Compensatory cerebellar activation during fluid intelligence processing following mild traumatic brain injury.

Cognitive outcome following mild traumatic brain injury (mTBI) vary widely, with many individuals experiencing long-term impairments associated with frontoparietal network dysfunction. Mild TBI patients have demonstrated functional reorganization, suggesting an expansion of activation to cerebellar regions during specific executive functions. In this study, we investigated cerebellar involvement in fluid intelligence processing using a novel fMRI paradigm based on Raven's Progressive Matrices in 51 acute mTBI patients and 61 healthy controls.

The Cerebellar Cognitive Affective/Schmahmann Syndrome Scale: Updates and Insights.

The Cerebellar Cognitive Affective / Schmahmann Syndrome scale (CCAS-S) detects cognitive and neuropsychiatric changes in cerebellar disease (CD). It has good sensitivity and specificity, but a false positive rate ~ 5%. We determined that healthy controls (HC) fail digit span tasks (DS) when presented with one repetition opportunity.

The Natural History Study and Biomarker Collection of the Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA).

Hereditary ataxias are progressive neurodegenerative disorders primarily affecting the cerebellum. Since 2009, the Clinical Research Consortium for the Study of Cerebellar Ataxias (CRC-SCA) has studied the natural history of common types of spinocerebellar ataxias (SCAs). The CRC-SCA is a 17-site academic collaboration supported by the National Ataxia Foundation.

Spinocerebellar Ataxia Type 27B can be Suspected Based on Clinical Phenotype: The Massachusetts General Hospital Ataxia Center Experience.

Spinocerebellar Ataxia type 27B (SCA27B) is caused by an intronic GAA repeat expansion in the fibroblast growth factor 14 (FGF14) gene. The core clinical phenotype is a slowly progressive, adult-onset cerebellar ataxia, often with downbeat nystagmus (DBN) and episodic worsening. We tested whether clinical phenotyping could predict this genetic disorder.

Progression of biological markers in spinocerebellar ataxia type 3: longitudinal analysis of prospective data from the ESMI cohort.

Background: Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominantly inherited adult-onset disease. We aimed to describe longitudinal changes in clinical and biological findings and to identify predictors for clinical progression.

Methods: We used data from participants enrolled in the ESMI cohort collected between Nov 09, 2016 and July 18, 2023.

The Cerebellar Neuropsychiatric Rating Scale in the Spinocerebellar Ataxias.

There is currently no established screening instrument that detects neuropsychiatric features in individuals with cerebellar ataxia. We hypothesized that the Cerebellar Neuropsychiatric Rating Scale (CNRS) would capture the neuropsychiatry of patients enrolled in the natural history study of the Clinical Research Consortium for the Study of Cerebellar Ataxia, and provide novel insights not revealed by other measures. We studied CNRS data in 362 patients with spinocerebellar ataxia types 1, 2, 3, 6, 7, 8, 10, and 27B, and cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS).

At-home wearables and machine learning capture motor impairment and progression in adult ataxias.

A significant barrier to developing disease-modifying therapies for spinocerebellar ataxias (SCAs) and multiple system atrophy of the cerebellar type (MSA-C) is the scarcity of tools to sensitively measure disease progression in clinical trials. Wearable sensors worn continuously during natural behavior at home have the potential to produce ecologically valid and precise measures of motor function by leveraging frequent and numerous high-resolution samples of behavior. Here we test whether movement-building block characteristics (i.

Validation of the Spanish version of the cerebellar cognitive-affective syndrome scale.

 To validate the Spanish version of the Cerebellar Cognitive-Affective Syndrome scale (CCAS-S), originally published in 2018, in patients with cerebellar ataxia and healthy subjects, as an adapted Spanish version based on normative data has not yet been published or validated.  Spanish CCAS-S was -administered prospectively to 158 patients with cerebellar ataxia and 164 matched healthy subjects from -different regions of Spain. Discriminant validity and reliability were evaluated.

Contrastive Learning Model for Wearable-based Ataxia Assessment.

