Genotype-specific spinal cord damage in spinocerebellar ataxias: an ENIGMA-Ataxia study.

BACKGROUND: Spinal cord damage is a feature of many spinocerebellar ataxias (SCAs), but well-powered in vivo studies are lacking and links with disease severity and progression remain unclear. Here we characterise cervical spinal cord morphometric abnormalities in SCA1, SCA2, SCA3 and SCA6 using a large multisite MRI dataset. METHODS: Upper spinal cord (vertebrae C1-C4) cross-sectional area (CSA) and eccentricity (flattening) were assessed using MRI data from nine sites within the ENIGMA-Ataxia consortium, including 364 people with ataxic SCA, 56 individuals with preataxic SCA and 394 nonataxic controls. Correlations and subgroup analyses within the SCA cohorts were undertaken based on disease duration and ataxia severity. RESULTS: Individuals in the ataxic stage of SCA1, SCA2 and SCA3, relative to non-ataxic controls, had significantly reduced CSA and increased eccentricity at all examined levels. CSA showed large effect sizes (d>2.0) and correlated with ataxia severity (r<-0.43) and disease duration (r<-0.21). Eccentricity correlated only with ataxia severity in SCA2 (r=0.28). No significant spinal cord differences were evident in SCA6. In preataxic individuals, CSA was significantly reduced in SCA2 (d=1.6) and SCA3 (d=1.7), and the SCA2 group also showed increased eccentricity (d=1.1) relative to nonataxic controls. Subgroup analyses confirmed that CSA and eccentricity are abnormal in early disease stages in SCA1, SCA2 and SCA3. CSA declined with disease progression in all, whereas eccentricity progressed only in SCA2. CONCLUSIONS: Spinal cord abnormalities are an early and progressive feature of SCA1, SCA2 and SCA3, but not SCA6, which can be captured using quantitative MRI.

Bilateral Simultaneous Magnetic Resonance-Guided Focused Ultrasound Pallidotomy for Life-Threatening Status Dystonicus.

BACKGROUND: Invasive treatments like radiofrequency stereotactic lesioning or deep brain stimulation of the globus pallidus internus can resolve drug-resistant status dystonicus (SD). However, these open procedures are not always feasible in patients with SD. OBJECTIVE: The aim was to report the safety and efficacy of simultaneous asleep bilateral transcranial magnetic resonance-guided focused ultrasound (MRgFUS) pallidotomy for life-threatening SD. METHODS: We performed bilateral simultaneous MRgFUS pallidotomy under general anesthesia in 2 young patients with pantothenate kinase-associated neurodegeneration and GNAO1 encephalopathy. Both patients had medically refractory SD and severe comorbidities contraindicating open surgery. RESULTS: SD resolved at 4 and 12 days after MRgFUS, respectively. Adverse events (intraoperative hypothermia and postoperative facial paralysis) were mild and transient. CONCLUSION: Bilateral simultaneous MRgFUS pallidotomy under general anesthesia is safe and may be a valid alternative therapeutic option for fragile patients. Further studies are needed to assess long-term efficacy of the procedure. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Distinct neural signatures of pulvinar in C9orf72 amyotrophic lateral sclerosis mutation carriers and noncarriers.

BACKGROUND AND PURPOSE: Thalamic alterations have been reported as a major feature in presymptomatic and symptomatic patients carrying the C9orf72 mutation across the frontotemporal dementia-amyotrophic lateral sclerosis (ALS) spectrum. Specifically, the pulvinar, a high-order thalamic nucleus and timekeeper for large-scale cortical networks, has been hypothesized to be involved in C9orf72-related neurodegenerative diseases. We investigated whether pulvinar volume can be useful for differential diagnosis in ALS C9orf72 mutation carriers and noncarriers and how underlying functional connectivity changes affect this region. METHODS: We studied 19 ALS C9orf72 mutation carriers (ALSC9+) accurately matched with wild-type ALS (ALSC9-) and ALS mimic (ALSmimic) patients using structural and resting-state functional magnetic resonance imaging data. Pulvinar volume was computed using automatic segmentation. Seed-to-voxel functional connectivity analyses were performed using seeds from a pulvinar functional parcellation. RESULTS: Pulvinar structural integrity had high discriminative values for ALSC9+ patients compared to ALSmimic (area under the curve [AUC] = 0.86) and ALSC9- (AUC = 0.77) patients, yielding a volume cutpoint of approximately 0.23%. Compared to ALSmimic, ALSC9- showed increased anterior, inferior, and lateral pulvinar connections with bilateral occipital-temporal-parietal regions, whereas ALSC9+ showed no differences. ALSC9+ patients when compared to ALSC9- patients showed reduced pulvinar-occipital connectivity for anterior and inferior pulvinar seeds. CONCLUSIONS: Pulvinar volume could be a differential biomarker closely related to the C9orf72 mutation. A pulvinar-cortical circuit dysfunction might play a critical role in disease progression and development, in both the genetic phenotype and ALS wild-type patients.

