Deirdre MacManus

Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H

Background: To assess the long-term effect of the lymphocyte-depleting humanized monoclonal antibody Campath 1H on MR markers of disease activity and progression in secondary progressive MS patients. Methods: Twenty-five patients participated in a crossover treatment trial with monthly run-in MR scans for 3 months, followed (after a single pulse of Campath 1H) by monthly MR scans from months 1 to 6 and again from months 12 to 18. MR analysis was performed to provide measurements of the number and volume of gadolinium (Gd)-enhancing lesions as well as the hypointense lesion volume on a T1-weighted sequence. In addition, serial measurements of T2 brain lesion volume, brain volume, and spinal cord cross-sectional area were made over the duration of the study. The relationship between clinical and MR measures of disease evolution was also assessed. Results: Treatment was associated with a reduction in the number and volume of Gd-enhancing lesions (p < 0.01). Despite this, a decrease in brain volume was seen in 13 patients during the 18 months post-treatment. The mean pretreatment Gd-enhancing lesion volume was predictive of subsequent reduction in brain volume (r = 0.77, p = 0.002). Reduction in brain volume also correlated with the change in T1 hypointense lesion volume after treatment (r = 0.53, p < 0.01). A reduction in spinal cord area was also seen throughout the study duration, and this correlated with an increase in disability (r = 0.65, p = 0.01). Conclusion: Campath 1H treatment was associated with a sustained and marked reduction in the volume of Gd enhancement, indicating suppression of active inflammation. Nevertheless, many patients developed increasing brain and spinal cord atrophy, T1 hypointensity, and disability. This study highlights the potential role for novel MR techniques in monitoring the effect of treatment on the pathologic process in MS.

Violent offending by UK military personnel deployed to Iraq and Afghanistan: a data linkage cohort study

BACKGROUND Violent offending by veterans of the Iraq and Afghanistan conflicts is a cause for concern and there is much public debate about the proportion of ex-military personnel in the criminal justice system for violent offences. Although the psychological effects of conflict are well documented, the potential legacy of violent offending has yet to be ascertained. We describe our use of criminal records to investigate the effect of deployment, combat, and post-deployment mental health problems on violent offending among military personnel relative to pre-existing risk factors. METHODS In this cohort study, we linked data from 13,856 randomly selected, serving and ex-serving UK military personnel with national criminal records stored on the Ministry of Justice Police National Computer database. We describe offending during the lifetime of the participants and assess the risk factors for violent offending. FINDINGS 2,139 (weighted 17.0%) of 12,359 male UK military personnel had a criminal record for any offence during their lifetime. Violent offenders (1,369 [11.0%]) were the most prevalent offender types; prevalence was highest in men aged 30 years or younger (521 [20.6%] of 2,728) and fell with age (164 [4.7%] of 3027 at age >45 years). Deployment was not independently associated with increased risk of violent offending, but serving in a combat role conferred an additional risk, even after adjustment for confounders (violent offending in 137 [6.3%] of 2178 men deployed in a combat role vs 140 (2.4%) of 5,797 deployed in a non-combat role; adjusted hazard ratio 1.53, 95% CI 1.15-2.03; p=0.003). Increased exposure to traumatic events during deployment also increased risk of violent offending (violent offending in 104 [4.1%] of 2753 men with exposure to two to four traumatic events vs 56 [1.6%] of 2944 with zero to one traumatic event, 1.77, 1.21-2.58, p=0.003; and violent offending in 122 [5.1%] of 2582 men with exposure to five to 16 traumatic events, 1.65, 1.12-2.40, p=0.01; test for trend, p=0.032). Violent offending was strongly associated with post-deployment alcohol misuse (violent offending in 120 [9.0%] of 1363 men with alcohol misuse vs 155 [2.3%] of 6768 with no alcohol misuse; 2.16, 1.62-2.90; p<0.0001), post-traumatic stress disorder (violent offending in 25 [8.6%] of 344 men with post-traumatic stress disorder vs 221 [3.0%] of 7256 with no symptoms of post-traumatic stress disorder; 2.20, 1.36-3.55; p=0.001), and high levels of self-reported aggressive behaviour (violent offending in 56 [6.7%] of 856 men with an aggression score of six to 16 vs 22 [1.2%] of 1685 with an aggression score of zero; 2.47, 1.37-4.46; p=0.003). Of the post-traumatic stress disorder symptoms, the hyperarousal cluster was most strongly associated with violent offending (2.01, 1.50-2.70; p<0.0001). INTERPRETATION Alcohol misuse and aggressive behaviour might be appropriate targets for interventions, but any action must be evidence based. Post-traumatic stress disorder, though less prevalent, is also a risk factor for violence, especially hyperarousal symptoms, so if diagnosed it should be appropriately treated and associated risk monitored. FUNDING Medical Research Council and the UK Ministry of Defence.

