Fibromyalgia and chronic fatigue syndrome: management issues.

Fibromyalgia and chronic fatigue syndrome represent two of the most commonly encountered functional somatic syndromes in clinical practice. Both have been contentious diagnoses in the past, and this diagnostic dispute has resulted in a therapeutic nihilism that has been of great detriment to their management and to alleviation of the intense suffering and disability that they have caused their innumerable sufferers. A new age has dawned in terms of a better understanding of these syndromes' physiology and improved approaches to their management. Here, the diagnosis and management of these closely related disorders are discussed, with particular reference to the recent empirical evidence that has come to light as a consequence of neurophysiological insights and robustly designed randomised clinical trials. Much work remains to be done in this vein, but we are better placed to facilitate recovery from these disorders than we have been previously. Whilst remission should always be a goal, complete symptom resolution is not the norm, but 'moderate' improvements are certainly attainable with appropriate management.

Mild cognitive impairment with associated inflammatory and cortisol alterations as independent risk factor for postoperative delirium.

AIMS: The present study aimed to determine the impact of mild cognitive impairment (MCI) on the development of postoperative delirium and, secondly, to assess the association between MCI and raised perioperative cortisol, cytokine, cobalamin and homocysteine levels. METHODS: The study recruited 113 consecutive adult patients scheduled for cardiac surgery with cardiopulmonary bypass. The patients were examined preoperatively with the Montreal Cognitive Assessment and Trail Making Test. A diagnosis of MCI was established based upon the criteria of the National Institute on Aging and Alzheimer's Association. Patients were screened for delirium within the first 5 days postoperatively. RESULTS: MCI was diagnosed in 24.8% of the patients, whereas the frequency of delirium was 36%. A multivariate analysis demonstrated that individuals with MCI were at a significantly higher risk of postoperative delirium (OR = 6.33, p = 0.002). Preoperative cortisol, postoperative cortisol and IL-2 plasma levels were higher in the MCI group as compared to non-MCI subjects. CONCLUSION: MCI is associated with a higher risk of postoperative delirium. Perioperative cortisol and inflammatory alterations observed in MCI may provide a physiological explanation for this increased risk.

Raised IL-2 and TNF-α concentrations are associated with postoperative delirium in patients undergoing coronary-artery bypass graft surgery.

BACKGROUND: The knowledge base regarding the pathogenesis of postoperative delirium is limited. The primary aim of this study is to investigate whether increased levels of IL-2 and TNF-α are associated with delirium in patients who underwent coronary-artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB). The secondary aim is to establish whether any association between raised cytokine levels and delirium is related to surgical and anesthetic procedures or mediated by pre-existing conditions associated with raised cytokine levels, such as major depressive disorder (MDD), cognitive impairment, or aging. METHODS: Patients were examined and screened for MDD and cognitive impairment one day preoperatively, using the Mini International Neuropsychiatric Interview and The Montreal Cognitive Assessment and Trail Making Test Part B. Blood samples were collected postoperatively for cytokine levels. RESULTS: Postoperative delirium screening was found positive in 36% (41 of 113) of patients. A multivariate logistic regression revealed that an increased concentration of pro-inflammatory cytokines is associated with delirium, and related to advancing age, preoperative cognitive decline of participants, and duration of CPB. According to receiver operating characteristic analysis, the most optimal cut-off for IL-2 and TNF-α concentrations in predicting the development of delirium were 907.5 U/ml and 10.95 pg/ml, respectively. CONCLUSIONS: The present study suggests that raised postoperative cytokine concentrations are associated with delirium after CABG surgery. Postoperative monitoring of pro-inflammatory markers combined with regular surveillance may be helpful in the early detection of postoperative delirium in this patient group.

Cortisol levels and neuropsychiatric diagnosis as markers of postoperative delirium: a prospective cohort study.

