Neuroablative surgical interventions involve the interruption of peripheral and central nervous system pain pathways. Although the rationale appears logical, the results have not been consistent. Newer treatments including neurostimulation and intrathecal pump placement have replaced most of the neuroablative interventions. Some procedures such as dorsal root entry zone lesion and cordotomy remain useful.
Keywordscordotomy, DREZ lesion, neuroablative procedures, peripheral ganglionectomy, sympathectomy
The destruction of the nervous system is an irreversible technique to control otherwise intractable pain. However, prior to the development of effective augmentative techniques, such as intrathecal drug delivery and neurostimulation (both peripheral and central), these were the mainstay of neurosurgical pain treatment. Options exist for lesioning the brain and brain stem, cranial nerves, spinal cord, and peripheral nerves. Although the rise of these newer therapies has pushed aside many ablative procedures, several still remain valuable components of the neurosurgical armamentarium.
The interruption of peripheral or central nervous system pathways carrying pain has always seemed the most direct and logical manner to solve the problem of medically intractable pain, whether benign or malignant in origin. The targets for these interventions are myriad, beginning with peripheral nerves and ganglia and extending to the ascending spinothalamic tract and central aspects of the spinal cord, as well as the trigeminothalamic tract ( Figs. 57.1 and 57.2 ). Supratentorial structures such as the thalamus and cingulate gyrus have also been destroyed in the quest for pain control. Unfortunately, the results of these interventions have not been as straightforward as the theories behind their use, once again demonstrating that the physiology underlying the development and maintenance of chronic pain is more complex than we understand.
Several methods have been used to lesion the nervous system. The easiest is simply avulsion/resection of a peripheral nerve or cranial nerve branch. Thermocoagulation (TC) or radiofrequency (RF) lesioning has been most often used in the central nervous system, including the creation of ganglionic, spinal cord, and intracerebral lesions. Cryoablation found some favor in the 20th century but is rarely used nowadays.
Patients selected for these procedures should have chronic pain that has failed to adequately respond to multiple other conservative nonsurgical treatments. These may include rehabilitation, oral medications (antiinflammatory medications, opioids, anticonvulsants, antidepressants), and injections. Given the advances in neurostimulation and intrathecal drug delivery, it is also reasonable to conduct a trial of these therapies prior to considering ablative procedures. This is true both for patients with pain due to late stage malignancies (due to their higher medical risk in undergoing surgery) and those with pain from nonmalignant causes (due to the risk of permanent neurologic morbidity from the procedures).
After the patient is selected, it is just as important to carefully select the correct ablative procedure, considering both the etiology of the pain and its location within the nervous system, so as to maximize the chance of achieving pain relief. For instance, central neuropathic pain will not likely respond well to a peripheral neurectomy or dorsal root ganglion lesion.
This chapter reviews the published experience with several neuroablative procedures, beginning with those that are still most commonly in use. Certain procedures (such as trigeminal ganglionic lesions and spinal facet denervation) are covered elsewhere in this book ( Chapter 65, Chapter 66, Chapter 82 ).
Dorsal Root Entry Zone Lesions/Caudalis Dorsal Root Entry Zone
The dorsal horn of the spinal cord serves as both a relay center and an integration site for sensory signaling. First performed by Sindou in 1972 (via coagulation) and then Nashold and Ostdahl in 1974 (via RF energy), lesioning of the dorsal root entry zone (DREZ) was seen as a way to remove the portions of the central nervous system that had already undergone central sensitization in response to a peripheral lesion, such as malignancy or nerve injury. The lesions are intended to injure Lissauer tract and preserve fibers subserving proprioception and certain aspects of touch that travel in the dorsal rootlets to the dorsal columns. It continues to have clinical application primarily for the treatment of pain due to traumatic brachial plexus root avulsions.
Intradural exposure of the intended anatomic levels is accomplished, followed by microsurgical dissection of the dorsal rootlets to free them from each other. After identifying the correct anatomic levels, either by electrical stimulation or by the presence of avulsed rootlets, lesions are created on the inferolateral aspect of the rootlet entry zone. The small unmyelinated or lightly myelinated fibers that carry pain signals to the dorsal horn enter from the lateral aspect of the DREZ, whereas the medial side contains primarily those fibers destined for the dorsal columns. Lesions are created either by coagulating and opening the pia on the lateral aspect of the dorsal rootlets followed by microbipolar coagulation of the DREZ (Sindou’s method) or by using a DREZ RF needle (0.25-mm diameter) to make 1 mm–spaced lesions at 75°C for 15 seconds. Laser and ultrasonically created lesions have also been described.
