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Funded Studies

The role of White Matter Pathology in the development of the Postural Instability and Gait Disturbance (PIGD) type of Parkinson's disease (PD)-1

Objective/Rationale:
It is not clear why a subset of patients with Parkinson's disease develop postural instability and gait disturbances (PIGD), while others do not. White matter (WM) changes that may sometimes reflect subtle alterations in brain structure and function are known to contribute to PIGD-like symptoms in older adults and in other patient groups. The relationship between WM changes and PIGD symptoms in PD has not been well-studied. The overall objective of the present proposal is to evaluate if WM changes contribute to PIGD symptoms in PD.
Project Description:
PD patients with PIGD will be compared to PD patients who do not share these symptoms, e.g., patients whose primary symptom is tremor. This case-control comparison will be supplemented by the evaluation of within group associations between PIGD symptoms, measures of WM and dopamine network pathology. All study participants will undergo testing including: a) A comprehensive evaluation of PIGD-symptoms using balance, gait, and neurological testing as well as assessment of cognitive and autonomic function; and b) MRI-based evaluation of brain WM integrity. The two groups will be compared with respect to brain WM burden using volumetric methods and more sensitive techniques such as diffusion tensor imaging and diffusion-weighted. These findings will be used to develop statistical models that identify biomarkers and predict the development and severity of PIGD.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The proposed study of patients with PIGD-PD is designed to provide invaluable insight into the pathways, pathological and neurological substrates that contribute to PIGD, a frequent cause of disability and reduced quality of life among many patients with PD. Evidence in support of the role of occult white matter pathology will help guide diagnostic, prognostic and intervention studies, and prepare the ground work for prevention and therapeutic intervention trials that specifically address the generally intractable symptoms of PIGD.
Anticipated Outcome:
We anticipate quantifying the degree to which WM changes contribute to PIGD symptoms in PD. The proposed study should also generate data that will improve the objective identification of patients with PIGD and that will enhance the understanding and treatment of these otherwise intractable parkinsonian symptoms.

Progress Report

The overall objective of the present work is to evaluate, for the first time, if white matter (WM) changes contribute to PIGD symptoms among patients with Parkinson's disease (PD). A key aim is to compare brain WM burden using MRI in PD patients with and without PIGD using volumetric methods and more sensitive diffusion tensor imaging (DTI) analysis techniques to enable visualization and quantification of WM tracts (e.g., lesions and lacunar infarcts). We hypothesize greater WM changes in PIGD-PD patients compared to PD patients who do not have prominent PIGD symptoms. To quantify the association between MRI findings and PIGD symptoms, participating patients undergo a battery of tests that evaluate motor symptoms (e.g., gait and balance), cognition, olfaction, cerebro-vascular disease, and other symptoms. To date, 44 PD patients have been studied. The planned work on a much larger cohort is needed to evaluate the results and understand their implications.

Final Outcome

We characterized the clinical differences between patients with Parkinson's disease (PD) who have gait disturbances and balance problems (PIGD) and patients with considerable tremor (TD) in order to identify the neural mechanisms that contribute to these two sub-types. Magnetic resonance imaging (MRI) was used to determine group differences in brain networks and white matter fibers. We hypothesized that there will be greater white matter abnormalities in the PIGD patients. Patients in the PIGD group walked more slowly, with shorter steps, greater fear of falling, and performed worse on challenging conditions. The PIGD patients were more unstable while walking and fell more often (3 fold higher fall risk in prospective follow-up). In contrast to our hypothesis, we found that the white matter abnormalities apparently do no provide the explanation for the different PD sub-types. However, other MRI findings are consistent with the possibility that the PIGD patients have exaggerated connectivity of brain networks related to pathological processes, especially in central areas in the brain related to higher-level cognitive function and those related to the integration of sensory and motor inputs.

Presentations & Publications

The below abstracts were accepted for presentation at the:

World Congress of ISPGR (International Society for Posture and Gait Research) and Gait & Mental Function, Norway, June, 2012

 

1. Towards the detection of the neural correlates of Parkinson's disease sub-types using MRI

Rosenberg K2,Herman T1,  Jacob Y2, Giladi N 1,3 , Hendler T,2,3, Hausdorff J.M.1,3,4

 

1) Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. 2) Functional Brain Imaging Unit, Wohl Institute for Advanced Imaging,Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. 3) Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 4)Harvard Medical School, Boston, MA, USA.

 

2. Do the sub-types of Parkinson's Disease patients respond differently to challenging walking conditions?

Herman T1 ,Weiss A1, Brozgol M1 , Giladi N 1,2   Hausdorff JM1,2,3

1) Laboratory for Gait & Neurodynamics, Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.  2) Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 3) Harvard Medical School, Boston, MA, USA.

 

3. Performance of alternating hand tapping and its relation to gait and postural disturbances in Parkinson's disease

Talia Herman1, Hagar Bernad1, Marina Brozgol1, Nir Giladi1,2, Jeffrey M. Hausdorff1,3,4, Meir Plotnik1

1Laboratory for Gait and Neurodynamics, Movement Disorders Unit, Dept Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel;  2Dept Neurology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Isarel;  3Dept Physical Therapy, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Isarel;  4Dept of Medicine, Harvard Medical School, Boston, MA, USA

 

The below abstract was presented at the:

6th Posture Symposium, September 2011, Smolenice, Slovakia

Characterization of Parkinson’s disease subtypes using an accelerometer-based postural analysis: a clustering approach

1L. Rocchi, 1L. Palmerini, 2A. Weiss,  1G. Ganesan, 1L. Chiari, 2T. Herman, 2J.M. Hausdorff

1Dept. Electronics Computer Science & Systems, University of Bologna Italy

2Laboratory for Gait and Neurodynamics, Movement Disorders Unit, Department of Neurology, Tel Aviv Sourasky  Medical Center, Israel



Researchers

  • Jeffrey M. Hausdorff, PhD

    Tel Aviv Israel


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