Associations between multiple neurological biomarkers and distal sensorimotor polyneuropathy: KORA F4/FF4 study.

AIMS: The aim of this study was to assess associations between neurological biomarkers and distal sensorimotor polyneuropathy (DSPN). MATERIALS AND METHODS: Cross-sectional analyses were based on 1032 participants aged 61-82 years from the population-based KORA F4 survey, 177 of whom had DSPN at baseline. The prevalence of type 2 diabetes was 20%. Prospective analyses used data from 505 participants without DSPN at baseline, of whom 125 had developed DSPN until the KORA FF4 survey. DSPN was defined based on the examination part of the Michigan Neuropathy Screening Instrument. Serum levels of neurological biomarkers were measured using proximity extension assay technology. Associations between 88 biomarkers and prevalent or incident DSPN were estimated using Poisson regression with robust error variance and are expressed as risk ratios (RR) and 95% CI per 1-SD increase. Results were adjusted for multiple confounders and multiple testing using the Benjamini-Hochberg procedure. RESULTS: Higher serum levels of CTSC (cathepsin C; RR [95% CI] 1.23 (1.08; 1.39), pB-H = 0.044) and PDGFRα (platelet-derived growth factor receptor A; RR [95% CI] 1.21 (1.08; 1.35), pB-H = 0.044) were associated with prevalent DSPN in the total study sample. CDH3, JAM-B, LAYN, RGMA and SCARA5 were positively associated with DSPN in the diabetes subgroup, whereas GCP5 was positively associated with DSPN in people without diabetes (all pB-H for interaction <0.05). None of the biomarkers showed an association with incident DSPN (all pB-H>0.05). CONCLUSIONS: This study identified multiple novel associations between neurological biomarkers and prevalent DSPN, which may be attributable to functions of these proteins in neuroinflammation, neural development and myelination.

Polyneuropathy Associated with Age of Starting the Transfusion and Serum Ferritin Level in Iranian Patients with Thalassemia Major and Intermedia.

Considering the importance of managing patients with ß-thalassemia and the importance of early detection of disease complications, we examined the rate of sensorimotor neuropathy in patients with ß-thalassemia and the risk factors related to it. This cross-sectional study included 44 blood transfusion-dependent ß-thalassemia patients aged 5 years and older. Nerve conduction studies (NCSs) were performed via standard procedures for both motor and sensory nerves. Neuropathy was observed in 14 patients (31.8%). NCS results for sensorimotor nerves in patients were within normal range. In motor NCS results, increased ulnar nerve amplitude was observed in patients with increasing age, and peroneal nerve delay in patients with an increase in serum ferritin level (p < 0.05). In sensory NCS results, delayed ulnar and sural nerves latencies were found in patients with an increase in serum ferritin level (p < 0.05). We provide data that sensorimotor neuropathy exists in thalassemia patients. It seems that with the increase of serum ferritin level and the age of patients, neuropathy becomes more obvious, while other factors such as gender, body mass index, and the number of transfusions may not be associated with neuropathy.

Prevalence of polyneuropathies among systemic sclerosis patients and impact on health-related quality of life.

INTRODUCTION: Systemic sclerosis (SSc) is a chronic rheumatic disease that affects multiple organ systems, including the peripheral nervous system. However, studies into the involvement of polyneuropathies (PNP) have shown inconsistent results. The aim of this study was to determine the prevalence of small (SFN) and large (LFN) fibre neuropathy among SSc patients and the impact on health-related quality of life (HRQoL). MATERIAL AND METHODS: The study enrolled 67 patients with diagnosed SSc. The severity of neuropathic symptoms was evaluated using shortened and revised total neuropathy scoring criteria. Nerve conduction studies were used for LFN, and quantitative sensory testing was used to evaluate SFN. Neuropathic pain was evaluated using a Douleur Neuropathique en 4 questionnaire, and the severity of anxiety symptoms was assessed using a Generalised Anxiety Disorder-7 scale. The Health Assessment Questionnaire-Disability Index was used to assess HRQoL. Previous data on antinuclear autoantibodies (ANA) test results was obtained. Statistical analysis was performed using SPSS software. RESULTS: LFN was diagnosed in 47.8% (n = 32/67) and SFN in 40.3% (n = 27/67) of the subjects. ANA positivity was not associated with the presence of LFN/SFN. The severity of neuropathic pain had a significant correlation with anxiety symptoms (r = 0.61, p < 0.001), the severity of neuropathy symptoms (r = 0.51, p < 0.001) and HRQoL (r = 0.45, p < 0.001). The severity of neuropathy symptoms correlated with HRQoL (r = 0.39, p = 0.001). CONCLUSIONS: We demonstrated that PNP are found in almost all SSc patients. Also, SFN is as common as LFN. Additionally, we found that the severity of neuropathy symptoms and neuropathic pain are both associated with a worse HRQoL.

