PAKISTAN ARMED FORCES
MEDICAL JOURNAL (Category Y)

A Journal of Army Medical & Dental Corps

Being published since 1956

ISSN (online) 2411-8842
ISSN (print) 0030-9648

VOL 61, No. 2, JUNE 2011

OLYNEUROPATHY IN A COHORT OF DIABETIC PATIENTS HAVING SYMPTOMS OF POLYNEUROPATHY USING ELECTRODIAGNOSTIC PROCEDURE

Sahibzada Nasir Mansoor, Farooq Azam Rathore, Nadeem Ahmed, Sahibzada Salma Rahman, Rehana Yasmeen

Abstract

Objective: To determine the frequency of peripheral polyneuropathy in patients having diabetes mellitus with symptoms of polyneuropathy using electrodiagnostic procedure.
Study design: Observational descriptive study
Place and duration of study: Armed Forces Institute of Rehabilitation Medicine (AFIRM), Rawalpindi. June 2008 to June 2009 (one year)
Patients and Methods: Sixty three patients of diabetes mellitus having symptoms of peripheral polyneuropathy fulfilling the inclusion criteria were sampled by purposive sampling. Informed consent was taken. Their demographic data and common symptoms were recorded. All patients underwent Electrodiagnostic procedures for the presence or absence of polyneuropathy, using nerve conduction studies by recording amplitudes, velocities and latencies of minimal two (sural, peroneal) and maximum six nerves. Electromyography was performed only in patients with abnormalities in nerve conduction findings or conditions other than polyneuropathy. Frequencies as percentages were calculated for the presence or absence of polyneuropathy, type of polyneuropathy, associated symptoms and other related diagnosis (if any).
Results: There were thirty three males (52.4%) and thirty female (47.6%). Forty one (65%) patients had confirmed polyneuropathy on electrodiagnosis, out of which forty patients (97.6%) had axonal polyneuropathy, only one patient (2.4%) had demyelinating polyneuropathy. Twenty two had no polyneuropathy (35%), out of which 65% had other diagnosis like Carpal Tunnel Syndrome (CTS), Radiculopathy and other Compression neuropathies.
Conclusion: Majority of symptomatic diabetic patients actually had polyneuropathy.  Electrodiagnostic studies are a sensitive tool for early detection of peripheral polyneuropathy, its types and extent.

Keywords : Diabetes mellitus, Electrodiagnostics, Polyneuropathy.