Tracking longitudinal thalamic volume changes during early stages of SCA1 and SCA2.

PURPOSE: Spinocerebellar ataxia SCA1 and SCA2 are adult-onset hereditary disorders, due to triplet CAG expansion in their respective causative genes. The pathophysiology of SCA1 and SCA2 suggests alterations of cerebello-thalamo-cortical pathway and its connections to the basal ganglia. In this framework, thalamic integrity is crucial for shaping efficient whole-brain dynamics and functions. The aims of the study are to identify structural changes in thalamic nuclei in presymptomatic and symptomatic SCA1 and SCA2 patients and to assess disease progression within a 1-year interval. MATERIAL AND METHODS: A prospective 1-year clinical and MRI assessment was conducted in 27 presymptomatic and 23 clinically manifest mutation carriers for SCA1 and SCA2 expansions. Cross-sectional and longitudinal changes of thalamic nuclei volume were investigated in SCA1 and SCA2 individuals and in healthy participants (n = 20). RESULTS: Both SCA1 and SCA2 patients had significant atrophy in the majority of thalamic nuclei, except for the posterior and partly medial nuclei. The 1-year longitudinal evaluation showed a specific pattern of atrophy in ventral and posterior thalamus, detectable even at the presymptomatic stage of the disease. CONCLUSION: For the first time in vivo, our exploratory study has shown that different thalamic nuclei are involved at different stages of the degenerative process in both SCA1 and SCA2. It is therefore possible that thalamic alterations might significantly contribute to the progression of the disease years before overt clinical manifestations occur.

Longitudinal neurofunctional changes in medication overuse headache patients after mindfulness practice in a randomized controlled trial (the MIND-CM study).

BACKGROUND: Mindfulness practice has gained interest in the management of Chronic Migraine associated with Medication Overuse Headache (CM-MOH). Mindfulness is characterized by present-moment self-awareness and relies on attention control and emotion regulation, improving headache-related pain management. Mindfulness modulates the Default Mode Network (DMN), Salience Network (SN), and Fronto-Parietal Network (FPN) functional connectivity. However, the neural mechanisms underlying headache-related pain management with mindfulness are still unclear. In this study, we tested neurofunctional changes after mindfulness practice added to pharmacological treatment as usual in CM-MOH patients. METHODS: The present study is a longitudinal phase-III single-blind Randomized Controlled Trial (MIND-CM study; NCT03671681). Patients had a diagnosis of CM-MOH, no history of neurological and severe psychiatric comorbidities, and were attending our specialty headache centre. Patients were divided in Treatment as Usual (TaU) and mindfulness added to TaU (TaU + MIND) groups. Patients underwent a neuroimaging and clinical assessment before the treatment and after one year. Longitudinal comparisons of DMN, SN, and FPN connectivity were performed between groups and correlated with clinical changes. Vertex-wise analysis was performed to assess cortical thickness changes. RESULTS: 177 CM-MOH patients were randomized to either TaU group or TaU + MIND group. Thirty-four patients, divided in 17 TaU and 17 TaU + MIND, completed the neuroimaging follow-up. At the follow-up, both groups showed an improvement in most clinical variables, whereas only TaU + MIND patients showed a significant headache frequency reduction (p = 0.028). After one year, TaU + MIND patients showed greater SN functional connectivity with the left posterior insula (p-FWE = 0.007) and sensorimotor cortex (p-FWE = 0.026). In TaU + MIND patients only, greater SN-insular connectivity was associated with improved depression scores (r = -0.51, p = 0.038). A longitudinal increase in cortical thickness was observed in the insular cluster in these patients (p = 0.015). Increased anterior cingulate cortex thickness was also reported in TaU + MIND group (p-FWE = 0.02). CONCLUSIONS: Increased SN-insular connectivity might modulate chronic pain perception and the management of negative emotions. Enhanced SN-sensorimotor connectivity could reflect improved body-awareness of painful sensations. Expanded cingulate cortex thickness might sustain improved cognitive processing of nociceptive information. Our findings unveil the therapeutic potential of mindfulness and the underlying neural mechanisms in CM-MOH patients. TRIAL REGISTRATION: Name of Registry; MIND-CM study; Registration Number ClinicalTrials.gov identifier: NCT0367168; Registration Date: 14/09/2018.

