Background
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. Severe pain can be extensively disabling, resulting in poor quality of life, severe depression and even suicide. 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. The painful sensations generally occur within a larger area of sensory impairment. 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. Mediciation-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.
Clinical Trials
The first clinical trial of focused ultrasound for a functional neurosurgical indication was in the treatment of patients with chronic neuropathic pain (see above). After analysis of the first 12 patients is complete, the team in Zürich is planning to initiate the next phase of clinical studies.
Accrual for the next phase of clinical studies in Zürich is expected to commence in late 2010 or early 2011.
Equipment Manufacturer
ExAblate Neuro InSightec LTD
http://www.insightec.com/ExAblate-Neuro.html
http://www.insightec.com/Neuropathic_Pain.html
Notable Papers
1. ab Ithel Davies I, Gavrilov LR, Tsirulnikov EM: Application of focused ultrasound for research on pain. Pain 67:17-27, 1996
2. Baker KG, Robertson VJ, Duck FA: A Review of Therapeutic Ultrasound: Biophysical Effects. PHYS THER 81:1351-1358, 2001
3. Bradley WG, Jr.: MR-guided focused ultrasound: a potentially disruptive technology. J Am Coll Radiol 6:510-513, 2009
4. Colucci V, Strichartz G, Jolesz F, Vykhodtseva N, Hynynen K: Focused Ultrasound Effects on Nerve Action Potential in vitro. Ultrasound Med Biol, 2009
5. Gavrilov LR, Tsirulnikov EM, Davies IA: Application of focused ultrasound for the stimulation of neural structures. Ultrasound Med Biol 22:179-192, 1996
6. Jeanmonod D, Magnin M, Morel A: Low-threshold calcium spike bursts in the human thalamus - Common physiopathology for sensory, motor and limbic positive symptoms. Brain 119:363-375, 1996
7. Jolesz FA: MRI-guided focused ultrasound surgery. Annu Rev Med 60:417-430, 2009
8. Lindquist C, Kihlstrom L, Hellstrand E: Functional neurosurgery--a future for the gamma knife? Stereotact Funct Neurosurg 57:72-81, 1991
9. Martin E, Jeanmonod D, Morel A, Zadicario E, Werner B: High-intensity focused ultrasound for noninvasive functional neurosurgery. Ann Neurol 66:858-861, 2009
10. Tsirul'nikov EM: [Somatosensory and auditory perception based on research data from using focused ultrasound]. Zh Evol Biokhim Fiziol 21:591-596, 1985
11. Tyler WJ, Tufail Y, Pati S: Pain: Noninvasive functional neurosurgery using ultrasound. Nat Rev Neurol 6:13-14, 2010