Critical lower limb ischaemia. Is distal revascularisation worthwhile?

Many patients with gangrene in this country are still offered amputation without any attempt at revascularisation. At Regional Vascular Services (RVS) all patients are investigated and a variety of surgical procedures performed. At many district general hospitals (DGH) the repertoire of surgical procedures is smaller. This study aims to evaluate whether it is worthwhile to apply the most sophisticated methods of revascularisation to patients with critical lower limb ischaemia. Differences in demography are noted between patients with critical lower limb ischaemia, intermittent claudication and abdominal aortic aneurysms. Diabetes mellitus is most prevalent in patients with critical limb ischaemia. Comparing the demographic data of patients with critical ischaemia presenting to the RVS and the DGH there were no significant differences in risk factors, but, the annual presentation rate at the RVS was two and a half times greater than at a DGH in the North West Thames Region. Moreover, the RVS had more patients with distal disease. There were no overall differences in the cumulative limb salvage and survival rates comparing the RVS and the DGH, but for patients with distal disease the cumulative limb salvage rates were 78% and 18% respectively at one year. At the RVS when revascularisation failed and major amputation was needed 72% were at the below knee level compared to 50% at the DGH. 31-Phosphorus magnetic resonance spectroscopy was used to study the small muscles of the foot at rest to see if the system could predict which limbs had potentially reversible ischaemia. Changes in the 31P spectra were seen at rest, but proved to be of limited clinical value. Quality of life studies demonstrated significant improvement in reduction in pain and mobility in the reconstruction group with time. Surprisingly, we were unable to demonstrate statistically significant differences between the reconstruction and amputation groups, presumably due to the small sample size

Magnetic resonance spectroscopy in the management of tophaceous gout: A case report

Development of chronic tophaceous arthritis with marked joint impairment may follow repeated acute attacks. We present a 60 year-old man with huge urate deposits and severe gouty arthropathy with underlying hypothyroidism. During the past years, he had undergone several surgeries with different degrees of amputation to remove the tophus. Magnetic resonance spectroscopy (MRS) of foot finger revealed high peak of lactate, suggesting that high lactate levels is linked with chronic gout and frequent attacks. The patient was treated with levothyroxine along with gout medication, and his thyroid-stimulating hormone (TSH) and urate levels were soon normal, suggesting that the underlying hypothyroidism had aggravated his gout condition

An investigation into central nervous system involvement in distal symmetrical diabetic neuropathy in type 1 diabetes mellitus.

Diabetes is a leading cause of peripheral neuropathy. It is the main initiating factor for foot ulceration and amputation resulting in considerable morbidity and remarkable consumption of scarce medical resources. Relatively little is known about the pathophysiology underlying DPN. Research into DPN has focused mainly on the peripheral nervous system (PNS) with central nervous system (CNS) involvement relatively overlooked. The studies undertaken have been designed to investigate CNS involvement in DPN. 1. Before embarking on spinal cord studies, I reviewed and modified the techniques employed in the pilot study to improve the precision and accuracy of cord cross sectional area measurements. These modifications were patiented to quality control studies, which are reported in Chapter 2. 2. I performed in-vivo cross-sectional magnetic resonance imaging of the cervical spine and reported evidence of spinal cord shrinkage (atrophy) in Painless DPN (Chapter 3). This study showed spinal cord atrophy to be an early phenomenon, present even in subclinical DPN. As the spinal cord is the caudal portion of the CNS, its involvement made us question whether the brain too may be involved. 3. Using MR spectroscopy I examined thalamic involvement in Painless DPN (Chapter 4). This deep brain nucleus is considered the gateway to all somatosensory information entering the brain, and responsible for modulation of sensory information prior to presentation to the cerebral cortex. I demonstrated thalamic biochemical abnormalities consistent with possible neuronal dysfunction in patients with Painless DPN. 4. The demonstration of thalamic neuronal dysfunction in DPN suggests that CNS involvement is not limited to the spinal cord but other important areas, responsible for somatosensory perception, may also be involved. Although the pathogenesis of thalamic involvement is unknown, it is likely that both vascular and metabolic factors that have been implicated in the pathogenesis of DPN are involved. In Chapter 4, I examined the possible role of metabolic factors in the pathogenesis of thalamic neuronal dysfunction in DPN. Using MR spectroscopy, I demonstrated a significant elevation in thalamic glutamine/glutamate in patients with diabetes. Glutamate is the most abundant excitatory neurotransmitter and implicated in various models of neuronal cell death. Astrocytes, which play an important role in glutamate/glutamine metabolism, were impaired in the thalamus of diabetic patients in this study. The combination of elevated glutamate and impaired thalamic astrocytes may provide a pathophysiological explanation for thalamic dysfunction in DPN. 5. In Chapter 5, an alternative hypothesis for thalamic neuronal dysfunction in DPN was tested. Using dynamic contrast enhanced MR perfusion imaging, I demonstrated that Painful DPN is associated with unique thalamic perfusion abnormalities. Intriguingly, these abnormalities were present in patients with Painful but not Painless DPN. 6. Finally, in Chapter 6, I conducted a randomised, double blind and placebo-control trial (RCT) comparing the efficacy and tolerability of sativex, a cannabis based medicinal extract (CBME), with placebo in the symptomatic treatment of painful DPN. This is the first ever RCT using a CBME in painful DPN. We report no significant difference in the primary outcome measure due to a massive placebo effect and that depression is a potential major confounder in such clinical trials

