Movement Disorders

Movement disorders are the 3rd most common cause of disability worldwide. Such disorders can be classified according to their clinical manifestations and prevalence as:

  • Parkinson’s disease and Multiple System Atrophy — Parkinson’s disease (PD) and Multiple system Atrophy (MSA) are part of a group of motor disorders generally defined as Parkinsonism. They are slowly progressing, neurodegenerative diseases which result from the loss of dopamine-producing brain cells.
  • Dystonia — Dystonia is a neurological condition with a very broad range of manifestations. The basic underlying problem involves over-activity of the main muscles needed for a movement, extra activation of other muscles that are not needed for the movement, and simultaneous activation of muscles that work against each other.
  • Restless Leg Syndrome: Restless Leg Syndrome (RLS) is often an unpleasant feeling in the legs that improves somewhat with moving them. Occasionally the arms may also be affected.

Although clinically different, such pathologies share common symptoms such as motor symptoms alterations and impairments of the quality life such as sleep alterations or autonomic system dysregulation (dysautonomia).

 

Motor Symptoms

The clinical manifestations are mainly tremor and motor coordination. Animal models are used to measure tremors using electromyography (EMG). Recently, a research group was able to characterize the bilateral hind limb EMG frequency and amplitudes components in a mouse model of dystonia.

Non-Motor Symptoms

Impairments of the autonomous system or sleep architecture are considered very important because they occur prior to any manifestation of motor symptoms. The autonomic impairment can be quantified by measuring blood pressure, heart rate variability (HRV) and changes during the sleep REM stage; these changes are used as markers in clinics for diagnosis of the disease.

In animal models for PD, MSA, and RLS, changes during HRV or REM states have also proven to be important endpoints for early disease detection and for disease progression.

Therefore, further characterization of the disease through studying these biomarkers could lead to drug optimization and early detection of the disease.

Shared symptoms/parameters include

  • Autonomic nervous system dysregulation1-3 at the level of the heart, e.g. heart rate variability (HRV) changes (HRV)
  • Aberrant EEG patterns in sleep stages4 (changes in frequency component/sleep deprivation) (Sleep)
  • Changes at EMG power and frequencies5(EMG)

 

Selected Publications

  1. Haensch, C. A., Lerch, H., Jorg, J. & Isenmann, S. Cardiac denervation occurs independent of orthostatic hypotension and impaired heart rate variability in Parkinson's disease. Parkinsonism Relat Disord 15, 134-137, doi:10.1016/j.parkreldis.2008.04.031 (2009).
  2. Kuzdas, D. et al. Oligodendroglial alpha-synucleinopathy and MSA-like cardiovascular autonomic failure: experimental evidence. Exp Neurol 247, 531-536, doi:10.1016/j.expneurol.2013.02.002 (2013).
  3. Fleming, S. M. Cardiovascular autonomic dysfunction in animal models of Parkinson's disease. J Parkinsons Dis 1, 321-327, doi:10.3233/JPD-2011-11042 (2011).
  4. Verhave, P. S. et al. REM sleep behavior disorder in the marmoset MPTP model of early Parkinson disease. Sleep 34, 1119-1125, doi:10.5665/SLEEP.1174 (2011).
  5. DeAndrade, M. P. et al. Electromyographic evidence in support of a knock-in mouse model of DYT1 Dystonia. Mov Disord 31, 1633-1639, doi:10.1002/mds.26677 (2016).