Decompressive surgery of lower limbs for symmetrical diabetic peripheral neuropathy

Abstract

Background

Symmetrical peripheral neuropathy is a common complication of diabetic neuropathy. No treatments are known to be effective for progressive pain and sensory loss associated with diabetic neuropathy. Alternative effective treatment strategies have been sought.

Objectives

To systematically review the evidence from randomized controlled trials concerning the role of decompressive surgery of lower limbs for symmetrical diabetic peripheral neuropathy.

Search methods

We searched the Cochrane Neuromuscular Disease Trials Register (May 2006), CENTRAL (The Cochrane Library, Issue 2 2006), MEDLINE from (January 1966 to August 2006), EMBASE (from January 1980 to August 2006), LILACS (from January 1982 to August 2006), and CINAHL (from January 1982 to August 2006).

Selection criteria

We included all randomized or quasi‐randomized controlled human trials in which any form of decompressive surgery of the lower limbs nerves had been used to treat diabetic symmetrical distal polyneuropathy (DSDP) compared with no treatment or medical therapy. Patients with DSDP were included if they had decompression (with or without neurolysis) of at least two of the following nerves in both lower limbs, for the treatment of DSDP: the posterior tibial nerve (including calcaneal, medial and lateral plantar nerves), deep peroneal nerve at the ankle, common peroneal nerve at the knee, lateral femoral cutaneous nerve and sural nerves in the posterior calf region. The primary outcome measure was the change in pain measured by the visual analogue scale (VAS) between the baseline and a follow‐up period of greater than three months.

Data collection and analysis

We identified 142 publications from the above search strategies. The three authors of this manuscript reviewed abstracts of all papers independently. Only eight of these were considered relevant to the question at hand. The data from these 8 studies were entered onto standardized data extraction forms. We planned to use Review Manager to pool the results from appropriate studies comparing the same treatments; dichotomous outcomes to obtain pooled relative risks (RR); measured outcomes to obtain pooled weighted mean differences; and a fixed‐effect analysis unless there was evidence of serious heterogeneity between studies sufficient to justify the use of random‐effects analysis.

Main results

This review failed to identify a single randomized controlled trial or any other well designed prospective study controlling for the non‐operated limb that showed improvements in pre defined end points after decompressive surgery.

Authors' conclusions

The results of this review suggest that the role of decompressive surgery for diabetic symmetric distal neuropathy is unproven.

Plain language summary

Lower limb surgery to release trapped nerves in diabetic neuropathy

This review analyzed the role of decompressive surgery of lower limb nerves for symmetrical diabetic peripheral neuropathy. Peripheral neuropathy is one of the most common complications of diabetes. Pain and numbness in the feet are common features. Pain may impair the quality of life and lack of feeling puts the diabetic foot at increased risk of ulceration. Strict glucose control may reduce the risk of developing diabetic neuropathy but once developed, neuropathy is irreversible and slowly progressive. New treatment strategies are needed to treat diabetic neuropathy. In this review, the role of surgical decompression of "entrapped" peripheral nerves as an alternative approach to treatment for diabetic neuropathy was analyzed.

Background

Diabetes mellitus

Diabetes mellitus is a disorder of carbohydrate metabolism that results from either absolute or relative insulin deficiency or insulin resistance, or both. A consequence of this is chronic hyperglycemia (elevated levels of blood glucose) with long‐term complications including retinopathy, nephropathy, cardiovascular disease, and peripheral neuropathy. World Health Organization (WHO) data suggest that there will be 353 million people with diabetes mellitus by 2030, a marked increase from the current (2000) estimates of 175 million (Yach 2006). In the US, 20.8 million people, 7% of the population, have diabetes (NIDDK 2005). For a detailed overview of diabetes mellitus, please see under 'About this group' in the information on the Metabolic and Endocrine Disorders Review Group in the Cochrane Library. For an explanation of methodological terms, see the main Glossary of terms in the Cochrane Library.

