Practice Advisory: Utility of surgical decompression for treatment of diabetic neuropathy
Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology
Vinay Chaudhry, MD,
James C. Stevens, MD,
John Kincaid, MD and
Yuen T. So, MD, PhD
From the Johns Hopkins Outpatient Center (V.C.), Baltimore, MD; Lutheran Medical Office (J.C.S.), Fort Wayne, IN; Indiana University (J.K.), Indianapolis; and Stanford University (Y.T.S.), Stanford, CA.
Address correspondence and reprint requests to the American Academy of Neurology, 1080 Montreal Avenue, Saint Paul, MN 55116; e-mail: rsikka{at}aan.com
Surgical decompression at the site of anatomic narrowing hasbeen promoted as an alternative treatment for patients withsymptomatic diabetic neuropathy. Systematic review of the literaturerevealed only Class IV studies concerning the utility of thistherapeutic approach. Given the current evidence available,this treatment alternative should be considered unproven (LevelU). Prospective randomized controlled trials with standard definitionsand outcome measures are necessary to determine the value ofthis therapeutic intervention.
Diabetic peripheral neuropathy (DPN) is a common complicationof diabetes. Population-based cohort studies have shown that66% of type I and 59% of type 2 diabetics have objective evidenceof peripheral neuropathy.1 Complications of DPN are a majorcause for hospitalization among people with diabetes, and neuropathyranks third in lifetime expenditures associated with the complicationsof diabetes, behind macrovascular disease and nephropathy.2Several evidence-based reviews for treatment modalities forDPN are available.3–7 Surgical decompression of multipleperipheral nerves is being utilized as an alternative approachto treatment of symptomatic diabetic neuropathy.8–15 Thisis based on the hypothesis that diabetic nerves are more vulnerableto compressive injury at potential sites for entrapment.16–18This forms the "double crush" or "double pathology" hypothesis,19a term originally coined for increased susceptibility of nerveswith proximal and distal compressive lesions.17 The metabolicstress of diabetes is the first crush, and compression of thenerve at the potential site of entrapment will cause the secondcrush. According to this hypothesis, most patients remain asymptomaticdespite having diabetic nerve disease. Only when the secondpathology occurs (compression of the nerves at entrapment sites)will the patients become symptomatic. Thus it has been hypothesizedthat symptoms in diabetic sensorimotor neuropathy may be due,in part, to compression of multiple peripheral nerves.19 Althoughthis hypothesis has some experimental support,17,20–22evidence to the contrary showing resistance to axonal degenerationafter nerve compression also exists.23
More than 240 surgeons in 41 states in the United States andin 15 different countries have been trained to perform the decompressivesurgery.24 As of January 31, 2006, 1,280 surgeries on 990 patientsby 34 surgeons have been registered in the International NeuropathyDecompression Registry sponsored by the Diabetic NeuropathyFoundation of the Southwest (http://www.neuropathyregistry.com/).The public interest about this subject has generated severalcommunications both to individuals and to organizations to developa statement on this topic. Due to the controversial nature ofthis treatment, the large number of patients with diabetes mellitus(estimated 18.2 million in the United States), and the typicallyprogressive and irreversible nature of diabetic neuropathy,the Therapeutics and Technology Subcommittee of the AAN posedthe question, "Is there evidence to support the use of decompressivesurgery in the treatment of diabetic neuropathy?"
A MEDLINE, EMBASE, and PUBMED literature search was conductedby two of the authors (V.C. and J.C.S.) for all articles publishedbetween 1966 and July 2005, in the English language with thekey words "diabetes mellitus," "diabetic neuropathy," and "surgicaldecompression." Seventy-five articles were identified by thissearch. An additional two articles, published in September 2005,identified after the initial search, were reviewed by two authors(V.C. and Y.T.S.). Since the intent of this review was to providea statement for length dependent sensory motor distal neuropathy,articles solely dealing with upper extremity decompressive surgeryfor documented entrapments were excluded. Abstracts of the articleswere reviewed and 18 full articles that pertained to the topicwere selected. Accompanying editorials and related discussionswere reviewed for content. The articles were classified forquality of evidence based on the AAN classification system (appendix 1).Evidence tables were constructed from 10 selected articles whichdealt directly with surgical decompression in human subjectswith diabetic neuropathy. This resulted in one Class III (laterdowngraded to Class IV) and nine Class IV studies being identifiedfor the purpose of this Practice Advisory.
