Infratentorial Research Articles

Clinical correlates of R1 relaxometry and magnetic susceptibility changes in multiple sclerosis: a multi-parameter quantitative MRI study of brain iron and myelin

ObjectivesThe clinical impact of brain microstructural abnormalities in multiple sclerosis (MS) remains elusive. We aimed to characterize the topography of longitudinal relaxation rate (R1) and quantitative susceptibility (χ) changes, as indices of iron and myelin, together with brain atrophy, and to clarify their contribution to cognitive and motor disability in MS.MethodsIn this cross-sectional study, voxel-based morphometry, and voxel-based quantification analyses of R1 and χ maps were conducted in gray matter (GM) and white matter (WM) of 117 MS patients and 53 healthy controls. Voxel-wise between-group differences were assessed with nonparametric permutation tests, while correlations between MRI metrics and clinical variables (global disability, cognitive and motor performance) were assessed both globally and voxel-wise within clusters emerging from the between-group comparisons.ResultsMS patients showed widespread R1 decrease associated with more limited modifications of χ, with atrophy mainly involving deep GM, posterior and infratentorial regions (p < 0.02). While R1 and χ showed a parallel reduction in several WM tracts (p < 0.001), reduced GM R1 values (p < 0.001) were associated with decreased thalamic χ (p < 0.001) and small clusters of increased χ in the caudate nucleus and prefrontal cortex (p < 0.02). In addition to the atrophy, χ values in the cingulum and corona radiata correlated with global disability and motor performance, while focal demyelination correlated with cognitive performance (p < 0.04).ConclusionsWe confirmed the presence of widespread R1 changes, involving both GM and WM, and atrophy in MS, with less extensive modifications of tissue χ. While atrophy and χ changes are related to global and motor disability, R1 changes are meaningful correlates of cognition.Key Points• Compared to healthy controls, multiple sclerosis patients showed R1 and χ changes suggestive of iron increase within the basal ganglia and reduced iron and myelin content within (subnuclei of) the thalamus.• Thalamic volume and χ changes significantly predicted clinical disability, as well as pulvinar R1 and χ changes, independently from atrophy.• Atrophy-independent R1 and χ changes, suggestive of thalamic iron and myelin depletion, may represent a sensitive marker of subclinical inflammation.

Incidence and Surgical Outcome of the Intracranial Epidermoid Cyst at Punjab Institute of Neurosciences Lahore, Pakistan

Objectives: The incidence and microsurgical outcomes of intracranial epidermoid cysts in the Department of Neurosurgery III, Punjab Institute of Neurosciences (PINS), Lahore, Pakistan, are described in this case series.&#x0D; Materials and Methods: This study was a data analysis of a case series of 15 patients (mean age, 40 years) of both gender with intracranial epidermoid cysts who had microsurgical surgical excision over five years.&#x0D; Results: This study comprised 11 (73.3%) male and 4 (26.7%) female patients, 11 (73.3%) cases were infratentorial and 4 (26.7%) cases were in supratentorial region. The epidermoid was located in the CP angle in 11 (73.3%) patients, 3 (20%) in the midline supra sellar region, and 1 (6.66%) in the frontotemporal region. The presenting complaints were mainly headache in 11 (73.33%), cranial nerve palsy and cerebellar signs in 8 (53.3%) patients, Trigeminal neuralgia in 3 (20%) patients, Fits and hydrocephalus in 2 (13.3%) patients. There were 14 (93.3%) patients with GTR (gross total resection), 1 (6.6%) patients STR (subtotal resection). According to Karnofsky's performance scoring (KPS), 3 (20%) patients improved, 11 (73.3%) patients had the same KPS, and 1 (6.6%) patient had a lower KPS.&#x0D; Conclusion: The epidermoid cysts in the brain are usually found in the infratentorial region rather than the supratentorial region. Infratentorial lesions typically cause cranial nerve deficits, whereas the supratentorial area symptom is a headache.

MRI Markers of Small Vessel Disease and the APOE Allele in Cognitive Impairment.