Diabetic neuropathy

Diabetic peripheral neuropathy is one of the most common complications of diabetes. Population based cohort studies have shown that 66% of people with type 1 diabetes and 59% of people with type 2 have objective evidence of peripheral neuropathy (Dyck 1993). A recent review estimates that neuropathy is present in about 30% of people attending hospital diabetes clinics, 20% of people with diabetes in primary care settings, and 10% of the entire population of patients with diabetes (Shaw 1999). Complications are a major cause for hospitalization among people with diabetes, and neuropathy ranks third in lifetime expenditures associated with the complications of diabetes, behind macrovascular disease and nephropathy (Caro 2002; Polydefkis 2003). Distal symmetrical diabetic polyneuropathy (DSDP) is the most common form of diabetic neuropathy. It is characterized by a stocking‐glove pattern of symmetrical sensory symptoms and signs and distal weakness in the hands and feet. Distal symmetrical diabetic neuropathy can be associated with negative symptoms such as loss of sensory or motor function presenting as foot numbness and weakness; or more troublesome positive sensory symptoms described variably as burning, electric shock‐like, stabbing, tingling, prickling, pins or needles, sharp and shooting pains. The positive and negative symptoms typically involve the toes, followed by the feet, with a gradual march up to the legs before involving the hands (Wolfe 1999).

Longitudinal studies of people with diabetic polyneuropathy have demonstrated that their clinical and electrophysiological abnormalities worsen with time, although slowly. For example, in the population based Rochester Diabetic Neuropathy Study, patients were assessed with the Neuropathy Impairment Score (NIS), in which the minimum detectable meaningful change is two points. In this patient cohort, those who were followed for at least two years worsened at a rate of only 0.85 NIS points per year (Dyck 1997).

Peripheral neuropathy, once developed, is irreversible and slowly progressive. A variety of treatments aimed at altering the metabolic abnormalities, such as aldose reductase inhibitors, myoinositol supplementation, alpha‐lipoic acid, and nerve growth factor have been tried but none are proven effective (Sinnreich 2005). A number of agents have been used to treat the pain in DSDP, including desipramine, amitriptyline, capsaicin, tramadol, gabapentin, duloxetine, pregabalin, bupropion, and venlafaxine (Singleton 2005). Citalopram, nonsteroidal antiinflammatory drugs, and opioid analgesics may be used as adjuvant agents. Lamotrigine, oxcarbazepine, paroxetine, levodopa, and alpha‐lipoic acid are alternatives (Duby 2004; Llewelyn 2003). Pain medications reduce neuropathic symptoms but do not alter the underlying nerve pathology or progression of neuropathy. Thus, new treatment strategies are needed to treat underlying DSDP.

Surgical decompression for diabetic neuropathy

One proposed treatment strategy is to use surgical decompression of lower limb nerves. This method is being increasingly used as an alternative approach to treatment for diabetic neuropathy. (Aszmann 2000; Aszmann 2004; Biddinger 2004; Dellon 1992; Hollis 2000; Tambwekar 2001; Wieman 1995; Wood 2003) This is based on the hypothesis that diabetic nerves are more vulnerable to compressive injury at potential sites of entrapment (Dellon 1988; Lee 2003; Upton 1973). For the lower limbs, these potential sites include the tibial nerve at the ankle, calcaneal, medial plantar, and lateral plantar nerves in their own separate tunnels in the foot, and peroneal nerve at the ankle and knee. The supposed basis for this hypothesis is so‐called "double crush or double pathology hypothesis" (Dellon 1991). Hence, diabetes is one crush or pathology and compression of the nerve at hypothesized sites of entrapment will form the second crush or pathology. According to this hypothesis, the coexistence of the diabetic nerve lesion (one "crush") and chronic focal compression (second "crush") results in a "double crush" of a peripheral nerve. Using this hypothesis, a numb or painful foot in a diabetic patient could be explained by double crush of the sural, peroneal and tibial nerves. Hence, reversal of the second crush or pathology by surgical decompression may result in symptomatic improvement. The double‐crush hypothesis both in general and specifically in diabetes remains controversial. While there is some experimental evidence in support of this double‐crush hypothesis (Dellon 1988; Dellon 1991; Kale 2003), contrary evidence also exists. For example, Dyck et al. have shown that diabetic nerve fibers are in fact less vulnerable to compression injury (Dyck 1989). Paresthesia, increase of vibratory perception and development of nerve conduction block fail sooner during compression in controls than in people with diabetes (Jaramillo 1985; Seneviratne 1969; Steiness 1959; Steiness 1961) 
 In addition, this hypothesis does not explain why patients with DSDP develop symptoms that are typically symmetrical, not conforming to the distribution of individual entrapped nerves. Longitudinal studies such as the Rochester Diabetes Neuropathy Study have also shown a slow progression of neuropathy in a symmetrical fashion, not what would be expected if multifocal entrapment of named peripheral nerves were occurring (Dyck 1992; Dyck 1993).

