White matter integrity assessment in spinocerebellar ataxia type 2 (SCA2) patients.

AIM: To assess the burden of white matter (WM) damage in the cerebrum and cerebellum of spinocerebellar ataxia type 2 (SCA2) patients in an attempt to identify key regions affected by the neurodegenerative processes using diffusion tensor imaging (DTI). MATERIALS AND METHODS: Nine SCA2 patients and 16 age-matched healthy controls were examined twice (SCA2 patients 3.6 ± 0.7 years and controls 3.3 ± 1.0 years apart) on the same 1.5 T scanner by acquiring T1-weighted and diffusion-weighted (b-value = 1,000 s/mm2) images. Using tract-based spatial statistics, DTI analysis on fractional anisotropy (FA), mean diffusivity (MD), axial (AD)/radial (RD) diffusivity was performed. RESULTS: At baseline magnetic resonance imaging (MRI), FA was significantly decreased in SCA2 patients in the corticospinal tracts, inferior and superior cerebellar peduncles, middle cerebellar peduncles, cerebral peduncles, right superior and posterior corona radiata. RD was only significantly increased in SCA2 patients in the middle cerebellar peduncles. No significant AD and MD changes were observed. Tract-based spatial statistics (TBSS) analysis between SCA2 patients at baseline and at follow-up showed no significant changes in any of the DTI metrics. CONCLUSIONS: DTI is a sensitive tool for following the progression of WM neurodegeneration and severity assessment in patients with SCA2. These findings add to a better understanding of the neurological underpinnings of the symptoms experienced by SCA2 patients.

Assessment and recovery of visually guided reaching deficits following cerebellar stroke.

The cerebellum is known to play an important role in the coordination and timing of limb movements. The present study focused on how reach kinematics are affected by cerebellar lesions to quantify both the presence of motor impairment, and recovery of motor function over time. In the current study, 12 patients with isolated cerebellar stroke completed clinical measures of cognitive and motor function, as well as a visually guided reaching (VGR) task using the Kinarm exoskeleton at baseline (∼2 weeks), as well as 6, 12, and 24-weeks post-stroke. During the VGR task, patients made unassisted reaches with visual feedback from a central 'start' position to one of eight targets arranged in a circle. At baseline, 6/12 patients were impaired across several parameters of the VGR task compared to a Kinarm normative sample (n = 307), revealing deficits in both feed-forward and feedback control. The only clinical measures that consistently demonstrated impairment were the Purdue Pegboard Task (PPT; 9/12 patients) and the Montreal Cognitive Assessment (6/11 patients). Overall, patients who were impaired at baseline showed significant recovery by the 24-week follow-up for both VGR and the PPT. A lesion overlap analysis indicated that the regions most commonly damaged in 5/12 patients (42% overlap) were lobule IX and Crus II of the right cerebellum. A lesion subtraction analysis comparing patients who were impaired (n = 6) vs. unimpaired (n = 6) on the VGR task at baseline showed that the region most commonly damaged in impaired patients was lobule VIII of the right cerebellum (40% overlap). Our results lend further support to the notion that the cerebellum is involved in both feedforward and feedback control during reaching, and that cerebellar patients tend to recover relatively quickly overall. In addition, we argue that future research should study the effects of cerebellar damage on visuomotor control from a perception-action theoretical framework to better understand how the cerebellum works with the dorsal stream to control visually guided action.

The assessment of cognitive functions in patients with isolated cerebellar infarctions: A follow-up study.

The role of the cerebellum on cognitive functions have been well-defined; however, the information related to the progress in time process is limited. In this study, we aimed to evaluate the cognitive function of patients with isolated cerebellar infarction in both the acute stage and the follow-up period. Twenty-three patients with isolated cerebellar infarction and 22 healthy control were examined through an extensive neuropsychological assessment battery. The patients were evaluated in the acute stage and at least six months after the stroke in the follow-up period. There were no significant differences between the patients and the controls regarding age (52.2 ± 7.0 and 54.9 ± 6.6, p = 0.184) and gender (Female/Male: 6/17 and 7/15, p = 0.672). There was no statistically significant difference between patients with right cerebellar infarction and left cerebellar infarction in terms of cognitive functions. Verbal fluency, attention, and verbal and non-verbal episodic memory scores were significantly lower in patient group in the acute stage when compared to the control group. When the follow-up evaluation was compared to acute stage, it was revealed that patients had recovered in all areas; however, less improvement was seen in word reading time. Our results support that lesions of the cerebellum affect cognitive functions in the acute stage. However, the improvement was demonstrated in all cognitive functions in the follow-up period.

