Neural correlates of lower limbs proprioception: An fMRI study of foot position matching.

Little is known about the neural correlates of lower limbs position sense, despite the impact that proprioceptive deficits have on everyday life activities, such as posture and gait control. We used fMRI to investigate in 30 healthy right-handed and right-footed subjects the regional distribution of brain activity during position matching tasks performed with the right dominant and the left nondominant foot. Along with the brain activation, we assessed the performance during both ipsilateral and contralateral matching tasks. Subjects had lower errors when matching was performed by the left nondominant foot. The fMRI analysis suggested that the significant regions responsible for position sense are in the right parietal and frontal cortex, providing a first characterization of the neural correlates of foot position matching.

Composite MRI measures and short-term disability in patients with clinically isolated syndrome suggestive of MS.

BACKGROUND: The use of composite magnetic resonance imaging (MRI) measures has been suggested to better explain disability in patients with multiple sclerosis (MS). However, little is known about the utility of composite scores at the earliest stages of the disease. OBJECTIVE: To investigate whether, in patients with clinically isolated syndrome (CIS), a composite MRI measure, rather than the single metrics, would explain conversion to MS and would better correlate with disability at baseline and at 1 year of follow-up. METHODS: Corticospinal tract (CST), corpus callosum (CC) and optic radiation (OR) volume, fractional anisotropy (FA), and mean diffusivity (MD) values were measured in 27 CIS patients and 24 healthy controls (HCs). Z-scores of FA, MD, and tract volume measures were calculated in patients, based on the corresponding measures obtained from HCs, and then combined in a composite score for each tract. Correlations between Z-scores at baseline and both the Expanded Disability Status Scale (EDSS) at baseline and at follow-up (FU-EDSS) were investigated. RESULTS: Only CST, CC, and OR composite scores as well as the CST volume were significantly associated with FU-EDSS ( p = 0.005, p = 0.007, p = 0.020, and p = 0.010, respectively). CONCLUSION: The combination of MRI measures rather than the individual metrics better captured the association between tissue damage in both the CC, OR and CST and short-term follow-up disability.

Safety and tolerability of fingolimod in patients with relapsing-remitting multiple sclerosis: results of an open-label clinical trial in Italy.

The safety profile of fingolimod is well established in clinical trials and post-marketing studies. This study aimed to evaluate the safety and tolerability of fingolimod in a cohort of Italian patients with relapsing-remitting multiple sclerosis (RRMS). This is a non-comparative, open-label, multicentre, interventional study conducted in patients with RRMS with no suitable alternative treatment option. Safety and tolerability of fingolimod 0.5 mg were assessed by recording adverse events (AEs) and serious AEs (SAEs). Of the 906 patients enrolled in the study, 91 % of the patients completed the study. AEs and SAEs were reported in 35.4 and 2.9 % of the patients, respectively. Most common AEs reported were headache (4.1 %), influenza (2.1 %), lymphopenia (1.8 %), asthenia (1.8 %) and pyrexia (1.8 %). Increased alanine aminotransferase levels and hypertension were reported as AE in 1.0 and 1.4 % of the patients, respectively. Macular oedema was reported in three patients. These results emphasize the safety of fingolimod in patients representing the real-world clinical practice in the Italian population. Fingolimod was safe and well tolerated in this population, which, compared to those enrolled in pivotal trials in terms of concomitant diseases and used medications, is broader. TRIAL REGISTRATION: EudraCT 2011-000770-60.

Delirium in the acute phase after stroke: comparison between methods of detection.

Delirium is an acute neuropsychiatric syndrome, very common in hospitalized people with medical and neurological conditions. The identification of delirium after stroke is not an easy task and validated psychometric instruments are needed to correctly identify it. We decided to verify if (1) formal training in DSM-V criteria is needed to correctly identify post-stroke delirium, (2) if the use of a brief psychometric instrument such as 4AT improves its identification, (3) the applicability of these scales in the stroke setting. In the first phase of this study we retrospectively studied 102 acute stroke patients in Stroke Units of San Martino Hospital (Genova, Italy) to evaluate delirium with clinical criteria, first by a neurologist without a formal training in DSM-V criteria and after training. Then, we enrolled 100 new acute stroke patients who underwent screening for delirium using 4AT scale and DSM-V criteria. In the first phase, DSM-V criteria training significantly increased the ability to capture delirium (5 vs. 15%). In the second phase, the 4AT was used for delirium screening revealing a 52% of cases of delirium, the same observed by the consensus diagnosis of two senior neurologists (that was 50%). In the second phase, the use of 4AT scale allowed to capture post-stroke delirium as well as the consensus diagnosis by two neurologists. The identification of post-stroke delirium is not an easy task and requires both formal training in DSM-V criteria as well as the application of brief scales, such as the 4AT.

