ABSTRACT
The present study aims to investigate the relationship between cerebellar volumes and cognitive reserve in individuals with Mild Cognitive Impairment (MCI). A description of proxies of cerebellar cognitive reserve in terms of different volumes across lobules is also provided. 36 individuals with MCI underwent neuropsychological (MoCA, MMSE, Clock test, CRIq) assessment and neuroimaging acquisition with magnetic resonance imaging at 3 T. Simple linear correlations were applied between cerebellar volumes and cognitive measures. Multiple linear regression models were then used to estimate standardized regression coefficients and 95% confidence intervals. Simple linear correlations between cerebellar lobules volumes and cognitive features highlighted a significant association between CRIq_Working activity and specific motor cerebellar volumes: Left_V (ρ = 0.40, p = 0.02), Right_V (r = 0.42, p = 0.002), Vermis_VIIIb (ρ = 0.47, p = 0.003), Left_X (ρ = -0.46, p = 0.002) and Vermis_X (r = 0.35, p = 0.03). Furthermore, CRIq_Working activity scores correlated with certain cerebellar lobules implicated in cognition: Left_Crus_II, Vermis VIIb, Left_IX. MMSE was associated only with the Right_VIIB volume (r = 0.35, p = 0.02), while Clock Drawing Test scores correlated with both Left_Crus_I and Right_Crus_I (r = -0.42 and r = 0.42, p = 0.02, respectively). This study suggests that a higher cognitive reserve is associated with specific cerebellar lobule volumes and that Working activity may play a predominant role in this association. These findings contribute to the understanding of the relationship between cerebellar volumes and cognitive reserve, highlighting the potential modulatory role of Working activity on cerebellum response to cognitive decline.
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We compared choroid plexus (ChP) manual segmentation on non-contrast-enhanced (non-CE) sequences and reference standard CE T1- weighted (T1w) sequences in 61 multiple sclerosis patients prospectively included. ChP was separately segmented on T1w, T2-weighted (T2w) fluid-attenuated inversion-recovery (FLAIR), and CE-T1w sequences. Inter-rater variability assessed on 10 subjects showed high reproducibility between sequences measured by intraclass correlation coefficient (T1w 0.93, FLAIR 0.93, CE-T1w 0.99). CE-T1w showed higher signal-to-noise ratio and contrast-to-noise ratio (CE-T1w 23.77 and 18.49, T1w 13.73 and 7.44, FLAIR 13.09 and 10.77, respectively). Manual segmentation of ChP resulted 3.073 ± 0.563 mL (mean ± standard deviation) on T1w, 3.787 ± 0.679 mL on FLAIR, and 2.984 ± 0.506 mL on CE-T1w images, with an error of 28.02 ± 19.02% for FLAIR and 3.52 ± 12.61% for T1w. FLAIR overestimated ChP volume compared to CE-T1w (p < 0.001). The Dice similarity coefficient of CE-T1w versus T1w and FLAIR was 0.67 ± 0.05 and 0.68 ± 0.05, respectively. Spatial error distribution per slice was calculated after nonlinear coregistration to the standard MNI152 space and showed a heterogeneous profile along the ChP especially near the fornix and the hippocampus. Quantitative analyses suggest T1w as a surrogate of CE-T1w to estimate ChP volume.Relevance statement To estimate the ChP volume, CE-T1w can be replaced by non-CE T1w sequences because the error is acceptable, while FLAIR overestimates the ChP volume. This encourages the development of automatic tools for ChP segmentation, also improving the understanding of the role of the ChP volume in multiple sclerosis, promoting longitudinal studies.Key points ⢠CE-T1w sequences are considered the reference standard for ChP manual segmentation.⢠FLAIR sequences showed a higher CNR than T1w sequences but overestimated the ChP volume.⢠Non-CE T1w sequences can be a surrogate of CE-T1w sequences for manual segmentation of ChP.
