Comparison between Results of Surgical and Conservative Treatment for Diabetic Peripheral Neuropathy

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1 Med. J. Cairo Univ., Vol. 3, No. 1, Setember: , Comarison between Results of Surgical and Conservative Treatment for Diabetic Periheral Neuroathy AMR M. SAFWAT, M.D.*; AHMED A. TAHER, M.D.*; AHMED E. AHMED, M.D.*; DALIA R.A. ABD EL-RAHMAN, M.D.** and ABD EL-HAMID H. SHADY, M.Sc.* The Deartments of Neurosurgery* and Internal Medicine**, Faculty of Medicine, Cairo University Abstract Background: Diabetic Periheral Neuroathy (DPN) is a common comlication of diabetes. Poulation-based cohort studies have shown that 66% of tye I and 59% of tye 2 diabetics have objective evidence of eriheral neuroathy. Comlications of DPN are a major cause for hositalization among eole with diabetes, and neuroathy ranks third in lifetime exenditures associated with the comlications of diabetes, behind macrovascular disease and nehroathy. Although this hyothesis has some exerimental suort, evidence to the contrary showing resistance to axonal degeneration after nerve comression also exists. Surgical decomression of multile eriheral nerves is being utilized as an alternative aroach to treatment of symtomatic diabetic neuroathy. This is based on the hyothesis that diabetic nerves are more vulnerable to comressive injury at otential sites for entrament. Objective: To comare the results of surgical decomression in atients with comlicated diabetic eriheral neuroathy with the results of conservative medical treatment. Methods: This study was conducted in the Neurosurgery Deartment, Faculty of Medicine, Cairo University Hositals in the eriod from Decembe 211 to November 213. The study included two grous: Grou 1: Fifty atients with comlicated diabetic eriheral neuroathy who are surgically managed by eriheral nerve decomression in the region of the caral and tarsal tunnels and Grou 2: Fifty atients with comlicated diabetic eriheral neuroathy who are treated with conservative medical treatment. All atients were subjected to: Full history taking, comlete general medical examination, fasting blood sugar, ostrandial blood sugar and electromyograhy. Surgical candidates were subjected to division of the flexor retinaculum in the hand or feet. Nonsurgical candidates were subjected to conservative medical treatment and follow-u. Results: The atients' age ranged from years for Grou I and from years for Grou II. The mean age was 5.5± 1.3 years for Grou I and was 57 ±. years for Grou II. There is a good clinical imrovement of % of cases by surgical decomression of eriheral nerves. 62% of cases show ersistent comlaints with conservative medical Corresondence to: Dr. Amr M. Safwat, The Deartment of Neurosurgery, Faculty of Medicine, Cairo University treatment. There is an imrovement in nerve conduction velocity after decomression of affected eriheral nerves in % of atients of the surgical grou. The imrovement was % in surgical grou comared to 3% in medical grou and the difference was statistically highly significant. About 73% of the surgically managed atients showed imrovement of ischemia in the erihery as well as about 2% showed imrovement of the neurologic condition as regarding neuroathic ain and muscle weakness imrovement in the form of imroved hand-gri and good walking. Conclusions: It could be concluded that atients with comlicated Diabetic Periheral Neuroathy (DPN) could be surgically managed successfully by decomression of eriheral nerves at site of comression in caral and tarsal tunnels with good results in atients resistant to medical treatment. Key Words: Periheral neuroathy Diabetes. Introduction 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 hyerglycemia (elevated levels of blood glucose) with longterm comlications including retinoathy, nehroathy, cardiovascular disease, and eriheral neuroathy. World Health Organization (WHO) data suggested that there will be 353 million eole with diabetes mellitus by 23 [1]. Diabetic Periheral Neuroathy (DPN) is one of the most common comlications of diabetes, 66% of eole with tye 1 diabetes and 59% of eole with tye 2 have objective evidence of eriheral neuroathy [2]. Distal Symmetrical Diabetic Polyneuroathy (DSDP) is the most common form of diabetic neuroathy. It is characterized by a stocking-glove attern of symmetrical sensory symtoms and signs and distal weakness in the hands and feet [3]. 739