Occipital Proton Magnetic Resonance Spectroscopy ((1)H-MRS) Reveals Normal Metabolite Concentrations in Retinal Visual Field Defects

BACKGROUND: Progressive visual field defects, such as age-related macular degeneration and glaucoma, prevent normal stimulation of visual cortex. We investigated whether in the case of visual field defects, concentrations of metabolites such as N-acetylaspartate (NAA), a marker for degenerative processes, are reduced in the occipital brain region. METHODOLOGY/PRINCIPAL FINDINGS: Participants known with glaucoma, age-related macular degeneration (the two leading causes of visual impairment in the developed world), and controls were examined by proton MR spectroscopic ((1)H-MRS) imaging. Absolute NAA, Creatine and Choline concentrations were derived from a single-voxel in the occipital region of each brain hemisphere. No significant differences in metabolites concentrations were found between the three groups. CONCLUSIONS/SIGNIFICANCE: We conclude that progressive retinal visual field defects do not affect metabolite concentration in visual brain areas suggesting that there is no ongoing occipital degeneration. We discuss the possibility that metabolite change is too slow to be detectable

Changes in metabolites in the brain of patients with fibromyalgia after treatment with an NMDA receptor antagonist

The aims of this work were to evaluate whether the treatment of patients with fibromyalgia with memantine is associated with significant changes in metabolite concentrations in the brain, and to explore any changes in clinical outcome measures. Magnetic resonance spectroscopy was performed of the right anterior and posterior insula, both hippocampi and the posterior cingulate cortex. Questionnaires on pain, anxiety, depression, global function, quality of life and cognitive impairment were used. Ten patients were studied at baseline and after three months of treatment with memantine. Significant increases were observed in the following areas: N-acetylaspartate (4.47 at baseline vs. 4.71 at three months, p¿=¿0.02) and N-acetylaspartate+N-acetylaspartate glutamate in the left hippocampus (5.89 vs. 5.98; p¿=¿0.007); N-acetylaspartate+N-acetylaspartate glutamate in the right hippocampus (5.31 vs 5.79; p¿=¿0.01) and the anterior insula (7.56 vs. 7.70; p¿=¿0.033); glutamate+glutamine/creatine ratio in the anterior insula (2.03 vs. 2.17; p¿=¿0.022) and the posterior insula (1.77 vs. 2.00; p¿=¿0.004); choline/creatine ratio in the posterior cingulate (0.18 vs. 0.19; p¿=¿0.023); and creatine in the right hippocampus (3.60 vs. 3.85; p¿=¿0.007). At the three-month follow-up, memantine improved cognitive function assessed by the Cognition Mini-Exam (31.50, SD¿=¿2.95 vs. 34.40, SD¿=¿0.6; p¿=¿0.005), depression measured by the Hamilton Depression Scale (7.70, SD¿=¿0.81 vs. 7.56, SD¿=¿0.68; p¿=¿0.042) and severity of illness measured by the Clinical Global Impression severity scale (5.79, SD¿=¿0.96 vs. 5.31, SD¿=¿1.12; p¿=¿0.007). Depression, clinical global impression and cognitive function showed improvement with memantine. Magnetic resonance spectroscopy could be useful in monitoring response to the pharmacological treatment of fibromyalgia