Ventralis intermedius nucleus anatomical variability assessment by MRI structural connectivity.

The ventralis intermedius nucleus (Vim) is centrally placed in the dentato-thalamo-cortical pathway (DTCp) and is a key surgical target in the treatment of severe medically refractory tremor. It is not visible on conventional MRI sequences; consequently, stereotactic targeting currently relies on atlas-based coordinates. This fails to capture individual anatomical variability, which may lead to poor long-term clinical efficacy. Probabilistic tractography, combined with known anatomical connectivity, enables localisation of thalamic nuclei at an individual subject level. There are, however, a number of confounds associated with this technique that may influence results. Here we focused on an established method, using probabilistic tractography to reconstruct the DTCp, to identify the connectivity-defined Vim (cd-Vim) in vivo. Using 100 healthy individuals from the Human Connectome Project, our aim was to quantify cd-Vim variability across this population, measure the discrepancy with atlas-defined Vim (ad-Vim), and assess the influence of potential methodological confounds. We found no significant effect of any of the confounds. The mean cd-Vim coordinate was located within 1.88 mm (left) and 2.12 mm (right) of the average midpoint and 3.98 mm (left) and 5.41 mm (right) from the ad-Vim coordinates. cd-Vim location was more variable on the right, which reflects hemispheric asymmetries in the probabilistic DTC reconstructed. The method was reproducible, with no significant cd-Vim location differences in a separate test-retest cohort. The superior cerebellar peduncle was identified as a potential source of artificial variance. This work demonstrates significant individual anatomical variability of the cd-Vim that atlas-based coordinate targeting fails to capture. This variability was not related to any methodological confound tested. Lateralisation of cerebellar functions, such as speech, may contribute to the observed asymmetry. Tractography-based methods seem sensitive to individual anatomical variability that is missed by conventional neurosurgical targeting; these findings may form the basis for translational tools to improve efficacy and reduce side-effects of thalamic surgery for tremor.

18 F-2-fluoro-2-deoxy-D-glucose-positron emission tomography metabolic pattern assessment in the brain of betel quid dependent individuals.

The primary objective of this study was to identify the metabolic pattern in the brains of betel quid dependent (BQD) individuals using 18 F-2-fluoro-2-deoxy-D-glucose-positron emission tomography (18 F-FDG-PET). A total of 42 individuals (16 BQD individuals and 26 healthy controls, HCs) enrolled at the Department of Nuclear Medicine of Xiangya Hospital underwent brain 18 F-FDG-PET. Group comparisons using statistical parametric mapping (SPM) were performed to identify the 18 F-FDG-PET patterns. Standardized uptake value ratios of anterior cingulate, frontal, thalamus, parietal, occipital, temporal and cerebellum were calculated by SPM. The characteristics of abnormal metabolism in brain regions were quantified using the xjView toolbox, and a 3-D brain map was drawn using BrainNet Viewer. We found significant metabolic reduction in the bilateral middle prefrontal cortex (PFC) and the left orbital frontal gyrus (OFC). In contrast, hypermetabolism was observed in the inferior cerebellum, fusiform, superior cerebellum, parahippocampal, vermis, lingual and thalamus. However, we found no significant difference between the BQD and HC group in the anterior cingulate, thalamus, cerebellum and frontal, temporal, parietal and occipital lobes. In summary, we found abnormal 18 F-FDG-PET metabolic pattern in BQD individuals, and this pattern may help the treatment of BQD.

Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in vivo fetal and neonatal MRI assessment.

Down Syndrome (DS) is the most frequent genetic cause of intellectual disability with a wide spectrum of neurodevelopmental outcomes. At present, the relationship between structural brain morphology and the spectrum of cognitive phenotypes in DS, is not well understood. This study aimed to quantify the development of the fetal and neonatal brain in DS participants, with and without a congenital cardiac defect compared with a control population using dedicated, optimised and motion-corrected in vivo magnetic resonance imaging (MRI). We detected deviations in development and altered regional brain growth in the fetus with DS from 21 weeks' gestation, when compared to age-matched controls. Reduced cerebellar volume was apparent in the second trimester with significant alteration in cortical growth becoming evident during the third trimester. Developmental abnormalities in the cortex and cerebellum are likely substrates for later neurocognitive impairment, and ongoing studies will allow us to confirm the role of antenatal MRI as an early biomarker for subsequent cognitive ability in DS. In the era of rapidly developing technologies, we believe that the results of this study will assist counselling for prospective parents.