Complex Ataxia-Dementia Phenotype in Patients with Digenic TBP/STUB1 Spinocerebellar Ataxia.

BACKGROUND AND OBJECTIVES: Spinocerebellar ataxias (SCAs) are autosomal dominant disorders with extensive clinical and genetic heterogeneity. We recently identified a form of SCA transmitted with a digenic pattern of inheritance caused by the concomitant presence of an intermediate-length expansion in TATA-box binding protein gene (TBP40-46 ) and a heterozygous pathogenic variant in the Stip1-homologous and U-Box containing protein 1 gene (STUB1). This SCATBP/STUB1 represents the first example of a cerebellar disorder in which digenic inheritance has been identified. OBJECTIVES: We studied a large cohort of patients with SCATBP/STUB1 with the aim of describing specific clinical and neuroimaging features of this distinctive genotype. METHODS: In this observational study, we recruited 65 affected and unaffected family members from 21 SCATBP/STUB1 families and from eight families with monogenic SCA17. Their characteristics and phenotypes were compared with those of 33 age-matched controls. RESULTS: SCATBP/STUB1 patients had multi-domain dementia with a more severe impairment in respect to patient carrying only fully expanded SCA17 alleles. Cerebellar volume and thickness of cerebellar cortex were reduced in SCATBP/STUB1 compared with SCA17 patients (P = 0.03; P = 0.008). Basal ganglia volumes were reduced in both patient groups, as compared with controls, whereas brainstem volumes were significantly reduced in SCATBP/STUB1 , but not in SCA17 patients. CONCLUSIONS: The identification of the complex SCATBP/STUB1 phenotype may impact on diagnosis and genetic counseling in the families with both hereditary and sporadic ataxia. The independent segregation of TBP and STUB1 alleles needs to be considered for recurrence risk and predictive genetic tests. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A discriminative event-based model for subtype diagnosis of sporadic Creutzfeldt-Jakob disease using brain MRI.

INTRODUCTION: Sporadic Creutzfeldt-Jakob disease (sCJD) comprises multiple subtypes (MM1, MM2, MV1, MV2C, MV2K, VV1, and VV2) with distinct disease durations and spatiotemporal cascades of brain lesions. Our goal was to establish the ante mortem diagnosis of sCJD subtype, based on patient-specific estimates of the spatiotemporal cascade of lesions detected by diffusion-weighted magnetic resonance imaging (DWI). METHODS: We included 488 patients with autopsy-confirmed diagnosis of sCJD subtype and 50 patients with exclusion of prion disease. We applied a discriminative event-based model (DEBM) to infer the spatiotemporal cascades of lesions, derived from the DWI scores of 12 brain regions assigned by three neuroradiologists. Based on the DEBM cascades and the prion protein genotype at codon 129, we developed and validated a novel algorithm for the diagnosis of the sCJD subtype. RESULTS: Cascades of MM1, MM2, MV1, MV2C, and VV1 originated in the parietal cortex and, following subtype-specific orderings of propagation, went toward the striatum, thalamus, and cerebellum; conversely, VV2 and MV2K cascades showed a striatum-to-cortex propagation. The proposed algorithm achieved 76.5% balanced accuracy for the sCJD subtype diagnosis, with low rater dependency (differences in accuracy of ± 1% among neuroradiologists). DISCUSSION: Ante mortem diagnosis of sCJD subtype is feasible with this novel data-driven approach, and it may be valuable for patient prognostication, stratification in targeted clinical trials, and future therapeutics. HIGHLIGHTS: Subtype diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) is achievable with diffusion MRI. Cascades of diffusion MRI abnormalities in the brain are subtype-specific in sCJD. We proposed a diagnostic algorithm based on cascades of diffusion MRI abnormalities and demonstrated that it is accurate. Our method may aid early diagnosis, prognosis, stratification in clinical trials, and future therapeutics. The present approach is applicable to other neurodegenerative diseases, enhancing the differential diagnoses.

