Oral and Topical Treatment of Painful Diabetic Polyneuropathy: Practice Guideline Update Summary

ObjectiveTo update the 2011 American Academy of Neurology (AAN) guideline on the treatment of painful diabetic neuropathy (PDN) with a focus on topical and oral medications and medical class effects.MethodsThe authors systematically searched the literature from January 2008 to April 2020 using a structured review process to classify the evidence and develop practice recommendations using the AAN 2017 Clinical Practice Guideline Process Manual.ResultsGabapentinoids (standardized mean difference [SMD] 0.44; 95% confidence interval [CI], 0.21–0.67), serotonin-norepinephrine reuptake inhibitors (SNRIs) (SMD 0.47; 95% CI, 0.34–0.60), sodium channel blockers (SMD 0.56; 95% CI, 0.25–0.87), and SNRI/opioid dual mechanism agents (SMD 0.62; 95% CI, 0.38–0.86) all have comparable effect sizes just above or just below our cutoff for a medium effect size (SMD 0.5). Tricyclic antidepressants (TCAs) (SMD 0.95; 95% CI, 0.15–1.8) have a large effect size, but this result is tempered by a low confidence in the estimate.Recommendations SummaryClinicians should assess patients with diabetes for PDN (Level B) and those with PDN for concurrent mood and sleep disorders (Level B). In patients with PDN, clinicians should offer TCAs, SNRIs, gabapentinoids, and/or sodium channel blockers to reduce pain (Level B) and consider factors other than efficacy (Level B). Clinicians should offer patients a trial of medication from a different effective class when they do not achieve meaningful improvement or experience significant adverse effects with the initial therapeutic class (Level B) and not use opioids for the treatment of PDN (Level B).

TREATMENT OF A COMBINATION OF DIABETIC POLYNEUROPATHY WITH TYPE 2 DIABETES AND GOUT

The purpose of the work. To show the expediency of using a complex DPN therapy with thio-gammoy-600 in combination with TPP, B12-ankerman and febuxostat. Materials and research methods. The study involved 28 male patients suffering from DM2 aged 56-77 years, with an av-erage age of 64.6±0.7 years. The initial values of average fasting blood glucose were 7.8 ± 1.52 mmol/l, glycosylated hemoglobin 7.4 ± 0.13%. Two groups were identified: group 1 (main) – 14 people and group 2 (control) - 16 people. In group 2, basic DPN therapy was used (thiogamma 600 mg/day for 4 months). For the first 14 days, the drug was administered intravenously, and then administered orally. In group 1, in addition to basic DPN therapy, B12-ankerman and febuxostat (adenuric) – 80 mg/day were received. TPP was carried out on a portable device TPP-03 for 15 minutes daily. This treatment regimen was used for 4 months. The assessment of the quality of life (QL) was carried out using the MOS SF-36 questionnaire. Results and their discussion. Four months after the start of therapy, more pronounced changes were observed in patients of the first group. The total score of the NSS scale in this group increased by 28.9%, and in group 2 - by 18.8%. The positive effect of therapy with adenuric and TES on the course of DPN shows that the use of this treatment will naturally lead to an improve-ment in the quality of life of patients, the dynamics of which was studied according to the results of the SF-36 questionnaire.

Transdermal electroneurostimulation in patients with diabetic neuropathy

BACKGROUND: The dynamics of pain syndrome determined using various algic tests in the treatment of patients with diabetic neuropathic pain syndrome using tansdermal electroneurostimulation has been little studied. AIMS: To study the dynamics of projection zones of neuropathic pain syndrome in patients with diabetic polyneuropathy while using TENS. MATERIAL AND METHODS: 75 patients with diabetic polyneuropathy were examined. The control group (n=25; 33.3%) received a course of standard pharmacotherapy. The main group consisted of 2 groups. The first group (n=25; 33.3%) underwent a course of high-frequency low-amplitude (HL TENS) transdermal electroneurostimulation, and the second group (n=25; 33.3%) underwent a course of low-frequency high-amplitude (LH TENS) therapy. Pain syndrome was determined using a visual analogue scale (VAS) and a body diagram before, after treatment and in the long-term period. RESULTS: Using a visual analogue scale (VAS), the dynamics of pain syndrome after the use of LF TENS was lower than after the use of HFTENS by an average of 35% (p 0.05). The data obtained indicate that the regression of pain syndrome after physiotherapeutic treatment of TENS in patients from the main comparison groups exceeds similar indicators in patients from the control group by an average of 63% (p 0.05) both immediately after the course of exposure and in the distant the observation period by 23%. Against the background of TENS, the area of pain syndrome according to the body pattern significantly decreased by 53% after treatment (p 0.05) and by 65.6% in the long-term period (p 0.05), compared with a decrease in the area of pain syndrome in the control group. CONCLUSION: There were revealed significant differences between the quantitative and projection forms of pain measurement. The use of TENS enhances the analgesic effect of drug therapy in the treatment of diabetic neuropathic pain syndrome by 1.37 times while maintaining this effect without negative dynamics for 2 months after the end of the course of non-drug therapy. The developed technique for assessing pain syndrome using a body diagram in combination with a visual analogue scale (VAS) in patients with diabetic polyneuropathy provides a more reliable assessment of pain syndrome.

