Incidence Of Polyneuropathy Research Articles

Incidence of Polyneuropathy among Uremic Patients Undergoing Hemodialysis: Cross-Sectional Study among Iraqis

Background: Peripheral neuropathy (PNP) is among the commonest neurological disorders. NP is a disorder of sensory or motor neurons. Peripheral NP impacts around 60-100% of cases admitted for dialysis units due to chronic kidney disease (CKD). In dialysis-dependent patients, a progressive uremic sensorimotor axonal NP is a well-known complication. Nevertheless, the precise polyneuropathy (PNP) among CKD patients has to be further investigated especially in our country. Objectives: This cross-sectional study aimed to evaluate the incidence of polyneuropathy among Iraqi uremic patients undergoing hemodialysis. Materials and Methods: This cross-sectional study was performed on patients 215 patients (99 women and 116 men). All participants were suffering from ESRD were assessed by expert specialists, aging 17-80 years, attending hemodialysis unit, receiving standardized maintenance hemodialysis. All patients had completed neurophysiological assessment in the same hospital, for sensory and motor nerves including median, ulnar, tibial, peroneal, and sural nerves, regardless of whether they had clinical findings of NP or not. SPSS (V-25) software was used for statistical analysis. A confidence level of 95% had considered significant. Results: Mean age and weight of patients was (48.16 ±13.4 years and 66.9 ± 12.9 kg), respectively, and the mean duration of dialysis was 4.7 ± 1.4 years. The majority of patients (85.1%) had a frequency of dialysis three times/week. The prevalence of UNP was 63.7% among the studied candidates. More than half of patients (51.8%) presented with moderate UPN, (29.2%) with mild UPN, and (19. 0%) with severe UPN (P<0.05). There were significant differences between means of age and frequency of dialysis with the incidence of UPN. Conclusion: Polyneuropathy is a very common complication in patients with uremia undergoing dialysis. Polyneuropathy is not associated with the frequency of dialysis, but with a duration of uremia.

The V122I mutation in hereditary transthyretin-mediated amyloidosis is significantly associated with an increased incidence of polyneuropathy

Abstract Background Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, life-threatening disease caused by mutations in the transthyretin (TTR) gene. hATTR amyloidosis phenotypes can vary by patient and mutation. The V122I (Val122Ile; p.V142I) variant is one of the most common pathogenic TTR mutations, is primarily found in people of West African descent and has historically been associated with cardiomyopathy (CM). Purpose To characterize the cumulative incidence of diagnoses frequently seen with hATTR amyloidosis in V122I carriers and non-carriers in the UK Biobank (UKBB) and the Penn Medicine BioBank (PMBB). Methods UKBB and PMBB are prospective studies with ∼500,000 and ∼60,000 subjects, respectively. Clinical presentations frequently seen with hATTR amyloidosis were assessed using ICD10 diagnosis codes: G62–polyneuropathy (PN), I50 or I098–heart failure (HF), G560–carpal tunnel syndrome (CTS), I42–CM, and E85–amyloidosis. The cumulative incidence of diagnoses was estimated using Kaplan-Meier curves. Time to first hATTR amyloidosis-related diagnosis was compared between V122I carriers and non-carriers using Cox proportional hazards regression, controlling for age, sex, smoking, and genetic ancestry. Results Of the 6,062 unrelated black participants in the UKBB, 243 were V122I carriers. Only 0.8% of V122I carriers had a formal diagnosis of hATTR amyloidosis. V122I carriers were significantly more likely to have a PN diagnosis than non-carriers (p=6.35x10–5), a finding which was replicated in the PMBB. Of the ICD10 codes assessed, Cox proportional hazards regression revealed a significant association between V122I genotype and time to first diagnosis (p=2.6x10–5), with 11.1% of V122I carriers having at least one diagnosis during follow-up versus 4.9% of non-carriers. The calculated population attributable risk showed an excess risk of 16.7% for a PN diagnosis, 6.5% for HF, 4.1% for CTS, and 2.4% for CM in V122I carriers. The cumulative incidence of any hATTR amyloidosis-related diagnosis among V122I carriers by age 65 was 11.9% (95% CI=3.1–19.8%). The incidence increased to 37.4% (95% CI=20.5–50.7%) by age 75, which was significantly higher than non-carriers (13.8%, 95% CI=11.6–16%). Additionally, an assessment of the cumulative incidence of each diagnosis separately revealed that PN became more prevalent at younger ages, while HF and CM became more prevalent at older ages. Conclusions V122I carriers were significantly more likely to receive diagnoses frequently seen with hATTR amyloidosis than non-carriers. Although these diagnoses may not all be attributed to amyloidosis, the small fraction of patients diagnosed with hATTR amyloidosis suggests a potential underdiagnosis of disease. The V122I mutation has historically been associated with a cardiac phenotype, yet these data also suggest an increased incidence of PN. Increased vigilance for the mixed phenotype may lead to earlier diagnoses and treatment of V122I carriers. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Alnylam Pharmaceuticals

