Enlarged perivascular spaces are associated with brain microangiopathy and aging in multiple sclerosis.

BACKGROUND: Growing evidence links brain-MRI enlarged perivascular spaces (EPVS) and multiple sclerosis (MS), but their role remains unclear. OBJECTIVE: This study aimed to investigate the cross-sectional associations of EPVS with several neuroinflammatory and neurodegenerative features in a large multicentric-MS cohort. METHODS: In total, 207 patients underwent 3T axial-T2-weighted brain-MRI for EPVS assessment (EPVS dichotomized into high/low according to ⩾ 2/< 2 rating categories). MRI biomarkers included brain-predicted age and brain-predicted age difference (brain-PAD), central vein sign (CVS)-positive lesion percentage (CVS%), paramagnetic rim and cortical lesions, T2-lesion load, and brain volumetry. The variable relative importance for EPVS-category prediction was explored using a classification random forest approach. RESULTS: High EPVS patients were older (49 vs 44 years, p = 0.003), had ⩾ 1 vascular risk factors (VRFs; p = 0.005), lower CVS% (67% vs 78%, p < 0.001), reduced brain volumes (whole brain: 0.63 vs 0.73, p = 0.01; gray matter: 0.36 vs 0.40; p = 0.002), and older brain-predicted age (58 vs 50 years, p < 0.001). No differences were found for neuroinflammatory markers. After adjusting for age and VFRs (multivariate analyses), the high EPVS category correlated with lower CVS% (odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.96-0.99; p = 0.02), lower whole brain (OR = 0.01, 95% CI = 0.0003-0.5; p = 0.02), gray matter (OR = 0.0004, 95% CI = 0.0000004-0.4; p = 0.03) volumes, and higher brain-PAD (OR = 1.05, 95% CI = 1.01-1.09; p = 0.02). Random forest identified brain-PAD as the most important predictor of high EPVS. CONCLUSION: EPVS in MS likely reflect microangiopathic disease rather than neuroinflammation, potentially contributing to accelerated neurodegeneration.

The impact of perfusion computed tomography on the diagnosis and outcome of delayed cerebral ischemia after subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) is a preventable cause of poor neurological outcome in aneurysmal subarachnoid hemorrhage (aSAH). Advances in radiological methods, such as cerebral perfusion computed tomography (CTP), could help diagnose DCI earlier and potentially improve outcomes in aSAH. The objective of this study was to assess whether the use of CTP to diagnose DCI early could reduce the risk of infarction related to DCI. METHODS: Retrospective cohort study of patients in the intensive care unit of Erasme Hospital (Brussels, Belgium) between 2004 and 2021 with aSAH who developed DCI. Patients were classified as: "group 1" - DCI diagnosed based on clinical deterioration or "group 2" - DCI diagnosed using CTP. The primary outcome was the development of infarction unrelated to the initial bleeding or surgery. RESULTS: 211 aSAH patients were diagnosed with DCI during the study period: 139 (66%) in group 1 and 72 (34%) in group 2. In group 1, 109 (78%) patients developed a cerebral infarction, compared to 45 (63%) in group 2 (p = 0.02). The adjusted cumulative incidence of DCI over time was lower in group 2 than in group 1 [hazard ratio 0.65 (95% CI 0.48-0.94); p = 0.02]. The use of CTP to diagnose DCI was not independently associated with mortality or neurological outcome. CONCLUSIONS: The use of CTP to diagnose DCI might help reduce the risk of developing cerebral infarction after aSAH, although the impact of such an approach on patient outcomes needs to be further demonstrated.

Diagnostic and therapeutic approaches in refractory insular epilepsy.

Due to heterogenous seizure semiology and poor contribution of scalp electroencephalography (EEG) signals, insular epilepsy requires use of the appropriate diagnostic tools for its diagnosis and characterization. The deep location of the insula also presents surgical challenges. The aim of this article is to review the current diagnostic and therapeutic tools and their contribution to the management of insular epilepsy. Magnetic resonance imaging (MRI), isotopic imaging, neurophysiological imaging, and genetic testing should be used and interpretated with caution. Isotopic imaging and scalp EEG have demonstrated a lower value in epilepsy from insular compared to temporal origin, which increases the interest of functional MRI and magnetoencephalography. Intracranial recording with stereo-electroencephalography (SEEG) is often required. The insular cortex, being highly connected and deeply located under highly functional areas, is difficult to reach, and its ablative surgery raises functional issues. Tailored resection based on SEEG or alternative curative treatments, such as radiofrequency thermocoagulation, laser interstitial thermal therapy, or stereotactic radiosurgery, have produced encouraging results. The management of insular epilepsy has benefited from major advances in the last years. Perspectives for diagnostic and therapeutic procedures will contribute to better management of this complex form of epilepsy.