ObjectiveThe apolipoprotein E (APOE) ε4 allele is the main genetic risk factor for dementia and Alzheimer's disease (AD), but the underlying mechanism for the increased risk is not well understood. Cerebral small vessel disease (SVD) is prevalent among patients with cognitive impairment and is thought to play an important role in the pathophysiology of dementia. We aimed to investigate the association between the APOE ε genotype and magnetic resonance imaging (MRI) markers of SVD in a memory clinic population.Material and MethodsThis is a cross-sectional study with a total of 520 patients undergoing dementia investigation, including an MRI brain scan and APOE genotyping in all patients enrolled, and cerebrospinal fluid (CSF) analysis for routine AD biomarkers in 399 patients. MR images were assessed for markers of SVD: cerebral microbleeds (CMBs), cortical superficial siderosis, intracerebral hemorrhage, white matter hyperintensities, lacunar infarcts, and enlarged perivascular spaces.ResultsApolipoprotein E carriers with AD had a higher number of CMBs when looking at all brain regions and lobar brain regions (p < 0.001). A lower number of CMBs were seen in APOE ε2 (p < 0.05), ε3 and ε3/3 carriers (p < 0.001) when looking at all brain regions. A higher number of CMBs in deep and infratentorial regions were seen in APOE ε2 and ε3 (p < 0.05). In APOE ε4/4 carriers, CMBs, cortical superficial siderosis, white matter hyperintensities, and enlarged perivascular spaces were associated with lower levels of CSF amyloid β (Aβ) 42 in the whole cohort, and in individuals with AD and mild cognitive impairment (p < 0.05).ConclusionApolipoprotein E ε4 is associated with MRI markers of SVD related to amyloid pathology, specifically CMBs and Aβ42 plaque formation in the brain, as reflected by decreased CSF Aβ42 levels, whereas APOE ε3 and ε2 are associated with the markers of hypertensive arteriopathy, as reflected by the association with CMBs in deep and infratentorial brain regions.

Quantification of individual remyelination during short-term disease course by synthetic magnetic resonance imaging.

MRI is an important diagnostic tool for evaluation of myelin content in multiple sclerosis and other CNS diseases, being especially relevant for studies investigating remyelinating pharmacotherapies. In this study, we evaluated a new synthetic MRI–based myelin estimation in methylenetetrahydrofolate reductase deficiency as a treatable primary demyelinating disorder and compared this method with established diffusion tensor imaging in both methylenetetrahydrofolate reductase deficiency patients and healthy controls. This is the first synthetic MRI–based in vivo evaluation of treatment-associated remyelination. 1.5 T synthetic MRI and 3 T diffusion MRI were obtained from three methylenetetrahydrofolate reductase deficiency patients at baseline and 6 months after therapy initiation, as well as from age-matched healthy controls (diffusion tensor imaging: n = 14, synthetic MRI: n = 9). Global and regional synthetic MRI parameters (myelin volume fraction, proton density, and relaxation rates) were compared with diffusion metrics (fractional anisotropy, mean/radial/axial diffusivity) and related to healthy controls by calculating z-scores and z-deviation maps. Whole-brain myelin (% of intracranial volume) of the index patient was reduced to 6 versus 10% in healthy controls, which recovered to a nonetheless subnormal level of 6.6% following initiation of high-dosage betaine. Radial diffusivity was higher at baseline compared with healthy controls (1.34 versus 0.79 × 10−3 mm2/s), recovering at follow-up (1.19 × 10−3 mm2/s). The index patient’s lesion volume diminished by 58% under treatment. Regional analysis within lesion area and atlas-based regions revealed lower mean myelin volume fraction (12.7Baseline/14.71Follow-up%) and relaxation rates, higher proton density, as well as lower fractional anisotropy and higher radial diffusivity (1.08 × 10−3Baseline/0.94 × 10−3Follow-up) compared with healthy controls. The highest z-scores were observed for myelin volume fraction in the posterior thalamic radiation, with greater deviation from controls at baseline and reduced deviation at follow-up. Z-deviations of diffusion metrics were less pronounced for radial and mean diffusivity than for myelin volume fraction. Z-maps for myelin volume fraction of the index patient demonstrated high deviation within and beyond lesion areas, among others in the precentral and postcentral gyrus, as well as in the cerebellum, and partial remission of these alterations at follow-up, while radial diffusivity demonstrated more widespread deviations in supra- and infratentorial regions. Concordant changes of myelin volume fraction and radial diffusivity after treatment initiation, accompanied by dramatic clinical and paraclinical improvement, indicate the consistency of the methods, while myelin volume fraction seems to characterize remyelinated regions more specifically. Synthetic MRI–based myelin volume fraction provides myelin estimation consistent with changes of diffusion metrics to monitor short-term myelin changes on individual patient level.

Abstract 3886: 3D genome conformation analysis in ST-EPN-ZFTA ependymoma identifies RCOR2 as a potential target