Levodopa-Carbidopa Intestinal Gel Infusion Therapy Discontinuation: A Ten-Year Retrospective Analysis of 204 Treated Patients.

BackgroundParkinson’s disease (PD) is the second most common progressive neurodegenerative disease. In the advanced stages, the continuous delivery of levodopa (LD) as levodopa-carbidopa intestinal gel (LCIG) has demonstrated significant improvement of motor and nonmotor complications and improvement of the patients’ quality of life (QoL). Despite the growing global experience with this treatment, anumber of unsolved practical issues remain, and currently, the data on the reasons that can lead to the discontinuation of LCIG are scarce.ObjectiveIn the present study, we aimed to analyze the causes that led to the discontinuation of LCIG therapy.MethodsIn this retrospective study, after 10 years of experience with LCIG as a therapeutic option in advanced PD, we analyzed the data of all dropout cases among the 204 patients that initiated LCIG therapy in two Romanian centers.ResultsOf the 204 patients enrolled, 43 patients dropped out. Disease duration until LCIG infusion was significantly longer (11.67±4.98 vs 9.44±3.44) and the overall clinical picture more sever (both regarding motor symptoms and cognitive decline) in dropout patients (compared to patients who continued treatment). The dropout patients also presented significant differences regarding the incidence of polyneuropathy (32.5% vs 11.18%). The main cause of discontinuation was death.ConclusionThe causes of discontinuation from LCIG therapy in Romanian patients are similar to those from other centers; however, the rate of dropouts is somewhat lower. The clinician’s experience in selecting and treating the patients in advanced stages of PD can increase therapeutic adherence. Also, the presence of a well-trained caregiver along with the availability of a proper aftercare system is mandatory for maintaining the long-term benefits of the therapy and the overall best outcome possible. Targeted prospective studies are needed to confirm whether a more severe stage of the disease and cognitive impairment at the time of initiation, respectively, the association of polyneuropathy can be considered as predictive factors for dropout.

The Effect of Uric Acid as a Predisposing Factor on Polyneuropathy in Patients with Type 2 Diabetes Mellitus

Background: Since serum uric acid is a controllable and modifiable factor in diabetic patients, identifying the risk factors and accelerating the incidence of neuropathy in these patients plays an important role, and can reduce its level, and the patient's disability, as well as additional therapeutic costs for the patient and the health system in the country. Method: In this retrospective cohort study conducted at the Golestan Hospital in 2015-2017, the study population was 100 type 2 diabetic patients based on NCS of 54 patients with polyneuropathy. First, the demographic data on clinical examinations, lab tests, and uric acid levels in these patients were recorded on a checklist. Then, in 2017, patients were reassessed for clinical investigations and lab tests, and all data entered on the previous checklist. Finally, all the data were analyzed using the SPSS v23. Results: The mean age of patients with polyneuropathy was 51.77 years, and there was a significant relationship between age, BMI and duration of diabetes with neuropathy, but there was no significant difference in gender, smoking and hypertension. The mean serum level of uric acid in the two years ago was 3.85 mg/dl, and at the time of the study, it was 4.18±1.55 mg/dl. There was no significant difference in serum levels of this substance after two years of follow up in patients with polyneuropathy (P=0.139). The incidence of polyneuropathy was reported by NCS findings of 54%. In other words, 54% of diabetic patients developed diabetic polyneuropathy for two years. Conclusion: Polyneuropathy is a common complication in diabetic patients, and the serum levels of uric acid over time cannot have a significant effect on the incidence of this disorder.

