BACKGROUND:To date, few cases of multiple sclerosis (MS) patients with concomitant Human Immunodeficiency Virus (HIV) infection have been described. However, none of the previously described cases has been treated with Natalizumab, probably due to the increasing risk of progressive multifocal leukoencephalopathy (PML).CASE:We report the case of a patient concomitantly diagnosed for HIV infection and MS treated with combined antiretroviral therapy (cART) and Natalizumab for 19 months, without clinical or radiological MS activity.CONCLUSIONS:Our case might suggest considering Natalizumab in patients with concomitant HIV infection, especially for those with significant disease activity requiring a high efficacy disease modifying treatment.

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.

Dear editor, Over the last years, advances in spontaneous intracranial hypotension (SIH) have allowed earlier and more accurate diagnosis, when compared with the past, with better management and lower rates of complications. Most cases of SIH are deemed to result from spontaneous cerebrospinal fluid (CSF) leaks. CSF leakage from disrupted spinal meninges can cause epidural collections, then leading to intracranial hypotension and postural headache. Accordingly, MRI frequently shows such spinal CSF collections in association with brain abnormalities including pachymeningeal enhancement, subdural effusions and sagging brainstem. In keep with this, we read with great interest the recent work from Cheema et al ‘Multidisciplinary consensus guideline for the diagnosis and management of SIH’, and specifically commend their efforts at homogenising SIH workflow. Their paper brilliantly highlights consensus guidelines to diagnose, investigate and manage SIH due to CSF leak. Authors proposed a systematic approach to identify and early treat patients affected by SIH, thus raising great interest for neurology and general clinical practice, which often provides suboptimal care to people with SIH. However, this consensus guideline is challenged by a case we recently saw in clinic. A woman in her 30s presented with rapidly progressive myelopathy causing right leg weakness, brisk reflexes, reduced superficial and pain sensation, and urinary retention. Patient did not report on headache nor history of trauma. Sagittal and axial T2weighted MRI showed anterior displacement of the spinal cord due to epidural CSF longitudinal collection with dural detachment, likely from thoracic disc osteophyte complex (figure 1). Brain MRI was normal. Both transcranial magnetic stimulation and somatosensory evoked potentials confirmed involvement of motor and somatosensory pathways of the right lower limb. The patient was immediately treated with methylprednisolone 500 mg/day for 5 days, showing clinical improvement. After 7 days from the end of steroids, CT myelography did not show any CSF collection nor leakage. After 21 days from first MRI, CSF collection disappeared on MRI. Further clinical improvements followed. Our peculiar case of CSF leakage provides some hints going beyond the consensus guidelines. First, authors suggest SIH should be hypothesised in any patient with orthostatic headache, while our case presented with myelopathy in the absence of headache. Also, consensus guidelines advice that MRI of the brain is essential to confirm the diagnosis of SIH, and that MRI of the whole spine is not always necessary for the diagnosis. By contrast, we found what Cheema et al deemed typical of SIH on spinal cord MRI (figure 1), in the absence of brain changes. Overall, if we assume that SIH is due to CSF leakage from disrupted spinal meninges, we shall expect that spinal cord changes can precede brain changes, and that, even if uncommon, spinal cord symptoms can occur, as anecdotally described. In conclusion, our case report shows that spinal CSF leakage and related hypotension can present with isolated myelopathy, in the absence of typical postural headache and brain MRI changes. While a single case is not expected to change consensus guidelines, clinical practice should consider CSF leakage among possible causes of acute spinal cord symptoms, also in the absence of postural headache.

