Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Migraine is one of the common diseases suffering 8.4 million patients in Japan. The pathophysiology of migraine remains unclear. The genetic and basic studies of the familial hemiplegic migraine, a specific subtype of migraine with aura, have demonstrated the dysfunction of mutant brain-expressed calcium ion channel and/or the Na+/K+ ion transporter and suggested the association between cortical spreading depression (CSD) and migraine with aura. It is suggested that the CSD, neurogenic inflammation and vasodilatation caused by unknown triggers may activate the 'brainstem migraine generator' and amplified back way. In consequence, headache and/or aura will be appeared and strengthened. Our etiological data of headache in Daisen located in Western Japan clarified as follows; 1) Overall prevalence of migraine in Daisen was 6.0%. Women observed a 5.9-fold higher risk of migraine than men. 2) Fatigue, mental stress, and lack of sleep were the main headache triggers. 3) Only 7.3% of those with migraine with aura and 5.3% of those with migraine without aura had consulted a physician. 4) Migraineurs consume significantly more fatty/oily foods, coffee, and tea than nonheadache subjects of the same community. Migraineurs consume significantly fewer fish than nonheadache residents. As a conclusion, only a few Japanese migraineurs receive benefits of medical services and recent advances of headache medicine. The Japanese guideline for chronic headache treatment has declared in 2002. The International Classification of headache disorders has reedited to the 2nd edition. Public education concerning headaches is one of the most urgent issues in Japan.
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PMID:[Migraine update]. 1621 83

Migraine headache is triggered by and associated with a variety of hormonal, emotional, nutritional, and physiological changes. The perception of migraine headache is formed when nociceptive signals originating in the meninges are conveyed to the somatosensory cortex through the trigeminal ganglion, medullary dorsal horn, and thalamus. Is there a common descending pathway accounting for the activation of meningeal nociceptors by different migraine triggers? We propose that different migraine triggers activate a wide variety of brain areas that impinge on parasympathetic neurons innervating the meninges. According to this hypothesis, migraine triggers such as perfume, stress, or awakening activate multiple hypothalamic, limbic, and cortical areas, all of which contain neurons that project to the preganglionic parasympathetic neurons in the superior salivatory nucleus (SSN). The SSN, in turn, activates postganglionic parasympathetic neurons in the sphenopalatine ganglion, resulting in vasodilation and local release of inflammatory molecules that activate meningeal nociceptors. Are there ascending pathways through which the trigeminovascular system can induce the wide variety of migraine symptoms? We propose that trigeminovascular projections from the medullary dorsal horn to selective areas in the midbrain, hypothalamus, amygdala, and basal forebrain are functionally positioned to produce migraine symptoms such as irritability, loss of appetite, fatigue, depression, or the quest for solitude. Bidirectional trafficking by which the trigeminovascular system can activate the same brain areas that have triggered its own activity in the first place provides an attractive network of perpetual feedback that drives a migraine attack for many hours and even days.
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PMID:Unitary hypothesis for multiple triggers of the pain and strain of migraine. 1625 3

This study was performed to document the frequency, duration and types of symptoms of postdrome in migraine patients. Eight hundred and twenty-seven consecutive headache clinic patients (IHS 1.1, 1.2 and 1.5.1) were evaluated at first visit. Postdrome frequency, duration and characteristics were analysed. Sixty-eight per cent of 827 patients reported postdrome (69.1% females; 56.8% males, P<0.007). The average duration of the postdrome was 25.2 h. Fifty-six per cent had postdrome for <or=12 h, 32% for 12-24 h, 88% for <or=24 h, and 12% for >24 h. The commonest symptoms were tiredness (71.8%), head pain (33.1%), cognitive difficulties (11.7%), 'hangover' (10.7%), gastrointestinal symptoms (8.4%), mood change (6.8%), and weakness (6.2%). Patients with postdrome compared with patients without postdrome have more characteristic and more frequent migraine features. This study demonstrated postdrome in 68% of patients, duration<or=24 h in most patients, more often associated with a full-blown migraine attack, more common in females, and with commonest symptoms being tiredness and low-grade headache.
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PMID:The postdrome of the acute migraine attack. 1642 78

