Neuropathic Conditions Research Articles

The Effect of Aerobic Exercise on Collagen Type I and IV Gene Expression and Collagen Type I Protein Changes in the Sciatic Nerve of Diabetic Rats

Background: Neuropathy is one of the complications of diabetes, probably due to the destruction of the extracellular matrix and the thickening of the peripheral nerve basement membrane. However, its mechanisms and the impact of exercise on these disorders has not fully understood. The purpose of the present study was to investigate the effect of aerobic exercise on collagen levels of type I and IV and collagen type I protein changes in the sciatic nerve of diabetic rats. Materials and Methods: Eighteen 10-week-old Wistar male rats weighing 250 ± 20 g were randomly divided into three groups of healthy control (n=6), diabetic (n=6) and diabetic + aerobic exercise (n=6). For this purpose, after introduction and adaptation of rats to new environment, diabetes was induced by single dose injection of dissolved streptozotocin in sodium citrate buffer at pH=4.5 at 45 mg/kg intraperitoneal. After confirming neuropathic conditions (with behavioral tests), diabetic+exercise rats underwent moderate-intensity aerobic exercise on the treadmill for 8 week. At the beginning and at the end of the period, blood glucose of all rats was measured by glucometer and the mean of each group was measured separately. Changes in collagen type I and IV gene expression, and collagen type I protein levels in sciatic nerve of rats were evaluated by real-time PCR technique and immunohistochemistry, respectively. Results: Diabetes increased collagen type I and IV gene expression and collagen type I protein levels in the sciatic nerve samples of rats. However, exercise reduced blood sugar levels and expression of collagen type I and IV genes (p=0.05) and collagen type I protein significantly reduced in sciatic nerve (p=0.001). Conclusion: The results of the present study showed that aerobic exercise as a non-pharmacological strategy by negative regulating type I and IV collagen factors at the gene and protein level, was able to control and inhibit the effects of diabetes on extracellular matrix components in the sciatic nerve.

Intercellular communication and ion channels in neuropathic pain chronicization.

Neuropathic pain is caused by primary lesion or dysfunction of either peripheral or central nervous system. Due to its complex pathogenesis, often related to a number of comorbidities, such as cancer, neurodegenerative and neurovascular diseases, neuropathic pain still represents an unmet clinical need, lacking long-term effective treatment and complex case-by-case approach. We analyzed the recent literature on the role of selective voltage-sensitive sodium, calcium and potassium permeable channels and non-selective gap junctions (GJs) and hemichannels (HCs) in establishing and maintaining chronic neuropathic conditions. We finally focussed our review on the role of extracellular microenvironment modifications induced by resident glial cells and on the recent advances in cell-to-cell and cell-to-extracellular environment communication in chronic neuropathies. In this review, we provide an update on the current knowledge of neuropathy chronicization processes with a focus on both neuronal and glial ion channels, as well as on channel-mediated intercellular communication.

Chronic facial pain: different comorbidities and characteristics between neuropathic and nonneuropathic conditions

The aim of this study was to investigate the association between comorbidities and chronic diseases and neuropathic and nonneuropathic orofacial pain diagnoses to suggest subclassifications of disease. This was a cross-sectional, retrospective, case-control study. We evaluated 174 patients with orofacial pain and 132 controls by using a systematic protocol that consisted of medical history and demographic, pain, and orofacial characteristics. Patients were grouped according to their diagnosis-neuropathic or non-neuropathic pain; medical comorbidities; and exclusion criteria. Analyses included Z-score normalization, χ2 test, Fisher's exact test, 1-way analysis of variance (ANOVA), Student t test, Pearson's correlation coefficient, 2-step clustering, and logistic regression at 95% confidence level. Functional chronic diseases were prevalent and correlated with pain and orofacial features. Three groups were identified in the cluster analysis: neuropathic facial pain, other orofacial pain syndromes, and fibromyalgia/temporomandibular disorders (TMDs). Logistic regression showed that hypothyroidism and gastritis were predictors for nonneuropathic orofacial conditions. Psychiatric diseases and gastritis were more prevalent among patients with generalized pain syndromes and TMDs and less prevalent among patients with neuropathic pain. Functional comorbidities were associated with orofacial and dental features and may correspond to multimorbidity states in patients with chronic orofacial pain. The findings support the hypothesis that nonneuropathic orofacial pain syndromes could be functional disorders.

