Thalamic DBS for Neuropathic Pain After Amputation

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Thalamic DBS for Neuropathic Pain After Amputation

Abstract and Introduction

Abstract


Object Fifteen hundred patients have received deep brain stimulation (DBS) to treat neuropathic pain refractory to pharmacotherapy over the last half-century, but few during the last decade. Deep brain stimulation for neuropathic pain has shown variable outcomes and gained consensus approval in Europe but not the US. This study prospectively evaluated the efficacy at 1 year of DBS for phantom limb pain after amputation, and deafferentation pain after brachial plexus avulsion (BPA), in a single-center case series.

Methods Patient-reported outcome measures were collated before and after surgery, using a visual analog scale (VAS) score, 36-Item Short-Form Health Survey (SF-36), Brief Pain Inventory (BPI), and University of Washington Neuropathic Pain Score (UWNPS).

Results Twelve patients were treated over 29 months, receiving contralateral, ventroposterolateral sensory thalamic DBS. Five patients were amputees and 7 had BPAs, all from traumas. A postoperative trial of externalized DBS failed in 1 patient with BPA. Eleven patients proceeded to implantation and gained improvement in pain scores at 12 months. No surgical complications or stimulation side effects were noted. In the amputation group, after 12 months the mean VAS score improved by 90.0% ± 10.0% (p = 0.001), SF-36 by 57.5% ± 97.9% (p = 0.127), UWNPS by 80.4% ± 12.7% (p < 0.001), and BPI by 79.9% ± 14.7% (p < 0.001). In the BPA group, after 12 months the mean VAS score improved by 52.7% ± 30.2% (p < 0.001), SF-36 by 15.6% ± 30.5% (p = 1.000), UWNPS by 26.2% ± 40.8% (p = 0.399), and BPI by 38.4% ± 41.7% (p = 0.018). Mean DBS parameters were 2.5 V, 213 microseconds, and 25 Hz.

Conclusions Deep brain stimulation demonstrated efficacy at 1 year for chronic neuropathic pain after traumatic amputation and BPA. Clinical trials that retain patients in long-term follow-up are desirable to confirm findings from prospectively assessed case series.

Introduction


Phantom limb pain is uncommon, with an incidence of 1–2 cases per 100,000 individuals, but presents a significant burden to the patient, affecting up to 85% of amputees. Stump pain usually occurs at some time during the first month following amputation and resolves in many patients after 2–3 years without treatment, except in cases in which phantom pain develops. The incidence of phantom pain is variable but increases with more proximal amputations. The origin and pathophysiological mechanisms of phantom pain are not clearly defined. However, both peripheral and central neural mechanisms have been described, along with superimposed psychological mechanisms. The management of phantom limb pain has little evidence base in the scientific literature; while numerous treatments have been described, there is little clinical evidence supporting any particular therapy.

Brachial plexus avulsion (BPA) commonly results in early deafferentation pain, with 25% of sufferers going on to experience severe neuropathic pain several years later that is usually refractory to pharmacotherapy. Brachial plexus avulsion pains have been dichotomized into either continuous, often burning or throbbing pain and likely involving thalamic neuroplasticity, or shooting paroxysms associated with dorsal horn hyperactivity. Both phantom limb pain after amputation and deafferentation pain after BPA fulfill a recently revised definition of neuropathic pain as pain caused by a lesion or disease of the somatosensory system. Neuropathic pain symptom severity and duration are often greater than other forms of chronic pain, leading patients and clinicians to consider neurosurgery.

Deep brain stimulation (DBS) is an invasive neurosurgical intervention established in movement disorders and also used to treat "off-label" clinical indications of epilepsy, Tourette syndrome, obsessive-compulsive disorders, depression, and cluster headache. Deep brain stimulation has been performed for more than half a century for chronic pain amelioration, its use preceding gate-control theory by a decade. After rodent self-stimulation experiments and reported analgesia in patients receiving septal DBS, cancer pain was being relieved by intermittent stimulation by the 1960s. Evidence supporting the ventroposterolateral nucleus of the sensory thalamus (ventroposterolateral) as a target for limb pain came from ablative surgery. The ventroposterolateral nucleus of the sensory thalamus has been targeted successfully for 4 decades, as has periaqueductal and periventricular gray matter.

Two multicenter trials of DBS for pain were conducted to seek US FDA approval. Neither trial satisfied efficacy criteria of at least half of the patients reporting at least 50% pain relief 1 year after surgery. United States FDA approval was therefore not sought. Deep brain stimulation for pain was decreed "off label," precluding medical insurance reimbursement. Consequently, few surgeons currently report DBS for pain outside of Europe, where it has approval by the European Federation of Neurological Societies (EFNS) and the United Kingdom National Institute for Health and Clinical Excellence (NICE). Nevertheless, a recent growing interest in its use for chronic pain refractory to medical treatment has paralleled advances in DBS technology, neuroimaging, and the publication of more rigorous case series regarding its long-term efficacy. Successful results have been shown for multiple origins of pain, in particular for poststroke pain, face pain, amputation, and BPA.

In this paper we describe a prospectively studied, open-label, consecutive case series of patients receiving ventroposterolateral DBS for chronic neuropathic pain after amputation or BPA. These patients were treated at a single Portuguese center that was establishing DBS for pain service after a decade's experience of using DBS for movement disorders in more than 200 patients. Improvements in patient-reported outcome measures of pain and quality of life were analyzed, and challenges to DBS for pain are discussed.

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