Resting-state functional connectivity and motor imagery brain activation.

Motor imagery (MI) relies on the mental simulation of an action without any overt motor execution (ME), and can facilitate motor learning and enhance the effect of rehabilitation in patients with neurological conditions. While functional magnetic resonance imaging (fMRI) during MI and ME reveals shared cortical representations, the role and functional relevance of the resting-state functional connectivity (RSFC) of brain regions involved in MI is yet unknown. Here, we performed resting-state fMRI followed by fMRI during ME and MI with the dominant hand. We used a behavioral chronometry test to measure ME and MI movement duration and compute an index of performance (IP). Then, we analyzed the voxel-matched correlation between the individual MI parameter estimates and seed-based RSFC maps in the MI network to measure the correspondence between RSFC and MI fMRI activation. We found that inter-individual differences in intrinsic connectivity in the MI network predicted several clusters of activation. Taken together, present findings provide first evidence that RSFC within the MI network is predictive of the activation of MI brain regions, including those associated with behavioral performance, thus suggesting a role for RSFC in obtaining a deeper understanding of neural substrates of MI and of MI ability. Hum Brain Mapp 37:3847-3857, 2016. © 2016 Wiley Periodicals, Inc.

Effect of ethylic alcohol on attentive functions involved in driving abilities.

The burden of injuries due to drunk drivers has been estimated only indirectly. Indeed, alcohol is considered one of the most important contributing cause of car crash injuries and its effect on cognitive functions needs to be better elucidated. Aims of the study were i) to examine the effect of alcohol on attentive abilities involved while driving, and ii) to investigate whether Italian law limits for safe driving are sufficiently accurate to prevent risky behaviours and car crash risk while driving. We conducted a cross-over study at IRCCS Fondazione Santa Lucia Rehabilitation Hospital in Rome. Thirty-two healthy subjects were enrolled in this experiment. Participants were submitted to an attentive test battery assessing attention before taking Ethylic Alcohol (EA-) and after taking EA (EA+). In the EA+ condition subjects drank enough wine until the blood alcohol concentration, measured by means of Breath Analyzer, was equal to or higher than 0.5 g/l. Data analysis revealed that after alcohol assumption, tonic and phasic alertness, selective, divided attention and vigilance were significantly impaired when BAC level was at least 0.5 g/l. These data reveal that alcohol has a negative effect on attentive functions which are primarily involved in driving skills and that Italian law limits are adequate to prevent risky driving behaviour.

Safety of the first dose of fingolimod for multiple sclerosis: results of an open-label clinical trial.

BACKGROUND: In patients with relapsing-remitting MS (RRMS) fingolimod prevents disease relapses and delays disability progression. First dose administration of fingolimod is associated with a transient, dose-dependent decrease in heart rate (HR) in the 6 hours after drug intake.The aim of the study is to to assess safety and tolerability of the first dose of fingolimod in a cohort of Italian patients with RRMS without alternative therapeutic options. METHODS: Open-label, single arm, multicentre study. After the first dose of fingolimod, patients were observed for 6 hours and had their vital signs monitored hourly. Extended on-site monitoring was provided when required. RESULTS: Of the 906 patients enrolled in the study, most (95.2%) did not experience any adverse event (AE) following fingolimod administration. Cardiovascular AEs occurred in 18 patients and included bradycardia (1.3%), first-and second-degree atrioventricular block (0.1% and 0.2%), palpitations (0.1%), sinus arrhythmia (0.1%) and ventricular premature beats (0.1%). All events were self-limiting and did not require any intervention. Extended monitoring was required in 34 patients. CONCLUSIONS: These results, in a population who better resembled real-world clinical practice in terms of concomitant diseases and medications, are consistent with previous clinical trials and confirmed that the first dose administration of fingolimod is generally safe and well tolerated. TRIAL REGISTRATION: EudraCT 2011-000770-60.

Clinical baseline factors predict response to natalizumab: their usefulness in patient selection.

