Electrophysiological changes in sensorimotor nerves in diabetes mellitus & usefulness of nerve conduction studies for early diagnosis of diabetic neuropathy

Dr.Neha H. Pandya*1, Dr. Kinnar S. Desai2, Dr. Toral M. Goswami1, Dr. Vaishali N. Patel1, Dr. Amita K. Mevada3, Dr. Mitesh N. Suthar4 1Assistant professor, Physiology department, B. J. Medical College, Ahmedabad, India 2Assistant professor, Anatomy Department, B. J. Medical College, Ahmedabad, India 3Tutor, Physiology department, B. J. Medical College, Ahmedabad, India 4Assistant professor, Medicine department, N.H.L. Municipal Medical College, Ahmedabad.,India *Correspondence Info: Dr. Neha H. Pandya, 61, Hari Om Villa, Near Iscon flower Flats, Bopal-Ghuma road, Ghuma, Ahmedabad. 380062 Email – nehahpandya@yahoo.com


Introduction
DM is an endocrine disorder that is characterized by defect in insulin secretion &/or insulin action resulting in hyperglycaemia. Diabetic neuropathies(DN) are neuropathic disorders that are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervosum) in addition to macrovascular conditions that can culminate in DN cause significant morbidity & mortality 1,2 .
Symptoms of DN include a sensation of pain, numbness, tingling, burning or prickling that begins in the feet. In later stages of DN, the hands can be affected as well. In some cases of DN, the abnormal sensations can extend to the arms, legs, & trunk(truncal neuropathy). There are three general types of diabetic neuropathy that affect the nerves of the nervous system. They include sensory neuropathy, also called peripheral neuropathy(PN), in which the nerves that carry messages about sensation to the brain are damaged. Motor neuropathy occurs when the nerves that carry messages about movement from the brain to the muscles are damaged. Autonomic neuropathy occurs when the nerves that control involuntary activities of the body, such as digestion & sweating, are affected 3 .
Evaluation of neuropathy is undertaken by electrophysiological measurements 4 . Electrodiagnostic assessments are sensitive, specific & reproducible measures of the presence & severity of peripheral neuropathy & they define quantitative nerve dysfunction 5 . NCS are used for the assessment of DN not only to evaluate the degree of abnormality but also to document serial changes in the clinical course of the disease.
The present study was designed to observe the effects of long duration of DM on electrophysiological study of peripheral nerves that can help for the better management of the patients suffering from DN.

Methods & Materials
This study was carried out at Civil Hospital, Ahmedabad in DM patients attending OPD of Medicine. 50 diabetic patients were selected on basis of following criteria: (1)   Motor NCS are performed by electrical stimulation of a peripheral nerve & recording from a muscle supplied by this nerve. Sensory NCS are performed by electrical stimulation of a peripheral nerve & recording from a purely sensory portion of the nerve, such as on a finger. Neurological parameters studied were: nerve conduction velocity(NCV) expressed in meter/second(m/S), distal latency(DL) expressed in millisecond(ms), compound muscle action potential(CMAP).
For median motor NCS, the recording electrode is placed close to the motor point of abductor pollicis brevis & stimulating electrode at flexor carpi radialis near wrist joint. For median sensory NCS by orthodromic stimulation the recording electrode is placed 3 cm proximal to the distal wrist crease & stimulating electrodes are placed at the second or third digits. Ulnar motor NCS is performed by placing stimulating electrode at 3 cm proximal from wrist joint & recording electrode over abductor digiti minimi. Ulnar sensory NCS by orthodromic conduction is recorded by stimulating digital nerve at interphalangeal joint of the little finger & recording electrode 3 cm proximal from wrist joint along course of ulnar nerve. Peroneal NCS is performed by placing stimulating electrode at ankle, 2 cm distal to fibular neck & recording electrode over extensor digitorum brevis. For sural NCS by antidromic conduction recording electrode is placed between lateral malleolus & tendoachilles; stimulating electrode is placed 10-16 cm proximal to recording electrode, distal to lower border of gastrocnemius at the junction of middle & lower third of leg. The DL, NCV, SNAP & CMAP are recorded following stimulation.

Statistical Method
Data were summarized with unpaired 't' test, p-value < 0.05 were considered as significant (S), < 0.001 as highly significant (HS) & > 0.05 as not significant (NS). Level of significance used was 95%. All parameters are expressed in Mean ± SD.

Results
In our present study 50 DM patients were selected with chief complains of paresthesia, tingling, numbness & burning sensations in limbs. All patients FBS & glycosylated Hb(HbA1c) was measured for their glycaemic status.     Sensory amplitude of all sensory nerves is significantly reduced in both study groups. (Table 5).

Discussion
The detection of DN is an area of ongoing interest for the researchers & clinicians, not only for diagnosing & managing it earlier but also for understanding the disease which is still under exploration. Mostly NCS have been accepted as an essential part of diagnosis for DN as it has many benefits 6,7 .
Hyperglycaemia is now well established risk factor in both patients with type I 8,9 & type II diabetes 10 . Other correlates & associations include age, duration of DM, quality of metabolic control, height, presence or absence of background or proliferative diabetic retinopathy, cigarette smoking, high density lipoprotein, cholesterol & presence of cardiovascular disease 11,12,13,14 .
Most recognized neurologic complications associated with diabetes involve the peripheral nervous system. Disorders of the nervous system associated with DM were first recognized by Rollo in 1798. It was Marchal de Calvi in 1864 who first suggested that DM might be the cause rather than the effect of neuropathy 15

Pathophysiology of DN
Hyperglycaemia cause a non-enzymatic covalent bonding of glucose with proteins that alters their structure & inhibits their functions. These glycosylated proteins can lead DN 16,17 . Hyperglycaemia also increases intracellular diacylglycerol, which activates protein kinase C(PKC); that causes increased vascular permeability, impaired nitric oxide(NO) synthesis & compromise nerve regeneration 18 . Elevated levels of glucose results in activation of Polyol or Aldose reductase pathway. Excessive activation of polyol pathway leads to increased levels of sorbitol & increased activity of oxygen free radicals. It decreases dihydronicotinamide adenine dinucleotide phosphate(NADPH), NO & glutathione, as well as increases osmotic stress on the cell membrane. By impairing Na⁺-K ⁺ ATPase activity it causes nodal swelling & other structural changes 19,20 . Oxidative stress causes breaking of DNA strand; leads activation of poly(ADP-Ribose) polymerase(PARP) that further mediate pathways of hyperglycaemia induced damage 21 . One cause of microangiopathy is long term hyperglycemia. In DN there is thickening of basement membrane & endothelial cell hyperplasia as entry of glucose in cells remain unchecked by insulin 22

Summary & Conclusion
The physiological properties of nerve & muscle are modified due to pathophysiological changes resulting from DM. Distal sensorimotor polyneuropathy, the most common complication of DM may cause severe morbidity. In our study results conclude that the changes of DN affected sensorimotor nerves in both limbs. NCS not only used to diagnose the DM but also monitor the effect of treatment of DN. By regular NCS & good glycaemic control, symptoms of DN can be reversed & further complications like foot ulceration, Charcot's joint & amputation can be prevented.