Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Episodic brain disorders (EBD) form an intriguing group of neurological diseases in which at least some of the symptoms occur in attacks. The hypothalamus integrates many brain functions, including endocrine and autonomic control, and governs various body rhythms. It seems a likely site in which the initiation of attacks of EBD can be modulated. Indeed, the hypothalamus has a crucial role in EBD such as narcolepsy and cluster headache. The same may be true for migraine and depression. Here we summarise the evidence supporting an important role for the hypothalamus in the initiation of disease episodes in various EBD. Study of the various pathophysiological concepts of EBD within the context of the hypothalamus may prove a fruitful example of cross-fertilisation between various research areas.
 ...
PMID:The hypothalamus in episodic brain disorders. 1284 66

In order to evaluate a possible association between migraine and idiopathic narcolepsy, we performed a multicentre case-control study on the comorbidity of narcolepsy and different headaches. In total, 96 patients with idiopathic narcolepsy were enrolled. The migraine frequency in the patients and in the control group was 21.9% and 19.8%, respectively (P = 0.722). The migraine features did not differ significantly between both groups. However, headache fulfilling the criteria for tension-type headache was significantly more often reported by narcolepsy patients than by the control group (60.3% vs. 40.7%, P= 0.006). We conclude that there is no association between migraine and narcolepsy but that patients with narcolepsy show more unspecific headache, probably due to sleep disturbances.
Cephalalgia 2003 Oct
PMID:Migraine and idiopathic narcolepsy--a case-control study. 1451 Sep 22

In a multicenter, randomized, double-blind study the authors compared the efficacy of modafinil 400 mg once daily, 400 mg given in a split dose, or 200 mg once daily for maintaining wakefulness throughout the day in patients (N = 32) with narcolepsy reporting a positive daytime response to modafinil but late-afternoon/evening sleepiness. Efficacy evaluations included an extended Maintenance of Wakefulness Test (9:00 am to 9:00 pm), the Clinical Global Impression of Change scale, and the Epworth Sleepiness Scale. Modafinil demonstrated significant improvement in wakefulness as assessed by the Epworth Sleepiness Scale compared with placebo at baseline (all P < 0.001). Modafinil significantly improved patients' ability to sustain wakefulness, as demonstrated by mean sleep latency at week 3 compared with placebo at baseline (all P < 0.001). The 400-mg split-dose regimen improved wakefulness significantly in the evening compared with the 200-mg and 400-mg once-daily regimen (both P < 0.05). The percentage of patients rated as "much improved" or "very much improved" with respect to evening sleepiness was 27%, 82%, and 80% in the 200-mg, 400-mg once-daily, and 400-mg split-dose groups, respectively. Adverse events were mild to moderate in nature and included headache, nausea, nervousness, dyspepsia, pain, and vomiting (all 6%). Some patients may benefit from 400-mg doses of modafinil taken once daily compared with 200-mg doses. A split-dose 400-mg regimen may be superior to once-daily dosing for sustaining wakefulness throughout the entire waking day.
 ...
PMID:Dosing regimen effects of modafinil for improving daytime wakefulness in patients with narcolepsy. 1452 Jan 65

This trial was conducted to evaluate the pharmacokinetics and safety of a sodium oxybate (gamma-hydroxybutyrate [GHB]) oral solution in narcoleptic patients after acute and chronic treatment. An open-label, two-period, two-treatment study design was used. Trial subjects included 13 patients with polysomnographically confirmed narcolepsy. The patients were administered a bedtime dose of 4.5 g of sodium oxybate while in a sleep research center. They were subsequently treated with sodium oxybate at the nightly dose of 4.5 g for 8 weeks. The patients then returned to the sleep center and were again treated with the 4.5-g sodium oxybate dose at bedtime. Blood samples (5 mL) were collected at 18 time points before and up to 7 hours after both the first dose of sodium oxybate and following 8 weeks of dosing. Plasma samples were analyzed for oxybate content by a validated liquid chromatography/tandem mass spectrometry (LC/MS/MS) method. Noncompartmental methods were applied in the determination of pharmacokinetic parameters from each patient's plasma oxybate concentration versus time curve. No serious adverse events were recorded, and all patients completed the study. Headache, enuresis, and leg cramps were reported as adverse experiences. With both acute and chronic dosing, sodium oxybate was rapidly absorbed and eliminated with an apparent half-life of about 40 minutes. The only changes observed in the kinetics of oxybate after 8 weeks of treatment were a 13% and 16% increase in peak concentration (C(max)) and systemic exposure (AUC), respectively. The pharmacokinetics of sodium oxybate in narcoleptic patients were not changed in any clinically significant manner when the drug was chronically administered. The drug was well tolerated.
 ...
PMID:The pharmacokinetics of sodium oxybate oral solution following acute and chronic administration to narcoleptic patients. 1497