BOLD fMRI and DTI fiber tracking for preoperative mapping of eloquent cerebral regions in brain tumor patients: impact on surgical approach and outcome.

PURPOSE: Task-based BOLD fMRI and DTI-fiber tracking have become part of the routine presurgical work-up of brain tumor patients in many institutions. However, their potential impact on both surgical treatment and neurologic outcome remains unclear, in despite of the high costs and complex implementation. METHODS: We retrospectively investigated whether performing fMRI and DTI-ft preoperatively substantially impacted surgical planning and patient outcome in a series of brain tumor patients. We assessed (i) the quality of fMRI and DTI-ft results, by using a scale of 0-2 (0 = failed mapping; 1 = intermediate confidence; 2 = good confidence), (ii) whether functional planning substantially contributed to defining the surgical strategy to be undertaken (i.e., no surgery, biopsy, or resection, with or without ESM), the surgical entry point and extent of resection, and (iii) the incidence of neurological deficits post-operatively. RESULTS: Twenty-seven patients constituted the study population. The mean confidence rating was 1.9/2 for fMRI localization of the eloquent cortex and lateralization of the language function and 1.7/2 for DTI-ft results. Treatment strategy was altered in 33% (9/27) of cases. Surgical entry point was modified in 8% (2/25) of cases. The extent of resection was modified in 40% (10/25). One patient (1/25, 4%) developed one new functional deficit post-operatively. CONCLUSION: Functional MR mapping - which must not be considered an alternative to ESM - has a critical role preoperatively, potentially modifying treatment strategy or increasing the neurosurgeons' confidence in the surgical approach hypothesized based on conventional imaging.

The central vein sign in multiple sclerosis patients with vascular comorbidities.

BACKGROUND: The central vein sign (CVS) is an imaging biomarker able to differentiate multiple sclerosis (MS) from other conditions causing similar appearance lesions on magnetic resonance imaging (MRI), including cerebral small vessel disease (CSVD). However, the impact of vascular risk factors (VRFs) for CSVD on the percentage of CVS positive (CVS+) lesions in MS has never been evaluated. OBJECTIVE: To investigate the association between different VRFs and the percentage of CVS+ lesions in MS. METHODS: In 50 MS patients, 3T brain MRIs (including high-resolution 3-dimensional T2*-weighted images) were analyzed for the presence of the CVS and MRI markers of CSVD. A backward stepwise regression model was used to predict the combined predictive effect of VRF (i.e. age, hypertension, diabetes, obesity, ever-smoking, and hypercholesterolemia) and MRI markers of CSVD on the CVS. RESULTS: The median frequency of CVS+ lesions was 71% (range: 35%-100%). In univariate analysis, age (p < 0.0001), hypertension (p < 0.001), diabetes (p < 0.01), obesity (p < 0.01), smoking (p < 0.05), and the presence of enlarged-perivascular-spaces on MRI (p < 0.005) were all associated with a lower percentage of CVS+ lesions. The stepwise regression model showed that age and arterial hypertension were both associated with the percentage of CVS+ lesions in MS (adjusted R2 = 0.46; p < 0.0001 and p = 0.01, respectively). CONCLUSION: The proportion of CVS+ lesions significantly decreases in older and hypertensive MS patients. Although this study was conducted in patients with an already established MS diagnosis, the diagnostic yield of the previously proposed 35% CVS proportion-based diagnostic threshold appears to be not affected. Overall these results suggest that the presence of VRF for CSVD should be taken into account during the CVS assessment.

Radiological and clinical features of cerebral sinovenous thrombosis in newborns and older children.