Effect of obesity on the associations of 25-hydroxyvitamin D with prevalent and incident distal sensorimotor polyneuropathy: population-based KORA F4/FF4 study.

BACKGROUND/OBJECTIVES: The association between vitamin D and DSPN has been investigated in cross-sectional studies in individuals with diabetes. However, evidence from prospective and population-based studies is still lacking. Also, the potential modifying effect of obesity and glucose tolerance has not been investigated. Therefore, we examined the cross-sectional and prospective associations of serum 25(OH)D with DSPN and assessed possible effect modifications. SUBJECTS/METHODS: The study included individuals aged 62-81 years who participated in the German KORA F4 (2006-2008) and FF4 (2013-2014) studies. DSPN was assessed using the Michigan Neuropathy Screening Instrument. Cross-sectional analyses (n = 1065; 33% of the participants had obesity) assessed the associations of baseline 25(OH)D with prevalent DSPN, while prospective analyses (n = 422) assessed the associations of 25(OH)D with incident DSPN. RESULTS: No association was found between 25(OH)D and prevalent DSPN in the total sample after adjustment for age, sex, season of blood sampling, BMI, metabolic variables, lifestyle factors, and comorbidities. However, a decrease by 10 nmol/L in 25(OH)D was associated with prevalent DSPN (RR (95% CI) 1.08 (1.01, 1.16)) in individuals with obesity but not in normal-weight individuals (RR (95% CI) 0.97 (0.92, 1.02), pinteraction = 0.002). No evidence for effect modification by glucose tolerance was found (p > 0.05). In the prospective analysis, 25(OH)D levels in the first and second tertiles were associated with higher risk of DSPN (RR (95% CI) 1.18 (1.02; 1.38) and 1.40 (1.04; 1.90)) compared to the third tertile after adjustment for age, sex, season of blood sampling, and BMI. There was no evidence for effect modification by obesity or glucose tolerance categories. CONCLUSIONS: Our study did not show consistent evidence for cross-sectional and prospective associations between serum 25(OH)D levels and DSPN in the total study population of older individuals. However, there was evidence for an association between lower serum 25(OH)D levels and higher prevalence of DSPN in individuals with obesity.

Statins and the risk of polyneuropathy: A systematic review and two meta-analyses.

INTRODUCTION/AIMS: Previous studies have shown inconsistent data on the relationship between statin use and polyneuropathy (PN). The current systematic review and meta-analyses were conducted to comprehensively investigate the risk of incident PN among statin-users compared with non-users by identifying all available studies and summarizing their results. METHODS: A systematic review was conducted from MEDLINE and EMBASE databases from inception to October 31, 2020. We included cohort and case-control studies that compared the risk of incident PN between statin-users and non-users. Point estimates and standard errors from eligible studies were pooled together using the generic inverse variance method. RESULTS: Of 4968 retrieved articles, 6 studies in non-diabetic populations and 2 studies in diabetic populations fulfilled the inclusion criteria. Two meta-analyses were performed. The pooled analyses did not find a statistically significant association between the use of statins and risk of incident PN with the pooled odds ratio of 1.24 (95% confidence interval [CI], 0.88-1.76; I2 74%) and 0.82 (95% CI, 0.56-1.21; I2 80%) in non-diabetic and diabetic groups respectively. DISCUSSION: No significant association between the use of statins and the risk of PN was observed in this systematic review and these two meta-analyses. However, there was a high degree of heterogeneity of the meta-analyses.

