MR Imaging Signs of Gadolinium Retention Are Not Associated with Long-Term Motor and Cognitive Outcomes in Multiple Sclerosis.

BACKGROUND AND PURPOSE: The long-term impact of gadolinium retention in the dentate nuclei of patients undergoing administration of seriate gadolinium-based contrast agents is still widely unexplored. The aim of this study was to evaluate the impact of gadolinium retention on motor and cognitive disability in patients with MS during long-term follow-up. MATERIALS AND METHODS: In this retrospective study, clinical data were obtained from patients with MS followed in a single center from 2013 to 2022 at different time points. These included the Expanded Disability Status Scale score to evaluate motor impairment and the Brief International Cognitive Assessment for MS battery to investigate cognitive performances and their respective changes with time. The association with qualitative and quantitative MR imaging signs of gadolinium retention (namely, the presence of dentate nuclei T1-weighted hyperintensity and changes in longitudinal relaxation R1 maps, respectively) was probed using different General Linear Models and regression analyses. RESULTS: No significant differences in motor or cognitive symptoms emerged between patients showing dentate nuclei hyperintensity and those without visible changes on T1WIs (P = .14 and 0.92, respectively). When we tested possible relationships between quantitative dentate nuclei R1 values and both motor and cognitive symptoms, separately, the regression models including demographic, clinical, and MR imaging features explained 40.5% and 16.5% of the variance, respectively, without any significant effect of dentate nuclei R1 values (P = .21 and 0.30, respectively). CONCLUSIONS: Our findings suggest that gadolinium retention in the brains of patients with MS is not associated with long-term motor or cognitive outcomes.

Quantitative MRI in Multiple Sclerosis: From Theory to Application.

Quantitative MR imaging techniques allow evaluating different aspects of brain microstructure, providing meaningful information about the pathophysiology of damage in CNS disorders. In the study of patients with MS, quantitative MR imaging techniques represent an invaluable tool for studying changes in myelin and iron content occurring in the context of inflammatory and neurodegenerative processes. In the first section of this review, we summarize the physics behind quantitative MR imaging, here defined as relaxometry and quantitative susceptibility mapping, and describe the neurobiological correlates of quantitative MR imaging findings. In the second section, we focus on quantitative MR imaging application in MS, reporting the main findings in both the gray and white matter compartments, separately addressing macroscopically damaged and normal-appearing parenchyma.

A Combined Radiomics and Machine Learning Approach to Overcome the Clinicoradiologic Paradox in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Conventional MR imaging explains only a fraction of the clinical outcome variance in multiple sclerosis. We aimed to evaluate machine learning models for disability prediction on the basis of radiomic, volumetric, and connectivity features derived from routine brain MR images. MATERIALS AND METHODS: In this retrospective cross-sectional study, 3T brain MR imaging studies of patients with multiple sclerosis, including 3D T1-weighted and T2-weighted FLAIR sequences, were selected from 2 institutions. T1-weighted images were processed to obtain volume, connectivity score (inferred from the T2 lesion location), and texture features for an atlas-based set of GM regions. The site 1 cohort was randomly split into training (n = 400) and test (n = 100) sets, while the site 2 cohort (n = 104) constituted the external test set. After feature selection of clinicodemographic and MR imaging-derived variables, different machine learning algorithms predicting disability as measured with the Expanded Disability Status Scale were trained and cross-validated on the training cohort and evaluated on the test sets. The effect of different algorithms on model performance was tested using the 1-way repeated-measures ANOVA. RESULTS: The selection procedure identified the 9 most informative variables, including age and secondary-progressive course and a subset of radiomic features extracted from the prefrontal cortex, subcortical GM, and cerebellum. The machine learning models predicted disability with high accuracy (r approaching 0.80) and excellent intra- and intersite generalizability (r ≥ 0.73). The machine learning algorithm had no relevant effect on the performance. CONCLUSIONS: The multidimensional analysis of brain MR images, including radiomic features and clinicodemographic data, is highly informative of the clinical status of patients with multiple sclerosis, representing a promising approach to bridge the gap between conventional imaging and disability.