Abstract Ependymoma (EPN) is a tumor of the central nervous system that occurs in children and adults. Childhood EPNs are one of the most aggressive pediatric brain tumors, arising both in infratentorial and supratentorial (ST) regions of the brain. Molecular profiling has identified distinct subgroups of ependymomas, including ST-EPN-ZFTA and PF-EPN-A as the most common and most aggressive ones in children. To this date, the only curative and indispensable treatment option is surgical resection followed by radiation. Unfortunately, there are no targeted therapies in clinical use. However, EPN cells have been extremely difficult to culture and expand in vitro, which explains why molecular studies on EPN cells have been hampered. This shortcoming has recently been overcome by establishing EPN models including human cell lines and organoids as well as patient derived xenografts (PDX). 3D genome conformation analysis has emerged as a powerful approach to understand tumor development and to identify novel drug targets for the treatment of different tumors. In this project we have used genome-wide chromosome conformation capture (Hi-C), complemented with H3K27ac (active enhancers) as well as gene expression in primary ependymoma tumors and cell lines to identify regulatory mechanisms underlying aberrant expression of genes that are essential for ependymoma tumorigenesis. Results of this study showed that the fusion between ZFTA and RELA leads to the formation of new regulatory environments that are recurrently associated with aberrant overexpression of RCOR2 only in ST-EPN-ZFTA ependymoma cells. Indeed, compared to all other ependymoma subgroups as well as to normal brain, RCOR2 is significantly upregulated only in ST-EPN-ZFTA patient samples. To test oncogenic relevance of RCOR2 for growth and maintenance, we depleted RCOR2 by RNAi and observed a strongly reduced cell survival in several ST-EPN-ZFTA cell lines but not or to a lesser extent in PF-EPN-A cells. Since RCOR2 is an adaptor protein lacking enzymatic activity, we looked at the expression of the proteins known as an interacting partner of RCOR2. Lysine-histone demethylase 1 (LSD1) is one of them and its expression in ST-EPN-ZFTA significantly correlates with RCOR2 expression. We therefore hypothesized that ST-EPN-ZFTA cells may be sensitive to LSD1 depletion, too. Indeed, depletion of LSD1 by RNAi resulted in a strong growth inhibition in ST-EPN-ZFTA cells, but not in PF-EPN-A cells. However, none of the tested LSD1 inhibitors exerted anti-proliferative activity at clinically reachable doses in the ST-EPN-ZFTA cells indicating a potential LSD1 non-enzymatic function in this particular tumor type. In summary, our study nominates RCOR2 as a oncogenic gene specific for ST-EPN-ZFTA ependymomas. Current studies focus on the identification of other interacting partners of the RCOR2-LSD1 complex and how to target these for therapeutic approaches. Citation Format: Aylin Camgöz, Konstantin Okonechnikov, Owen Chapman, Monika Maurmann, Frank Buchholz, Stefan Pfister, Lukas Chavez, Marcel Kool. 3D genome conformation analysis in ST-EPN-ZFTA ependymoma identifies RCOR2 as a potential target [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3886.

Magnetic resonance imaging findings of intracranial tuberculoma patients in a tertiary hospital in Mogadishu, Somalia: A retrospective study

IntroductionTuberculosis (TB) is a fatal disease caused by Mycobacterium tuberculosis (M.TB) with over eight million annual mortality reported worldwide attributed to the disease's direct or indirect effects. Among the most severe form of M. TB is an infection of the Central nervous system (CNS-TB). This infection is characterized by meningitis, tuberculoma, and tuberculous brain abscess. Tuberculomas are the most common variety of intracranial parenchymal tuberculosis. They occur because of conglomeration and conjugation of tubercular microgranulomas, which tend to occur at the grey-white matter junction due to the arrest of the hematogenous disseminating microbes caused by a decrease in the caliber of vessels in that region. Intracranial tuberculoma shows central hypointensity compared to grey matter, seeing this centrally on T2W images is helpful, as it is not seen in most other ring-enhancing lesions. ObjectivesThe purpose of this study was to evaluate the findings of the magnetic resonance imaging (MRI) scan of patients with intracranial tuberculoma using retrospective hospital records. MethodologyWe conducted a retrospective data analysis of 73 patients with an age range of 3–70 years between 2018 and 2021 who were diagnosed with intracranial tuberculoma using MRI features at the Radiology Department, Somali-Turkey Recep Tayyip Erdogan Hospital. All the patients' MRI were evaluated, including conventional and contrast sequences and as well as MR diffusion. ResultsThis study revealed that most tuberculoma patients were female with 43 (58.9%) and 30 (41.1%) male. According to age group, the majority of patients 30 (41.1%) were 18–30 years of age. Based on the distribution of the conglomerates’ tubercles, 39 (53.4%) were located in the supratentorial region, while 24 (32.9%) were found in both the supra-tentorial and infra-tentorial regions, with 10 (13.7%) residing in the infratentorial region. Interestingly, this study also discovered that the majority of the tuberculoma patients 43 (58.9%) had multifocal lesions, with 30 (41.1%) having single lesions. Also, associated abnormalities were detected in 28 (38.4%) of the patients with meningitis, while 7 (9.6%) had both hydrocephalus and meningitis, 2 (2.7%) had hydrocephalus, and one patient had cerebral infarction. ConclusionThe outcome of this investigation shows MRI as a suitable diagnostic tool for the diagnosis of intracranial tuberculoma and associated abnormalities in geographic areas where tuberculosis is endemic.

Demyelinating Syndromes in Systemic Lupus Erythematosus: Data From the "Attikon" Lupus Cohort.