Fibromyalgia (FMS) is a debilitating disorder characterized by chronic diffuse muscle pain, fatigue, sleep disturbance, depression and skin sensitivity. There are no genetic or biochemical markers and patients often present with other comorbid diseases, such as migraines, interstitial cystitis and irritable bowel syndrome. Diagnosis includes the presence of 11/18 trigger points, but many patients with early symptoms might not fit this definition. Pathogenesis is still unknown, but there has been evidence of increased corticotropin-releasing hormone (CRH) and substance P (SP) in the CSF of FMS patients, as well as increased SP, IL-6 and IL-8 in their serum. Increased numbers of activated mast cells were also noted in skin biopsies. The hypothesis is put forward that FMS is a neuro-immunoendocrine disorder where increased release of CRH and SP from neurons in specific muscle sites triggers local mast cells to release proinflammatory and neurosensitizing molecules. There is no curative treatment although low doses of tricyclic antidepressants and the serotonin-3 receptor antagonist tropisetron, are helpful. Recent nutraceutical formulations containing the natural anti-inflammatory and mast cell inhibitory flavonoid quercetin hold promise since they can be used together with other treatment modalities.
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PMID:Fibromyalgia--new concepts of pathogenesis and treatment. 1656 42

Phosphoglycerate kinase (PGK) deficiency is a rare X-linked disease that is characterised by mild to severe haemolytic anaemia, rhabdomyolysis, and variable defects in the central nervous system. In a white American family, two sons presented with haemolytic anaemia, seizures, and developmental delay. The diagnosis of PGK deficiency was made based on the remarkably low (<5% of normal) erythrocyte PGK enzyme activity level and the identification of a missense (c. 491A --> T) PGK1 gene mutation. This mutation results in an Asp164Val amino acid substitution, which has previously been designated PGK-Amiens and PGK-New York. The two new patients have the full clinical syndrome of PGK deficiency including haemolytic anaemia, developmental delay and seizures, and in the proband, hemiplegic migraines, retinal dystrophy and muscle fatigue. The PGK-Amiens/New York mutation had previously been found in a French patient and also in a large Chinese-Australian kindred, indicating that either the c. 91A --> T mutation is a recurrent mutation or that there is shared ancestry between the patients that have been identified so far with the mutation. Haplotype analysis of the c. 91A --> T mutation indicated that this was a recurrent mutation.
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PMID:The identification of a recurrent phosphoglycerate kinase mutation associated with chronic haemolytic anaemia and neurological dysfunction in a family from USA. 1674 Jan 38

Milnacipran is a serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor currently available for use as an antidepressant in several countries. Phase III clinical trials are currently underway to assess its potential role in the treatment of fibromyalgia syndrome, and in pursuit of US Food and Drug Administration approval for this indication. Evidence has accumulated suggesting that in animal models, milnacipran may exert pain-mitigating influences involving NE- and 5-HT-related processes at supraspinal, spinal and peripheral levels of pain transmission. Preliminary evidence suggests that milnacipran may be useful in mitigating pain and fatigue associated with fibromyalgia. However, its role in addressing comorbidities associated with fibromyalgia, including visceral pain and migraine, has yet to be investigated.
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PMID:Clinical potential of milnacipran, a serotonin and norepinephrine reuptake inhibitor, in pain. 1686 17

Cyclic vomiting syndrome, which is characterized by severe discrete episodes of nausea, vomiting, and lethargy, is a fairly common, disabling, predominately childhood condition. Approximately 25% of cases have coexisting neuromuscular disease manifestations (cyclic vomiting syndrome plus). To determine whether patients with cyclic vomiting syndrome and neuromuscular disease represent a distinct subentity within cyclic vomiting syndrome, a clinical interview was conducted regarding 80 randomly ascertained sufferers of cyclic vomiting syndrome from a disease association database. Cyclic vomiting syndrome plus and "cyclic vomiting syndrome minus," herein defined as the presence of at least two and zero neuromuscular disease manifestations, were present in 23 and 44 subjects, respectively. Neuromuscular disease manifestations, including cognitive disorders, skeletal myopathy, cranial nerve dysfunction, and seizure disorders, were found to statistically cluster together among the same subjects. In addition, subjects with cyclic vomiting syndrome with neuromuscular disease had an earlier age at onset for vomiting episodes and a three- to eightfold statistically increased prevalence for certain dysautonomia-related (migraine, chronic fatigue, neurovascular dystrophy) and constitutional (growth retardation and birth defects) disorders. However, subjects with cyclic vomiting syndrome with and without neuromuscular disease were equally likely to have a sibling affected with neuromuscular disease manifestations. We conclude that cyclic vomiting syndrome plus, although likely not genetically distinct from cyclic vomiting syndrome minus, represents a distinct phenotypic entity that predicts an earlier onset of disease and increased comorbidity with a distinct list of medical conditions, possibly owing to a higher degree of mitochondrial dysfunction.
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PMID:Cyclic vomiting syndrome plus. 1690 17

