Type Of Peripheral Neuropathy Research Articles

Spinal pituitary adenylate cyclase-activating polypeptide and PAC1 receptor signaling system is involved in the oxaliplatin-induced acute cold allodynia in mice

Chemotherapy-induced peripheral neuropathy (CIPN) is a type of peripheral neuropathy that develops in patients treated with certain anticancer drugs. Oxaliplatin (OXA) causes CIPN in approximately 80–90 % of patients; thus, it is necessary to elucidate its underlying mechanism and develop effective treatments and prevention methods. The purpose of this study was to determine whether the pituitary adenylate cyclase-activating polypeptide (PACAP)/PAC1 receptor system in the spinal dorsal horn is involved in OXA-induced acute cold allodynia and examine the effect of a PAC1 receptor antagonist. Administration of OXA induced acute cold allodynia in wild-type mice, but not in PACAP-/- mice. In the dorsal root ganglia, OXA upregulated PACAP expression, particularly in small-sized neurons. OXA-induced cold allodynia was ameliorated by intrathecal (i.t.) injection of PACAP6–38 (peptide antagonist for PACAP receptor) and PA-8 (small-molecule antagonist specific for PAC1 receptor). I.t. PACAP, but not vasoactive intestinal polypeptide, resulted in cold allodynia, which was blocked by PA-8. OXA induced the activation of spinal astrocytes in a PAC1 receptor-dependent manner. The results suggest that spinal PACAP/PAC1 receptor systems are involved in OXA-induced acute cold allodynia through astrocyte activation. Furthermore, we demonstrated that the systemic administration of PA-8 resulted in therapeutic and preventative effects on OXA-induced acute cold allodynia. Because PA-8 did not affect the anticancer effects of OXA, we propose PAC1 receptor inhibition as a new strategy for the treatment and prevention of CIPN. PerspectiveCold allodynia is a hallmark of OXA-induced peripheral neuropathy. This study demonstrated the involvement of spinal PACAP/PAC1 receptors in OXA-induced acute cold allodynia. We propose PAC1 receptor inhibition as a new strategy for the treatment and prevention of OXA-induced acute cold allodynia.

Pain hypersensitivity, sensorimotor impairment, and decreased muscle force in a novel rat model of radiation-induced peripheral neuropathy.

Radiation-induced peripheral neuropathy is a rare, but serious complication often resulting in profound morbidity, life-long disability, and chronic debilitating pain. Unfortunately, this type of peripheral neuropathy is usually progressive, and almost always irreversible. To date, a standardized rat model of radiation-induced peripheral neuropathy has not been established. The purpose of the present study was to examine neuropathic pain, sensorimotor impairment, and muscle force parameters following the administration of a clinically relevant radiation dose in a rat model. Ten rats were randomly assigned to one of two experimental groups: (1) radiation and (2) sham-radiated controls. Radiated animals were given a clinically relevant dose of 35 Gray (Gy) divided into five daily doses of 7 Gy/day. This regimen represents a human equivalent dose of 70 Gy, approximating the same dosage utilized for radiotherapy in oncologic patients. Sham-radiated controls were anesthetized and placed in the radiation apparatus but were not given radiation. All animals were tested for baseline values in both sensorimotor and pain behavioral tests. Sensorimotor testing consisted of the evaluation of walking tracks with the calculation of the Sciatic Functional Index (SFI). Pain-related behavioral measures consisted of mechanical allodynia (von Frey test), cold allodynia (Acetone test), and thermal allodynia (Hargreaves test). Animals were tested serially over an 8-week period. At the study endpoint, electrophysiological and muscle force assessments were completed, and histomorphometric analysis was performed on all sciatic nerves. Animals that underwent radiation treatment displayed significantly greater pain hypersensitivity to mechanical stimulation as compared to sham radiated controls from weeks 4 to 8 of testing. SFI values indicated sensorimotor impairments in the overground gait of radiated animals as compared to non-radiated animals. Furthermore, radiated animals displayed reduced twitch and tetanic muscle force when compared to sham radiated controls. A clinically relevant human equivalent dose of fractionated 35 Gy in rats established significant pain hypersensitivity, impairments in sensorimotor locomotion, and decreased muscle force capacity. This novel rodent model of radiation-induced peripheral neuropathy can be utilized to assess the potential efficacy of therapeutic treatments to either prevent or remediate this clinically debilitating condition.