2 7 Comarison between Results of Surgical & Conservative Treatment for DPN Diabetic eriheral neuroathy, once develoedd, is irreversible and slowly rogressive. A variety of treatments aimed at altering the metabolic abnormalities has been tried but none are roven effective. A number of agents have been used to treat the neuroathic ain []. Surgical decomression for diabetic eriheral neuroathy is a roosed treatment strategies by using surgical decomression of uer and lower limb nerves. This method is being increasingly used as an alternative aroach to treatment for diabetic neuroathy. This is based on the hyothesis that diabetic nerves are more vulnerable to comressive injury at otential sites of entrament [5]. The results of nerve decomression surgery for cases of DPN in the otential sites of anatomical narrowings is encouraging because it was found that a good ercentage of atients showed imrovement in ain and sensations, also decomression has been dshown to reduce the risk of ulceration, reulceration and amutations [6]. The aim of the work is to evaluate the results of surgical decomression in atients with comlicated diabetic eriheral neuroathy. Patients and Methods This study was conducted in the Neurosurgery Deartment, Faculty of Medicine, Cairo University Hositals in the eriod from December 211 to November 213. Study grous: The study included two grous: Grou 1: Fifty atients with comlicated diabetic eriheral neuroathy who are surgically managed by eriheral nerve decomssion in the region of the caral and tarsal tunnels. Grou 2: Fifty atients with comlicated diabetic eriheral neuroathy who are treated with conservative medical treatment. Inclusion criteria: 1- Comlicated diabetic atients. 2- EMG-and NCS-roved neuroathy. Exclusion criteria: 1- Entrament or eriheral neuroathies in nondiabetic atients. 2- Neuroathic atients with other medical diseases. Intervention methods: All atients were subjected to: 1- Full history taking. 2- Comlete general medical examination. 3- Fasting Blood Sugar (FBS) and Postrandial Blood Sugar (PBS). - EMG on the affected sites for all atients and for surgical candida follow-u EMG after surgery. The results are analyzed statistically and comared in the two grous of atients. 5- For surgical candidates, by division of the flexor retinaculum in the hand or feet. 6- For non-surgical candidates were subjected to conservative medical treatment and follow-u. Intervention results: Results were observed according to rimary and secondary outcome arameters. A- Primary outcome arameters include: 1- Imrovement of neuroathic ain. 2- Faster healing of diabetic foot ulcers. B- Secondary outcome arameters e.g. 1- Less medications used in neuroathic ain. 2- Imrovement of vacularity of hands and feet after surgery with less incidence of ischaemia or gangrene. 3- Neurologic condition imrovement with stronger handgri or easy walking after surgery. Statistical analysis: Data were checked, entered and analyzed by using SPSS comuter rogram (Statistical Package for Social Sciences) verison (2.). Data were exressed as mean and standard deviation (±SD) for quantitative variables and number and ercentage for categorical variables. Chi-square test is used for association between qulitative data. t-test is used for comarison of mean and standard deviation (±SD) of two grous. Probability is considered significant when - value equals or is less than.5. -value >.5 = Insignificant difference. -value <.5 = Significant difference. -value <.1 = Highly significant. Results The atients' age ranged from years for Grou I and from years for Grou II. The mean age was 5.5 ± 1.3 years for Grou I and

