Amylase quantification in the terminal Ileum following formation of an Ileostomy.

Amylase is elevated in the foregut and has been used to confirm anastomotic integrity after pancreatic surgery. The physiological activity of pancreatic enzymes in the ileum has been studied in healthy volunteers but not quantitated with the simple and readily available amylase measurements employed with serum tests. We aim to quantitate the levels of amylase in the terminal ileum. This was a prospective, non-randomised, non-blinded, consecutive cohort study conducted at the Royal Brisbane and Women's Hospital. Consecutive patients undergoing routine surgery with an ileostomy were invited to participate in the study. Ileostomy effluent was collected and analysed daily for the first 5 post-operative days. This validation cohort included 8 males and 3 females, with a mean age of 49 years. Median daily amylase levels ranged from 4470 U/L to 23,000 U/L, with no specimens falling within the laboratory serum reference range of 40 to 130 U/L. Two specimens were not available on day one post-operative due to complete ileus. The sample size of 11 patients is small but was considered sufficient given that 55 effluent specimens were anticipated for analysis. Amylase levels remain highly elevated as the enzyme transits through the length of the small intestine and measured in the terminal ileum, and can be readily quantitated by the existing testing methodology routinely available.

Anastomotic leak does not affect long-term and longitudinal functional outcomes after ileal pouch surgery for ulcerative colitis when managed aggressively.

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is an effective surgical alternative to a permanent ileostomy following proctocolectomy in patients with ulcerative colitis (UC). Anastomotic leakage (AL) is a serious postoperative complication of an intestinal anastomosis that is associated with increased morbidity and mortality. The aim of this study was to evaluate the longitudinal long-term functional outcomes of patients who had IPAA that was complicated by AL. METHODS: A retrospective longitudinal cohort study was performed of patients who had an IPAA procedure at a tertiary referral centre and a metropolitan private centre in Australia, over a 14-year period (October 2003-October 2017). The long-term functional outcome was assessed using objective clinical measures such as the number of bowel motions during the day and overnight, ability to defer defaecation and the presence of faecal incontinence, and repeated at annual intervals. RESULTS: A total of 138 patients [mean age 38.5 (± 16.9) years, 72 males] satisfied the inclusion criteria. AL was diagnosed in 14 (10%) patients [mean age 38.8 (± 17) years, 10 males], 11 (79%) of which were managed with surgery. The median bowel motion frequency during the day and overnight remained stable over a median of 62 (28-91) months follow-up, with no significant difference between those who had AL or not (p = 0.6, p = 0.1 respectively). The incidence of faecal incontinence remained low, and the majority of patients in both groups were able to defer defaecation for more than 60 min. Six patients (4.3%) had their pouch excised. CONCLUSIONS: There is no statistical difference in longitudinal function between patients who experienced AL after IPAA surgery for UC compared with those who did not. Therefore, an acute AL does not negatively impact long-term functional outcomes in IPAA patients.

Kinetics of maternally-derived serogroup A, C, Y and W-specific meningococcal immunoglobulin G in Malian women and infants.

A prospective, randomised, controlled observer-blind trial measuring the efficacy and immunogenicity of trivalent influenza vaccine (TIV) and the immunogenicity of quadrivalent meningococcal conjugate vaccine (MCV) in pregnant women and their infants up to 6 months of age was conducted in Mali. Here we reported the immunogenicity of MCV, which was used as a comparator vaccine to TIV, in this population. Third-trimester pregnant Malian women were randomized to receive TIV or MCV. Blood samples were collected from women prior to vaccination, 28 days post-vaccination, at delivery and 3 and 6 months post-delivery and from infants at birth and 3 and 6 months of age. Meningococcal-specific serogroup (Men) A, C, Y and W-specific antibodies were measured by enzyme linked immunosorbent assay in a randomly selected subset of 50 mother-infant pairs where the mother had received MCV. At birth, 94.0% (47/50) of infants had MenA specific IgG levels ≥ 2 µg/mL decreasing to 72.9% and 30.4% at 3 and 6 months of age. For MenC, 81.3% (39/48) of infants had MenC specific IgG levels ≥ 2 µg/mL at birth decreasing to 29.4% and 17.8% at 3 and 6 months of age. For MenY, 89.6% (43/48) of infants had MenY specific IgG levels ≥ 2 µg/mL at birth decreasing to 64.6% and 62.5% at 3 and 6 months of age. For MenW, 89.6% (43/48) of infants had MenW specific IgG levels ≥ 2 µg/ml at birth decreasing to 62.5% and 41.7% at 3 and 6 months of age. Maternal immunization with MCV conveyed protective levels of IgG at birth through to 3 months of age in the majority of infants.