Genetic evidence for the most common risk factors for chronic axonal polyneuropathy in the general population.

BACKGROUND AND PURPOSE: Chronic axonal polyneuropathy is a common disease, but the etiology remains only partially understood. Previous etiologic studies have identified clinical risk factors, but genetic evidence supporting causality between these factors and polyneuropathy are largely lacking. In this study, we investigate whether there is a genetic association of clinically established important risk factors (diabetes, body mass index [BMI], vitamin B12 levels, and alcohol intake) with chronic axonal polyneuropathy. METHODS: This study was performed within the population-based Rotterdam Study and included 1565 participants (median age = 73.6 years, interquartile range = 64.6-78.8, 53.5% female), of whom 215 participants (13.7%) had polyneuropathy. Polygenic scores (PGSs) for diabetes, BMI, vitamin B12 levels, and alcohol intake were calculated at multiple significance thresholds based on published genome-wide association studies. RESULTS: Higher PGSs of diabetes, BMI, and alcohol intake were associated with higher prevalence of chronic axonal polyneuropathy, whereas higher PGS of vitamin B12 levels was associated with lower prevalence of polyneuropathy. These effects were most pronounced for PGSs with lenient significance thresholds for diabetes and BMI (odds ratio [OR]diabetes, p < 1.0  = 1.21, 95% confidence interval [CI] = 1.05-1.39 and ORBMI, p < 1.0  = 1.21, 95% CI = 1.04-1.41) and for the strictest significance thresholds for vitamin B12 level and alcohol intake (OR vitamin B12, p < 5e-6  = 0.79, 95% CI = 0.68-0.92 and ORalcohol, p < 5e-8  = 1.17, 95% CI = 1.02-1.35). We did not find an association between different PGSs and sural sensory nerve action potential amplitude, nor between individual lead variants of PGSp < 5e-8 and polyneuropathy. CONCLUSIONS: This study provides evidence for polygenic associations of diabetes, BMI, vitamin B12 level, and alcohol intake with chronic axonal polyneuropathy. This supports the hypothesis of causal associations between well-known clinical risk factors and polyneuropathy.

Cutaneous manifestations of small fibre polyneuropathy.

BACKGROUND: Because typical and atypical features of small fibre polyneuropathy (SFN) in the skin have not been fully elucidated, the diagnosis is often made by the exclusion of alternative conditions rather than by its identification as a primary syndrome. OBJECTIVE: The objective of this study was to characterize dermatologic manifestations in patients with SFN. METHODS: Large retrospective series of biopsy-proven SFN cases seen at the Massachusetts General Hospital and Brigham and Women's Hospital (January 2000 to December 2019). RESULTS: The majority of the 301 participants included presented with at least one cutaneous manifestation [292/301 (97%)]. Pain was most common with 254/301 (84.4%) perceiving this as occurring in the skin. It was frequently described as 'burning' [95/254 (37.4%)] and affected distal [174/254 (68.5%)] slightly more than proximal [111/254 (43.7%)] limbs. Numbness [182/301 (60.5%)], edema [61/301 (20.3%)] and skin colour changes [53/301 (17.6%)], which include redness [23/53 (43%)], also had predominant distal distribution. Characteristic loss of distal hair occurred among 17/29 (59%) those reporting hair loss. Other findings with classic limb involvement, Raynaud's phenomenon [33/301 (11%)] and erythromelalgia [26/301 (8.6%)] were seen. Itch [45/301 (15%)], mostly localized [22/45 (49%)] and localized eczematous dermatitis were also found. CONCLUSION: SFN has a wide range of clinical features in which the skin is affected, with characteristic findings affecting the extremities.

Intensive care unit-acquired weakness: Questions the clinician should ask.