MRI of the optic nerve in benign intracranial hypertension

Abstract We investigated the MRI appearance of the optic nerve and its cerebrospinal-fluid-containing sheath in 17 patients with benign intracranial hypertension (BIH) and 15 normal controls. Using phased-array local coils, 3-mm coronal T2-weighted fat-suppressed fast spin-echo images were obtained with an in-plane resolution of < 0.39 mm. The optic nerve and its sheath were clearly differentiated. An enlarged, elongated subarachnoid space around the optic nerve was demonstrated in patients with BIH. High-resolution MRI of the optic nerve offers additional information which may be of value for diagnosis and in planning and monitoring treatment.

Violent behaviour in UK military personnel returning home after deployment

BACKGROUND There is growing concern about an alleged rise in violent behaviour amongst military personnel returning from deployment to Iraq and Afghanistan. The aims of this study were to determine the prevalence of violence in a sample of U.K. military personnel following homecoming from deployment in Iraq and to examine the impact of deployment-related experiences, such as combat trauma, on violence, and the role of sociodemographics and pre-enlistment antisocial behaviour. METHOD This study used baseline data from a cohort study of a large randomly selected sample of U.K. Armed Forces personnel in service at the time of the Iraq war (2003). Regular personnel (n=4928) who had been deployed to Iraq were included. Data, collected by questionnaire, included information on deployment experiences, sociodemographic and military characteristics, pre-enlistment antisocial behaviour, post-deployment health outcomes and a self-report measure of physical violence in the weeks following return from deployment. RESULTS Prevalence of violence was 12.6%. This was strongly associated with pre-enlistment antisocial behaviour [adjusted odds ratio (aOR) 3.6, 95% confidence interval (CI) 2.9-4.4]. After controlling for pre-enlistment antisocial behaviour, sociodemographics and military factors, violence was still strongly associated with holding a combat role (aOR 2.0, 95% CI 1.6-2.5) and having experienced multiple traumatic events on deployment (aOR for four or more traumatic events 3.7, 95% CI 2.5-5.5). Violence on homecoming was also associated with mental health problems such as post-traumatic stress disorder (aOR 4.8, 95% CI 3.2-7.2) and alcohol misuse (aOR 3.1, 95% CI 2.5-3.9). CONCLUSIONS Experiences of combat and trauma during deployment were significantly associated with violent behaviour following homecoming in U.K. military personnel. Post-deployment mental health problems and alcohol misuse are also associated with increased violence.

Lesion discrimination in optic neuritis using high-resolution fat-suppressed fast spin-echo MRI

Fast spin-echo (FSE) is a new sequence with acquisition times currently down to one-sixteenth of those obtained with conventional spin-echo sequences, which allows high-resolution (512×512 matrix) images to be acquired in an acceptable time. We compared the higher resolution of FSE with the medium resolution of a short inversion-time inversion-recovery (STIR) sequence in depicting the optic nerves of healthy controls and patients with optic neuritis. Optic nerve MRI examinations were performed in 18 patients with optic neuritis and 10 normal controls. Two sequences were obtained coronally: fat-suppressed FSE (FSE TR 3250 ms/TEef 68 ms, echo-train length 16, 4 excitations, 24 cm rectangular field of view, 3 mm interleaved contiguous slices, in-plane resolution 0.5×0.5 mm) and STIR (TR 2000 ms/TE 50 ms/TI 175 ms, inplane resolution 0.8×0.8 mm, slice thickness 5 mm). FSE demonstrated much more anatomical detail than STIR, e. g. distinction of optic nerve and sheath. Lesions were seen in 20 of 21 symptomatic nerves using FSE and in 18 of 21 using STIR. Nerve swelling or partial cross-sectional lesions of the optic nerve were each seen only on FSE in 3 cases. Fatsuppressed FSE imaging of the optic nerve improves anatomical definition and increases lesion detection in optic neuritis.