Unraveling Deep Gray Matter Atrophy and Iron and Myelin Changes in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Modifications of magnetic susceptibility have been consistently demonstrated in the subcortical gray matter of MS patients, but some uncertainties remain concerning the underlying neurobiological processes and their clinical relevance. We applied quantitative susceptibility mapping and longitudinal relaxation rate relaxometry to clarify the relative contribution of atrophy and iron and myelin changes to deep gray matter damage and disability in MS. MATERIALS AND METHODS: Quantitative susceptibility mapping and longitudinal relaxation rate maps were computed for 91 patients and 55 healthy controls from MR images acquired at 3T. Applying an external model, we estimated iron and myelin concentration maps for all subjects. Subsequently, changes of deep gray matter iron and myelin concentration (atrophy-dependent) and content (atrophy-independent) were investigated globally (bulk analysis) and regionally (voxel-based and atlas-based thalamic subnuclei analyses). The clinical impact of the observed MRI modifications was evaluated via regression models. RESULTS: We identified reduced thalamic (P < .001) and increased pallidal (P < .001) mean iron concentrations in patients with MS versus controls. Global myelin and iron content in the basal ganglia did not differ between the two groups, while actual iron depletion was present in the thalamus (P < .001). Regionally, patients showed increased iron concentration in the basal ganglia (P ≤ .001) and reduced iron and myelin content in thalamic posterior-medial regions (P ≤ .004), particularly in the pulvinar (P ≤ .001). Disability was predicted by thalamic volume (B = -0.341, P = .02), iron concentration (B = -0.379, P = .005) and content (B = -0.406, P = .009), as well as pulvinar iron (B = -0.415, P = .003) and myelin (B = -0.415, P = .02) content, independent of atrophy. CONCLUSIONS: Quantitative MRI suggests an atrophy-related iron increase within the basal ganglia of patients with MS, along with an atrophy-independent reduction of thalamic iron and myelin correlating with disability. Absolute depletions of thalamic iron and myelin may represent sensitive markers of subcortical GM damage, which add to the clinical impact of thalamic atrophy in MS.

Diffuse brain connectivity changes in Charcot-Marie-Tooth type 1a patients: a resting-state functional magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Changes of brain structure and function have been described in peripheral neuropathies. The aim of our study was to systematically investigate possible modifications of major large-scale brain networks using resting-state functional magnetic resonance imaging (RS-fMRI) in Charcot-Marie-Tooth disease type 1A (CMT1A) patients. METHODS: In this cross-sectional study, 3-T MRI brain scans were acquired of right-handed genetically confirmed CMT1A patients and age- and sex-comparable healthy controls. Patients also underwent clinical and electrophysiological examinations assessing neurological impairment. RS-fMRI data were analysed using a seed-based approach, with 32 different seeds sampling the main hubs of default mode, sensorimotor, visual, salience (SN), dorsal attention, frontoparietal, language and cerebellar networks. Between-group differences in terms of functional connectivity (FC) with the explored seeds were tested voxelwise, correcting for local grey matter density to account for possible structural abnormalities, whilst the relationship between FC modifications and neurological impairment was investigated using robust correlation analyses. RESULTS: Eighteen CMT1A patients (34.0 ± 11.4 years; M/F 11/7) were enrolled, along with 20 healthy controls (30.1 ± 10.2 years; M/F 11/9). In the CMT group compared to controls, clusters of increased FC with the visual cortex (P = 0.001), SN (P < 6 × 10-4 ), dorsal attention network (P < 8 × 10-5 ) and language network (P < 7 × 10-4 ) were found, along with a single cluster of reduced FC with the visual cortex in the left lentiform nucleus (P = 10-6 ). A significant correlation emerged between neurophysiological impairment and increased FC with right temporal language areas (r = 0.655, P = 0.006), along with an association between walking ability and increased FC with the left supramarginal gyrus (SN) (r = 0.620, P = 0.006). CONCLUSIONS: Our data show evidence of diffuse functional reorganization involving multiple large-scale networks in the CMT1A brain, independent of structural modifications and partially correlating with peripheral nerve damage and functional impairment.

Determinants of Deep Gray Matter Atrophy in Multiple Sclerosis: A Multimodal MRI Study.

BACKGROUND AND PURPOSE: Deep gray matter involvement is a consistent feature in multiple sclerosis. The aim of this study was to evaluate the relationship between different deep gray matter alterations and the development of subcortical atrophy, as well as to investigate the possible different substrates of volume loss between phenotypes. MATERIALS AND METHODS: Seventy-seven patients with MS (52 with relapsing-remitting and 25 with progressive MS) and 41 healthy controls were enrolled in this cross-sectional study. MR imaging investigation included volumetric, DTI, PWI and Quantitative Susceptibility Mapping analyses. Deep gray matter structures were automatically segmented to obtain volumes and mean values for each MR imaging metric in the thalamus, caudate, putamen, and globus pallidus. Between-group differences were probed by ANCOVA analyses, while the contribution of different MR imaging metrics to deep gray matter atrophy was investigated via hierarchic multiple linear regression models. RESULTS: Patients with MS showed a multifaceted involvement of the thalamus and basal ganglia, with significant atrophy of all deep gray matter structures (P < .001). In the relapsing-remitting MS group, WM lesion burden proved to be the main contributor to volume loss for all deep gray matter structures (P ≤ .006), with a minor role of local microstructural damage, which, in turn, was the main determinant of deep gray matter atrophy in patients with progressive MS (P ≤ .01), coupled with thalamic susceptibility changes (P = .05). CONCLUSIONS: Our study confirms the diffuse involvement of deep gray matter in MS, demonstrating a different behavior between MS phenotypes, with subcortical GM atrophy mainly determined by global WM lesion burden in patients with relapsing-remitting MS, while local microstructural damage and susceptibility changes mainly accounted for the development of deep gray matter volume loss in patients with progressive MS.

