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Jadad A, O'Brien MA, Wingerchuk D, et al. Management of Chronic Central Neuropathic Pain Following Traumatic Spinal Cord Injury. Rockville (MD): Agency for Healthcare Research and Quality (US); 2001 Sep. (Evidence Reports/Technology Assessments, No. 45.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

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Management of Chronic Central Neuropathic Pain Following Traumatic Spinal Cord Injury.

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7Dorsal Root Entry Zone Lesions and Other Surgical Interventions

Introduction

DREZ lesions are used to ablate neurons that may demonstrate paroxysmal hyperactivity after deafferentation injury (Sampson, Cashman, Nashold Jr., et al., 1995). In 1942, a Lissauer's tractotomy, the first known operative approach to the human DREZ, was performed for pain relief (Hyndman, 1942). This was followed, in 1966, by the development of an experimental pain relieving procedure -- performed in cats -- called radiofrequency DREZ nucleolysis (Kerr, 1966; Yaksh, 1988). Over the years, the procedure was refined until 1979 when Nashold and Ostahl first performed the DREZ microcoagulation for brachial plexus avulsion pain (Nashold Jr. and Ostdahl, 1979). In 1981, Nashold and Bullitt used it for post-traumatic spinal differentiation pain (Nashold Jr. and Bullitt, 1981).

Rawlings and colleagues suggest that the Rexed's layers I through V are the primary target regions of the DREZ procedure (Rawlings, el-Naggar, and Nashold Jr., 1989). They suggest that these regions are the origin of the spinothalamic tract and, following deafferentiation, there appears to be hyperactive neuronal discharges and changes in the relative concentrations of substance P and beta-endorphins in these layers (Rawlings, el-Naggar, and Nashold Jr., 1989). The putative mode of action of the DREZ procedure remains largely unexplained (Richter and Seitz, 1984). However, pain relief from DREZ lesioning may stem from the following three mechanisms (Richter and Seitz, 1984): interruption of ascending pain pathways within dorsal and dorsal-lateral columns, destruction of pain-generating centers in the spinal cord, or

rebalancing of the inhibitory and excitatory inputs within the damaged sensory network.

DREZ lesions can either be made using radiofrequency or laser (Powers, Barbaro, and Levy, 1988). Computer assisted (CA) guidance has recently been incorporated into the radiofrequency DREZ procedure to improve the accuracy of the lesion placement (Edgar, Best, Quail, et al., 1993). With the advance of technology, laser DREZ procedures have been developed to produce smaller and more discrete lesions (Powers, Barbaro, and Levy, 1988). Specific laser types include carbon dioxide (CO2), argon, and Neodymium: yttrium aluminum garnet (Nd:YAG).

This chapter addresses the question posed by the CSCM: "What is the evidence of effectiveness and safety of DREZ lesioning in treating CNP in patients with TSCI?" We have complemented it with a separate brief description, at the end, of the evidence on other surgical procedures.

Methods

The specific search strategies and methods for data extraction are summarized in Chapter 2.

Results

DREZ Lesions

Search Yield

The literature search located 17 studies of DREZ interventions published between 1981 and 1999 (Edgar, Best, Quail, et al., 1993; Friedman and Nashold Jr., 1986; 1997; Levy, Nutkiewicz, Ditmore, et al., 1983; Moossy, Nashold Jr., Osborne, et al., 1987; Nashold Jr. and Bullitt, 1981; Nashold Jr., Vieira, and el-Naggar, 1990; Powers, Barbaro, and Levy, 1988; Rath, Braun, Soliman, et al., 1996; Rath, Seitz, Soliman, et al., 1997; Richter and Seitz, 1984; Samii and Moringlane, 1984; Sampson, Cashman, Nashold Jr., et al., 1995; Spaic, Petkovic, Tadic, et al., 1999; Stranjalis and Torrens, 1997; Wiegand and Winkelmuller, 1985; Young, 1990). Three of them (Rath, Braun, Soliman, et al., 1996; Rath, Seitz, Soliman, et al., 1997; Richter and Seitz, 1984) described the same sample of subjects and were considered as one study (Rath, Seitz, Soliman, et al., 1997). Five studies were case reports, and details of those studies are found in Supplemental Table 7.1 (Gronning, Ertzgaard, and Myrseth, 1997) (Levy, Nutkiewicz, Ditmore, et al., 1983) (Supplemental Evidence Table 7.1) (Samii and Moringlane, 1984; Spaic, Petkovic, Tadic, et al., 1999; Stranjalis and Torrens, 1997). One study was excluded because the lesions were sacral root avulsions (Moossy, Nashold Jr., Osborne, et al., 1987). The search yielded no controlled trials. Therefore, nine unique studies are included in this review (Evidence Table 7.1).