Effect of forced running on rat skeletal muscle with acrylamide neuropathy

This study was performed to evaluate the effect of prolonged forced running on rat lower limb muscles with acrylamide neuropathy. Twenty-four 4-week-old rats were divided into three groups of eight rats. Acrylamide was given to two groups of sixteen rats to induce mild paralysis. Eight rats with acrylamide injections were forced to run 3,200 m/day on a treadmill for five weeks. Running activities slowed the rate of body weight gain and aggravated paralysis. Although the wet weight of tibialis anterior (TA) and extensor digitorum longus (EDL) muscles was reduced by running, that of soleus (SOL) muscles was unchanged. The ratio of their weight to their body weight (BW) remained constant regardless of exercise. Protein content (PC) of muscles was not altered by exercise, either. We postulated that exercise-induced worsening of paralysis in acrylamide neuropathy rats was not caused by muscle pathology. Deterioration of neuropathic condition due to exercise was suggested.

Characterization of experimental diabetic neuropathy using multicontrast magnetic resonance neurography at ultra high field strength

In light of the limited treatment options of diabetic polyneuropathy (DPN) available, suitable animal models are essential to investigate pathophysiological mechanisms and to identify potential therapeutic targets. In vivo evaluation with current techniques, however, often provides only restricted information about disease evolution. In the study of patients with DPN, magnetic resonance neurography (MRN) has been introduced as an innovative diagnostic tool detecting characteristic lesions within peripheral nerves. We developed a novel multicontrast ultra high field MRN strategy to examine major peripheral nerve segments in diabetic mice non-invasively. It was first validated in a cross-platform approach on human nerve tissue and then applied to the popular streptozotocin(STZ)-induced mouse model of DPN. In the absence of gross morphologic alterations, a distinct MR-signature within the sciatic nerve was observed mirroring subtle changes of the nerves’ fibre composition and ultrastructure, potentially indicating early re-arrangements of DPN. Interestingly, these signal alterations differed from previously reported typical nerve lesions of patients with DPN. The capacity of our approach to non-invasively assess sciatic nerve tissue structure and function within a given mouse model provides a powerful tool for direct translational comparison to human disease hallmarks not only in diabetes but also in other peripheral neuropathic conditions.

Localized sympathectomy reduces peripheral nerve regeneration and pain behaviors in 2 rat neuropathic pain models.

Previous studies have shown that the peripheral nerve regeneration process is linked to pain in several neuropathic pain models. Other studies show that sympathetic blockade may relieve pain in some pain models and clinical conditions. This study examined reduction in peripheral nerve regeneration as one possible mechanism for relief of neuropathic pain by sympathetic blockade. A "microsympathectomy," consisting of cutting the gray rami containing sympathetic postganglionic axons where they enter the L4 and L5 spinal nerves, reduced mechanical hypersensitivity in 2 different rat neuropathic pain models. In the spinal nerve ligation model, in which some functional regeneration and reinnervation of the ligated spinal nerve can be observed, microsympathectomy reduced functional and anatomical measures of regeneration as well as expression of growth-associated protein 43 (GAP43), a regeneration-related protein. In the spared nerve injury model, in which functional reinnervation is not possible and the futile regeneration process results in formation of a neuroma, microsympathectomy reduced neuroma formation and GAP43 expression. In both models, microsympathectomy reduced macrophage density in the sensory ganglia and peripheral nerve. This corroborates previous work showing that sympathetic nerves may locally affect immune function. The results further highlight the challenge of improving pain in neuropathic conditions without inhibiting peripheral nerve regeneration that might otherwise be possible and desired.

Evaluating the Discordant Relationship Between Tarlov Cysts and Symptoms of Pudendal Neuralgia

(Abstracted from Am J Obstet Gynecol 2020;222:70.e1–70.e6) Pudendal neuralgia is a painful chronic neuropathic pelvic condition involving the pudendal nerve dermatome. It is often debilitating and can greatly decrease quality of life among both men and women.

Post Herpetic Neuralgia: Recent Advancements

To discuss updates and recommendations for the treatment of postherpetic neuralgia (PHN), a painful neuropathic condition caused by reactivation of the latent varicella-zoster virus (VZV). The focus of this review will include prevention, evaluation, diagnosis, and management. Using a multidisciplinary approach to management yields the best results, including oral and topical medication, physical therapy, psychotherapy, injections, complementary, and other procedural interventions, as well as neural stimulation. Recent advancements in the management of neuropathic pain conditions have led to opioid sparing options for postherpetic neuralgia and can help prevent its progression in order to minimize disability.

