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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sickle cell disease (SCD) is the most common genetic disorder of the blood. The disease produces significantly abnormal hemoglobin (Hgb) molecules in red blood cells (RBCs). The sickling of RBCs occurs when partially or totally deoxygenated Hgb molecules distort their normal disk shape, producing stiff, sticky, sickle-shaped cells that obstruct small blood vessels and produce vasoocclusion as well as the disruption of oxygen to body tissues. Because tissue damage can occur at multiple foci, patients with SCD are at risk for other medical complications including, but not limited to, delayed growth and sexual maturation; acute and chronic pulmonary dysfunction; stroke; aseptic necrosis of the hip, shoulders, or both; sickle cell retinopathy; dermal ulcers; and severe chronic pain. The chronicity of the illness combined with frequent hospitalizations for pain and other medical management can contribute significantly to impaired psychosocial functioning, altered intra- and interpersonal relationships, and reduced quality of life. Unlike previous qualitative reviews of SCD, this article describes the relevant clinical and research data on the relation between psychosocial functioning and SCD in adult and child populations. The authors discuss the significant role of psychosocial issues in the trajectory and management of the disease and conclude that understanding the pathophysiology of SCD without thoroughly understanding the equally important psychosocial influences is misunderstanding SCD.
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PMID:A brief review of the pathophysiology, associated pain, and psychosocial issues in sickle cell disease. 1608 20

Many patients suffer from neuropathic pain as a result of injury to the peripheral nervous system (e.g. post-herpetic neuralgia or diabetic neuropathy) or to the central nervous system (e.g. spinal cord injury or stroke). The most distinctive symptom of neuropathic pain is allodynia, whereby normally non-painful stimuli, such as light touch, become painful. Traditionally, inflammatory and neuropathic pain syndromes have been considered distinct entities; however, recent evidence belies this strict dichotomy. Nerve damage can stimulate macrophage infiltration and increase the number of activated T cells. Under these conditions, neuroinflammatory and immune responses contribute as much to the development and maintenance of pain as the initial damage itself. Recently, studies using animal models have shown that upregulation of chemokines is one of the mechanisms underlying the development and maintenance of chronic pain.
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PMID:Chemokines, chemokine receptors and pain. 1609 20

There is convincing evidence that acupuncture (AP) is effective for the treatment of postoperative and chemotherapy-induced nausea/vomiting, as well as postoperative dental pain. Less convincing data support AP's efficacy for chronic pain conditions, including headache, fibromyalgia and low back pain. There is no evidence that AP is effective in treating addiction, insomnia, obesity, asthma or stroke deficits. AP seems to be efficacious for alleviating experimental pain by increasing pain thresholds in human subjects and it appears to activate analgesic brain mechanisms through the release of neurohumoral factors, some of which can be inhibited by the opioid antagonist naloxone. In contrast to placebo analgesia, AP-related pain relief takes some time to develop and to resolve. Furthermore, repetitive use of AP analgesia can result in tolerance that demonstrates cross-tolerance with morphine. However, it appears that not all forms of AP are equally effective for providing analgesia. In particular, electro-AP seems to best deliver stimuli that activate powerful opioid and nonopioid analgesic mechanisms. Thus, future carefully controlled clinical trials using adequate electro-AP may be able to provide the necessary evidence for relevant analgesia in chronic pain conditions, such as headache, fibromyalgia, irritable bowel syndrome and low back pain.
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PMID:Mechanisms of acupuncture analgesia for clinical and experimental pain. 1673 14

The higher prevalence of depression in specific diseases and older persons is discussed. This prevalence varies greatly according to the method used to collect data. A risk group can only be defined if information on diseases and other influencing factors are collected uniformly. The target diagnoses Parkinson's disease, stroke, myocardial infarction, cancer, diabetes mellitus, chronic pain, multiple infarct syndrome, Alzheimer's and other dementia were recorded from 1208 geriatric patients of the ZAGF municipal hospital in Munich, Germany. Logistic regression was used to identify chronic pain as the main cofactor for an association with depression (clinical diagnoses by ICD-10) and depressive symptoms (via GDS [Geriatric Depression Scale]). This association was also found for multimorbid patients with chronic pain. Impairment of the activities of daily living and the clinical setting were important additional cofactors. Pain patients are therefore at higher risk for depression.
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PMID:[Relation between certain diseases and frequency of depression in geriatric patients]. 1682 Oct 65

