anatomical, anamnestic and hemodynamic data in 57 consecutive young Fontan patients (median age 14.7 years) who underwent cardiopulmonary exercise test. We studied their exercise cardiac performance using a thoracic bioelectrical impedance device that allows measurement of the peak cardiac index (pCI). Results The median age at Fontan was 6.4±3 years. In multivariable models, pCI was negatively influenced by cyanosis duration (B=−0.240; P=0.0002). Peak indexed stroke volume (pSVi) was negatively influenced by Norwood procedure (B=-8.415; P=0.005) and cyanosis duration (B=−1.591; P=0.0002) and peak heart rate (pHR) by pre-Fontan peripheral oxygen saturation (B=0.602 P=0.009). Cyanosis duration≤6.9 years predicted a pSVi≥45 mL/m2 (AUC=0.747; P=0.001). Furthermore, pSVi and pHR were correlated with post-Fontan ventricular filling pressure (post-VFP) (respectively rp=−0.539, p=0.012 and rp=−0.552; P=0.010) and post-VFP was correlated with bidirectional cavopulmonary shunt duration (rs=0.498, P=0.023). Conclusion In young Fontan patients, the duration of cyanosis and low peripheral oxygen saturation prior to the Fontan procedure affect both components of cardiac exercise performance probably through increased ventricular filling pressure. Shortening the duration of cyanosis could help preserve cardiac performance in the long term.

We show how to properly extract the local charge order in two-dimensional materials from scanning tunneling microscopy/spectroscopy (STM/STS) measurements. When the charge order presents spatial variations at the atomic scale inside the unit cell and is energy dependent, particular care should be taken. In such cases the use of the lock-in technique, while acquiring an STM topography in closed feedback loop, leads to systematically incorrect dI/dV measurements giving a false local charge order. A correct method is either to perform a constant height measurement or to perform a full grid of dI/dV(V) spectroscopies, using a bias voltage setpoint outside the material bandwidth where the local density-of-states (LDOS) is spatially homogeneous. We take as a paradigmatic example of two-dimensional material the 1/3 single-layer Pb/Si(111). As large areas of this phase cannot be grown, charge ordering in this system is not accessible to angular resolved photoemission or grazing x-ray diffraction. Previous investigations by STM/STS supplemented by {\it ab initio} Density Functional Theory (DFT) calculations concluded that this material undergoes a phase transition to a low-temperature $3\times 3$ reconstruction where one Pb atom moves up, the two remaining Pb atoms shifting down. A third STM/STS study by Adler {\it et al.} [PRL 123, 086401 (2019)] came to the opposite conclusion, i.e. that two Pb atoms move up, while one Pb atom shifts down. This latter erroneous conclusion comes from a misuse of the lock-in technique. In contrast, using a full grid of dI/dV(V) spectroscopy measurements, we show that the energy-dependent LDOS maps agree very well with state-of-the-art DFT calculations confirming the one-up two-down charge ordering. This structural and charge re-ordering in the $3\times 3$ unit cell is equally driven by electron-electron interactions and the coupling to the substrate.

Ependymomas are the most common intramedullary tumors in adults. While gross total resection is the aim of surgery, tumor infiltration might limit resection. In cases of subtotal removal, the necessary adjuvant management remains unclear. The aim of our study was to assess the need for adjuvant radiotherapy after an incomplete resection of grade II intramedullary ependymomas (IME-II). We retrospectively reviewed all cases of IME-II operated upon at a single tertiary neurosurgical center from 2009 to 2018. Patients with anaplastic or myxopapillary ependymomas, and patients with a follow-up of less than three years, were excluded. We included 46 patients: 19 (41.3%) had a gross total resection; 21 (45.7%) had a subtotal resection; and 6 (13%) had a partial resection. None of the patients underwent adjuvant radiotherapy. Over a median follow-up of 79 months (range = 36-186), seven patients presented a radiological tumor progression with a mean delay of 50.9 months (range = 18-85), of which two were symptomatic (4.3%). Progression-free survival (PFS) was 90.1% at 5 years and 76.8% at 10 years. The extent of the resection was the only significant risk factor for secondary tumor progression (p = 0.012). Four of the seven patients with recurring IME-II were treated: three patients had a second surgery, leading to two GTR and one STR, followed by radiotherapy in one case, and one patient underwent radiotherapy alone. In this study, the rate of symptomatic progression and retreatment after incomplete resection of IME-II without adjuvant radiotherapy was low, suggesting a conservative approach in such cases.

