Investigating the Use of Complex Pulse Shapes for DBS in Movement Disorders
Investigating the Use of Complex Pulse Shapes for DBS in Movement Disorders
Parkinson's disease and essential tremor are chronic movement disorders for which there is no
 cure. When medication is no longer effective, deep brain stimulation (DBS) is recommended.
 Standard DBS is a neuromodulation method that uses a simple monophasic pulse, delivered from
 an electrode to stimulate neurons in a target brain area. This monophasic pulse spreads out
 from the electrode creating a broad, electric field that stimulates a large neural
 population. This can often effectively reduce motor symptoms. However, many DBS patients
 experience side effects - caused by stimulation of non-target neurons - and suboptimal
 symptom control - caused by inadequate stimulation of the correct neural target. The ability
 to carefully manipulate the stimulating electric field to target specific neural
 subpopulations could solve these problems and improve patient outcomes. The use of complex
 pulse shapes, specifically biphasic pulses and asymmetric pre-pulses, can control the
 temporal properties of the stimulation field. Evidence suggests that temporal manipulations
 of the stimulation field can exploit biophysical differences in neurons to target specific
 subpopulations. Therefore, our aim is to evaluate the effectiveness of complex pulse shapes
 to reduce side effects and improve symptom control in DBS movement patients.
The study had three stages. In the first stage, a wide range of investigatory pulse shapes in
 a small number of patients. The effect of the pulses on the therapeutic window will be
 assessed.

 Stage 2 will perform a short-term chronic evaluation (30 minutes and if safe, 1 week) in a
 larger number of patients.

 In Parkinson's disease (PD) patients (after 30 minutes):

 - MDS-UPDRS-III (Movement Disorders Society - Unified Parkinson's Disease Rating Scale, part
 III)

 In essential tremor (ET) patients (after 30 minutes):

 - FTM (Fahn Tolosa Marin Tremor Rating Scale)

 In PD patients (after one week):

 -  MDS-UPDRS-III

 -  PDQ-39 (Parkinson's disease questionnaire - 39 items)

 -  NMSS (Non-motor Symptoms Scale)

 In ET patients (after one week):

 -  FTM

 -  QUEST (Questionnaire for Quality of Life in Essential Tremor)

 -  MOCA (Montreal Cognitive Assessment)

 Stage 3 will then focus on long-term evaluation (upto 2 years). The same tests are used as
 after the one-week testing.
Inclusion Criteria for PD:

 -  Diagnosis of idiopathic Parkinson's disease where the diagnosis was made by a Movement
 Disorder Specialist according to the MDS criteria of 2015, with a Hoehn and Yahr scale
 (H&Y) of at least 2 (bilateral involvement).

 -  Onset of the symptoms more than five years ago.

 -  MDS-UPDRS-III score of ≥30 without medication or DBS.

 -  Electrodes are implanted in target area STN.

 Inclusion Criteria for ET:

 -  Patient is diagnosed with essential tremor by a Movement Disorder Specialist.

 -  Diagnosis since more than 3 years.

 -  Patient has a disabling medical-refractory upper extremity tremor without medication
 or DBS.

 -  Patient has a postural or kinetic tremor severity score of at least 3 out of 4 in the
 extremity intended for treatment on the Fahn-Tolosa-Marin Clinical Rating Scale for
 Tremor without medication or DBS.

 -  Electrodes are implanted in target area VIM.

 General Inclusion Criteria:

 -  Post-op the implanted electrodes pass an integrity check, i.e. no open or shorted
 electrodes.

 -  Stable medications

 -  Lack of dementia or depression.

 -  Patient is willing and able to comply with all visits and study related procedures

 -  Patient understands the study requirements and the treatment procedures and provides
 written informed consent before any study-specific tests or procedures are performed.

 -  Patient can tolerate at least 12 hours OFF medication and per clinical judgement be
 able to perform all study related procedures

 Exclusion Criteria:

 -  Any significant psychiatric problems, including unrelated clinically significant
 depression.

 -  Any current drug or alcohol abuse.

 -  Any history of recurrent or unprovoked seizures.

 -  Have any significant medical condition that is likely to interfere with study
 procedures or likely to confound evaluation of study endpoints, including any terminal
 illness with survival <12 months.