Article

Introduction
Diabetic neuropathy is recognized as the most frequent neurological complication of diabetes mellitus1   and is manifest mainly on the peripheral nervous system. It is responsible for substantial morbidity and impaired quality of life2. It is the commonest form of neuropathy in the developed world3. It occur secondary to metabolic disturbance and is related to duration of diabetes and degree of metabolic control4 .It includes several neuropathic syndromes including focal and symmetrical neuropathies, by far the commonest of which is distal symmetrical neuropathy5. Correlates of diabetic neuropathy include increasing age, increasing duration of diabetes, poor glycemic control, retinopathy, albuminuria, and vascular risk factors6
Pain is the most distressing symptom of neuropathy and is the main factor that prompts the patient to seek medical advice7. The two main clinical consequences, foot ulceration sometimes leading to amputation and painful neuropathy, are associated with much patient morbidity and mortality8.  It has a clinical prevalence of 60% and problematic peripheral neuropathy occurs in about 20%9 of the patients. The prevalence of neuropathy in type 2 diabetics has been found to be about 40% in some areas of Pakistan10.  Most patients present with a combination of sensory and motor symptoms and signs in the feet which may spread proximally in the legs, hands and arms. Symptomatic diabetic sensorimotor polyneuropathy is considered progressive and irreversible11.
There are many methods for detecting and monitoring diabetic Polyneuropathy. The includes clinical examination, clinical screening devices12 like Semmes Weinstien monofilament, graduated Rydel Seiffer tuning fork and neuropen. Established paradigms like neuropathic symptom score (NSS), quantitative sensory testing (QST) 13 and autonomic function testing are also used. Electrodiagnostic studies are a useful method for diagnosis and nerve conduction studies (NCS) are generally considered to be the most sensitive and reproducible14. Electrophysiological studies can be used to confirm the presence of polyneuropathy, to assess the severity and the pattern, to determine whether motor, sensory or a combination of fibers are involved and most importantly to assess whether the underlying pathology is axonal loss or demyelination13.
This study was carried out to establish the frequency of polyneuropathy in diabetic patients by detecting it early from the symptoms and confirming it through electrodiagnostic studies. It determined that electrodiagnosis in early diagnosis of diabetic peripheral polyneuropathy in patients with symptoms of polyneuropathy and helped  to rule out other associated conditions and causes of polyneuropathy thereby early  initiation of treatment helping in better outcome, and prevention of early complicatons.
Patients and Methods
This descriptive study was conducted at the department of electrodiagnostics, Armed Forces Institute of Rehabilitation Medicine (AFIRM) Rawalpindi from June 2008 to June 2009. Approval of the hospital ethical committee was obtained. Sixty three cases of diabetes mellitus with symptoms of polyneuropathy were taken from AFIRM OPD/indoor patients. All the patients were selected by purposive sampling and based on inclusion criteria i.e patients of both sexes with age less than 60 years and having diabetes mellitus with symptoms of polyneuropathy. All asymptomatic diabetic patients, autoimmune diseases, infections and other diseases known to cause neuropathy were excluded. Careful history was taken about demographic information and relevant complaints regarding symptoms of neuropathy. In addition duration of diabetes, presence or absence of polyneuropathy, type of polyneuropathy and other diagnosis were also calculated.
The nerve conduction study was conducted after taking informed consent and explaining the procedure to the patient. Electrodiagnostic studies were done at room temperature 25Ċ, with MEDTRONIC, KP 3.0 ® model 2003 using surface electrodes.
Nerve conduction study protocol followed was as under:
1)
  Nerve conduction studies were carried out initially for sural sensory and common peroneal motor nerve in one of the lower limbs, being the most sensitive and if found normal other nerves and Electromyography were not done further.
2)  In cases where any abnormality suggestive of polyneuropathy was detected i.e smaller or absent CMAP, reduced velocities and prolonged DML then contra lateral tibial motor, one median motor and one ulnar, both motor and sensory were done and further evaluation for polyneuropathy was sought in these nerves.
3)  F wave was recorded for common peroneal nerve bilaterally.
4)  Electromyography (EMG) was only done in selected muscles in patients with nerve conduction findings suggestive of a polyneuropathy. EMG parameters included observation for amplitude, morphology, involuntary activity, recruitment and interference pattern.
5)  In all the recorded nerves, amplitudes, latencies and velocities were assessed.
6)  Based on their standard numerical value they were assigned for presence or absence of polyneuropathy and it was labeled as outcome. Symptoms of the patients, duration of diabetes, type of polyneuropathy and any other associated diagnosis were also recorded.
Statistical Analysis
Data was analyzed using Statistical Package for Social Sciences (SPSS) version 12. Frequencies as percentages were calculated for qualitative variables i.e diagnosis and symptoms of polyneuropathy.
Results
Sixty three patients underwent electrodiagnostic studies based on symptoms of polyneuropathy. There were 33 (52.4%) males and 30 (47.6%) female. Mean age was 49.8 years. The most common age group (61.9%) was between 50-60 years. Duration of diabetes mellitus was between 1-10 years in majority of the patients, shown in figure 2.

Among the sampled 63 symptomatic patients 41 (67%) had confirmed polyneuropathy. Axonal polyneuropathy was the most frequent (33.3%) as shown in figure 1. Twenty two (34.9%) patients had normal study on electrodiagnosis (Figure 1).

