Prevalence, Risk Factors and Consequences of Chronic Polyneuropathy : The Rotterdam Study

Polyneuropathy is a chronic disease characterized by symmetric tingling sensations, numbness and neuropathic pain in the hands and feet. There is a lack of knowledge about the prevalence and risk factors of this disease, especially on population level. Within the Rotterdam Study, a large population-based study, we employed an extensive polyneuropathy screening consisting of a symptom questionnaire, neurological examination and nerve conduction studies. With this screening we prospectively screened 1310 participants and found a definite polyneuropathy in 5.5% of persons above 45 years of age, and this percentage increased drastically with age. In 46% of persons with polyneuropathy, no established risk factor was present (chronic idiopathic axonal polyneuropathy), which highlights the need for further studies on risk factors for this disease. Aside from diabetes, which probably is the most important known risk factor for chronic polyneuropathy, we identified metabolic syndrome and especially (abdominal) obesity and dyslipidemia as potential risk factors for polyneuropathy. Importantly, these factors also associated with decreased peripheral nerve function in persons (yet) without signs or symptoms of polyneuropathy. This suggest that these factors have role in the pathophysiology of chronic axonal polyneuropathies, but longitudinal studies are required to confirm these associations. We also studied the effect of polyneuropathy on daily life and found that polyneuropathy associated with impairment in several basic activities of daily living, such as arising, dressing and grooming, eating and walking. Furthermore, persons with polyneuropathy have an increased risk of falling, and on the potential consequences of falling, such as head trauma and fractures. To conclude, polyneuropathy is a very common, often idiopathic, disabling disorder. More research is necessary to elucidate the pathophysiology of this multifactorial disease

Emergency medicine in Paarl, South Africa: a cross-sectional descriptive study

Background: Emergency Medicine (EM) in South Africa is in its earliest stages of development. There is a paucity of data about emergency department (ED) patient demographics, epidemiology, consultation and admission criteria and other characteristics. Aims: This information is absolutely necessary to properly guide the development of EM and appropriate emergency care systems. In order to provide this information, we performed a study in a rural hospital in Paarl, 60 km outside Cape Town. Methods: All patients who were seen in the ED between 1 January 2008 and 31 May 2008 were eligible for our research. We designed a cross-sectional descriptive study and retrieved information from a randomized sample of all consecutive patient charts seen during this period using a 40-point questionnaire (see Appendix 1). Results: We investigated 2,446 charts, of which 2,134 were suitable for our research The majority (88.2%) of these patients were self-referred. In our sample, 24.1% were children under 12 years old. Almost 20% of patients had a serious pathological condition or were physiologically unstable; 36.0% of all presentations were trauma related. Besides trauma-related problems, gastrointestinal- (21.9%) and respiratory tract- (12.4%) related problems were most common in the ED; 16.5% of the patients were admitted to a ward. Conclusion: This descriptive epidemiological study provides necessary data that will be used for further needs assessments and for future EM development in Paarl, and can be used as a template in other EDs and hospitals to provide similar data necessary for initial EM development strategy

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 OR(BMI, 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 OR(alcohol, 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 PGS (p ) (< 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

Diet quality and chronic axonal polyneuropathy: a population-based study

Objective: To investigate the association between diet quality and chronic axonal polyneuropathy. Methods: Between June 2013 and January 2017, among 1650 participants of the Rotterdam Study (median age 69.1 years, 54.2% women), diet quality was quantified based on food frequency questionnaires as a sum score of adherence (yes/no) to 14 components of the Dutch dietary guidelines. Presence of polyneuropathy was determined based on a questionnaire, neurological examination of the legs, and nerve conduction studies. We used logistic regression to associate diet quality with the presence of chronic axonal polyneuropathy and linear regression to associate with sural sensory nerve action potential (SNAP) amplitude in participants without polyneuropathy. Results were adjusted for age, sex, time between measurement

Age-Related Changes in Neurologic Examination and Sensory Nerve Amplitude in the General Population:Aging of the Peripheral Nervous System