3 Amr M. Safwat, et al. 71 was 57±. years for Grou II. The studied grous were comarable as regarding age and gender. There is no statistically significant difference between the two grous as regarding age and sex (Table 1). There were non-significant differences between medical and surgical grous as regard Fasting Blood Sugar (FBS) and Postrandial sugar (PP) (Table 2). Persistent neuroathic ain was higher in medical than surgical (% comared to 22%), but the difference was not statistically significant (Table 3). There is a good clinical imrovement of % of cases by surgical decomression of eriheral nerves (Table ). 62% of cases show ersistent comlaints with Table (3): Persistent comlaint of surgical and medical cases. - Persistent neuroathic ain - Stock hyothesia - Glove hyothesia - Stock and glove hyothesia - Diabetic foot ulcer - Stock hyothesia and foot ulcer - Stock, glove hyothesia and foot ulcer Surgical Medical * χ * Total Table (): Success rates among surgical cases. - Persistent neuroathic ain (n= 16) - Stock hyothesia (n=1 ) - Glove hyothesia (n=) - Stock and glove hyothesia (n=9) Imroved Not imroved conservative medical treatment (Table 5). - Diabetic foot ulcer (n=) Stock hyothesia and foot ulcer (n=2) - Stock, glove hyothesia and foot ulcer (n=1) There is an imrovement in nerve conduction velocity after decomression of affected eriheral nerves in % of atients of the surgical grou (Table 6). χ Total (n=5) The imrovement was % in surgical grou comared to 3% in medical grou and the difference was statistically highly significant (Table 7). About 73% of the surgically managed atients showed imrovement of ischemia in the erihery as well as about 2% showed imrovement of the neurologic condition as regarding neuroathic ain and muscle weakness imrovement in the form of imroved hand-gri and good walking (Table ). Table (1): Demograhic data: Frequency of age and sex of the studied atients. I II t Age (years): Mean ± SD 5.5± ±..1.1 Range (NS) Gender: Male 17 (3%) 1 (2%) χ 2 =.51 Female 33 (66%) 36 (72%).2 (NS) Table (2): Fasting and ostrandial blood sugar. I (Medical) II (Surgical) t FBS: Mean ± SD 12.2±3.9 1± Range (NS) PP: Mean ± SD 26.5±9. 29.± Range (NS) Table (5): Results of medical cases. - Persistent neuroathic ain (n=2) - Stock hyothesia (n=) - Glove hyothesia (n=) - Stock and glove hyothesia (n=12) - Diabetic foot ulcer (n=2) Imroved Not imroved χ Total (n=5) Table (6): Results of Electromyograhy (EMG) and Nerve Conduction Studies (NCS) in surgically managed atients. Imroved Not imroved No % 2 16 Table (7): Comarison between surgical and medical outcomes. - Persistent neuroathic ain - Stock hyothesia - Glove hyothesia - Stock and glove hyothesia - Diabetic foot ulcer Surgical Medical 13/16 /1 / 7/9 /11 χ / (S) / 2/ / (S).2 (NS). (S) 72 1/ (NS) - Total /5 19/ (HS)

4 72 Comarison between Results of Surgical & Conservative Treatment for DPN Table (): Secondary outcome arameter comarison between the two grous. Surgical grou Medical grou Secondary outcome arameters Imroved Not imroved Imroved Not imroved Vascularity imrovement (ischemia or gangrene) / / /2 2/2 1 Neurologic imrovement (neuroathic ain and muscle weakness) 32/ / / 7.5 3/ 62.5 Discussion Diabetic Periheral Neuroathy (DPN) is a wellknown microvascular comlication of diabetes mellitus attributed to chronic hyerglycemia, and is defined as the resence of eriheral nerve dysfunction in diabetics after exclusion of other causes [7]. DPN leads to further infections, increasing the risk of foot ulcers and nontraumatic amutations. Estimates of foot infections in diabetes mellitus range from a leftime risk of -7% annually []. The most frequently occurring comlication in tye 2 diabetes is DPN or Distal Polyneuroathy (DSP). DPN affects u to 5% of the oulation with diabetes. Comlications of PN include severe ain, loss of ambulation, and increased risk of foot ulceration and amutation [9]. As with other diabetic microvascular comlications, such as retinoathy and nehroathy, DPN is thought to result form multile factors [1]. Putative mechanisms for the develoment of DPN include glycosylation of neural roteins, microangioathy, the develoment of neural autoantibodies, and ischemia from