Subject(s)
Multiple Sclerosis , Humans , Multiple Sclerosis/diagnostic imaging , Reproducibility of Results , Choroid Plexus/diagnostic imaging , Magnetic Resonance Imaging , Signal-To-Noise RatioABSTRACT
Background: Paediatric-onset multiple sclerosis (POMS) therapeutic approach derives from of adult-onset multiple sclerosis (AOMS) tailored algorithms. Objectives: To evaluate in a common clinical scenario the efficacy and safety of alemtuzumab (ALZ) in POMS and AOMS. Methods: All patients switching from natalizumab (NTZ) to ALZ for safety concerns (high anti-John Cunningham Virus Antibody Index value, anti-JCV Index) were enrolled in this single-centre, retrospective, case-control open-label study. Results: Ten POMS and 27 AOMS were followed up for 51.3 months. After month 12, we found a lower risk of clinical or radiological relapses among AOMS patients and among patients with older age at ALZ (both p < 0.05). Survival analysis revealed an increased risk of relapse in POMS compared with AOMS (logrank p = 0.00498) and patients starting ALZ before age 22.75 years than the elder ones (logrank p = 0.0018). Survival analysis did not disclose any difference between AOMS and POMS (logrank p = 0.27) in terms of progression independent of any relapse activity (PIRA). In addition, no evidence of relapse-associated worsening was observed. Autoimmune events were reported by 5 AOMS and no POMS (29.4% versus 0.0%, p = 0.057), and survival analysis was not significant (logrank p = 0.0786). Conclusion: ALZ seems more effective in AOMS than in POMS following NTZ. These findings underrate ALZ effectiveness when shifting from NTZ in POMS.
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Importance: The prognosis of overall survival (OS) in patients with glioblastoma (GBM) may depend on the underlying structural connectivity of the brain. Objective: To examine the association between white matter tracts affected by GBM and patients' OS by means of a new tract density index (TDI). Design, Setting, and Participants: This prognostic study in patients with a histopathologic diagnosis of GBM examined a discovery cohort of 112 patients who underwent surgery between February 1, 2015, and November 30, 2020 (follow-up to May 31, 2023), in Italy and 70 patients in a replicative cohort (n = 70) who underwent surgery between September 1, 2012, and November 30, 2015 (follow-up to May 31, 2023), in Germany. Statistical analyses were performed from June 1, 2021, to May 31, 2023. Thirteen and 12 patients were excluded from the discovery and the replicative sets, respectively, because of magnetic resonance imaging artifacts. Exposure: The density of white matter tracts encompassing GBM. Main Outcomes and Measures: Correlation, linear regression, Cox proportional hazards regression, Kaplan-Meier, and prediction analysis were used to assess the association between the TDI and OS. Results were compared with common prognostic factors of GBM, including age, performance status, O6-methylguanine-DNA methyltransferase methylation, and extent of surgery. Results: In the discovery cohort (n = 99; mean [SD] age, 62.2 [11.5] years; 29 female [29.3%]; 70 male [70.7%]), the TDI was significantly correlated with OS (r = -0.34; P < .001). This association was more stable compared with other prognostic factors. The TDI showed a significant regression pattern (Cox: hazard ratio, 0.28 [95% CI, 0.02-0.55; P = .04]; linear: t = -2.366; P = .02). and a significant Kaplan-Meier stratification of patients as having lower or higher OS based on the TDI (log-rank test = 4.52; P = .03). Results were confirmed in the replicative cohort (n = 58; mean [SD] age, 58.5 [11.1] years, 14 female [24.1%]; 44 male [75.9%]). High (24-month cutoff) and low (18-month cutoff) OS was predicted based on the TDI computed in the discovery cohort (accuracy = 87%). Conclusions and Relevance: In this study, GBMs encompassing regions with low white matter tract density were associated with longer OS. These findings indicate that the TDI is a reliable presurgical outcome predictor that may be considered in clinical trials and clinical practice. These findings support a framework in which the outcome of GBM depends on the patient's brain organization.