Two of the nine studies made indirect comparisons: one studied radiofrequency DREZ procedures and CO2 laser DREZ (Young, 1990), and the other examined three different laser procedures -- CO2, argon, and Nd:YAG (Powers, Barbaro, and Levy, 1988).

Quality of Studies

Generally, the study quality was poor. Two studies were prospective (Nashold Jr., Vieira, and el-Naggar, 1990; Powers, Barbaro, and Levy, 1988) and five studies were retrospective (Edgar, Best, Quail, et al., 1993; Friedman and Nashold Jr., 1986; Rath, Seitz, Soliman, et al., 1997; Sampson, Cashman, Nashold Jr., et al., 1995; Young, 1990). In two studies, the direction could not be determined from the published report (Nashold Jr. and Bullitt, 1981; Wiegand and Winkelmuller, 1985). A high risk of selection bias may be present because eight of nine studies did not explicitly report the inclusion/exclusion criteria for subjects (Edgar, Best, Quail, et al., 1993; Friedman and Nashold Jr., 1986; Nashold Jr. and Bullitt, 1981; Nashold Jr., Vieira, and el-Naggar, 1990; Powers, Barbaro, and Levy, 1988; Rath, Seitz, Soliman, et al., 1997; Wiegand and Winkelmuller, 1985; Young, 1990). In all but one study (Nashold Jr. and Bullitt, 1981), descriptive information about patients with TSCI was either absent (Edgar, Best, Quail, et al., 1993; Powers, Barbaro, and Levy, 1988; Young, 1990); limited (Rath, Seitz, Soliman, et al., 1997; Wiegand and Winkelmuller, 1985); or inextractable from the complete sample (Friedman and Nashold Jr., 1986; Nashold Jr., Vieira, and el-Naggar, 1990; Sampson, Cashman, Nashold Jr., et al., 1995).

The sample sizes varied from 9 to 54 patients, with a median of 20 patients. Cumulatively, the nine studies examined 215 TSCI patients from a total sample of 459 patients exhibiting a wide range of neurological pathologies (e.g., other conditions included cauda equina injury, nerve root avulsions, tumors). A range was used to describe the number of TSCI patients in one study because six patients with avulsion injuries could not be excluded from the sample (Sampson, Cashman, Nashold Jr., et al., 1995).

Only two studies defined CNP (Edgar, Best, Quail, et al., 1993; Nashold Jr. and Bullitt, 1981). Their specific definitions can be found in their respective evidence tables (Evidence Table 7.1).

Eight out of the nine studies reported 100 percent patient followup (Friedman and Nashold Jr., 1986; Nashold Jr. and Bullitt, 1981; Nashold Jr., Vieira, and el-Naggar, 1990; Powers, Barbaro, and Levy, 1988; Rath, Seitz, Soliman, et al., 1997; Sampson, Cashman, Nashold Jr., et al., 1995; Wiegand and Winkelmuller, 1985; Young, 1990). One study (Edgar, Best, Quail, et al., 1993) reported 91 percent followup of the entire sample (n=112, including non-TSCI patients). Therefore, it was not possible to extract whether TSCI patients contributed to those lost at followup. In all studies, the length of followup ranged from the immediate postoperative period to 5.25 years.

Types of Study Participants

Five studies clearly reported the gender and age of the patients (Friedman and Nashold Jr., 1986; Nashold Jr. and Bullitt, 1981; Nashold Jr., Vieira, and el-Naggar, 1990; Rath, Seitz, Soliman, et al., 1997; Wiegand and Winkelmuller, 1985). The mean ages for four of these studies were 47.4, 39.8, 47, and 46 years, respectively. While Freidman reported a range of 27 to 72 years. In addition, in these five studies, male subjects represented 85 percent, 78 percent, 56 percent, 83 percent, and 88 percent of the TSCI sample. The level of injury was not reported in five studies (Edgar, Best, Quail, et al., 1993; Friedman and Nashold Jr., 1986; Nashold Jr., Vieira, and el-Naggar, 1990; Wiegand and Winkelmuller, 1985; Young, 1990). Of the remaining studies, one examined patients with conus medullaris lesions (Sampson, Cashman, Nashold Jr., et al., 1995). In the other studies, the thoracic region was the most common level of injury (Nashold Jr. and Bullitt, 1981; Powers, Barbaro, and Levy, 1988; Rath, Seitz, Soliman, et al., 1997).