Peripheral neuropathy in patients with gout, beyond focal nerve compression: a cross-sectional study.

Neuropathies secondary to tophus compression in gout patients are well known; however, limited data exist on other types of peripheral neuropathies (PN). Our aim was to describe PN frequency, characteristics, distribution, patterns, and associated factors in gout patients through clinical evaluation, a PN questionnaire, and nerve conduction studies (NCS). This cross-sectional descriptive study included consecutive gout patients (ACR/EULAR 2015 criteria) from our clinic. All underwent evaluation by Rheumatology and Rehabilitation departments, with IRB approval. Based on NCS, patients were categorized as PN + (presence) or PN- (absence). PN + patients were further classified as local peripheral neuropathy (LPN) or generalized somatic peripheral neuropathy (GPN). We enrolled 162 patients, 98% male (72% tophaceous gout). Mean age (SD): 49.4 (12) years; mean BMI: 27.9 (6.0) kg/m2. Comorbidities included dyslipidemia (53%), hypertension (28%), and obesity (23.5%). Abnormal NCS: 65% (n = 106); 52% LPN, 48% GPN. PN + patients were older, had lower education, and severe tophaceous gout. GPN patients were older, had lower education, and higher DN4 scores compared to LPN or PN- groups (p = 0.05); other risk factors were not significant. Over half of gout patients experienced neuropathy, with 48% having multiplex mononeuropathy or polyneuropathy. This was associated with joint damage and functional impairment. Mechanisms and risk factors remain unclear. Early recognition and management are crucial for optimizing clinical outcomes and quality of life in these patients. Key Points Peripheral neuropathies in gout patients had been scarcely reported and studied. This paper report that: • PN in gout is more frequent and more diverse than previously reported. • Mononeuropathies are frequent, median but also ulnar, peroneal and tibial nerves could be injured. • Unexpected, generalized neuropathies (polyneuropathy and multiplex mononeuropathy) are frequent and associated to severe gout. • The direct role of hyperuricemia /or gout in peripheral nerves require further studies.

Semiquantitative assessment of preganglionic nerves for chronic immune-mediated neuropathies using brachial plexus magnetic resonance imaging.

Brachial plexus magnetic resonance imaging (MRI) is an important noninvasive supplementary diagnostic method of chronic immune peripheral neuropathies, but few MRI studies on the preganglionic nerves have been conducted. This retrospective cross-sectional study aimed to establish a reliable assessment for brachial plexus preganglionic nerve thickness and to use this method to assess and compare nerve characteristics in various types of peripheral neuropathies. Hospitalized patients diagnosed as positive for anti-neurofascin-155 (NF155)-positive autoimmune nodopathy (AN) (NF155+), chronic inflammatory demyelinating polyneuropathy (CIDP), or multifocal motor neuropathy (MMN) at Huashan Hospital of Fudan University in Shanghai, China, who underwent brachial plexus MRI between October 2011 and August 2023 were consecutively recruited for this study. We also recruited participants who underwent brachial plexus MRI during this period with no history of trauma, inflammation, tumors, compression, or degenerative conditions as healthy controls. According to our self-developed semiquantitative assessment of preganglionic nerves, we assessed the bilateral preganglionic C5-C8 nerves individually and scored the enlargement degree from 0 to 4 points. Furthermore, a sum score ≥20 was defined as definite enlargement. A total of 122 participants were enrolled, including 28 with NF155+, 40 with CIDP, 15 with MMN, and 39 healthy controls. In the comparison of the single-nerve scores, we found that there was a significant difference distribution among the four groups (χ2 test; P<0.001), with the patients with NF155+ exhibiting the highest scores in each of the bilateral C5-C8 nerves. In the comparison of the sum scores, a descending tendency was observed in patients NF155+, CIDP, and MMN, with median scores of 11, 4, and 0 points, respectively (Kruskal-Wallis test; P=0.003, P<0.001, and P=0.005, respectively for NF155+ vs. CIDP, NF155+ vs. MMN, and CIDP vs. MMN). The proportion of definite enlargement in those with NF155+ was greater than that in healthy controls (21% vs. 0%; χ2 test; P=0.004), and the sum score at 0 points was lower in the NF155+ group than in CIDP, MMN, and healthy control groups (7% vs. 37%, 87%, and 41%, respectively; χ2 test; P<0.001). This semiquantitative assessment can be a valuable tool for measuring preganglionic nerve enlargement, which was found to be decreased, respectively, in those with NF155+, CIDP, and MMN. Presence of definite enlargement could be a strong indicator of NF155+ in clinic.