Subject(s)
Brain Neoplasms , Glioblastoma , White Matter , Humans , Male , Female , Middle Aged , Glioblastoma/diagnostic imaging , Glioblastoma/surgery , Glioblastoma/drug therapy , White Matter/diagnostic imaging , White Matter/pathology , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Brain Neoplasms/genetics , Prognosis , Brain/pathology , Retrospective StudiesABSTRACT
Background: Resting-state functional-MRI studies identified several cortical gray matter functional networks (GMNs) and white matter functional networks (WMNs) with precise anatomical localization. Here, we aimed at describing the relationships between brain's functional topological organization and glioblastoma (GBM) location. Furthermore, we assessed whether GBM distribution across these networks was associated with overall survival (OS). Materials and methods: We included patients with histopathological diagnosis of IDH-wildtype GBM, presurgical MRI and survival data. For each patient, we recorded clinical-prognostic variables. GBM core and edema were segmented and normalized to a standard space. Pre-existing functional connectivity-based atlases were used to define network parcellations: 17 GMNs and 12 WMNs were considered in particular. We computed the percentage of lesion overlap with GMNs and WMNs, both for core and edema. Differences between overlap percentages were assessed through descriptive statistics, ANOVA, post-hoc tests, Pearson's correlation tests and canonical correlations. Multiple linear and non-linear regression tests were employed to explore relationships with OS. Results: 99 patients were included (70 males, mean age 62 years). The most involved GMNs included ventral somatomotor, salient ventral attention and default-mode networks; the most involved WMNs were ventral frontoparietal tracts, deep frontal white matter, and superior longitudinal fasciculus system. Superior longitudinal fasciculus system and dorsal frontoparietal tracts were significantly more included in the edema (p < 0.001). 5 main patterns of GBM core distribution across functional networks were found, while edema localization was less classifiable. ANOVA showed significant differences between mean overlap percentages, separately for GMNs and WMNs (p-values<0.0001). Core-N12 overlap predicts higher OS, although its inclusion does not increase the explained OS variance. Discussion and conclusion: Both GBM core and edema preferentially overlap with specific GMNs and WMNs, especially associative networks, and GBM core follows five main distribution patterns. Some inter-related GMNs and WMNs were co-lesioned by GBM, suggesting that GBM distribution is not independent of the brain's structural and functional organization. Although the involvement of ventral frontoparietal tracts (N12) seems to have some role in predicting survival, network-topology information is overall scarcely informative about OS. fMRI-based approaches may more effectively demonstrate the effects of GBM on brain networks and survival.
ABSTRACT
Resting state fMRI has been used in many studies to investigate the impact of brain tumours on functional connectivity (FC). However, these studies have so far assumed that FC is stationary, disregarding the fact that the brain fluctuates over dynamic states. Here we utilised resting state fMRI data from 33 patients with high-grade gliomas and 33 healthy controls to examine the dynamic interplay between resting-state networks and to gain insights into the impact of brain tumours on functional dynamics. By employing Hidden Markov Models, we demonstrated that functional dynamics persist even in the presence of a high-grade glioma, and that patients exhibited a global decrease of connections strength, as well as of network segregation. Furthermore, through a multivariate analysis, we demonstrated that patients' cognitive scores are highly predictive of pathological dynamics, thus supporting our hypothesis that functional dynamics could serve as valuable biomarkers for better understanding the traits of high-grade gliomas.
