Measuring the value of neurology

Determining the value of a cup of coffee is relatively straightforward. When defined as a ratio of quality over cost, the value equation in this setting is easy to solve. How good are the coffee beans? What about the coffee maker? How fresh is the coffee? Finally, to determine the cost, simply look at the sign in the coffee shop or the price on the package. The best value comes from high-quality coffee offered at a low cost

Neurology 2016

Hepatitis C virus infection as a risk factor for Parkinson disease A nationwide cohort study

Objective: To determine whether hepatitis C virus (HCV) infection is a risk factor for developing Parkinson disease (PD).

Methods: This nationwide population-based cohort study was based on data obtained from a dataset of the Taiwan National Health Insurance Research Database for the period 2000 to 2010. A total of 49,967 patients with viral hepatitis were included for analysis. Furthermore, 199,868 people without viral hepatitis were included for comparisons. Patients with viral hepatitis were further grouped into 3 cohorts: hepatitis B virus (HBV) infection, HCV infection, and HBV-HCV coinfection. In each cohort, we calculated the incidence of developing PD. A Cox proportional hazards model was applied to estimate the risk of developing PD in terms of hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: The crude HRs for developing PD was 0.66 (95% CI = 0.55–0.80) for HBV infection, 2.50 (95% CI = 2.07–3.02) for HCV infection, and 1.28 (95% CI = 0.88–1.85) for HBV-HCV coinfection. The association between HCV and PD remained statistically significant after adjustments for age, sex, and comorbidities (adjusted HR = 1.29, 95% CI = 1.06–1.56).

Conclusions: We conducted a large nationwide population-based study and found that patients with HCV exhibit a significantly increased risk of developing PD.

Neurology 2016

Critically re-evaluating a common technique Accuracy, reliability, and confirmation bias of EMG

Objectives: (1) To assess the diagnostic accuracy of EMG in radiculopathy. (2) To evaluate the intrarater reliability and interrater reliability of EMG in radiculopathy. (3) To assess the presence of confirmation bias in EMG.

Methods: Three experienced academic electromyographers interpreted 3 compact discs with 20 EMG videos (10 normal, 10 radiculopathy) in a blinded, standardized fashion without information regarding the nature of the study. The EMGs were interpreted 3 times (discs A, B, C) 1 month apart. Clinical information was provided only with disc C. Intrarater reliability was calculated by comparing interpretations in discs A and B, interrater reliability by comparing interpretation between reviewers. Confirmation bias was estimated by the difference in correct interpretations when clinical information was provided.

Results: Sensitivity was similar to previous reports (77%, confidence interval [CI] 63%–90%); specificity was 71%, CI 56%–85%. Intrarater reliability was good (κ 0.61, 95% CI 0.41–0.81); interrater reliability was lower (κ 0.53, CI 0.35–0.71). There was no substantial confirmation bias when clinical information was provided (absolute difference in correct responses 2.2%, CI −13.3% to 17.7%); the study lacked precision to exclude moderate confirmation bias.

Conclusions: This study supports that (1) serial EMG studies should be performed by the same electromyographer since intrarater reliability is better than interrater reliability; (2) knowledge of clinical information does not bias EMG interpretation substantially; (3) EMG has moderate diagnostic accuracy for radiculopathy with modest specificity and electromyographers should exercise caution interpreting mild abnormalities.

Classification of evidence: This study provides Class III evidence that EMG has moderate diagnostic accuracy and specificity for radiculopathy.

Neurology 2016

Shared genetic susceptibility of vascular-related biomarkers with ischemic and recurrent stroke

Objective: To investigate the genetic contributors to cerebrovascular disease and variation in biomarkers of ischemic stroke.

Methods: The Vitamin Intervention for Stroke Prevention Trial (VISP) was a randomized, controlled clinical trial of B vitamin supplementation to prevent recurrent stroke, myocardial infarction, or death. VISP collected baseline measures of C-reactive protein (CRP), fibrinogen, creatinine, prothrombin fragments F₁₊₂, thrombin-antithrombin complex, and thrombomodulin prior to treatment initiation. Genome-wide association scans were conducted for these traits and follow-up replication analyses were performed.

Results: We detected an association between CRP single nucleotide polymorphisms (SNPs) and circulating CRP levels (most associated SNP, rs2592902, p = 1.14 × 10⁻⁹) in 2,100 VISP participants. We discovered a novel association for CRP level in the AKR1D1 locus (rs2589998, p = 7.3 × 10⁻⁸, approaching genome-wide significance) that also is an expression quantitative trait locus for CRP gene expression. We replicated previously identified associations of fibrinogen with SNPs in the FGB and LEPR loci. CRP-associated SNPs and CRP levels were significantly associated with risk of ischemic stroke and recurrent stroke in VISP as well as specific stroke subtypes in METASTROKE. Fibrinogen levels but not fibrinogen-associated SNPs were also found to be associated with recurrent stroke in VISP.