BACKGROUND: Optimal patient selection would improve the risk-benefit ratio of natalizumab treatment for relapsing-remitting multiple sclerosis (RR MS). Clinical features of subjects responding to natalizumab have not been univocally recognized. METHODS: Longitudinal data on RR MS patients treated with natalizumab in Liguria, Italy are reported. Predictors of relapse occurrence and disability improvement were analyzed with a logistic regression method in subjects treated for one year (N = 62). A new score, called "Better EDSS Trend (BET)", was devised to describe the impact of the treatment on disability. Changes in annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) after one and two years and proportion of disease-free patients were evaluated. RESULTS: Previous EDSS worsening plus ARR ≥ 2 increased the risk of relapse during the treatment [Odds Ratio (OR) 4.12, P = 0.04], but this was not associated with an increase in disability at one year. EDSS 3.0-3.5 or high disease activity were associated with neurological improvement in the first year of treatment (respectively OR 5.78, P = 0.05 and OR 4.80, P = 0.05). Positive BET score, i.e. improvement in the disability trend, was observed in 40.3% of patients, and correlated with high ARR in the year before treatment (OR 1.69, P = 0.03). CONCLUSION: Subjects with EDSS 3.0-3.5 and those with very active disease in the year before treatment are most likely to improve in neurological function under natalizumab. A relapse in the first year of treatment is associated to high pre-treatment disease activity; however, since the occurrence of a relapse did not have a negative impact on clinical improvement at one year, we suggest that it should not lead to treatment discontinuation. We propose BET as an additional endpoint of treatment response in MS.

Safe and effective outcome of intravenous thrombolysis for acute ischemic stroke in patients aged 90 years or older.

Concerning intravenous thrombolysis, only inconclusive data are available for patients older than 90. We retrospectively evaluated 11 such patients whom we treated with thrombolysis from June 2007 through April 2012, comparing them to 41 patients of the same age whom we treated conventionally in the same period. Baseline clinical data were superimposable, except for shorter onset-to-hospital time for thrombolyzed patients. Mortality and hemorrhagic transformation did not differ. Functional status (modified Rankin scale) 3 months after was better in treated patients, even when compared to controls who arrived early in the hospital. Treated patients were more often discharged home or to intensive rehabilitation, less often to a nursing home. We conclude that safety and effectiveness of intravenous thrombolysis in eligible nonagenarians are evident in a setting of everyday practice, and that patients 90 years or older should not be denied thrombolysis solely on the basis of their age.

Hematopoietic Stem Cell Transplantation in People With Active Secondary Progressive Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Uncontrolled evidence suggests that autologous hematopoietic stem cell transplantation (AHSCT) can be effective in people with active secondary progressive multiple sclerosis (SPMS). In this study, we compared the effect of AHSCT with that of other anti-inflammatory disease-modifying therapies (DMTs) on long-term disability worsening in active SPMS. METHODS: We collected data from the Italian Bone Marrow Transplantation Study Group and the Italian Multiple Sclerosis Register. Patients were considered eligible if treatment had been started after the diagnosis of SPMS. Disability worsening was assessed by the cumulative proportion of patients with a 6-month confirmed disability progression (CDP) according to the Expanded Disability Status Scale (EDSS) score. Key secondary endpoints were the EDSS time trend after treatment start and the prevalence of disability improvement over time. Time to first CDP was assessed by means of proportional hazard Cox regression models. A linear mixed model with a time × treatment group interaction was used to assess the longitudinal EDSS time trends. Prevalence of improvement was estimated using a modified Kaplan-Meier estimator and compared between groups by bootstrapping the area under the curve. RESULTS: Seventy-nine AHSCT-treated patients and 1975 patients treated with other DMTs (beta interferons, azathioprine, glatiramer-acetate, mitoxantrone, fingolimod, natalizumab, methotrexate, teriflunomide, cyclophosphamide, dimethyl fumarate, and alemtuzumab) were matched to reduce treatment selection bias using propensity score and overlap weighting approaches. Time to first CDP was significantly longer in transplanted patients (hazard ratio [HR] = 0.50; 95% CI = 0.31-0.81; p = 0.005), with 61.7% of transplanted patients free from CPD at 5 years. Accordingly, EDSS time trend over 10 years was higher in patients treated with other DMTs than in AHSCT-treated patients (+0.157 EDSS points per year compared with -0.013 EDSS points per year; interaction p < 0.001). Patients who underwent AHSCT were more likely to experience a sustained disability improvement: 34.7% of patients maintained an improvement (a lower EDSS than baseline) 3 years after transplant vs 4.6% of patients treated by other DMTs (p < 0.001). DISCUSSION: The use of AHSCT in people with active SPMS is associated with a slowing of disability progression and a higher likelihood of disability improvement compared with standard immunotherapy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that autologous hematopoietic stem cell transplants prolonged the time to CDP compared with other DMTs.