BACKGROUND AND PURPOSE: Cerebral sinovenous thrombosis (CSVT) represents an increasingly recognized cause of pediatric stroke. Our purpose was to assess gender and age differences in the etiology, clinical presentation, and imaging features of CSVT in neonates and older children. METHODS: Subjects aged newborn to 18 years diagnosed with CSVT at the Lille university hospital between 2011 and 2014 were included. RESULTS: Eleven neonates and 16 non-neonates constituted the study population. The incidence of CSVT was significantly higher in male newborns. Clinical presentation did not vary significantly between the groups. Risk factors were age-dependent, with acute systemic illnesses significantly predominating in neonates (54%), whereas local infections, prothrombotic conditions, and trauma were more common in older children (36, 27, and 27% respectively). No predisposing factor could be identified in 36% of the neonates as compared to less than 5% of the non-neonates. Thrombosis of the deep venous structures was documented in 73% of the neonates whereas involvement of the superficial sinuses was significantly more frequent in the non-neonates group. Venous infarctions and extraparenchymal hemorrhages were significantly more frequent in the neonates group. CONCLUSION: Male patients are at higher risk for CSVT than females. In neonates, involvement of the deep venous structures is significantly more common. Brain parenchymal and extraparenchymal changes occur more frequently in this age group than in older children.

Chédiak-Higashi syndrome: brain MRI and MR spectroscopy manifestations.

Chédiak-Higashi syndrome is a rare inherited metabolic disorder characterized by partial oculocutaneous albinism, immunodeficiency, and neurological dysfunction. We present the brain magnetic resonance imaging (MRI) and MR spectroscopy (MRS) findings obtained during the accelerated phase of the disorder in an 8-year-old. The brain MRI manifestations at recurrences 15 months and 24 months later are reported as well.

A First Case of Acute Flaccid Myelitis Related to Enterovirus D68 in Belgium: Case Report.

Introduction: We describe the first case of acute flaccid myelitis (AFM) related to enterovirus D68 (EV-D68) infection in Belgium. The clinical and radiological presentation of AFM associated with EV-D68 although well described currently remains a challenging diagnosis. Through this interesting clinical case, we aimed to review the differential diagnosis of acute flaccid palsy in a child and discuss the specific point of interest related to AFM. Case Presentation: We present the case of a 4-year-old girl with a torticollis associated with an acute palsy of the right upper limb. The magnetic resonance imaging revealed an increased T2 signal intensity of the entire central gray matter of the cervical cord with involvement of the posterior brainstem. A polymerase chain reaction (PCR) conducted on a nasopharyngeal swab was found positive for EV-D68. The definition of AFM proposed by the Center for Disease Control and Prevention (CDC) is an acute-onset flaccid weakness of one or more limbs in the absence of a clear alternative diagnosis and the radiological evidence of gray matter involvement on an MRI picture, and our case fits these two criteria. A prompt and detailed workup is required to distinguish this emergent disease from other forms of acute flaccid palsy. The functional prognosis of AFM is poor, and there are no evidence-based treatment guidelines so far. Conclusion: AFM is an emerging pathology that requires the attention of pediatricians to quickly rule out differential diagnoses and adequately manage the patient. Further research is needed to optimize treatments, improve outcomes, and provide scientifically based guidelines.

Radiological characterization of pediatric intramedullary astrocytomas: Do they differ from adults?

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.

Treatment of Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage using the Neurospeed Semi-compliant Balloon.

BACKGROUND AND PURPOSE: Cerebral vasospasm (CV) following aneurysmal subarachnoid hemorrhage (aSAH) may lead to morbidity and mortality. Endovascular mechanical angioplasty may be performed if symptomatic CV is refractory to noninvasive medical management. Off-label compliant remodelling balloons tend to conform to the course of the vessel, contrary to noncompliant or semi-compliant balloons. Our objective is to describe our initial experience with the semi-compliant Neurospeed balloon (approved for intracranial stenosis) in cerebral vasospasm treatment following aSAH. METHODS: All patients included in the prospective observational SAVEBRAIN PWI (NCT05276934 on clinicaltrial.gov) study who underwent cerebral angioplasty using the Neurospeed balloon for the treatment of medically refractory and symptomatic CV after aSAH were identified. Patient demographic information, procedural details and outcomes were obtained from electronic medical records. RESULTS: Between February 2022 and June 2023, 8 consecutive patients underwent CV treatment with the Neurospeed balloon. Angioplasty of 48 arterial segments (supraclinoid internal carotid artery, A1 and A2 segments of the anterior cerebral artery, M1 and M2 segments of the middle cerebral artery) was attempted and 44/48 (92%) were performed. The vessel diameter significantly improved following angioplasty (+81%), while brain hypoperfusion decreased (-81% of the mean TMax). There was no long-term clinical complication, 4% periprocedural complications occurred. CONCLUSION: The semi-compliant Neurospeed balloon is effective in the treatment of cerebral vasospasm following aSAH, bringing a new device into the armamentarium of the neurointerventionalist to perform intracranial angioplasty.