Clinical-MRI correlations in a European trial of interferon beta-1b in secondary progressive MS

Background: The recently completed placebo-controlled multicenter randomized trial of interferon beta-1b (Betaferon) in 718 patients with secondary progressive MS shows significant delay of disease progression and reduction of relapse rate. This study provides an opportunity to assess the level of relationship between clinical and MRI outcomes in this cohort of patients with secondary progressive MS. Methods: Brain T2-weighted lesion volume was measured annually in all available patients, with visual analysis to identify any new or enlarging (active) T2 lesions at each annual time point. A subgroup of 125 patients had monthly gadolinium-enhanced, T1-weighted imaging at months 0 to 6 and 18 to 24. Relapses were documented and expanded disability status scale (EDSS) was measured every 3 months. Results: For the annual MRI outcomes, a significant but modest correlation was identified between the change in T2 lesion volume from baseline to the final scan and the corresponding change from baseline in EDSS (r = 0.17, p < 0.0001). There were significant correlations between the cumulative number of active T2 lesions and 1) change in EDSS (r = 0.18, p < 0.0001) and 2) relapse rate (r = 0.24, p < 0.0001). In the subgroup of 125 patients undergoing monthly imaging, MRI lesion activity was correlated with relapse rate over months 0 to 24 (r = 0.24, p = 0.006) but not with change in EDSS. Conclusions: These results confirm that the clinical–MRI relationships previously identified in relapsing-remitting MS still are apparent in the secondary progressive phase of the disease and support the use of MRI as a relevant outcome measure. In view of the relatively modest nature of the correlations, it seems unwise to rely on such MRI measures alone as primary efficacy variables in secondary progressive MS trials.

Mental health and health service use among post-national service veterans: results from the 2007 Adult Psychiatric Morbidity Survey of England

BACKGROUND There is concern surrounding the psychological health and uptake of treatment services among veterans of the UK Armed Forces. METHOD Data from a cross-sectional, nationally representative sample were used to compare health outcomes and treatment seeking among 257 post-national service veterans aged 16-64 years and 504 age and sex frequency-matched non-veterans living in the community in England. Early leavers (<4 years service) were compared with longer serving veterans. RESULTS Male veterans reported more childhood adversity and were more likely to have experienced a major trauma in adulthood than non-veterans. There was no association between any measure of mental health and veteran status in males, except reporting more violent behaviours [adjusted odds ratio (aOR) 1.44, 95% confidence interval (CI) 1.01-2.06]. In females, a significant association was found between veteran status and ever having suicidal thoughts (aOR 2.82, 95% CI 1.13-7.03). No differences in treatment-seeking behaviour were identified between veterans and non-veterans with any mental disorder. Early service leavers were more likely to be heavy drinkers (aOR 4.16, 95% CI 1.08-16.00), to have had suicidal thoughts (aOR 2.37, 95% CI 1.21-4.66) and to have self-harmed (aOR 12.36, 95% CI 1.61-94.68) than longer serving veterans. CONCLUSIONS The findings of this study do not suggest that being a veteran is associated with adversity in terms of mental health, social disadvantage or reluctance to seek treatment compared with the general population. Some evidence implies that early service leavers may experience more mental health problems than longer-serving veterans.

Aggressive and Violent Behavior Among Military Personnel Deployed to Iraq and Afghanistan: Prevalence and Link With Deployment and Combat Exposure

A systematic review and meta-analyses were conducted on studies of the prevalence of aggressive and violent behavior, as well as of violent offenses and convictions, among military personnel following deployment to Iraq and/or Afghanistan; the relationship with deployment and combat exposure; and the role that mental health problems, such as post-traumatic stress disorder (PTSD), have on the pathway between deployment and combat to violence. Seventeen studies published between January 1, 2001, and February 12, 2014, in the United States and the United Kingdom met the inclusion criteria. Despite methodological differences across studies, aggressive behavior was found to be prevalent among serving and formerly serving personnel, with pooled estimates of 10% (95% confidence interval (CI): 1, 20) for physical assault and 29% (95% CI: 25, 36) for all types of physical aggression in the last month, and worthy of further exploration. In both countries, rates were increased among combat-exposed, formerly serving personnel. The majority of studies suggested a small-to-moderate association between combat exposure and postdeployment physical aggression and violence, with a pooled estimate of the weighted odds ratio = 3.24 (95% CI: 2.75, 3.82), with several studies finding that violence increased with intensity and frequency of exposure to combat traumas. The reviews findings support the mediating role of PTSD between combat and postdeployment violence and the importance of alcohol, especially if comorbid with PTSD.

