Serum phosphorylated neurofilament-heavy chain levels in multiple sclerosis patients.

OBJECTIVES: We evaluated whether the measurement of serum phosphorylated neurofilament heavy chain (pNF-H) titre is likely to be a valid biomarker of axonal injury in multiple sclerosis (MS). METHODS: Serum pNF-H concentrations were measured by ELISA in cases with relapsing-remitting (RR)-MS (n=81), secondary progressive (SP) MS (n=13) and primary progressive (PP)-MS; n=6) MS; first demyelinating event (FDE; n=82); and unaffected controls (n=135). A subset of MS cases (n=45) were re-sampled on one or multiple occasions. The Multiple Sclerosis Severity Score (MSSS) and MRI measures were used to evaluate associations between serum pNF-H status, disease severity and cerebral lesion load and activity. RESULTS: We confirmed the presence of pNF-H peptides in serum by ELISA. We showed that a high serum pNF-H titre was detectable in 9% of RR-MS and FDE cases, and 38.5% of SP-MS cases. Patients with a high serum pNF-H titre had higher average MSSS scores and T2 lesion volumes than patients with a low serum pNF-H titre. Repeated sampling of a subset of MS cases showed that pNF-H levels can fluctuate over time, likely reflecting temporal dynamics of axonal injury in MS. CONCLUSIONS: A subset of FDE/MS cases was found to have a high serum pNF-H titre, and this was associated with changes in clinical outcome measures. We propose that routine measurement of serum pNF-H should be further investigated for monitoring axonal injury in MS.

Self-administered, inhaled methoxyflurane improves patient comfort during nasoduodenal intubation for computed tomography enteroclysis for suspected small bowel disease: a randomized, double-blind, placebo-controlled trial.

AIM: To determine the efficacy and safety of self-administered, inhaled analgesic, methoxyflurane, used to improve patient comfort during computed tomography enteroclysis (CTE). MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled trial was performed at two Australian hospitals (one tertiary referral public hospital and one private hospital). Patients were randomized to 3 ml methoxyflurane or saline (scented to maintain blindness) via hand-held inhaler. The main outcome measures were patient comfort during each stage of CTE and an overall rating as recorded by patients 1h post-procedure on a 10 cm visual analogue scale. Patient willingness to undergo repeat CTE, radiologist-rated ease of nasoduodenal intubation, and patient-rated ease of use of the inhaler were also assessed. RESULTS: Sixty patients (mean age 45 years; 41 women) were enrolled; 30 received methoxyflurane and were well matched to 30 receiving placebo. Procedural success was 98%. The mean dose of methoxyflurane consumed was 0.9 ml (SD 0.5). Patient comfort during nasoduodenal intubation was better with methoxyflurane {5.0 [95% confidence intervals (CI) 4.0-6.0]} than with placebo [2.7 (95% CI 1.8-3.7); p=0.002, t-test), but there were no significant differences for comfort levels at other times or overall. The inhaler was easy to use, was well tolerated, and there were no episodes of oxygen desaturation, aspiration, or anaphylaxis. CONCLUSIONS: Inhalational methoxyflurane safely improves patient comfort during nasoduodenal intubation, but does not improve overall procedure comfort.

Early post-operative ankle pressure indices help predict late patency rates after femoro-distal vein bypass grafting.

A prospective graft surveillance programme included 115 femorodistal autogenous vein bypass grafts that were patent when studied by measurements of ankle/brachial pressure indices (ABIs) at 3-5 weeks after operation. The grafts were followed for up to 3 years to determine whether early ABIs helped to predict subsequent failures, defined as graft thrombosis or graft or anastomotic stenosis causing diameter reduction greater than 75% treated by surgery or balloon dilatation. Receiving operating characteristics curves showed that resting ABIs predicted failure better than post-exercise ABIs or the differences between the two, and that an early resting ABI less than 0.85 was the optimal value to predict failure. Primary patency rates at 2 years were 88% for resting ABI greater than or equal to 0.85 and 36% for resting ABI less than 0.85 (p less than 0.0005). Most stenoses occurred in the grafts and not at anastomoses. Arteriographic grading of crural artery outflow was not significantly different for successful or failed grafts or for grafts with resting ABI greater than or equal to 0.85 or less than 0.85. The observation that late graft failure was 3-4 times more likely if the early post-operative ABI was low suggests that most graft failures result from faults relating to the operation.