Objective: Frequent and objective assessment of ataxia severity is essential for tracking disease progression and evaluating the effectiveness of potential treatments. Wearable-based assessments have emerged as a promising solution. However, existing methods rely on inertial data features directly correlated with subjective and coarse clinician-evaluated rating scales, which serve as imperfect gold standards.

Spinocerebellar Ataxia Progression Measured with the Patient-Reported Outcome Measure of Ataxia.

Background: The Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia) has been validated cross-sectionally but not longitudinally.

Objective: We aimed to validate PROM-Ataxia as a measure of patient experience of disease over time, examine overall and domain-specific progression, and test convergent validity with other clinical outcome assessments (COAs).

Methods: We derived PROM-Ataxia data from 176 patients with spinocerebellar ataxia types 1, 2, 3, 6, 7, 8, or 10 in the Clinical Research Consortium for the Study of Cerebellar Ataxia at baseline and 1 year.

The Cerebellar Neuropsychiatric Rating Scale.

The triad of cerebellar ataxiology is the cerebellar motor, vestibular, and cerebellar cognitive affective / Schmahmann syndrome (CCAS). The CCAS affective component comprises 5 domains: Attentional control, Emotional control, Autism spectrum, Psychosis spectrum, and Social Skill Set, each with hypermetric / overshoot and hypometric / undershoot poles reflecting the dysmetria of thought and universal cerebellar transform theories. There is no validated screening instrument to assess neuropsychiatric impairments in patients with cerebellar disorders.

Progression of biological markers in spinocerebellar ataxia type 3: analysis of longitudinal data from the ESMI cohort.

Background: Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominantly inherited adult-onset disease. We aimed to describe longitudinal changes in clinical and biological findings and to identify predictors for clinical progression.

Methods: We used data from participants enrolled in the ESMI cohort collected between Nov 09, 2016 and July 18, 2023.

Multimodal Digital Phenotyping of Behavior in a Neurology Clinic: Development of the Neurobooth Platform and the First Two Years of Data Collection.

Quantitative analysis of human behavior is critical for objective characterization of neurological phenotypes, early detection of neurodegenerative diseases, and development of more sensitive measures of disease progression to support clinical trials and translation of new therapies into clinical practice. Sophisticated computational modeling can support these objectives, but requires large, information-rich data sets. This work introduces Neurobooth, a customizable platform for time-synchronized multimodal capture of human behavior.

Brainstem Substructure Atrophy in Late-Onset GM2-Gangliosidosis Imaging Using Automated Segmentation.

Late-Onset GM2-Gangliosidoses (LOGG) are rare, neurodegenerative lysosomal disorders that include late-onset Tay-Sachs (LOTS) and Sandhoff disease (LOSD) subtypes. Cerebellar atrophy is common, even in the absence of clinical ataxia, particularly in LOTS. Recent reports have also described brainstem atrophy in LOTS.

Longitudinal Changes in Patient- and Clinical-Reported Outcomes in Early Spinocerebellar Ataxia Types 1, 2, 3, and 6 from the IDEA Study.

Background: Clinical outcomes assessments (COAs) in spinocerebellar ataxia (SCA) need to be standardized, ataxia-specific, sensitive to change, clinically relevant, and meaningful to patients.

Objectives: To evaluate the longitudinal 1- and 2-year performances of different patient reported outcomes, including the Patient Reported Outcome Measure of Ataxia (PROM-Ataxia), and clinician reported outcomes, including FARS and SARA, in those with early manifest symptoms of SCA 1, 2, 3, and 6.

Methods: We studied 53 patients with early stage SCA1-3 and SCA6 from The Instrumented Data Exchange for Ataxia Study and 24 age-matched healthy controls.

A digital measure of eye movements during reading sensitively captures oculomotor and speech dysfunction, early changes, and disease progression in ataxias.

Objective: Sensitive behavioral measures are needed for clinical trials in ataxias and other neurodegenerative diseases. We hypothesized that quantitative analysis of eye movements during a natural multi-component task (passage reading) could produce a measure capable of capturing subclinical signs and disease progression.