The ratio of cavum septi pellucidi width to anteroposterior cerebellar diameter: A novel index as a diagnostic adjunct for prenatal diagnosis of trisomy 18.

AIM: To explore the effectiveness of cavum septi pellucidi (CSP) width to anteroposterior cerebellar diameter (APCD) ratio as a diagnostic adjunct for prenatal diagnosis of trisomy 18. METHODS: Images of normal fetal brain within 15 and 35 weeks were stored in our center from 2016 to 2017. Images of aneuploid fetuses were retrospectively collected from 2004 to 2017. The transverse cerebellar diameter, APCD and CSP width were measured. CSP/APCD and APCD/transverse cerebellar diameter ratios were calculated and compared between euploid and aneuploid fetuses. RESULTS: One thousand and forty one fetuses were analyzed, including 817 euploid fetuses and 224 aneuploid fetuses (trisomy 21 117 cases, trisomy 18 82 cases, trisomy 13 9 cases, sex-linked 16 cases). No correlation had been found between both ratios and gestational weeks (P > 0.05). In aneuploid groups, means of ratios were both significantly different just between trisomy 18 group and euploid group (P < 0.05). The best area under the curve was shown by the CSP/APCD ratio. The cutoff value of CSP/APCD was 0.46 (sensitivity 87.0%, specificity 85.0%). CONCLUSION: A wide CSP or cerebellar hypoplasia warrants a more detailed ultrasound screening and genetic counseling. A larger CSP/APCD ratio alerts us to trisomy 18 syndrome, especially in cases with subtle anomalies.

Real-Time Quantitative Assessment of Accuracy and Precision of Blood Volume Derived from DCE-MRI in Individual Patients During a Clinical Trial.

Accuracy and precision of quantitative imaging (QI) metrics should be assessed in real time in each patient during a clinical trial to support QI-based decision-making. We developed a framework for real-time quantitative assessment of QI metrics and evaluated accuracy and precision of dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI)-derived blood volume (BV) in a clinical trial for head and neck cancers. Patients underwent DCE-MRI before and after 2 weeks of radiation therapy (2wkRT). A mean as a reference value and a repeatability coefficient (RC) of BV values established from n patients in cerebellum volumes of interest (VOIs), which were normal and affected little by therapy, served as accuracy and precision measurements. The BV maps of a new patient were called accurate and precise if the values in cerebellum VOIs and the difference between the 2 scans agreed with the respective mean and RC with 95% confidence. The new data could be used to update reference values. Otherwise, the data were flagged for further evaluation before use in the trial. BV maps from 62 patients enrolled on the trial were evaluated. Mean BV values were 2.21 (±0.14) mL/100 g pre-RT and 2.22 (±0.17) mL/100 g at 2wkRT; relative RC was 15.9%. The BV maps from 3 patients were identified to be inaccurate and imprecise before use in the clinical trial. Our framework of real-time quantitative assessment of QI metrics during a clinical trial can be translated to different QI metrics and organ-sites for supporting QI-based decision-making that warrants success of a clinical trial.

LittleBrain: A gradient-based tool for the topographical interpretation of cerebellar neuroimaging findings.

Gradient-based approaches to brain function have recently unmasked fundamental properties of brain organization. Diffusion map embedding analysis of resting-state fMRI data revealed a primary-to-transmodal axis of cerebral cortical macroscale functional organization. The same method was recently used to analyze resting-state data within the cerebellum, revealing for the first time a sensorimotor-fugal macroscale organization principle of cerebellar function. Cerebellar gradient 1 extended from motor to non-motor task-unfocused (default-mode network) areas, and cerebellar gradient 2 isolated task-focused processing regions. Here we present a freely available and easily accessible tool that applies this new knowledge to the topographical interpretation of cerebellar neuroimaging findings. LittleBrain illustrates the relationship between cerebellar data (e.g., volumetric patient study clusters, task activation maps, etc.) and cerebellar gradients 1 and 2. Specifically, LittleBrain plots all voxels of the cerebellum in a two-dimensional scatterplot, with each axis corresponding to one of the two principal functional gradients of the cerebellum, and indicates the position of cerebellar neuroimaging data within these two dimensions. This novel method of data mapping provides alternative, gradual visualizations that complement discrete parcellation maps of cerebellar functional neuroanatomy. We present application examples to show that LittleBrain can also capture subtle, progressive aspects of cerebellar functional neuroanatomy that would be difficult to visualize using conventional mapping techniques. Download and use instructions can be found at https://xaviergp.github.io/littlebrain.