Objectives

The objective was to systematically review the evidence from randomized controlled trials concerning the role of decompressive surgery of lower limbs for symmetrical diabetic peripheral neuropathy.

Methods

Criteria for considering studies for this review

Types of studies

We will include all randomized or quasi‐randomized controlled human trials in which any form of decompressive surgery of the lower limbs nerves has been used to treat DSDP compared with no treatment or medical therapy.

Types of participants

We included adult (>18 years of age) diabetic (both type 1 and type 2) participants of either sex who had undergone decompressive surgery of lower limbs for DSDP.

Types of interventions

We included all diabetic patients who had undergone decompression (with or without neurolysis) of at least two of the following nerves in both lower limbs, for the treatment of DSDP: the posterior tibial nerve (including calcaneal, medial and lateral plantar nerves), deep peroneal nerve at the ankle, common peroneal nerve at the knee, lateral femoral cutaneous nerve and sural nerves in the posterior calf region.

Types of outcome measures

Primary outcomes

The primary outcome measure was change in pain measured by the visual analogue scale (VAS) at the foot between the baseline and a follow‐up period of greater than three months.

Secondary outcomes

Secondary outcome measures included any validated measures of nerve function between baseline and a follow‐up period of greater than three months. Examples of secondary outcome measures included: 
 (a) Nerve conduction measures of sensory response amplitude. When responses had been measured in more than one nerve, an average measure over the nerves involved was used. This nerve conduction measure was considered a sensitive and specific indicator of sensory neuropathy. 
 (b) Impairment measured on a validated scale such as, the Neuropathy Impairment Scale (Dyck 2005) 
 (c) Functional measures of activities of daily living measured with a validated scale. 
 (d) Side effects of decompressive surgery such as delayed wound healing, infections, or persistent pain.

Search methods for identification of studies

We searched the Cochrane Neuromuscular Disease Group Trials Register (May 2006) using the search terms listed below. We also searched CENTRAL (The Cochrane Library, Issue 2 2006), MEDLINE (January 1966 to August 2006), EMBASE (January 1980 to August 2006), LILACS (January 1982 to August 2006), and CINAHL (January 1982 to August 2006). We adapted the strategy to search each database using an appropriate combination of MeSH and textword terms.

(1) Initial search 
 (a) Decompression, surgical OR decompression surgery OR decompression operation AND 
 (b) (Diabetic neuropathy OR diabetic polyneuropathy) OR diabetes mellitus AND (neuropathies or peripheral nervous system diseases OR polyneuropathy)

(2) Expanded search 
 (a) Tarsal tunnel surgery AND 
 (b) As above

Electronic searches 
 See Appendix 1, Appendix 2, Appendix 3, and Appendix 4.

Data collection and analysis

Titles and abstracts identified from the register were checked by all three authors. The full text of all potentially relevant studies was obtained for independent assessment by the individual author. The reviewers decided which trials fitted the inclusion criteria and graded their methodological quality. Serious adverse events were defined as per FDA definition and included hospitalization requiring intervention and other adverse events considered life threatening.

The methodological quality assessment took into account allocation concealment, patient blinding, explicit diagnostic criteria, explicit outcome criteria, how studies deal with baseline differences of the experimental groups, and completeness of follow‐up. Allocation concealment or masking, as used in this review, relates to the randomization procedures, whereby investigators involved in subject allocation should not be able to influence how the groups are assembled. It involves concealment of the next allocation in the randomization sequence, such that neither the investigators nor the subjects can be aware of the next group assignment until after the decision about whether an individual is eligible for the trial has been finalized. We graded these items A: adequate, B: moderate risk of bias; C: inadequate, and D: not done. If the information was not available, the item was graded inadequate. We included in the discussion consideration of adverse events, and, if available, information on cost benefits, taking into account the non‐randomized literature.

Data extraction were performed independently by all three authors. 
 We summarized the types of outcomes reported (quantitative sensory testing, nerve conduction studies, clinical, functional measure).