Drug utilization patterns for peripheral neuropathy in a neurology outpatient department at a tertiary care center: A cross-sectional observational study

Background: Peripheral neuropathy is a broad term encompassing any condition that impacts the peripheral nerves. It encompasses a wide range of conditions, presenting with a variety of abnormalities that affect different aspects of both the voluntary (somatic) and involuntary nervous systems (autonomic nervous system). The manifestations of peripheral neuropathy can vary significantly based on the specific nerves affected. This disorder can induce numbness, tingling, or pins and needles sensations along with sharp and pulsating pain. Commonly employed medications for treating peripheral neuropathy encompass analgesics such as opioids and over-the-counter pain relievers, as well as anti-epileptic drugs such as topiramate, gabapentin, and pregabalin. For enhancing the management of peripheral neuropathy, it is imperative to gather data regarding the prevailing utilization trends of medications prescribed for neuropathic pain. Drug utilization studies constitute continuous activity for evidence based therapeutic practices; it implies rational therapy with focus on the prime parameters. This study aims to assess the drug utilization pattern for peripheral neuropathy under various prescriptions which provides the scope for various etiologies and severity requiring judicious choice of drug use. Aims and Objectives: The objective of the study was to assess the pattern of medications dispensed to patients diagnosed with various types of peripheral neuropathy at a tertiary care center and to evaluate the drug regimen given for particular type of peripheral neuropathy. Materials and Methods: It is a cross-sectional observational study conducted at a neurology outpatient department at a tertiary care center. Patients diagnosed with peripheral neuropathy due to various disease conditions were included in the study. Patients were selected through convenient sampling. Prescriptions were reviewed to evaluate the medication profile, comprehensiveness, and concordance with the diagnosed condition. Drug details were analyzed utilizing the descriptive statistics within Statistical Package for the Social Sciences software version 29.0. Results: Our study included a cohort of 110 patients diagnosed with peripheral neuropathy due to various disease conditions. The mean age of the study participants were 43.4 years, 58 were males, and 52 were females. Out of 110 patients 58 (52.7%) patients were prescribed pregabalin + methylcobalamin, 38 (34.5%) patients received methylcobalamin alone, 8 (7.2%) patients received duloxetine, 5 (4.5%) patients received the combination of pregabalin and amitriptyline, and 1 patient with peripheral neuropathy due to hypothyroidism received levothyroxine. Conclusion: In our study, the predominant medication utilized for peripheral neuropathy treatment is the combination of pregabalin and methylcobalamin, with methylcobalamin monotherapy being the subsequent choice.

Quantitative sensory testing in a large cohort of neuropathy patients

Background:&#x0D; Quantitative sensory testing (QST) is a subjective but reliable and quantifiable method to detect patient thresholds to different sensory stimuli. QST is used to measure small- and large-fiber nerve function and can be used in conjunction with other diagnostic modalities in the evaluation of peripheral neuropathy (PN). The utility of QST to distinguish among different types of PN, however, has not been explored. The objective of the study was to evaluate if different patterns of QST abnormalities could distinguish between PN types.&#x0D; Methods:&#x0D; This single-center retrospective cohort study evaluated the frequency of QST abnormalities to vibratory, cold and heat detection thresholds in a large population of PN cases evaluated at the University of Texas Southwestern Medical Center peripheral neuropathy clinic between 1995-2000. PN was categorized by etiology.&#x0D; Results:&#x0D; A total of 559 QST studies were performed in this study. The average age of patients (n=557) was 60 years with a male-to-female ratio of 1:1. The most common diagnosis was cryptogenic sensory polyneuropathy (CSPN, n=294), followed by Charcot–Marie–Tooth disease (n=84)). Meta-regression of vibration and cold indicate that the expected proportion of abnormal responses is less for the vibration test (p = 0.0002), relative to the cold test. However, no differences were observed between diagnoses.&#x0D; Conclusions:&#x0D; Though abnormal QST thresholds were seen in most patients with PN, patterns of QST abnormalities do not distinguish between different types of PN. The routine clinical utility of QST is likely limited.