Central Nervous System (CNS) embryonal tumors represent a heterogeneous group of highly aggressive tumors occurring preferentially in children but also described in adolescents and adults. In 2021, the CNS World Health Organization (WHO) classification drastically changed the diagnosis of the other CNS embryonal tumors including new histo-molecular tumor types. Here, we report a pediatric case of a novel tumor type among the other CNS embryonal tumors classified within the methylation class "CNS Embryonal Tumor with BRD4-LEUTX Fusion". The patient was a 4-year girl with no previous history of disease. For a few weeks, she suffered from headaches, vomiting and mild fever associated with increasing asthenia and loss of weight leading to a global deterioration of health. MRI brain examination revealed a large, grossly well-circumscribed tumoral mass lesion located in the left parietal lobe, contralateral hydrocephalus and midline shift. Microscopic examination showed a highly cellular tumor with a polymorphic aspect. The majority of the tumor harbored neuroectodermal features composed of small cells with scant cytoplasm and hyperchromatic nuclei associated with small "medulloblastoma-like" cells characterized by syncytial arrangement and focally a streaming pattern. Tumor cells were diffusely positive for Synaptophysin, CD56, INI1 and SMARCA4 associated with negativity for GFAP, OLIG-2, EMA, BCOR, LIN28A and MIC-2. Additional IHC features included p53 protein expression in more than 10% of the tumor's cells and very interestingly, loss of H3K27me3 expression. The Heidelberg DNA-methylation classifier classified this case as "CNS Embryonal Tumor with BRD4:LEUTX Fusion". RNA-sequencing analyses confirmed the BRD4 (exon 13)-LEUTX (exon 2) fusion with no other molecular alterations found by DNA sequencing. Our case report confirmed that a new subgroup of CNS embryonal tumor with high aggressive potential, loss of H3K27me3 protein expression, BRDA4-LEUTX fusion, named "Embryonal CNS tumor with BRD4-LEUTX fusion", has to be considered into the new CNS WHO classification.

Introduction: The incidence of intramedullary spinal cord tumors ranges from 2 to 4% of all central nervous system tumors. Only 6-8% are astrocytomas. The gold standard to diagnose a spinal cord tumor is the spinal cord MRI in toto. Specific radiological criteria orient the diagnosis of the intradural intramedullary lesion. Most of the authors studied adult populations of astrocytomas. However, pediatric astrocytomas present certain particularities.Research question: This work aims to determine if the usual radiological criteria of intramedullary astrocytomas (IMAs) are different depending on the patient's age. Material & methods: We evaluated the radiological features of IMAs in adult and pediatric groups through a retrospective study.Results: We collected 31 patients with IMAs (11 children and 20 adults). We observed some trends but we did not highlight any statistically significant difference between all the radiological criteria studied (sagittal and axial spinal cord localization, T1-and T2-weighted characteristics, contrast uptake, infiltrating character, presence of necrosis, heterogeneous lesion, necrotic, hemorrhagic, presence of edema) and the patient's age.Discussion & conclusion: Given the rarity of IMAs and the lack of large specific pediatric studies, it seems essential to routinely report all cases encountered and create multicentric pediatric databases to draw more robust conclusions.

Aims The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis. Methods Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy. Results We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia. Conclusions These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

Intramedullary spinal cord tumors (ISCT) are rare tumors requiring multidisciplinary care in an expert center. Here, we report a single-center experience including 247 patients with ISCT: 134 ependymomas, 54 astrocytomas and 59 hemangioblastomas. Preoperative evaluation and surgical considerations are discussed to share our principles in managing these patients. Ependymomas are largely benign lesions (95% of WHO grade II) for which total resection (91% rate of gross total resection (GTR)) without neurological impairment (79% of patients remained stable or improved) is the goal in order to ensure long-term oncological control (94.5% overall survival at 5 years, excluding anaplastic ependymomas). On the other hand, astrocytomas are more frequently high-grade tumors (30% of WHO grade III or IV) for which partial resection (60% of cases) is often necessary to preserve neurological status (48% of patients deteriorate at one year), leading to higher rates of recurrence (60% recurrence rate at 5 years for grade III astrocytomas). Lastly, spinal hemangioblastomas require a specific microsurgical resection with particular attention to the vasculature in order to ensure en bloc resection (95% GTR), allowing excellent neurological results (12% of patients improved, 86% remained stable). Altogether, these results demonstrate that ISCT can be managed surgically with good functional outcome, while oncological results will mostly depend on the histopathological grading.

