Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of deep brain stimulation (DBS) has recently been expanding for the treatment of many neurologic disorders such as Parkinson disease, dystonia, essential tremor, Tourette's syndrome, cluster headache, epilepsy, depression, and obsessive compulsive disorder. The target structures for DBS include specific segregated territories within limbic, associative, or motor regions of very small subnuclei. In this review, we summarize current clinical techniques for DBS, the cognitive/mood/motor outcomes, and the relevant neuroanatomy with respect to functional territories within specific brain targets. Future development of new techniques and technology that may include a more direct visualization of "motor" territories within target structures may prove useful for avoiding side effects that may result from stimulation of associative and limbic regions. Alternatively, newer procedures may choose and specifically target non-motor territories for chronic electrical stimulation.
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PMID:Limbic, associative, and motor territories within the targets for deep brain stimulation: potential clinical implications. 1761 33

The field of neurology was long infamous for a lack of therapeutic options. How many of you have once thought: "Neurologists don't cure the disease, they admire it". But those days have passed into history, and the field is now vibrant with new treatments and hope even for patients with the worst neurodegenerative diseases. We summarized in the present review the latest major advances in therapeutic principles and practice for some of the most frequent chronic neurological disorders such as headaches, epilepsy, multiple sclerosis, dementias, Parkinson's disease, sleep/wake disturbances and peripheral neuropathies. We cannot cure or prevent, but we can now halt or control symptoms and disease progression to provide physical and psychological relief, and a better quality of life for patients who suffer from these otherwise devastating neurological conditions.
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PMID:[Therapeutic armamentarium in neurology: the birth of a new era]. 1772 19

Deep brain stimulation is a minimally invasive targeted neurosurgical intervention that enables structures deep in the brain to be stimulated electrically by an implanted pacemaker. It has become the treatment of choice for Parkinson's disease, refractory to, or complicated by, drug therapy. Its efficacy has been demonstrated robustly by randomized, controlled clinical trials, with multiple novel brain targets having been discovered in the last 20 years. Multifarious clinical indications for deep brain stimulation now exist, including dystonia and tremor in movement disorders; depression, obsessive-compulsive disorder and Tourette's syndrome in psychiatry; epilepsy, cluster headache and chronic pain, including pain from stroke, amputation, trigeminal neuralgia and multiple sclerosis. Current research argues for novel indications, including hypertension and orthostatic hypotension. The development, principles, indications and effectiveness of the technique are reviewed here. While deep brain stimulation is a standard and widely accepted treatment for Parkinson's disease after 20 years of experience, in chronic pain it remains restricted to a handful of experienced, specialist centers willing to publish outcomes despite its use for over 50 years. Reasons are reviewed and novel approaches to appraising clinical evidence in functional neurosurgery are suggested.
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PMID:Deep brain stimulation: indications and evidence. 1785 Jan 94

The number of dopamine agonists (DA) used in Parkinson's disease (PD) is gradually increasing. They have different affinity to the dopamine receptor subtypes. When choosing one of these drugs one should consider its efficacy in monotherapy in early phase and in combined therapy with levodopa in advanced PD, side effects profile, effectiveness in non-motor symptoms of PD, dosing and route of administration. The efficacy of new DA (pramipexol, ropinirol, cabergoline) is probably higher than bromocriptine and comparable to pergolide with similar profile of the most common side effects (headache, vertigo, nausea, somnolence, oedema). However, fibrosis of the pleura, peritoneum and pericardium as well as valvular heart disease (caused by noninflammatory fibrotic degeneration) are significantly more common after ergoline DA (pergolide, cabergoline). Pramipexol shows antidepressant activity. Ropinirol is metabolised by the liver and can be safely administered in renal insufficiency. Pramipexol is excreted in urine and the risk of interaction with other drugs metabolised in the liver is reduced. Rotigotine is the only DA available as skin patches. Whenever necessary, one DA agent can be changed safely overnight to another one.
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PMID:[Choosing a dopamine agonist in Parkinson's disease]. 1794 54