Subject(s)
Brain Neoplasms , Glioma , Humans , Neural Pathways , Brain , Brain Mapping , Brain Neoplasms/diagnostic imaging , Glioma/diagnostic imaging , Magnetic Resonance ImagingABSTRACT
AIM: Nodopathies and paranodopathies are autoimmune neuropathies associated with antibodies to nodal-paranodal antigens (neurofascin 140/186 and 155, contactin-1, contactin-associated protein 1 [Caspr1]) characterized by peculiar clinical features, poor response to standard immunotherapies (e.g., intravenous immunoglobulins, IVIg). Improvement after anti-CD20 monoclonal antibody therapy has been reported. Data on Caspr1 antibodies pathogenicity are still preliminary, and longitudinal titers have been poorly described. METHODS: We report on a young woman who developed a disabling neuropathy with antibodies to the Caspr1/contactin-1 complex showing a dramatic improvement after rituximab therapy, mirrored by the decrease of antibody titers. RESULTS: A 26-year-old woman presented with ataxic-stepping gait, severe motor weakness at four limbs, and low frequency postural tremor. For neurophysiological evidence of demyelinating neuropathy, she was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy and treated with IVIg without benefit. MRI showed symmetrical hypertrophy and marked signal hyperintensity of brachial and lumbosacral plexi. Cerebrospinal fluid showed 710 mg/dL protein. Despite intravenous methylprednisolone, the patient progressively worsened, and became wheelchair-bound. Antibodies to nodal-paranodal antigens were searched for by ELISA and cell-based assay. Anticontactin/Caspr1 IgG4 antibodies resulted positive. The patient underwent rituximab therapy with slow progressive improvement that mirrored the antibodies titer, measured throughout the disease course. CONCLUSIONS: Our patient had a severe progressive course with early disability and axonal damage, and slow recovery starting only a few months after antibody-depleting therapy. The close correlation between titer, disability, and treatment, supports the pathogenicity of Caspr1 antibodies, and suggest that their longitudinal evaluation might provide a potential biomarker to evaluate treatment response.
Subject(s)
Immunoglobulins, Intravenous , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating , Female , Humans , Adult , Immunoglobulins, Intravenous/therapeutic use , Rituximab/therapeutic use , Antibodies , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/drug therapy , Contactins , AutoantibodiesABSTRACT
A 27-year-old woman was admitted to our hospital for fever, associated with headache, nausea, and vomiting, and she rapidly developed mild left facial nerve palsy and diplopia. Neurological examination revealed mild meningitis associated with bilateral VI cranial nerve palsy and mild left facial palsy. As central nervous system (CNS) infection was suspected, a diagnostic lumbar puncture was performed, which revealed 1,677 cells/µl, 70% of which were polymorphonuclear leukocytes. Moreover, multiplex PCR immunoassay was positive for Neisseria meningitidis, supporting the diagnosis of bacterial meningitis. Finally, IgG oligoclonal bands (IgGOB) were absent in serum and cerebrospinal fluid (CSF). Therefore, ceftriaxone antibiotic therapy was started, and in the following days, the patient's signs and symptoms improved, with complete remission of diplopia and meningeal signs within a week. On the contrary, left facial nerve palsy progressively worsened into a severe bilateral deficit. A second lumbar puncture was therefore performed: the CSF analysis revealed a remarkable decrease of pleocytosis with a qualitative modification (only lymphocytes), and oligoclonal IgG bands were present. A new brain MRI was performed, showing a bilateral gadolinium enhancement of the intrameatal VII and VIII cranial nerves bilaterally. Due to suspicion of para-infectious etiology, the patient was treated with oral steroid (prednisolone 1 mg/kg/day), with a progressive and complete regression of the symptoms. We suggest that in this case, after a pathogen-driven immunological response (characterized by relevant CSF mixed pleocytosis and no evidence of IgGOB), a para-infectious adaptive immunity-driven reaction (with mild lymphocyte pleocytosis and pattern III IgGOB) against VII and VIII cranial nerves started. Indeed, steroid administration caused a rapid and complete restoration of cranial nerve function.
Subject(s)
Cranial Nerve Diseases , Meningitis, Bacterial , Female , Humans , Adult , Oligoclonal Bands , Ceftriaxone , Gadolinium , Diplopia , Leukocytosis , Contrast Media , Cranial Nerve Diseases/diagnosis , Cranial Nerve Diseases/drug therapy , Cranial Nerve Diseases/etiology , Prednisolone , Meningitis, Bacterial/complications , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/drug therapy , Paralysis , Immunoglobulin G , Anti-Bacterial AgentsABSTRACT
Gliomas are amongst the most common primary brain tumours in adults and are often associated with poor prognosis. Understanding the extent of white matter (WM) which is affected outside the tumoral lesion may be of paramount importance to explain cognitive deficits and the clinical progression of the disease. To this end, we explored both direct (i.e., tractography based) and indirect (i.e., atlas-based) approaches to quantifying WM structural disconnections in a cohort of 44 high- and low-grade glioma patients. While these methodologies have recently gained popularity in the context of stroke and other pathologies, to our knowledge, this is the first time they are applied in patients with brain tumours. More specifically, in this work, we present a quantitative comparison of the disconnection maps provided by the two methodologies by applying well-known metrics of spatial similarity, extension, and correlation. Given the important role the oedematous tissue plays in the physiopathology of tumours, we performed these analyses both by including and excluding it in the definition of the tumoral lesion. This was done to investigate possible differences determined by this choice. We found that direct and indirect approaches offer two distinct pictures of structural disconnections in patients affected by brain gliomas, presenting key differences in several regions of the brain. Following the outcomes of our analysis, we eventually discuss the strengths and pitfalls of these two approaches when applied in this critical field.