Skeletal Muscle Impairments in People with Diabetes and Peripheral Neuropathy

Abstract of the Dissertation Skeletal Muscle Impairments in People with Diabetes and Peripheral Neuropathy by Lori Jeanne Tuttle Doctor of Philosophy in Movement Science Washington University in St. Louis, 2011 Dr. Michael J. Mueller, Chairperson Diabetes mellitus: DM) is a chronic disease that affects almost 24 million people and has large socioeconomic costs. Of these 24 million people, 60-70 % will develop some form of nervous system impairment, including peripheral neuropathy: PN). It is important to understand muscle structure and impairments in people with DM+PN in order to determine appropriate interventions to limit the disability that is associated with DM+PN. The objectives of this research are to describe skeletal muscle structure in people with DM+PN, to determine whether neuropathic muscle structure and composition are associated with movement impairments and functional limitations, and whether neuropathic muscle can be modulated by activity level and/or an exercise intervention. In Chapter 2, we examine whether intermuscular adipose tissue: IMAT) volumes are different between groups with DM, DM+PN, and a group without DM or PN: NoDMPN). We report that there is no difference in IMAT volumes in these groups, but that increased IMAT is associated with poorer physical performance and the DM+PN group had the lowest measures of physical performance. In Chapter 3, we examine whether activity level in people with DM+PN is associated with IMAT. We report that activity level is inversely associated with IMAT volumes. In Chapter 4, we examine whether an exercise intervention for people with DM+PN is able to improve function and change IMAT and muscle volumes. We report that our duration-based exercise program was successful in increasing 6 minute walk distance, but there was no change in IMAT or muscle volumes. In Chapter 5, we provide a case report detailing an exercise intervention for a specific individual with DM+PN who was able to increase his average activity level and shows improvement in muscle performance and physical function. Overall, our results suggest that people with DM+PN have lower levels of physical performance than their peers and increased IMAT is associated with poor physical performance. Increased activity levels are associated with decreased IMAT volume. People with DM+PN are able to safely increase their walking distance following an exercise intervention, but we did not see a change in muscle composition. Additional research is needed to determine the specific roles of IMAT in skeletal muscle and function

Microcirculatory changes and skeletal muscle oxygenation measured at rest by non-infrared spectroscopy in patients with and without diabetes undergoing haemodialysis

Introduction: Haemodialysis has direct and indirect effects on skin and muscle microcirculatory regulation that are severe enough to worsen tolerance to physical exercise and muscle asthenia in patients undergoing dialysis, thus compromising patients' quality of life and increasing the risk of mortality. In diabetes these circumstances are further complicated, leading to an approximately sixfold increase in the incidence of critical limb ischaemia and amputation. Our aim in this study was to investigate in vivo whether haemodialysis induces major changes in skeletal muscle oxygenation and blood flow, microvascular compliance and tissue metabolic rate in patients with and without diabetes. Methods: The study included 20 consecutive patients with and without diabetes undergoing haemodialysis at Sant Andrea University Hospital, Rome from March to April 2007. Near-infrared spectroscopy (NIRS) quantitative measurements of tissue haemoglobin concentrations in oxygenated [HbO(2)] and deoxygenated forms [HHb] were obtained in the calf once hourly for 4 hours during dialysis. Consecutive venous occlusions allowed one to obtain muscular blood flow (mBF), microvascular compliance and muscle oxygen consumption (mVO(2)). The tissue oxygen saturation (StO(2)) and content (CtO(2)) as well as the microvascular bed volume were derived from the haemoglobin concentration. Nonparametric tests were used to compare data within each group and among the groups and with a group of 22 matched healthy controls. Results: The total haemoglobin concentration and [HHb] increased significantly during dialysis in patients without and with diabetes. Only in patients with diabetes, dialysis involved a [HbO(2)], CtO(2) and mVO(2) increase but left StO(2) unchanged. Multiple regression analysis disclosed a significant direct correlation of StO(2) with HbO(2) and an inverse correlation with mVO(2). Dialysis increased mBF only in diabetic patients. Microvascular compliance decreased rapidly and significantly during the first hour of dialysis in both groups. Conclusions: Our NIRS findings suggest that haemodialysis in subjects at rest brings about major changes in skeletal muscle oxygenation, blood flow, microvascular compliance and tissue metabolic rate. These changes differ in patients with and without diabetes. In all patients haemodialysis induces changes in tissue haemoglobin concentrations and microvascular compliance, whereas in patients with diabetes it alters tissue blood flow, tissue oxygenation (CtO(2), [HbO(2)]) and the metabolic rate (mVO(2)). In these patients the mVO(2) is correlated to the blood supply. The effects of haemodialysis on cell damage remain to be clarified. The absence of StO(2) changes is probably linked to an opposite [HbO(2)] and mVO(2) pattern

Challenges of functional imaging research of pain in children

Functional imaging has revolutionized the neurosciences. In the pain field it has dramatically altered our understanding of how the brain undergoes significant functional, anatomical and chemical changes in patients with chronic pain. However, most studies have been performed in adults. Because functional imaging is non-invasive and can be performed in awake individuals, applications in children have become more prevalent, but only recently in the pain field. Measures of changes in the brains of children have important implications in understanding neural plasticity in response to acute and chronic pain in the developing brain. Such findings may have implications for treatments in children affected by chronic pain and provide novel insights into chronic pain syndromes in adults. In this review we summarize this potential and discuss specific concerns related to the imaging of pain in children