Drain fluid amylase as a sensitive biomarker for the early detection of anastomotic leakage in ileal pouch surgery.

AIM: We studied the levels of amylase in drain fluid to investigate its utility as a biomarker of anastomotic leak in ileal pouch patients who did not have a covering loop ileostomy. The luminal contents of the small intestine are high in amylase. Ileal J pouches are formed for restoration of continuity in patients with ulcerative colitis after removal of the colon and rectum. A drain is placed alongside the ileal pouch in the pelvis. METHOD: This study is a retrospective analysis of prospectively collected daily drain fluid amylase levels in consecutive patients undergoing restorative proctectomy and ileal J pouch anal anastomosis, without a covering loop ileostomy, between November 2016 and April 2018. RESULTS: Thirteen patients underwent surgery without a covering loop ileostomy. Two patients suffered an anastomotic leak and were returned to theatre, one on day 5 and the other on day 6 postoperatively. The mean daily drain fluid amylase level in those who did not leak was between 25 and 46 U/l with a range of 22-139 U/l for all samples collected. In the two patients who suffered a clinical leak the drain fluid amylase level rose to 22 432 and 10 212 U/l on the day of clinical leak diagnosis. The mean rectal tube (intraluminal) amylase level was 63 097 U/l as measured on day 1 postoperatively. CONCLUSION: In this small cohort of patients, the measurement of drain fluid amylase is a highly sensitive biomarker of clinical anastomotic leak.

Trochleoplasty with a flexible osteochondral flap: results from an 11-year series of 214 cases.

AIMS: The Bereiter trochleoplasty has been used in our unit for 12 years to manage recurrent patellar instability in patients with severe trochlea dysplasia. The aim of this study was to document the outcome of a large consecutive cohort of patients who have undergone this operation. PATIENTS AND METHODS: Between June 2002 and August 2013, 214 consecutive trochleoplasties were carried out in 185 patients. There were 133 women and 52 men with a mean age of 21.3 years (14 to 38). All patients were offered yearly clinical and radiological follow-up. They completed the following patient reported outcome scores (PROMs): International Knee Documentation Committee subjective scale, the Kujala score, the Western Ontario and McMaster Universities Arthritis Index score and the short-form (SF)-12. RESULTS: Outcomes were available for 199 trochleoplasties in 173 patients giving a 93% follow-up rate at a mean of 4.43 years (1 to 12). There were no infections or deep vein thromboses. In total, 16 patients reported further patella dislocation, giving an 8.3% rate of recurrence. There were 27 re-operations, giving a rate of re-operation of 14%. Overall, 88% were satisfied with the operation and 90% felt that their symptoms had been improved. CONCLUSION: All PROMs improved significantly post-operatively except for the mental component score of the SF-12. Trochleoplasty performed using a flexible osteochondral flap is an effective treatment for recurrent patellar instability in patients with severe trochlea dysplasia and gives good results in the medium term. Cite this article: Bone Joint J 2017;99-B:344-50.

Clinical and laboratory features of human herpesvirus 6 chromosomal integration.