Antibiotic prophylaxis in high-risk pediatric spine surgery: Is cefazolin enough?

Retrospective study. To describe pathogens found in SSI during pediatric-instrumented spine surgery, and to assess the relationship between pathogens and the etiology of the spinal deformity. Surgical site infection (SSI) after pediatric spine fusion is a well-known complication with incidence rates between 0.5 and 42%, associated with the patient underlying disorder. Pathogens involved in SSI seem to be related to patient characteristics, such as the etiology of the spinal deformity. GNB (gram-negative bacilli) are more frequent in neuropathic, muscular, and syndromic conditions. High-risk pediatric patients with a spine deformity undergoing instrumented surgery might benefit from receiving perioperative intravenous prophylaxis for GNB. We conducted a retrospective study at our tertiary-care pediatric hospital from January 2010 to January 2017. We reviewed records of all episodes of SSI that occurred in the first 12months postoperatively. All patients who underwent instrumented spine surgery were included in this study. We assessed 1410 pediatric-instrumented spine surgeries; we identified 68 patients with deep SSIs, overall rate of 4.8%. Mean age at instrumented spine surgery was 12years and 9months. Time elapsed between instrumented surgery and debridement surgery was 28.8days. Cultures were positive in 48 and negative in 20. Of the 48 positive culture results, 41 (72%) were GNB, 12 (21%) gram-positive cocci (GPC), three (5%) gram-positive anaerobic cocci (GPAC), and one (2%) coagulase-negative staphylococci (CoNS). Of the 68 patients with primary SSIs, 46 were considered to have a high risk of infection, which reported GNB in 81%, GPC in 15%, GPAC in 2%, and CoNS in 2%. Cefazolin prophylaxis covers GPC and CoNS, but GNB with unreliable effectiveness. Gram-negative pathogens are increasingly reported in SSIs in high-risk patients. Adding prophylaxis for GNB in high-risk patients should be taken into account when considering spine surgery. IV.

In Vitro and In Vivo Effects of Flavonoids on Peripheral Neuropathic Pain.

Neuropathic pain is a common symptom and is associated with an impaired quality of life. It is caused by the lesion or disease of the somatosensory system. Neuropathic pain syndromes can be subdivided into two categories: central and peripheral neuropathic pain. The present review highlights the peripheral neuropathic models, including spared nerve injury, spinal nerve ligation, partial sciatic nerve injury, diabetes-induced neuropathy, chemotherapy-induced neuropathy, chronic constriction injury, and related conditions. The drugs which are currently used to attenuate peripheral neuropathy, such as antidepressants, anticonvulsants, baclofen, and clonidine, are associated with adverse side effects. These negative side effects necessitate the investigation of alternative therapeutics for treating neuropathic pain conditions. Flavonoids have been reported to alleviate neuropathic pain in murine models. The present review elucidates that several flavonoids attenuate different peripheral neuropathic pain conditions at behavioral, electrophysiological, biochemical and molecular biological levels in different murine models. Therefore, the flavonoids hold future promise and can be effectively used in treating or mitigating peripheral neuropathic conditions. Thus, future studies should focus on the structure-activity relationships among different categories of flavonoids and develop therapeutic products that enhance their antineuropathic effects.

Effects of mTOR inhibitors on neuropathic pain revealed by optical imaging of the insular cortex in rats

In the pain matrix, the insular cortex (IC) is mainly involved in discriminative sensory and motivative emotion. Abnormal signal transmission from injury site causes neuropathic pain, which generates enhanced synaptic plasticity. The mammalian target of rapamycin (mTOR) complex is the key regulator of protein synthesis; it is involved in the modulation of synaptic plasticity. To date, there has been no report on the changes in optical signals in the IC under neuropathic condition after treatment with mTOR inhibitors, such as Torin1 and XL388. Therefore, we aimed to determine the pain-relieving effect of mTOR inhibitors (Torin1 and XL388) and observe the changes in optical signals in the IC after treatment. Mechanical threshold was measured in adult male Sprague-Dawley rats after neuropathic surgery, and therapeutic effect of inhibitors was assessed on post-operative day 7 following the microinjection of Torin1 or XL388 into the IC. Optical signals were acquired to observe the neuronal activity of the IC in response to peripheral stimulation before and after treatment with mTOR inhibitors. Consequently, the inhibitors showed the most effective alleviation 4 h after microinjection into the IC. In optical imaging, peak amplitudes of optical signals and areas of activated regions were reduced after treatment with Torin1 and XL388. However, there were no significant optical signal changes in the IC before and after vehicle application. These findings suggested that Torin1 and XL388 are associated with the alleviation of neuronal activity that is excessively manifested in the IC, and is assumed to diminish synaptic plasticity.

