ORIGINAL ARTICLES

Persistent Postoperative ComplaintsAfter Whole Sural Nerve Biopsies inDiabetic and Non-diabetic SubjectsLars B. Dahlin*1, Karl-Fredrik Eriksson2, Goran Sundkvist2

1Department of Hand Surgery, University Hospital, Malmo, Sweden2Department of Endocrinology, University Hospital, Malmo, Sweden

The postoperative effects of a whole sural nerve biopsy in diabetic (11) and non-diabetic(10 healthy controls, 10 patients with impaired glucose tolerance and 2 patients withpolyneuropathy) subjects were investigated by a mailed questionnaire 20–44 months afterthe surgical procedure (10/11 vs 21/22 answers received). Pain in the biopsy area atfollow-up was reported in 4/10 of the diabetic patients (p = 0.01) but in none of the non-diabetic subjects (0/21). An increased number (p = 0.01) of diabetic patients (5/10 vs1/21) had cold intolerance in their foot or leg whereas 11/31 of all patients haddysaesthesia in the affected skin. Overall 6/31 patients described serious problems at thetime of the questionnaire, and 4 of this 6 having diabetes. Loss of sensation was reportedin almost all subjects irrespective of diabetes or not; however, a decrease in the area ofloss of sensation was reported most often in diabetic patients (8/10 vs 8/21, p = 0.02). Itis concluded that whole surval nerve biopsies give rise to persistent problems both indiabetic and non-diabetic subjects. The reason for a sural nerve biopsy has always to becarefully considered before being conducted. 1997 by John Wiley & Sons, Ltd.

No of Figures: 1. No of Tables: 1. No of Refs: 12

KEY WORDS Sural nerve Nerve biopsy Sequele

Received 13 May 1996; revised 5 November 1996; accepted 24 November 1996

Introduction Subjects and Methods

Patient MaterialSural nerve biopsies are used for diagnosis of polyneuro-pathies of unclear origin,1 but the procedure is rare in

During 1991 and 1993 whole sural nerve biopsies werecommon clinical practice. It is used, however, inperformed in 33 male subjects (median age 64, rangepharmacological trials of potential treatments for diabetic42–76 years). The project was approved by the Ethicalneuropathy.2 The differences between fascicular andCommittee of Lund University. All patients received oralwhole nerve sural biopsies in this context have beenand written information concerning the biopsy procedurediscussed,1,3 but there are few reports concerning thepreoperatively. The material consisted of 11 diabeticlong-term consequences of sural nerve biopsies. Onepatients (all with non-insulin-dependent (Type 2) diabetesrecent study found no increase in postoperative compli-mellitus), 10 subjects with impaired glucose tolerance,cations following sural nerve biopsies in diabetic as10 healthy control subjects, and 2 patients with poly-opposed to non-diabetic subjects4 but such data are rare.neuropathy of unclear origin. Of the diabetic patientsWe recently performed a study of peripheral nerve6/11 had symptoms or clinical signs of diabetic peripheralfunction in subjects with normal, impaired, and diabeticneuropathy (lack of ankle reflexes in 4/11, paraesthesiaglucose tolerance.5 Sural nerve biopsies were obtainedin 2/11).from these subjects to correlate nerve function to

biochemical or morphological alterations and the resultswill be reported elsewhere. The aim of the present paper Surgical Procedureis to report the short-term and, most importantly, persistent

After infiltration anaesthesia (local anaesthetics: 1 %complications 20–44 months after sural nerve biopsy inmepivacaine without adrenaline), a 7–8 cm length longi-human subjects with and without diabetes mellitus.tudinal incision was made between the lateral malleolusand the achilles tendon without the use of a tourniquet.The sural nerve was identified and was then blocked atleast 1.5 cm proximal to the proximal incision. The nervewas then freed from the surrounding connective tissueand the proximal end was cut. Thereafter the nerve was* Correspondence to: Lars B. Dahlin, Department of Hand Surgery,

University Hospital, S-205 02 Malmo, Sweden carefully dissected for 6 cm and the distal end was

353CCC 0742–3071/97/050353–04$17.50 1997 by John Wiley & Sons, Ltd. DIABETIC MEDICINE, 1997; 14: 353–356