Subtype Diagnosis of Sporadic Creutzfeldt-Jakob Disease with Diffusion Magnetic Resonance Imaging.

OBJECTIVE: Sporadic Creutzfeldt-Jakob disease (sCJD) comprises several subtypes as defined by genetic and prion protein characteristics, which are associated with distinct clinical and pathological phenotypes. To date, no clinical test can reliably diagnose the subtype. We established two procedures for the antemortem diagnosis of sCJD subtype using diffusion magnetic resonance imaging (MRI). METHODS: MRI of 1,458 patients referred to the National Prion Disease Pathology Surveillance Center were collected through its consultation service. One neuroradiologist blind to the diagnosis scored 12 brain regions and generated a lesion profile for each MRI scan. We selected 487 patients with autopsy-confirmed diagnosis of "pure" sCJD subtype and at least one positive diffusion MRI examination. We designed and tested two data-driven procedures for subtype diagnosis: the first procedure-prion subtype classification algorithm with MRI (PriSCA_MRI)-uses only MRI examinations; the second-PriSCA_MRI + Gen-includes knowledge of the prion protein codon 129 genotype, a major determinant of sCJD subtypes. Both procedures were tested on the first MRI and the last MRI follow-up. RESULTS: PriSCA_MRI classified the 3 most prevalent subtypes with 82% accuracy. PriSCA_MRI + Gen raised the accuracy to 89% and identified all subtypes. Individually, the 2 most prevalent sCJD subtypes, MM1 and VV2, were diagnosed with sensitivities up to 95 and 97%, respectively. The performances of both procedures did not change in 168 patients with longitudinal MRI studies when the last examination was used. INTERPRETATION: This study provides the first practical algorithms for antemortem diagnosis of sCJD subtypes. MRI diagnosis of subtype is likely to be attainable at early disease stages to prognosticate clinical course and design future therapeutic trials. ANN NEUROL 2021;89:560-572.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy May Spare Dopaminergic Therapy in Early-Stage Tremor-Dominant Parkinson's Disease: A Pilot Study.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is a safe and effective procedure for drug-resistant tremor in Parkinson's disease (PD). OBJECTIVE: The aim of this study was to demonstrate that MRgFUS ventralis intermedius thalamotomy in early-stage tremor-dominant PD may prevent an increase in dopaminergic medication 6 months after treatment compared with matched PD control subjects on standard medical therapy. METHODS: We prospectively enrolled patients with early-stage PD who underwent MRgFUS ventralis intermedius thalamotomy (PD-FUS) and patients treated with oral dopaminergic therapy (PD-ODT) with a 1:2 ratio. We collected demographic and clinical data at baseline and 6 and 12 months after thalamotomy. RESULTS: We included 10 patients in the PD-FUS group and 20 patients in the PD-ODT group. We found a significant increase in total levodopa equivalent daily dose and levodopa plus monoamine oxidase B inhibitors dose in the PD-ODT group 6 months after thalamotomy. CONCLUSIONS: In early-stage tremor-dominant PD, MRgFUS thalamotomy may be useful to reduce tremor and avoid the need to increase dopaminergic medications. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Spinocerebellar Ataxia Type 1: One-Year Longitudinal Study to Identify Clinical and MRI Measures of Disease Progression in Patients and Presymptomatic Carriers.

Spinocerebellar ataxias type 1 (SCA1) is an autosomal dominant disease usually manifesting in adulthood. We performed a prospective 1-year longitudinal study in 14 presymptomatic mutation carriers (preSCA1), 11 ataxic patients, and 21 healthy controls. SCA1 patients had a median disease duration of 6 years (range 2-16) and SARA score of 7 points (range 3.5-20). PreSCA1 had an estimated time before disease onset of 9.7 years (range 4-30), and no signs of ataxia. At baseline, SCA1 patients significantly differed from controls in SARA score (Scale for Assessment and Rating of Ataxia), cognitive tests, and structural MRI measures. Significant volume loss was found in cerebellum, brainstem, basal ganglia, and cortical thinning in frontal, temporal, and occipital regions. PreSCA1 did not differ from controls. At 1-year follow-up, SCA1 patients showed significant increase in SARA score, and decreased volume of cerebellum (- 0.6%), pons (- 5.5%), superior cerebellar peduncles (- 10.7%), and midbrain (- 3.0%). Signs of disease progression were also observed in preSCA1 subjects, with increased SARA score and reduced total cerebellar volume. Our exploratory study suggests that clinical scores and MRI measures provide valuable data to monitor and quantify the earliest changes associated with the preclinical and the symptomatic phases of SCA1 disease.

