Prevalence and Risk Factors of Distal Symmetric Polyneuropathy Among Predominantly Non-Hispanic Black, Low-Income Patients.

BACKGROUND AND OBJECTIVES: Distal symmetric polyneuropathy (DSP) is a disabling, often painful condition associated with falls and reduced quality of life. Non-Hispanic Black people and people with low income are underrepresented in existing DSP studies; therefore, it is unknown whether data accurately reflect the prevalence, risk factors, and burden of disease in these populations. METHODS: Patients older than 40 years presenting to an outpatient internal medicine clinic predominantly serving Medicaid patients in Flint, Michigan, were enrolled in a cross-sectional study. Demographics, clinical characteristics, including medication use, anthropomorphic measurements, fasting lipids, and hemoglobin A1c were collected. DSP was defined using the modified Toronto Clinical Neuropathy Score (mTCNS). Multivariable logistic regression was performed to model DSP and undiagnosed DSP as a function of potential risk factors age, metabolic syndrome, and race. DSP burden was measured using Peripheral Neuropathy Quality of Life Instrument-97. RESULTS: Two hundred participants were enrolled, and 169 (85%) completed all data collection. The population was 55% female of mean age (SD) 58.2 years (10.4) and 69% non-Hispanic Black. Among the population, 50% had diabetes, 67% had metabolic syndrome, and 47% had a household income <$20,000. DSP was present in 73% of the population, of which 75% were previously undiagnosed. Neuropathic pain was documented in 57% of participants with DSP. DSP based on mTCNS criteria was associated with older age (odds ratio [OR] 1.1 [95% confidence interval (CI) 1.03-1.2]) and metabolic syndrome (OR 4.4 [1.1-18.1]). Non-Hispanic Black participants had lower odds of DSP (OR 0.1 [0.01-0.4]) than non-Hispanic White and Hispanic participants. DSP burden was high, including increased pain, health-related worry, and poorer quality of life (all p < 0.001). DISCUSSION: DSP is extremely common and often underrecognized in this predominantly non-Hispanic Black, low-income population and leads to substantial disease burden. Metabolic syndrome is a highly prevalent, modifiable risk factor in this population that should be managed to lower DSP prevalence.

Association of the transthyretin variant V122I with polyneuropathy among individuals of African ancestry.

Hereditary transthyretin-mediated (hATTR) amyloidosis is an underdiagnosed, progressively debilitating disease caused by mutations in the transthyretin (TTR) gene. V122I, a common pathogenic TTR mutation, is found in 3-4% of individuals of African ancestry in the United States and has been associated with cardiomyopathy and heart failure. To better understand the phenotypic consequences of carrying V122I, we conducted a phenome-wide association study scanning 427 ICD diagnosis codes in UK Biobank participants of African ancestry (n = 6062). Significant associations were tested for replication in the Penn Medicine Biobank (n = 5737) and the Million Veteran Program (n = 82,382). V122I was significantly associated with polyneuropathy in the UK Biobank (odds ratio [OR] = 6.4, 95% confidence interval [CI] 2.6-15.6, p = 4.2 × 10-5), which was replicated in the Penn Medicine Biobank (OR = 1.6, 95% CI 1.2-2.4, p = 6.0 × 10-3) and Million Veteran Program (OR = 1.5, 95% CI 1.2-1.8, p = 1.8 × 10-4). Polyneuropathy prevalence among V122I carriers was 2.1%, 9.0%, and 4.8% in the UK Biobank, Penn Medicine Biobank, and Million Veteran Program, respectively. The cumulative incidence of common hATTR amyloidosis manifestations (carpal tunnel syndrome, polyneuropathy, cardiomyopathy, heart failure) was significantly enriched in V122I carriers compared with non-carriers (HR = 2.8, 95% CI 1.7-4.5, p = 2.6 × 10-5) in the UK Biobank, with 37.4% of V122I carriers having at least one of these manifestations by age 75. Our findings show that V122I carriers are at increased risk of polyneuropathy. These results also emphasize the underdiagnosis of disease in V122I carriers with a significant proportion of subjects showing phenotypic changes consistent with hATTR amyloidosis. Greater understanding of the manifestations associated with V122I is critical for earlier diagnosis and treatment.

Description of a large cohort of Caucasian patients with V122I ATTRv amyloidosis: Neurological and cardiological features.