For the treatment of facial pain, the lesions may be made in the trigeminal nucleus caudalis. This is essentially a cranial continuation of the dorsal horn, extending from the brain stem down into the upper cervical spinal cord, and receives much of the nociceptive signaling from the trigeminal system. As pioneered by Bernard et al. these lesions are made from the upper rootlets of C2 to a point just above the obex. In the nucleus caudalis, cells receiving input from the first division are located in a more ventrolateral position, whereas cells receiving input from the third division are located in a more dorsomedial position. Moreover, the third division is represented only in the more cranial aspect of the nucleus, whereas the first division has a much broader extent.
Great care must be exercised in targeting DREZ lesions due to the presence of the corticospinal tract just laterally to the dorsal horn. Moreover, the size and angulation of the DREZ and dorsal horn vary depending on the spinal level, being much thinner in the thoracic region. Moreover, the inherently tenuous vascular supply to the spinal cord must not be disrupted. The incidence of weakness ranges from 0% to 69%.
Larger series show reasonable rates of pain control. Dreval published results of 124 patients with brachial plexus avulsion pain followed a mean of 47.5 months after DREZ and reported an 87% rate of good pain control. Most series for this indication note good pain relief in a majority of patients (usually between 50% and 80% of the cohort). The limited series of results of DREZ lesioning for phantom limb pain show less favorable outcomes (14%–67% good pain relief). This is similar for pain due to spinal cord injury and truncal postherpetic pain. More recent publications have shown successful pain reduction (even if not complete) in approximately two-thirds of patients ( Table 57.1 ). Patients do better if the DREZ is not involved in the original injury. A systematic review of the efficacy of REZ in spinal cord injury pain revealed mostly level 4 studies. The DREZ was noted to be effective in segmental pain compared with diffuse pain after spinal cord injury.
|Study||Etiology of Pain; Nature of Study||Results||Comments|
|Haninec et al. 2014||Brachial plexus injury; retrospective; DREZ over 17 years (1995–2011); 52 patients; 3 groups based on decrease in pain scores: I (>75% decrease of pain), II (50%–75% decrease); III (<50%)||71% had >75% decrease (group I); 21% had 50%–75% (group II)||Group I patients complained of residual nociceptive pain; group II had pain of unclear origin; group III had residual neuropathic pain. Surgery was successful in 92%, unsuccessful in 8%.|
|Awad et al. 2013||Etiology of pain different (brachial plexus avulsion, spinal cord injury pain); retrospective study; patients who had DREZ from 1986 to 2011; 19 of 101 patients contacted||Seven (37%) had complete relief; six (32%) reported good improvement; three (16%) had mild relief; three (16%) reported poor results.||More than half of patients reported good quality of life.|
|Ko et al. 2016||Brachial plexus injury; retrospective; patients had DREZ from 1995 to 2012; 27 patients||Initial success rate of 73% which declined to 66% at median follow-up of 62.5 months.||Damage to DREZ or dorsal horn correlated with poorer outcomes. Longer duration of pain before DREZ predicted treatment success.|
Initially, the caudalis DREZ procedure was plagued by a high incidence of postoperative ataxia (up to 90%) due to the location of the nucleus caudalis deep to the spinocerebellar tract. Nashold developed new angled, insulated RF needles specifically for this procedure that protected this pathway from damage during lesioning of the nucleus caudalis, reducing the ataxia complication rate down to 39%. As opposed to spinal DREZ, the best indication for caudalis DREZ is postherpetic facial pain (71% excellent to good relief in the Duke series). Newer series have shown approximately 50%–60% pain reduction with this procedure with approximately one-third of patients experiencing recurrence in the first year and overall less than half of patients maintaining relief over 5 years.
Resection of a peripheral nerve found its most significant use in the treatment of trigeminal neuralgia and peripheral neuromas. Although it is not often used for the former indication, it remains a mainstay of treatment for the latter.
Avulsion of the peripheral branches of V1 (supraorbital and supratrochlear nerves) was often used in the treatment of trigeminal neuralgia in this region so as to selectively cause cutaneous anesthesia and spare the corneal anesthesia that often results from RF trigeminal ganglionolysis that includes V1. This has also been applied to the V2 and V3 branches in those patients deemed inappropriate candidates for other procedures for relief of trigeminal pain.
