Citations

Abstract Background: Vasculitic neuropathies usually present acutely to subacutely, with an asymmetric pattern, involving multiple peripheral nerve territories. Drug-induced vasculitis is an often overlooked etiology of vasculitic neuropathy. Methods: We present the first reported case of nitrofurantoin-associated and an illustrative case of minocycline-associated vasculitic neuropathy, with a review of the literature. Results: The first patient is a 60-year-old woman who developed axonal sensorimotor peripheral neuropathy after nitrofurantoin use, with a superficial radial nerve biopsy confirming vasculitis. The second patient is a 23-year-old woman, with a history of acne vulgaris treated with minocycline, who presented with a subacute right common peroneal mononeuropathy followed by a left deep peroneal mononeuropathy, with elevated antinuclear, perinuclear-antineutrophil cytoplasmic, and myleoperoxidase antibodies, and MPO titers, and a sural nerve biopsy showing large arteriole vasculitis. Finally, we provide a comprehensive review of previously published cases. Conclusions: Medications should be considered as a trigger for medication-induced vasculitic neuropathy. Accurate diagnosis would ensure timely treatment.

AbstractIntroduction/AimsRecently, our group found an association between diabetes mellitus (DM) and lumbosacral radiculoplexus neuropathy (LRPN) in Olmsted County, Minnesota; we found a higher risk (odds ratio [OR], 7.91) for developing LRPN in diabetic compared with nondiabetic patients. However, the influence of other comorbidities and anthropomorphic variables was not studied.MethodsDemographic and clinical data from 59 LRPN patients and 177 age/sex‐matched controls were extracted using the Rochester LRPN epidemiological study. Differences between groups were compared by chi‐square/Fisher exact test or Wilcoxon rank‐sum test. Uni‐ and multivariate logistic regression analysis were performed.ResultsFactors predictive of LRPN on univariate analysis were DM (OR, 7.91; 95% confidence interval [CI], 4.11‐15.21), dementia (OR, 6.36; 95% CI, 1.13‐35.67), stroke (OR, 3.81; 95% CI, 1.32‐11.01), dyslipidemia (OR, 2.844; 95% CI, 1.53‐5.27), comorbid autoimmune disorders (OR, 2.72; 95% CI, 1.07‐6.93), hypertension (OR, 2.25; 95% CI, 1.2‐4.13), obesity (OR, 2.05; 95% CI, 1.11–3.8), body mass index (BMI) (OR, 1.1; 95% CI, 1.04‐1.15), and weight (OR, 1.02; 95% CI, 1.009‐1.037). On multivariate logistic regression analysis only DM (OR, 8.03; 95% CI, 3.86‐16.7), comorbid autoimmune disorders (OR, 4.58; 95% CI, 1.45‐14.7), stroke (OR, 4.13; 95% CI, 1.2‐14.25), and BMI (OR, 1.07; 95% CI, 1.01‐1.13) were risk factors for LRPN.DiscussionDM is the strongest risk factor for the development of LRPN, followed by comorbid autoimmune disorders, stroke, and higher BMI. Altered metabolism and immune dysfunction seem to be the most influential factors in the development of LRPN.

Abstract Background/Introduction Cardiomyopathy (CM) with associated heart failure and polyneuropathy (PN) are common manifestations of hereditary transthyretin amyloidosis (ATTRv), a progressive, debilitating, and fatal disease that results from the deposition of misfolded transthyretin (TTR) protein throughout the body. NEURO-TTR (NCT01737398) showed that inotersen, an antisense oligonucleotide inhibitor of TTR protein production, slowed the progression of PN and maintained quality of life in patients with ATTRv. Purpose To report efficacy and safety from the open-label extension (OLE) of the NEURO-TTR study in patients with ATTRv PN overall and in CM subgroups. Methods Patients who completed NEURO-TTR, enrolled in the OLE (NCT02175004), and either switched from placebo in NEURO-TTR to inotersen in the OLE (placebo-inotersen) or received inotersen in NEURO-TTR and remained on inotersen in the OLE (inotersen-inotersen) were included. Assessments included the modified Neuropathy Impairment Score +7 composite score (mNIS+7 [range –22.3 to 346.3], a measure of neuropathy with higher scores indicative of poorer function), TTR levels, and safety monitoring. Utilizing patients from Europe and North America (EU+NA) as of 28 July 2020, this post hoc analysis examined two subgroups: CM ECHO and severe CM ECHO. CM was defined as a diagnosis of ATTRv CM at study entry or all of the following criteria: a left ventricular wall thickness of ≥1.3 cm on transthoracic echocardiography at baseline, no known history of persistent hypertension (systolic blood pressure ≥150 mm Hg) within 12 months before study screening, and evaluable baseline ECHO obtained by central assessment. Severe CM was defined as an interventricular septum thickness ≥1.5 cm at baseline. Descriptive statistics are reported. Results In the overall population and both CM subgroups, the placebo-inotersen group demonstrated slowing of neurological disease progression compared with natural history based on NEURO-TTR placebo projection (estimated natural history will be presented). Furthermore, in the overall population and both CM subgroups, the inotersen-inotersen group demonstrated sustained benefit compared with the placebo-inotersen group (Table). Change in serum TTR levels will be presented. There have been no reports of grade 4 thrombocytopenia or acute glomerulonephritis under enhanced monitoring in patients in the EU+NA despite the increased duration of exposure. No new safety concerns were identified. Conclusions Inotersen treatment for >3 years slowed the progression of PN associated with ATTRv in patients with CM, including severe CM. In both subgroups, greater neurological preservation was observed in those who initiated inotersen earlier (inotersen-inotersen group), underscoring the benefits of early treatment. No new safety signals were detected in this OLE analysis; enhanced monitoring is successful in managing the risk for thrombocytopenia and acute glomerulonephritis. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This study was sponsored by Akcea Therapeutics, an affiliate of Ionis Pharmaceuticals, Inc.

Abstract Variable differences of nerve conduction amplitudes vs velocities and distal latencies (DLs) of healthy subjects assessed in ethnic cohorts. Introduction/Aims The variables affecting reference compound muscle (CMAP) and sensory nerve action potential (SNAP) amplitudes as compared to ones affecting conduction velocities and DLs have not been adequately evaluated in previous studies. In this report, this subject is studied in healthy subject cohorts mainly of Northern European extraction, Northern Plains Indians, and Latinos. Methods Nineteen variables and 18 attributes of nerve conductions (NCs) were assessed using highly standard testing conditions and techniques. Classification and Regression Tree analyses were used to assess variable differences among amplitudes, conduction velocities, and DLs. Results The most important variable affecting CMAP and SNAP amplitudes was age. For conduction velocities (CVs) and DLs, the variables were height, ethnic cohort, and age. Discussion The variables affecting attributes of NCs were similar for the three ethnic cohorts evaluated. The differences of variables affecting amplitudes compared to CVs and DLs need to be taken into account in interpretation of NC results and in setting reference limits for use in medical practice, epidemiology surveys, and therapeutic trials. Scores of CMAP and SNAP amplitudes are suitable measures of sensorimotor polyneuropathy severity, whereas conduction velocities and DLs reflect physiologic/pathologic abnormality of nerve fibers.