Human herpesvirus 6 (HHV-6) comprises two separate viruses, HHV-6A and HHV-6B, although this distinction is not commonly made. HHV-6B is ubiquitous in the population with primary infection usually occurring in early childhood, and often resulting in febrile illness. HHV-6B is also recognized as a pathogen in the immunocompromised host, particularly in transplant recipients. HHV-6A is less well characterized and may have a more restricted prevalence. Both viruses are unique among the human herpesviruses in that the entire viral genome can be found integrated into the telomeric regions of host cell chromosomes. Approximately 1% of persons have inherited integrated viral sequences through the germline, and these individuals characteristically have very high viral loads in blood and other sample types. Emerging evidence suggests that HHV-6A and HHV-6B chromosomal integration may not just be an uncommon biological observation, but more likely a characteristic of the replication properties of these viruses. The integrated viral genome appears capable of excision from the chromosomal site and potentially allows viral replication. The clinical consequences of inherited chromosomally integrated HHV-6 have yet to be fully appreciated.

Comparison of five commercially available immunochromatographic tests for the detection of norovirus in faecal specimens.

Five CE-marked immunochromatography assay kits for the rapid detection of norovirus were compared with the reference method of real-time polymerase chain reaction (PCR) for the detection of acute norovirus infection. The sensitivity of the assays ranged between 23% and 59% with specificity being 75‒100% when compared with real-time PCR. The data suggest that a reactive immunochromatographic assay indicates norovirus infection. However, the sensitivity of the assay would need to be significantly improved to be suitable for routine diagnostic purposes or as an alternative to laboratory analysis for near-patient testing.

Supplementing lactating dairy cows fed high-quality pasture with black wattle (Acacia mearnsii) tannin.

A reduction in urinary nitrogen (N) excretion from dairy cows fed pasture containing a high N concentration in the dry matter (DM) will have environmental benefits, because losses to soil water and air by leachate and nitrous oxides (N2O) will be reduced. Condensed tannins (CT) reduce digestion of N, and provision as a dietary additive could have nutritional benefits for production, but the amount required and the responses to different sources of CT on milk production have not been defined. Two experiments were conducted to evaluate effects of supplementation with CT extracted from black wattle (Acacia mearnsii De Wild.) on milk production and faecal N concentration by lactating dairy cows grazing a vegetative Perennial ryegrass (Lolium perenne L.)-based pasture. In one experiment, CT was administered as a drench, twice daily, to 38 multiparous Holstein-Friesian cows assigned to four treatments; control (CONT, 0 g/day), low CT (LCT, 111 g/day), medium CT (MCT, 222 g/day) and high CT (HCT, 444 g/day), grazing as a single group. The CT supplementation affected milk yield (P < 0.001) with a trend of declining milk yield as CT concentration increased from about 0.6 to about 2.9% of dietary DM. Milk urea nitrogen (MUN) decreased at MCT and HCT levels of supplementation (P < 0.01) but milk fat, CP and lactose percentage were not affected by CT supplementation. The CT supplementation increased N concentration in faeces for LCT and MCT treatments (P < 0.05), suggesting partitioning of dietary N away from urine. When CT was pelleted with grain, in a second experiment and fed twice daily as a supplement at milking, it reduced the acceptability relative to pellets without CT, and tended to lower milk production from 25.4 to 24.5 kg/day, although the decline was not significant (P > 0.05). The diet of cows fed pellets with CT contained about 1.2% CT in the DM but neither milk constituents nor MUN were affected by CT-supplemented grain (P > 0.05). These findings demonstrate beneficial effects for production of low concentrations (c. 0.6% DM) of CT from black wattle when given to cows grazing pasture with an N concentration of 3.8%, and suggest a diversion of N from urine, but when CT exceeded about 1.4% of dietary DM, milk production was depressed. The value of supplementing a pasture diet for lactating dairy cows with black wattle tannin extract will depend on costs of supplementation, returns from milk production and liabilities associated with N losses to urine.