Among the diagnosed polyneuropathy patients there were 28 males (68.3%) and 13 females (31.7%).
Neurological conditions other than polyneuropathy diagnosed on electrodiagnostic studies included carpal tunnel syndrome in 7 patients; L5 radiculopathy, S1 radiculopathy, combined L5 S1 radiculopathy and bilateral median neuropathy at wrist in one patient each. Numbness alone was the most frequent symptom (16 patients), followed by pain (4 patients), weakness and combination of numbness and tingling, and numbness and pain, 6 patient each. Combination of multiple symptoms including numbness, weakness, burning, tingling and leg cramps was present in 8 patients as shown in table.

 
Discussion
Diabetic neuropathy is one of the common outcomes of the diabetes and is a subject of ongoing research in order for the better understanding of the disease and better management and prevention. There are multiple methods for detecting and monitoring diabetic polyneuropathy including clinical examination, clinical screening devices12 like Semmes Weinstien monofilament, graduated Rydel Seiffer tuning fork and Neuropen. Established paradigms like neuropathic symptom score (NSS), quantitative sensory testing (QST)13and autonomic function testing are also used. Electrodiagnostic studies are a useful method for diagnosis and nerve conduction studies (NCS) are generally considered to be the most sensitive and reproducible14. In conjunction with the information obtained from the neurological history and examination, electrophysiology can be used to assist in isolating a specific diagnosis. Electrophysiological studies can be used to confirm the presence of polyneuropathy, to assess the severity and the pattern, to determine whether  motor, sensory or a combination of fibers are involved and most importantly to assess whether the underlying pathology is axonal loss or demyelination15. Electrodiagnosis helps to exclude other common causes like polyradiculopathy or focal mononeuropathies.
When electrodiagnostic studies were carried out in diabetic patients 67% had confirmed polyneuropathy and numbness, pain and weakness were the commonest symptoms. The most common type was axonal polyneuropathy, and the common associated diagnosis were carpal tunnel syndrome, radiculopathy and other compression neuropathy.
Similar results have been obtained by most of the studies. In Pakistan Niazi et al16 evaluated diabetic polyneuropathy by doing electrodiagnostic study in 41 patients in 2001 and found that 34 out of 41 patients had confirmed polyneuropathy. They suggested that electrodiagnostic studies can diagnose diabetic polyneuropathy even before clinical manifestation. In our study   42 out of 63 patients had polyneuropathy.
Another local study carried out by Asad A et al17 in 2007 compared nerve conduction studies with diabetic neuropathy symptom score and diabetic neuropathy examination score in type II diabetes for detection of sensorimotor polyneuropathy. They found that although the diabetic neuropathy symptom score and diabetic neuropathy examination score together can help in prompt clinical evaluation of diabetic polyneuropathy, electrodiagnosis was a more sensitive test and can help diagnose subclinical cases as well.