Eleven articles were identified that dealt with decompressivesurgery for the treatment of diabetic neuropathy (table E-1on the Neurology Web site at www.neurology.org). There was onlyone prospective study that employed blinded outcome assessmentin a small cohort of patients.10 This article was downgradedto Class IV because of a lack of detail concerning nerve conductionstudies, lack of definition and lack of clarity in segregatingpatients into peripheral neuropathy or compression categories,and use of arbitrarily defined scales of improvement. However,this study was prospective, with a blinded evaluator, and involveda consecutive series of eligible patients with "symptomatic"diabetic neuropathy determined by subjective report and thepresence of a Tinel’s sign over an involved peripheralnerve entrapment site. This series consisted of 20 patients(14 type I and 6 type II diabetics) who underwent a total of31 nerve decompression procedures. Electrodiagnostic studieswere performed preoperatively in each patient and showed that22% had nerve compression, 56% had a peripheral neuropathy withsuperimposed nerve compression, and 22% had a peripheral neuropathywithout a superimposed nerve compression (the details of howthese diagnoses were reached was not provided). Patients wereassessed preoperatively and postoperatively with a standardizedtwo-point discrimination test using the Pressure-Specified SensoryDevice (Sensory Management Services, LLC).25 The postoperativeexamination was administered to 14 patients (six patients electedto have bilateral extremity decompression procedures) by a blindedtherapist. Surgical scars were covered by clothing and the operatedlimb was compared to the contralateral nonoperated side. Improvementwas considered to have occurred if the two-point discriminationchanged from "absent" to "any numerical value" or demonstrateda decrease of >2 mm. Postoperative assessment was performedat a mean of 23.3 months (range 12 to 41 months) after the procedure.
This study revealed that 79% of the surgically decompressednerves improved in their two-point discrimination test postoperatively.None of the decompressed nerves worsened, whereas 32% of thecontralateral non-treated nerves worsened in their two-pointdiscrimination (p < 0.001). Twenty-one percent of the surgicallytreated nerves and 59% of the non-surgically treated nervesremained unchanged at follow-up assessment. The author did notreport the results according to the preoperative electrodiagnosticstudies. Therefore, one cannot discern whether the positiveresults were due to decompression of "compressed" nerves asdetermined by electrodiagnostic studies or decompression ofdiabetic peripheral neuropathy without a superimposed nervecompression.
The remaining 10 studies8,9,11–15,26–28 were comprisedof non-blinded case series reporting results of decompressionof the posterior tibial, deep peroneal, common peroneal at theankle and knee, median and ulnar nerves at the wrist and elbow,with one study8 that also included decompression of the radialnerve in the forearm. The assessments used a variety of outcomemeasures, all collected by the operating surgeon. Eight of the10 studies reported a reduction in subjectively reported pain(80 to 92% of the treated patients), as well as an improvementin two-point discrimination (67 to 79% of the treated patients).The number of patients in these series who had "diabetic neuropathy"ranged from a minimum of 10 to a maximum of 60. Definitionsfor what constituted diabetic neuropathy and the methodologyfor pain measurement/reporting were non-uniform between thestudies. One study14 involved a questionnaire/phone interviewof 50 patients who had previously undergone unilateral lowerextremity nerve decompression surgery to determine if the non-operatedlimb had a propensity to develop ulcerations or require amputationat a greater rate than the surgically treated extremity. Thesurgeon reported that none of the surgically treated limbs developedulcers or required amputation whereas 12 patients developedulcers and three required amputations in their non-surgicallytreated leg or foot (p < 0.001). The mean follow-up periodwas 4.5 years (range 2 to 7 years). There was no indicationthat the limbs were examined by the independent investigators.
The current evidence supporting the utility of decompressivesurgery for the treatment of diabetic neuropathy is of poorquality and design. Although purported as a potential alternatetherapy for this progressive and often debilitating condition,the data are insufficient to support or refute its benefits.None of these studies provided randomization or a control group(other than one weak Class III study which was downgraded toClass IV, in which the patient served as his or her own control).The patients and evaluators were unblinded in 9 of the 10 studies,allowing the opportunity for significant bias in determiningoutcomes. The definition of peripheral neuropathy in these studiesis unclear.
The standard testing of distal sensory loss of small and largefiber modalities (outside of two-point discrimination), distalweakness, deep tendon reflexes, gait, and Romberg’s testingwere not included in these studies. Only a few8–10 reportthe performance of nerve conduction studies, but specific datawere not provided. One cannot discern whether the positive resultsreported were simply due to release of traditionally compressednerves as would be determined by electrodiagnostic studies,or the result of treatment of a process that would be considereda symmetric diabetic sensorimotor neuropathy. In a majorityof the studies, improvement was based on subjective measuresand observations of the operating surgeon. Precise descriptionof the location and degree of improvement was not clear in manyof these reports. The statistical analyses utilized have nonstandardizedmeasurements.