Redefining the Pulvinar Sign in Fabry Disease.

BACKGROUND AND PURPOSE: The pulvinar sign refers to exclusive T1WI hyperintensity of the lateral pulvinar. Long considered a common sign of Fabry disease, the pulvinar sign has been reported in many pathologic conditions. The exact incidence of the pulvinar sign has never been tested in representative cohorts of patients with Fabry disease. The aim of this study was to assess the prevalence of the pulvinar sign in Fabry disease by analyzing T1WI in a large Fabry disease cohort, determining whether relaxometry changes could be detected in this region independent of the pulvinar sign positivity. MATERIALS AND METHODS: We retrospectively analyzed brain MR imaging of 133 patients with Fabry disease recruited through specialized care clinics. A subgroup of 26 patients underwent a scan including 2 FLASH sequences for relaxometry that were compared with MRI scans of 34 healthy controls. RESULTS: The pulvinar sign was detected in 4 of 133 patients with Fabry disease (3.0%). These 4 subjects were all adult men (4 of 53, 7.5% of the entire male population) with renal failure and under enzyme replacement therapy. When we tested for discrepancies between Fabry disease and healthy controls in quantitative susceptibility mapping and relaxometry maps, no significant difference emerged for any of the tested variables. CONCLUSIONS: The pulvinar sign has a significantly lower incidence in Fabry disease than previously described. This finding, coupled with a lack of significant differences in quantitative MR imaging, allows hypothesizing that selective involvement of the pulvinar is a rare neuroradiologic sign of Fabry disease.

Upper motor neuron evaluation in multiple sclerosis patients treated with Sativex®.

BACKGROUND: Spasticity in multiple sclerosis (MS) results from an imbalance of inputs from descending pathways to the spinal motor circuits, as well as from a damage of the corticospinal tract (CST). OBJECTIVES: To assess CST impairment in MS patients with and without spasticity and to evaluate its evolution under Sativex® treatment. METHODS: Ten MS patients with spasticity ("cases") underwent clinical (EDSS, 9-hole Peg, Ashworth scale, Timed 25-Foot Walk, and NRS for spasticity), MRI (CST fractional anisotropy [FA]), and electrophysiological (central motor conduction time [CMCT] and H/M ratio) evaluations at baseline and after 12 months. We selected 20 MS patients without spasticity as control group at baseline. RESULTS: At baseline, cases showed a lower CST FA (0.492±0.045 vs 0.543±0.047; P=.01) and a higher CMCT (P=.001) compared to the control group. No correlations were found between clinical, electrophysiological, and MRI features. After 12 months, cases showed a decrease in non-prevalent degree of impairment (PDI) side FA (0.502±0.023 vs 0.516±0.033; P=.01) without differences for electrophysiological features compared to baseline. Treatment with Sativex® resulted in a reduction of NRS for spasticity (P=.01). CONCLUSIONS: We confirm the presence of CST impairment in MS patients with spasticity. We did not identify structural/electrophysiological correlates that could explain Sativex® clinical effect.

A multiparametric and multiscale approach to automated segmentation of brain veins.

Cerebral vein analysis provides a fundamental tool to study brain diseases such as neurodegenerative disorders or traumatic brain injuries. In order to assess the vascular anatomy, manual segmentation approaches can be used but are observer-dependent and time-consuming. In the present work, a fully automated cerebral vein segmentation method is proposed, based on a multiscale and multiparametric approach. The combined investigation of the R2(*)- and a Vesselness probability-map was used to obtain a fast and highly reliable classification of venous voxels. A semiquantitative analysis showed that our approach outperformed the previous state-of-the-art algorithm both in sensitivity and specificity. Inclusion of this tool within a parametric brain framework may therefore pave the way for a quantitative study of the intracranial venous system.