Surgical outcomes in steroid refractory acute severe ulcerative colitis: the impact of rescue therapy.

AIM: The advent of rescue medical therapy (cyclosporin or infliximab) and laparoscopic surgery has shifted the paradigm in managing steroid refractory acute severe ulcerative colitis (ASUC). We investigated prospectively the impact of rescue therapy on timing and postoperative complications of urgent colectomy and subsequent restorative surgery for steroid refractory ASUC. METHOD: All consecutive presentations of steroid refractory ASUC at the Royal Brisbane Hospital (1996-2009) were entered in the study. Data collated included demographics, clinical and laboratory parameters on admission, medical therapy and operative and postoperative details. Steroid refractory ASUC patients undergoing immediate colectomy were compared with those failing rescue therapy and requiring same admission colectomy. RESULTS: Of 108 steroid refractory ASUC presentations, 19 (18%) received intravenous steroids only and proceeded directly to colectomy. Rescue medical therapy was instituted in 89 (82%) patients with 30 (34%) failing to respond and proceeding to colectomy. There was no significant difference in the median time from admission to colectomy for rescue therapy compared with steroid-only cases (12 vs 10 days, P = 0.70) or 30-day complication rates (27%vs 47%, P = 0.22). The interval from colectomy to a subsequent restorative procedure was significantly longer for patients who failed rescue therapy (12 vs 5 months, P = 0.02). Furthermore 30-day complications following pouch surgery were significantly higher in patients who failed rescue therapy (32%vs 0%, P = 0.01). CONCLUSION: Rescue therapy in steroid refractory ASUC is not related to delay in urgent colectomy or increased post-colectomy complications.

The correct rotation of the femoral component in patellofemoral replacement: a laboratory assessment of a surgical technique.

Ensuring correct rotation of the femoral component is a challenging aspect of patellofemoral replacement surgery. Rotation equal to the epicondylar axis or marginally more external rotation is acceptable. Internal rotation is associated with poor outcomes. This paper comprises two studies evaluating the use of the medial malleolus as a landmark to guide rotation. We used 100 lower-leg anteroposterior radiographs to evaluate the reliability of the medial malleolus as a landmark. Assessment was made of the angle between the tibial shaft and a line from the intramedullary rod entry site to the medial malleolus. The femoral cut was made in ten cadaver knees using the inferior tip of the medial malleolus as a landmark for rotation. Rotation of the cut relative to the anatomical epicondylar axis was assessed using CT. The study of radiographs found the position of the medial malleolus relative to the tibial axis is consistent. Using the inferior tip of the medial malleolus in the cadaver study produced a mean external rotation of 1.6° (0.1° to 3.7°) from the anatomical epicondylar axis. Using the inferior tip of the medial malleolus to guide the femoral cutting jig avoids internal rotation and introduces an acceptable amount of external rotation of the femoral component.

The ideal ileal-pouch design: a long-term randomized control trial of J- vs W-pouch construction.

BACKGROUND: The IPAA has become established as the preferred technique for restoring intestinal continuity postproctocolectomy. The ideal pouch design has not been established. W-pouches may give better functional results owing to increased volume, whereas the J-pouch's advantage is its straightforward construction. We report short- and long-term results of an randomized control trial designed to establish the ideal pouch. DESIGN: Ninety-four patients were randomly assigned to J- and W-pouches (49:45) and assessed at 1 and 8.7 years postoperatively. Assessment was questionnaire based and designed to assess pouch function and patient quality of life. RESULTS: Eighty-five percent of patients were followed up at 1 year, and 68% were followed up at 8.7 years. At 1 year, there was a significant difference in 24-hour bowel movement frequency J- vs W-pouches 7 vs 5(p < 0.001) and in daytime frequency J- vs W-pouches 6 vs 4 (p < 0.001), with no difference in nocturnal function. At 9-year follow-up, function had equilibrated between the 2 groups: 24-hour bowel movement frequency J- vs W-pouches 6.5 vs 6 (p = 0.36), daytime frequency 5.5 vs 5 (p = 0.233), and nocturnal function 1 vs 1 (p = 0.987). Mean operating time of J- and W-pouches was 195 and 215 minutes (p < 0.05). All other parameters, pad usage, urgency, incontinence, and quality of life, did not differ significantly between groups. CONCLUSION: These data demonstrate that the theoretical functional advantage conferred on the W-pouch by its greater volume exists only in the short term and is of little consequence to patients' long-term quality of life. This advantage is attenuated as the pouches mature, resulting in no disparity in pouch function. This, combined with the more consistent, efficient, and easily taught construction of the J-pouch, should conclusively establish it as the optimum ileal-pouch design.