ORIGINAL ARTICLESexcised by a scalpel. Before closing the wound, the and dysaesthesia (increased skin sensation when touched;

4/10 vs 7/21; p = 1.0) was frequent in both groups.proximal nerve end was pulled down and at least 1.5 cmwas excised to keep the cut end away from the Of the non-diabetic subjects 19/21 reported mild or

no symptoms 2–4 years after the operation whereaswound bed. The wound was closed with interrupted4.0 monofilament proline sutures. A normal dressing was 4/10 diabetic patients reported symptoms affecting their

activities of daily living. Only 1 of 10 diabetic patientsapplied (paraffin gauze dressing, gauze swabs with saline,elastic gauze bandages, foam swabs, and a long stretch would theoretically accept a second sural nerve biopsy.compression bandage). The patient was asked to keephis foot elevated for at least 3 hours. The procedure was Discussionusually performed on a Friday, to permit rest during thefollowing days. The dressing was changed on day 3 Two to four years after sural nerve biopsies most subjects,

whether diabetic or non-diabetic, complained of loss ofpostoperatively and the sutures were removed between10 and 14 days later. sensation and, to a lesser extent, paraesthesia and

dysaesthesia in the foot. The frequency of pain in thefew days after surgery in our subjects correlates wellQuestionnairewith previous reports4,6,7 and is quite high. While noneof the control subjects reported pain in the operationIn the summer of 1995, i.e. 20–44 months after biopsy,area at later follow-up, between one-third and one-halfa questionnaire was mailed to 32/33 patients (Table 1);of the diabetic patients did. Such persistent pain in theone diabetic patient had died. We received 31 answers.operation area, but not in the foot, has been reportedDue to Swedish regulation all questionnaires had to bepreviously; 10–58 % of the diabetic or patients withunidentified and therefore it is not possible to attributepolyneuropathy have persistent pain after sural nerveresponses to particular individuals.biopsy.1,4,6–8 In our study, this persistent pain affecteddaily living and caused sleep disturbance in some of the

Statistics diabetic subjects, although no problems with woundhealing or foot ulcers have been reported.

The results are presented as absolute values in Table 1. Surprisingly, more diabetic than non-diabetic subjectsThe Fisher’s exact test (two-tailed) was used to evaluate reported that the area with loss of sensation had decreasedany statistical significant difference between the diabetic by the time of the questionnaire. The decrease in sensoryand the non-diabetic patients. A p-value less than 0.05 loss in the subjects might be due to collateral sproutingwas regarded as significant. although it is unlikely that this would be more frequent

in diabetic patients who are considered to have impairednerve regeneration.9,10 It is possible that progression ofResultsdiabetic neuropathy leads to less discriminative ability.

Cold intolerance was most common in diabetic patientsSubjects with impaired glucose tolerance, control sub-jects, and the two non-diabetic patients were considered and these symptoms may reflect neuropathy. Cold

intolerance is also frequently reported in subjects exposedas one group (= non-diabetic subjects). The questionnaireand the answers are summarized in Table 1. No infection to hand-held vibration tools11 and may be an early

sign of nerve injury. Such a phenomenon as well aswas seen postoperatively but one patient had a minorwound rupture 13 days post biopsy which healed without dysaesthesia, which was reported by about one third of

subjects, are common symptoms following nerve injuriescomplications. 11 subjects, 4 with diabetes, experiencedlocal discomfort in the days following surgery. such as transection injuries.

Most of our diabetic patients said they would refuseTwo to four years after the biopsy, local pain in thearea of operation had disappeared in all (21/21) non- a second biopsy on the contralateral side. Such infor-

mation is important to consider when performing drugdiabetic subjects but was still present in 4/10 diabeticpatients (p = 0.01). In contrast, few subjects in either studies in which bilateral biopsies are required. Our data

show that the area of loss of sensation decreases withgroup (1/21 non-diabetic subjects and 2/10 diabeticpatients, p = 0.24) reported pain in the foot (innervation time and the persistence of symptoms of pain and

discomfort may be due to the neuropathic process, so itarea of the sural nerve). Almost all (29/31) subjects hadsensory loss to a variable extent (Figure 1) immediately might well be reasonable to conduct sural nerve biopsies