Peripheral Neuropathy in Systemic Autoimmune Rheumatic Diseases-Diagnosis and Treatment.

Peripheral neuropathy (PN) is frequently observed in systemic rheumatic diseases and is a challenge in clinical practice. We aimed to review the evidence on the subject and proposed a comprehensive approach to these patients, facilitating diagnosis and management. We searched the MEDLINE database for the terms (and its respective Medical Subject Headings (MeSH) terms): "peripheral neuropathy" AND "rheumatic diseases" OR "systemic lupus erythematosus", "rheumatoid arthritis", "Sjogren syndrome", and "vasculitis" from 2000 to 2023. This literature review focuses on the diagnostic workup of PNs related to systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, and systemic vasculitis. For every type of PN, we provide a pragmatic flowchart for diagnosis and also describe evidence-based strategies of treatment.

Preparation of Primary Mixed Glial Cell Cultures from Adult Mouse Spinal Cord Tissue.

Central nervous system glial cells are known to mediate many neurocognitive/neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. Similar glial responses have been recognized as critical factors contributing to the development of diseases in the peripheral nervous system, including various types of peripheral neuropathies, such as peripheral nerve injury-induced neuropathic pain, diabetic neuropathy, and HIV-associated sensory neuropathy. Investigation of the central mechanisms of these peripherally-manifested diseases often requires the examination of spinal cord glial cells at cellular/molecular levels in vitro. When using rodent models to study these diseases, many investigators have chosen to use neonatal cerebral cortices to prepare glial cultures or immortalized cell lines in order to obtain sufficient numbers of cells for assessment. However, differences in responses between cell lines versus primary cultures, neonatal vs. adult cells, and brain vs. spinal cord cells may result in misleading data. Here, we describe a protocol for preparing mixed glial cells from adult mouse spinal cord that can be used for direct in vitro evaluations or further preparation of microglia-enriched and microglia-depleted cells. In this protocol, spinal cord tissue is enzymatically dissociated and adult mixed glial cells are ready to be used between 12 and 14 days after the establishment of the culture. This protocol may be further refined to prepare spinal cord glial cells from spinal cord tissues of adult rats and potentially other species. Mixed glial cultures can be prepared from animals of different strains or post-in vivo manipulations and therefore are suitable for studying a variety of diseases/disorders that involve spinal cord pathological changes, such as amyotrophic lateral sclerosis and multiple sclerosis, as well as toxin-induced changes. © 2023 Wiley Periodicals LLC. Basic Protocol: Preparation of primary mixed glial cell cultures from adult mouse spinal cord tissue.

Primary Sjögren syndrome-related peripheral neuropathy: Asystematic review and meta-analysis.

Primary Sjögren syndrome (pSS) is a chronic, systemic, autoimmune disorder characterized by lymphocytic infiltrates of the exocrine organs, leading to sicca symptoms and parotid enlargement. pSS has been linked to various neurological manifestations, including peripheral neuropathy (PN). We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS-related PN. A literature search in the PubMed database was performed, and 49 papers were eligible to be included in this systematic review and meta-analysis. The pooled prevalence of PN in pSS is estimated to be 15.0% (95% confidence interval=10.7%-20.7%). The mean age of pSS patients at PN diagnosis is 59 years. Among the patients with pSS and PN, 83% are females. Neuropathic symptoms usually precede or lead to the pSS diagnosis at a 2:1 ratio in patients with pSS-related PN. The commonest type of pSS-related PN is distal axonal polyneuropathy (80% of patients with pSS-related PN), followed by sensory ganglionopathy. Peripheral and cranial mononeuropathies-particularly trigeminal-are also frequent. Risk factors for developing PN include increasing age and presence of vasculitis. Immune-mediated pathogenetic mechanisms are discussed. Glucocorticoids are the most commonly used treatment option for managing pSS-related PN, when associated with vasculitis, followed by the use of intravenous immunoglobulin. PN is very common in pSS patients. Evidence on long-term prognosis of PN in pSS is limited, and further research is needed. Research into the use of immunosuppressive medication in nonvasculitic neuropathies in the context of pSS merits further consideration.