Expansion diverticulum of the suprapineal recess causing cerebellar ataxia. A case report.

As a result of long-standing cerebrospinal fluid (CSF) pulsation against the thinnest segments of the ventricular walls, focal enlargement of the ventricular system (diverticulum) may occur, mainly at the medial wall of the trigone of the lateral ventricles (atrial diverticula) or at the posterior wall of the third ventricle (expansion of the suprapineal recess). In the latter case, ocular signs are the most common symptoms, due to the severe deformation of the periaqueductal region. We describe a case of non-communicating hydrocephalus in a 36-year-old woman who presented a three-year history of cerebellar ataxia. Preoperative brain magnetic resonance (MR) scan showed marked supratentorial hydrocephalus with an apparently patent aqueduct of Sylvius, and an enlarged suprapineal recess causing cerebellar and tentorial dislocation. The patient was successfully treated by endoscopic third ventriculostomy and monitored by MR scans with phase-contrast sequences for assessment of CSF flow. Cerebellar ataxia is a very rare symptomatic onset for a suprapineal recess expansion diverticulum, which may cause obstructive hydrocephalus that can be effectively treated by endoscopic third ventriculostomy.

Endovascular treatment of vertebro-vertebral arteriovenous fistula. A report of three cases and literature review.

This report describes endovascular approaches for occlusion of vertebro-vertebral arteriovenous fistula (VV-AVF) in a series of three cases and a review of the literature. Complete neuroimaging assessment, including CT, MR and DSA was performed in three patients (two female, one male) with VV-AVF. Based on DSA findings, the VV-AVF were occluded by endovascular positioning of detachable balloons (case 1), coils (case 2), or a combination of both (case 3) with parent artery patency in two out of three cases. In this small series, endovascular techniques for occlusion of VV-AVF were safe and effective methods of treatment. To date, there are no guidelines on the best treatment for VV-AVF. Detachable balloons, endovascular coiling, combined embolization procedures could all be considered well-tolerated treatments.

Spontaneous intracranial hypotension and epidural blood patch: a report involving seven cases.

Spontaneous intracranial hypotension is a rare condition caused by spontaneous cerebrospinal fluid leak. It is characterised by orthostatic headache, diffuse pachymeningeal enhancement on brain imaging and low cerebrospinal fluid pressure. Seven patients with spontaneous intracranial hypotension were treated conservatively: of these, four responded to drug treatment and three underwent a lumbar autologous epidural blood patch (EBP). A complete response was obtained in two patients after a single EBP; one patient underwent a second EBP and then became asymptomatic. Clinical improvement coincided with a dramatic reduction of pachymeningeal enhancement. The aetiology and brain imaging findings, and the technique and effectiveness of EBP are discussed.

MR-Cisternography with T2-Weighted Single-Shot Fast Spin Echo Sequence in the Diagnosis of a Spontaneous CSF Fistula of the Sphenoid Sinus Causing Massive Pneumocephalus.

A spontaneous CSF fistula of the sphenoid sinus was preoperatively diagnosed in a young woman presenting with massive pneumocephalus and rhinorrhea. Diagnosis was established by MR cisternography using a heavily T2-weighted 3D single-shot FSE sequence with half-Fourier analysis (3D-EXPRESS(®)), originally developed for imaging the inner ear. While unenhanced CT failed to detect the site of the fistula, MR permitted complete evaluation of the sellar/sphenoid region and tracked the CSF signal down to the nasal cavity.

Radiofrequency ablation of bone metastases induces long-lasting palliation in patients with untreatable cancer.

INTRODUCTION: In oncological patients, life quality can be greatly impaired by the presence of painful bone metastases, as standard forms of treatment often achieve inadequate palliation. The aim of our study was to evaluate the clinical efficacy of radiofrequency ablation (RFA) with respect to pain relief in patients with refractory bone metastases or who are ineligible to conventional treatments. METHODS: 12 patients with 13 painful osteolytic skeletal metastases, and who were unresponsive to analgesic drug therapy, underwent one (seven lesions) or two (five lesions) RFA sessions under computed tomography (CT) guidance. The RFA procedure was completed in all patients without complications. One patient also received cementoplasty after the RFA procedure. To obtain semiquantitative pain scores, the brief pain inventory (BPI) was administered before treatment and during follow-up. The local effects of RFA were monitored for at least one year in eight of 12 patients with CT and/or magnetic resonance imaging. RESULTS: Immediate pain relief after treatment was experienced by nine of 12 patients, but in two cases, pain recurred within the first week. Long-lasting palliation was obtained in seven of 12 patients. BPI mean scores for worst and average daily pain decreased from 7.7 and 5.0, respectively, at baseline, to 3.1 and 1.8, respectively, at one year. Imaging follow-up showed large areas of necrosis in nine of 12 lesions. CONCLUSION: In our preliminary experience, RFA showed good and long-lasting efficacy for pain control in bone metastases. A possible role of RFA as a coadjuvant palliative treatment in these cases is suggested.