Results

Description of studies

Our search strategy identified 142 titles and abstracts from which eight were possibly relevant. On further inspection of the papers none of the eight were randomized controlled studies and so all were excluded from the Results section of the review in accordance with Collaboration policy. They are reported in the Discussion section of the review. Four studies were prospective although none was randomized, controlled, or crossover (Aszmann 2000; Dellon 1992; Ducic 2006; Rader 2005). Three used comparison to the opposite non‐operative side to assess improvement (Aszmann 2004; Dellon 1992; Rader 2005). Two were retrospective studies, without a controlled arm (Aszmann 2004; Maloney 2006) although the opposite extremity was used for comparison in one study (Aszmann 2004). The other two did not present any data and were either personal opinion or discussion of a paper (Seckel 1992; Baravarian 2006).

Risk of bias in included studies

None of the studies included diagnostic criteria for diagnosis of peripheral neuropathy. For example, the distribution or presence of paresthesias, numbness, or pain, or weakness was not available. Similarly, none of the studies alluded to any description of neurological examination in terms of abnormalities of sensory testing, motor examination, or reflexes; presence and location of ulcerations and precise sensory loss was not defined. Nerve conduction study was done in only one study (Dellon 1992) but data were not provided and upper extremity entrapments were mixed in with lower extremity and diffuse peripheral neuropathy. Except for the presence of Tinel's sign, there was no other direct clinical or nerve conduction data given to identify the presence of compressive neuropathies. Baseline pain score was only described for one study (Rader 2005). None had functional measures defined at baseline. Although the presence of diabetes was described in six studies, only three reported the number of patients with type 1 and 2 diabetes (Aszmann 2000; Dellon 1992; Rader 2005). Visual analogue pain scale was the primary end point in one study (Rader 2005). End points in the other studies included static or moving two‐point discrimination in three (Aszmann 2000; Dellon 1992; Rader 2005) pressure‐specific sensory device testing in three (Aszmann 2000; Ducic 2006; Rader 2005), testing of sway in one (Ducic 2006) and presence of ulcerations in one (Aszmann 2004).

None of the studies were randomized so the authors could not comment on allocation concealment or security method of randomization. None were subject blinded and only two had partial blinding by the assessor (Aszmann 2000; Rader 2005). Lack of randomization also makes any comment on completeness of follow up meaningless.

Effects of interventions

No randomized controlled studies were identified but non randomized controlled studies have been considered in the Discussion.

Discussion

In the absence of data from randomized controlled trials we considered the data from non randomized observational studies. From six such studies a total of 218 treated patients were available. Two other studies did not provide any data. Only 183 had definite diabetes identified. Two studies identified a total of 80 limbs that underwent operation (Dellon 1992; Rader 2005). A total of 123 patients had operations on the tibial nerve at the ankle (including calcanean, medial, and lateral plantar), peroneal nerve at the knee, and deep peroneal nerve at the ankle. Twenty had operations only on the tibial nerve at the ankle (including calcanean, medial, and lateral plantar nerves). In 92 it was not clear which lower extremity nerves and in which combination were operated. One hundred and fifteen had unilateral surgery and at least 10 had bilateral surgery and in the 66 others, it was not clear if unilateral or bilateral surgery was done. The follow up ranged from 3 to 84 months.

Primary outcome measure

Only one study defined VAS as the primary end point (Rader 2005). Lack of randomization, blinding, and adequate baseline information on neuropathy or compression makes this study suboptimal.

Secondary outcome measures

(1) Nerve conduction data of sensory nerve action potential (SNAP) amplitudes for sural, superficial peroneal, medial or lateral plantar nerves were not available for any study. Neither was there data for compound muscle action potential (CMAP) amplitudes, distal motor latency or conduction velocity provided for peroneal or tibial nerves. 
 (2) None of the studies included any validated clinical impairment or neurological examination validated scale. 
 (3) Although two studies (Ducic 2006; Rader 2005) reported an improvement of 2 point discrimination, lack of controlled data, lack of blinding, and lack of formal statistically significant values, makes any assessment or comment difficult. 
 (4) None of the studies included any validated functional measures of impairment or disability. 
 (5) One study reported no ulcerations in the surgery group and 12 ulcerations and 3 amputations in the non decompressed side two to seven years after surgery (Aszmann 2004).

This analysis failed to identify any controlled study or well designed prospective study controlling for the non‐operated limb that showed improvements in pre‐defined end points after decompressive surgery. In the studies which were identified, definitions for peripheral neuropathy and compressive neuropathy were not available. The side of surgery (generally more symptomatic), the number of nerves operated upon, the end points, and follow‐up, all differed. These many methodological flaws hindered any interpretation of the data, most of which were biased, given the lack of blinding, and subjective (pain or patient's response to 2 point discrimination).