Whether chemotherapy (ChT) and radiotherapy (RT) determine neurocognitive impairment in acute lymphoblastic leukemia long-term survivors (ALL LTSs) through similar mechanisms affecting the same brain regions is still unknown. We compared neurocognitive alterations, regional brain tissue volumes (by voxel-based morphometry), and functional connectivity of the main default-mode network hubs (by seed-based analysis of resting state functional MRI data), in 13 ALL LTSs treated with RT and ChT (Group A) and 13 treated with ChT only (Group B). Group A performed significantly worse than Group B at the digit span and digit symbol tests (p = 0.023 and 0.013, respectively). Increased connectivity between the medial prefrontal cortex (the main anterior hub of the default-mode network) and the rolandic operculi was present in Group A compared to Group B, along with the absence of significant differences in regional brain tissue volumes. In these regions, the functional connectivity correlated inversely with the speed of processing scores, independent of treatment group. These results suggest that similar mechanisms may be involved in the neurocognitive deficits in ALL LTS patients, regardless of the treatment group. Further studies are needed to clarify whether these changes represent a direct expression of the mechanisms underlying the cognitive deficits or ineffective compensatory phenomena.

(1) The co-occurrence of AQP4 and myelin oligodendrocyte glycoprotein (MOG) antibodies in patients with demyelinating disorders is extremely rare. In addition, a concomitant involvement of the peripheral nervous system (PNS) has been described either in association with AQP4 antibodies-positive neuromyelitis optica spectrum disorder (NMOSD), or MOG-associated disease. We report on a case of NMOSD with co-occurrence of AQP4 and MOG antibodies and concomitant central and peripheral nervous system involvement. We also reviewed available cases of AQP4-MOG double-positive patients. (2) Brain and spine MRI, cerebrospinal fluid studies, and electrophysiological test were performed. Serum AQP4 and MOG positivity was assessed with live cell-based assay. (3) A 62-year-old woman presented with recurrent optic neuritis, myelitis, and radiculitis, tested positive for AQP4 and MOG antibodies, and was treated successfully with rituximab. (4) Although few cases of AQP4-MOG double-positive patients were already described mostly affecting females with a concomitant spinal cord and optical nerve involvement, we describe the first case of double-positive NMOSD with the peculiar involvement of both central and peripheral nervous system.

SUMMARY: 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.

Background Progressive multifocal leukoencephalopathy (PML) can rarely occur in Multiple Sclerosis (MS) patients undergoing dimethyl fumarate (DMF) treatment. Our case stresses the limits of current diagnostic and stratification risk criteria, highlighting the potential role of Magnetic Resonance Imaging (MRI) in advising clinical choices. Case presentation A 54 years old MS male patient treated with DMF, after 3 years of clinical stability developed a subacute clinical worsening. He had no severe lymphopenia but MRI signs suggestive of a coexistence of PML and MS activity. Although his viral title was negative, DMF was discontinued, with clinical and radiological improvement. Conclusions This case highlights the challenges behind PML diagnosis, especially in patients not fulfilling the risk stratification criteria and that might present with concurrent disease activity, stressing the potential role of MRI in informing therapeutic decisions.

Accurate and reproducible measurement of blood flow profile is very important in many clinical investigations for diagnosing cardiovascular disorders. Given that many factors could affect human circulation, and several parameters must be set to properly evaluate blood flows with phase-contrast techniques, we developed an MRI-compatible hydrodynamic phantom to simulate different physiological blood flows. The phantom included a programmable hydraulic pump connected to a series of pipes immersed in a solution mimicking human soft tissues, with a blood-mimicking fluid flowing in the pipes. The pump is able to shape and control the flow by driving a piston through a dedicated software. Periodic waveforms are used as input to the pump to move the fluid into the pipes, with synchronization of the MRI sequences to the flow waveforms. A dedicated software is used to extract and analyze flow data from magnitude and phase images. The match between the nominal and the measured flows was assessed, and the scope of phantom variables useful for a reliable calibration of an MRI system was accordingly defined. Results showed that the NO-HYPE phantom is a valuable tool for the assessment of MRI scanners and sequence design for the MR evaluation of blood flows.

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. 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.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely related to severe respiratory syndrome; however, recent reports showed that it is capable of causing neurological disease. Here we report a case-series of 4 critically ill COVID-19 patients who recovered from pneumonia but showed serious neurological symptoms and eventually died.