BackgroundThe demyelinating syndromes of the central nervous system (CNS) that occur in the context of systemic lupus erythematosus (SLE) may represent a manifestation of neuropsychiatric lupus (NPSLE) or an overlap of SLE and multiple sclerosis (MS). The differential diagnosis between the two entities has important clinical implications because the therapeutic management differs.ObjectivesTo characterize CNS demyelinating syndromes in a large SLE cohort as neuropsychiatric SLE (NPSLE) or SLE-MS overlap using a multidisciplinary approach and existing diagnostic (for MS) and classification criteria (for SLE).MethodsPatients from the “Attikon” lupus cohort (n = 707) were evaluated for demyelinating syndromes. Clinical, laboratory, and neuroimaging data were recorded for each patient. Following multidisciplinary evaluation and application of criteria, the demyelinating syndrome was attributed to either SLE or MS. Patients with transverse myelitis were not included in this study.ResultsWe identified 26 patients with demyelinating syndromes (3.7%). Of them, 12 were diagnosed as primary SLE-demyelination (46.2%) and 14 as overlap SLE-MS (53.8%). The two groups did not differ with respect to rheumatologic and neurologic manifestations or autoantibodies. SLE patients with demyelination manifested mild extra-CNS disease mainly involving joints and skin, while severe non-CNS manifestations were rare. However, these patients were less likely to have elevated IgG index (OR 0.055 95% CI: 0.008–0.40) and positive oligoclonal bands (OR 0.09 95% CI: 0.014–0.56), as well as brain lesions in the spinal cord, infratentorial, periventricular, and juxtacortical regions. A single brain region was affected in 9 patients with SLE-demyelination (75%), while all patients with MS-SLE had multiple affected brain regions. MS-SLE overlap was associated with an increased likelihood of neurologic relapses (OR 18.2, 95% CI: 1.76–188), while SLE-demyelination patients were less likely to exhibit neurological deficits (EDSS >0) at the last follow-up visit (50 vs. 78.6% in SLE-MS, respectively).ConclusionsDemyelination in the context of SLE follows a more benign course compared to a frank SLE-MS overlap. Extension of follow-up will ascertain whether patients with SLE-demyelination evolve to MS, or this is a bona fide NPSLE syndrome.

Hemangioblastoma, a rare tumor of supratentorial and infratentorial regions: A report of two cases with review of literature

Hemangioblastoma (HBL) is a rare benign neoplasm arising from the vascular stromal cells. It is a WHO Grade 1 neoplasm with solid and cystic components. In majority of the cases, it is a sporadic tumor, and in few cases, association with Von Hippel–Lindau syndrome has been found. Here, we present two separate cases of intracranial HBL. One tumor is from the supratentorial region and another one is from the infratentorial region. Although infratentorial HBL is commonly found, supratentorial HBL is very rare. Microscopical similarity with metastatic clear cell renal cell carcinoma can be a diagnostic pitfall.

A Cross Sectional Study of Clinical and Histopathological Spectrum of Pediatric Brain Tumours

Introduction: Brain tumors are the most common tumor of the childhood and the second most common malignancies after haematological malignancies. Childhood central nervous system (CNS) tumors differ significantly from adult brain tumors in reference to their sites of origin, clinical presentation, tendency to disseminate early, histological features and their biological behaviour. Aims and Objective: Analyse the Clinical and histopathological spectrum of brain tumors, in pediatric patients ≤18 year of age. Materials and Method: This was a cross sectional study conducted at the department of pathology, SMS medical college, Jaipur from January 2020 to October 2021. This is a laboratory based descriptive type of observational study and data of brain tumors in children equal or less than 18 year of age procured and their clinico-histopathological spectrum were analyszed. Result: In our study, Out of 116 patients 51.8 % were male and 48.2 % were female. Mean age for the male cases were 10.11 and for female cases were 9.78. we observed intracranial pediatric tumors 67 cases (57.7%) were located in infratentorial region and 49 cases (43.3%) were located in supratentorial region and incidence for intracranial tumor was 39(33.62%) cases of astrocytomas followed by 25 (21.55%)cases of medulloblastoma, 20 (17.24%)cases of ependymoma, 13 (11.20%) cases of craniopharyngioma, 5 (4.31%) cases of pituitary adenoma, 4 (3.44%) cases of meningioma, 3 (2.58%) cases of embryonal and choroid plexus tumor, 2 (1.72%) cases of ganglioglioma and 1 (0.86%) case of Schwannoma and PNET. In this article, Based on tumor location, the symptoms of CNS tumors on the supratentorial region were headache (22 cases, 44.8%), impaired vision (10 cases, 20.4%), seizures (6 cases, 12.2%), vomiting (4 cases, 8.1%). Symptoms of CNS tumors on the infratentorial region were headache (48 cases, 71.6%), vomiting (5 cases, 7.4%), impaired vision (4 cases, 5.9%), seizures (3 cases, 4.4%). Conclusion: Infratentorial cases, maximum number of cases were medulloblastomas and supratentorial cases, maximum number of cases were astrocytic tumours. Overall astrocytic tumours in all senses constituted the most common group of CNS tumours. Within astrocytoma, low grade astrocytoma (grade I &amp; II) was most common CNS paediatric tumour.