The cognitive phenotypes of Creutzfeldt-Jakob disease: comparison with secondary metabolic encephalopathy.

BACKGROUND: Rapidly progressive cognitive impairment is a diagnostic criterion in Creutzfeldt-Jakob disease (CJD), but the diagnosis is usually reached when an analysis of cognitive aspects is no longer possible. OBJECTIVE: This study aims to delineate the cognitive phenotypes preceding severe dementia in CJD compared to secondary metabolic encephalopathies (SME) with rapid cognitive impairment. METHODS: Patients with rapidly progressive neurological symptoms underwent neuropsychological evaluation, analysis of cerebrospinal fluid (CSF) and codon 129 polymorphism of the prion protein gene (PRNP), magnetic resonance imaging (MRI), and single positron emission computed tomography (99mTcSPECT). CSF real-time quaking-induced conversion analysis was applied in CJD patients. Based on literature and clinical expertise, cognitive profiles were correlated with brain areas. RESULTS: Thirty-one patients were diagnosed with CJD (n = 17) or SME; 77 cases of CJD were extracted from the literature. In patients with CJD, verbal initiative, lexical search, long-term memory, attention, and abstract reasoning were the most frequently impaired abilities. Cognitive profiles were mainly related to dysfunction in fronto-temporal areas. Furthermore, they were consistent with areas of hypoperfusion detected by 99mTc SPECT in six patients and cortical and subcortical MRI hyperintensities in eight and 14 patients, respectively, and were similar to those described in the literature. In contrast, cognitive profiles were different from those in SME characterized by visuospatial and constructive deficits relating to posterior brain areas. CONCLUSION: In CJD, clinical and neuropsychological analyses outline a salient cognitive phenotype suggestive of fronto-temporal dysfunction preceding severe dementia. This phenotype is different from that observed in other rapidly progressive encephalopathies.

GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease-study protocol and preliminary results.

BACKGROUND: GENetics of mOyaMoyA (GEN-O-MA) project is a multicenter observational study implemented in Italy aimed at creating a network of centers involved in moyamoya angiopathy (MA) care and research and at collecting a large series and bio-repository of MA patients, finally aimed at describing the disease phenotype and clinical course as well as at identifying biological or cellular markers for disease progression. The present paper resumes the most important study methodological issues and preliminary results. METHODS: Nineteen centers are participating to the study. Patients with both bilateral and unilateral radiologically defined MA are included in the study. For each patient, detailed demographic and clinical as well as neuroimaging data are being collected. When available, biological samples (blood, DNA, CSF, middle cerebral artery samples) are being also collected for biological and cellular studies. RESULTS: Ninety-eight patients (age of onset mean ± SD 35.5 ± 19.6 years; 68.4% females) have been collected so far. 65.3% of patients presented ischemic (50%) and haemorrhagic (15.3%) stroke. A higher female predominance concomitantly with a similar age of onset and clinical features to what was reported in previous studies on Western patients has been confirmed. CONCLUSION: An accurate and detailed clinical and neuroimaging classification represents the best strategy to provide the characterization of the disease phenotype and clinical course. The collection of a large number of biological samples will permit the identification of biological markers and genetic factors associated with the disease susceptibility in Italy.

Correction: Sciacca, F. L., et al. Microduplication of 15q13.3 and Microdeletion of 18q21.32 in a Patient with Moyamoya Syndrome. Int. J. Mol. Sci. 2018, 19, 3675.

The authors wish to make the corrections to this paper [...].

Microduplication of 15q13.3 and Microdeletion of 18q21.32 in a Patient with Moyamoya Syndrome.