Intramedullary spinal cord tumors (ISCT) are rare tumors requiring multidisciplinary care in an expert center. Here, we report a single-center experience including 247 patients with ISCT: 134 ependymomas, 54 astrocytomas and 59 hemangioblastomas. Preoperative evaluation and surgical considerations are discussed to share our principles in managing these patients. Ependymomas are largely benign lesions (95% of WHO grade II) for which total resection (91% rate of gross total resection (GTR)) without neurological impairment (79% of patients remained stable or improved) is the goal in order to ensure long-term oncological control (94.5% overall survival at 5 years, excluding anaplastic ependymomas). On the other hand, astrocytomas are more frequently high-grade tumors (30% of WHO grade III or IV) for which partial resection (60% of cases) is often necessary to preserve neurological status (48% of patients deteriorate at one year), leading to higher rates of recurrence (60% recurrence rate at 5 years for grade III astrocytomas). Lastly, spinal hemangioblastomas require a specific microsurgical resection with particular attention to the vasculature in order to ensure en bloc resection (95% GTR), allowing excellent neurological results (12% of patients improved, 86% remained stable). Altogether, these results demonstrate that ISCT can be managed surgically with good functional outcome, while oncological results will mostly depend on the histopathological grading. (C) 2020 Published by Elsevier Masson SAS.

Background Hemangioblastomas (HBL) are benign tumors occurring sporadically or associated with Von Hippel-Lindau syndrome (VHL). Method We present the pre-, per-, and postoperative course of a rare case with radicular HBL presenting with subarachnoid hemorrhage (SAH) in the frame of VHL. We describe the microsurgical approach. Conclusion Complete microsurgical in bloc resection has been performed. Postoperative course was uneventful.

Introduction. - Subarachnoid haemorrhage (SAH), secondary to spinal hemangioblastoma (HBL), is extremely rare, with only a few case reports to date. We report the experience of our reference centre for spinal tumours and Von Hippel-Lindau (VHL) disease in patients with spinal HBL presenting with SAH. We further performed a systematic review of the literature. Methods. - We report two cases. A systematic search was performed using the PubMed, Embase and Cochrane databases, with no limit for publication date. Inclusion criteria were: patients with HBL presenting with SAH, with or without VHL. The systematic review retrieved only 10 studies, including 16 patients. Results. - In our centre, the first case concerned radicular HBL at D12 level, presenting with spinal and brain SAH. The patient underwent uneventful microsurgical en bloc resection. Postoperative course was normal. The second case concerned HBL with SAH at the cervico-medullary junction, with rapidly fatalcourse. The systematic review revealed female predominance, at a median age of 40 years, with HBL predominantly located at cervical level, common preoperative symptoms being headache and signs of meningeal irritation. Conclusions. - In conclusion, spinal HBL is an extremely rare cause of SAH. The systematic review found putative risk factors: female gender, age 40-50 years, cervical location, and median size 2 cm. Diagnosis can be difficult when presentation mimics intracerebral SAH. We advocate early surgical removal. The risk of rapidly fatal course, in case of major haemorrhage, needs to be borne in mind. (C) 2020 Elsevier Masson SAS. All rights reserved.

BACKGROUND:Population aging raises questions about extending treatment indications in elderly patients with aneurysmal subarachnoid hemorrhage (aSAH). We therefore assessed functional status 1 year after treatment. METHODS:This study involved 310 patients, aged over 70 years, with ruptured brain aneurysm, enrolled between 2008 and 2014 in a prospective multicentre trial (FASHE study: NCT00692744) but considered unsuitable for randomisation and therefore analysed in the observational arms of the study: endovascular occlusion (EV), microsurgical exclusion (MS) and conservative treatment. The aims were to assess independence, cognition, autonomy and quality of life (QOL) at 1 year post-treatment, using questionnaires (MMSE, ADLI, IADL, EORTC-QLQ-C30) filled in by independent nurses after discharge. RESULTS:The 310 patients received the following treatments: 208 underwent EV (67.1%), 54 MS (17.4%) and 48 were conservatively managed (15.5%). At 1 year, independence rates for patients admitted with good clinical status (WFNS I-III) were, according to the aneurysm exclusion procedure (EV, MS or conservative), 58.9%, 50% and 12.1% respectively. MMSE score was pathological in 26 of the 112 EV patients (23.2%), 10 of the 25 MS patients (40%) and 4 of the 9 patients treated conservatively (44%), without any statistically significant difference [Pearson's Chi2 test, F ratio=4.29; P=0.11]. Regarding QoL, overall score was similar between the EV and MS cohorts, but significantly lower with conservative treatment. CONCLUSION:Elderly patients in good clinical condition with aSAH should be treated regardless of associated comorbidities. Curative treatment (EV or MS) reduced mortality without increasing dependence, in comparison with conservative treatment.