Comparative assessment of linear least-squares, nonlinear least-squares, and Patlak graphical method for regional and local quantitative tracer kinetic modeling in cerebral dynamic 18 F-FDG PET.

PURPOSE: Dynamic 18 F-FDG PET allows quantitative estimation of cerebral glucose metabolism both at the regional and local (voxel) level. Although sensitive to noise and highly computationally expensive, nonlinear least-squares (NLS) optimization stands as the reference approach for the estimation of the kinetic model parameters. Nevertheless, faster techniques, including linear least-squares (LLS) and Patlak graphical method, have been proposed to deal with high resolution noisy data, representing a more adaptable solution for routine clinical implementation. Former research investigating the relative performance of the available algorithms lack precise evaluation of kinetic parameter estimates under realistic acquisition conditions. METHODS: The present study aims at the systematic comparison of the feasibility and pertinence of kinetic modeling of dynamic cerebral 18 F-FDG PET using NLS, LLS, and Patlak method, based on numerical simulations and patient data. Numerical simulations were used to study the bias and variance of K1 and Ki parameters estimation under representative noise levels. Patient data allowed to assess the concordance between the three methods at the regional and voxel scale, and to evaluate the robustness of the estimations with respect to patient head motion. RESULTS AND CONCLUSIONS: Our findings indicate that at the regional level NLS and LLS provide kinetic parameter estimates (K1 and Ki ) with similar bias and variance characteristics (K1 bias ± relative standard deviation [RSD] 0.0 ± 5.1% and 0.1% ± 4.9% for NLS and LLS respectively, Ki bias ± RSD 0.1% ± 4.5% and -0.7% ± 4.4% for NLS and LLS respectively). NLS estimates appear, however, to be slightly less sensitive to patient motion. At the voxel level, provided that patient motion is negligible or corrected, LLS offers an appealing alternative solution for local K1 mapping. It yields K1 estimates that are highly correlated, with high correlation with NLS values (Pearson's r = 0.95 on actual data) within computations times less than two orders of magnitude lower. Last, Patlak method appears as the most robust and accurate technique for the estimation of Ki values at the regional and voxel scale, with or without head motion. It provides low bias/low variance Ki quantification (bias ± RSD -1.5 ± 9.5% and -4.1 ± 19.7% for Patlak and NLS respectively) as well as smooth parametric images suitable for visual assessment.

A diagnostic decision tree for adult cerebellar ataxia based on pontine magnetic resonance imaging.

Cerebellar ataxias (CAs) are heterogeneous conditions often require differential diagnosis. This study aimed to establish a diagnostic decision tree for differentiating CAs based on pontine MRI findings. Two-hundred and two consecutive ataxia patients were clinically classified into 4 groups: (1) spinocerebellar ataxia (SCA) with brainstem involvement (SCA-BSI), (2) Pure cerebellar SCA, (3) cerebellar dominant multiple system atrophy (MSA-c), and (4) Other CA. Signal intensity in pons was graded into 3 types: hot cross bun sign (HCBS), pontine midline linear T2-hyperintensity (PMH), or normal. The distance ratio of pontine base to tegmentum, named "BT-ratio", was measured. The presence of HCBS indicated either MSA-c with a specificity of 97.7%, or SCA2. When PMH was observed, a BT-ratio above 3.54 strongly indicated SCA-BSI, namely Machado-Joseph disease, SCA1, or dentatorubral-pallidoluysian atrophy, whereas a BT-ratio below 3.54 indicated MSA-c or SCA2. When the signal intensity was normal, a BT-ratio above 3.52 indicated SCA-BSI, whereas a BT-ratio below 3.52 suggested Pure cerebellar SCA or Other CA with pure cerebellar type. The decision tree was confirmed useful in a different 30 CA patients. We propose that differential diagnosis of CAs can be supported by combining pontine MRI signal intensity changes and BT-ratio.

Quantitative assessment of changes in diffusion tensor imaging (DTI) metrics along the courses of the cortico-ponto-cerebellar tracts secondary to supratentorial human brain glial tumors.