Polyneuropathy in older individuals

The peripheral nervous system is subject to changes during the aging process, e.g., deep tendon reflexes decrease, as proprioception does. In contrast, polyneuropathies have to be distinguished from age-associated changes as independent diseases with etiologies similar to those in younger ages. Incidence of polyneuropathies is reported about 118/100,000, the overall prevalence in the general population is estimated to be about 1% and rises to up to 7% in the elderly. Etiology includes metabolic disorders, primary inflammatory polyneuropathies, systemic disorders and vasculitic neuropathies. Due to the age-specific increase of the prevalence of certain etiologies, neuropathies associated with diabetes, malignancy, and monoclonal gammopathies are even more common in older patients. However, the proportion of cryptogenic neuropathies, e.g. neuropathies without obvious cause, increases also with age. In older age, polyneuropathies additionally impair mobility and increase the risk of falling, thus the assessment of functional abilities is mandatory. It is essential to try to identify the underlying cause by asystematic approach including history, clinical investigation, neurophysiological and lab exams. Treatment of polyneuropathies is based on therapy of underlying conditions and requires management of neuropathic pain in the majority of cases. Physiotherapy and rehabilitation target pain relief and sustaining activities of daily living.

Peripheral polyneuropathy in patients receiving long-term statin therapy.

Peripheral neuropathy is an important potential side effect of statin use. This study was an investigation of the incidence of peripheral neuropathy in patients taking atorvastatin or rosuvastatin for hypercholesterolemia and the relationship to the dose and duration of the treatment. In all, 50 patients using a statin treatment and 50 healthy controls matched for age and gender who had never taken a statin were included in the study. Polyneuropathy was assessed with a neurological examination and electroneuromyography (ENMG). While no polyneuropathy was detected in the control group, polyneuropathy was seen in 33 (66%) of the patients in the statin group (p<0.01). There was no significant difference between the 2 statin groups in the results of the neurological examination or the ENMG findings regarding the incidence of polyneuropathy (p=0.288 and p=0.720, respectively). Neuropathy was observed in a neurological examination performed within the first year in 50% of the rosuvastatin users and 18% of those taking atorvastatin. The severity of the polyneuropathy increased with the duration of the treatment in the atorvastatin group (p=0.030). This study revealed an increased risk of peripheral neuropathy with long-term statin use (>1 year). Electrodiagnostic changes have been detected in motor and sensory nerves in nerve conduction studies of patients on long-term statin treatment. The assessment of neurological symptoms, like tingling, numbness, pain and tremor in the hands and feet, and unsteadiness during walking associated with peripheral neuropathy may be useful in the follow-up of the patients on long-term statin treatment. Early detection of peripheral neuropathy and changing hypercholesterolemia treatment may prevent permanent nerve damage.

What's in the Literature?

In this edition of this column, we review new studies concerning the pathophysiology, treatment, and outcomes of patients with necrotizing myopathy, genetic testing in congenital myopathies, and limb girdle muscular dystrophies, and the incidence of polyneuropathy in the myotonic dystrophies. Various studies in myasthenia gravis, including those concerning antibody testing, clinical features, and quality of life are also reviewed as are recent findings in congenital myasthenic syndromes. Finally, 2 studies concerning polyneuropathy are discussed, including one on the association of polyneuropathy in patients with the metabolic syndrome and one on laboratory testing in patients with otherwise idiopathic small fiber polyneuropathy.

The frequency of polyneuropathy and comparison of laboratory parameters in patients with multiple myeloma

Objective : Multiple myeloma(MM) is a B-cell neoplasia, characterized by clonal expansion of malignant plasma cells in bone marrow. Polyneuropathy (PN) is the most important complications in the treatment of MM. The aim of our study is to find out whether the lab parameters and the incidence of PN, are markers in MM patients or not. Methods: Totally 70 patients (31 male, 39 female) who presented to hematology outpatient department were retrospectively evaluated. Pre-treatment laboratory parameters and electromyography records of the patients taken from the file. Results: 15.7% of the cases the diagnosis was immediately available PN. Levels of β2 microglubin, uric acid, total protein, calcium, ALT, AST, creatinine, LDH and albumin levels didn’t differ significantly between two groups (p>0.05). Conclusion: Presence or development of PN in MM and its readiness to be used as an early marker, will obviously facilitate the treatment and follow-up of MM. Key words: Multiple myeloma, polyneuropathy, electromyography

Incidence of polyneuropathy in Utrecht, the Netherlands.