Subject(s)
Brain Neoplasms , Glioma , White Matter , Adult , Humans , Glioma/diagnostic imaging , Glioma/pathology , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , White Matter/diagnostic imaging , White Matter/pathology , Brain Mapping/methods , Brain/diagnostic imaging , Brain/pathologyABSTRACT
Background: Glioblastoma (GBM) is the most commonly occurring primary malignant brain tumor, and it carries a dismal prognosis. Focusing on the tumor microenvironment may provide new insights into pathogenesis, but no clinical tools are available to do this. We hypothesized that the infiltration of different leukocyte populations in the tumoral and peritumoral brain tissues may be measured by magnetic resonance imaging (MRI). Methods: Pre-operative MRI was combined with immune phenotyping of intraoperative tumor tissue based on flow cytometry of myeloid cell populations that are associated with immune suppression, namely, microglia and bone marrow-derived macrophages (BMDM). These cell populations were measured from the central and marginal areas of the lesion identified intraoperatively with 5-aminolevulinic acid-guided surgery. MRI features (volume, mean and standard deviation of signal intensity, and fractality) were derived from all MR sequences (T1w, Gd+ T1w, T2w, FLAIR) and ADC MR maps and from different tumor areas (contrast- and non-contrast-enhancing tumor, necrosis, and edema). The principal components of MRI features were correlated with different myeloid cell populations by Pearson's correlation. Results: We analyzed 126 samples from 62 GBM patients. The ratio between BMDM and microglia decreases significantly from the central core to the periphery. Several MRI-derived principal components were significantly correlated (p <0.05, r range: [-0.29, -0.41]) with the BMDM/microglia ratio collected in the central part of the tumor. Conclusions: We report a significant correlation between structural MRI clinical imaging and the ratio of recruited vs. resident macrophages with different immunomodulatory activities. MRI features may represent a novel tool for investigating the microenvironment of GBM.
ABSTRACT
Assessment of impaired/preserved cortical regions in brain tumours is typically performed via intraoperative direct brain stimulation of eloquent areas or task-based functional MRI. One main limitation is that they overlook distal brain regions or networks that could be functionally impaired by the tumour. This study aims (i) to investigate the impact of brain tumours on the cortical synchronization of brain networks measured with resting-state functional magnetic resonance imaging (resting-state networks) both near the lesion and remotely and (ii) to test whether potential changes in resting-state networks correlate with cognitive status. The sample included 24 glioma patients (mean age: 58.1 ± 16.4 years) with different pathological staging. We developed a new method for single subject localization of resting-state networks abnormalities. First, we derived the spatial pattern of the main resting-state networks by means of the group-guided independent component analysis. This was informed by a high-resolution resting-state networks template derived from an independent sample of healthy controls. Second, we developed a spatial similarity index to measure differences in network topography and strength between healthy controls and individual brain tumour patients. Next, we investigated the spatial relationship between altered networks and tumour location. Finally, multivariate analyses related cognitive scores across multiple cognitive domains (attention, language, memory, decision making) with patterns of multi-network abnormality. We found that brain gliomas cause broad alterations of resting-state networks topography that occurred mainly in structurally normal regions outside the tumour and oedema region. Cortical regions near the tumour often showed normal synchronization. Finally, multi-network abnormalities predicted attention deficits. Overall, we present a novel method for the functional localization of resting-state networks abnormalities in individual glioma patients. These abnormalities partially explain cognitive disabilities and shall be carefully navigated during surgery.
