Peripheral neuropathy is becoming an increasing focal point for clinicians when treating patients because of the plethora of causes to which the disorder has been attributed. Characterized by damage to the peripheral nervous system, peripheral neuropathy causes sharp, burning pain; numbness of the extremities that can travel proximally; muscle weakness; and an overall diminished quality of life. Rather than being a self-developing disease, peripheral neuropathy has mostly been identified as a symptom of causative disorders and therapeutic agents – making prevention and treatment extremely important for patients and providers.
Yun Seo Lee
The etiology of peripheral neuropathy has been studied thoroughly over the past 2 decades. In this review, we summarize the landscape of peripheral neuropathy, including the more common causative entities; diagnostic tools that can potentially be employed to identify the disorder; and treatments that are in use or being tested to prevent, slow, or reverse the effects of peripheral neuropathy.
DIABETIC PERIPHERAL NEUROPATHY
The most common cause of peripheral neuropathy is diabetes mellitus. Diabetic peripheral neuropathy (DPN) is a symmetrical, length-dependent neuropathy that affects more than 50% of type I and type II diabetes patients.1 Not only is DPN an initiating factor of foot ulcers and nontraumatic lower-limb amputation, but it also leads to a severely lower quality of life, financial burden, and increased risk of death after major surgical procedures.2
Jonathan Kosacki
Once DPN has progressed significantly, its effects are irreversible; there are no agents capable of reversing or halting DPN past initial stages of disease.3 It is important to detect and treat DPN early on, as it has a favorable prognosis and most DPN-related amputations are preventable.
Diagnosis
Nerve-conduction studies are the preferred diagnostic tool for DPN; however, these studies are costly and difficult to conduct in a clinical setting.2 Currently, such diagnostic tools as the 10-g monofilament and tuning fork are more commonly utilized to detect loss of protective foot sensation to decrease the risk of foot ulceration.2 In addition, other common aspects of diagnosing DPN include assessment of symptoms in the patient’s hands or feet and patient-reported symptoms.
Dr. Kanika Bhandari
Several diagnostic devices are in experimental stages and have shown potential for utilization in clinical settings.
DPNCheck is a handheld device, with a turnaround time of 3 minutes, that measures sural nerve conduction velocity, which can identify DPN early in asymptomatic cases; and amplitude of sensory-nerve action potentials, which decrease with the degeneration of axons, a clinical characteristic of DPN. In a study of patients with diabetes (n = 162 [type 1, n = 80; type 2, n = 82]) and healthy controls (n = 80), a comparative analysis of DPNCheck and reference techniques showed a strong linear relationship between between clinical neuropathy scores and LDIFLARE (r = 0.64-0.84; P < 0.03), which suggests that the device might be viable in clinical settings.4 LDIFLARE is a method developed to assess axon reflex to detect neuropathy in type 2 diabetes.4
Dr. Amanda Tran
Neuropad, a 10-minute test, measures foot plantar-surface sweat production, indicated by a cobalt compound color change on the device. The test is advantageous because it is highly sensitive – 73% more sensitive than DPNCheck – and does not rely on patient response or require operator training.5 A study of Neuropad showed that a drier foot and, therefore, increased risk of foot ulceration correlated with greater abnormal readings on the device, which might indicate onset of more severe DPN in the future.6
Sudoscan measures sudomotor function in 3 minutes through an electrochemical reaction between stimulated sweat glands and electrodes.2 A study performed in China in patients with type 2 diabetes (n = 394) showed that electrical conductance in the feet is associated with increasing risk and severity of symptoms of DPN in asymptomatic patients (r = 0.98 [95% confidence interval, 0.962-0.993]; P < .01) and might serve as a biomarker of DPN.7
Although these three techniques present favorable data, each is a nerve conduction study that can access only small-fiber nerves. Additional testing is required for larger-fiber nerves that are also affected by DPN.2 Also, some of the studies of these devices have high heterogeneity and a small sample size. Further research utilizing these three methods should include larger sample sizes to appropriately assess any clinically significant patient outcomes.
Corneal confocal microscopy (CCM), another potential technique for DPN screening, is a noninvasive ophthalmic device for assessing corneal small-fiber nerves. A study of patients with diabetes or obesity or both (n = 35) showed high reproducibility of corneal-nerve pathology identification using CCM.8 A larger-scale study showed that CCM can detect a reduction in corneal-nerve parameters in DPN patients, as well as in patients who have yet to develop DPN – thus demonstrating the technique’s ability to detect both early subclinical and established DPN.9 Once CCM is approved as a point-of-care device, it might provide a reliable, sensitive screening method for DPN as an early-intervention tool.