Methods: Binocular gaze sampled at 1000 Hz was collected from 102 individuals with ataxia (including 36 spinocerebellar ataxias, 12 Friedreich's ataxia, and 5 multiple system atrophy) and 70 healthy controls.

Azygos Vein Stenosis in Frontotemporal Dementia Sagging Brain Syndrome.

Background And Purpose: Symptoms indistinguishable from behavioral-variant frontotemporal dementia (bvFTD) can develop in patients with spontaneous intracranial hypotension associated with severe brain sagging. An underlying spinal CSF leak can be identified in only a minority of these patients and the success rate of nondirected treatments, such as epidural blood patching and dural reduction surgery, is low. The disability associated with bvFTD sagging brain syndrome is high and, because of the importance of the venous system in the pathophysiology of CSF leaks in general, we have investigated the systemic venous circulation in those patients with recalcitrant symptoms.

Content Validity of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia.

Introduction: The Friedreich Ataxia Rating Scale-Activities of Daily Living (FARS-ADL) is a validated and highly utilized measure for evaluating patients with Friedreich Ataxia. While construct validity of FARS-ADL has been shown for spinocerebellar ataxia (SCA), content validity has not been established.

Methods: Individuals with SCA1 or SCA3 (n = 7) and healthcare professionals (HCPs) with SCA expertise (n = 8) participated in qualitative interviews evaluating the relevance, clarity, and clinical meaningfulness of FARS-ADL for assessment of individuals with SCA.

Sensitive Quantification of Cerebellar Speech Abnormalities Using Deep Learning Models.

Objective, sensitive, and meaningful disease assessments are critical to support clinical trials and clinical care. Speech changes are one of the earliest and most evident manifestations of cerebellar ataxias. This work aims to develop models that can accurately identify and quantify clinical signs of ataxic speech.

At-home wearables and machine learning capture motor impairment and progression in adult ataxias.

A significant barrier to developing disease-modifying therapies for spinocerebellar ataxias (SCAs) and multiple system atrophy of the cerebellar type (MSA-C) is the scarcity of tools to sensitively measure disease progression in clinical trials. Wearable sensors worn continuously during natural behavior at home have the potential to produce ecologically valid and precise measures of motor function by leveraging frequent and numerous high-resolution samples of behavior. Here we test whether movement-building block characteristics (i.

The Human Cerebellum: A Digital Anatomical Atlas at the Level of Individual Folia.

Scientific interest in the cerebellum has surged in the last few decades with an emerging consensus on a multifaceted functionality and intricate, but not yet fully understood, functional topography over the cerebellar cortex. To further refine this structure-function relationship and quantify its inter-subject variability, a high-resolution digital anatomical atlas is fundamental. Using a combination of manual labeling and image processing, we turned a recently published reconstruction of the human cerebellum, the first such reconstruction fine enough to resolve the individual folia, into a digital atlas with both surface and volumetric representations.

Structural covariation between cerebellum and neocortex intrinsic structural covariation links cerebellum subregions to the cerebral cortex.

The human cerebellum is increasingly recognized to be involved in nonmotor and higher-order cognitive functions. Yet, its ties with the entire cerebral cortex have not been holistically studied in a whole brain exploration with a unified analytical framework. Here, we characterized dissociable cortical-cerebellar structural covariation patterns based on regional gray matter volume (GMV) across the brain in = 38,527 UK Biobank participants.

Physical Therapy and Aminopyridine for Downbeat Nystagmus Syndrome: A Case Report.

Background And Purpose: Individuals with downbeat nystagmus (DBN) syndrome present with DBN, dizziness, blurred vision, and unsteady gait. Pharmacological intervention with 4-aminopyridine (4-AP) may be effective in improving oculomotor function, but there is minimal evidence to date that it improves gait. This suggests the possible benefit of combining pharmacotherapy with physical therapy to maximize outcomes.