ABSTRACT
Though the assessment of cognitive functions is proven to be a reliable prognostic indicator in patients with brain tumors, some of these functions, such as cognitive control, are still rarely investigated. The objective of this study was to examine proactive and reactive control functions in patients with focal brain tumors and to identify lesioned brain areas more at "risk" for developing impairment of these functions. To this end, a group of twenty-two patients, candidate to surgery, were tested with an AX-CPT task and a Stroop task, along with a clinical neuropsychological assessment, and their performance was compared to that of a well-matched healthy control group. Although overall accuracy and response times were similar for patients and control groups, the patient group failed more on the BX trials of the AX-CPT task and on the incongruent trials of the Stroop task, specifically. Behavioral results were associated with the damaged brain areas, mostly distributed in right frontal regions, by means of a lesion-symptom mapping multivariate approach. This analysis showed that a white matter cluster in the right prefrontal area was associated with lower d'-context values on the AX-CPT, which reflected the fact that these patients rely more on later information (reactive processes) to respond to unexpected and conflicting stimuli, than on earlier contextual cues (proactive processes). Taken together, these results suggest that patients with brain tumors present an imbalance between proactive and reactive control strategies in high interfering conditions, in association with right prefrontal white matter lesions.
Subject(s)
Brain Neoplasms , Cognitive Dysfunction , Brain Mapping , Brain Neoplasms/complications , Brain Neoplasms/diagnostic imaging , Cognition/physiology , Humans , Prefrontal Cortex/physiology , Reaction Time/physiologyABSTRACT
Diffusion-based biophysical models have been used in several recent works to study the microenvironment of brain tumours. While the pathophysiological interpretation of the parameters of these models remains unclear, their use as signal representations may yield useful biomarkers for monitoring the treatment and the progression of this complex and heterogeneous disease. Up to now, however, no study was devoted to assessing the mathematical stability of these approaches in cancerous brain regions. To this end, we analyzed in 11 brain tumour patients the fitting results of two microstructure models (Neurite Orientation Dispersion and Density Imaging and the Spherical Mean Technique) and of a signal representation (Diffusion Kurtosis Imaging) to compare the reliability of their parameter estimates in the healthy brain and in the tumoral lesion. The framework of our between-tissue analysis included the computation of 1) the residual sum of squares as a goodness-of-fit measure 2) the standard deviation of the models' derived metrics and 3) models' sensitivity functions to analyze the suitability of the employed protocol for parameter estimation in the different microenvironments. Our results revealed no issues concerning the fitting of the models in the tumoral lesion, with similar goodness of fit and parameter precisions occurring in normal appearing and pathological tissues. Lastly, with the aim of highlight possible biomarkers, in our analysis we briefly discuss the correlation between the metrics of the three techniques, identifying groups of indices which are significantly collinear in all tissues and thus provide no additional information when jointly used in data-driven analyses.
Subject(s)
Brain Neoplasms , Diffusion Magnetic Resonance Imaging , Brain/diagnostic imaging , Brain Neoplasms/diagnostic imaging , Diffusion Magnetic Resonance Imaging/methods , Diffusion Tensor Imaging/methods , Humans , Reproducibility of Results , Tumor MicroenvironmentABSTRACT
Rhinocerebral mucormycosis (RCM) may result in severe intracranial ischemic and hemorrhagic lesions. Both computed tomography (CT) and magnetic resonance imaging (MRI) play an essential role in the diagnosis of RCM, but whereas CT is better for assessing bone erosion, MRI is superior in evaluating soft tissue, intraorbital extension, and in assessing intracranial and vascular invasion. Specific CT and MRI techniques, such as CT angiography or enhanced MR angiography, and more advanced MRI sequences such as gadolinium-3D Black Blood imaging, contribute to the assessment of the extension of vascular invasion.In this pictorial review, we describe specific CT and MRI signs of RCM, mainly focusing on its life-threatening complications due to vascular involvement.