Supraorbital neurectomy is most commonly performed via an incision through the eyebrow, whereas infraorbital neurectomy uses an approach to the maxilla via the gingivolabial margin. After the nerve is located, it is wound around a small instrument and avulsed.
In the series of Grantham and Segerberg the average duration of pain relief from these procedures was 33.6 months. Oturai et al. compared RF coagulation and neurectomy and found that only 51% of patients undergoing neurectomy were pain free postoperatively and 78% had pain recurrence, compared with a pain-free rate of 83% of the RF cohort, with only 49% pain recurrence.
Neurectomy has also been used for orbital pain, thoracic pain, shoulder pain, and pelvic pain. It is sometimes applied as a treatment for postoperative neuropathic pain that afflicts 5%–8% of people undergoing hernia repair. Among the 26 patients with postherniorraphy pain reported by Zacest et al., 19 had significant pain improvement after ilioinguinal neurectomy, but 13 had later pain recurrence. Others have also reported results that indicate that the long-term results for this procedure are not durable. Publications that do report better pain relief from this procedure are either small series or more limited in their follow-up time.
Ganglionectomy is intended to avoid the issue of peripheral nerve regeneration, which may follow peripheral RF ablation or avulsion. Although selecting patients who will benefit most from the procedure is still a challenge, most investigators agree that diagnostic anesthetic nerve blocks of the prospective target root should produce significant temporary pain relief.
The dorsal root ganglion contains the cell bodies of the sensory neurons whose central projections enter the dorsal horn of the spinal cord. The ganglion itself lies in the lateral aspect of the neural foramen, distal to the termination of the subarachnoid space in the nerve root sleeve. It may be exposed by resection of the lateral portion of the facet joint and inferior aspect of the lamina of the superior vertebral segment overlying the target root. Opening the root sleeve exposes the ganglion, which can be separated from the underlying ventral root and resected.
The C2 ganglion has been resected as a therapy for intractable occipital neuralgia. In this procedure the ganglion is located ventral to the copious venous plexus in between the laminae of C1 and C2. The inferior aspect of the C1 lamina must sometimes be removed to gain access to the ganglion.
Results from ganglionectomy have been highly variable. In Taub’s large series of 61 patients who underwent ganglionectomy for persistent radicular pain following lumbar surgery, 59% of patients achieved good pain relief. Strait and Hunter reported that 66% of his patients who had both the L5 and S1 ganglia resected for this same indication were pain free. However, of the 37 patients in a series by Wetzel et al. followed at least 2 years after ganglionectomy, only 19% of patients had durable pain relief from the procedure. North et al. published even more disappointing results, with only 1 of the 13 patients reporting greater than 50% pain relief at 5.5 years postoperatively. There was little effect on medication intake and minimal functional improvement in the cohort.
Despite these issues, ganglionectomy may yet have a role to play. Young and Arbit et al. both published series of patients treated with ganglionectomy for cancer pain. In the latter series, 13 of 14 patients had excellent or good results following thoracic ganglion resection for malignant chest wall pain. However, the median follow-up was only 22 weeks (long 45 weeks), which may provide one explanation for the greater utility of the procedure in cancer pain.
Acar et al. found that the procedure may also be useful for treatment of intractable occipital neuralgia in patients who received good temporary relief from selective C2 and C3 blocks. At final follow-up (mean, 42.5 months), 60% of patients reported either excellent or moderate pain relief. In Lozano’s series, 80% of patients with neuropathic occipital pain or a traumatic etiology reported an excellent or good response to the procedure. Not surprisingly, those individuals who had undergone a prior peripheral neurectomy or RF ablation procedure did not obtain additional pain relief from the procedure.
Currently the most common indication for sympathectomy is palmar hyperhidrosis. However, for many decades, interruption of the sympathetic chain has been performed for a variety of pain syndromes, such as complex regional pain syndrome (I and II) and angina pectoris, as well as painful vasospastic disorders such as syndrome X and Raynaud syndrome. Often these conditions are characterized by pain that does not conform to traditional peripheral nerve or dermatomal innervation patterns and whose intensity is out of proportion to the inciting event and/or imaging findings. Vascular and dystrophic changes often accompany the pain.