Intensive care unit (ICU)-acquired weakness (ICU-AW) is defined as clinically detected weakness in critically ill patients in whom there is no plausible etiology other than critical illness. Using electrophysiological methods, patients with ICU-AW are classified in three subcategories: critical illness polyneuropathy, critical illness myopathy and critical illness neuromyopathy. ICU-AW is a frequent complication occurring in critical ill patients. Risk factors include illness severity and organ failure, age, hyperglycemia, parenteral nutrition, drugs and immobility. Due to short- and long-term complications, ICU-AW results in longer hospital stay and increased mortality. Its management is essentially preventive avoiding modifiable risk factors, especially duration of sedation and immobilization that should be as short as possible. Pharmacological approaches have been studied but none have proven efficacy. In the present review, we propose practical questions that the clinician should ask in case of acquired weakness during ICU stay: when to suspect ICU-AW, what risk factors should be identified, how to diagnose ICU-AW, what is the prognosis and how can recovery be improved?

Cardiovascular health and chronic axonal polyneuropathy: A population-based study.

BACKGROUND AND PURPOSE: Chronic axonal polyneuropathy is a common, usually multifactorial, disease for which there is no treatment yet available. We investigated the association between cardiovascular health, defined by the health score of the American Heart Association, and chronic axonal polyneuropathy. METHODS: Between June 2013 and January 2017, we investigated participants of the Rotterdam Study, a population-based cohort study. Participants were screened for polyneuropathy and categorized as having no, possible, probable or definite polyneuropathy. The cardiovascular health score (range 0-14; higher score reflecting better health) consisted of four health behaviours (diet, physical activity, smoking and body mass index) and three health factors (blood pressure, serum cholesterol and fasting glucose level). RESULTS: We included 1919 participants, of whom 120 (6.3%) had definite polyneuropathy. The median (interquartile range [IQR]) age was 69.0 (58.6-73.7) years and 53.4% were women. A higher cardiovascular health score was associated with a lower prevalence of definite polyneuropathy (per point increase: odds ratio [OR] 0.90, 95% confidence interval [CI] 0.84-0.96). Optimal cardiovascular health (score≥10) was strongly associated with a lower prevalence of definite polyneuropathy (OR 0.55, 95% CI 0.32-0.90). An increase in health factors and health behaviour scores separately was associated with a lower prevalence of polyneuropathy (per point increase: OR 0.82, 95% CI 0.71-0.95 and OR 0.86, 95% CI 0.78-0.96, respectively). The association between a lower cardiovascular health score and lower sural nerve amplitude was not significant after correction for covariates (difference 0.07µV, 95% CI -0.02-0.17). CONCLUSIONS: Better cardiovascular health, consisting of both modifiable health behaviours and health factors, is associated with a lower prevalence of chronic axonal polyneuropathy.

Electrodiagnostic findings in patients with non-COVID-19- and COVID-19-related acute respiratory distress syndrome.

BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) is a frequent neurological manifestation in patients with acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19) infection. CIPNM diagnosis is usually limited to clinical evaluation. We compared patients with ARDS from COVID-19 and other aetiologies, in whom a neurophysiological evaluation for the detection of CIPNM was performed. The aim was to determine if there were any differences between these two groups in frequency of CINPM and outcome at discharge from the intensive care unit (ICU). MATERIALS AND METHODS: This was a single-centre retrospective study performed on mechanically ventilated patients consecutively admitted (January 2016-June 2020) to the ICU of Careggi Hospital, Florence, Italy, with ARDS of different aetiologies. Neurophysiological evaluation was performed on patients with stable ventilation parameters, but marked widespread hyposthenia (Medical Research Council score <48). Creatine phosphokinase (CPK), lactic dehydrogenase (LDH) and mean morning glycaemic values were collected. RESULTS: From a total of 148 patients, 23 with COVID-19 infection and 21 with ARDS due to other aetiologies, underwent electroneurography/electromyography (ENG/EMG) recording. Incidence of CIPNM was similar in the two groups, 65% (15 of 23) in COVID-19 patients and 71% (15 of 21) in patients affected by ARDS of other aetiologies. At ICU discharge, subjects with CIPNM more frequently required ventilatory support, regardless the aetiology of ARDS. CONCLUSION: ENG/EMG represents a useful tool in the identification of the neuromuscular causes underlying ventilator wean failure and patient stratification. A high incidence of CIPNM, with a similar percentage, has been observed in ARDS patients of all aetiologies.

