Neurology® Journal

Objective: This study estimated the annual economic cost of Guillain-Barre syndrome (GBS) in the United States in 2004, including the direct costs of medical care and the indirect costs due to lost productivity and premature death.Methods: The cost-of-illness method was used to determine the costs of medical care and lost productivity, and a modified value of a statistical life approach was used to determine the cost of premature deaths. Data were obtained from the Nationwide Inpatient Sample, the Medical Expenditure Panel Survey, the Compressed Mortality File, a telephone survey of 180 adult patients with GBS, and other sources.Results: The estimated annual cost of GBS was $1.7 billion (95% CI, $1.6 to 1.9 billion), including $0.2 billion (14%) in direct medical costs and $1.5 billion (86%) in indirect costs. Most of the medical costs were for community hospital admissions. Most of the indirect costs were due to premature deaths. The mean cost per patient with GBS was $318,966 (95% CI, $278,378 to 359,554).Conclusions: The economic cost of Guillain-Barre syndrome (GBS) was substantial, and largely due to disability and death. The cost estimate summarizes the lifetime health burden due to GBS in monetary terms, and provides some of the information needed to assess the cost-effectiveness of health measures that affect GBS.(C)2008AAN Enterprises, Inc.

Objective: To determine whether the presence of Nogo-A protein in CSF is a useful biomarker for multiple sclerosis (MS).Methods: We performed Western blots on CSF from patients with MS and controls with the commercially available Nogo-A antibody and secondary antibody used in a prior report. We used densitometry to measure band density on Western blot. Controls included blots without primary antibody, samples without dithiothreitol (DTT), CSF passed through a protein G column, and Western blots with anti-Ig-light chain antibody. IgG concentration in CSF was measured by ELISA.Results: A band at about 25 kD band was detectable in almost all CSF specimens, but was darker in samples from patients with MS. The density relative to a reference sample (mean +/- SD) was 0.84 +/- 0.67 for relapsing MS (n = 17), 1.16 +/- 0.74 for primary progressive MS (n = 11), and 0.49 +/- 0.22 in controls (n = 12). This band was still present when the primary antibody was omitted, but was absent if the sample buffer did not include DTT or if the CSF was first adsorbed with protein G. IgG concentration was higher in MS CSF and correlated closely with the 25 kD band density (r = 0.78).Conclusions: A 25 kD band is detectable on Western blots stained with Nogo-A antibody in almost all CSF specimens, but is darker in MS specimens. Our results suggest this band is immunoglobulin light chains rather than Nogo-A. It is not likely to be a useful biomarker for multiple sclerosis.(C)2008AAN Enterprises, Inc.

Objective: To investigate whether secondary impairment of the transmethylation pathway is a mechanism underlying the neurologic involvement in homocystinuria due to remethylation defects.Methods: Twelve patients with neurologic disease due to remethylation defects were examined by brain magnetic resonance spectroscopic imaging (1H MRSI). Brain N-acetylaspartate, choline-containing compounds (Cho), and creatine (Cr) were quantified and compared to with controls. Metabolites of remethylation cycle and creatine biosynthesis pathway were measured in plasma and urine.Results: MRSI revealed isolated Cho deficiency in all regions examined (mean concentration units +/- SD, patients vs controls): frontal white matter (0.051 +/- 0.010 vs 0.064 +/- 0.010; p = 0.001), lenticular nucleus (0.056 +/- 0.011 vs 0.069 +/- 0.009; p < 0.001), and thalamus (0.063 +/- 0.010 vs 0.071 +/- 0.007; p = 0.006). In contrast to controls, the Cho/Cr ratio decreased with age in patients in the three brain regions examined. Low creatine urinary excretion (p < 0.005), normal urine and plasma guanidinoacetate, and a paradoxical increase in plasma S-adenosylmethionine (p < 0.005) concentrations were observed.Conclusion: Patients with homocystinuria due to remethylation defects have an isolated brain choline deficiency, probably secondary to depletion of labile methyl groups produced by the transmethylation pathway. Although biochemical studies suggest mild peripheral creatine deficiency, brain creatine is in the reference range, indicating a possible compartmentation phenomenon. Paradoxical increase of S-adenosylmethionine suggests that secondary inhibition of methylases contributes to the transmethylation defect in these conditions.(C)2008AAN Enterprises, Inc.

Background: Clinical practice guidelines (CPGs) shape clinical care worldwide but are prone to potential error and bias due to conflicts of interest (COI).Objective: To explore the extent and scope of American Academy of Neurology (AAN) guideline author reported COI and implications for management; and to review process of AAN guideline COI management to highlight challenges, establish comparative benchmarks, and identify areas to be improved.Methods: Authors of AAN clinical practice guidelines with an active membership panel completed a COI reporting form. Authors were asked to report current interests including the 1 year prior to the date of completing the form. Interests include personal income relationships (consulting, speaker's bureaus, advisory boards), equity (stocks/stock options), patent/royalties, research, clinical practice, fiduciary interest in a company, and expert testimony. Comparisons were made between the two committees that oversee CPG development at the AAN: the Quality Standards Subcommittee (QSS) and the Therapeutics and Technology Assessment (TTA) Subcommittee.Results: There were 50 CPG with an average of 8.5 authors per CPG. There were a total of 425 available authors, 351 of whom completed a COI reporting form (83% response rate). Forty-six of the 50 guidelines had at least one author with a COI. The most commonly reported COIs were research-related (45% of authors), clinical practice-related (42%), and personal income relationships (33%). Authors of QSS guidelines were more likely to have personal income COIs with pharmaceutical and medical device companies (39% vs 24%, p < 0.01), whereas authors of TTA guidelines were more likely to have clinical practice-related COIs (50% vs 38%, p < 0.05). A minority of authors had individual COIs exceeding >$25,000 or had multiple interests (>10) that overlapped with content of the guidelines.Conclusion: Conflicts of interest are common for authors of American Academy of Neurology clinical practice guidelines across many domains of personal and professional interests. More research is needed to improve the methods to identify and quantify the types of conflicts and their potential biasing effects on selecting guideline topics, grading research evidence, and formulating practice recommendations.(C)2008AAN Enterprises, Inc.