Moyamoya angiopathy (MA) is a cerebrovascular disease determining a progressive stenosis of the terminal part of the internal carotid arteries (ICAs) and their proximal branches and the compensatory development of abnormal "moyamoya" vessels. MA occurs as an isolated cerebral angiopathy (so-called moyamoya disease) or in association with various conditions (moyamoya syndromes) including several heritable conditions such as Down syndrome, neurofibromatosis type 1 and other genomic defects. Although the mechanism that links MA to these genetic syndromes is still unclear, it is believed that the involved genes may contribute to the disease susceptibility. Herein, we describe the case of a 43 years old woman with bilateral MA and peculiar facial characteristics, having a 484-kb microduplication of the chromosomal region 15q13.3 and a previously unreported 786 kb microdeletion in 18q21.32. This patient may have a newly-recognized genetic syndrome associated with MA. Although the relationship between these genetic variants and MA is unclear, our report would contribute to widening the genetic scenario of MA, in which not only genic mutation, but also genome unbalances are possible candidate susceptibility factors.

Genotype-specific patterns of atrophy progression are more sensitive than clinical decline in SCA1, SCA3 and SCA6.

Spinocerebellar ataxias are dominantly inherited disorders that are associated with progressive brain degeneration, mainly affecting the cerebellum and brainstem. As part of the multicentre European integrated project on spinocerebellar ataxias study, 37 patients with spinocerebellar ataxia-1, 19 with spinocerebellar ataxia-3 and seven with spinocerebellar ataxia-6 were clinically examined and underwent magnetic resonance imaging at baseline and after a 2-year follow-up. All patients were compared with age-matched and gender-matched healthy control subjects. Magnetic resonance imaging analysis included three-dimensional volumetry and observer-independent longitudinal voxel-based morphometry. Volumetry revealed loss of brainstem, cerebellar and basal ganglia volume in all genotypes. Most sensitive to change was the pontine volume in spinocerebellar ataxia-1, striatal volume in spinocerebellar ataxia-3 and caudate volume in spinocerebellar ataxia-6. Sensitivity to change, as measured by standard response mean, of the respective MRI measures was greater than that of the most sensitive clinical measure, the Scale for the Assessment and Rating of Ataxia. Longitudinal voxel-based morphometry revealed greatest grey matter loss in the cerebellum and brainstem in spinocerebellar ataxia-1, in the putamen and pallidum in spinocerebellar ataxia-3 and in the cerebellum, thalamus, putamen and pallidum in spinocerebellar ataxia-6. There was a mild correlation between CAG repeat length and volume loss of the bilateral cerebellum and the pons in spinocerebellar ataxia-1. Quantitative volumetry and voxel-based morphometry imaging demonstrated genotype-specific patterns of atrophy progression in spinocerebellar ataxias-1, 3 and 6, and they showed a high sensitivity to detect change that was superior to clinical scales. These structural magnetic resonance imaging findings have the potential to serve as surrogate markers, which might help to delineate quantifiable endpoints and non-invasive methods for rapid and reliable data acquisition, encouraging their use in clinical trials.

Substantia nigra in Parkinson's disease: a multimodal MRI comparison between early and advanced stages of the disease.

This study focused on the substantia nigra (SN) in Parkinson's disease (PD). We measured its area and volume, mean diffusivity (MD), fractional anisotropy (FA) and iron concentration in early and late PD and correlated the values with clinical scores. Twenty-two early PD (EPD), 20 late PD (LPD) and 20 healthy subjects (age 64.7 ± 4.9, 60.5 ± 6.1, and 61 ± 7.2 years, respectively) underwent 1.5 T MR imaging with double-TI-IR T1-weighted, T2*-weighted and diffusion tensor imaging scans. Relative SN area, MD, FA and R2* were measured in ROIs traced on SN. Correlation with Unified Parkinson Disease Rating Scale (UPDRS) scores was assessed. In LPD, the SN area was significantly reduced with respect to EPD (p = 0.04) and control subjects (p < 0.001). In EPD, the SN area was also significantly smaller than in controls (p = 0.006). Similarly, the SN volume significantly differed between LPD and controls (p = 0.001) and between EPD and LPD (p = 0.049), while no significant differences were found between controls and EPD. Both SN area (r = 0.47, p = 0.004) and volume (r = 0.46, p = 0.005) correlated with UPDRS scores. At 1.5 T, SN morphological measurements were sensitive to early PD changes and able to track the disease progression, while MD and FA measures and relaxometry did not provide significant results.