Magnetic Resonance Imaging of Multiple Cerebral and Spinal Cavernous Malformations of a Patient with Dementia and Tetraparesis

Cavernomas are rare cerebrovascular malformations that usually occur in sporadic forms with solitary lesions located most often in the hemispheric white matter, but also in the infratentorial or spinal region. Multiple lesions at different CNS levels are considered a hallmark for the familial form of the disease. The diagnostic modality of choice for cerebral cavernous malformations (CCMs) is magnetic resonance imaging (MRI). We present an intriguing case of a 65-year-old male admitted to our hospital with tetraparesis and cognitive impairment where highly sensitive MRI sequences identified many cerebral cavernous lesions at the supra-, infratentorial and cervical–thoracic spine levels, some of them with recent signs of bleeding in a patient with oral anticoagulant therapy due to atrial fibrillation. The mechanism of cognitive impairment in this patient is most probably the interruption of strategic white matter tracts, as it is known to happen in other subcortical vascular pathologies. MRI can be helpful not only in mapping the anatomical distribution of lesions, but also in weighing the risks and making decisions regarding whether or not to continue oral anticoagulant therapy.

Multiple different remote epidural hematomas after craniotomy: A case report

BACKGROUNDEpidural hematoma is one of the common postoperative complications after craniotomy. However, multiple remote epidural hematomas in different sites, including supratentorial and infratentorial regions, are exceedingly rare.CASE SUMMARYWe present a rare case in which three remote epidural hematomas occurred after craniotomy. A 21-year-old woman was admitted with a headache for 1 mo, vomiting, and rapid vision loss for 1 wk. Brian magnetic resonance imaging indicated a right thalamic tumor. The intraoperative diagnosis was a cystic tumor, posterior cerebral artery aneurysm, and vascular malformation. The operation was successful. Unfortunately, the patient developed three extradural hematomas within 48 h. Family members consented to the first two hematoma evacuations but refused the third.CONCLUSIONMore attention should be paid to this kind of rare complication. Adequate preoperative evaluation is important, especially for acute patients. Monitoring neural function and early computed tomography scanning of the brain after surgery should be highlighted.

Diagnostic utility of 3D DIR MRI in the estimation of MS lesions overall load with special emphasis on cortical subtypes

BackgroundA number of magnetic resonance imaging studies have shown that a significant proportion of multiple sclerosis (MS) lesions are located in the cerebral cortex and correlate with the patient's disability level. Double inversion recovery (DIR) has a higher sensitivity to detect cortical lesions and their different types. The aim of our study was to assess the superiority of 3D DIR as compared to FLAIR in detecting the different cortical subtypes and to enhance its role as a test for the clinical disability of the patient.ResultsThe current study included 82 MS patients (60 female and 22 male with mean age of 34.5 ± 8.2 years); 59 cases having relapsing–remitting MS, 5 having secondary progressive MS, and 4 having primary progressive MS, as well as eight clinically isolated syndrome cases, and six radiologically isolated syndrome cases. DIR was superior to FLAIR in MS plaque number detection of cortical plaque-types 1, 2, 3 and 4 with a p value < 0.001. DIR was superior to FLAIR for detection of overall cortical types, juxtacortical and juxtacortical extended MS plaques with p = < 0.001, 0.010 and < 0.001, respectively. DIR was significantly better than FLAIR for MS plaque number detection in the periventricular white matter, subcortical white matter, infratentorial region and the overall MS plaques burden with a p < 0.001, 0.038, < 0.001, < 0.001, respectively. No significant difference was noted between both sequences for plaques number detection in deep white matter and deep gray matter. A significant correlation between MS disease duration, number of attacks and EDSS and the overall cortical MS plaques types and the overall MS plaque burden.Conclusion3D DIR is a reliable tool and provides superior delineation in detecting cortical subtypes. In addition, DIR is of value in assessing the degree of clinical and cognitive impairment of MS affected patients.

Clinical Neurophysiology of Zika Virus Encephalitis.

Zika virus (ZIKV) has been shown to be highly neurotropic; neurologic disorders are a common complication of this infection. Encephalitis-an inflammation of the brain parenchyma associated with neurologic dysfunction-is a rare complication of ZIKV infections. It affects patients from young to elderly ages. Clinical presentation of ZIKV encephalitis may be heterogeneous, including altered mental status (decreased or altered level of consciousness, lethargy, or personality change), seizures, and focal deficits. Complementary diagnostic investigation should include neuroimaging, lumbar puncture, and EEG. Neuroimaging findings in ZIKV encephalitis are not specific and may be diverse, including normal findings, hyperintense lesions on MRI involving cortical or subcortical structures, symmetric or asymmetric lesions involving supra or infratentorial regions, and more widespread involvement such as brain swelling. A remarkable scarcity of neurophysiological data on ZIKV encephalitis was found in the literature. In line with other diagnostic examinations, there are no neurophysiological findings suggestive or specific of the disease. EEG in ZIKV encephalitis showed different results: normal or diffuse disorganization of background activity, asymmetry with abnormal focal slow waves, focal epileptic discharges or generalized spike-wave and multispike-wave complexes, and periods of generalized voltage attenuation.