Impact of Natural Killer (NK) Cells on Immune Reconstitution, and Their Potential as a Biomarker of Disease Activity, in Alemtuzumab-Treated Patients with Relapsing Remitting Multiple Sclerosis: An Observational Study.

BACKGROUND: Defining immune mechanisms leading to multiple sclerosis (MS) is difficult, due to the great inter-individual difference in immune system responses. The anti-CD52 antibody alemtuzumab transiently abolishes differences in immune parameters among individuals, allowing analysis of subsequent immune cell repopulation patterns, and their possible role in MS. OBJECTIVE: To evaluate the correlation between innate and adaptive immune cell subsets and disease activity in MS in the context of treatment with alemtuzumab. METHODS: A two-center observational cohort of patients treated with alemtuzumab underwent immune profiling of T, B, and natural killer (NK) cells, biomarker, clinical and radiological follow-up. RESULTS: After treatment, the percentage of NK and B cells increased; NK, T- and B-cell populations underwent a profound rearrangement. Within the effector T-cell compartment, treatment led to a transient decrease, followed by an increase, of T-helper 1 cells, and to a transient decrease of T-helper 17 cells. Within the T-regulatory compartment, naïve T-regulatory cells increased. Within the B-cell compartment, memory B cells and mature B cells decreased, whereas transitional B cells increased. Within the NK cell compartment, CD56bright NK cells increased. Subjects without disease activity had a greater decrease in serum NfL and greater NK cell/CD3+ T cell ratio. NK cell numbers at baseline and after treatment influenced reconstitution of T and B cells, being inversely correlated with the reconstitution of proinflammatory CD3+ T cells and mature B cells, and directly correlated to the increase in transitional B cells. CONCLUSIONS: The results of this study provide novel evidence that NK cells influence reconstitution of adaptive immune cells upon alemtuzumab and that patients with a successful response to alemtuzumab have an early immune reconstitution dominated by NK cells.

A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis.

The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 [odds ratio (OR) = 1.17 and 1.18, and P-values = 6.98 x 10(-7) and 1.16 x 10(-6)], were located on chromosome 7p13.3 within a 175 kb linkage disequilibrium block containing the SUNC1, HUS1 and C7orf57 genes. These associations did not achieve genome-wide significance in the original cohort and failed to replicate in an additional independent cohort of 989 US cases and 327 controls (OR = 1.18 and 1.19, P-values = 0.08 and 0.06, respectively). Thus, we chose to cautiously interpret our data as hypothesis-generating requiring additional confirmation, especially as all previously reported loci for ALS have failed to replicate successfully. Indeed, the three loci (FGGY, ITPR2 and DPP6) identified in previous GWAS of sporadic ALS were not significantly associated with disease in our study. Our findings suggest that ALS is more genetically and clinically heterogeneous than previously recognized. Genotype data from our study have been made available online to facilitate such future endeavors.

Structural integrity of callosal midbody influences intermanual transfer in a motor reaction-time task.

Training one hand on a motor task results in performance improvements in the other hand, also when stimuli are randomly presented (nonspecific transfer). Corpus callosum (CC) is the main structure involved in interhemispheric information transfer; CC pathology occurs in patients with multiple sclerosis (PwMS) and is related to altered performance of tasks requiring interhemispheric transfer of sensorimotor information. To investigate the role of CC in nonspecific transfer during a pure motor reaction-time task, we combined motor behavior with diffusion tensor imaging analysis in PwMS. Twenty-two PwMS and 10 controls, all right-handed, were asked to respond to random stimuli with appropriate finger opposition movements with the right (learning) and then the left (transfer) hand. PwMS were able to improve motor performance reducing response times with practice with a trend similar to controls and preserved the ability to transfer the acquired motor information from the learning to the transfer hand. A higher variability in the transfer process, indicated by a significantly larger standard deviation of mean nonspecific transfer, was found in the PwMS group with respect to the control group, suggesting the presence of subtle impairments in interhemispheric communication in some patients. Then, we correlated the amount of nonspecific transfer with mean fractional anisotropy (FA) values, indicative of microstructural damage, obtained in five CC subregions identified on PwMS's FA maps. A significant correlation was found only in the subregion including posterior midbody (Pearson's r = 0.74, P = 0.003), which thus seems to be essential for the interhemispheric transfer of information related to pure sensorimotor tasks.