Department of Advanced Biomedical Sciences, University of Naples “Federico II”, Naples, Italy Department of Neurosciences and Reproductive and Odontostomatological Sciences, University of Naples “Federico II”, Naples, Italy Department of Public Health, Nephrology Unit, University of Naples “Federico II”, Naples, Italy Institute of Biostructure and Bioimaging, National Council of Research, Naples, Italy

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.

This work focuses on brain stroke imaging via microwave technology. In particular, the open issue of monitoring patients after stroke onset is addressed here in order to provide clinicians with a tool to control the effectiveness of administered therapies during the follow-up period. In this paper, a novel prototype is presented and characterized. The device is based on a low-complexity architecture which makes use of a minimum number of properly positioned and designed antennas placed on a helmet. It exploits a differential imaging approach and provides 3D images of the stroke. Preliminary experiments involving a 3D phantom filled with brain tissue-mimicking liquid confirm the potential of the technology in imaging a spherical target mimicking a stroke of a radius equal to 1.25 cm.

BACKGROUND:Lymphocytic vasculitis of the central nervous system is an uncommon subtype of primary angiitis of the central nervous system (PACNS) - a rare inflammatory disorder affecting parenchymal and leptomeningeal arteries and veins.CASE REPORT:Establishing diagnosis on the basis of neuroimaging only is difficult, as it can mimic a brain tumor. Thus, histological diagnosis is essential for appropriate management. We present a case of biopsy-proven lymphocytic vasculitis mimicking a brain tumor on neuroimaging that was subsequently successfully treated with steroid therapy. We also discuss the findings in perfusion MR (PWI) and MR spectroscopy (MRS).CONCLUSIONS:Regional hypoperfusion on PWI and elevation of glutamate and glutamine levels on MRS (without associated typical tumor spectra) are common findings in inflammatory disorders, including PACNS, and can be useful in differential diagnosis with tumors.

Background and purposeChanges 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.MethodsIn 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.ResultsEighteen 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).ConclusionsOur 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.

Central nervous system involvement has been described in peripheral neuropathies, including different forms of Charcot-Marie-Tooth (CMT) disease. The aimof our study was to systematically investigate possible brain structural modifications in CMT1A patients, using volumetric MRI, and diffusion tensor imaging (DTI). In this prospective cross-sectional study, from May 2017 to May 2019, we acquired 3T MRI brain scans of genetically confirmed CMT1A patients and age- and sex-comparable healthy controls. Patients also underwent clinical and electrophysiological examinations assessing motor and sensory domains. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analyses were performed using a non-parametric approach based on permutations, including age and sex (and total intracranial volume for VBM) as nuisance covariates. When between-group differences emerged at VBM or TBSS analyses, the first eigenvariate was extracted from the cluster and its age- and sex-adjusted standardized residuals tested for correlation with clinical and electrophysiological variables. Twenty CMT1A patients (34.5 +/- 11.1 years; M/F:11/9) were enrolled, along with 20 healthy controls (30.1 +/- 10.2 years; M/F:11/9). The VBM analysis revealed clusters of significantly increased GM volume in CMT1A patients compared to healthy controls, encompassing the bilateral cerebellar lobules III-VI and the left hippocampus (all ps = 0.04), with no differences in terms of DTI metrics at the TBSS analysis. A negative correlation (r = -0.502, p = 0.03) emerged between ulnar compound motor action potential and the z-scores corresponding to the right cerebellar cluster of augmented GM volume. Our data show evidence of structural reorganization in the brain of CMT1A patients, possibly reflecting neural plasticity mechanisms in response to peripheral nerve pathology and modulating the effect of axonal degeneration on functional impairment.

