Neuropathic pain is a broad term that encompasses symptoms resulting from lesions or dysfunction within the nervous system. It lingers beyond the expected healing period, exhibits symptoms of both positive and negative sensory phenomena and is poorly responsive to traditional analgesics. The more common etiologies include trauma, diabetes, stroke, multiple sclerosis, infections, toxins and cancer. Approximately four million people in the United States are affected each year.
Classification is largely based on etiology, but distinctions can be made based on the central or peripheral location of the lesion, as well as the focality (i.e. the diffuse involvement that occurs with diabetes versus an isolated traumatic lesion).These distinctions are important as they guide treatment to the appropriate target.
As with classification, diagnosis is etiology specific. As an example, central post-stroke pain is characterized by constant or intermittent pain following ischemic or hemorrhagic infarction. Stroke is only one of the multitude of mechanisms leading to a lesion in the central nervous system that can result in pain. Given the subjective and individual nature of the condition, the physician must accurately characterize the patient’s symptomatology using various visual and numeric pain rating scales. This affords a basis to monitor treatment progress.
Focused Ultrasound Treatment
An investigator-sponsored study in the treatment of neuropathic pain was conducted at the University Hospital Zürich (Zürich, Switzerland) using the InSightec ExAblate Transcranial MRgFUS (650KHz) system. In 2008 and 2009, 12 patients with chronic, medication-resistant neuropathic pain underwent selective central lateral thalamotomy (CLT) using the ExAblate Transcranial MRgFUS device. Medication-resistant was the designation given to patients whose pain was not effectively treated by anti-epileptic and anti-depressant analgesic medications.
The site of ablation for each patient was in the posterior part of the thalamic central lateral nucleus. Localization of this target site on MR images was achieved using the Morel atlas of the human thalamus and basal ganglia. Before delivering a therapeutic level of acoustic energy to the target site, confirmation of alignment of the thermal spot within this target site was necessary. Therefore, several sub-threshold sonications (low power, short duration = 10-20s) were performed for which the peak tissue temperature was below the threshold for ablation (45oC) but could still be visualized on MR thermometry images (>38oC). After this targeting confirmation procedure, sequential sonications of incremental acoustic energy levels were applied to the site to induce tissue ablation (peak temperatures of 53 to 60oC).
Professors Daniel Jeanmonod and Ernst Martin published their initial results in the Annals of Neurology (see Bibliography) and presented them at the American Association of Neurological Surgeons annual meeting in Philadelphia in May 2010. They were able to use MRI to demonstrate precise control of FUS energy deposition and temperature during the process of target assessment and lesioning.
The first clinical trial of focused ultrasound for a functional neurosurgical indication was in the treatment of patients with chronic neuropathic pain (see above).
Follow-up studies were conducted at the Center of Ultrasound Functional Neurosurgery‚ Solothurn and the MR Center‚ University Children's Hospital‚ Zurich‚ Switzerland.
Regulatory approval and reimbursement
CE approval in Europe was awarded on the end of 2012 to a MRgFUS device for the indication of Neuropathic pain.
At this stage no other regulatory approval is in place in the USA, Canada and Asia.
At this stage there is no reimbursement anywhere in the world for the usage of Focused Ultrasound as a treatment for Neuropathic pain.
ExAblate Neuro InSightec LTD
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