Dyck et al18 in their study, “The Rochester Diabetic Neuropathy Study” found that 66% of the patients with type I and 59% of the patients with type II diabetes mellitus had some type of neuropathy. These study results are comparable with our study in which 67% of the sampled diabetic patients had polyneuropathy confirmed on electrodiagnosis. In the same study diabetic polyneuropathy was the commonest form of neuropathy followed by compression neuropathy of median nerve at wrist (carpel tunnel syndrome). Electrophysiological evidence of median neuropathy at the wrist was found in 22% of type I and 29% of type II diabetes mellitus. This is also comparable to our study in which the second most common neuropathy was carpal tunnel syndrome and 11.6% patients had confirmed carpal tunnel syndrome on electrodiagnosis.
Partenan J et al19 in a study on 133 patients with newly diagnosed IDDM followed for up to 10 years, showed that nerve conduction velocity diminished in six nerves evaluated. The maximum deficit was recorded in sural and peroneal nerve. Our study also calculated the electrodiagnostic variables for the same nerves and sural was found to be the most consistently absent in the polyneuropathy followed by peroneal nerve with diminished velocity and amplitude, though the velocity and amplitude variables of the electrodiagnostic procedure were not directly part of the study and were only taken to prove either the presence or absence of polyneuropathy.
European Diabetes (EURODIAB) prospective study20 demonstrated that nearly 25% of type I diabetes patients enrolled developed neuropathic pain symptoms over a period of seven years. In our study pain was the second most common symptom of patients having confirmed polyneuropathy.
In Early Diabetes Intervention Trial (EDIT)21, out of 414 patients with mild diabetic neuropathy, 23% had median neuropathy at the wrist and in Rochester Diabetic Neuropathy Cohort electrophysiological evidence of median neuropathy at wrist was found in 22% of the type I diabetes patients and 29% of type II diabetes patients. Both of these studies relate to our study in terms that carpal tunnel syndrome was the commonest diagnosis among the patients found normal for polyneuropathy.
Dyck et al22 showed that Diabetic lumbosacral radiculoplexopathy occurs in approximately 1% of diabetic patients. In our study out of 63 diabetic patients, 3 had lumbosacral radiculopathy, which shows relatively higher frequency in our study.
Aaron I et al23 found out that upon electrodiagnosis of diabetic patients Distal Motor Latency (DML) and F Wave Latency (FWL) were prolonged relative to control cohort and Compound Motor Action Potential (CMAP)  was reduced. The FWL and CMAP had the highest abnormality rates. Among patients with clinically significant symptoms, 40% did not have Diabetic Polyneuropathy (DPN) on nerve conduction, and in asymptomatic patients, 45% had DPN on nerve conduction. This is comparable to our study in 37 % of clinically symptomatic patients did not have polyneuropathy and that DML, FWL were consistently prolonged in the recorded nerves of patients having DPN.
Conclusion
Majority of diabetic patients having symptoms of polyneuropathy actually have polyneuropathy. Pain and numbness are the most common symptoms of polyneuropathy. Electrodiagnosis is a sensitive tool for the diagnosis and early detection of diabetic polyneuropathy. It helps to localize the entrapment neuropathies and segregating axonal from demyelinating polyneuropathies. Routine electrodiagnosis studies should be carried out in diabetic patients on yearly basis.