High-Mobility Group Box 1 Protein Signaling in Painful Diabetic Neuropathy.

Diabetes is a global epidemic and more than 50% diabetic patients are also diagnosed with neuropathy, which greatly affects the quality of life of the patients. Available treatments are not always successful due to the limited efficacy and complications, such as addiction and dependency. Studies have implicated that high mobility group box1 (HMGB1) protein plays a crucial role in neuroinflammation and the development of neuropathic conditions. HMGB1 is a proinflammatory cytokine that can be released from necrotic cells in passive form or in response to inflammatory signals as an active form. HMGB1 is the ligand for the receptor for advanced glycation end products (RAGE), and toll-like receptors, (TLR)-2 and TLR4, which also indirectly activates C-X-C chemokine receptor type 4 (CXCR4). We investigated whether blocking of HMGB1 can reduce pain and inflammation in diabetic neuropathic animals to further understand the role of HMGB1 in diabetic neuropathy. Type 2 diabetic rats and mice were treated with natural inhibitor of HMGB1, glycyrrhizin (GLC) for five days/week for four weeks at a dose of 50 mg/kg per day by intraperitoneal injection. The animals were divided into three categories: naïve control, diabetic alone, diabetic with GLC treatment. All of the behavioral analyses were conducted before and after the treatment. The expression of inflammatory markers and changes in histone acetylation in the peripheral nervous system were measured by immunohistochemistry and Western blot analysis after the completion of the treatment. Our study revealed that TLR4, HMGB1, CXCR4, and Nod-like receptor protein 3 (NLRP3) levels were increased in the spinal and dorsal root ganglia (DRG) neurons of Type 2 diabetic mice and rats with painful neuropathy. GLC treatment inhibited the increases in TLR4, NLRP3, and CXCR4 expressions and improved the mechanical and thermal pain threshold in these animals. Immunohistochemical studies revealed that hyperglycemia mediated inflammation influenced HMGB1 acetylation and its release from the neurons. It also altered histone 3 acetylation in the microglial cells. The inhibition of HMGB1 by GLC prevented the release of HMGB1 as well as H3K9 acetylation. These findings indicate that the interruption of HMGB1 mediated inflammation could ameliorate diabetic neuropathy and might exhibit a unique target for the treatment.

Behavioral pharmacology of the mixed-action delta-selective opioid receptor agonist BBI-11008: studies on acute, inflammatory and neuropathic pain, respiration, and drug self-administration.

The present study characterized the behavioral pharmacology of a novel, mixed-action delta-selective (78:1) opioid receptor agonist, BBI-11008. This glycopeptide drug candidate was tested in assays assessing antinociception (acute, inflammatory, and neuropathic pain-like conditions) and side-effect endpoints (respiratory depression and drug self-administration). BBI-11008 had a 78-fold greater affinity for the delta opioid receptor than the mu receptor, and there was no binding to the kappa opioid receptor. BBI-11008 (3.2-100; 10-32mgkg-1, i.v.) and morphine (1-10; 1-3.2mgkg-1, i.v.) produced antinociceptive and anti-allodynic effects in assays of acute thermal nociception and complete Freund's adjuvant (CFA)-induced inflammatory pain, with BBI-11008 being less potent than morphine in both assays. BBI-11008 (1-18mgkg-1, i.v.) had similar efficacy to gabapentin (10-56mgkg-1, i.v.) in a spinal nerve ligation (SNL) model of neuropathic pain. In the respiration assay, with increasing %CO2 exposure, BBI-11008 produced an initial increase (32mgkg-1, s.c.) and then decrease (56mgkg-1, s.c.) in minute volume (MV) whereas morphine (3.2-32mgkg-1, s.c.) produced dose-dependent decreases in MV. In the drug self-administration procedure, BBI-11008 did not maintain self-administration at any dose tested. These results suggest that the glycopeptide drug candidate possesses broad-spectrum antinociceptive and anti-allodynic activity across a range of pain-like conditions. Relative to morphine or fentanyl, the profile for BBI-11008 in the respiration and drug self-administration assays suggests that BBI-11008 may have less pronounced deleterious side effects. Continued assessment of this compound is warranted.