Improvement of motor activity may occur after stroke. It may be because of recovery of marginally functional neurons. It may also occur by relearning, a process that strengthens existing pathways and may lead to new functional or structural changes- neuroplasticity. Clinical investigation into the treatment of chronic pain after thalamic infarction has shown improvement in motor function when pain relief is achieved with motor cortex stimulation. More recently, laboratory studies in rats and primates demonstrate significant improvement in forelimb reaching tasks in rats and primates after induced ischemic cortical infarction when rehabilitation is paired with stimulation of the injured cortex and cortical margin at low frequency (50 Hz). Structural changes have also been observed. Dendritic density in layer V of the cortex near the lesion increases after cortical stimulation, consistent with a restorative cortical plasticity. Also, stimulation combined with rehabilitation increases the area of the injured cortex from which movements can be evoked in response to stimulation of the injured cortex in rats. Unilateral cortical stimulation reduces secondary cortical hyperexcitability in the impaired hemisphere after stroke. These findings form the basis for the first clinical study motor cortex stimulation after chronic stroke in humans. A prospective, randomized multicenter study of subthreshold motor cortical electrical stimulation during rehabilitation in patients has been completed. The eight patients entered into this study had weakness from a stroke that occurred at least four months before enrollment. Results demonstrate that the treatment is safe. In addition, there was significant improvement in upper extremity function. These improvements persisted through the 12-week follow-up assessment period after completion of stimulation and rehabilitation. Recently, non-invasive transcranial magnetic stimulation of the motor cortex demonstrates improvements in hand function that persist after stimulation for at least 25 minutes. Such work represents a paradigm shift in the approach towards rehabilitation of the stroke-injured brain away from pharmacologic flooding of neuronal receptors, instead towards targeted physiologic stimulation.
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PMID:Recovery of motor function after stroke. 1704 74

One of the major problems in modern medicine is to find remedies for the group of people with chronic pain syndromes. Low back pain is one of the most frequent syndromes and perhaps the most invalidating of all of them. Chronic pain seems to develop through several pathways affecting the spinal cord and the brain: (1) neuro-anatomical reorganisation, (2) neuro-physiological changes, and (3) activation of glia cells (immune reaction in the central nervous system). Although all of these pathways seem to provide a (partial) plausible explanation for chronic pain, treatments influencing these pathways often fail to alleviate chronic pain patients. This could be because of the probability that chronic pain develops by all three mechanisms of disease. A treatment influencing just one of these mechanisms can only be partially successful. Other factors that seem to contribute to the development of chronic pain are psychosocial. Fear, attention and anxiety are part of the chronic pain syndrome being cause or consequence. The three pathways and the psycho-emotional factors constitute a psycho-neuro-immunological substrate for chronic pain syndromes; a substrate which resembles the substrate for phantom pain and functional invalidity after stroke. Both phantom pain and functional invalidity are considered non-use syndromes. The similarity of the substrate of both these two neurological disorders and chronic pain makes it reasonable to consider chronic pain a non-use disease (the hypothesis). To test this hypothesis, we developed a "paradoxal pain therapy". A therapy which combines the constraint induced movement therapy and strategies to dissociate pain from conditioning factors like fear, anxiety and attention. The aim of the therapy is to establish a behaviour perpendicular on the pathological pain-behaviour. Clinically, the treatment seems promising, although we just have preliminary results. Further clinical and laboratory studies are needed to measure eventual changes at neuro-anatomical and neuro-psychological level using modern neuro-imaging instruments (PET, SPECT, fMRI). Randomised clinical trials should be carried out to test our hypothesis for all-day use in clinical practice. The hypothesis: chronic pain is a non-use disease produced by psycho-emotional factors like fear, attention and anxiety. Optimal treatment should be based on physiological use, and dissociation of pain and the mentioned psycho-emotional factors. Paradoxal pain therapy could serve these treatment conditions.
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PMID:Chronic pain: a non-use disease. 1707 Oct 12

This study used positron emission tomography (PET) and [11C]diprenorphine to compare the in vivo distribution abnormalities of brain opioid receptors (OR) in patients with peripheral (n=7) and central post-stroke pain (CPSP, n=8), matched for intensity and duration. Compared with age- and sex-matched controls, peripheral neuropathic pain (NP) patients showed bilateral and symmetrical OR binding decrease, while in CPSP binding decrease predominated in the hemisphere contralateral to pain. In CPSP patients, interhemispheric comparison demonstrated a significant decrease in opioid binding in posterior midbrain, medial thalamus and the insular, temporal and prefrontal cortices contralateral to the painful side. Peripheral NP patients did not show any lateralised decrease in opioid binding. Direct comparison between the central and peripheral groups confirmed a significant OR decrease in CPSP, contralateral to pain. While bilateral binding decrease in both NP groups may reflect endogenous opioid release secondary to chronic pain, the more important and lateralised decrease specific to CPSP suggests opioid receptor loss or inactivation in receptor-bearing neurons. Opioid binding decrease was much more extensive than brain anatomical lesions, and was not co-localised with them; metabolic depression (diaschisis) and/or degeneration of OR neurons-bearing secondary to central lesions appears therefore as a likely mechanism. Central and peripheral forms of NP may differ in distribution of brain opioid system changes and this in turn might underlie their different sensitivity to opiates.
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PMID:Differential brain opioid receptor availability in central and peripheral neuropathic pain. 1713 14