Fat emboli and critical illness-associated cerebral microbleeds (CICMs) in a patient with sickle cell disease: Do these 2 entities coexist?

We report the case of a 30-year-old female patient with sickle cell disease presenting with an acute chest syndrome and neurological deterioration. Cerebral magnetic resonance imaging revealed a handful of foci of diffusion restriction and numerous microbleeds with marked involvement of corpus callosum and subcortical white matter, with relative sparing of the cortex and deep white matter. Corpus callosum-predominant and juxtacortical microbleeds have been typically documented in cerebral fat embolism syndrome, but also in the so-called "critical-illness-associated cerebral microbleeds", a recently described entity associated with respiratory failure. We discussed whether these 2 entities may coexist.

Clinicopathological and molecular characterization of a case classified by DNA­methylation profiling as "CNS embryonal tumor with BRD4-LEUTX fusion".

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.

B cell depletion therapy does not resolve chronic active multiple sclerosis lesions.

BACKGROUND: Chronic active lesions (CAL) in multiple sclerosis (MS) have been observed even in patients taking high-efficacy disease-modifying therapy, including B-cell depletion. Given that CAL are a major determinant of clinical progression, including progression independent of relapse activity (PIRA), understanding the predicted activity and real-world effects of targeting specific lymphocyte populations is critical for designing next-generation treatments to mitigate chronic inflammation in MS. METHODS: We analyzed published lymphocyte single-cell transcriptomes from MS lesions and bioinformatically predicted the effects of depleting lymphocyte subpopulations (including CD20 B-cells) from CAL via gene-regulatory-network machine-learning analysis. Motivated by the results, we performed in vivo MRI assessment of PRL changes in 72 adults with MS, 46 treated with anti-CD20 antibodies and 26 untreated, over ∼2 years. FINDINGS: Although only 4.3% of lymphocytes in CAL were CD20 B-cells, their depletion is predicted to affect microglial genes involved in iron/heme metabolism, hypoxia, and antigen presentation. In vivo, tracking 202 PRL (150 treated) and 175 non-PRL (124 treated), none of the treated paramagnetic rims disappeared at follow-up, nor was there a treatment effect on PRL for lesion volume, magnetic susceptibility, or T1 time. PIRA occurred in 20% of treated patients, more frequently in those with ≥4 PRL (p = 0.027). INTERPRETATION: Despite predicted effects on microglia-mediated inflammatory networks in CAL and iron metabolism, anti-CD20 therapies do not fully resolve PRL after 2-year MRI follow up. Limited tissue turnover of B-cells, inefficient passage of anti-CD20 antibodies across the blood-brain-barrier, and a paucity of B-cells in CAL could explain our findings. FUNDING: Intramural Research Program of NINDS, NIH; NINDS grants R01NS082347 and R01NS082347; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; Cariplo Foundation (grant #1677), FRRB Early Career Award (grant #1750327); Fund for Scientific Research (FNRS).

Atypical acute disseminated encephalomyelitis with systemic inflammation after a first dose of AztraZaneca COVID-19 vaccine. A case report.

Background: Only a few cases of acute disseminated encephalomyelitis (ADEM) following coronavirus disease 19 (COVID-19) vaccination have been described since the beginning of the vaccination campaign. Results: Here we report the first case of central nervous system (CNS) demyelination with systemic inflammatory findings on whole body 19-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) following the ChAdOx1 nCoV-19 vaccine. Conclusions: Clinicians should stay aware of potential new adverse events after immunization.

Prognosis of patients treated in a single neurosurgical reference centre for brain metastasis caused by dormant disseminated cells.

Brain metastasis (BM) is a frequent complication of systemic cancer usually associated with poor prognosis. Survival depends on numerous factors, which complicates prognosis and treatment. It has been suggested that BM growing from previously dormant disseminated tumour cells (DTCs) may exhibit a milder phenotype than BM derived from continuously progressing metastatic cells; however, to the best of our knowledge, the prognosis of patients presenting with BM from dormant DTCs is unknown. The present study retrospectively compared survival data, collected from a single neurosurgical centre, between patients presenting with BM from previously dormant DTCs and patients with non-dormant BM. A total of 262 medical records were reviewed. In the univariate Cox regression analysis, the median survival of the dormant BM group was statistically longer than that of the non-dormant group (P=0.048); a trend towards a longer survival persisted after correcting for age, presence of breast cancer and treatment options (P=0.057), which are all factors known to influence outcome. The improved outcome of these patients could be considered in models for prognostication. Moreover, the development of therapies able to eradicate dormant DTCs could provide a new promising strategy to prolong the survival of patients with a favourable prognosis.