Comparison of the QIAGEN artus HIV-1 QS-RGQ test with the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 test v2.0.

BACKGROUND: Regular HIV-1 viral load monitoring is standard of care in the developed world for patients infected with HIV-1. OBJECTIVES: Here we report a comparative evaluation of the established Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 v2.0 test (Roche Diagnostics Ltd, Burgess Hill, UK) and the new artus HIV-1 QS-RGQ test (QIAGEN Ltd, Crawley, UK). STUDY DESIGN: 169 clinical EDTA-plasma samples were tested, all of known HIV-1 subtype. RESULTS: The mean overall log(10)c/ml difference was 0.10 (QIAGEN - Roche). CONCLUSION: The artus HIV-1 QS-RGQ test compared well with the Roche TaqMan HIV-1 v2.0 test, and Bland-Altman analysis showed good agreement between the two systems across a wide range of subtypes.

The relationship between milk production and farm-gate nitrogen surplus for the Waikato region, New Zealand.

As the scope and scale of New Zealand (NZ) dairy farming increases, farmers and the industry are being challenged by Government and the New Zealand public to address growing environmental concerns. Dairying has come under increasing scrutiny from local authorities tasked with sustainable resource management. Despite recent efforts of farmers and industry to improve resource use efficiency, there is increasing likelihood of further regulatory constraints on water use and nutrient management. This study uses available data on farm-gate nitrogen (N) surpluses and milk production from the Waikato, New Zealand's largest dairying region, together with a farm scale modeling exercise, to provide a perspective on the current situation compared to dairy farms in Europe. It also aims to provide relevant guidelines for N surpluses and efficiencies under NZ conditions. Waikato dairy farms compare favorably with farms in Europe in terms of N use efficiency expressed as L milk/kg farm-gate N surplus. Achievable and realistic good practice objectives for Waikato dairy farmers could be 15,000 L milk/ha (1200 kg milk fat plus protein/ha) with a farm-gate N surplus of 100 kg/ha giving an eco-efficiency (L milk/kg N surplus) of 150, and long-term average nitrate leaching losses of approximately 25-30 kg/ha/yr. This can be achieved by increasing the N conversion efficiency through lower replacement rates (16 versus 22%), lower stocked (< 3 cows/ha) high genetic merit cows (30 L milk/day at peak) milked for longer (277 versus 240 days), feeding effluent-irrigated, home-grown, low-protein supplements to cows on high-protein, grass-clover pastures to dilute N concentration in the diet, removing some of the urinary N from the paddocks during critical times by standing cows on a loafing pad for part of the day, and through lower N fertilizer rates (50-70 kg/ha/yr compared to the norm of 170-200 kg/ha/yr) and using a nitrification inhibitor and gibberellins to boost pasture growth and the former to reduce N leaching.

Nosocomial transmission of parainfluenza 3 virus in hematological patients characterized by molecular epidemiology.

We report an outbreak of parainfluenza 3 virus involving 17 hematology-oncology patients on 2 hospital wards. Sequence analysis of clinical samples confirmed homology of strains for 16/17 patients and 1 healthcare worker. Epidemiological analysis of the outbreak supported the molecular data with nosocomial transmission of the same genetic strain as the cause of the outbreak.