Six studies did not report the completeness of the lesion (Edgar, Best, Quail, et al., 1993; Friedman and Nashold Jr., 1986; Nashold Jr., Vieira, and el-Naggar, 1990; Powers, Barbaro, and Levy, 1988; Wiegand and Winkelmuller, 1985; Young, 1990). Two studies categorized patients' injuries as complete/incomplete but failed to report the percentages (Rath, Seitz, Soliman, et al., 1997; Sampson, Cashman, Nashold Jr., et al., 1995). The remaining study reported 78 percent of the patients had complete injuries and 22 percent had incomplete motor injuries (Nashold Jr. and Bullitt, 1981). Although all studies failed to clearly report or present extractable data on duration of pain, onset of pain, and time since injury, they did provide descriptors of neuropathic pain. The more common descriptors were "burning" (8/9 studies), "electric," "sharp," and "deafferentation pain" (3/9 studies). Other descriptors are reported in the evidence tables.

Types of DREZ

Six studies used radiofrequency DREZ (Friedman and Nashold Jr., 1986; Nashold Jr. and Bullitt, 1981; Nashold Jr., Vieira, and el-Naggar, 1990; Rath, Seitz, Soliman, et al., 1997; Sampson, Cashman, Nashold Jr., et al., 1995; Wiegand and Winkelmuller, 1985). One study used two variations of radiofrequency DREZ (temperature controlled and frequency controlled) and CO2 laser DREZ (Young, 1990). Another study used CA radiofrequency DREZ (CA DREZ) (Rath, Seitz, Soliman, et al., 1997), and the final study used three types of laser DREZ (CO2, argon, Nd:YAG) (Powers, Barbaro, and Levy, 1988).

Outcome Measures

Although all studies used some type of categorical or binary outcome measure, there was variability across studies regarding the names and definitions of outcomes. Three studies used a binary outcome (greater or less than 50 percent pain relief) to report results (Edgar, Best, Quail, et al., 1993) (Powers, Barbaro, and Levy, 1988; Young, 1990), and another study used a binary outcome of success/failure in achieving 100 percent pain relief (Wiegand and Winkelmuller, 1985).

Five studies used a categorical outcome measure (Friedman and Nashold Jr., 1986; Nashold Jr. and Bullitt, 1981; Nashold Jr., Vieira, and el-Naggar, 1990; Rath, Seitz, Soliman, et al., 1997; Sampson, Cashman, Nashold Jr., et al., 1995). Categorical pain outcomes were determined by patients' ratings of pain relief, decreased pain medication usage, and interference with daily activities. None of the studies reported the validity, reliability, and responsiveness of the outcome measures. Furthermore, no study reported blinding of the outcome assessors.

Statistical Analysis

There was no report of statistical analysis performed in any of the studies.

Effectiveness of DREZ

In three radiofrequency DREZ studies (Friedman and Nashold Jr., 1986; Nashold Jr., Vieira, and el-Naggar, 1990; Sampson, Cashman, Nashold Jr., et al., 1995), the authors reported 26-28 of 54 (48-52%), 12 of 16 (75%), and 12-15 of 29 (41-52%) TSCI patients experienced good pain relief 1 year postsurgery, immediately postsurgery, and at a mean followup of 3 years, respectively. Good pain relief was defined as no analgesic use and no limitation of activity by pain. In these same studies, the authors also reported that three to five of 54 (6-9%), four of 16 (25%) and seven of 29 (24%) TSCI patients experienced fair pain relief (nonnarcotic use and no limitation of activity by pain) at the same followup. A range was used to describe the number of TSCI patients in the first study because two patients with spinal tumors could not be excluded from the sample (Friedman and Nashold Jr., 1986).

Another radiofrequency DREZ study reported that eight of 15 (53 percent) patients experienced 100 percent pain relief at an unreported followup (Wiegand and Winkelmuller, 1985). In a similar study, the authors reported that 11 of 23 (47%) TSCI patients had greater than 75 percent pain relief at a mean followup of 51 months after undergoing radiofrequency DREZ (Rath, Seitz, Soliman, et al., 1997). The remaining radiofrequency DREZ study reported greater than 50 percent pain relief in seven of nine (78%) TSCI patients at followups ranging from 5-38 months (Nashold Jr. and Bullitt, 1981).

In the only study using CA DREZ (Edgar, Best, Quail, et al., 1993), the authors reported that 84 percent of TSCI patients experienced 100 percent pain relief, and 92 percent experienced 50-100 percent pain relief at a mean followup of 44 months.

In the only study reporting the effectiveness of radiofrequency DREZ and CO2 laser DREZ, satisfactory pain relief (defined as pain reduction of at least 50%, cessation of narcotic use, and improvement in functional capacity) was found in eight of 15 (53 percent) TSCI patients undergoing radiofrequency DREZ and three of six (50%) undergoing laser DREZ (Young, 1990). The followup range of the entire sample (n=78) was 3.0-5.1 years.

One study examined the use of three different types of laser DREZ (CO2, argon, Nd:YAG) (Powers, Barbaro, and Levy, 1988). The results for TSCI patients were reported in aggregate across the three laser types. The authors reported that five of nine TSCI patients experienced greater than 50 percent pain relief with no narcotic use at a mean followup of 24 months.