if new therapeutic strategies emerge from the findings.following the procedure; however, while the area withsensory loss had remained unchanged in 13/21 of the It is evidently important that careful information is given

to patients who may be included in drug studies.non-diabetic subjects 2–4 years after the biopsy, it haddecreased in 8/10 subjects with diabetes (p = 0.02). With regard to non-diabetic, healthy subjects, there is

a question as to whether biopsies should be performedCold intolerance (increased sensation to cold but noblanching of the skin) was more frequent in diabetic at all. This study clearly shows that while pain disappears

in such subjects, loss of sensation, dysaesthesia andpatients than non-diabetic subjets (5/10 vs 1/21; p = 0.01)whereas paraesthesia (tingling) (8/10 vs 10/21; p = 0.13) paraesthesia may persist. It is of course difficult to

354 L. DAHLIN ET AL.

ORIGINAL ARTICLESTable 1. Questionnaire

Diabetic Non- Total p-value(n = 10) diabetic (n = 31)

(n = 21)

1. Did you have any discomfort Yes 0 0 0(a) during the operation? No 10 21 31 1.0(b) directly after the operation? Yes 4 2 6

No 6 19 25 0.072. Did you experience any loss of sensation in the Yes 8 19 27

operated area after the operation? No 2 2 4 0.583. Did you have pain in the operated area during Yes 4 7 11

the days after surgery? No 6 14 20 1.04. Do you still have pain in the area of operation? Yes 4 0 4

No 6 21 27 0.015. Could you work as usual after surgery? Yes 8 19 27

No 0 1 1 0.30Retired 2 0 2No reply 0 1 1

6. Do you have loss of sensation in the operated Yes 10 19 29foot compared to the other foot? No 0 2 2 0.55

7. Mark the area with sensory deficit in the figure 0 0 2 2(see Figure 1 for explanation of I–IV). I 3 6 9

II 3 5 8III 2 4 6IV 1 4 5No reply 1 0 1

8. (a) Has the area with loss of sensation decreased Yes 8 8 16compared to the time directly following surgery? No 1 13 14 0.02

No reply 1 0 1(b) If yes, how much (%)? 0–25 4 2 6

25–50 3 1 450–75 1 3 475–100 0 2 2

9. (a) Do you feel pain in the foot? Yes 2 1 3No 8 20 28 0.24

(b) When? Day 1 0 1Night 0 0 0Day and night 1 1 2

10. (a) Do you have a problem with cold intolerance Yes 5 1 6in the operated foot/leg? No 5 20 25 0.01(b) If yes, how often? Often 3 0 3

Seldom 2 1 3 –11. (a) Have you experienced problems with Yes 4 7 11

increased skin sensation when the skin is touch- No 6 14 20ed? 1.0(b) If yes, how often? Often 2 0 2

Sometimes 2 4 6Seldom 0 3 3 –

12. Do you experience discomfort (tingling) along Yes 8 10 18the outside of the foot? No 2 11 13 0.13

13. If so: when do these symptoms occur? Rest 0 3 3Walking 3 1 4If the area is knocked 5 6 11 –

14. How would you describe your problems at Disturbed sleep 1 0 1the moment? Powerful 1 1 2

Affecting daily living 2 1 3Mild 1 11 12None 4 8 12No reply 1 0 1

15. Do you have to take painkillers often? Yes 2 0 2No 8 21 29 0.10

16. Do you have diabetes? Yes 10 0 10No 0 21 21 –

17. A theoretical question: would you be prepared Yes 1 7 8to have a surgical biopsy on the other side? No 9 14 23 0.22

355SEQUELE OF SURAL NERVE BIOPSIES

ORIGINAL ARTICLESbiopsy is performed and the procedure should beperformed by an experienced surgeon. The indicationsfor the procedure must be rigorous and clear.

Acknowledgements

The work was supported by the Swedish MedicalResearch Council (5188, 7507), the Faculty of Medicine,Lund University, Lundstrom Foundation, Malmo DiabetesAssociation, Swedish Diabetes Association, and HeartLung Foundation.