Roberts proposed the term sympathetically mediated pain (SMP) to describe the phenomenon of pain abolition due to cessation (temporary or permanent) of sympathetic transmission. However, there is still a dearth of concrete understanding of the exact mechanisms by which the sympathetic nervous system either generates or maintains neuropathic pain syndromes despite significant research in this area. In determining a patient’s candidacy for sympathectomy, a determination must be made as to the relative contributions of SMP and sympathetically independent pain (SIP) to the overall level of pain. Most commonly this is determined by observing the clinical response to local anesthetic sympathetic blocks. Intravenous phentolamine (α 2 —adrenergic blockade) and guanethidine Bier (intravenous regional) block, resulting in adrenergic depletion, may also be used. Sympathectomy is offered to those patients with appropriate pain syndromes who have failed other therapies and have demonstrated substantial temporary relief from these injections.
Surgical sympathectomy may be performed via several routes, depending on the region of the chain to be disrupted. Thoracic sympathectomy is most commonly performed by resecting the T2 and T3 ganglia for the treatment of upper extremity pain. This region is approached either anteriorly via a small thoracotomy or, most typically, via thoracoscopic approaches. In the thoracoscopic procedure, ports are placed after deflating the ipsilateral lung. After elevating or opening the pleura, the sympathetic chain is identified in the paramedial posterior thoracic wall. The chain is coagulated and sectioned above and below the intended ganglia, and the specimen is removed. Pneumothorax is evacuated with a small red rubber catheter or chest tube prior to closing. It is rare to leave a chest tube following a thoracoscopic sympathectomy. The chain may also be approached posteriorly, via costotransverectomies at T2 and T3. The pleura is dissected away from the underside of the rib heads and transverse processes prior to their resection. The chain is located over the pleura near the lateral vertebral body. This is clipped/coagulated and resected. A similar approach may be conducted in the lower thoracic region for relief of neuropathic visceral pain (such as chronic pancreatitis) that has responded temporarily to splanchnic blockade. For this purpose, the ganglia from T9 to T12 are resected, along with the splanchnic nerves. This most frequently is performed as a bilateral procedure.
Lumbar sympathectomy is performed for relief of pain in the lower extremities. Typically the ganglia at L2 and L3 are resected. This may be approached via an open, muscle-splitting retroperitoneal approach through a flank incision, sweeping the peritoneal sac away from the vena cava or aorta (depending on the side of symptoms). The chain is found at the junction of vertebral body and psoas muscle.
Wilkinson has pioneered RF thoracic sympathectomy. This involves fluoroscopically placing RF needle electrodes at the levels of the T2 and T3 sympathetic ganglia. The ganglion is located near the dorsal half of the vertebral body near the craniocaudal midpoint of the vertebral body. Multiple lesions are created in the craniocaudal direction to ensure appropriate lesioning. Intraprocedural monitoring of limb temperature may be used to determine the procedural endpoint. A 2°C rise in temperature in the ipsilateral limb is considered significant. Complications from thoracic procedures include pneumothorax, Horner syndrome, vascular injury, and intercostal neuralgia. Lumbar sympathectomy carries the risk of ejaculation problems in men. Rarely, patients may experience “postsympathectomy neuralgia,” a constant, aching pain in the proximal portion of the targeted limb. This is almost always self limited to several months.
Series of patients undergoing thoracic sympathectomy for pain have reported rates of 65%–100% at achieving significant pain relief, at least initially. Success rates for lumbar sympathectomy are similar.
Wilkinson performed 37 RF sympathectomies for pain in 27 patients (3 bilateral). Eight were diagnosed with complex regional pain syndrome (CRPS) and 14 with causalgia. Useful pain relief was initially noted in 93% of targeted regions, but this declined to 69% at 1-year follow-up. In his entire series of 110 patients undergoing RF sympathectomy for a variety of indications, there were 6 symptomatic pneumothoraces. Two patients developed persistent Horner syndrome, and seven patients had transient intercostal neuralgia.