Subject(s)
Brain Diseases/diagnostic imaging , Brain Diseases/parasitology , Magnetic Resonance Imaging , Mucormycosis/diagnostic imaging , Neuroimaging , Sinusitis/diagnostic imaging , Sinusitis/parasitology , Tomography, X-Ray Computed , Brain Diseases/complications , Brain Ischemia/etiology , Cavernous Sinus Thrombosis/etiology , Cerebral Hemorrhage/etiology , Diagnosis, Differential , Humans , Intracranial Aneurysm/etiology , Mucormycosis/complications , Orbital Diseases/complications , Orbital Diseases/diagnostic imaging , Orbital Diseases/parasitology , Sinusitis/complicationsABSTRACT
A few 18F-FDG PET/CT studies have revealed the presence of brain hypermetabolism in the brain stem and cervical spinal cord of patients within the amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) continuum. We aimed to investigate this finding through a hybrid PET/MRI system, allowing a more precise depiction of the spatial pattern of metabolic changes in the brain stem and cervical spinal cord. Methods: Twenty-eight patients with a diagnosis of ALS or a diagnosis of the behavioral variant of FTD plus motoneuron disease, as well as 13 control subjects, underwent 18F-FDG PET/MRI. Mean normalized 18F-FDG uptake in the midbrain/pons, medulla oblongata, and cervical spinal cord as defined on the individual's MRI scans were compared between groups. Furthermore, the associations between regional 18F-FDG uptake and clinical and demographic characteristics-including gene mutation, type of onset (bulbar, spinal, dementia), and clinical characteristics-were investigated. Results: A significant (P < 0.005) increment in glucose metabolism in the midbrain/pons and medulla oblongata was found in ALS/FTD patients (spinal-ALS and FTD-motor neuron disease subgroups) in comparison to controls. No relevant associations between clinical and metabolic features were reported, although medulla oblongata hypermetabolism was associated with shortened survival (P < 0.001). Conclusion: Increased glucose metabolism in the brain stem might be due to neuroinflammation, one of the key steps in the pathogenic cascade that leads to neurodegeneration in ALS/FTD. 18F-FDG PET/MRI could be a valuable tool to assess glial changes in the ALS/FTD spectrum and could serve as a prognostic biomarker. Large prospective initiatives would likely shed more light on the promising application of PET/MRI in this setting.
Subject(s)
Amyotrophic Lateral Sclerosis , Frontotemporal Dementia , Amyotrophic Lateral Sclerosis/diagnostic imaging , Brain Stem , Fluorodeoxyglucose F18 , Frontotemporal Dementia/diagnostic imaging , Glucose , Humans , Magnetic Resonance Imaging , Positron Emission Tomography Computed Tomography , Prospective Studies , Tomography, X-Ray ComputedABSTRACT
Dementia in Lewy Body Diseases (Parkinson's disease and dementia with Lewy Bodies) affects progression of disabilities, quality of life and well-being. Understanding its pathogenetic mechanisms is critical to properly implement disease-modifying strategies. It has been hypothesized that synuclein- and amyloid-pathology act synergistically aggravating cognitive decline in elderly patients but their precise contribution to dementia is debated. In this study, we aimed at exploring if presence of amyloid deposits influences clinical, cognitive and neuroanatomical correlates of mental decline in a cohort of 40 Parkinson's disease patients with normal cognition (n = 5), mild cognitive impairment (n = 22), and dementia (n = 13) as well as in Dementia with Lewy Bodies (n = 10). Patients underwent simultaneous 3 T PET/MRI with [18F]-flutemetamol and were assessed with an extensive baseline motor and neuropsychological examination, which allowed level II diagnosis of mild cognitive impairment and dementia. The role of amyloid positivity on each cognitive domain, and on the rate of conversion to dementia at 1-year follow-up was explored. A Kaplan Meier and the Log Rank (Mantel-Cox) test were used to assess the pairwise differences in time-to-develop dementia in Parkinson's disease patients with and without significant amyloidosis. Furthermore, the presence of an Alzheimer's dementia-like morphological pattern was evaluated using visual and automated assessment of T1-weighted and T2-weighted MRI images. We observed similar percentage of amyloid deposits in Parkinson's disease dementia and dementia with Lewy Bodies cohorts (50% in each group) with an overall prevalence of 34% of significant amyloid depositions in Lewy Body Diseases. PET amyloid positivity was associated with worse global cognition (Montreal Cognitive Assessment and Mini Mental State Examination), executive and language difficulties. At 12-month follow-up, amyloid positive Parkinson's disease patients were more likely to have become demented than those without amyloidosis. Moreover, there was no difference in the presence of an Alzheimer's disease-like atrophy pattern and in vascular load (at Fazekas scale) between Lewy Body Diseases with and without significant amyloid deposits. Our findings suggest that in Lewy Body Diseases, amyloid deposition enhances cognitive deficits, particularly attention-executive and language dysfunctions. However, the large number of patients without significant amyloid deposits among our cognitively impaired patients indicates that synuclein pathology itself plays a critical role in the development of dementia in Lewy Body Diseases.