The prothrombinase activity of FGL2 contributes to the pathogenesis of experimental arthritis.

OBJECTIVE: Fibrin deposition is integral to the pathogenesis of collagen-induced arthritis (CIA), an experimental model of rheumatoid arthritis (RA). Membrane-associated fibrinogen-like protein 2 (mFGL2), a novel inducible prothrombinase, generates fibrin by an alternate pathway and has been reported to be involved in the pathogenesis of a number of immune-mediated diseases. We hypothesized that expression of mFGL2 in inflamed synovium contributes to the fibrin deposition and subsequent inflammation in arthritis. METHODS: DBA/1 mice were immunized with 100 µg bovine collagen type II (CII) emulsified in complete Freund's adjuvant (CFA) followed by lipopolysaccharide (LPS) injection. Expression of mFGL2 prothrombinase in association with fibrin deposition was examined in mice with CIA and CD200-treated mice following induction of CIA. To directly assess the contribution of mFGL2, fgl2(-/-) mice were injected with antibody to CII (anti-CII). RESULTS: Levels of fgl2 mRNA transcripts and mFGL2 protein were markedly up-regulated in joints of mice that developed CIA. Fibrin deposition was prominent within the synovial lining and articular joint space associated with expression of mFGL2. Inhibition of CIA by the immunosuppressant CD200 was associated with decreased expression of fgl2 mRNA and mFGL2 protein and absence of fibrin deposition. Following injection of anti-CII, all fgl2(+/+) mice developed severe arthritis with clinical and histological manifestations characteristic of RA, whereas fgl2(-/-) mice failed to develop any clinical manifestation or histological evidence of arthritis. CONCLUSIONS: This study demonstrates that the prothrombinase activity of mFGL2 contributes to the pathogenesis of experimental arthritis. These studies may have therapeutic implications for patients with RA.

Laparoscopic resection of advanced colorectal cancer.

BACKGROUND: Palliative resection of the primary tumour in asymptomatic patients with stage IV colorectal cancer is associated with improved survival and fewer complications. Laparoscopic surgery is widely employed in the curative treatment of colorectal cancer, but its value in advanced colorectal cancer remains unclear. METHODS: All patients who underwent laparoscopic resection of primary colorectal cancer in this unit between June 1991 and Jan 2010 were entered into a prospective computerized database. Outcomes for patients with laparoscopic resection of stage IV colorectal cancer were compared with those of patients who had laparoscopic surgery for stage I disease. RESULTS: Some 185 patients with stage IV colorectal cancer who underwent laparoscopic resection were compared with 310 patients who had stage I colorectal cancer. Some 94·1 and 98·4 per cent of operations respectively were completed laparoscopically. Hospital stay was slightly longer in the group with stage IV disease (mean 6·2 versus 5·3 days; P = 0·091). The 30-day mortality rate was 2·7 per cent in patients with stage IV disease and 0·6 per cent in those with stage I tumours (P = 0·061). There was no difference in complications. One-year survival rates were 77·8 and 99·0 per cent respectively (P < 0·001). CONCLUSION: Short-term outcomes after laparoscopic surgery for stage IV colorectal cancer in selected patients are equivalent to those for stage I cancers.

Salvage of a failed Sauve-Kapandji procedure using a total distal radio-ulnar joint replacement.

This is the first report in the literature of a patient treated with a DRUJ replacement after Sauvé-Kapandji procedure failed due to pain and instability. The DRUJ replacement is an unconstrained, biomechanically more advantageous implant which can confer stability in cases where soft tissues are inadequate. We describe the treatment and outcome of persistent ulnar instability with a distal radio-ulnar joint replacement following failed salvage procedures for a malunion of a distal radius fracture.

Upper limb deep vein thrombosis: a potentially fatal complication of a clavicle fracture.