Progranulin expression in brain tissue and cerebrospinal fluid levels in multiple sclerosis.

BACKGROUND: Progranulin (PGRN) is a fundamental neurotrophic factor, and is also involved in inflammation and wound repair. PGRN may have pro- or anti-inflammatory properties, depending upon proteolysis of the anti-inflammatory parent PGRN protein and the generation of pro-inflammatory granulin peptides. OBJECTIVES: Our objectives were as follows: (1) to evaluate the presence and distribution of PGRN in multiple sclerosis (MS) brain tissue, correlating it with demyelination and inflammation; (2) to evaluate cerebrospinal fluid (CSF) PGRN concentrations in patients with MS and controls, in relationship to the clinical features of the disease. METHODS: Our study involved the following: (1) neuropathological study of PGRN on post-mortem tissue of 19 MS and six control brains; (2) evaluation of PGRN CSF concentration in 40 MS patients, 15 non-inflammatory controls and five inflammatory controls (viral encephalitis). RESULTS: In active demyelinating lesions, PGRN was expressed on macrophages/microglia. In the normal-appearing white matter (NAWM), expression of PGRN was observed on activated microglia. PGRN was expressed by neurons and microglia in cortical lesions and in normal-appearing cortex. No expression of PGRN was observed in controls, except on neurons. PGRN CSF concentrations were significantly higher in patients with relapsing-remitting MS during relapses and in progressive MS patients, compared with relapsing-remitting MS patients during remissions and with non-inflammatory controls. CONCLUSIONS: PGRN is strongly expressed in MS brains, by macrophages/microglia in active lesions, and by activated microglia in the NAWM; PGRN CSF concentrations in MS are correspondingly increased in conditions of enhanced macrophage/microglia activation, such as during relapses and in progressive MS.

Erythropoietin therapy in a case of neonatal anemia after exposure to natalizumab throughout pregnancy.

BACKGROUND: Natalizumab is a monoclonal antibody approved for the treatment of patients with relapsing-remitting multiple sclerosis. According to the current clinical recommendations, its use during pregnancy should be carefully evaluated only in women with highly active disease who plan a pregnancy or have an unplanned pregnancy, after accurate counseling about eventual maternal disease relapse due to therapy suspension. CASE PRESENTATION: This brief case report describes a case of documented anemia that we observed in a newborn whose mother with relapsing-remitting multiple sclerosis was treated with an extended dosing protocol of natalizumab throughout pregnancy. The newborn received the infusion of erythropoietin every seven days from the fortieth day of life; subsequently, the status of anemia underwent clinical resolution. CONCLUSIONS: This case report confirmed that natalizumab can cause disorders of hematopoiesis, including anemia, thrombocytopenia, or pancytopenia, in newborns of patients treated during pregnancy. A multidisciplinary team, including experienced pediatricians and pediatric hematologists, has a critical role in managing newborns delivered by women, being treated with natalizumab for treating relapsing-remitting multiple sclerosis during pregnancy.

Enlarging clinical spectrum of FALS with TARDBP gene mutations: S393L variant in an Italian family showing phenotypic variability and relevance for genetic counselling.

OBJECTIVE: The present study was aimed to enlarge the Italian ALS sample analysed for TARDBP gene mutations. METHODS: Genomic DNA from 47 patients, 70 FTD patients and 158 controls was extracted from peripheral blood samples according to a standard protocol. The five coding exons (2-6) of the TARDBP gene and the flanking exon-intron boundaries were analysed by direct sequencing. Using ClustalW2 human TDP-43, protein sequence was aligned with TDP-43 protein sequence of different species. RESULTS: A heterozygous c.1178 C-->T transition that leads to a change p.S393L was observed in a 75-years-old male patient and in his two affected siblings. A patient's brother had died at 69 years of age after a two-year history of ALS. In FTD patients no mutations were found. CONCLUSIONS: We describe a further Italian family with FALS, in which a variant (p.S393L) of the TARDBP gene was identified. Clinical course and phenotypic variability in three affected siblings is presented and relevance for genetic counselling of patients and their families is underlined. At the present state of knowledge, we suggest that the same guidelines established for SOD1 molecular testing could be proposed also for TARDBP analysis in FALS.