There are inadequate data concerning the efficacy of decompressivesurgery for the treatment of diabetic neuropathy. Given ourcurrent knowledge, this treatment is unproven (Level U) (seeappendix 2 for classification of recommendations).
1. Randomized controlled trials with standard definitions ofperipheral neuropathy, control for concurrent treatments, andvalidated functional outcome measures with independent, blindedevaluations should be performed.
2. Distinction between entrapment neuropathy and peripheralsensorimotor neuropathy should be clarified in these studies.
3. Monitoring of glycemic control should be conducted and well-documentedin future studies.
4. Detailed reporting of postoperative complications shouldbe included in all future studies.
5. Data should be provided to allow calculation of number neededto treat to result in a benefit (NNT) and the number of surgeriesrequired to result in harm to the patient (NNH).
This statement is provided as an educational service of theAmerican Academy of Neurology. It is based on an assessmentof current scientific and clinical information. It is not intendedto include all possible proper methods of care for a particularneurologic problem or all legitimate criteria for choosing touse a specific procedure. Neither is it intended to excludeany reasonable alternative methodologies. The AAN recognizesthat specific patient care decisions are the prerogative ofthe patient and the physician caring for the patient, basedon all of the circumstances involved.
The Therapeutic and Technology Assessment Subcommittee (TTA)oversees the development of AAN technology assessments and therapeuticassessments, which are evidence-based statements that assessthe safety, utility and effectiveness of new, emerging, or establishedtherapeutic agents or technologies in the field of neurology.Technology assessments and therapeutic assessments are developedthrough a rigorous process of defining the topic, evaluatingand rating the quality of the evidence, and translating theconclusions of the evidence into practical assessments thatcan be used to guide the use of technologies and therapeuticagents in the practice of neurology.
Classification of evidence for therapeutic articles
Class I: Prospective, randomized, controlled clinical trialwith masked outcome assessment, in a representative population.The following are required:
a) Primary outcome(s) is/are clearly defined.
b) Exclusion/inclusion criteria are clearly defined.
c) Adequate accounting for drop-outs and cross-overs with numberssufficiently low to have minimal potential for bias.
d) Relevant baseline characteristics are presented and substantiallyequivalent among treatment groups or there is appropriate statisticaladjustment for differences.
Class II: Prospective, matched, group cohort study in a representativepopulation with masked outcome assessment that meets a-d aboveOR a RCT in a representative population that lacks one criteriona–d.
Class III: All other controlled trials including well-definednatural history controls or patients serving as own controlsin a representative population, where outcome assessment isindependently assessed or independently derived by objectiveoutcome measurement (an outcome measure that is unlikely tobe affected by an observer’s [patient, treating physician,investigator] expectation or bias [e.g., blood tests, administrativeoutcome data]).
Class IV: Evidence from uncontrolled studies, case series, casereports, or expert opinion.
A = Established as effective, ineffective, or harmful for thegiven condition in the specified population. (Level A ratingrequires at least two consistent Class I studies.)
B = Probably effective, ineffective, or harmful for the givencondition in the specified population. (Level B rating requiresat least one Class I study or at least two consistent ClassII studies.)
C = Possibly effective, ineffective, or harmful for the givencondition in the specified population. (Level C rating requiresat least one Class II study or two consistent Class III studies.)
U = Data inadequate or conflicting given current knowledge,treatment is unproven.
Therapeutics and Technology Assessment Subcommittee Members:Janis Miyasaki, MD (co-chair); Yuen T. So, MD, PhD (co-chair);Carmel Armon, MD, MHS (ex-officio); Vinay Chaudhry, MD; RichardM. Dubinsky, MD, MPH: Douglas S. Goodin, MD (ex-officio); MarkHallett, MD; Cynthia Harden, MD; Kenneth J. Mack, MD, PhD; FenwickT. Nichols III, MD; Michael A. Sloan, MD, MS; James C. Stevens,MD.
Additional material related to this article can be found onthe Neurology Web site. Go to www.neurology.org and scroll downthe Table of Contents for the June 27 issue to find the titlelink for this article.
Approved by the Therapeutics and Technology Assessment Subcommitteeon October 23, 2005; by the Practice Committee on April 5, 2006;and by the AAN Board of Directors on May 4, 2006.
Disclosure: The authors report no conflicts of interest.
Received December 12, 2005. Accepted in final form March 16,2006.
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