INTRODUCTION: The pathophysiology of delirium after cardiac surgery is largely unknown. The purpose of this study was to investigate whether increased concentration of preoperative and postoperative plasma cortisol predicts the development of delirium after coronary artery bypass graft surgery. A second aim was to assess whether the association between cortisol and delirium is stress related or mediated by other pathologies, such as major depressive disorder (MDD) or cognitive impairment. METHODS: The patients were examined 1 day preoperatively with the Mini International Neuropsychiatric Interview and the Montreal Cognitive Assessment and the Trail Making Test to screen for depression and for cognitive impairment, respectively. Blood samples for cortisol levels were collected both preoperatively and postoperatively. The Confusion Assessment Method for the Intensive Care Unit was used within the first 5 days postoperatively to screen for a diagnosis of delirium. RESULTS: Postoperative delirium developed in 36% (41 of 113) of participants. Multivariate logistic regression analysis revealed two groups independently associated with an increased risk of developing delirium: those with preoperatively raised cortisol levels; and those with a preoperative diagnosis of MDD associated with raised levels of cortisol postoperatively. According to receiver operating characteristic analysis, the most optimal cutoff values of the preoperative and postoperative cortisol concentration that predict the development of delirium were 353.55 nmol/l and 994.10 nmol/l, respectively. CONCLUSION: Raised perioperative plasma cortisol concentrations are associated with delirium after coronary artery bypass graft surgery. This may be an important pathophysiological consideration in the increased risk of postoperative delirium seen in patients with a preoperative diagnosis of MDD.

Irritable bowel syndrome in the UK military after deployment to Iraq: what are the risk factors?

PURPOSE: Diarrhoea and vomiting (D & V) was common in military personnel during deployment to the initial phases of the Iraq war. D & V is an established risk factor for irritable bowel syndrome (IBS). This study examined the prevalence of IBS in a military sample with a history of deployment to Iraq and the association between D & V and common mental disorder (CMD) with IBS. METHODS: The study used data from a two-phase cohort study of military/personnel. The sample was restricted to individuals who had been deployed to Iraq before phase 1 of the study and who had completed the self-report D & V question. A measure of probable IBS was derived at both phases of the study based on self-reported symptoms in the previous month. CMD was assessed by the General Health Questionnaire (GHQ-12). RESULTS: Fifty-nine percent of the sample reported a D & V event and 6.6 % met the criteria for probable IBS at phase 1. Reporting D & V, thinking one might be killed on deployment, poor physical health and CMD were associated with probable IBS at phase 1. CMD at phase 1 was strongly associated with chronic symptoms of IBS. CONCLUSIONS: There was a high prevalence of D & V during deployment to the early stages of the Iraq war, yet the prevalence of probable IBS on return from deployment was relatively low. D & V was strongly associated with IBS after deployment, and CMD was a risk factor for chronic symptoms of IBS.

Central sensitisation in chronic fatigue syndrome and fibromyalgia; a case control study.

INTRODUCTION: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are both complex conditions that are challenging to treat. This may be related to an incomplete understanding of their pathophysiology, itself obfuscated by their heterogeneity. The symptomatic overlap between them and their common comorbidity suggests a shared vulnerability, which might be explained by central sensitisation. METHODS: 19 CFS cases, 19 FM cases and 20 age and sex matched healthy controls (HC) were recruited primarily from secondary care clinics in London. Those with other pain disorders, psychiatric diagnoses and those taking centrally acting or opiate medications were excluded. Participants were asked to abstain from alcohol and over the counter analgaesia 48 h prior to assessment by static and dynamic quantitative sensory tests, including measures of temporal summation (TS) and conditioned pain modulation (CPM). RESULTS: CS, as defined by the presence of both enhanced TS and inefficient CPM, was present in 16 (84%) CFS cases, 18 (95%) FM cases, and none of the HC (p < 0.001). Pressure pain thresholds were lower in CFS (Median222kPaIQR 146-311; p = 0.04) and FM cases (Median 189 kPa; IQR 129-272; p = 0.003) compared to HC (Median 311 kPa; IQR 245-377). FM cases differed from HC in cold-induced (FM = 22.6 °C (15.3-27.7) vs HC = 14.2 °C (9.0-20.5); p = 0.01) and heat-induced (FM = 38.0 °C (35.2-44.0) vs HC = 45.3 °C (40.1-46.8); p = 0.03) pain thresholds, where CFS cases did not. CONCLUSION: Central sensitisation may be a common endophenotype in chronic fatigue syndrome and fibromyalgia. Further research should address whether central sensitisation is a cause or effect of these disorders.

Depression in Dementia or Dementia in Depression? Systematic Review of Studies and Hypotheses.