Gabapentinoid prescription in oral medicine and oral surgery practice. Part I − Experience from a French Orofacial pain clinic

Gabapentinoids, pregabalin and gabapentin, are neuronal voltage-gated calcium channel inhibitors mainly prescribed for the treatment of partial epilepsy and neuropathic pain. Although their efficacy as first-line treatments for painful neuropathic conditions (and several non-neuropathic painful conditions) has been well established in general medical practice, their efficacy and prescription in Oral Medicine and Oral Surgery practice has received little attention so far. This didactic article, the first of a two-part series, aims to present the experience of a French tertiary orofacial pain clinic regarding the prescription of gabapentinoids in Orofacial pain conditions that fall within the scope of the oral surgeon's practice.

Gabapentinoid prescription in Oral Medicine and Oral Surgery practice. Part II − a systematic scoping review of the literature

Introduction: Gabapentinoids, pregabalin and gabapentin, neuronal voltage-gated calcium channel inhibitors are first-line treatments for painful neuropathic conditions (and several non-neuropathic painful conditions). Nevertheless, their efficacy and prescription in Oral Medicine and Oral Surgery practice has received little attention so far. A previous article, the first of a two-part series, presented the experience of a French tertiary orofacial pain clinic regarding the prescription of gabapentinoids in orofacial conditions. This second article aimed to explore the scientific literature on the subject. Material and methods: A systematic scoping review was conducted on multiple relevant databases (MEDLINE®, Cochrane®, Agence Nationale de Sécurité du Médicament et des produits de santé, Haute Autorité de Santé) and journal archives (JOMOS, JSOMFS) to assess the indications, non-indications and contraindications of gabapentinoids in an Oral Medicine/Oral Surgery context. Results: Out of 131 records selected during the initial screening, 34 matched the inclusion criteria and were used for subsequent analyses. Gabapentinoids were prescribed in three clinical contexts: orofacial pain management (32 studies), anxiolysis (1 study) and prevention of postoperative nausea/vomiting (1 study), with variable quality of evidence: high (6 studies), moderate (3 studies), low (5 studies) and very low (20 studies) quality studies (GRADE scale). Untoward effects of gabapentinoids were reported in 16 studies, mainly neurological (vertigo, drowsiness, sedation) and gastro-intestinal (nausea, vomiting, diarrhea, constipation). Gabapentinoids were ineffective in preemptive and postoperative analgesia and for the management of mucositis-related pain. Discussion: There is some evidence supporting the use of gabapentinoids in Oral Medicine/Oral Surgery in adherence with current practices observed in France and other countries (practices often extrapolated from their use in other non-orofacial painful conditions). The methodological quality of the studies included in this scoping review is often poor and publication bias is most probable in this field. Therefore, any conclusion drawn from such studies must be subject to circumspection. Conclusion: Data obtained from the present scoping review suggests the potential use of gabapentinoids as second-line treatments for anxiolysis, prevention of postoperative nausea/vomiting and the management of trigeminal neuralgia and masticatory myalgia. Other potential indications of gabapentinoids in Oral Medicine/Oral Surgery practice include cranial neuralgias, post-traumatic trigeminal neuropathies, first bite syndrome, burning mouth syndrome and migraine prophylaxis, when other treatment options are inefficient or unavailable.