Paresthesia Predicts Increased Risk of Distal Neuropathic Pain in Older People with HIV-Associated Sensory Polyneuropathy.

OBJECTIVE: Distal sensory polyneuropathy (DSP) is a disabling consequence of human immunodeficiency virus (HIV), leading to poor quality of life and more frequent falls in older age. Neuropathic pain and paresthesia are prevalent symptoms; however, there are currently no known curative treatments and the longitudinal course of pain in HIV-associated DSP is poorly characterized. METHODS: This was a prospective longitudinal study of 265 people with HIV (PWH) enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study with baseline and 12-year follow-up evaluations. Since pain and paresthesia are highly correlated, statistical decomposition was used to separate the two symptoms at baseline. Multivariable logistic regression analyses of decomposed variables were used to determine the effects of neuropathy symptoms at baseline on presence and worsening of distal neuropathic pain at 12-year follow-up, adjusted for covariates. RESULTS: Mean age was 56 ± 8 years, and 21% were female at follow-up. Nearly the entire cohort (96%) was on antiretroviral therapy (ART), and 82% had suppressed (≤50 copies/mL) plasma viral loads at follow-up. Of those with pain at follow-up (n = 100), 23% had paresthesia at the initial visit. Decomposed paresthesia at baseline increased the risk of pain at follow-up (odds ratio [OR] 1.56; 95% confidence interval [CI] 1.18, 2.07), and decomposed pain at baseline predicted a higher frequency of pain at follow-up (OR 1.96 [95% CI 1.51, 2.58]). CONCLUSIONS: Paresthesias are a clinically significant predictor of incident pain at follow-up among aging PWH with DSP. Development of new therapies to encourage neuroregeneration might take advantage of this finding to choose individuals likely to benefit from treatment preventing incident pain.

Intensive Care Unit-Acquired Weakness in Children: A Prospective Observational Study Using Simplified Serial Electrophysiological Testing (PEDCIMP Study).

BACKGROUND: To study the incidence and time of onset of intensive care unit-acquired weakness in a prospective cohort of children (2-12 years) by serial simplified electrophysiological assessment (Pediatric Critical Illness Myopathy Polyneuropathy study, PEDCIMP). METHODS: A single-center, prospective cohort study (Trial Registry Number: NCT02763709; PEDCIMP2016) was conducted at the pediatric intensive care unit of a tertiary care hospital in North India. A complete electrophysiological evaluation (4 motor nerves and 2 sensory nerves) was performed at baseline in children (2-12 years) admitted to the ICU with a pediatric risk of mortality (PRISM) of > 20 with more than 24-h stay. Following the entry evaluation, a minimal alternate day simplified electrophysiological testing of the unilateral common peroneal nerve and the sural nerve was assessed. A 25% reduction in compound muscle action potential (CMAP) and sensory nerve action potential from baseline was considered significant for ICUAW and was confirmed by complete electrophysiological re-evaluation. RESULTS: Of the total 481 children assessed for eligibility, 97 were enrolled. The median age of the cohort was 7 years. Sepsis (81%); need for vasoactive support (43%); multiorgan dysfunction (26%) were the common reasons for admission. Of the 433 eligible patient ICU days, 380 electrophysiological observations were done. A significant decrease of > 25% in CMAP of common peroneal nerve was not detected in any of the 380 observations. However, two children unfit for inclusion were diagnosed with ICUAW during the study period. CONCLUSIONS: Children admitted with PRISM > 20 have a very low incidence of intensive care unit-acquired weakness by serial clinical and abbreviated electrophysiological evaluation.

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

INTRODUCTION: Hereditary 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. OBJECTIVE: To 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. METHOD: We 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. RESULTS: Among 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%). CONCLUSION: h-ATTR may have a wide spectrum of clinical profiles, and should be considered in the screening of polyneuropathies of unknown origin.

The impact of COPD on polyneuropathy: results from the German COPD cohort COSYCONET.