For 20 years, deep brain stimulation (DBS) at high frequency has been developed as a substitute for the classical lesioning methods previously used in stereotactic and functional neurosurgery. This method has proven its efficacy, based on its reversibility and adaptability: two factors that are responsible for low morbidity. The method has been initially developed for and applied to movement disorders in several target areas; such as the thalamus, the pallidum and the subthalamic nucleus. It has now also been extended to other indications, such as epilepsy, dystonias and cluster headache and, more recently, to psychiatric disorders, such as obsessive-compulsive disorder, Gilles de la Tourette tics and depression. Several other disorders are currently under investigation and these may become new indications in the future. The mechanism of action is likely to be complex; associating cell-firing inhibition, neurotransmitter depletion, jamming and excitation of inhibitory pathways that lead to functional inhibition, mimicking the effects of lesioning of the stimulated structures. High-frequency stimulation of the subthalamic nucleus induces neuroprotection in animal models but has not yet been demonstrated in human patients suffering from Parkinson's disease. Technological development will enhance and refine the effects of high-frequency stimulation, and allow further extension of this method to new targets and new indications.
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PMID:What the future holds for deep brain stimulation. 1803 54

The role of Helicobacter pylori (HP) in some digestive diseases (gastritis, ulcer, gastric cancer, MALT lymphoma) is well known. It has been suggested relatively recently that infection with HP can be involved in various extra-digestive conditions: respiratory disorders (chronic obstructive pulmonary disease, bronchiectasis, lung cancer, pulmonary tuberculosis, bronchial asthma); vascular disorders (ischaemic heart disease, stroke, primary Raynaud phenomena, primary headache); autoimmune disorders (Sjogren syndrome, Henoch-Schonlein purpura, autoimmune thrombocytopenia, autoimmune thyroiditis, Parkinson's disease, idiopathic chronic urticaria, rosacea, alopecia areata); other disorders (iron deficiency anaemia, growth retardations, liver cirrhosis). Case studies, small patient series and non-randomized trials that have shown a beneficial effect of HP eradication in different conditions are not convincing. According to Mastricht III the only conditions where HP eradication is indicated are immune thrombocytopenic purpura and iron deficiency anaemia.
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PMID:Extragastric manifestations of Helicobacter pylori infection. 1829 84

The aim of this study was to estimate the cost of "brain" disorders in Italy. Country-specific prevalence and health-economic data on addiction, affective, anxiety and psychotic disorders, tumours, dementia, epilepsy, migraine/other headaches, multiple sclerosis, Parkinson's disease, stroke and head trauma were reviewed. Direct medical/non-medical and indirect costs were computed. Population-based samples and national or regional registries were used. The Italian population expected with a brain disorder was 12.4 million in 2004. The highest cost per case was for tumours and multiple sclerosis; the lowest was for anxiety disorders and migraine. Dementia (8.6 billion euros), psychotic and affective disorders (18.7 billion euros), migraine (3.5 billion euros) and stroke (3.4 billion euros) represented the highest total costs. Direct medical costs were predominant for psychiatric and neurosurgical disorders, direct non-medical costs for dementia, and indirect costs for neurological disorders. The total cost of brain disorders in Italy was 40.8 billion euros, 3% of the gross national product, and 706 euros per Italian citizen/year. This figure is however likely to be underestimated as it is based on retrospective methodology and samples of brain disorders, and does not include intangible costs.
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PMID:Cost of disorders of the brain in Italy. 1848 7

The protein botulinum neurotoxin A (BoNT/A) is one of seven distinct neurotoxins produced by Clostridium botulinum. BoNT/A blocks cholinergic synapses with an extremely high specificity and potency. Appropriately purified and diluted, BoNT/A serves as a reliable and well tolerated drug that is applied by local injection.The efficacy of BoNT/A is evident in the symptomatic therapy of disorders in which muscular hyperactivity plays a prominent role, such as focal dystonias and hemifacial spasm; in these disorders, BoNT/A is considered first-line therapy. BoNT/A is also beneficial in the treatment of both adults and children with spasticity of various causes. The pain that frequently accompanies these conditions is effectively reduced by BoNT/A. A genuine analgesic effect for BoNT/A unrelated to skeletal muscle spasmolysis has been suggested on the basis of in vitro and in vivo (animal) data. However, studies in humans designed to detect such an effect were negative, as were controlled studies of BoNT/A in patients with primary headache disorders.BoNT/A also acts on cholinergic synapses of the autonomic nervous system, and injection of BoNT/A into salivary glands significantly decreases the production of saliva. This may be beneficial for patients with Parkinson's disease, in whom the excessive production of saliva may be problematic.Overall, BoNT/A has been confirmed as an efficacious, predictable and well tolerated drug in an ever-increasing number of neurological disorders.
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PMID:Use of botulinum toxin A in adult neurological disorders: efficacy, tolerability and safety. 1869 73