BACKGROUND AND OBJECTIVES: Chronic axonal polyneuropathy is a common disease of the peripheral nervous system with increasing prevalence with age. Typical neurologic signs are present in patients with polyneuropathy but may also occur in individuals without disease. Owing to limited knowledge on normal aging of the peripheral nervous system, it can be difficult to distinguish peripheral nerve dysfunction due to disease from variations in normal aging. Therefore, we described the changes in neurologic examination and nerve conduction studies that accompany aging in the general population. METHODS: In this cross-sectional population-based study, we screened participants for chronic polyneuropathy in a controlled environment using standardized methods including a symptom questionnaire, neurologic examination, and nerve conduction studies (NCS). Inclusion criteria were 40 years or older and living in a suburb of Rotterdam, the Netherlands. Participants not diagnosed with chronic polyneuropathy, based on the discussion of findings in the screening by an expert team, were included to determine the effect of age (range 41-96 years) on features of neurologic examination and NCS using frequency calculations and quantile regression analysis. RESULTS: In total, 4,179 participants (mean age 64.5 ± 12.7 years, 54.9% female) were included of whom 3,780 (90.5%) did not fulfil the criteria for polyneuropathy. In the population without polyneuropathy, the frequency of normal features at neurologic examination declined with age, most pronounced for vibration sense at the hallux (from 6.6 [SD ± 1.5] in 40-49 years to 3.6 [SD ± 3.1] in 80 years or older) and Achilles tendon reflexes (absent in 9% in 40-49 years up to 33% in 80 years or older). Superficial pain sensation and patellar tendon reflexes remained stable over time. Sural sensory nerve action potential (SNAP) amplitude declined with age from 11.2 μV in 40-49 years to 3.3 μV in 80 years or older. Nonrecordable SNAP amplitudes were found in 25.1% of the participants older than 80 years, more often in men (30.3%) than in women (21.0%). DISCUSSION: This study showed the effect of age on features of neurologic examination and sural nerve amplitude in the general population. These findings are helpful to distinguish features suggesting polyneuropathy from variations of normal aging of the peripheral nervous system.</p

Prevalence and Risk Factor Profiles for Chronic Axonal Polyneuropathy in the General Population

Background and ObjectivesChronic axonal polyneuropathy is a common disease with increasing prevalence with age. It majorly affects quality of life and leads to difficulties with various activities. Persons with polyneuropathy often not seek medical care and thus the societal burden of disease is likely underreported. Given the aging populations, contemporary data on the prevalence and risk factor profiles of polyneuropathy in the general population are required. Therefore, we estimated the current and expected prevalence and investigated the (co-)occurrence of risk factors in participants with chronic axonal polyneuropathy.MethodsBetween June 2013 and January 2020, participants of the population-based Rotterdam Study underwent extensive in-person examination to diagnose polyneuropathy. Age-standardized prevalence's were calculated for populations age 40 years or older of the Netherlands, Europe, the United States, and the world population. Putative risk factors were identified using laboratory findings, interviews, questionnaire data, and a review of medical records.ResultsIn total, 4,114 participants were included (mean age 64.3 years, 55.2% females), of whom 167 had chronic axonal polyneuropathy. More than half (54.5%) had yet not received the diagnosis through regular care. Age-standardized prevalence's were 3.3% (95% CI 2.8-4.0) for the European, 3.0% (95% CI 2.5-3.5) for the United States, and 2.3% (95% CI 1.9-2.8) for the world population. Based on the expected age distributions, the prevalence of chronic axonal polyneuropathy will increase with ±25% in the next 20 years. Known risk factors were present in 62.9% (N = 105) of the cases with polyneuropathy and most often included diabetes (34.1%) and vitamin deficiencies (15.1%). Importantly, combinations of various risk factors were found in 20.4% (N = 34) of cases with polyneuropathy.DiscussionPrevalence of chronic axonal polyneuropathy increases with age and is expected to further rise over time. Combinations of multiple known risk factors are often present, indicating the need for a full diagnostic workup, even when a single risk factor for polyneuropathy is known. These findings suggest that cumulative effects of multiple risk factors are important in the development and course of disease

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.</p

Diagnostic value of symptoms in chronic polyneuropathy : The Erasmus Polyneuropathy Symptom Score

In this study, we evaluated the diagnostic value of symptoms of chronic polyneuropathy and to construct and validate a simple questionnaire that can help diagnose chronic polyneuropathy. In a multi-step procedure, we initially compiled a 12-item questionnaire concerning polyneuropathy symptoms. The questionnaire was completed by 117 polyneuropathy patients and 188 controls (headache, transient ischemic attack, multiple sclerosis). First, we calculated sensitivity, specificity and likelihood ratios of each symptom. Next, we used multi-variable logistic regression to create a model that could discriminate patients from controls, using only the most informative symptoms and their frequency of occurrence. Based on the regression coefficients, we developed a simple scoring system (Erasmus Polyneuropathy Symptom Score, E-PSS), which was externally validated in 140 cases with chronic idiopathic axonal polyneuropathy and 96 controls without polyneuropathy. We assessed performance with discrimination (area under the curve, AUC) and calibration analyses. Numb and tingling feet were most frequently reported by polyneuropathy patients and had the highest sensitivity. Walking on cotton wool and allodynia had the highest specificity. Logistic regression yielded a model that contained these four symptoms, complemented with balance problems and tingling hands. Based on this analysis, the E-PSS was created, ranging from 0 to 14. The E-PSS had a good performance (AUC = 0.92) in the derivation set and proved to be valid in the external population (AUC = 0.95). In conclusion, the Erasmus Polyneuropathy Symptom Score (E-PSS) is a simple, validated six-item score that takes the presence and frequency of six different symptoms into account and it may be a helpful tool to screen individuals for the presence of chronic polyneuropathy