Diffusion tractography of superior cerebellar peduncle and dentatorubrothalamic tracts in two autopsy confirmed progressive supranuclear palsy variants: Richardson syndrome and the speech-language variant

BackgroundProgressive supranuclear palsy (PSP) is a 4-repeat tauopathy with neurodegeneration typically observed in the superior cerebellar peduncle (SCP) and dentatorubrothalamic tracts (DRTT). However, it is unclear how these tracts are differentially affected in different clinical variants of PSP. ObjectivesTo determine whether diffusion tractography of the SCP and DRTT can differentiate autopsy-confirmed PSP with Richardson’s syndrome (PSP-RS) and PSP with predominant speech/language disorder (PSP-SL). MethodsWe studied 22 autopsy-confirmed PSP patients that included 12 with PSP-RS and 10 with PSP-SL. We compared these two groups to 11 patients with autopsy-confirmed Alzheimer’s disease with SL problems, i.e., logopenic progressive aphasia (AD-LPA) (disease controls) and 10 healthy controls. Whole brain tractography was performed to identify the SCP and DRTT, as well as the frontal aslant tract and superior longitudinal fasciculus. We assessed fractional anisotropy and mean diffusivity for each tract. Hierarchical linear modeling was used for statistical comparisons, and correlations were assessed with clinical disease severity, ocular motor impairment, and parkinsonism. DRTT connectomics matrix analysis was also performed across groups. ResultsThe SCP showed decreased fractional anisotropy for PSP-RS and PSP-SL and increased mean diffusivity in PSP-RS, compared to controls and AD-LPA. Right DRTT fibers showed lower fractional anisotropy in PSP-RS and PSP-SL compared to controls and AD-LPA, with PSP-RS also showing lower values compared to PSP-SL. Reductions in connectivity were observed in infratentorial DRTT regions in PSP-RS vs cortical regions in PSP-SL. PSP-SL showed greater abnormalities in the frontal aslant tract and superior longitudinal fasciculus compared to controls, PSP-RS, and AD-LPA. Significant correlations were observed between ocular motor impairment and SCP in PSP-RS (p = 0.042), and DRTT in PSP-SL (p = 0.022). In PSP-SL, the PSP Rating Scale correlated with the SCP (p = 0.045) and DRTT (p = 0.008), and the Unified Parkinson’s Disease Rating Scale correlated with the DRTT (p = 0.014). ConclusionsDegeneration of the SCP and DRTT are diagnostic features of both PSP-RS and PSP-SL and associations with clinical metrics validate the role of these tracts in PSP-related clinical features, particularly in PSP-SL.

Risk factors of cerebral microbleeds in young and middle-aged patients with hypertension

Background &amp; Objectives: This study aimed to explore the incidence and potential risk factors of cerebral microbleeds (CMBs) in young and middle-aged patients with hypertension. Methods: We retrospectively analyzed the clinical data of young and middle-aged patients with hypertension in the Department of Neurology, General Hospital of Western Theater Command, Chengdu, China between August 2018 and December 2020. The demographic baseline, laboratory parameters and clinical imaging data were collected. Microbleed anatomical rating scale (MARS) was applied to evaluate the presence, amount, and topographical distributions of CMBs. Results: Among 196 young and middle-aged patients with hypertension, 84 (42.9%) patients had CMBs. CMBs were more likely to occur in the deep brain tissue regions (41.8%), followed by lobar or infratentorial region. White matter hyperintensity (OR, 5.262; 95%CI, 1.314-21.075; P=0.019), abnormal lipid metabolism (OR, 3.832; 95%CI, 1.578-9.306; P=0.003), usage of anti-platelet aggregation drugs (OR, 2.947; 95%CI, 1.138-7.632; P=0.026), smoking history (OR, 3.218; 95%CI, 1.073-9.651; P=0.037), and hyperhomocysteinemia (OR, 1.415; 95%CI, 1.018-1.967; P=0.039) were independently associated with deep or infratentorial CMBs in young and middle-aged patients with hypertension. However, the occurrence of strictly lobar CMBs was only independently associated with abnormal lipid metabolism (OR, 4.162; 95%CI, 1.685-10.282; P=0.002). Conclusions: The rate of CMBs was high in young and middle-aged patients with hypertension, most commonly occurring in the deep brain tissue region. While multiple risk factors were identified to be associated with deep or infratentorial CMBs, the occurrence of strictly lobar CMBs was only associated with abnormal lipid metabolism.