Aim of this study was to investigate the reliability and validity of 2D linear measures of ventricular enlargement as indirect markers of brain atrophy and possible predictors of clinical disability. In this retrospective longitudinal analysis of relapsing-remitting MS patients, brain volumes were computed at baseline and after 2 years. Frontal horn width (FHW), intercaudate distance (ICD), third ventricle width (TVW), and 4th ventricle width were obtained. Two-dimensional measures associated with brain volume at correlation analyses were entered in linear and logistic regression models testing the relationship with baseline clinical disability and 10-year confirmed disability progression (CDP), respectively. Possible cutoff values for clinically relevant atrophy were estimated via receiver operating characteristic (ROC) analyses and probed as 10-year CDP predictors using hierarchical logistic regression. Eighty-seven patients were available (61/26 = F/M; 34.1 ± 8.5 years). Moderate negative correlations emerged between ICD and TVW and normalized brain volume (NBV; p < 0.001) and percentage brain volume change per year (PBVC/y) and FHW, ICD, and TVW annual changes (p ≤ 0.005). Baseline disability was moderately associated with NBV, ICD, and TVW (p < 0.001), while PBVC/y predicted 10-year CDP (p = 0.01). A cutoff percentage ICD change per year (PICDC/y) value of 4.38%, corresponding to − 0.91% PBVC/y, correlated with 10-year CDP (p = 0.04). These estimated cutoff values provided extra value for predicting 10-year CDP (PBVC/y: p = 0.001; PICDC/y: p = 0.03). Two-dimensional measures of ventricular enlargement are reproducible and clinically relevant markers of brain atrophy, with ICD and its increase over time showing the best association with clinical disability. Specifically, a cutoff PICDC/y value of 4.38% could serve as a potential surrogate marker of long-term disability progression. • Assessment of ventricular enlargement as a rapidly accessible indirect marker of brain atrophy may prove useful in cases in which brain volume quantification is not practicable. • Two-dimensional linear measures of ventricular enlargement represent reliable, valid, and clinically relevant markers of brain atrophy. • A cutoff annualized percentage brain volume change of − 0.91% and the corresponding annualized percentage increase of 4.38% for intercaudate distance are able to discriminate patients who will develop long-term disability progression.

Objective: Investigate reliability and validity of linear measures of ventricular enlargement as indirect markers of brain atrophy and explore their relationship with clinical disability. Background: Brain atrophy is a relevant neuroradiologic correlate of disability in Multiple Sclerosis (MS), but its evaluation in clinical practice is limited by variety of acquisition and post-processing protocols. Design/Methods: In this retrospective longitudinal analysis of relapsing-remitting MS patients evaluated from January 2006 to December 2009, brain volumes were computed at baseline and after 2-years. Frontal Horn Width (FHW), Intercaudate Distance (ICD), Third Ventricle Width (TVW) and 4th Ventricle Width (4VW) were obtained. Linear measures correlating with brain volume were entered in regression models testing the relationship between MR metrics and clinical disability. Possible cut-offs for clinically relevant brain atrophy were estimated and tested as 10-years disability progression predictors. Results: Eighty-seven patients were available (61/26=F/M; 34.14±8.50 years). Both ICD and TVW correlated with normalized brain volume (NBV; p Conclusions: Linear measures of ventricular enlargement are reproducible and clinically relevant markers of brain atrophy. In particular, ICD and its increase over time show the best association with clinical disability, with a cut-off PICDC/y value of 4.38% as a potential surrogate marker of long-term disability progression. Disclosure: Dr. Petracca has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with novartis. Dr. Pontillo has nothing to disclose. Dr. Cocozza has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi Genzyme, AMICUS. Dr. Di Stasi has nothing to disclose. Dr. Carotenuto has nothing to disclose. Dr. Paolella has nothing to disclose. Dr. Cipullo has nothing to disclose. Dr. Perillo has nothing to disclose. Dr. Vola has nothing to disclose. Dr. Russo has nothing to disclose. Dr. Masullo has nothing to disclose. Dr. Moccia has nothing to disclose. Dr. Lanzillo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with personal fees for public speaking or consultancy from Merck, Novertis, Biogen, Genzyme, Teva, Roche and Almirall.. Dr. Tedeschi has nothing to disclose. Dr. Elefante has nothing to disclose. Dr. Brescia Morra has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Almirall, Bayer, Biogen Idec, Merk, Novartis, Roche, Teva. Dr. Quarantelli has nothing to disclose. Dr. Brunetti has nothing to disclose.