Adverse Effects

Two studies, using radiofrequency DREZ, did not report the assessment of adverse effects (Nashold Jr., Vieira, and el-Naggar, 1990; Wiegand and Winkelmuller, 1985). Four studies reported adverse effects for TSCI subjects only (Nashold Jr. and Bullitt, 1981; Powers, Barbaro, and Levy, 1988; Sampson, Cashman, Nashold Jr., et al., 1995; Young, 1990). An adverse effect common in all four studies was motor weakness. This was observed in 14 of 61-67 patients. Cerebral spinal fluid leak and wound infections were reported in two of these studies (Powers, Barbaro, and Levy, 1988; Sampson, Cashman, Nashold Jr., et al., 1995). Each of these adverse effects was observed in 3 of 32-38 patients, and the severity was not reported. As indicated previously, a range was used to describe the number of TSCI patients in one study because six patients with avulsion injuries could not be excluded from the sample (Sampson, Cashman, Nashold Jr., et al., 1995). Three studies reported adverse effects for the entire sample (Edgar, Best, Quail, et al., 1993; Friedman and Nashold Jr., 1986; Rath, Seitz, Soliman, et al., 1997). Although there was greater variability in the adverse effects reported by these studies, motor and sensory deficits remained the most commonly reported adverse effects (Edgar, Best, Quail, et al., 1993; Friedman and Nashold Jr., 1986; Rath, Seitz, Soliman, et al., 1997).

Other Surgical Procedures

The search identified six case series (Bohlman, Kirkpatrick, Delamarter, et al., 1994) (Falci, Lammertse, Best, et al., 1999; Jefferson, 1983; Livshits and Kereselidze, 1990; Schaller, Mindermann, and Gratzl, 1999; Virozub, Bublik, and Chernovskii, 1990) and three case reports evaluating different types of spinal surgeries (Durward, Rice, Ball, et al., 1982; Loeser, Ward, and White, Jr., 1968; Pagni and Canavero, 1995). The case series are found in Evidence Table 7.2 and the case reports are in Supplemental Evidence Table 7.2.

Cumulatively, the six case series described 157 subjects. The types of surgical interventions included the following: anterior depression (1 study); spinal cord untethering (1); cordectomy (1); and a variety of interventions such as cordotomy, myelotomy, and arachnoid grafting (3). Across the six case series, improvement in pain varied from 20 percent to 85 percent in selected patients. Specific data related to duration of pain and onset of pain were not reported in five of six studies. Adverse effects included serious complications such as death due to pulmonary embolism (one patient), kyphosis, cerebrospinal fluid leak, meningitis, and refracture of the spine at another level.

Discussion

The nine studies reviewed indicate that DREZ lesioning in the treatment of CNP may offer promising results. Regardless of type of DREZ procedure, this intervention seems to have favorable pain relief results for more than half of the patients. As DREZ lesioning has been successfully used to treat neuropathic pain resulting from avulsion injuries, these results for CNP must be interpreted carefully. Given the traumatic nature of the injuries experienced by patients included in this review, it must be a difficult task for investigators to effectively rule out the presence of peripheral pathology in their patients. Therefore, it is possible that some of the patients described in the studies as having central pathology may as well have had concurrent peripheral pathology. Therefore, even as this review attempted to exclude patients with peripheral pathologies such as avulsion injuries, the positive results of DREZ lesioning may reflect the successful reduction of neuropathic pain due to peripheral pathology.

More importantly, the strength of evidence provided by the nine DREZ lesioning studies and the four studies of other surgical procedures reviewed was poor. The studies were observational in nature and did not use a control group (through either random allocation or matching on relevant variables) or blinded assessments. These shortcomings lead to the potential for confounded or invalid results. For this reason, it is uncertain whether improvement in patients' CNP should be attributed to chance, natural progression of the pain, or to the effectiveness of the DREZ lesioning or the other spinal surgical procedures.

As well, all of the studies on DREZ lesioning and other spinal surgeries had poorly defined, or lacked, inclusion and exclusion criteria for their samples. Moreover, there were insufficient descriptions of patient characteristics. Therefore, it is not easy to generalize the results of these studies to other groups of TSCI patients with CNP.

Implications for Practice

Even recognizing the problems regarding the validity and generalizability of the studies, some may look to DREZ lesioning or other spinal surgeries as a last resort when other palliative efforts have failed. Given that the studies did not adequately report the severity of the adverse effects experienced by patients, it is unknown whether DREZ lesioning and other spinal surgeries pose unwarranted risks to patients. For these reasons, even in situations where previous interventions have failed, the evidence is weak for the support of DREZ lesioning or other spinal surgeries to relieve CNP in TSCI patients.

Implications for Research

A discussion of the implications for future research is found in Chapter 8.

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