Reference

1. Ziegler D. Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review. Treat Endocrinol 2004; 3:173-89
2. Uzun N, Uluduz D, Mikla S, Aydin A. Evaluation of asymptomatic central neuropathy in type I diabetes mellitus. Electromyogr Clin   Neurophysiol, 2006; 46:131-37
3. Kazemm SS, Behzad D. Role of blink reflex in diagnosis of sub clinical cranial neuropathy in diabetic mellitus type II. Am J Phys Rehabil 2006; 85:449-52
4. Vinik AI, Emley MS, Megerian JT,Gozani SN. Median and ulnar nerve conduction measurements in patients with symptoms of diabetic peripheral neuropathy using the NC-stat system, Diabetes Technol Ther. 2004; 6:816-24.
5. Apfel SC, Asbury AK, Bril V, et al. Positive neuropathic sensory symptoms as endpoints in diabetic neuropathy trials. J Neurol Sci 2001;189:3–5.
6. Sumner CJ, Sheth S, Griffin JW, Cornblath DR, Polydefkis M. The spectrum of neuropathy in diabetes and impaired glucose tolerance. Neurology2003; 60:108–11
7. Dobretsov M, Romanovsky D, Stimers JR. Early diabetic neuropathy: triggers and mechanisms.World J Gastroenterol 2007; 13: 175-91.
8. Boulton AJ, Malik RA, Arezzo JC, Sosenko JM. Diabetic somatic neuropathies. Diabetes Care 2004;27:1458–1486.
9. Martin CL, Albers J, Herman WH, Cleary P, Waberski B, Greene DA, Stevens MJ, Feldman EL. Neuropathy among the diabetes control and complications trial cohort 8 years after trial completion Diabetes Care2006;29:340–344.
10. Shera AS, Jawad F, Maqsood A, Jamal S, Azfar M, Ahmed U. Prevalence of chronic complications and associated factors in Type 2 Diabetes. J Pak Med Assoc 2004: 54-59
11. Magda P , Lato VN, Brannagan TH, Weimer LH, Chin RL, Sander HW.Comparison of Electrodiagnostic Abnormalities and Criteria in a Cohort of Patients With Chronic Inflammatory Demelinating Polyneuropathy. Arch Neurol. 2003; 60:1755-9
12. Oyer DS, Saxon D, Shah A. Quantitative assessment of diabetic peripheral neuropathy with use of the clanging tuning fork test.2007; 13:5–10.
13. Sorensen L, Molyneaux L, Yue DK  The level of small nerve fiber dysfunction does not predict pain in diabetic neuropathy: a study using quantitative sensory testing. Clin J Pain 2006;22:261–5.
14. Vinik AI, Bril V, Litchy WJ, Price KL, Bastyr EJ, MBBG Study Group. Sural sensory action potential identifies diabetic peripheral neuropathy responders to therapy. Muscle Nerve 2005;32:619–625.
15. Malik RA, Tesfaye S, Newrick PG, Walker D, Rajbhandari SM, Siddique I, Sharma AK, Boulton AJ, King RH, Thomas PK, Ward JD. Sural nerve pathology in diabetic patients with minimal but progressive neuropathy. Diabetologia 2005; 48:578–585.
16. Niazi PHK, Ahmed K, Hussain A, Butt A W, Alam A.Electrodiagnosis Evaluation of diabetic polyneuropathy. Pak Armed Forces Med J  2001;51:75-77
17. Asad A, Hameed MA, Khan UA, Butt MA, Ahmed N, Nadeem A. Comparison of nerve conduction studies with diabetic neuropathy symptom score and diabetic neuropathy examination score in type-2 diabetes for detection of sensorimotor polyeuropathy. J Pak Med Assoc; 2009;59:594-8.
18. Dyck PJ, Davies JL, Wilson DM, Service FJ, Melton LJ , O’Brien PC. Risk factors for severity of diabetic polyneuropathy: intensive longitudinal assessment of the Rochester Diabetic Neuropathy Study cohort. Diabetes Care 1999;22:1479–1486
19. Partanen J, Niskanen L, Lehtinen J, et al. Natural history of peripheral neuropathy in  patients with noninsulin dependent diabetes mellitus. N Engl J Med 1995;333:89–94.
20. Tesfaye S, Stephens LK, Stephenson JM, et al. Prevalence of diabetic peripheral neuropathy and its relation to glycemic control and potential risk factors: the EURODIAB IDDM complications study. Diabetologia 1996; 39: 1377–1384.
21. Albers JW, Brown,MB, Sima AA, Greene DA. Frequency of median mononeuropathy in patients with mild diabetic neuropathy in the early diabetes intervention trial (EDIT). Tolestat Study Group for EDIT. Muscle Nerve 1996;19(2):140-6.
22. Dyck PJ, O’Brien PC, Litchy WJ, Harper CM, Klein CJ. Monotonicity of nerve tests in diabetes: subclinical nerve dysfunction precedes diagnosis of polyneuropathy. Diabetes Care 2005;28:2192–2200.
23. Aaron I, Vinik MD, Xuan K, Megerian JT, Gozani SN. Diabetic nerve conduction abnormalities in primary care settings. Diabetes Technology and Therapeutics 2006; vol 8:39-46.
24. Chao CC, Hsieh SC, Yang WS, Lin YH,  Lin WM, Tai TY, Hsieh ST. Glycemic control is related to the severity of impaired thermal sensations in type 2 diabetes. Diabetes Met Res Rev 2007; 23:612–620.



Creative Commons License
This is an Open Access article distributed under the terms of the Creative Commons Attribution License Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.