BACKGROUND: Peripheral neuropathy is a common comorbidity in COPD. We aimed to investigate associations between alterations commonly found in COPD and peripheral neuropathy, with particular emphasize on the distinction between direct and indirect effects. METHODS: We used visit 4 data of the COPD cohort COSYCONET, which included indicators of polyneuropathy (repeated tuning fork and monofilament testing), excluding patients with diabetes a/o increased HbA1c. These indicators were analysed for the association with COPD characteristics, including lung function, blood gases, 6-min walk distance (6-MWD), timed-up-and-go-test (TUG), exacerbation risk according to GOLD, C-reactive protein (CRP), and ankle-brachial index (ABI). Based on the results of conventional regression analyses adjusted for age, BMI, packyears and gender, we utilized structural equation modelling (SEM) to quantify the network of direct and indirect relationships between parameters. RESULTS: 606 patients were eligible for analysis. The indices of polyneuropathy were highly correlated with each other and related to base excess (BE), ABI and TUG. ABI was linked to neuropathy and 6-MWD, exacerbations depended on FEV1, 6-MWD and CRP. The associations could be summarized into a SEM comprising polyneuropathy as a latent variable (PNP) with three measured indicator variables. Importantly, PNP was directly dependent on ABI and particularly on BE. When also including patients with diabetes and/or elevated values of HbA1c (n = 742) the SEM remained virtually the same. CONCLUSION: We identified BE and ABI as major determinants of peripheral neuropathy in patients with COPD. All other associations, particularly those with lung function and physical capacity, were indirect. These findings underline the importance of alterations of the micromilieu in COPD, in particular the degree of metabolic compensation and vascular status.

Comorbidities, anthropometric, demographic, and lifestyle risk factors for ulnar neuropathy at the elbow: A case control study.

We performed a prospective multicenter case-control study to explore the association between ulnar neuropathy at elbow (UNE) and body and elbow anthropometric measures, demographic and lifestyle factors, and comorbidities. Cases and controls were consecutively enrolled among subjects admitted to four electromyography labs. UNE diagnosis was made on clinical and neurographic findings. The control group included all other subjects without signs/symptoms of ulnar neuropathy and with normal ulnar nerve neurography. Anthropometric measurements included weight, height, waist, hip circumferences, and external measures of elbow using a caliper. The participants filled in a self-administered questionnaire on personal characteristics, lifestyle factors, and medical history. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by fitting unconditional logistic regression models adjusted by center and education level. We enrolled 220 cases (males 61.8%; mean age 51.7 years) and 460 controls (47.4% males; mean age 47.8 years). At multivariable analysis, UNE was associated to male gender (OR = 2.4, 95%CI = 1.6-3.7), smoking habits (>25 pack-years (OR = 2.3, 95%CI = 1.3-4.1), body mass index (OR = 1.05, 95%CI 1.01-1.10), polyneuropathies (OR = 4.1, 95%CI 1.5-11.5), and leaning with flexed elbow on a table/desk (OR = 1.5, 95%CI 1.0-2.2). Cubital groove width (CGW) turned out to be negatively associated with UNE (OR = 0.80, 95%CI = 0.74-0.85). Our study suggests that some personal factors especially anthropometric measures of the elbow may play a role in UNE pathogenesis as the measures of wrist in CTS. We demonstrated that for each millimeter of smaller CGW the risk of idiopathic UNE increases of 25%.

Vitamin D serum level in subjects with critical illness polyneuropathy and myopathy.

BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) is a disabling neuropathy that occurs in intensive care unit (ICU) subjects. It was hypothesized that a low serum level or deficiency of 25(OH)D might be associated with CIPNM. The aim of the present study was to ascertain the 25(OH)D serum level in subjects with CIPNM. METHOD: Consecutive ICU patients admitted to neuro-rehabilitation were prospectively enrolled. At admission, vitamin D serum levels were measured and EMG examination was performed to ascertain those with CIPNM. 25(OH)D was stratified as sufficient (≥30 ng/mL) insufficient (20-29.9 ng/mL), and deficient (<20 ng/mL). RESULTS: Eighty-four patients (31 F, 53 M; mean age 51.7±12.6) were identified and 63 (21 F, 42 M) enrolled. CIPNM was detected in 38 (9 F, 29 M) patients. A deficient mean serum level of vitamin D was observed in the whole population: 18.1 ± 9.2 ng/mL. No difference of vitamin D serum levels was detected in subjects with and without CIPNM: 17.5 ± 8.4 and 19.0 ± 10.5 ng/mL (p=0.58), respectively. CONCLUSION: Almost all subjects showed Vitamin D deficiency. No difference was detected between those with and without CIPNM. The condition might represent a secondary phenomenon resulting from the inflammatory process as well as from conditions that could interfere with vitamin D metabolism.