basement membrane thickening of the nerve caillaries (vasa nervorum). Abnormalities of the olyol athway and defects in metabolism of myoinositol and rotein kinase C3 leading to neuronal demyelination have also been described in DPN [11]. There are two metabolic changes in the eriheral nerves of the diabetic that render the nerve suscetible to chronic comrssion. The most critical is the increased water content within the nerve as the result of glucose being metabolized into sorbitol. This increased water content causes the nerves to have an increased volume. The second metabolic change is a decrease in the slow anterograde comonent of axolasmic flow. This comonent of axolasmic flows transorts the lioroteins necessary to maintain and rebuild the nerve [12]. The combination of decreased elasticity in the eriheral nerve, combined with the nerve's normal hysiologic requirement to stretch as it glides across joints, increases the stress and strain of the eriheral nerve within these areas of known anatomic narrowing. This increasing tension along the nerve further decreases blood flow within the nerve [13]. Since PDN is traditionally considered an irreversible disorder, treatment has been aimed to revent the develoment of comlications. However, in a novel concet, it is ostulated that decomression surgery of the affected nerve may reverse the natural course of PDN [1]. This method is being increasingly used as an alternative aroach for treatment of diabetic neuroathy [15-2]. This is based on the hyothesis that diabetic nerves are more vulnerable to comressive injury at otential sites of entrament [5,21,22]. The suosed basis for this hyothesis is socalled double crush or double athology hyothesis. According to this hyothesis, the coexistence of the diabetic nerve lesion (one crush ) and chronic focal comression (second crush ) results in a double crush of a eriheral nerve. Using this hyothesis, a numb or ainful foot in a diabetic atient could be exlained by double crush of the sural, eroneal and tibial nerves. Hence, reversal of the second crush or athology by surgical decomression may result in symtomatic imrovement [23]. The recommended aroach is to decomrss all sites of otential anatomic entrament involving tarsal tunnel and caral tunnel. External neurolysis is achieved by division of the constricting fibroosseous tunnel tissue and since the origin of entrament is systemic and metabolic, all otential entramenjt sites are considered sites for nerve decomression [2]. The results of nerve decomression surgery for cases of DPN in the otential sites of anatomical narrowings is encouraging because it was found that a good ercentage of atients showed imrovement in ain and sensations, also decomression has been dshown to reduce the risk of ulceration, reulceration and amutations, as observed by Nickerson et al., [6] and Dellon et al., [25].

5 Amr M. Safwat, et al. 73 In our study, we comare results of surgical decomression of eriheral nerves in cases of comlicated diabetic eriheral neuroathy with the results of conservative medical treatment. Our study included 1 cases of comlicated diabetic eriheral neuroathy atients roved clinically and by Electromyograhy (EMG) and Nerve Conduction Studies (NCS). Fifty cases (Grou I) are treated by nerve decomression surgically in the region of caral or tarsal tunnel and EMG and NCS are done ostoeratively for follow-u and fifty cases (Grou II) are treated conservatively by medical treatment and followu. Then, the results of the two grous are comared and statistically analyzed. Our study shows no statistically difference between the two grous of atients as regarding age and the atients' age ranges from 35 to 72 years for surgical grou and from 35 to 75 years for the medical grou. Also, there is no significant difference between the two grous as regarding fsatng and ostrandial blood sugar. In our study, the atients of diabetic eriheral neuroathy were comlicated with ersistent neuroathic ain, decreased sensations in the form of stock or glove hyothesia or both and food ulcers. Our results showed that in the