The majority of research works to date suggest that Major Depressive Disorder (MDD) is a risk factor for dementia and may predispose to cognitive decline in both early and late onset variants. The presence of depression may not, however, reflect the cause, rather, an effect: it may be a response to cognitive impairment or alters the threshold at which cognitive impairment might manifest or be detected. An alternative hypothesis is that depression may be part of a prodrome to Alzheimer's Disease (AD), suggesting a neurobiological association rather than one of psychological response alone. Genetic polymorphisms may explain some of the variances in shared phenomenology between the diagnoses, the instance, when the conditions arise comorbidly, the order in which they are detected that may depend on individual cognitive and physical reserves, as well as the medical history and individual vulnerability. This hypothesis is biologically sound but has not been systematically investigated to date. The current review highlights how genetic variations are involved in the development of both AD and MDD, and the risk conferred by these variations on the expression of these two disorders comorbidly is an important consideration for future studies of pathoaetiological mechanisms and in the stratification of study samples for randomised controlled trials.

A pilot study investigating whether quantitative sensory testing alters after treatment in patients with fibromyalgia.

BACKGROUND: Fibromyalgia is a chronic musculoskeletal pain condition that is often associated with sleep disturbances and fatigue. The pathophysiology of fibromyalgia is not understood, but indirect evidence suggests a central dysfunction of the nociceptive modulating system. The aim of this study was to evaluate whether quantitative sensory testing detects a change in pain thresholds in fibromyalgia patient receiving pregabalin treatment. METHODS: A total of 25 patients were recruited for the study and received routine pregabalin, but only 14 patients completed the treatment. Assessment of pressure pain thresholds and changes in conditioned pain modulation using ischaemic pain as a conditioning stimulus were measured at baseline and every 4 weeks for 12 weeks. Fibromyalgia impact questionnaire, PainDETECT and SF-12 were also completed. RESULTS: Patients with fibromyalgia demonstrated a less-efficient conditioned pain modulation at baseline. An efficient conditioned pain modulation was observed at 1 month and this was maintained until the final visit. Pressure pain thresholds (PPTs) showed a significant improvement from baseline. Patients also reported a similar magnitude of improvements in PainDETECT, fibromyalgia impact questionnaire (FIQ) and its impact on daily life and change in outcome for SF-12. CONCLUSION: This pilot study reports an increase in PPTs and improved conditioned pain modulation response after commencing pregabalin, which was maintained at 12 weeks, and this was supported by positive pain scores. Pregabalin is a licenced treatment for fibromyalgia in Europe, and its response to central sensitisation, particularly 'dynamic responses', has not been reported. We conclude that pregabalin has the potential to reduce peripheral and central sensitisation in patients with fibromyalgia, as measured using quantitative sensory testing.

phMRI: methodological considerations for mitigating potential confounding factors.

Pharmacological Magnetic Resonance Imaging (phMRI) is a variant of conventional MRI that adds pharmacological manipulations in order to study the effects of drugs, or uses pharmacological probes to investigate basic or applied (e.g., clinical) neuroscience questions. Issues that may confound the interpretation of results from various types of phMRI studies are briefly discussed, and a set of methodological strategies that can mitigate these problems are described. These include strategies that can be employed at every stage of investigation, from study design to interpretation of resulting data, and additional techniques suited for use with clinical populations are also featured. Pharmacological MRI is a challenging area of research that has both significant advantages and formidable difficulties, however with due consideration and use of these strategies many of the key obstacles can be overcome.

The common link between functional somatic syndromes may be central sensitisation.

OBJECTIVES: Functional somatic syndromes are common and disabling conditions that all include chronic pain, and which may be related to central nervous system sensitisation. Here, we address the concept of central sensitisation as a physiological basis for the functional somatic syndromes. METHODS: A narrative review of the current literature on central sensitisation and physiological studies in the functional somatic syndromes. RESULTS: Central sensitisation may be a common neurophysiological process that is able to explain non-painful as well as painful symptoms in these disorders. Furthermore, central sensitisation may represent an endophenotypic vulnerability to the development of these syndromes that potentially explains why they cluster together. CONCLUSIONS: Further research is needed to verify these findings, including prospective studies and the standardisation of combined methods of investigation in the study of central sensitisation in functional somatic syndromes. In turn, this may lead to new explanatory mechanisms and treatments being evaluated. Our conclusions add to the debate over the nomenclature of these syndromes but importantly also provide an explanation for our patients.