Clinical and neurophysiological spectrum of polyneuropathies in children.

Peripheral neuropathy is a disorder of the peripheral nerves and results from a disturbance of structure and/or function of the peripheral sensory, motor and/or autonomic neurons. The possible aetiology of peripheral neuropathies is diverse, but inflammatory and hereditary diseases of the peripheral nerves predominate in childhood. The aim of this study was to determine the clinical and electrophysiological profile of large nerve fibre neuropathy detected by nerve conduction studies (NCS) in children over a 10-year period at the Children's Clinical University Hospital in Latvia. Based on NCS findings, 165 children between 2008 and 2018 were diagnosed with polyneuropathy. In our study, the majority of children had peripheral neuropathy due to acquired causes, mostly due to diabetes mellitus; roughly one in five of the patients had hereditary neuropathy. Almost half of the patients had motor deficits, which were more prevalent in toxic and inflammatory neuropathies. A little less than a third of patients complained of pain as well as presenting with autonomic dysfunction symptoms. The NCS demonstrated a demyelinating neuropathy in 52 cases (31%), an axonal neuropathy in 34 cases (21%), and mixed polyneuropathy in 79 cases (48%). Our study investigated the clinical and electrophysiological characteristics of polyneuropathies diagnosed with NCS in children. Most of the polyneuropathies in our study were hereditary and diabetic neuropathies with combined (myelin and axon) damage to nerve fibres. Almost all clinical symptoms of polyneuropathy were present in all aetiological groups.

Peripheral nervous system involvement in systemic lupus erythematosus: a retrospective study on prevalence, associated factors and outcome.

BACKGROUND: Despite its potentially significant impact on disease outcome, peripheral nervous system involvement in systemic lupus erythematosus has received little attention. OBJECTIVE: The objective of this study was to assess the prevalence and clinical features of peripheral nervous system involvement in a large cohort of systemic lupus erythematosus patients. METHODS: The records of systemic lupus erythematosus patients examined at two tertiary referral centres over a period of 14 years (from 2000 to 2014) were analyzed. Peripheral nervous system events were ascertained according to the 1999 American College of Rheumatology case definitions and by using an attribution algorithm for neuropsychiatric events. Prevalence of peripheral nervous system in systemic lupus erythematosus and demographic, clinical and laboratory features were assessed. Patients with peripheral nervous system events were compared with a control group of systemic lupus erythematosus patients without peripheral nervous system involvement. RESULTS: In a retrospective cohort of 1224 patients, the overall prevalence of peripheral nervous system involvement was 6.9% (85 patients, 95% confidence interval 0.06-0.08), with 68% of peripheral nervous system events attributable to systemic lupus erythematosus. Polyneuropathy was the most common manifestation observed (38 events, 39.2%), followed by cranial neuropathy in 30 cases (30.9%) and 12 cases of single (12.4%) or multiple (eight events, 8.2%) mononeuritis. The average age of systemic lupus erythematosus onset was significantly higher in patients with peripheral nervous system events than in controls (mean ± standard deviation: 45.9 ± 14.8 vs. 37.1 ± 14.0) and they were more likely to have higher SLEDAI-2K and SLICC/ACR Damage Index scores, as well as hypertension and livedo reticularis. A subgroup analysis of events deemed to be systemic lupus erythematosus-related provided similar results. CONCLUSION: Peripheral nervous system manifestations are a potential complication of systemic lupus erythematosus. Careful neurological assessment should therefore be included in the diagnostic workup of patients with systemic lupus erythematosus, especially in those with later onset and greater damage and disease activity.

