Repetitive Transcranial Magnetic Stimulation Treatment For Parkinson's

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Parkinson's Disease

Parkinson disease (PD) is a progressive neurodegenerative disorder caused by degradation of dopamine-producing cells in the Substantia Nigra Pars Compacta (Kalia & Lang, 2015). The resulting decrease in dopamine produces motor symptoms characterized by resting tremor, bradykinesia, rigidity, mobilization difficulties, and balance deficits (Chou et al, 2015). In addition to motor symptoms, PD also includes non-motor symptoms including cognitive impairment, depression, hallucinations, autonomic features and sleep problems (Williams-Gray & Worth, 2016). PD affects all races and ethnicities, and it is estimated that 6-10 million people worldwide are afflicted by the disease (Chou et al, 2015). Kalia & Lang (2015) report that the incidence of Parkinson’s disease ranges from 10–18 per 100 000 person-years, and increases rapidly with age, affecting approximately 2-3% of the population older than 65 years of age. Clinical Diagnosis of PD is based on the presence of typical parkisonian motor symptoms, including bradykinesia plus rigidity and resting tremor (Kalia & Lang, 2015). Current medical therapy for PD only treats the symptoms of the disease, and primarily consists of medications which slow or stop the underlying neurodegenerative process (Kalia & Lang, 2015). However it is reported that most patients develop complications after 5 years, including dyskinesia and motor fluctuations (Williams-Gray & Worth, 2016). Novel treatments of PD have been emerging over the past decades, including Transcranial Magnetic Stimulation (TMS) which has generated interest as a potential therapeutic intervention (Chou et al, 2015).

Transcranial Magnetic Stimulation (TMS)

Transcranial magnetic stimulation (TMS) was developed in 1985 by Barker and colleagues which allowed them to non-invasively stimulate areas of the human cortex of the brain (Barker et al. 1985). Since then, this technology has developed to find a place in both clinical research and treatment of various populations such as those experiencing mood (REFs) or movement disorders (REFs). This modality is comprised of numerous conductive wires wrapped together into a circular coil within a hard plastic housing. By passing a brief electric pulse through these coil windings, a magnetic field is generated perpendicular to the coil which passes relatively unimpeded through the scalp and skull when placed on the head. This magnetic pulse, by the principles of electromagnetism, produce secondary electric fields in the opposite direction to the field generated by the coil (Figure 1.) (Barker et al. 1985; Hallett et al. 2000; 2007; Siebner & Rothwell, 2003). It is these secondary fields that influence any conductive material or tissue in the path of the magnetic field. In this case, that conductive tissue is neurons within the cortex of the brain. Using the above phenomenon, TMS can be used to stimulate or excite regions of the cortex to probe the function of various brain regions and their interactions (Siebner & Rothwell, 2003; Chou et al. 2005; Rossini et al. 2015).

Types of TMS

1. Single pulse TMS can be used to simply stimulate a given area while recording the output and is commonly used in research where an area such as the motor cortex is stimulated and a motor response can be recorded from muscles of the body via electromyography (Hallett, 2000; Siebner & Rothwell, 2003).
2. Paired-pulse TMS can be used to assess the effect of a preceding stimulus on a secondary stimulus (Chen et al. 2004). While this technique is also primarily used in research, it allows for the assessment of one brain region on another. For example, a TMS pulse delivered to the motor cortex of one hemisphere of the brain 10ms prior to a TMS pulse delivered over the opposite motor cortex results in an inhibitory effect in motor output to the arms, showing firing patterns that allow for unimanual control of the upper limbs (Ni et al. 2009; Ferbert et al. 1992).
3. Repetitive TMS (rTMS) techniques involve stringing a large number of consecutive TMS pulses together in rapid succession. This method is used both in research and clinically as it can produce changes in cortical activity that last beyond the duration of the TMS protocol (Chou et al. 2005; Rossini et al. 2015; Ishikawa et al. 2007; Wook-Chung et al. 2016), with some reports demonstrating excitability changes persisting for a number of hours (Huang et al. 2005). The rate of pulse delivery appears to dictate the effect of the rTMS protocol, whereas those that deliver pulses at rates of >5Hz (high frequency rTMS) tend to produce excitatory effects and those delivered at rates of < 2Hz (low frequency rTMS) tend to produce inhibitory effects in the brain (Rossini et al. 2015). These rTMS techniques have been approved as a treatment modality for those with non-responsive major depression disorder (MDD) in Canada (Downar et al. 2016). While the use of rTMS has not yet been approved for clinical use in the treatment of movement disorders such as stroke, spinal cord injury, multiple sclerosis, and Parkinson’s disease, the scientific literature suggests that it may provide some benefit to both motor and cognitive symptoms in these populations (REFs).