Quantitative assessment of cerebella ataxia through automated upper limb functional tests

Neurological disorders typically exhibit movement disabilities and disorders such as cerebellar ataxia (CA) can cause coordination inaccuracies often manifested as disabilities associated with gait, balance and speech. Since the severity assessment of the disorder is based on the expert clinical opinion, it is likely to be subjective. Automated versions of two upper limb tests: Finger to Nose test (FNT) and Diadochokinesia (DDK) test are investigated in this paper. Inertial Measurement Units (IMU) (BioKinTM ) are employed to capture the disability by measuring limb movements. Translational and rotational accelerations considered as kinematic parameters provided the features relevant to characteristic movements intrinsic to the disability. Principal Component Analysis (PCA) and multi-class Linear Discriminant classifier (LDA) were instrumental in dominant features correlating with the clinical scores. The relationship between clinicians assessment and the objective analysis is examined using Pearson Correlation. This study found that although FNT predominantly consist of translational movements, rotation was the dominant feature while for the case of DDK that predominantly consist of rotational movements, acceleration was the dominant feature. The degree of correlation in each test was also enhanced by combining the features in different tests

Bilateral vestibulopathy: a clinical update and proposed diagnostic algorithm

Bilateral vestibulopathy (BVP) is characterized by its heterogeneous and chronic nature with various clinical presentations and multiple etiologies. This current narrative review reflects on the main insights and developments regarding clinical presentation. In addition, it proposes a new diagnostic algorithm, and describes available and potential future therapeutic modalities

Quantification of axial abnormality due to cerebellar ataxia with inertial measurements

Cerebellar Ataxia (CA) leads to deficiencies in muscle movement and lack of coordination that is often manifested as gait and balance disabilities. Conventional CA clinical assessments are subjective, cumbersome and provide less insight into the functional capabilities of patients. This cross-sectional study investigates the use of wearable inertial sensors strategically positioned on the front-chest and upper-back locations during the Romberg and Trunk tests for objective assessment of human postural balance due to CA. The primary aim of this paper is to quantify the performance of postural stability of 34 patients diagnosed with CA and 22 healthy subjects as controls. Several forms of entropy descriptions were considered to uncover characteristics of movements intrinsic to CA. Indeed, correlation with clinical observation is vital in ascertaining the validity of the inertial measurements in addition to capturing unique features of movements not typically observed by the practicing clinician. Both of these aspects form an integral part of the underlying objective assessment scheme. Uncertainty in the velocity contained a significant level of information with respect to truncal instability and, based on an extensive clustering and discrimination analysis, fuzzy entropy was identified as an effective measure in characterising the underlying disability. Front-chest measurements demonstrated a strong correlation with clinical assessments while the upper-back measurements performed better in classifying the two cohorts, inferring that the standard clinical assessments are relatively influenced by the frontal observations. The Romberg test was confirmed to be an effective test of neurological diagnosis as well as a potential candidate for objective assessment resulting in a significant correlation with the clinical assessments. In contrast, the Trunk test is observed to be relatively less informative

Quantitative oculomotor assessment in hereditary ataxia: systematic review and consensus by the ataxia global initiative working group on digital-motor biomarkers

Oculomotor deficits are common in hereditary ataxia, but disproportionally neglected in clinical ataxia scales and as outcome measures for interventional trials. Quantitative assessment of oculomotor function has become increasingly available and thus applicable in multicenter trials and offers the opportunity to capture severity and progression of oculomotor impairment in a sensitive and reliable manner. In this consensus paper of the Ataxia Global Initiative Working Group On Digital Oculomotor Biomarkers, based on a systematic literature review, we propose harmonized methodology and measurement parameters for the quantitative assessment of oculomotor function in natural-history studies and clinical trials in hereditary ataxia. MEDLINE was searched for articles reporting on oculomotor/vestibular properties in ataxia patients and a study-tailored quality-assessment was performed. One-hundred-and-seventeen articles reporting on subjects with genetically confirmed (n=1134) or suspected hereditary ataxia (n=198), and degenerative ataxias with sporadic presentation (n=480) were included and subject to data extraction. Based on robust discrimination from controls, correlation with disease-severity, sensitivity to change, and feasibility in international multicenter settings as prerequisite for clinical trials, we prioritize a core-set of five eye-movement types: (i) pursuit eye movements, (ii) saccadic eye movements, (iii) fixation, (iv) eccentric gaze holding, and (v) rotational vestibulo-ocular reflex. We provide detailed guidelines for their acquisition, and recommendations on the quantitative parameters to extract. Limitations include low study quality, heterogeneity in patient populations, and lack of longitudinal studies. Standardization of quantitative oculomotor assessments will facilitate their implementation, interpretation, and validation in clinical trials, and ultimately advance our understanding of the evolution of oculomotor network dysfunction in hereditary ataxias