Creating Computational Models for Planning TTFields Treatment for Tumors in the Infratentorial Brain

Tumor Treating Fields (TTFields) is an FDA-approved treatment for glioblastoma multiforme (GBM) and malignant pleural mesothelioma (MPM), and is currently being investigated in a phase III trial for the treatment of brain metastases from non-small cell lung cancer (NSCLC). Increased TTFields dose density at the tumor is associated with longer patient survival. Therefore, estimating dose at the tumor utilizing computational simulations with patient-specific computational models are integral for treatment planning. NSCLC brain metastases are often observed in infratentorial brain regions. In these cases, TTFields arrays may be placed on the head, neck, and upper back. Manual segmentation of this large area is impractical and time consuming. Therefore, we developed a computational method for semi-automatic segmentation of infratentorial tissues relevant to TTFields treatment planning.We incorporated a dataset of 20 head T1w Gad MRIs of patients treated with TTFields with segmentation of the infratentorial area, and 20 CT images that incorporate head, neck and upper torso from a public database for segmentation of extracranial structures. For the segmentation of the infratentorial zone we developed an atlas-based method that deforms a predefined statistical atlas to best fit the patient's MRI. Our method then revises the initial fitting to ensure the segmented structures adhere to known anatomical relations. For supratentorial brain areas, we incorporate a custom atlas-based method. Extra-cranial zones (head, neck and upper torso) were segmented with threshold-based methods for the skin, muscle, fat, bones, and bronchi. User-defined landmarks were used to segment the esophagus and the artery. The spine and CSF were segmented automatically by identifying the relevant area and defining a constant ratio between their diameters. To evaluate the segmentation of the infratentorial regions, a trained annotator manually segmented the infratentorial area of the 20 head MRIs. We compared manual and automatic segmentations and measured the Dice overlap score.The average Dice coefficient between the human annotator and the algorithms' segmentation was 0.84 (SD = 0.05) for cerebellum and 0.67 (SD = 0.05) for brainstem. These results are comparable to those observed in supratentorial regions with a method that was verified previously. The radiation oncologist confirmed that the semi-automatic segmentation of the infratentorial, and extracranial head, neck and upper torso provides a quality result for TTFields treatment planning in a reasonable amount of time for all cases. The infratentorial segmentation is fully automatic and typically lasts a few minutes. Segmentation of extracranial structures is semi-automatic and typically lasts less than an hour.We have developed a fast method for the segmentation of infratentorial structures for TTFields planning.

Preoperative Dural Contact Correlates With the Risk of Nodular Leptomeningeal Failure Following Adjuvant Stereotactic Radiosurgery

Surgical resection followed by adjuvant stereotactic radiosurgery (SRS) has become a widely accepted treatment modality for brain metastases (BM). Compared to Whole Brain Radiation (WBRT), this approach achieves equivalent overall survival (OS) while reducing cognitive toxicities and preserving quality of life. However, this method of treatment is associated with a unique pattern of treatment failure, ¨nodular leptomeningeal disease" (nLMD), that is distinct in terms of behavior, prognosis and management compared to classic leptomeningeal disease (cLMD). We aimed to identify factors associated with the incidence of nLMD in surgical cavities treated with SRS.After identifying all patients treated with surgery and SRS of BM from a prospective registry, magnetic resonance imaging (MRI) before and after surgery were used to characterize tumors on the basis of dural contact, size and location. We also determined whether treatment volumes (TV) included the surgical tract or the pre-surgical areas of tumor contact with sinus or dura and, if so, whether that was expanded by a 1-5mm or 6-10mm margin. Failures were classified as nLMD, cLMD, or local failure (LF). Survival rates were calculated using the Kaplan Meier method. Outcomes for nLMD, cLMD, and LF were calculated using the cumulative incidence method. The difference in groups was tested using the Fine-Gray competing risk model.130 patients with 132 cavities were identified. Median patient age was 61.5 (23-90), median number of BM was 1 (1-10), median target volume was 15.1cc (4-54). Twenty-one percent of tumors were infra tentorial. Ninety-seven tumors contacted the dura pre-operatively. OS at 12 and 24 months was 68% and 39%, respectively. Cumulative incidence of nLMD at 12 and 24 months was 17% and 22%, respectively and for cLMD it was 3% and 6%, respectively. The incidence of LF at 12 and 24 months was 10% and 17%, respectively. OS following nLMD vs cLMD at 6 and 12 months were 49% and 29%, and 29% and 0%, respectively. Of the factors examined, only pre-surgical dural contact correlated with time to nLMD failure (HR 0.2 (0.05-0.81) (P = 0.024). No factors examined correlated with time to cLMD failure. Among 9 patients for whom a 6-10 mm dural margin was added to the region of pre-surgical dural contact, there were no nLMD.Preoperative dural contact correlated with time to nLMD but not cLMD. Patients with nLMD lived longer than those with cLMD. Including the surgical tract, the radiation target did not influence time to nLMD or cLMD.E. Gutierrez: None. C.J. Villafuerte: None. B. Millar: None. N.J. Laperriere: None. T.D. Conrad: None. A. Kalyvas: None. G. Zadeh: None. M. Bernstein: None. J. Weiss: None. P. Kongkham: None. D.B. Shultz: None.