Dejerine-Roussy Syndrome (thalamic pain syndrome) is characterised by the development of chronic, severe pain in the contralateral half of the body after a thalamic stroke. It is often largely refractory to treatment. In this paper we draw together a number of disparate pieces of knowledge to propose a novel therapy for this condition. There is already substantial evidence from neurological disease that the brain's left hemisphere serves to "smooth over" discrepancies in sensory input in order to impose order and maintain the existing view of the world around us. Conversely the right hemisphere acts on discrepant sensory input to cause a re-evaluation of one's world view. Based on this, it was proposed by Harris that pain is an organism's response to discrepancy. It is already known that cold water vestibular caloric irrigation of the ear leads to activation of a number of areas in the contralateral hemisphere - including the insular cortex. Indeed it is known that - presumably because it also activates the right parietal lobe - this technique can be used to treat anosognosia, somatoparaphrenia and neglect. In addition to being activated by vestibular stimulation, it has been shown that the posterior insula has a somatotopic map of the body for painful stimuli. We speculate that phylogenetically, close anatomical proximity between the pain and vestibular areas of the brain makes sense; as it would allow modulation of otherwise disabling chronic pain, when the organism makes a sudden movement to avoid a predator. Given Harris's theory we propose that post stroke thalamic pain may represent a pathological amplification of the thalamic posterior insular response to pain due to discrepant sensory input. Based on all the above we go on to hypothesise that cold vestibular caloric stimulation will be effective in treating Dejerine-Roussy Syndrome and we present provisional evidence from two patients which supports this conclusion. If our hypothesis is correct this will be the first time in clinical neurology that a chronic disorder, long considered refractory to treatment, is relieved by a simple non-invasive procedure.
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PMID:Can vestibular caloric stimulation be used to treat Dejerine-Roussy Syndrome? 1807 18

Fabry disease is an X-linked, hereditary, lysosomal storage disease caused by deficiency of the enzyme alpha-galactosidase A, which results in the accumulation of the neutral glycosphingolipid globotriaosylceramide (Gb3) in the walls of small blood vessels, nerves, dorsal root ganglia, renal glomerular and tubular epithelial cells, and cardiomyocytes. It is a complex, multisystem disorder that is characterized clinically by chronic pain and acroparesthesia, gastrointestinal disturbances, characteristic skin lesions (angiokeratomata), progressive renal impairment, cardiomyopathy, and stroke. Enzyme replacement therapy (ERT) with intravenous infusions of recombinant human alpha-galactosidase A consistently decreases Gb3 levels in plasma and clears lysosomal inclusions from vascular endothelial cells. The effects of ERT on other tissues are not as obvious, suggesting that treatment must be initiated early in the course of the disease to be optimally effective or that some complications of the disease are not responsive to enzymes delivered intravenously.
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PMID:Narrative review: Fabry disease. 1737 87

NSAIDs are a widely used class of analgesic and anti-inflammatory drugs that act by inhibiting the cyclo-oxygenase (COX) enzyme. However, because of their nonspecificity of action, use of these agents as long-term therapy for chronic pain in diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA) is often discouraged. Among NSAIDs, COX-2 inhibitors are promising candidates for long-term therapy of chronic diseases, particularly in the elderly, because of their reduced incidence of gastrointestinal adverse effects. However, in recent times these agents have also been shown to cause adverse effects such as cardiovascular effects (myocardial infarction, stroke and hypertension) and renal effects (decreased renal blood flow/glomerular filtration rate), which in 2004 led to the withdrawal of rofecoxib and in 2005 the withdrawal of valdecoxib from the US market. Importantly, these adverse effects can be effectively reduced by achieving site specific/targeted delivery through new formulation approaches. These formulations not only restrict the drug supply to specific organs but also reduce the dose required. As a result, use of new delivery systems such as nanoparticles, microparticles, microemulsions and nanogels has gained widespread applicability in the management of chronic disease, especially in the elderly, and particularly when there is a need to decrease dose-dependent adverse effects (as is the case with COX-2 inhibitors). This article reviews various new approaches to the delivery of COX-2 inhibitors and highlights issues related to the development of delivery systems for these agents for RA, OA, cancer (familial adenomatous polyposis, prostate, breast and non-small cell lung cancer), ocular diseases (such as diabetic retinopathy) and inflammatory diseases of the skin, with emphasis on their potential for use in the elderly. Emphasis is also placed on the preparation of these particulate systems, their release profile and behaviour in biological systems.
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PMID:New dosage formulations for targeted delivery of cyclo-oxygenase-2 inhibitors: focus on use in the elderly. 1757 10


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