Bioinformatics-Based Identification of Expanded Repeats: A Non-reference Intronic Pentamer Expansion in RFC1 Causes CANVAS

Genomic technologies such as next-generation sequencing (NGS) are revolutionizing molecular diagnostics and clinical medicine. However, these approaches have proven inefficient at identifying pathogenic repeat expansions. Here, we apply a collection of bioinformatics tools that can be utilized to identify either known or novel expanded repeat sequences in NGS data. We performed genetic studies of a cohort of 35 individuals from 22 families with a clinical diagnosis of cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Analysis of whole-genome sequence (WGS) data with five independent algorithms identified a recessively inherited intronic repeat expansion [(AAGGG)exp] in the gene encoding Replication Factor C1 (RFC1). This motif, not reported in the reference sequence, localized to an Alu element and replaced the reference (AAAAG)11 short tandem repeat. Genetic analyses confirmed the pathogenic expansion in 18 of 22 CANVAS-affected families and identified a core ancestral haplotype, estimated to have arisen in Europe more than twenty-five thousand years ago. WGS of the four RFC1-negative CANVAS-affected families identified plausible variants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type, and SCA45. This study identified the genetic basis of CANVAS and demonstrated that these improved bioinformatics tools increase the diagnostic utility of WGS to determine the genetic basis of a heterogeneous group of clinically overlapping neurogenetic disorders

A novel vestibulo-cerebellar ataxia, Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS): clinical phenotype, pathology, imaging, differential diagnoses and a quantitative bedside test

© 2014 Dr. David Joshua SzmulewiczPatients with combined cerebellar and vestibular impairment were first identified in about 1979 and were studied as a pathophysiological model. The syndrome of Cerebellar Ataxia with Bilateral Vestibulopathy (CABV) and it’s characteristic oculomotor abnormality, that is, the abnormal visually-enhanced vestibulo-ocular reflex (VVOR) was then subsequently described in 2005 in 4 patients, 3 of whom had a peripheral sensory deficit. Here I set out to establish whether these three patients actually had a totally new, so far undescribed, neurological disease. The work in this thesis defines this new neurological disease that is now called ‘CANVAS’: an acronym for Cerebellar Ataxia with Neuropathy and bilateral Vestibular Areflexia Syndrome. This thesis details the (A) clinical presentation and evolution, (B) essential oculomotor and vestibular abnormalities, (C) neuropathology, (D) otopathology, (E) anatomical pattern of cerebellar atrophy, (F) the neurophysiological characteristics of the somatosensory impairment, (G) differential diagnoses, (H) apparent genetic basis and (I) a diagnostic quantitative bedside oculomotor test

Characteristics of assessment and treatment in Benign Paroxysmal Positional Vertigo (BPPV)

QUESTION: Benign Paroxysmal Positional Vertigo (BPPV) is the most common cause of dizziness presenting to specialist vestibular centres and accounts for approximately 20–30% of referrals to these clinics. In spite of the amount of clinical knowledge surrounding its diagnosis and management, the treatment of BPPV remains challenging for even the most experienced clinicians. This study outlines the incidence of BPPV in a specialised vestibular physiotherapy clinics and discusses the various nuances encountered during assessment and treatment of BPPV. DESIGN: Observational Study PARTICIPANTS: 314 patients with various forms of Benign Paroxysmal Positional Vertigo (BPPV) INTERVENTION: Canalith repositioning manoeuvres (CRP) for posterior canal (PC) or horizontal canal (HC) BPPV depending on the canal and variant of BPPV. OUTCOME MEASURES: Negative Dix-Hallpike (DHP) or Supine roll test (SRT) examination. RESULTS: In 91% of cases, PC BPPV was effectively treated in 2 manoeuvres or less. Similarly, 88% of HC BPPV presentations were effectively managed with 2 treatments. Bilateral PC, multiple canal or canal conversions required a greater number of treatments. There was no noticeable difference in treatment outcomes for patients who had nystagmus and symptoms during the Epley manoeuvre (EM) versus those who did not have nystagmus and symptoms throughout the EM. Nineteen percent of patients experienced post treatment down-beating nystagmus (DBN) and vertigo or “otolithic crisis” after the first or even the second consecutive EM. CONCLUSION: Based on the data collected, we make several clinical recommendations for assessment and treatment of BPPV. Firstly, repeated testing and treatment of BPPV within the same session is promoted as a safe and effective approach to the management of BPPV with a low risk of canal conversion. Secondly, vertigo and nystagmus throughout the EM is not indicative of treatment success. Thirdly, clinicians must remain vigilant and mindful of the possibility of post treatment otolithic crisis following the treatment of BPPV. This is to ensure patient safety and to prevent possible injurious falls. Our results challenge several clinical assumptions about the assessment and treatment of BPPV including the utility of certain markers of treatment success; hence influencing the current clinical guidelines and clinical practice and paving the way for future studies of the assessment and management of patients with BPPV