V122I is one of more than 130 mutations in transthyretin gene associated with hereditary TTR (ATTRv) amyloidosis. Main clinical expression is an infiltrative pseudohypertrophic cardiomyopathy with mild or no neurological symptoms. It is particularly common among African-Americans (prevalence: 3%-4%). We report 12 subjects from seven unrelated Caucasian families hailing from Sicily and carrying the V122I mutation. One patient was homozygous for V122I and in another family two subjects also carried the E89Q variant in compound heterozygosity. All the subjects underwent neurologic/neurophysiologic evaluation and cardiologic baseline tests; in five of them, cardiac magnetic resonance and/or (99 m) Tc-DPD scintigraphy were performed. Three of 12 subjects were asymptomatic carriers. Of the remaining nine subjects, in four of nine patients, the nerve conduction studies revealed a polyneuropathy; in one of them, this represents the only sign of disease after 5 years of follow-up. In eight of nine subjects, we found a hypertrophic restrictive cardiomyopathy and cardiac failure, associated with a carpal tunnel syndrome. Although in non-Afro-American individuals V122I prevalence is low, subjects carrying this mutation have been identified in the United Kingdom, Italy, and France. Our report describes a large cohort of V122I Caucasian patients from a non-endemic area, confirming the possible underestimation of this mutation in the non-African population. Moreover, it highlights the heterogeneity in the genotype-phenotype correlation of ATTRv mutations, suggesting that the presence of a polyneuropathy has to be identified as soon as possible, since available treatments are, in Europe, so far authorized only for ATTRv amyloid peripheral neuropathy.

The relationship between race and HIV-distal sensory polyneuropathy in a large cohort of US women.

INTRODUCTION: HIV-distal sensory polyneuropathy (HIV-DSPN) is a common complication of HIV infection, yet race as a potential risk factor is not known. METHODS: Between April and October 2009, as part of the NIH Women's Interagency HIV Study (WIHS), 1414 women, 973 of whom were HIV-infected, were clinically evaluated for peripheral neuropathy. Utilizing available clinical, laboratory, and sociodemographic variables, we conducted a cross-sectional analysis of factors associated with HIV-DSPN. Multivariable logistic regression was used to examine factors independently associated with HIV-DSPN. RESULTS: 36% of HIV-infected women met our definition of HIV-DSPN. 41.3% of African Americans, 34.8% of Whites and 24.7% of Hispanics had DSPN. Age, Hepatitis C-co-infection, and diabetes were each significantly associated with HIV-DSPN. After controlling for age, diabetes, Hepatitis C co-infection, alcohol use, current dideoxy-nucleoside reverse transcriptase inhibitor use, current CD4 count, and plasma HIV viral load, HIV-DSPN was significantly associated with ethnicity; the odds ratio was 1.67 (p=0.001) in African-Americans compared to other racial groups. CONCLUSION: The prevalence of HIV-DSPN in women was lower than reported in prior studies. The likelihood of HIV-DSPN was higher in African-Americans compared to other racial groups. HIV-DSPN was more common in those co-infected with Hepatitis C, older individuals, and diabetics. Further prospective studies are needed to explore the relationship between gender, race, and HIV-DSPN, and the mechanistic basis for racial differences.

[Polyneuropathies in vitamin B1 deficiency in Reunion and Mayotte islands in 70 patients of Maori and Comorian descent]. / Polyneuropathies par hypovitaminose B1 aux îles de la Réunion et de Mayotte: à propos de 70 cas d'origine mahoraise et comorienne.

Beriberi is an uncommon disorder related to thiamine deficiency. It is mainly found in underdeveloped countries among populations with poorly diversified diet, consisting largely of milled white cereals, a poor source of thiamine. In industrialized countries, thiamine deficiency with cardiac failure is more frequently found than the dry beriberi in high risk groups like chronic alcoholics. Nevertheless our attention was drawn to an outbreak of 70 cases of dry beriberi which occurred from 1997 to 2005 in the French territories of Reunion and Mayotte islands. It was characterized by an acute or sub-acute sensorimotor polyneuropathy with axonal lesions, affecting the lower limbs and occasionally the upper limbs, sometimes associated with cardiac beriberi. It affected young, non alcoholic individuals from the Mahoran and Comorian community who were in apparent good health when the illness occurred. Our study highlighted the feeding habits which are partly responsible for the development of the disease due to a chronic lack of thiamine and which probably contributed together with multiple cofactors to trigger off the illness. But many elements and mainly biological ones, also lead us to think that there is a genetic predisposition to develop this neuropathy.

[A case of beriberi on the threshold of the year 2000]. / Un caso di Beri-beri alle soglie del 2000.

The authors report a case of beriberi due to a deficit in thiamine, which became apparent in a young Chinese woman with polyneuropathy, distal oedema and epigastralgia. Parenteral administration of thiamine lead to the virtually complete resolution of symptoms.