65. Pain Hypersensitivity, Sensorimotor Impairment, and Decreased Muscle Force in a Novel Rat Model of Radiation Induced Peripheral Neuropathy

Purpose: Radiation induced peripheral neuropathy is a rare but serious complication often resulting in profound morbidity, life-long disability, and chronic debilitating pain. Unfortunately, this type of peripheral neuropathy is usually progressive, and almost always irreversible. To date, a standardized rat model of radiation induced peripheral neuropathy has not been established. The purpose of the present study was to examine neuropathic pain, sensorimotor impairment, and muscle force parameters following administration of a clinically relevant radiation dose in a rat model. Methods: Ten rats were randomly assigned to one of two experimental groups: (1) radiation, and; (2) sham-radiated controls. Radiated animals were given a clinically relevant dose of 35 Gray (Gy) divided into 5 daily doses of 7 Gy/day. Sham-radiated controls were anesthetized and placed in the radiation apparatus, but were not given radiation. All animals were tested for baseline values in both sensorimotor and pain behavioral tests. Sensorimotor testing consisted of evaluation of walking tracks with calculation of the Sciatic Functional Index (SFI). Pain related behavioral measures consisted of mechanical allodynia (von Frey test), cold allodynia (Acetone test), and thermal allodynia (Hargreaves test). Animals were tested serially over an 8-week period. At study endpoint, electrophysiological and muscle force assessment were completed, and all sciatic nerves were taken for histomorphometric analysis. Results: Animals that underwent radiation treatment displayed significantly greater pain hypersensitivity to mechanical stimulation as compared to sham radiated controls from weeks 4-8 of testing. SFI values indicated sensorimotor impairments in the overground gait of radiated animals as compared to non-radiated animals. Furthermore, radiated animals displayed reduced twitch and tetanic muscle force when compared to sham radiated controls. Conclusions: A clinically relevant radiation dose of 35 Gy in rats established significant pain hypersensitivity, impairments in sensorimotor locomotion, and decreased muscle force capacity. This novel rodent model of radiation induced peripheral neuropathy can be utilized to assess the effect of pharmacological treatments on this debilitating condition.

Neuropathic Pain in Neurologic Disorders: A Narrative Review.

Neuropathic pain is defined as a painful condition caused by neurological lesions or diseases. Sometimes, neurological disorders may also be associated with neuropathic pain, which can be challenging to manage. For example, multiple sclerosis (MS) may cause chronic centralized painful symptoms due to nerve damage. Other chronic neuropathic pain syndromes may occur in the form of post-stroke pain, spinal cord injury pain, and other central pain syndromes. Chronic neuropathic pain is associated with dysfunction, disability, depression, disturbed sleep, and reduced quality of life. Early diagnosis may help improve outcomes, and pain control can be an important factor in restoring function. There are more than 100 different types of peripheral neuropathy and those involving sensory neurons can provoke painful symptoms. Accurate diagnosis of peripheral neuropathy is essential for pain control. Further examples are represented by gluten neuropathy, which is an extraintestinal manifestation of gluten sensitivity and presents as a form of peripheral neuropathy; in these unusual cases, neuropathy may be managed with diet. Neuropathic pain has been linked to CoronaVirus Disease (COVID) infection both during acute infection and as a post-viral syndrome known as long COVID. In this last case, neuropathic pain relates to the host’s response to the virus. However, neuropathic pain may occur after any critical illness and has been observed as part of a syndrome following intensive care unit hospitalization.

Peripheral neuropathy and livedoid vasculopathy.

Livedoid vasculopathy (LV) is a chronic dermatosis associated with micro-thrombosis of the vessels of the dermis, leading to ischemic lesions and painful skin ulcerations of the lower limbs. This thrombosing occlusive vasculopathy, clearly distinct from 'classical vasculitis' (not related to alteration of vessel walls), may lead to peripheral neuropathy. To clarify the main clinical, electrophysiological and pathological characteristics of peripheral neuropathy linked to LV. We presented a series of personal cases of peripheral neuropathy due to LV. We also conducted a review of the literature (since the first description of LV in 1974) using multiple combinations of keywords from 'PubMed', 'Google Scholar' and 'ScienceDirect' databases according to the 'Preferred Reporting Items for Systematic reviews and Meta-Analyses' guidelines. We identified 16 patients (6 personal cases and 10 cases from the medical literature). Our personal cases were five females and one male, with a median age (at the onset of cutaneous signs of LV) of 38 (range 25-62). Several types of skin lesions of the lower limbs were observed. Median age at the onset of peripheral neuropathy symptoms was 48years (range 29-66), with a main clinical and electrophysiological pattern of mononeuropathy multiplex. We observed a typical pattern of peripheral neuropathy, mostly mononeuropathy multiplex, whose pathophysiology might be related to occlusions of the small vessels of the nerves, as seen in the dermis. Moreover, LV may also be associated with other types of peripheral neuropathies (sometimes of autoimmune etiology) not directly related to the skin lesions. The 'ischemic form' of peripheral neuropathy linked to LV is mainly responsible for sensory disturbances (with multifocal distribution), sometimes for motor disturbances. This type of peripheral neuropathy has to be distinguished from 'classical vasculitic neuropathies' which are usually treated with antithrombotic therapies.