Pneumatic artificial muscle-based stimulator for passive functional magnetic resonance imaging sensorimotor mapping in patients with brain tumours.

BACKGROUND: Two concerns with respect to pre-operative task-based motor functional magnetic resonance imaging (fMRI) in patients with brain tumours are inadequate performance due to patients' impaired motor function and head motion artefacts. NEW METHOD: In the present study we validate the use of a stimulator based on a pneumatic artificial muscle (PAM) for fMRI mapping of the primary sensorimotor (SM1) cortex in twenty patients with rolandic or perirolandic brain tumours. All patients underwent both active and passive motor block-design fMRI paradigms, performing comparable active and passive PAM-induced flexion-extensions of the icontralesional index finger. RESULTS: PAM-induced movements resulted in a significant BOLD signal increase in contralateral primary motor (M1) and somatosensory (S1) cortices in 18/20 and 19/20 (p<.05 FWE corrected in 16/18 and 18/19) patients, versus 18/20 and 16/20 (p<.05 FWE corrected) during active movements. The two patients in whom the PAM-based stimulator failed to induce any significant BOLD signal change in the contralateral M1 cortex differed from the two in whom active motion was conversely ineffective. At the group level, no significant difference in contrast magnitude was observed within the contralateral SM1 cortex when comparing active with passive movements. During passive movements, head motion was significantly reduced. Comparison with existing method(s) As compared to the several robotic devices for passive motion that were introduced in the past decades, our PAM-based stimulator appears smaller, handier, and easier to use. CONCLUSION: The use of PAM-based stimulators should be included in routine pre-operative fMRI protocols along with active paradigms in such patients' population.

Remote Intracranial Hemorrhage after Cranio-Spinal Surgery. Report of Two Cases.

Post-operative intracranial bleeding at a distance from the surgical site is a rare complication of both cranial and spinal surgeries and is referred to as remote intracranial hemorrhage (RIH). Bleeding typically occurs in the cerebellum. Simultaneous hemorrhages in different cranial compartments have been rarely observed. We herein report two cases of RIH, which showed different imaging patterns and clinical signs and symptoms. RIH are typically self-limiting and do not usually require treatment. Physicians must be aware of this benign entity which needs not be misdiagnosed with other conditions. Teaching point: Remote intracranial hemorrhage is a rare but worthy of note complication of cranio-spinal surgery.

MRI Findings in Acute Hyperammonemic Encephalopathy: Three Cases of Different Etiologies: Teaching Point: To recognize MRI findings in acute hyperammonemic encephalopathy.

Acute hyperammonemic encephalopathy is a rare but life-threatening condition that might complicate liver disease as well as non-hepatic conditions. It can lead to coma and death, secondary to brain edema and intracranial hypertension. We present three cases of acute hyperammonemic encephalopathy of different etiologies and the observed brain MRI findings. Symmetrical extensive cortical signal abnormalities, typically involving the insular and cingulate cortices, often showing restricted diffusion, are commonly described. These specific imaging features should be recognized by the radiologist since prompt treatment of the condition is paramount.

Flexion MRI in a case of Hirayama disease.

We report the case of an 18-year old male with a history of asymmetric weakness and amyotrophy of distal upper extremities, suggestive of Hirayama disease. Magnetic resonance imaging (MRI) of the cervical spine was obtained both in flexion and neutral position. Flexion MRI showed forward displacement of the dura and subsequent cord compression, with associated marked enlargement and postcontrast enhancement of posterior epidural plexus. These findings are pathognomonic of the disorder. On neutral MRI abnormalities may be subtle: in our case, they included loss of physiological lordosis, asymmetric atrophy and increased T2 signal intensity of the lower anterior cervical cord. The ability to identify abnormalities on neutral MRI however is even more important in that it allows the radiologist to include a flexion sequence in the MRI examination, if not specifically requested by the referring physician, and in cases in which the suspicion of the disorder has not been raised.