Pain condition and sex differences in the descending noradrenergic system following lateral hypothalamic stimulation

The lateral hypothalamus (LH) is known to modulate nociception via the descending noradrenergic system in acute nociception, but less is known about its role in neuropathic pain states. In naïve females, LH stimulation produces opposing effects of α-adrenoceptors, with α2-adrenoceptors mediating antinociception, while pronociceptive α1-adrenoceptors attenuate the effect. Whether this opposing response is seen in neuropathic conditions or in naïve males is unknown. We used a mixed factorial design to compare male and female rats with chronic constriction injury (CCI) to naïve rats, measured by Total Paw Withdrawal (TPW) responses to a thermal stimulus. Rats received one of three doses of carbachol to stimulate the LH followed by intrathecal injection of either an α1- or an α2-adrenoceptor antagonist (WB4101 or yohimbine, resp.) or saline for control. Overall, naïve rats showed a more pronounced opposing alpha-adrenergic response than CCI rats (p<0.04). Naïve male and female rats demonstrated antinociception following α1-adrenoceptor blockade and hyperalgesia following α2-adrenoceptor blockade. Male CCI rats also showed dose dependent effects from either WB4101 or yohimbine (p<0.05), while female CCI rats had significant antinociception from WB4101 (p<0.05), but no effect from yohimbine. These results support the idea that peripheral nerve damage differentially alters the descending noradrenergic modulatory system in male and female rats, and notably, that female CCI rats do not show antinociception from descending noradrenergic input. These findings are suggestive that clinical therapies that recruit the descending noradrenergic system may require a different approach based on patient gender.

Blockade of peripheral nociceptive signal input relieves the formation of spinal central sensitization and retains morphine efficacy in a neuropathic pain rat model

Neural plasticity, especially central sensitization, is essential for developing and maintaining neuropathic pain. Unfortunately, the analgesic potency of morphine is greatly reduced in animal models and patients with neuropathic pain. We hypothesized that pre-activation of spinal N-methyl-d-aspartate receptors (NMDARs) by agonist or neuropathic pain facilitated the development of morphine-induced analgesic tolerance. We therefore investigated the effects of spinal NMDAR activation, induced by neuropathic pain, on the development of morphine-induced analgesic tolerance in male Sprague-Dawley rats. Four days of chronic constriction injury (CCI) induced upregulation of spinal NR1. Once established, spinal central sensitization accelerated the development of morphine-induced analgesic tolerance. Continuous ropivacaine infusion prevented CCI-induced increases in spinal Substance P (SP), NR1, and TRPV1. Blockade of peripheral nociceptive inputs prevented chronic morphine-induced increases in spinal SP, NR1, and TRPV1 and a rightward shift of the morphine dose-response curve in the CCI model. These findings suggest that pre-activation of spinal NMDARs contributes to central sensitization and potentiates the development of morphine-induced analgesic tolerance. Interruption of the peripheral nociceptive inputs during the induction phase could prevent spinal central sensitization and retain morphine efficacy, thereby delaying the development of morphine-induced tolerance in patients with neuropathic conditions.