Ascertain the incidence of cryptogenic axonal polyneuropathy (CAP) and how this relates to the overall incidence of polyneuropathy. Electronic diagnostic registries of all hospital-based neurologic practices in the province of Utrecht (population 1,224,852 = 7.4% of the Dutch population) were consulted in 2010 to identify incident cases with polyneuropathy. Medical files were reviewed to specify the final diagnosis. Age-adjusted incidence rates for the Netherlands were calculated using national age-specific population figures. The overall incidence of polyneuropathy was 77.0/100,000 person-years (95% confidence interval 71.1-82.8) in persons aged 18 years and older. Diabetic polyneuropathy (32%), CAP (26%), toxic polyneuropathy (14%), and immune-mediated polyneuropathy (9%) were the most frequent diagnoses. The incidence of CAP was 31.6/100,000 person-years (95% confidence interval 27.0-36.3) in persons aged 40 years and older. The incidence of polyneuropathy increased with age, as well as the proportion of patients diagnosed with CAP: 12% (40-49 years), 20% (50-59 years), 28% (60-69 years), 32% (70-79 years), and 35% (≥80 years) (χ(2) test, p = 0.005). The chance of establishing an etiologic diagnosis in patients presenting with a polyneuropathy decreases with age. Given the aging population, polyneuropathy in general and CAP in particular will pose a growing health care problem.

Hypothyroid polyneuropathy in a patient with autoimmune polyglandular syndrome type 2: case report

The incidence of polyneuropathy in patients with hypothyroidism is not precisely known, but some studies report that about 25% to 42% of patients may show neuropathic clinical signs. We report a case of autoimmune poliglandular syndrome type 2 (APS-2), whose initial presentation was hypothyroid polyneuropathy. A 41-year-old man complained of slowly progressive paresthesias and weakness affecting all four limbs, and associated with frequent drowsiness, weakness, cold intolerance, dizziness, nausea, and craving for salt. General physical examination showed hyperpigmentation of skin and mucous membranes, and hypotension. Neurological examination showed global, deep, and symmetrical hyporeflexia with slight signs of superficial hypoesthesia in the limbs. Electrodiagnostic studies (ENMG) together with laboratory tests, confirmed the suspicion of Hashimoto's thyroiditis associated with Addison's disease featuring the picture of APS-2. The patient was treated with fludrocortisone 0.05 mg/day and levothyroxine 100 mcg/day, and showed gradual and complete resolution of complaints. Changes were found in general physical and neurological examinations. ENMG repeated six months later showed complete resolution of neuropathy. This report shows a rare case of APS-2 presented as polyneuropathy hypothyroidism, and reinforces the importance of dosing thyroid hormone in polyneuropathy syndromes. Levothyroxine replacement was shown to be effective in reversing clinical and electrophysiologic neuropathy.

Peripheral neuropathy in adult type 1 Gaucher disease: a 2-year prospective observational study

Type 1 Gaucher disease is currently categorized as non-neuronopathic, although recent studies suggest peripheral neurological manifestations. We report prevalence and incidence data for peripheral neuropathy and associated conditions from a multinational, prospective, longitudinal, observational cohort study in patients with type 1 Gaucher disease, either untreated or receiving enzyme replacement therapy. The primary outcome parameters were the prevalence and incidence of polyneuropathy, evaluated by standardized assessments of neurological symptoms and signs, and electrophysiological studies. All diagnoses of polyneuropathy were adjudicated centrally. Secondary outcome parameters included the prevalence and incidence of mononeuropathy, other neurological or electrophysiological abnormalities not fulfilling the criteria for a mono- or polyneuropathy and general type 1 Gaucher disease symptoms. Furthermore, a literature search was performed to identify all studies reporting on prevalence and incidence of polyneuropathy in the general population. One hundred and three patients were enrolled [median (range) age: 42 (18-75) years; disease duration: 15 (0-56) years; 52% female]; 14 (13.6%) were untreated and 89 (86.4%) were on enzyme replacement therapy. At baseline, 11 patients [10.7%; 95% confidence interval (CI): 5.9-18.3] were diagnosed with sensory motor axonal polyneuropathy. Two (1.9%; 95% CI: 0.1-7.2) had a mononeuropathy of the ulnar nerve. The 2-year follow-up period revealed another six cases of polyneuropathy (2.9 per 100 person-years; 95% CI: 1.2-6.3). Patients with polyneuropathy were older than those without (P<0.001). Conditions possibly associated with polyneuropathy were identified in four patients only, being monoclonal gammopathy, vitamin B(1) deficiency, folic acid deficiency, type 2 diabetes mellitus, renal insufficiency, alcohol abuse and exposure to toxins related to profession. The 11 cases of polyneuropathy found at baseline were confirmed during follow-up. According to the literature, the prevalence of polyneuropathy in the general population was estimated between 0.09 and 1.3% and the incidence was estimated between 0.0046 and 0.015 per 100 person-years. Thus, we conclude that the prevalence and incidence of polyneuropathy in patients with type 1 Gaucher disease is increased compared with the general population.