The none-too-subtle premise of cordotomy is the interruption of the spinothalamic and spinoreticular pathways in the anterolateral quadrant of the cord carrying pain inputs to the brain from the periphery. These lesions are intended to preserve fine touch and proprioceptive tracts. Within the spinothalamic tract, the sacral fibers are located more dorsolaterally and the cervical fibers more ventromedially. Moreover, at any spinal level, axons composing the spinothalamic tract are primarily projections from cells located in the contralateral cord beginning two to three spinal segments below the specific level. Therefore a lesion should produce pain relief beginning two to three dermatomes below the level of the lesion. However, caution must be taken in lesioning the upper cervical cord, due to respiratory fibers of the reticulospinal tract lying medial to the spinothalamic tract. For this reason, bilateral upper cervical cordotomy is often not performed and patients with tenuous respiratory function are often considered unsuitable candidates. This procedure has found most utility in the treatment of refractory malignant pain. Although open cordotomy was first performed by Spiller in 1912, Mullan pioneered the percutaneous approach, which enabled even medically fragile patients with advanced malignancies to undergo the procedure.
In the open procedure, intradural exposure is first accomplished, followed by sectioning of the dentate ligament at the appropriate level. Grasping the free end of the dentate ligament allows the surgeon to gently rotate the cord away from the operative side and expose the ventral cord. A cordotomy hook with a 45-degree angle is inserted into the anterolateral quadrant and may be taken to the medial pia before sweeping ventrally. Care is taken to not violate the medial pia and risk injury to the anterior spinal vessels.
Percutaneous cordotomy is often performed in the upper cervical (C1-2) region to treat hemibody pain. This may be done using either computed tomography (CT) or fluoroscopic guidance combined with contrast myelography. Following dural puncture from a lateral approach, contrast is instilled into the cerebrospinal fluid (CSF), allowing identification of the dentate ligament and definition of the ventral hemicord. A stimulating/lesioning electrode is advanced through the needle, and impedance mapping is used to signal entry into the cord. Pial penetration is heralded by an increase in the impedance from approximately 300 ohms to more than 500 ohms. Patients may also report pain with this maneuver. Low-frequency electrical stimulation is used to obtain a motor threshold for approximation of the distance to corticospinal tract. High-frequency stimulation should produce contralateral sensations covering the painful region. Serial RF lesions are then created until the area of pinprick analgesia encompasses the patient’s area of pain.
The majority of the outcomes literature regarding cordotomy deals with percutaneous procedures. A review of the efficacy of cordotomy is difficult to perform because most publications are retrospective in nature, dealt with small number of cases, or combined it with other procedures. Sindou et al. culled 2022 patients from the literature and personal experience who underwent cordotomy for malignant pain and reported a 75% success rate at 6 months and 40% at 1 year. Tasker noted that he could complete the procedure with a single lesion 95.5% of the time, with 94.4% of patients achieving an adequate result, dropping to 84% at last follow-up. The most common complications are ataxia or paresis due to collateral lesioning of the nearby spinocerebellar and corticospinal tracts, respectively. This is transient in a significant percentage of patients (2.9%–100%) but permanent in a minority (1%–20%). Severe respiratory failure was noted in 0.5%–27% of patients, and some have advocated an anterior transdiscal approach in the lower cervical region as a method of avoiding this complication. Modern series have shown excellent immediate pain reduction with results sustained at least over several weeks. In this review of 45 patients who had different cancer diagnosis (mesothelioma, head and neck, bronchial, esophageal, colon, pelvic, rectal) and underwent cordotomy, significant reduction of pain was noted at 2 days (median score: 0, interquartile range [IR]: 0–5) and 28 days (median score: 0, IR: 0–3.3) after the procedure. Adverse events included headache, dysesthesia, motor weakness, and increase in pain, but no serious events were noted.
Cordotomy has also been used in combination with other palliative pain procedures, such as intrathecal neuromodulation. Unfortunately, one particularly devastating complication is the late onset of new pain following cordotomy. Of Nagaro’s series of 45 patients who underwent cordotomy, 33 experienced this problem. In 28 patients the new pain was in the mirror-image location of the original pain and could often be abolished by blockade of the nerves subserving the original pain. However, this pain is not always simple to treat. This issue has been reported as affecting 1%–16% of patients in various series. Bowsher suggested that this was due to destruction of pathways providing unilateral inhibition of nociceptive cells with naturally bilateral receptive fields.
Regarding surgical cordotomy, Cowie’s report of 56 patients listed a 95% immediate pain-free result, which diminished to 55% at 1-year follow-up. For patients with nonmalignant pain, the success rate was 85% initially, but only 35% at 1 year and 20% at 3 years. Two patients died from respiratory failure. More recent series of open thoracic cordotomy highlight the sometimes problematic nature of the procedure, with new pain, leg weakness, and urinary problems all complicating the outcome.