2 The condition, current treatments, unmet need and procedure

2 The condition, current treatments, unmet need and procedure

The condition

2.1

Parkinson's is a progressive neurodegenerative condition that damages the brain over many years. It is caused by a loss of the cells in the brain that produce dopamine, which helps to control and coordinate body movements. People with Parkinson's classically present with the symptoms and signs described as 'parkinsonism': these include bradykinesia (slow movements), rigidity, rest tremor (shaking) and postural instability (loss of balance). In later stages of Parkinson's, other symptoms sometimes described as the 'non-motor' manifestations of Parkinson's such as depression, cognitive impairment, dementia and autonomic disturbances may be prominent. The condition may progress to cause significant impairments, adversely affecting quality of life and, indirectly, the quality of life of family and carers.

Current treatments

2.2

For people with early Parkinson's, drug treatments such as levodopa, other dopamine agonists and monoamine oxidase B inhibitors may be considered. In the later stages, other drugs may be used with levodopa (as adjuvants) to reduce the motor complications associated with prolonged levodopa use. Non-pharmacological management such as physiotherapy, occupational therapy and speech and language therapy may be considered. Invasive surgical procedures may be considered for people with Parkinson's that is refractory to medical and supportive therapies. These include deep brain stimulation and, less commonly, radiofrequency thalamotomy. Treatments for non-motor symptoms such as sleep disturbance and depression may also be considered.

Unmet need

2.3

MRI-guided focused ultrasound thalamotomy is a minimally invasive procedure that may benefit a subgroup of people who do not want the risks of more invasive brain surgery (that is, deep brain stimulation or radiofrequency thalamotomy), or when brain surgery is not an option, especially in older and more frail people.

The procedure

2.4

This outpatient procedure is done with the patient lying supine inside an MRI scanner for several hours. The person's head is shaved, and a stereotactic head frame is attached. The person is usually kept awake during the procedure so they can be regularly assessed by the treating physician to evaluate the clinical response (report any improvement of symptoms or adverse events). Some people may be offered light sedation.

2.5

Real-time MRI guidance and thermal mapping are used to identify the target area of the brain (the thalamic nucleus) precisely, and monitor treatment. Low-power ultrasound is delivered to confirm the chosen location. Then, several high-power focused ultrasound pulses are delivered to ablate target tissue in the thalamus. The energy released and the location of the ultrasound focus are monitored in real time during the procedure by MRI thermometry, and adjusted to reach above the definitive ablation temperature (of 55°C) according to clinical response. Chilled water is circulated around the head during the treatment to prevent thermal damage to the scalp caused by the increase in bone temperature. The procedure is considered finished when there is sufficient clinical improvement, considering the total amount of energy delivered and the number of sonications. The procedure takes about 2 hours and symptom relief should be immediate.