Osteogenesis imperfecta: clinical, biochemical and molecular findings.

Mutations in COL1A1 and COL1A2 genes, encoding the alpha1 and alpha2 chain of type I collagen, respectively, are responsible for the vast majority of cases of osteogenesis imperfecta (OI) (95% of patients with a definite clinical diagnosis). We have investigated 22 OI patients, representing a heterogeneous phenotypic range, at the biochemical and molecular level. A causal mutation in either type I collagen gene was identified in 20 of them: no recurrent mutation was found in unrelated subjects; 15 out of 20 mutations had not been reported previously. In two patients, we could not find any causative mutation in either type I collagen gene, after extensive genomic DNA sequencing. Failure of COL1A1/COL1A2 mutation screening may be due, in a few cases, to further clinical heterogeneity, i.e. additional non-collagenous disease loci are presumably involved in OI types beyond the traditional Sillence's classification.

Anti-GD2-like IgM autoreactivity in multiple sclerosis patients.

Seric IgM autoreactivity in 100 multiple sclerosis (MS) and 106 control (70 of whom had other neurological diseases) patients was assessed either by immunohistochemistry on normal human CNS tissue or to GD2, GD1a, GD3 by ELISA and thin layer chromatography (TLC) techniques. By double immunohistochemistry, we found that 44% of the total MS population showed seric IgM reactivity to oligodendrocytes and myelin, this finding being particularly frequent in patients with secondary progressive MS. In the non-MS cohort, positive signals were seen only in one patient. In all cases, extraction of lipids from CNS sections abolished the immunoreactivity. Among the gangliosides investigated by ELISA, anti-GD2-like IgM autoantibodies were detected in the serum of 30% of MS patients, a subgroup of whom (below 10%) reacted also with GD1a and/or GD3. More than 85% of MS cases with anti-GD2-like IgM immunoreactivity by ELISA showed also IgM antioligodendrocyte/myelin staining by immunohistochemistry. However, no immunostaining in MS sera was observed when gangliosides were resolved by TLC. A positive correlation with neurological disability was observed, as the Expanded Disability Status Scale of MS patients with anti-GD2-like IgM autoreactivity by ELISA was significantly worse than seronegative MS cases. The results of the present study enforce the role of glycolipids as potential autoantigens and of IgM autoantibodies in MS pathogenesis.

Acute Encephalitis of Unknown Etiology: Early Diagnosis and Follow-up of Disease Evolution. MRI. A Pictorial Essay.

Two women with viral encephalitis of unknown etiology were studied with serial MR studies at 1.5 Tesla using: Spin-Echo (SE) T1-weighted (T1w) sequences before and after i.v. administration of paramagnetic contrast agent, with/without magnetization transfer (MT), Fast SE and Fluid-attenuated Inversion Recovery (FLAIR) T2-weighted sequences, Echo-Planar Single-Shot sequences for the assessment of water diffusivity (Diffusion Weighted, DW, and Apparent Diffusion Coefficient maps, ADC). The DW and T1w sequences with MT after contrast were most useful to detect the initial pathologic alterations, thereby reinforcing the clinical diagnostic hypothesis and prompting appropriate drug treatment, even if the laboratory data were not conclusive for viral etiology. In a later phase, both cases showed MR evidence of lacunar foci in the grey matter, and cortical laminar necrosis, probably indicating a concomitant hypoxic/ischemic mechanism.

Exclusively intracranial and cranial fasciitis of the adult age.

The unusual case of an exclusively intracranial localization of fasciitis (CF) in a man aged 47 is reported. The cystic lesion had been accidentally discovered 10 years before when the patient sustained a contralateral ischemic stroke; the cyst, being absolutely silent, was not operated on at that time. After 10 years, the patient complained of seizures and mild right-sided paresis. CT scan revealed a dramatic increase of the lesion whose mass effect caused an initial subfalcial herniation of the brain. The mass was grossly removed, the patient recovered and become seizure-free. CF, rare in childhood, is exceptional in the adult age. The importance of a correct histological diagnosis is hereby stressed, because CF is absolutely benign, self-limiting, and does not require further treatment, but may be misdiagnosed as sarcoma.