The spectrum of GNE mutations: allelic heterogeneity for a common phenotype.

Hereditary inclusion body myopathy (IBM2) was mainly reported in Middle Eastern Jewish patients. Distal myopathy with rimmed vacuoles has been described as a worldwide distributed distal myopathy. Both diseases are caused by mutations of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. Herein we report two patients: an Egyptian Muslim patient with the "common" Middle Eastern mutation (M712T), rarely described in non-Jewish patients; and an Italian patient carrying a novel GNE mutation (L179F) in the epimerase domain. Our patients share common clinical and histopathological features, with some interesting aspects. The first patient presented a clinical deterioration during her first pregnancy confirming that an increased requirement of sialic acid during pregnancy may trigger a clinical worsening. The second patient showed a slowly progressive deterioration, different from other patients carrying mutations in the epimerase domain, who had a severe and rapid progression.

Position Sense Deficits at the Lower Limbs in Early Multiple Sclerosis: Clinical and Neural Correlates.

Background/Objective. Position sense, defined as the ability to identify joint and limb position in space, is crucial for balance and gait but has received limited attention in patients with multiple sclerosis (MS). We investigated lower limb position sense deficits, their neural correlates, and their effects on standing balance in patients with early MS. Methods. A total of 24 patients with early relapsing-remitting MS and 24 healthy controls performed ipsilateral and contralateral matching tasks with the right foot during functional magnetic resonance imaging. Corpus callosum (CC) integrity was estimated with diffusion tensor imaging. Patients also underwent an assessment of balance during quiet standing. We investigated differences between the 2 groups and the relations among proprioceptive errors, balance performance, and functional/structural correlates. Results. During the contralateral matching task, patients demonstrated a higher matching error than controls, which correlated with the microstructural damage of the CC and with balance ability. In contrast, during the ipsilateral task, the 2 groups showed a similar matching performance, but patients displayed a functional reorganization involving the parietal areas. Neural activity in the frontoparietal regions correlated with the performance during both proprioceptive matching tasks and quiet standing. Conclusion. Patients with early MS had subtle, clinically undetectable, position sense deficits at the lower limbs that, nevertheless, affected standing balance. Functional changes allowed correct proprioception processing during the ipsilateral matching task but not during the more demanding bilateral task, possibly because of damage to the CC. These findings provide new insights into the mechanisms underlying disability in MS and could influence the design of neurorehabilitation protocols.

123I-FP-CIT SPECT validation of nigro-putaminal MRI tractography in dementia with Lewy bodies.

BACKGROUND: Assessment of nigrostriatal degeneration is a key element to discriminate between dementia with Lewy bodies (DLB) and Alzheimer disease (AD), and it is often evaluated using ioflupane (123I-FP-CIT) single-photon emission computed tomography (SPECT). Given the limited availability of 123I-FP-CIT SPECT, we evaluated if a mask-based approach to nigroputaminal magnetic resonance imaging (MRI) diffusion-weighted tractography could be able to capture microstructural changes reflecting nigroputaminal degeneration in DLB. METHODS: A nigroputaminal bundle mask was delineated on 12 healthy volunteers (HV) and applied to MRI diffusion-weighted data of 18 subjects with DLB, 21 subjects with AD and another group of 12 HV. The correlation between nigroputaminal fractional anisotropy (FA) values and 123I-FP-CIT SPECT findings was investigated. Shapiro-Wilk, ANOVA, ANCOVA, and parametric correlation statistics as well as receiver operating characteristic (ROC) analysis were used. RESULTS: DLB patients showed a higher nigroputaminal FA values compared with both AD and HV-controls groups (p = 0.001 for both comparisons), while no difference was observed between HV-controls and AD groups (p = 0.450); at ROC analysis, the area under the curve for the discriminating DLB and AD subjects was 0.820; FA values correlated with 123I-FP-CIT values (on the left, r = -0.670; on the right, r = -720). No significant differences were observed for the FA of the corticospinal tract across the three groups (p = 0.740). CONCLUSIONS: In DLB, nigroputaminal degeneration could be reliably assessed on MRI diffusion scans using a mask of nigroputaminal bundle trajectory. Nigroputaminal FA in DLB patients correlated with 123I-FP-CIT values data may allow to differentiate these patients from AD patients and HV-controls.