Figure 1. Schematic drawing of the lateral part of the foot. Thepatients were requested to mark on the figure the present area Referenceswith sensory deficit. Following their answers the area of thesensory deficit could be categorized into four groups: 0 = none, 1. Dyck PJ, Karnes J, Lais A, Lofgren EP, Stevens JC. PathologicI = lateral aspect of the heel, II = lateral aspect of the foot, alterations of the peripheral nervous system of human. In:III = lateral aspect of the heel and the foot, IV = lateral aspect Dyck PJ, Thomas PK,Lambert EH, Bunge R, eds. Peripheralof the heel and foot including the little toe Neuropathy, 2nd edn. Philadelphia: W.B. Saunders, 1984:

771–778.2. Sima AA, Bril V, Nathaniel, McEwen TA, Brown MB,

conclude from this small study that sural nerve biopsies Lattimer SA, Greene DA. Regeneration and repair oftherefore should not be conducted in healthy subjects. myelinated fibres in sural-nerve biopsy specimens from

patients with diabetic neuropathy treated with sorbinil. NNevertheless, our data emphasize that the scientificEngl J Med. 1988; 319: 548–555.indication for conducting sural nerve biopsies must be

3. Pollock M, Nukada H, Taylor P, Donaldson I, Carroll G.strong. The procedure to harvest a sural nerve for usingComparison between fascicular and whole sural nerve

as a graft when reconstructing major nerve injuries in biopsy. Ann Neurol 1983; 13: 65–68.the upper extremity is used in non-diabetic individuals 4. Perry JR, Bril V. Complications of sural nerve biopsy in

diabetic versus non-diabetic patients. Le Journal Canadienand probably leads to similar problems but in thesedes Sciences Neurologiques 1994; 21: 34–37.patients the discomfort from the upper extremity is

5. Eriksson KF, Nilsson H, Lindgarde F, Osterlin S, Dahlinsubstantial and the need for the procedure more evident.LB, Lilja B, et al. Diabetes mellitus but not impaired

It should be noted that our questionnaire data have glucose tolerance is associated with dysfunction in periph-not been validated outside the study, nor confirmed eral nerves. Diabetic Med 1994; 11: 279–285.

6. Solders G. Discomfort after fascicular sural nerve biopsy.objectively. Furthermore, our study examined only sub-Acta Neurol Scand 1988; 77: 503–504.jects after whole nerve biopsy. Whole sural nerve biopsies

7. Neundorfer B, Grahmann F, Engelhardt A, Harte U.have been recommended in preference to fascicularPostoperative effects and value of sural nerve biopsies: A

biopsies since the former are simpler, have greater retrospective study. Eur Neurol. 1990: 30: 350–352.diagnostic potential, allow for more complete morpho- 8. Poburski R, Malin JP, Stark E. Sequelae of sural nerve

biopsies. Clin Neurol Neurosurg 1985; 87: 193–198.logical evaluation3 and may be preferable as the risk of9. Ekstrom PA, Tomlinson DR. Impaired nerve regenerationartefacts is less. Moreover, if there are persistent problems

in streptozotocin-diabetic rats is improved by treatmentwith the formation of neuroma, it is possible to transposewith gangliosides. Exp Neurol 1990; 109: 200–203.

this into deeper fat tissue or beneath the fascia, leading 10. Longo FM, Powell HC, LeBeau J, Gerrero MR, Heckmanto an improvement in 70 to 80 % of patients.12 Our H, Myers RR. Delayed nerve regeneration in streptozotocin

diabetic rats. Muscle & Nerve 1986; 9: 385–393.study does not take this argument further.11. Stromberg T, Dahlin LB, Lundborg G. Hand problemsIn summary, whole sural nerve biopsies may give

among one hundred vibration-exposed symptomatic malepersistent problems in both diabetic and non-diabeticworkers. J Hand Surg (Br) 1996; 21B: 315–319.

subjects and there are differences in features between 12. Herndon JH, Hess AV. Neuromas. In: Gelberman RH, ed.these groups. It is important that careful and meticulous Operative Nerve Repair and Reconstruction. Philadelphia:

Lippincott Company, 1991; 1525–1540.information be given to patients before a sural nerve

356 L. DAHLIN ET AL.