Multiple step pattern as a biomarker in Parkinson disease

Abstract

Objective To evaluate quantitative measures of saccades as possible biomarkers in early stages of Parkinson disease (PD) and in a population at-risk for PD. Methods The study sample (n = 68) included mildly to moderately affected PD patients, their unaffected siblings, and control individuals. All participants completed a clinical evaluation by a movement disorder neurologist. Genotyping of the G2019S mutation in the LRRK2 gene was performed in the PD patients and their unaffected siblings. A high resolution, video-based eye tracking system was employed to record eye positions during a battery of visually guided, anti-saccadic (AS), and two memory-guided (MG) tasks. Saccade measures (latency, velocity, gain, error rate, and multiple step pattern) were quantified. Results PD patients and a subgroup of their unaffected siblings had an abnormally high incidence of multiple step patterns (MSP) and reduced gain of saccades as compared with controls. The abnormalities were most pronounced in the more challenging version of the MG task. For this task, the MSP measure demonstrated good sensitivity (87%) and excellent specificity (96%) in the ability to discriminate PD patients from controls. PD patients and their siblings also made more errors in the AS task. Conclusions Abnormalities in eye movement measures appear to be sensitive and specific measures in PD patients as well as a subset of those at-risk for PD. The inclusion of quantitative laboratory testing of saccadic movements may increase the sensitivity of the neurological examination to identify individuals who are at greater risk for PD.

The role of dentate nuclei in human oculomotor control: insights from cerebrotendinous xanthomatosis

“…; Blekher et al . ), but also in healthy subjects. Multistep saccades with shorter latencies than single‐step saccades have been observed in young subjects, possibly reflecting an immature development of cortical frontal areas that inhibit subcortical saccade‐generating structures (van Donkelaar et al .…”

“…Also, all CTX patients made more multistep saccades and significantly more directional errors than normal in the antisaccade task. Abnormally frequent or fragmented multistep saccades may occur in neurodegenerative diseases (Optican et al 2008;Blekher et al 2009), but also in healthy subjects. Multistep saccades with shorter latencies than single-step saccades have been observed in young subjects, possibly reflecting an immature development of cortical frontal areas that inhibit subcortical saccade-generating structures (van Donkelaar et al 2007).…”

“…; Blekher et al . ) we analysed the rate and characteristics of the steps composing such movements. We measured the global and regional brain atrophy volumes in both groups through a quantitative MRI assessment and correlated these volumes with the abnormal saccadic parameters, because neurodegeneration in CTX extends to other brain areas involved in oculomotor control, especially the frontal cortex.…”

“…Results were related to the presence or absence of DN involvement and compared with those of a matching group of 19 healthy subjects. Moreover, since multistep saccades have been proposed as a marker of basal ganglia and/or cerebellar impairment (Optican et al 2008;Blekher et al 2009) we analysed the rate and characteristics of the steps composing such movements. We measured the global and regional brain atrophy volumes in both groups through a quantitative MRI assessment and correlated these volumes with the abnormal saccadic parameters, because neurodegeneration in CTX extends to other brain areas involved in oculomotor control, especially the frontal cortex.…”

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

“…The combination of smell loss or RBD with DAT imaging has already been successfully used to identify groups of individuals with increased risk of developing PD (Ponsen et al, 2004;Stiasny-Kolster et al, 2005). These observations have led to the development of an extensive clinical effort called the PARS to generate a strategy that could help detect parkinsonism in a cohort of 30 000 first-degree relatives of PD patients using combined changes in olfaction and DAT imaging as biomarkers (Stern, 2004;Siderowf and Stern, 2006;Blekher et al, 2009;Marek and Jennings, 2009). Longitudinal clinical and imaging evaluations will help assess the progression of deficits and the state of DAT imaging in these individuals, and determine if these changes predict the eventual development of PD signs in a subset of patients.…”