Main metabolic and toxic polyneuropathies in clinical practice

Polyneuropathies are diseases of the peripheral nervous system with lesions of motor, sensory or autonomic fibers which are encountered by attending physicians of almost all specialties in outpatient and clinical settings. To date, more than 100 different causes of polyneuropathies have been identified. Metabolic and toxic polyneuropathies are the most common in the group of secondary polyneuropathies. Diabetic, alcoholic, uremic, and drug-induced polyneuropathies take the leading place among these diseases. The main forms of diabetic polyneuropathy are presented. The main clinical form is distal symmetrical polyneuropathy. Clinical symptoms depend on the type of fibers involved in the pathological process - thin or thick. There is an assessment scale in points to determine the severity of diabetic polyneuropathy, which helps in clarifying the diagnosis and prognosis of the disease. The next most frequent among metabolic polyneuropathies is uremic polyneuropathy as the most frequent complication in patients suffering from chronic renal insufficiency. Risk factors of uremic polyneuropathy development, clinical picture, the course of the disease are described. Within the framework of toxic polyneuropathies, the main place is given to alcoholic polyneuropathies, chemotherapy-induced, and drug-induced. For each of these categories, clinical forms and pathophysiology of development are described. For all polyneuropathies, the main diagnostic aspects are presented. The main therapeutic approaches are shown. A separate place is given to the use of alpha-lipoic acid.

Principles of Treatment of Patients with Diabetic Polyneuropathy in the COVID-19 Pandemic

Patients with COVID-19 may develop various neurological disorders of the central and peripheral nervous systems. It is known that diabetes mellitus (DM) type 1 or 2, cardiovascular diseases, obesity, old age and old age, male gender are risk factors for a severe course and complications of COVID-19. Currently, the COVID-19 pandemic is ongoing, and patients with the listed risk factors are recommended to follow a regime of social restriction or self-isolation. Outpatient treatment is most appropriate for this category of patients. Patients with diabetes who have undergone COVID-19 are at risk of developing or progressing diabetic polyneuropathy (DPN). It seems relevant to develop the principles of effective treatment of patients with DM and DPN in outpatient settings. Glycemic level correction, diet, weight normalization, therapy of combined cardiovascular diseases, an increase of physical activity, sleep normalization, maintenance of normal psychological state are the main principles of treatment of patients with DM and DPN in COVID-19 pandemic conditions. Pathogenetic therapy of DPN continues to be discussed, in our country the preparations of B vitamins, alpha-lipoic acid are widely used. B-group vitamin preparations can be used in the form of tablets or solutions for intramuscular injections. The effectiveness of B vitamins (B1, B6, B12) in the treatment of a severe course of COVID- 19, prevention of complications of COVID-19, especially in elderly patients and with diabetes is discussed.

Analysis of Macrophages and Peptidergic Fibers in the Skin of Patients With Painful Diabetic Polyneuropathy

Background and ObjectivesThe mechanisms of pain in patients with diabetic polyneuropathy are unknown. Studies have suggested a role of inflammation and increased neuropeptides peripherally in pain generation. This study examined the possible skin markers of painful diabetic polyneuropathy (P-DPN): macrophages, substance P (SP), and calcitonin gene-related peptide (CGRP).MethodsThe participants were included from a large Danish cross-sectional clinical study of type 2 diabetes. We diagnosed definite diabetic polyneuropathy using the Toronto criteria and used the Neuropathic Pain Special Interest Group classification for defining P-DPN. We included 60 skin biopsies from patients with diabetic polyneuropathy—30 with P-DPN and 30 with nonpainful diabetic polyneuropathy (NP-DPN)—and 30 biopsies from healthy controls of similar age and sex. The biopsies were stained using PGP 9.5, IbA1, and SP and CGRP primary markers.ResultsThere was increased macrophage density in patients with P-DPN (8.0%) compared with that in patients with NP-DPN (5.1%, p < 0.001), and there was increased macrophage density in patients with NP-DPN (5.1%) compared with that in healthy controls (3.1%, p < 0.001). When controlling for neuropathy severity, body mass index, age, and sex, there was still a difference in macrophage density between patients with P-DPN and patients with NP-DPN. Patients with P-DPN had higher median nerve fiber length density (274.5 and 155 mm−2 for SP and CGRP, respectively) compared with patients with NP-DPN (176 and 121 mm−2 for SP and CGRP, respectively, p = 0.009 and 0.04) and healthy controls (185.5 and 121.5 mm−2 for SP and CGRP, respectively), whereas there was no difference between patients with NP-DPN and controls without diabetes (p = 0.64 and 0.49, respectively). The difference between P-DPN and NP-DPN for SP and CGRP was significant only in female patients, although a trend was seen in male patients.DiscussionThe findings point to a possible involvement of the innate immune system in the pathogenesis of neuropathic pain in patients with DPN, although markers of activated macrophages were not measured in this study.