surgically managed grou (5 atients), atients were imroved as regarding these comlications in a success rate of %, while in the medical grou (5 atients), 19 imroved in a success rate of 3% and 31 atients with ersistent comlaint (62% failure rate) after conservative measures and follow-u. Also, there was imrovement in eriheral nerve functions by Electromyograhy (EMG) and Nerve Conduction Studies (NCS) by % in the surgical grou. In comarison with our study, we found that decomression surgery for cases of ersistent neuroathic ain showed imrovement of 1.25% of cases (13 of 16 cases in the surgical grou), and we found in agreement with these results that Dellon [16] in 31 atients with diabetic neuroathic ain the imrovement after nerve decomression surgery was 5%. Also, Chaffe [26] oerated uon 5 cases of diabetic ersistent neuroathic ain and 6% of cases showed imrovement of ain. Also, Yao [27] showed imrovement of 9% of 9 cases oerated for ersistent ainful diabetic neuroathy. In study of Perierra [2] also in 12 atients exosed to eriheral nerve decomression surgery for ainful diabetic eriheral neuroathy, % of atients showed imrovement of ain. In our study as regarding cases with imaired sensations or hyothesia in the form of stock or glove hyothesia or both, we oerated uon 23 of 5 atients in the surgical grou. We observed imrovement of touch and sensibility in 19 atients ina success rate of 2.6%. In comarison with these results, Aszmann [17] did eriheral nerve decomression surgery for 16 diabetic cases with imaired foot sensations and showed that 69% of cases imroved for touch sensations. In comarison with these results. This difference is attributed to advanced state of DPN in his study than that in our study. Also, Valdivia et al., [29] did surgery for diabetic eriheral neuroathy and hyothesia in 6 cases and showed imrovement of 7% of cases for neuroathic ain and imrovement of 5% of cases for touch sensation. Shaffiroff [3] studied 3 atients with DPN with imaired sensations, he observed imrovement of % of atients for touch and 5% of atients for ain after decomression surgery of eriheral nerves for these atients. As regarding cases with diabetic foot ulcers, in our study in the surgical grou, 1 1 atients out of 5 (22%) diagnosed with diabetic foot ulcers and treated by eriheral nerve decomression by division of the tarsal tunnel. We found that atients out of 11 (72%) imroved in the form of faster rate of ulcer healing, while in the medical grou treated conservatively, we observed ersistent ulcers with delayed healing with liability for infection. Nickerson et al., [15] reorted % reduction in risk of foot ulceration recurrence. Also, they found in a 3-year rosective study of unilateral nerve decomression surgery after diabetic foot ulcer that in the non-oerated intact legs have 5.5 times the risk of ulceration than oerated legs. Also, Zhang et al., [31] study included 2 atietns with distal symmetrical olyneuroathy who underwent bilateral decomression. They reorted that no atient had new ulcers, reulceration, wound infections or amutation in an 1- month follow-u. Some studies found the role of surgery for atients ewith DPN is still controversial. As in

6 7 Comarison between Results of Surgical & Conservative Treatment for DPN study of Biddinger and Amend [2], they noted that the erformance of decomrssive surgery to alleviate chronic neuroathic ain in atients with DPN remains controversial and has yielded equivocal results. Also, Chaudhry et al., [32] recommended erforming more randomized controlled trials for aroval of the utility of surgical decomssion for treatment of diabetic eriheral neuroathy. Finally, according to our study results and according to all suorting results mentioned and oosing oinions, we found that surgical decomression of eriheral nerves is considered a new and growing modality for treatment of comlications of diabetic eriheral neuroathy atients to limit rogression of the disease and imrove atients' quality of life. But, more studies with large samle size are still needed to rove the effectiveness and utility of this