POEMS Syndrome: A Review of Our Patient Population

Introduction The "POEMS" Syndrome, defined by its hallmark features of polyneuropathy, organomagaly, endocrinopathy, monoclonal plasma cell proliferative disorder, and skin changes has long been an enigma in terms of diagnosis and treatment. In recent years, clinicians and researchers have attempted to clarify diagnostic criteria. It is known that "VEGF," vascular endothelial growth factor, plays a large role in the pathophysiology of this disease.1Most recently, Angela Dispenzieri proposed a set of diagnostic criteria, which were published in the American Journal of Hematology.2We applied this suggested diagnostic criteria retrospectively to patients in our institution who carried a diagnosis of POEMS Syndrome. Additionally, we recorded the VEGF of these patients and their outcomes. Methods The.medical record was queried for patients with POEMS diagnosed in the last 5 years. A total of 16 patients met criteria. The primary outcome was to determine the percentage of patients who met the criteria proposed by Dispenzieri. A secondary outcome was to determine, in those patients who did not meet the criteria, the reason that they were not met. Another secondary outcome was to determine the percentage of patients who were alive or deceased. The criteria proposed by Dispenzieri (Table 1) were applied to each patient to assess whether they were met. If the diagnostic criteria were not met, the reason as to why they were not was recorded. Each patient outcome of "alive," "deceased," or "unknown" was recorded. Results Of the 16 patients analyzed, 14 (88%) had enough information to be included. Of these 14 patients, nine (64%) met the criteria proposed by Dispenzieri. Of the five patients that did not meet the criteria, four (80%) did not meet them due to the lack of a presence of a major criteria. One patient of the five (20%) that did not meet the criteria did not have the mandatory finding of polyneuropathy. VEGF levels ranged from 26-9504pg/mL, with an average of 1190pg/mL. The range for the patients who met the diagnostic criteria proposed by Dispenzieri was 1755pg/mL. Of our total patient population analyzed, 10 out of 14 patients (72%) were alive at time of retrospective review, including six out of nine (66%) that met the diagnostic criteria. Two out of 14 patients (14%) were found on review to be deceased, including one out of the nine (11%) that met the diagnostic criteria. Two out of 14 patients (14%) were determined to be "unknown" if alive or deceased, both of whom met the diagnostic criteria. Discussion Patients with POEMS syndrome often experience a delay in diagnosis due to the rarity of the disease as well as a lack of high index of suspicion for the condition in many cases. Additionally, POEMS syndrome is often mislabeled as another neuropathic condition. Efforts have been made to establish a standard criteria for diagnosis. We applied the criteria proposed by Dispenzieri this year in the American Journal of Hematology. In our retrospective study, we found that that 64% of our patients who carried a diagnosis of POEMS syndrome met the criteria for POEMS diagnosis using these proposed criteria. We found that the most common reason for not meeting the criteria in our patient population was the lack of a major criterion. Major criteria (Table 1) include Castleman Disease, sclerotic bone lesions and VEGF elevation, one of which must be met to receive a diagnosis of POEMS syndrome. Additionally, one of our patients did not meet the criteria due to the lack of the mandatory finding of polyneuropathy. The average VEGF levels in our patients were 1190pg/mL, but were higher at 1755pg/mL in the cohort who met the diagnostic criteria. 72% of our total patients were alive at time of review, including 66% of the patients who met the diagnostic criteria. We conclude that the criteria proposed by Dispenzieri provide a concise guideline to identify patients with POEMS syndrome. These criteria are simple to apply, and would potentially help to increase the index of suspicion and earlier diagnosis of patients with POEMS syndrome. This would be expected to lead to earlier initiation of therapy. Additionally, this analysis supports previous studies that show that VEGF levels are correlated with disease activity and that overall prognosis for patients with POEMS syndrome is favorable. Disclosures No relevant conflicts of interest to declare.

A Novel Technique Using Magnetic Resonance Imaging in the Supine and Prone Positions for Diagnosing Lumbar Adhesive Arachnoiditis: A Preliminary Study.

Lumbar adhesive arachnoiditis is a debilitating neuropathic condition and is difficult to diagnose owing to lack of definitive diagnostic criteria. By focusing on the intrathecal mobility of nerve roots, we assessed whether useful diagnostic criteria could be established using MRI. Seventeen patients with a high risk for lumbar adhesive arachnoiditis and 18 no-risk patients with chronic low back pain and/or leg pain participated in this study. The patients underwent MRI in both the supine and prone positions. Eleven axial T2-weighted images between the L2 and L5/S levels were obtained, and the proportion of the low-intensity area in the dorsal half to the total low-intensity area in the dural sac was calculated for each axial view. At some lumbar levels, the low-intensity area in the dorsal half of the dural sac was relatively larger in patients with a high risk for lumbar adhesive arachnoiditis than in the no-risk patients. In the no-risk group, the proportion of the low-intensity area in the dorsal half in the supine position was significantly higher than that in the prone position at all lumbar levels. However, in the high-risk group, at some levels, the proportions were not significantly different in the dorsal half of the dural sac between the supine and prone positions. In patients with a known risk for lumbar adhesive arachnoiditis, nerve roots lose their potential to migrate in the dural sac in the gravitational force direction on MRI.

Diabetic Neuropathy.

Diabetes mellitus is becoming increasingly common worldwide. As this occurs, there will be an increase in the prevalence of known comorbidities from this disorder of glucose metabolism. One of the most disabling adverse comorbidities is diabetic neuropathy. The most common neuropathic manifestation is distal symmetric polyneuropathy, which can lead to sensory disturbances, including diminished protective sense, making patients prone to foot injuries. However, focal, multifocal, and autonomic neuropathies are also common. Diabetic nerve pain and Charcot osteoarthropathy are advanced neuropathic conditions that portend a severe deterioration in quality of life. To combat these symptoms, along with glycemic control and establishment of health care systems to educate and support patients with the complexities of diabetes, there are pharmacologic remedies to ameliorate the neurologic symptoms. Several guidelines and review boards generally recommend the use of tricyclic antidepressants, serotonin/norepinephrine-reuptake inhibitors, α-2-delta ligands, and anticonvulsants as medications to improve painful diabetic neuropathy and quality of life.