In one study, the VAS was tested weekly for 3 to 18 months (Rader 2005). Preoperative VAS pain score was 8.72+1.6 and pain score was 0.63+0.4 at week 1 and 0.31+0.3 at the final visit. By Mann‐Whitney test for non parametric analysis this change was considered significant.

Four studies commented on 1 or 2 point discrimination. However only 2 of these actually provided any real data (Ducic 2006; Rader 2005). One study measured "sway" with eyes open and closed (Ducic 2006). The study design and barely significant values reported in a small number of patients make any conclusion difficult.

Adverse effects attributed to the study intervention were reported in two studies. One study (Dellon 1992) reported that one patient had loss of foot eversion following neurolysis of the common peroneal nerve and needed a foot brace; one patient had burning pain secondary to posterior tibial release and six patients developed medial ankle wound healing complications. One ankle wound required a skin graft for closure. Two ankle wounds had cellulitis requiring inpatient intravenous antibiotics in the surgery group and nine in control group withdrew because of toxicity. The second study (Rader 2005) reported separation of the medial ankle incision site but the number with this complication was not reported.

No information on the cost benefits was available.

Comment

The quality and characteristics of the studies reviewed were quite variable, and included different measures of neuropathy (qualitative and subjective), different interventions, different durations of follow‐up, and somewhat different analyses. Some studies mixed upper extremity with lower extremity entrapments and others did not clearly delineate lower extremity entrapments from distal symmetric neuropathy. Degree of diabetic control and baseline neuropathic medications were not controlled.

Authors' conclusions

Implications for practice.

The evidence reviewed suggests that the role of decompressive surgery for diabetic symmetric distal neuropathy is unproven.

Implications for research.

There is a need for randomized controlled clinical trials, using objective measures of neuropathy, and appropriate masking of subjects and examiners. These should include adequate numbers of participants to evaluate the efficacy of decompressive surgery for DSDP.

What's new

Date	Event	Description
1 March 2011	Amended	Contact details updated.

History

Protocol first published: Issue 3, 2006
 Review first published: Issue 3, 2008

Date	Event	Description
27 April 2008	Amended	Converted to new review format.

Appendices

Appendix 1. OVID MEDLINE search strategy

1. exp diabetes mellitus/ 
 2. diabet$.mp. 
 3. 1 or 2 
 4. neuropath$.mp. 
 5. exp Peripheral Nervous system diseases/ 
 6. peripheral$ nervous$ system$ disease$.mp. 
 7. polyneuropath$.mp. 
 8. peripheral nerves/su [surgery] 
 9. or/4‐8 
 10. 3 and 9 
 11. exp diabetic neuropathies/ 
 12. diabet$ neuropath$.mp. 
 13. diabet$ polyneuropath$.mp. 
 14. diabetic foot.mp. or diabetic foot/su [surgery] 
 15. or/11‐14 
 16. 10 or 15 
 17. decompression, surgical/ 
 18. decompress$ surg$.mp. 
 19. decompress$ operat$.mp. 
 20. nerve compression syndromes/su [surgery] 
 21. tarsal tunnel syndrome/su [surgery] 
 22. tarsal tunnel surger$.mp. 
 23. tarsal tunnel syndrome/ 
 24. surger$.mp. or surgery/ 
 25. 23 and 24 
 26. or/17‐22,25 
 27. 16 and 26

Appendix 2. OVID EMBASE search strategy

1. exp diabetes mellitus/ 
 2. diabet$.mp. 
 3. 1 or 2 
 4. neuropath$.mp. 
 5. exp Peripheral Nervous system diseases/ 
 6. peripheral$ nervous$ system$ disease$.mp. 
 7. polyneuropath$.mp. 
 8. peripheral nerve/ 
 9. or/4‐8 
 10. 3 and 9 
 11. exp diabetic neuropathies/ 
 12. diabet$ neuropath$.mp. 
 13. diabet$ polyneuropath$.mp. 
 14. diabetic foot.mp. or diabetic foot/su [surgery] 
 15. or/11‐14 
 16. 10 or 15 
 17. decompression, surgical/ 
 18. decompress$ surg$.mp. 
 19. decompress$ operat$.mp. 
 20. nerve compression syndromes/su [surgery] 
 21. tarsal tunnel syndrome/su [surgery] 
 22. tarsal tunnel surger$.mp. 
 23. tarsal tunnel syndrome/ 
 24. surger$.mp. or surgery/ 
 25. 23 and 24 
 26. or/17‐22,25 
 27. 16 and 26