ABSTRACT
BACKGROUND: Radiological parameters predicting the postoperative neurological outcome after resection of a spinal meningioma (SM) are poorly studied, with controversial results. METHODS: Observational multicenter cohort (2011-2018) of adult patients undergoing surgery for resection of SM. Tumor-canal volume ratio (TCR), the areas related to the cord and tumor occupancy at maximum compression, the presence of dural tail, calcifications, signs of myelopathy, and postoperative cord expansion were compared with the modified McCormick scale (mMCS) preoperative and at follow-up. RESULTS: In the cohort (n = 90 patients), cord and tumor occupancy as well as cord compression and tumor volume showed a correlation with preoperative mMCS (p < 0.05, R -0.23; p < 0.001, R 0.35; p < 0.005, R -0.29; p < 0.001, R 0.42). Cord occupancy had a strong correlation with cord compression (p < 0.001, R 0.72). Tumor occupancy and TCR were correlated with relative outcome at follow-up (p < 0.005 R 0.3; p < 0.005 R 0.29). No correlation was found between cord re-expansion and clinical outcome at follow-up. Finally, a correlation was shown between preoperative signs of cord myelopathy and mMCS (p < 0.05 R 0.21) at follow-up. CONCLUSIONS: Larger tumors showed lower preoperative functional status and a worse clinical outcome. Moreover, preoperative T2 cord signal changes are correlated with a poorer outcome.
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The pressure cooker technique was originally ideated to obtain wedge-flow conditions during arteriovenous malformation or arteriovenous fistula embolisation. The anti-reflux plug created with coils or glue around the tip of a detachable microcatheter enables a continuous injection with a more in-depth penetration. Here we describe two illustrative cases performed with a variation of the technique that we describe as the hand-compression pressure cooker technique.
Subject(s)
Arteriovenous Fistula , Arteriovenous Malformations , Embolization, Therapeutic , Arteriovenous Fistula/therapy , Humans , Treatment OutcomeABSTRACT
Awake surgery and intraoperative neuromonitoring represent the gold standard for surgery of lesion located in language-eloquent areas of the dominant hemisphere, enabling the maximal safe resection while preserving language function. Nevertheless, this functional mapping is invasive; it can be executed only during surgery and in selected patients. Moreover, the number of neuro-oncological bilingual patients is constantly growing, and performing awake surgery in this group of patients can be difficult. In this scenario, the application of accurate, repeatable and non-invasive preoperative mapping procedures is needed, in order to define the anatomical distribution of both languages. Repetitive navigated transcranial magnetic stimulation (rnTMS) associated with functional subcortical fiber tracking (nTMS-based DTI-FT) represents a promising and comprehensive mapping tool to display language pathway and function reorganization in neurosurgical patients. Herein we report a case of a bilingual patient affected by brain tumor in the left temporal lobe, who underwent rnTMS mapping for both languages (Romanian and Italian), disclosing the true eloquence of the anterior part of the lesion in both tests. After surgery, language abilities were intact at follow-up in both languages. This case represents a preliminary application of nTMS-based DTI-FT in neurosurgery for brain tumor in eloquent areas in a bilingual patient.