Conclusions: Our data identify a genetic contribution to inflammatory and hemostatic biomarkers in a stroke population. Additionally, our results suggest shared genetic contributions to circulating CRP levels measured poststroke and risk for incident and recurrent ischemic stroke. These data broaden our understanding of genetic contributors to biomarker variation and ischemic stroke risk, which should be useful in clinical risk evaluation.

Neurology 2016

Prevalence of HIV-associated neurocognitive disorders in the Multicenter AIDS Cohort Study

Objective: To evaluate the frequency of HIV-associated neurocognitive disorder (HAND) in HIV+ individuals and determine whether the frequency of HAND changed over 4 years of follow-up.

Methods: The Multicenter AIDS Cohort Study (MACS) is a prospective study of gay/bisexual men. Beginning in 2007, all MACS participants received a full neuropsychological test battery and functional assessments every 2 years to allow for HAND classification.

Results: The frequency of HAND for the 364 HIV+ individuals seen in 2007–2008 was 33% and for the 197 HIV+ individuals seen at all time periods during the 2007–2008, 2009–2010, and 2011–2012 periods were 25%, 25%, and 31%, respectively. The overall frequency of HAND increased from 2009–2010 to 2011–2012 (p = 0.048). Over the 4-year study, 77% of the 197 HIV+ individuals remained at their same stage, with 13% showing deterioration and 10% showing improvement in HAND stage. Hypercholesterolemia was associated with HAND progression. A diagnosis of asymptomatic neurocognitive impairment was associated with a 2-fold increased risk of symptomatic HAND compared to a diagnosis of normal cognition.

Conclusion: HAND remains common in HIV+ individuals. However, for the majority of HIV+ individuals on combination antiretroviral therapy with systemic virologic suppression, the diagnosis of HAND is not a progressive condition over 4 years of follow-up. Future studies should evaluate longitudinal changes in HAND and specific neurocognitive domains over a longer time period.

Neurology 2016

Mutations in HSPB8 causing a new phenotype of distal myopathy and motor neuropathy

Objective: To report novel disease and pathology due to HSPB8 mutations in 2 families with autosomal dominant distal neuromuscular disease showing both myofibrillar and rimmed vacuolar myopathy together with neurogenic changes.

Methods: We performed whole-exome sequencing (WES) in tandem with linkage analysis and candidate gene approach as well as targeted next-generation sequencing (tNGS) to identify causative mutations in 2 families with dominant rimmed vacuolar myopathy and a motor neuropathy. Pathogenic variants and familial segregation were confirmed using Sanger sequencing.

Results: WES and tNGS identified a heterozygous change in HSPB8 in both families: c.421A > G p.K141E in family 1 and c.151insC p.P173SfsX43 in family 2. Affected patients had a distal myopathy that showed myofibrillar aggregates and rimmed vacuoles combined with a clear neurogenic component both on biopsy and neurophysiologic studies. MRI of lower limb muscles demonstrated diffuse tissue changes early in the disease stage progressing later to fatty replacement typical of a myopathy.

Conclusion: We expand the understanding of disease mechanisms, tissue involvement, and phenotypic outcome ofHSPB8 mutations. HSPB8 is part of the chaperone-assisted selective autophagy (CASA) complex previously only associated with Charcot-Marie-Tooth type 2L (OMIM 60673) and distal hereditary motor neuronopathy type IIa. However, we now demonstrate that patients can develop a myopathy with histologic features of myofibrillar myopathy with aggregates and rimmed vacuoles, similar to the pathology in myopathies due to gene defects in other compounds of the CASA complex such as BAG3 and DNAJB6 after developing the early neurogenic effects

Neurology 2016

Acute bulbar palsy as a variant of Guillain-Barré syndrome

Objective: To categorize a syndrome manifesting as prominent acute bulbar palsy (ABP) without limb motor weakness as a variant form of Guillain-Barré syndrome (GBS) and differentiate it from Miller Fisher syndrome (MFS) and pharyngeal-cervical-brachial (PCB) variants.

Methods: We analyzed cases of ABP without limb motor weakness based on a dataset containing clinical information and the results of antiganglioside antibodies assays for acute immune-mediated neuropathies.

Results: Eleven cases with an age at onset ranging from 18 to 65 years (mean 33.8 years) were identified as ABP-plus syndrome. All of the enrolled cases manifested with ABP as the predominant symptom, and with no limb weakness. The following features accompanied ABP in order of decreasing frequency: ophthalmoplegia (n = 9, 82%), ataxia (n = 9, 82%), and facial palsy (n = 6, 55%). An enzyme-linked immunosorbent assay study disclosed that immunoglobulin G (IgG) anti-GT1a antibodies were the most frequent (n = 11), followed by IgG anti-GQ1b antibodies (n = 6).

Conclusions: We propose that ABP-plus syndrome without neck or limb weakness is a variant of GBS that is distinct from the MFS and PCB variants. The presence of IgG anti-GT1a antibodies can explain the relationships between the distinct clinical characteristics and the underlying pathomechanisms.

Neurology 2016