Appendix 3. OVID CINAHL search strategy

1. exp diabetes mellitus/ 
 2. diabet$.mp. 
 3. 1 or 2 
 4. neuropath$.mp. 
 5. exp Peripheral Nervous system diseases/ 
 6. peripheral$ nervous$ system$ disease$.mp. 
 7. polyneuropath$.mp. 
 8. peripheral nerves/su [surgery] 
 9. or/4‐8 
 10. 3 and 9 
 11. exp diabetic neuropathies/ 
 12. diabet$ neuropath$.mp. 
 13. diabet$ polyneuropath$.mp. 
 14. diabetic foot.mp. or diabetic foot/su [surgery] 
 15. or/11‐14 
 16. 10 or 15 
 17. decompression, surgical/ 
 18. decompress$ surg$.mp. 
 19. decompress$ operat$.mp. 
 20. nerve compression syndromes/su [surgery] 
 21. tarsal tunnel syndrome/su [surgery] 
 22. tarsal tunnel surger$.mp. 
 23. tarsal tunnel syndrome/ 
 24. surger$.mp. or surgery/ 
 25. 23 and 24 
 26. or/17‐22,25 
 27. 16 and 26

Appendix 4. LILACS search strategy

((Pt randomized controlled trial OR Pt controlled clinical trial OR Mh randomized controlled trials OR Mh random allocation OR Mh double‐blind method OR Mh single‐blind method) AND NOT (Ct animal AND NOT (Ct human and Ct animal)) OR 
 
 (Pt clinical trial OR Ex E05.318.760.535$ OR (Tw clin$ AND (Tw trial$ OR Tw ensa$ OR Tw estud$ OR Tw experim$ OR Tw investiga$)) OR ((Tw singl$ OR Tw simple$ OR Tw doubl$ OR Tw doble$ OR Tw duplo$ OR Tw trebl$ OR Tw trip$) AND (Tw blind$ OR Tw cego$ OR Tw ciego$ OR Tw mask$ OR Tw mascar$)) OR Mh placebos OR Tw placebo$ OR (Tw random$ OR Tw randon$ OR Tw casual$ OR Tw acaso$ OR Tw azar OR Tw aleator$) OR Mh research design) AND NOT (Ct animal AND NOT (Ct human and Ct animal)) OR 
 
 (Ct comparative study OR Ex E05.337$ OR Mh follow‐up studies OR Mh prospective studies OR Tw control$ OR Tw prospectiv$ OR Tw volunt$ OR Tw volunteer$) AND NOT (Ct animal AND NOT (Ct human and Ct animal))) AND 
 
 (((Mh diabetes mellitus OR diabet$) AND (neuropath$ OR Mh Peripheral Nervous system diseases OR peripheral$ nervous$ system$ disease$ OR polyneuropath$ OR Mh peripheral nerves)) OR (Mh diabetic neuropathies OR diabet$ neuropath$ OR diabet$ polyneuropath$ OR diabetic foot OR Mh diabetic foot)) AND (Mh decompression, surgical OR decompress$ surg$ OR decompress$ operat$ OR Mh nerve compression syndromes OR tarsal tunnel surger$ OR (Mh tarsal tunnel syndrome AND (surger$ or Mh surgery)))

Characteristics of studies

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Aszmann 2000	Prospective study but not a randomized controlled study. Used comparison to the opposite non‐operative side to assess improvement.
Aszmann 2004	Retrospective study with no control arm.
Baravarian 2006	Discussion of a paper.
Dellon 1992	Prospective study but not a randomized controlled study.
Ducic 2006	Prospective study but not a randomized controlled study.
Maloney 2006	Retrospective study with no control arm.
Rader 2005	Prospective study but not a randomized controlled study. Used comparison to the opposite non‐operative side to assess improvement.
Seckel 1992	Personal opinion.

Contributions of authors

Vinay Chaudhry wrote the first draft and James Russell and Allan Belzberg commented on the first draft and made revisions.

Sources of support

Internal sources

• Department of Neurology, University of Michigan and Department of Veteran Affairs, USA.

External sources

• National Institutes of Health and Juvenile Diabetes Foundation, USA.

Declarations of interest

Dr Chaudhry has nothing to disclose. 
 Dr Russell has nothing to disclose. 
 Dr Belzberg has nothing to disclose.

Edited (no change to conclusions)