The nosology of migraine premonitory (PS) and resolution (RS) symptoms was studied in 100 migraineurs consulting their general physician. They were asked to fill in, for three attacks, a PS and RS questionnaire. 'True' PS/RS were those experienced the day before (or the day after) the headache had started only if they were not present in a questionnaire completed in a pain-free period. True PS and RS were experienced by 84% and 80%, respectively, of subjects for the first attack. The mean and range (per patient) of PS were 6.8 and 0-21 and of RS 4.7 and 0-15. Anxiety, phonophobia, irritability, unhappiness and yawning were the commonest PS, whereas asthenia, tiredness, somnolence and concentration difficulties were the most common RS. Gender, age and Migraine Disability Assessment scores did not influence PS and RS. Both PS and RS were more frequent in migraine with aura subjects. Patients on preventatives showed a decreased frequency of PS and, to a lesser degree, of RS. Severity of headache was associated with a higher frequency of RS. Individual RS and especially PS were quite consistent after three attacks. Almost two-thirds of the symptoms were noticed in at least two out of three attacks, while more than a half of PS and more than a quarter of RS repeated in three out of three attacks. In conclusion, around 80% of unselected migraineurs experience RS and PS. Migraine with aura and severe pain are risk factors for experiencing PS and RS, while preventatives were protective, especially for PS.
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PMID:Premonitory and resolution symptoms in migraine: a prospective study in 100 unselected patients. 1691 55

Migraine headaches are among the leading causes of disability in the world. The burden of migraines is highest in women of reproductive age. This cross-sectional study characterized the prevalence, symptoms and correlates of migrainous headaches in 154 pregnant women attending a prenatal care clinic in Lima, Peru. Lifetime prevalence of migraine defined by modified IHS criteria was 9.1% (95% CI 4.6-13.6). When probable migraines were included, the lifetime prevalence of migraine in this population was 29.2% (95% CI 22.0-36.4). Migraine headaches were associated with a maternal history of headache, childhood carsickness, a diagnosis of allergies, and a high frequency of fatigue. Although headache-related disability was low in terms of missed work and recreation, high rates of headache pain and medicinal use reflect the true impact on this population.
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PMID:Prevalence and correlates of migraine among women attending a prenatal care clinic in Lima, Peru. 1691 59

Zonisamide is a new antiepileptic drug with multiple mechanisms of action and a favourable pharmacokinetic profile. Preliminary data suggest that zonisamide may be effective in migraine prophylaxis. We evaluated the efficacy and tolerability of zonisamide for migraine prophylaxis in refractory patients. We reviewed the charts of adult patients with International Headache Society-defined episodic migraine (EM) or with transformed migraine (TM) according to the Silberstein-Lipton criteria, who had been treated with zonisamide at our out-patient clinic for at least 60 days. Demographic data, zonisamide dosage and duration of treatment were collected and analysed. Headache frequency, attack duration, headache severity and headache-related disability before and after treatment initiation with zonisamide were compared. Thirty-three patients were included in the study (average age 43.9 +/- 8.4 years; 23 (70%) with TM and 10 (30%) with EM). The patients had failed an average of 6.2 migraine prophylactic drugs prior to zonisamide. The average zonisamide daily dose was 337.9 +/- 146.3 mg and the average duration of treatment was 186.4 +/- 174.0 days. The average number of days with headache per month was reduced in the entire study population from 20.7 +/- 9.5 before zonisamide treatment to 18.0 +/- 11.3 after its initiation (P = 0.06) [in TM from 24.7 +/- 7.3 to 21.0 +/- 10.7 (P = 0.06); in EM from 11.6 +/- 7.6 to 11.0 +/- 9.7 (P = NS)]. No significant changes in other headache parameters were found. Fourteen patients (42.4%) reported adverse events (AEs), the most common of which was fatigue. Most patients (12/14, 85.7%) rated AEs as mild or moderate. In this group of refractory migraine patients, zonisamide therapy did not result in a statistically significant beneficial effect on headache or on associated symptoms.
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PMID:Zonisamide for migraine prophylaxis in refractory patients. 1696 86


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