Peripheral neuropathy in Parkinson's disease: prevalence and functional impact on gait and balance.

Peripheral neuropathy is a common problem in patients with Parkinson's disease. Peripheral neuropathy's prevalence in Parkinson's disease varies between 4.8-55%, compared with 9% in the general population. It remains unclear whether peripheral neuropathy leads to decreased motor performance in Parkinson's disease, resulting in impaired mobility and increased balance deficits. We aimed to determine the prevalence and type of peripheral neuropathy in Parkinson's disease patients and evaluate its functional impact on gait and balance. A cohort of consecutive Parkinson's disease patients assessed by movement disorders specialists based on the UK Brain Bank criteria underwent clinical, neurophysiological (nerve conduction studies and quantitative sensory testing) and neuropathological (intraepidermal nerve fibre density in skin biopsy punches) evaluation to characterize the peripheral neuropathy type and aetiology using a cross-sectional design. Gait and balance were characterized using wearable health-technology in OFF and ON medication states, and the main parameters were extracted using validated algorithms. A total of 99 Parkinson's disease participants with a mean age of 67.2 (±10) years and mean disease duration of 6.5 (±5) years were assessed. Based on a comprehensive clinical, neurophysiological and neuropathological evaluation, we found that 40.4% of Parkinson's disease patients presented peripheral neuropathy, with a predominance of small fibre neuropathy (70% of the group). In the OFF state, the presence of peripheral neuropathy was significantly associated with shorter stride length (P = 0.029), slower gait speed (P = 0.005) and smaller toe-off angles (P = 0.002) during straight walking; significantly slower speed (P = 0.019) and smaller toe-off angles (P = 0.007) were also observed during circular walking. In the ON state, the above effects remained, albeit moderately reduced. With regard to balance, significant differences between Parkinson's disease patients with and without peripheral neuropathy were observed in the OFF medication state during stance with closed eyes on a foam surface. In the ON states, these differences were no longer observable. We showed that peripheral neuropathy is common in Parkinson's disease and influences gait and balance parameters, as measured with mobile health-technology. Our study supports that peripheral neuropathy recognition and directed treatment should be pursued in order to improve gait in Parkinson's disease patients and minimize balance-related disability, targeting individualized medical care.

A Retrospective Analysis of Pain Etiology in Middle-Aged Patients with Peripheral Neuropathy.

Background and Objectives: Correct assessment and a multidisciplinary approach appear to be extremely important in preventing peripheral neuropathy and its complications. The purpose of this study was to find the correlations and dissimilarities between different types of peripheral neuropathy, the occurrence of pain, and laboratory results. Materials and Methods: This retrospective study assessed 124 patients who were hospitalized in our neurology department due to various types of sensory or motor disturbances. The patients were eventually diagnosed with peripheral neuropathy, based on the electrophysiological study, anamnesis, physical examination, and laboratory results. The whole group was subjected to statistical analysis. Results: The mean age of patients was over 56 years, with a slight woman predominance. A statistically significant (p < 0.05) relationship between the place of residence and gender was seen, where more men than women live in the rural area, while more women than men live in the urban area. Most often we observed symmetric, sensorimotor, demyelinating, inflammatory, and chronic neuropathy. More than 40% of patients reported pain. A statistically significant correlation between the evolution/severity and the occurrence of pain was seen in subacute type (p < 0.05) and small fibre neuropathy (p < 0.01). Conclusions: A higher incidence of peripheral neuropathy in middle-aged people will become essential in the aging society with lifestyle and chronic disorders. Peripheral neuropathy is slightly more common in women than men and its occurrence may be influenced by work performed or internal and external factors. In the study group, more than 40% of patients reported pain, therefore the pain measurement for each patient should be implemented and repeated at every visit. An assessment of sodium level and, in women, markers of neuroinflammation level in the various types of peripheral neuropathy may be an interesting direction for the future.