Small Fiber Polyneuropathy Is Prevalent in Patients Experiencing Complex Chronic Pelvic Pain.

OBJECTIVE: To demonstrate the prevalence of small fiber polyneuropathy (SFPN) in patients with refractory chronic pelvic pain (CPP). DESIGN: Retrospective study of prospective database. SUBJECTS: Participants were complex CPP patients recruited from subspecity referral clinics defined as those who were refractory to initial treatment and/or exhibited comorbid pain syndromes at initial presentation. METHODS: Comprehensive treatment history for CPP was obtained, and participants referred as above; 3-mm punch biopsies were obtained of the lower extremity and sent to diagnostic reference labs to evaluate for SFPN. The reported lab sensitivity and specificity for SFPN are 78-92% and 65-90%, respectively. RESULTS: Twenty-five of 39 patients (64%) were positive for SFPN. Comorbid conditions noted in our population included gastroesophageal reflux disease (46%), migraine (38%), irritable bowel syndrome (33%), lower back pain (33%), fibromyalgia (38%), endometriosis (15%), interstitial cystitis (18%), vulvodynia (5%), and other chronic pain syndromes (36%). CONCLUSIONS: The prevalence of SFPN in our specialty referral patients with complex CPP is remarkably high vs published general population prevalence data (53/100,000). Identification of SFPN in this complex population shifts the focus from undefined syndromes to symptom complexes with linked potentially treatable mechanisms (e.g., SFPN, central sensitization). Most CPP patients with SFPN are undiagnosed. Considering the diagnosis may expand treatment options beyond conventional or so-called adjuvant analgesics. Treatment may expand to therapies such as IV lidocaine, IVIG, or other immunomodulatory options. In addition, the value to the patient of receiving a diagnosis for a multisystem or refractory pain syndrome, often attributed to negative psychologic factors, cannot be underestimated. Identifying SFPN should be contemplated in CPP patients who present with multisystem pain or who have not responded to initial evaluation and management.

Polyneuropathy in Critically Ill Mechanically Ventilated Children: Experience From a Tertiary Care Hospital in North India.

OBJECTIVES: To determine the prevalence of critical illness polyneuropathy and its risk factors in critically ill children mechanically ventilated for 7 days or more. DESIGN: Observational cohort study. SETTING: PICU of a tertiary care hospital from North India. PATIENTS: Children 1-15 years old admitted in PICU from June 2016 to September 2017, mechanically ventilated for 7 days or more, excluding those with diagnosed neuromuscular disease, stroke, or spinal pathology. INTERVENTION: Demographic details, diagnosis, treatment details, and anthropometry at admission and enrolment were recorded. Nerve conduction studies were performed after enrolment and repeated a week later, if the child was still in PICU. Medical Research Council scoring for muscle strength was performed in survivors. Risk factors including Pediatric Index of Mortality-2 score, sepsis, multiple organ dysfunction, hypoalbuminemia, use of steroids, neuromuscular-blocking agents, and vasopressors were recorded. Samples for the level of micronutrients (copper, zinc, folate, and vitamin B12) were collected at the time of enrolling the child and at the time of discharge. MEASUREMENTS AND MAIN RESULTS: Thirty-two children were enrolled, of whom 29 had features of critical illness polyneuropathy on evaluation at day 8 of mechanical ventilation (prevalence, 90.6% [95% CI, 80.5-100%]). The polyneuropathy was axonal in 26 (81.2%), mixed in one patient (3.1%), and uncharacterized in two (6.2%). Sepsis and multiple organ dysfunction were present in 31 subjects (96.9%). No risk factors for critical illness polyneuropathy could be identified although the study was not sufficiently powered to do so. The difference between serum micronutrient levels (copper, zinc, folate, and vitamin B12) between patients who developed polyneuropathy, and those who did not, was statistically insignificant. CONCLUSIONS: We observed a high prevalence of critical illness polyneuropathy in children in PICU, mechanically ventilated for 7 days or more; almost all of whom had underlying sepsis.