modality. Conclusion: It could be concluded that atients with comlicated Diabetic Periheral Neuroathy (DPN) could be surgically managed successfully by decomression of eriheral nerves at site of comression in caral and tarsal tunnels with good results in atients resistant to medical treatment. References 1- YACH D., STUCKLER D. and BROWNELL K.D.: Eidemiologic and economic consequences of the global eidemics of obesity and diabetes. Nature Medicine, 12 (1): 62-6, DYCK P.J., KRATZ K.M., KARNES J.L., et al.: The revalence by staged severity of various tyes of diabetic neuroathy, retionoathy, and nehroathy in a oulationbased cohort: The Rochester Diabetic Neuroathy Study. Neurology, 3 (): 17-2, WOLFFE G.I., BAKER N. S., AMATO A.A., et al.: Chronic crytogenic sensory olyneuroathy: Clinical and laboratory characteristics. Archives of Neurology, 56 (5): 5-7, SINGLETON Jr.: Evaluation and treatment of ainful eriheral neuroathy. Seminars in Neurology, 25 (2): 15-95, LEE J.S., LU M., LEE V.S., et al.: Lower-extremity amutation: Incidence,risk factors,and mortality in the Oklahoma Indian diabetes study. Diabetes, 2: 76-2, NICKERSON D. S. and RADER A.J.: Low long-term risk of foot ulcer recurrence after nerve decomression in a diabetes neuroathy cohort. J. Am. Podiatr. Med. Assoc., 13 (5): 3-6, CANDRILLI S.D., DAVIS K.L., KAN H.J., et al.: Prevalence and the associated burden of illness of symtoms of diabetic eriheral neuroathy and diabetic retinoathy. J. Diabetes Comlications, 21: 36-1, HAPPICH M., JOHN J., STAMENITIS S., et al.: The quality of life and economic burden of neuroathy in diabetic atients in Germany in 22: Results from the Diabetic Microvascular Comlications (DIMICO) study. Diabetes Res. Clin. Pract., 1: 223-3, DYCK P.J. and THOMAS P.K.: Disease of eriheral nervous systems. In: Ehlers J, editor. Periheral Neuroathy, th ed. Philadelhia: Elsevier Saunders, , VINIK A.I.: Advances in diabetes for the millennium: New treatments for diabetic neuroathies. Med. Gen. Med., 6: 13, TANENBERG R.J. and DONOFRIO P.D.: Neuroathic roblems of the lower extremities in diabetic atients. In: Bowker J.H., Pfeifer M.A., editors. Levin and O'Neal's the Diabetic Foot, 7 th ed. St. Louis: Moby; 36, JAKOBSEN J. and SIDENIUS P.: Decreased axonal transort of structural roteins in stretozotocindiabetic rats. J. Clin. Invest., 66: 292, RYDEVIK B. and LUNDBORG G.: Effects of graded comression non intraneural blood flow. J. Hand. Surg., 6A: 3-12, MELENHORST W.B., OVERGOOR M.L., GONERA E.G., et al.: Nerve decomression surgery as treatment for eriheral diabetic neuroathy: Literature overview and awareness among medical rofessionals. Ann. Plast. Surg., 63 (2): , Aszmann O, Tassler PL and Dellon AL. Changing the natural history of diabetic neuroathy: Incidence of ulcer/amutation in the contralateral limb of atients with a unilateral nerve decomression rocedure. Ann Plast Surg; 53(6): , DELLON A.L.: Treatment of symtoms of diabetic neuroathy by eriheral nerve decomression. Plast. Reconstr. Surg., 9: 69-97, ASZMANN O.C., KRESS K.M. and DELLON A.L.: Results of decomression of eriheral nerves in diabetics: A rosective, blinded study. Plast. Reconstr. Surg., 16: 16-22, HOLLIS CAFFEE H.: Treatment of diabetic neuroathy by decomression of the osterior tibial nerve. Plast. Reconstr. Surg., 16 (): 13-5, WOOD and WOOD M.A.: Decomression of eriheral nerves for diabetic neuroathy in the lower extremity. J. Foot. Ankle. Surg., 2 (5): 26-27, BIDDINGER K.R. and AMEND K.J.: The role of surgical decomrssionfor diabetic neuroathy. Foot. Ankle. Clin. N. Am., 9: , DELLON A.L., MACKINNON S.E. and SEILER W.A.: Suscetibility of the diabetic nerve to chronic comression. Ann. Plast. Surg., 2: 117-9, UPTON A. and McCOMAS A.: The double crush in nerve entrament syndromes. Lancet, 2 (725): , DELLON A.L.: Treatment of symtomatic diabetic neuroathy by surgical decomression of multile eriheral nerves. Plast. Reconstr. Surg., 99: 679-7, DELLON A.L. and KELLER K.M.: Comuter-assisted quantitative sensorimotor testing atients with caral and

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