Impact of pre-enlistment antisocial behaviour on behavioural outcomes among UK military personnel

PurposeConcern has been raised over alleged increases in antisocial behaviour by military personnel returning from the deployment in Iraq and Afghanistan. US-based research has shown that post-deployment violence is related not only to combat experience, but also to pre-enlistment antisocial behaviour (ASB). This study aimed to examine the association between pre-enlistment ASB and later behavioural outcomes, including aggression, in a large randomly selected UK military cohort.MethodsBaseline data from a cohort study of 10,272 UK military personnel in service at the time of the Iraq war in 2003 were analysed. The associations between pre-enlistment ASB and a range of socio-demographic and military variables were examined as potential confounders. Logistic regression analyses were performed to examine the relationship between pre-enlistment ASB and military behavioural outcomes such as severe alcohol use, violence/aggression and risk-taking behaviour, controlling for confounders.Results18.1% were defined as having displayed pre-enlistment ASB. Pre-enlistment ASB was significantly associated with factors such as younger age, low educational achievement, male gender, non-officer rank, Army personnel, being a regular, increasing time spent on the deployment and having a combat role. Pre-enlistment ASB was associated with increased risk of negative behavioural outcomes (severe alcohol misuse, outbursts of anger or irritability, fighting or assaultative behaviour and risk-taking behaviour), after controlling for confounders, suggesting that such background information may identify individuals who are more vulnerable to subsequent behavioural disturbance.ConclusionThe results of this study suggest that those already demonstrating ASB prior to joining the military are more likely to continue on this trajectory, thus emphasising the importance of considering pre-enlistment behaviour when exploring the aetiology of aggression in military personnel.

Veteran mental health services in the UK: Are we headed in the right direction?

King’s Centre for Military Health and Research, King’s College London,London, UKApproximately 10% of the UK Armed Forces, equivalent to 20 000 service personnel, leavethe military each year (DASA, 2007). For most individuals, service in the Armed Forces isbeneficial but a minority have a bleaker outlook as a result of health, behaviour and socialproblems, some of which are related to their experiences in military service (Hatch et al.,2013; Iversen et al., 2009; MacManus et al., 2012a, 2013; Rowe et al., 2013). Specifichealth care for veterans is a relatively recent development in the UK, but it has been inplace in other countries such as the USA for many years. The US systems developed afterWorld War I and developed significantly in response to the needs of the veteran populationin the aftermath of the Vietnam conflict. Indeed, that the current budget for the US Depart-ment of Veteran Affairs for an estimated population of 23 million veterans is roughly equiv-alent to that of the entire NHS emphasisesthe priority given toveteran health care in the US.Individuals who have served in the armed forces of the United States may be eligible for abroad range of mental health services provided by the US Department of Veterans Affairs(VA) (Kizer et al., 1997). However, despite the VA operating the nation’s largest integratedmental healthcare system, with more than 1400 sites of care, the majority of veterans still donot accessthese services (Goffman, 1963). The VA policy isto continue to increase its acces-sibility and address barriers to care (James & Woods, 2010), and in 2012 President Obamasigned an Executive Order that pledged to improve accessto mental health services for veter-ans, service members, and military families.Such impetus for veteran care in the UK arrived much later than in the US. The muchpublicised physical and psychological burden placed on the UK Armed Forces by the con-flicts in Iraq and Afghanistan (Caesar, 2010; King, 2009) has led to increased awarenessof the problems faced by some veterans. International estimates of the prevalence ofmental health problems among military personnel vary (Milliken et al., 2007; Sundinet al., 2010). Studies of UK military personnel have shown that depression, anxiety andalcohol misuse disorders are most prevalent (Iversen et al., 2009; Murphy et al., 2008),