Electro-clinical presentation of hereditary transthyretin related amyloidosis when presenting as a polyneuropathy of unknown origin in northern France

IntroductionHereditary transthyretin related amyloidosis (h-ATTR) classically presents as a small fiber neuropathy with positive family history, but can also be revealed by various other types of peripheral neuropathy. ObjectiveTo describe the initial electro-clinical presentation of patients from in a single region (northern France) of h-ATTR when it presents as a polyneuropathy of unknown origin. MethodWe reviewed the records of patients referred to two neuromuscular centers from northern France with a peripheral neuropathy of unknown origin who were subsequently diagnosed with h-ATTR. ResultsAmong 26 h-ATTR patients (10 Val30Met, 16 Ser77Tyr), only 14 patients had a suspicious family history (53.8%). The electro-clinical presentation was mostly a large-fiber sensory motor polyneuropathy (92.3%), which could be symmetric or not, length-dependent or not, or associated with nerve entrapment or not. Demyelinating signs were observed in 17 patients (70.8%), among whom nine fulfilled the criteria for a definite diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (37.5%). Conclusionh-ATTR may have a wide spectrum of clinical profiles, and should be considered in the screening of polyneuropathies of unknown origin.

Epidemiology and Treatment of Peripheral Neuropathy in Systemic Sclerosis.

The epidemiology and treatment of peripheral neuropathy in systemic sclerosis (SSc) is poorly understood. The objectives of this study were to evaluate the incidence, prevalence, risk factors, and treatments of peripheral neuropathy in SSc. A systematic review of MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for literature reporting peripheral neuropathy in SSc was performed. Studies evaluating incidence, prevalence, risk factors, and treatments were synthesized. A metaanalysis using a random effects model was used to evaluate the prevalence of peripheral neuropathy. This systematic review identified 113 studies that reported 949 of 2143 subjects with at least 1 type of peripheral neuropathy. The mean age was 48.5 years. The mean time between SSc onset and detection of peripheral neuropathy was 8.85 years. The pooled prevalence of neuropathy was 27.37% (95% CI 22.35-32.70). Risk factors for peripheral neuropathy in SSc included advanced diffuse disease, anticentromere antibodies, calcinosis cutis, ischemia of the vasa nervorum, iron deficiency anemia, metoclopramide, pembrolizumab, silicosis, and uremia. There were 73 subjects with successful treatments (n = 36 restoring sensation, n = 37 restoring motor or sensorimotor function). Treatments included decompression surgery, prednisone, cyclophosphamide, carbamazepine, transcutaneous electrical nerve stimulation, tricyclic antidepressants, and intravenous Ig. All-cause peripheral neuropathy is not uncommon in SSc. Compression neuropathies can be treated with decompression surgery. Observational data reporting immunosuppressives and anticonvulsants to treat peripheral neuropathy in SSc are limited and conflicting. Randomized controlled trials are needed to evaluate the efficacy of these interventions.

Intraepidermal Nerve Fiber Density as Measured by Skin Punch Biopsy as a Marker for Small Fiber Neuropathy: Application in Patients with Fibromyalgia.

Small fiber neuropathy (SFN) is a type of peripheral neuropathy that occurs from damage to the small A-delta and C nerve fibers that results in the clinical condition known as SFN. This pathology may be the result of metabolic, toxic, immune-mediated, and/or genetic factors. Small fiber symptoms can be variable and inconsistent and therefore require an objective biomarker confirmation. Small fiber dysfunction is not typically captured by diagnostic tests for large-fiber neuropathy (nerve conduction and electromyographic study). Therefore, skin biopsies stained with PGP 9.5 are the universally recommended objective test for SFN, with quantitative sensory tests, autonomic function testing, and corneal confocal imaging as secondary or adjunctive choices. Fibromyalgia (FM) is a heterogenous syndrome that has many symptoms that overlap with those found in SFN. A growing body of research has shown approximately 40–60% of patients carrying a diagnosis of FM have evidence of SFN on skin punch biopsy. There is currently no clearly defined phenotype in FM at this time to suggest whom may or may not have SFN, though research suggests it may correlate with severe cases. The skin punch biopsy provides an objective tool for use in quantifying small fiber pathology in FM. Skin punch biopsy may also be repeated for surveillance of the disease as well as measuring response to treatments. Evaluation of SFN in FM allows for better classification of FM and guidance for patient care as well as validation for their symptoms, leading to better use of resources and outcomes.

