A 5-Year Longitudinal Clinical and Magnetic Resonance Imaging Study in Spinocerebellar Ataxia Type 3.

BACKGROUND: The natural history of neurodegeneration in spinocerebellar ataxia type 3/Machado Joseph disease is still unclear. Here, we built a long-term longitudinal clinical and neuroimaging study to address this point. METHODS: Twenty-three patients with spinocerebellar ataxia type 3/Machado Joseph disease and 22 healthy controls underwent 3T MRI twice 5.0 years apart. T1 and diffusion tensor imaging sequences were obtained. We used T1 multiatlas, diffusion tensor imaging multiatlas, SpineSeg, and CERES-SUIT for cerebral gray and white matter, spinal cord and cerebellar analyses, respectively. Clinical severity was assessed with scale for assessment and rating of ataxia. Analysis of covariance evaluated longitudinal between-group changes. Effect sizes were calculated for each significant result. RESULTS: Progressive volumetric abnormalities were most evident in the cerebellum (Lobule X and Crus II; effect size, 2.0), followed by the basal ganglia (effect size, 0.7). The cerebellar peduncles had the largest white-matter diffusivity changes (effect size, 1.29). Scale for assessment and rating of ataxia-related effect size was 0.82. We failed to identify progressive spinal cord abnormalities. CONCLUSIONS: Longitudinal changes in spinocerebellar ataxia type 3/Machado Joseph disease are more evident in the cerebellum and connections, followed by the basal ganglia. © 2020 International Parkinson and Movement Disorder Society.

Structural signature of SCA3: From presymptomatic to late disease stages.

OBJECTIVE: Machado-Joseph disease (SCA3/MJD) is the most frequent spinocerebellar ataxia worldwide and characterized by brainstem, basal ganglia, and cerebellar damage. However, little is known about the natural history of the disease. This motivated us to determine the extension and progression of central nervous system involvement in SCA3/MJD using multimodal magnetic resonance imaging (MRI)-based analyses in a large cohort of patients (n = 79) and presymptomatic subjects (n = 12). METHODS: All subjects underwent MRI in a 3T device to assess gray and white matter. To evaluate the cerebral and cerebellar cortices, we used measures from FreeSurfer and SUIT. T1-multiatlas assessed deep gray matter. Diffusion tensor imaging multiatlas was used to investigate cerebral white matter (WM) and SpineSeg to assess the cervical spinal cord. RESULTS: There was widespread WM and cerebellar damage, in contrast to the restricted motor cortex involvement when all patients are compared to age- and sex-matched controls. Presymtomatic patients showed WM microstructural abnormalities mainly in the cerebellar and cerebral peduncles and volumetric reduction of midbrain, spinal cord, and substantia nigra. To assess the disease progression, we divided patients into four subgroups defined by time from ataxia onset. There was a clear pattern of evolving structural compromise, starting in infratentorial structures and progressing up to the cerebral cortex. CONCLUSION: Structural damage in SCA3/MJD begins in the spinal cord, cerebellar peduncles, as well as substantia nigra and progresses to cerebral areas in the long term. These structural differences reveal some insights into the pathogenesis of SCA3/MJD and suggest a staging scheme to map the progression of the disease. Ann Neurol 2018;84:401-408.

Spinal cord diffusion tensor imaging in patients with sensory neuronopathy.

INTRODUCTION: We investigated whether MR diffusion tensor imaging (DTI) analysis of the cervical spinal cord could aid the (differential) diagnosis of sensory neuronopathies, an underdiagnosed group of diseases of the peripheral nervous system. METHODS: We obtained spinal cord DTI and T2WI at 3 T from 28 patients, 14 diabetic subjects with sensory-motor distal polyneuropathy, and 20 healthy controls. We quantified DTI-based parameters and looked at the hyperintense T2W signal at the spinal cord posterior columns. Fractional anisotropy and mean diffusivity values at C2-C3 and C3-C4 levels were compared between groups. We also compared average fractional anisotropy (mean of values at C2-C3 and C3-C4 levels). A receiver operating characteristic (ROC) curve was used to determine diagnostic accuracy of average fractional anisotropy, and we compared its sensitivity against the hyperintense signal in segregating patients from the other subjects. RESULTS: Mean age and disease duration were 52 ± 10 and 11.4 ± 9.3 years in the patient group. Eighteen subjects had idiopathic disease and 6 dysimmune etiology. Fractional anisotropy at C3-C4 level and average fractional anisotropy were significantly different between patients and healthy controls (p < 0.001 and <0.001) and between patients and diabetic subjects (p = 0.019 and 0.027). Average fractional anisotropy presented an area under the curve of 0.838. Moreover, it had higher sensitivity than visual detection of the hyperintense signal (0.86 vs. 0.54), particularly for patients with short disease duration. CONCLUSION: DTI-based analysis enables in vivo detection of posterior column damage in sensory neuronopathy patients and is a useful diagnostic test for this condition. It also helps the differential diagnosis between sensory neuronopathy and distal polyneuropathies.

Neuroimaging in Sensory Neuronopathy.

Sensory neuronopathies (SN) are a group of disorders characterized by primary damage to the dorsal root ganglia neurons. Clinical features include multifocal areas of hypoaesthesia, pain, dysautonomia, and sensory ataxia, which is the major source of disability. Diagnosis relies upon clinical assessment and nerve conductions studies, but sometimes it is difficult to distinguish SN from similar conditions, such as axonal polyneuropathies and some myelopathies. In this scenario, underdiagnosis is certainly an important issue for SN patients and additional diagnostic tools are needed. MRI is able to evaluate the dorsal columns of the spinal cord and has proven useful in the workup of SN patients. Although T2 weighted hyperintensity restricted to the posterior fasciculi without contrast enhancement is the typical finding, additional abnormalities have been recently reported. The aim of this review is to gather available information on neuroimaging findings of SN, discuss their clinical correlates and the potential impact of novel MRI-based techniques.