BACKGROUND: The cortico-ponto-cerebellar tract (CPCT) is the largest projection pathway, which synapses at the pons. Remote effects of supratentorial brain tumors have not been evaluated along the infratentorial course of the CPCT. AIM: The purpose of this study is to evaluate the possible lateralization of the diffusion tensor metrics of the affected CPCT in patients with supratentorial brain tumor. METHODS AND RESULTS: We included 39 patients with 29 left-sided tumors (LST) and 10 right-sided tumors, retrospectively. We measured the magnitude of changes of the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of the CPCT prior to the brain surgery at the level of crus cerebri and middle cerebellar peduncle. Regions of interest (ROIs) were placed on the lateral side of crus cerebri, and ROI-1 (anterior 1/3), ROI-2 (middle 1/3), ROI-3 (posterior 1/3), and ROI-4 were placed at the level of middle cerebellar peduncle. We hypothesized that there would be decreased FA and increased ADC values of the ipsilesional CPCT compared with contralesional CPCT. Ipsilesional FA values were decreased with simultaneous increased ADC value along the CPCT compared with contralesional CPCT in following ROIs, ROI-1 (LST FA: P = .005, ADC: P = .037) and ROI-3 (LST FA: P = .049, ADC: P = .049), respectively. Affected ROI-4 in LST cases also showed lower FA values, although not statistically significant. CONCLUSION: We observed a statistically significant FA value decrease and ADC increase along the left ROI-1 and ROI-3 as well as the nonstatistically significant FA decrease of the left ROI-4 at the second neuron level when there was a related supratentorial tumor. These findings are suggestive of presynaptic and postsynaptic microstructural changes of these tracts following the presynaptic involvement by a primary supratentorial brain tumor.

Study on Lesion Assessment of Cerebello-Thalamo-Cortical Network in Wilson's Disease with Diffusion Tensor Imaging.

Wilson's disease (WD) is a genetic disorder of copper metabolism with pathological copper accumulation in the brain and any other tissues. This article aimed to assess lesions in cerebello-thalamo-cortical network with an advanced technique of diffusion tensor imaging (DTI) in WD. 35 WD patients and 30 age- and sex-matched healthy volunteers were recruited to accept diffusion-weighted images with 15 gradient vectors and conventional magnetic resonance imaging (MRI). The DTI parameters, including fractional anisotropy (FA) and mean diffusion (MD), were calculated by diffusion kurtosis estimator software. After registration, patient groups with FA mappings and MD mappings and normal groups were compared with 3dttest and receiver-operating characteristic (ROC) curve analysis, corrected with FDR simulations (p = 0.001, α = 0.05, cluster size = 326). We found that the degree of FA increased in the bilateral head of the caudate nucleus (HCN), lenticular nucleus (LN), ventral thalamus, substantia nigra (SN), red nucleus (RN), right dentate nucleus (DN), and decreased in the mediodorsal thalamus and extensive white matter. The value of MD increased in HCN, LN, SN, RN, and extensive white matter. The technique of DTI provides higher sensitivity and specificity than conventional MRI to detect Wilson's disease. Besides, lesions in the basal ganglia, thalamus, and cerebellum might disconnect the basal ganglia-thalamo-cortical circuits or dentato-rubro-thalamic (DRT) track and disrupt cerebello-thalamo-cortical network finally, which may cause clinical extrapyramidal symptoms.

Evaluation of the fetal cerebellum by magnetic resonance imaging. / Valoración del cerebelo fetal mediante resonancia magnética.

Obstetric protocols dictate that the fetal cerebellum should always be assessed during sonograms during pregnancy. For various reasons, including technical limitations or inconclusive sonographic findings, suspicion of cerebellar abnormalities is one of the most common indications for prenatal magnetic resonance imaging (MRI). Although sonography is the imaging technique of choice to assess the cerebellum, MRI shows the anatomy of the posterior fossa and abnormalities in the development of the fetal cerebellum in greater detail and thus enables a more accurate prenatal diagnosis. We describe and illustrate the normal anatomy of the fetal cerebellum on MRI as well as the different diseases that can affect its development. Moreover, we review the most appropriate terminology to define developmental abnormalities, their differential diagnoses, and the role of MRI in the prenatal evaluation of the posterior fossa.