Primary paragangliomas (PG) of the spine are extremely rare entities. The present study reviews our experience over a period of 30 years. This is a retrospective, single center, observational study. Patients surgically treated for a spinal PG with confirmed anatomopathological diagnosis were included. The McCormick classification was used as a reference for clinical evaluation. Follow-up MRI and clinical assessment took place at 6 weeks, 3 months, 6 months, and 1 year after surgery and on yearly basis after. Six cases have been operated in our institution. The mean age was 37.8 (median 35.5, 30–53). The mean follow-up period was 9.6 years (median 9.5, 1–23). Preoperative duration of symptoms varied between a few hours to 4 years. Low back pain was most common sign. One presented with hemorrhage and acute onset of paraplegia. All patients underwent single surgery, with the exception of one case, which had two surgeries on the same anatomical site and a third surgery on another location of the same tumor type. Preoperatively, McCormick scale was I in four cases, and II and IV in one case, respectively. Postoperatively, all patients in McCormick I retained the same class; one patient in McCormick II passed to McCormick III; the case in McCormick IV recovered to McCormick II. Five of eight surgeries achieved total resection, while two surgeries accomplished a partial microsurgical excision and one a gross total resection. Three patients had spinal leptomeningeal dissemination. Two of them benefited from extended spine radiotherapy, while the other of a “wait-and-scan” policy. Spinal leptomeningeal dissemination was stable in all patients at last follow-up. We consider surgery as primary treatment in all PG. In our experience, preoperative diagnosis is difficult and caution must be taken to perioperative course in these cases. We do not routinely perform postoperative radiation if there is a residual tumor. We regularly perform clinical and radiological follow-up, so as to be able to document recurrent cases, which have been reported even up to 30 years after primary surgical excision.

Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = -0.24 to -0.73; P < 1.49 × 10-4), and lower thickness in the precentral gyri bilaterally (d = -0.34 to -0.52; P < 4.31 × 10-6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = -1.73 to -1.91, P < 1.4 × 10-19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = -0.36 to -0.52; P < 1.49 × 10-4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = -0.29 to -0.54; P < 1.49 × 10-4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = -0.27 to -0.51; P < 1.49 × 10-4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < -0.0018; P < 1.49 × 10-4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed.

The common human epilepsies are associated with distinct patterns of reduced cortical thickness, detectable on neuroimaging, with important clinical consequences. To explore underlying mechanisms, we layered MRI-based cortical structural maps from a large-scale epilepsy neuroimaging study onto highly spatially-resolved human brain gene expression data, identifying >2,500 genes overexpressed in regions of reduced cortical thickness, compared to relatively-protected regions. The resulting set of differentially-expressed genes shows enrichment for microglial markers, and in particular, activated microglial states. Parallel analyses of cell-specific eQTLs show enrichment in human genetic signatures of epilepsy severity, but not epilepsy causation. Post mortem brain tissue from humans with epilepsy shows excess activated microglia. In an experimental model, depletion of activated microglia prevents cortical thinning, but not the development of chronic seizures. These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

Background. - Current aging of the population with good physiological status and the increasing incidence of subarachnoid hemorrhage (SAH) in elderly patients has enhanced the benefit of treatment in terms of independence and long-term quality of life (QoL). Methods. - From November 1, 2008 to October 30, 2012, 351 patients aged 70 years or older with aneurysmal SAH underwent adapted treatment: endovascular coiling (EV) for 228 (65%) patients, microsurgical clipping (MS) for 75 (29.3%) or conservative treatment for 48 (13.7%). Forty-one of these were randomized to EV (n = 20) or to MS (n = 21). The objectives were to determine the proportion of patients with modified Rankin Scale score <= 2 (independence) at 1 year, and, secondarily, to compare cognitive function on the Mini-Mental State Examination (MMSE), autonomy on the Activities of Daily Living Index (ADLI) and Instrumental Activities of Daily Living scale (IADL), and QoL, in the prospective and randomized arms, at 1 year. Results. - At 1 year, with 1 loss to follow-up in the EV arm, 11 patients (55%) were independent after EV occlusion and 8 (38.1%) after MS exclusion, without significant difference (P = 0.29). Mortality was higher after MS during the first 2 postoperative months, and thereafter the difference between MS and EV ceased to be significant. Cognitive function and autonomy scores were similar in both arms. Conclusion. - In elderly patients treated for aneurysmal SAH, approximately 50% were independent at 1 year, with conserved cognition and autonomy. EV and MS are valid procedures in this population, with similar results at 1 year in terms of independence, cognition, autonomy, and QoL. (C) 2018 Elsevier Masson SAS. All rights reserved.