Modafinil is a wake-promoting agent that is pharmacologically different from other stimulants. It has been investigated in healthy volunteers, and in individuals with clinical disorders associated with excessive sleepiness, fatigue, impaired cognition and other symptoms. This review examines the use of modafinil in clinical practice based on the results of randomized, double-blind, placebo-controlled clinical trials available in the English language in the MEDLINE database. In sleep-deprived individuals, modafinil improves mood, fatigue, sleepiness and cognition to a similar extent as caffeine but has a longer duration of action. Evidence for improved cognition in non-sleep-deprived healthy volunteers is controversial.Modafinil improves excessive sleepiness and illness severity in all three disorders for which it has been approved by the US FDA, i.e. narcolepsy, shift-work sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure (CPAP). However, its effects on safety on the job and on morbidities associated with these disorders have not been ascertained. Continued use of CPAP in obstructive sleep apnoea is essential. Modafinil does not benefit cataplexy.In very small, short-term trials, modafinil improved excessive sleepiness in patients with myotonic dystrophy. It was efficacious in fairly large studies of attention deficit hyperactivity disorder (ADHD) in children and adolescents, and was as efficacious as methylphenidate in a small trial, but has not been approved by the FDA, in part because of its serious dermatological toxicity. In a trial of 21 non-concurrent subjects, with 2-week treatment periods, modafinil was as effective as dexamfetamine in adult ADHD. Modafinil was helpful for depressive symptoms in bipolar disorder in a trial that excluded patients with stimulant-induced mania. A single dose of modafinil may hasten recovery from general anaesthesia after day surgery. A single dose of modafinil improved the ability of emergency room physicians to attend didactic lectures after a night shift, but did not improve their ability to drive home and caused sleep disturbances subsequently.Modafinil had a substantial placebo effect on outcomes such as fatigue, excessive sleepiness and depression in patients with traumatic brain injury, major depressive disorder, schizophrenia, post-polio fatigue and multiple sclerosis; however, it did not provide any benefit greater than placebo.Trials of modafinil for excessive sleepiness in Parkinson's disease, cocaine addiction and cognition in chronic fatigue syndrome provided inconsistent results; all studies had extremely small sample sizes. Modafinil cannot be recommended for these conditions until definitive data become available.Modafinil induces and inhibits several cytochrome P450 isoenzymes and has the potential for interacting with drugs from all classes. The modafinil dose should be reduced in the elderly and in patients with hepatic disease. Caution is needed in patients with severe renal insufficiency because of substantial increases in levels of modafinil acid. Common adverse events with modafinil include insomnia, headache, nausea, nervousness and hypertension. Decreased appetite, weight loss and serious dermatological have been reported with greater frequency in children and adolescents, probably due to the higher doses (based on bodyweight) used. Modafinil may have some abuse/addictive potential although no cases have been reported to date.
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PMID:Approved and investigational uses of modafinil : an evidence-based review. 1872 34

During immuno-mediated attack of the brain, activation of endocannabinoids represents a protective mechanism, aimed at reducing both neurodegenerative and inflammatory damage through various and partially converging mechanisms that involve neuronal and immune cells. Here, we review the main alterations of the endocannabinoid system (ECS) within the central nervous system and in peripheral blood mononuclear cells, in order to discuss the intriguing observation that elements of the peripheral ECS mirror central dysfunctions of endocannabinoid signaling. As a consequence, elements of blood ECS might serve as novel, non-invasive diagnostic tools of several neurological disorders, and targeting the ECS might be useful for therapeutic purposes. In addition, we discuss the appealing working hypothesis that the presence of type-1 cannabinoid receptors on the luminal side, and that of type-2 cannabinoid receptors on the abluminal side of the blood-brain barrier, could drive a unidirectional transport of AEA in the luminal --> abluminal direction (i.e., from blood to brain), thus implying that blood may be a reservoir of AEA for the brain. On this basis, it can be expected that an unbalance of the endogenous tone of AEA in the blood may sustain a similar unbalance of its level within the brain, as demonstrated in Huntington's disease, Parkinson's disease, multiple sclerosis, attention-deficit/hyperactivity disorder, schizophrenia, depression and headache.
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PMID:The endocannabinoid system in peripheral lymphocytes as a mirror of neuroinflammatory diseases. 1878 87


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