Regional volumetric assessment of the brain in moderately preterm infants (30-35 gestational weeks) scanned at term-equivalent age on magnetic resonance imaging.

BACKGROUND: Early volume analyses of the infantile brain may help predict neurodevelopmental outcome. However, brain volumes are not well understood in moderately preterm infants at term-equivalent age (TEA). AIM: This study retrospectively investigated the relationship between regional brain volumes and infant gestational age (GA) at birth in moderately preterm infants (30-35weeks' GA) on magnetic resonance imaging (MRI) at TEA. METHODS: Forty infants scanned at TEA were enrolled. Regional brain volumes were estimated by manual segmentation on MRI, and their relationship with GA at birth was assessed. RESULTS: The regional volumes of the cerebral hemispheres and deep gray matter were larger (Spearman ρ=0.40, P=0.01, and Spearman ρ=0.48, P<0.01, respectively), and volumes of the lateral ventricles were smaller (Spearman ρ=-0.32, P=0.04) in infants born at a later GA. The volumes of the cerebral hemispheres of the infants born at 30weeks' GA were significantly smaller than those born at 33 and 35weeks' GA (P<0.05). No associations were found between the volume of the cerebellum and brainstem, and GA at birth (Spearman ρ=0.24, P=0.13, and Spearman ρ=0.24, P=0.14, respectively). CONCLUSIONS: The volumes of the cerebral hemispheres at TEA may be smaller in infants born at 30weeks' GA, whereas those of the cerebellum and brainstem may not be correlated with GA among moderately preterm infants.

Reliability in cerebellar size assessment by 2D cranial ultrasonography in neonates.

BACKGROUND: Cerebellar size appears to be correlated with the long-term outcome of preterm infants. Two-dimensional cranial ultrasonography (2D-cUS) is the first-line, routine tool to characterize newborn cerebral structures. Information regarding the accuracy of 2D-cUS for assessing cerebellar size is scarce. OBJECTIVES: To assess the reliability of cerebellar size using 2D-cUS. METHODS: Fifty infants were prospectively scanned for a variety of clinical indications. The scans were stored and then independently analyzed offline by two observers. The transverse cerebellar diameter coronally from the anterior and mastoid fontanels (TCD-AF and TCD-MF, respectively); the midsagittal cerebellar vermis height and the anterior-posterior diameter from the AF; and the width and height of the fourth ventricle coronally from the MF view were measured. Interobserver variability was assessed using the intraclass correlation (ICC) with 95% confidence interval (CI) for each of the paired measures. RESULTS: A total 294 images were included in the analysis. The interobserver ICCs were TCD-AF = 0.85 (0.76-0.91), TCD-MF = 0.9 (0.83-0.94), vermis height = 0.79 (0.66-0.88), anterior-posterior vermis diameter = 0.71 (0.5-0.84), width of the fourth ventricle = 0.72 (0.33-0.9), height of the fourth ventricle = 0.86 (0.7-0.92). The ICC for the TCD comparing the AF and the MF approach was ≥0.9 for both observers. CONCLUSIONS: The reliability of the offline 2D-cUS cerebellar size assessments is good, and TCD-MF is the most consistent measure. Further studies should address the predictive value for the neurodevelopmental outcome of serial cerebellar size assessments by 2D-cUS for preterm infants.

Case Report: A Comprehensive Neuropsychological Assessment of a Case of Superficial Siderosis.

OBJECTIVE: Superficial siderosis (SS) is a neurodegenerative condition due to the long-term effects of hemosiderin deposition on the surface of the brain, cerebellum, brainstem, and spinal cord. SS symptoms include sensorineural hearing loss, ataxia and upper motor neuron signs. SS was diagnostically evasive until magnetic resonance imaging (MRI) became available. As the detection of SS improved, case studies have become more prevalent. To our knowledge, however, this is the first report of SS detailing a comprehensive neuropsychological assessment. METHOD: The current study presents a right-handed female in her early 60s, with a university level of education, who was diagnosed with SS. RESULTS: Her neuropsychological profile showed impairment across multiple domains, including memory and executive function, with consistent behavioral findings. The results from a comprehensive neuropsychological assessment include dementia and a cerebellar cognitive affective syndrome. CONCLUSIONS: Neuropsychological evaluation of a patient with new cognitive impairment in combination with unexplained hearing loss, gait disorder, or myelopathy should lead to a referral for MRI that includes techniques sensitive for iron deposition, in order to rule out SS.