Burning sensation in the feet and glycosylated haemoglobin levels in Swedish- and non–Swedish-born primary healthcare patients

BackgroundA painful burning sensation in the feet is a common problem. The most common cause is small fibre neuropathy, a type of peripheral neuropathy that is often a consequence of diabetes and prediabetes. AimTo examine the association between a self-reported burning sensation in the feet and HbA1c levels in primary healthcare patients. MethodsThis study used data from patients in the 4D diabetes project in Swedish primary healthcare. The study population included 824 patients. Logistic regression was performed to study the association between the outcome and explanatory variables. ResultsA total of 24% of patients reported a burning sensation in the feet. This sensation was not associated with HbA1c levels. However, the probability of reporting a burning sensation was two times higher in non-Swedish-born than Swedish-born patients (OR, 2.31; 95% CI, 1.55–3.44) and higher in smokers than those who had never smoked, regardless of region of birth (OR, 1.69; 95% CI, 1.07−2.65). ConclusionsOur results do not support the hypothesis that a self-reported burning sensation in the feet is associated with HbA1c levels. Rather, they indicate a strong relationship between a burning sensation and region of birth, as well as between a burning sensation and smoking.

Docetaxel-Induced Peripheral Neuropathy in Breast Cancer Patients Treated with Adjuvant or Neo-Adjuvant Chemotherapy

Background: Docetaxel-induced peripheral neuropathy (PN) is typically manifested as sensory and motor neuropathy. This study aimed to investigate the incidence, duration, and risk factors of sensory and motor PN and their impact on health-related quality of life (HRQOL) among breast cancer (BC) patients during the first year since starting docetaxel-based chemotherapy. Methods: We reported a secondary analysis of longitudinal data on docetaxel-induced PN and HRQOL among 127 BC patients. Results: Cumulative incidence rates of motor and sensory PN were 31.5 and 21.3%, while the median durations of motor and sensory PN were 6 and 13 weeks. A consistently significant risk factor for both PNs was a cumulative docetaxel dose of >300 mg/m². A significant interaction between sensory PN and time was found for physical and social functioning, while a significant motor PN and time interaction effect was identified for physical functioning only. Conclusions: Motor PN was more common than sensory PN in BC patients treated with docetaxel. Both types of PN had a significant impact on physical functioning.

Small fiber neuropathy in coeliac disease and gluten sensitivity

ABSTRACTObjectives: The commonest types of peripheral neuropathy in the context of Coeliac Disease (CD) and gluten sensitivity (GS) are length-dependent symmetrical sensorimotor neuropathies and sensory ganglionopathies. In patients with such neuropathy, (gluten neuropathy), peripheral neuropathic pain is prevalent suggesting involvement of small fibers. The purpose of this report was to describe the clinical characteristics of patients with CD or GS and pure small fiber neuropathy (SFN).Methods: We reviewed the records of all patients that had been referred to the Gluten-Related Neurological Disorders clinic who had clinical and neurophysiological evidence of SFN. All patients had serological evidence of gluten sensitivity (GS) prior to commencing GFD. All patients were offered a duodenum biopsy. Patients with comorbidities that could cause SFN were excluded.Results: We identified 13 patients (9 males) with SFN and gluten sensitivity. Of 11 patients who underwent duodenal biopsy 10 had evidence of enteropathy (CD). Mean age at onset of pain was 53.5 ± 11.4 years (range 34–72) and mean age of CD/GS diagnosis was 50.8 ± 10.4 years (range 34–68). In 8 patients (61.5%) pain was the presenting feature.Neurophysiological assessment suggested a length-dependent small fiber neuropathy in 11 patients, whereas in 2, a non-length dependent pattern was identifying suggesting that the predominant pathology lies in the dorsal root ganglia.Conclusion: SFN can be a presenting feature of CD and GS and, therefore, screening for CD and GS should be included in the diagnostic workup of patients with idiopathic SFN.