We present a case a 48-year-old man who was diagnosed with an upper limb deep vein thrombosis post clavicle fracture. He was successfully investigated with a computed tomography (CT) venogram, thrombophilia was excluded, and he was subsequently treated with a 3-month course of anticoagulation. We illustrate this case with photographs and a three-dimensional colour reconstruction of a CT venogram to raise awareness of the condition. A suitable level of clinical suspicion should be maintained by the orthopaedic surgeon; delayed arm swelling with venous congestion following a clavicle fracture should be investigated with CT venography and thrombophilia should be excluded.

Effects of reduced frequency of milk removal on gene expression in the bovine mammary gland.

Regulation of milk synthesis and secretion is controlled mostly through local (intramammary) mechanisms. To gain insight into the molecular pathways comprising this response, an analysis of mammary gene expression was conducted in 12 lactating cows shifted from twice daily to once daily milking. Tissues were sampled by biopsy from adjacent mammary quarters of these animals during the two milking frequencies, allowing changes in gene expression to be assessed within each animal. Using bovine-specific, oligonucleotide arrays representing 21,495 unique transcripts, a range of differentially expressed genes were found as a result of less frequent milk removal, constituting transcripts and pathways related to apoptotic signaling (NF-kappaB, JUN, ATF3, IGFBP5, TNFSF12A) mechanical stress and epithelial tight junction synthesis (CYR61, CTGF, THBS1, CLDN4, CLDN8), and downregulated milk synthesis (LALBA, B4GALT1, UGP2, CSN2, GPAM, LPL). Quantitative real-time PCR was used to assess the expression of 13 genes in the study, and all 13 of these were correlated (P < 0.05) with values derived from array analysis. It can be concluded that the physiological changes that occur in the bovine mammary gland as a result of reduced milk removal frequency likely comprise the earliest stages of the involution response and that mechano-signal transduction cascades associated with udder distension may play a role in triggering these events.

Humoral immune response to EBV in multiple sclerosis is associated with disease activity on MRI.

BACKGROUND: Evidence suggests that Epstein-Barr virus (EBV) plays a role in triggering or perpetuating disease activity in multiple sclerosis (MS). METHODS: We investigated 100 subjects (50 clinically isolated syndrome [CIS], 25 relapsing-remitting [RR] MS, 25 primary progressive [PP] MS) for 1) evidence of EBV reactivation and 2) disease activity as indicated by serial gadolinium (Gd)-enhanced MRIs over a 5-year period. EBV DNA in blood was quantified by real-time quantitative PCR and EBV serology for anti-Epstein-Barr virus nuclear antigen 1 (EBNA-1) immunoglobulin G (IgG), anti-viral capsid antigen (VCA) IgG, and anti-EBV IgM. Data were analyzed using repeated measures analysis, analysis of variance, and logistic regression analysis. RESULTS: All subjects had serologic evidence of previous EBV infection, but no lytic reactivation was detected. Significant differences in EBNA-1 IgG titers were found between subgroups, highest in the RRMS cohort compared with PPMS (p < 0.001) and CIS (p < 0.001). Gd-enhancing lesions on MRI correlated with EBNA-1 IgG (r = 0.33, p < 0.001) and EBNA-1:VCA IgG ratio (r = 0.36, p < 0.001). EBNA-1 IgG also correlated with change in T2 lesion volume (r = 0.27, p = 0.044) and Expanded Disability Status Scale score (r = 0.3, p = 0.035). CONCLUSIONS: The correlation between elevated Epstein-Barr virus nuclear antigen 1 (EBNA-1) immunoglobulin G (IgG) and gadolinium-enhancing lesions suggests an association between Epstein-Barr virus (EBV) infection and multiple sclerosis (MS) disease activity. The heightened immune response to EBV in MS is specifically related to EBNA-1 IgG, a marker of the latent phase of the virus. The lack of association between acute viral reactivation in the peripheral blood and Gd(+) lesions suggests a limited role of the former in driving disease activity.