Beneficial effects of intensive insulin therapy in critically ill patients

Critically ill patients in intensive care units (ICU) for more than a few days have a mortality of approximately 20% world-wide. These critically ill patients, in the absence of a previous diagnosis of diabetes, commonly exhibit stress hyperglycemia and insulin resistance [1]. Many of these critically ill patients die of multiorgan dysfunction (MOD) and sepsis. Since stress hyperglycemia has been shown to associate with impaired polymorphonuclear neutrophil function and bactericidal activity [2], the question arose whether lowering of blood glucose in critically ill patients would decrease morbidity and mortality. To address this question the Leuven group of Van den Berghe and associates performed a prospective, randomized control study in 1548 patients admitted to their surgical ICU who were receiving mechanical ventilation [3]. The patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose between 80 and 110 mg/dl) or conventional treatment (insulin treatment only if blood glucose exceeded 215 mg/dl and then to maintain blood glucose between 180 and 200 mg/dl). At baseline, the two groups were comparable relative to age, gender, body mass index, APACHE II score and therapeutic intervention scoring system (TISS) and blood glucose. Two-thirds of the admissions to the surgical ICU were due to cardiac surgery in both groups. The primary endpoint of the Leuven study was ICU mortality. The intensive insulin treatment group had a significantly lower ICU mortality (4.6 vs 8%, P ¼ 0.04). This difference in mortality was primarily observed in those 451 patients who were in the ICU longer than 5 days (10.6 vs 20.2%, P ¼ 0.005). Multiple organ dysfunction (MOD) with a proven septic focus was also decreased (8 vs 33 cases, P ¼ 0.02) in the intensive insulin group as was the percentage of patients requiring greater than 14 days of ventilatory support (7.5 vs 11.9%, P ¼ 0.003). Other beneficial effects of intensive insulin therapy as compared to conventional treatment are shown in Table 1. In the total Leuven study population, the mean morning blood glucose value was 103±19 mg/dl in the intensive treatment group and 153±33 mg/dl in the conventional treatment group. Hypoglycemia (blood glucose less than 40 mg/dl) occurred in approximately 5% of the intensive treatment group without serious complications. Blood glucose measurements were performed every 1–4 h and the insulin dose adjusted according to a strict algorithm by intensive care nurses supervised by a physician not involved in the study. Although the Leuven study was performed in a surgical ICU, similar results have been recently reported from a medical-surgical ICU [4]. In a posthoc analysis of the Leuven results, a linear correlation between hyperglycemia and risk for death was observed, thus suggesting a direct toxic effect of glucose [5]. Moreover, in the conventional treatment group those patients with moderate hyperglycemia (110–150 mg/dl) had a lower risk of death than those patients with a blood glucose between 150 and 200 mg/dl. The moderate hyperglycemia group in the conventional treatment arm of the study, however, had a higher risk of death than the intensive insulin treatment group who had a blood glucose less than 110 mg/dl. In the presence of insulin resistance, glucose toxicity could be mediated by glucose overload in tissue sites in which glucose uptake is independent of insulin, including endothelial, epithelial and immune cells as well as central and peripheral nervous system and hepatocytes [6]. In that regard, of note are the observations in the Leuven study that the incidence of acute renal failure, the need for red blood cell transfusions and critical illness polyneuropathy were significantly less in the intensive insulin treatment group [3]. The beneficial effect of the decreased incidence of polyneuropathy may have been a factor in the diminished duration of mechanical ventilation in the intensive insulin treatment group. In contrast to the mitochondrial abnormalities observed in hepatocytes of the conventional treatment group, there was no morphological or functional evidence of