Severe Brain Atrophy Predicts Poor Clinical Outcome After Endovascular Treatment of Acute Basilar Artery Occlusion: An Automated Volumetric Analysis of a Nationwide Registry.

Background: Brain atrophy globally reflects the effects of preexisting risk factors and biological aging on brain structures and normally predicts poor outcomes in anterior circulation stroke. However, comparing with these patients, acute basilar artery occlusion (ABAO) impairs infratentorial regions frequently and might benefit from brain atrophy due to the resulting residual space to reduce tissue compression and thus improve prognosis, which raises doubts that current understandings for prognostic roles of brain atrophy are also applicable for ABAO. Therefore, this study aims to evaluate brain atrophy automatically from CT images and investigates its impact on outcomes of ABAO following endovascular treatment (EVT).Methods: A total of 231 ABAO who underwent EVT from the BASILAR registry were enrolled. Brain atrophy was quantified as the ratio of brain parenchymal volume to cerebrospinal fluid volume on baseline CT. The primary outcome was the modified Rankin Scale (mRS) score at 3 months.Results: The frequency of favorable outcomes (90-day mRS ≤ 3) was significantly lower in the severe atrophy group (P = 0.014). Adjusted logistic models revealed that severe brain atrophy was significantly negatively associated with favorable outcome incidence (P = 0.006), with no relationship with either in-hospital or 90-day overall mortality (all P > 0.05). Adding a severe atrophy index into the baseline model obviously enhanced its discriminatory ability in predicting the outcome by obviously increasing areas under the receiver operating characteristic curve, net reclassification improvement algorithm, and integrated discrimination improvement algorithm values (all P < 0.05).Conclusion: Severe brain atrophy did not improve in-hospital or overall mortality but impaired the long-term recovery after EVT. This objective and automated marker has the potential to be incorporated into decision-support methods for treating ABAO.

Clinical, neuroradiological and genetic findings in a cohort of patients with multiple Cerebral Cavernous Malformations.

Cerebral cavernous malformations (CCM) consist of clusters of irregular dilated capillaries and represent the second most common type of vascular malformation affecting the central nervous system. CCM might be asymptomatic or cause cerebral hemorrhage, seizures, recurrent headaches and focal neurologic deficits. Causative mutations underlining CCM have been reported in three genes: KRIT1/CCM1, MGC4607/CCM2 and PDCD10/CCM3. Therapeutic avenues are limited to surgery. Here we present clinical, neuroradiological and molecular findings in a cohort of familial and sporadic CCM patients. Thirty subjects underwent full clinical and radiological assessment. Molecular analysis was performed by direct sequencing and MLPA analysis. Twenty-eight of 30 subjects (93%) experienced one or more typical CCM disturbances with cerebral/spinal hemorrhage being the most common (43%) presenting symptom. A molecular diagnosis was achieved in 87% of cases, with three novel mutations identified. KRIT1/CCM1 patients displayed higher risk of de novo CCMs appearance and bleedings. Magnetic Resonance Imaging (MRI) showed that infratentorial region was more frequently affected in mutated subjects while brainstem was often spared in patients with negative genetic testing.

Paediatric head computed tomography dose values and the impact on image quality

Abstract Background The purpose of this study is to analyse paediatric head Computed Tomography (CT) examination dose values, establish local Diagnostic Reference Levels (DRL), and perform objective image quality assessment per categorisation. Methods A total of 100 paediatric head CT examinations divided into 5 paediatric age categorisations were retrospectively selected: 0–3months, 3months to 1 year, 1 to 6 years, and more than 6 years. Computed Tomography Dose Index (CTDIvol - mGy) and Dose Lenght Product (DLP – mGy.cm), acquisition mode and CT scanner were collected per examination. Examinations with lower and higher dose values per categorisation were selected, and 10 Regions of Interest (ROI’s) were defined on supra and infra tentorial regions in order to access image quality, based on signal and noise values. Local DRLs were compare with the literature and with previous studies of this centre. Results The obtained DLP values were 580, 570, 700, 754 mGy.cm, for the categorisation of 0–3 months, 3 months to 1 year, 1 to 6 years, and more than 6 years, respectively. No significant differences were founded in dose values and image quality, per paediatric categorisation. Conclusions Despise previous local DRLs were defined using a different age categorisation, some paediatric aged categorisation revealed an increase of the dose values. These results must be related with the acquisition of a new CT scanner. Optimisation process is on-going and new protocols are being define.