In January 2004, the wake-promoting agent, modafinil, was approved in the US for the treatment of excessive sleepiness (ES) associated with obstructive sleep apnoea/hypopnoea syndrome (OSAHS) and shift-work sleep disorder (SWSD), representing an expansion of its labelling from the initial indication for ES associated with narcolepsy. A total of five randomised, placebo-controlled studies in these three disorders showed statistically significant benefits on various objective measures and subjective estimates of ES, including the Multiple Sleep Latency Test, Maintenance of Wakefulness Test, Epworth Sleepiness Scale and Karolinska Sleepiness Scale. Significant improvement was also seen in overall clinical condition (on the Clinical Global Impression of Change) and measures of sustained attention and reaction time (on the Psychomotor Vigilance Task). The clinical efficacy of modafinil, combined with improved safety over CNS stimulants, has made it the most prescribed medication for the treatment of ES associated with narcolepsy. Modafinil is the only medication approved for ES associated with OSAHS and SWSD (for OSAHS, it is indicated as an adjunct to standard treatments for the under-lying obstruction). Unlike many other medications used for ES, modafinil is not known to be abused. The most common adverse event reported in clinical studies was headaches; most were transient and mild-to-moderate in severity. Modafinil also has the potential for interactions with other drugs metabolised via cytochrome P450 enzyme pathways. Potential obstacles to the use of modafinil include an under-recognition of ES and its consequences. Increased education, both of the public and the medical community, should improve the recognition and therapy of ES.
 ...
PMID:Modafinil: new indications for wake promotion. 1570 89

To investigate the prevalence of sleep disorders and their symptoms in children with headaches, 64 patients in the outpatient clinics of the University of Chicago Department of Pediatric Neurology were interviewed. Investigated disorders included excessive daytime sleepiness, narcolepsy, insomnia, sleep apnea, restlessness, and parasomnias. Unlike previous studies, subjects were compared with matched control patients by age and sex. Both headache and nonheadache groups completed a 111-item questionnaire detailing sleep symptoms and behaviors. It was found that children with headaches have a significantly higher prevalence of excessive daytime sleepiness, narcolepsy, and insomnia than children without headaches (P < 0.005), which is consistent with prior literature. A similar result was obtained in examining only migraines. However, we did not find a significantly higher prevalence of symptoms of sleep apnea, restlessness, and parasomnias, which contradicts previous literature. Also, the effect of medications taken by headache patients as a confounding factor was insignificant. Overall, pediatricians may find it beneficial to ask about daytime sleepiness, narcolepsy, and insomnia when treating a headache patient.
 ...
PMID:Characterization of symptoms of sleep disorders in children with headache. 1637 71

gamma-Hydroxybutyrate (GHB) is an endogenous short chain fatty acid and a, mostly oral, pharmacological compound that has been utilised in a variety of ways. Endogenously, GHB is synthesised locally within the CNS, mostly from its parent compound GABA. Sodium oxybate is the sodium salt of GHB and is used for the exogenous oral administration of GHB. It is likely that supraphysiological concentrations of GHB from exogenous administration produce qualitatively different neuronal actions than those produced by endogenous GHB concentrations. Evidence suggests a role for GHB as a neuromodulator/neurotransmitter. Under endogenous conditions and concentrations, and depending on the cell group affected, GHB may increase or decrease neuronal activity by inhibiting the release of neurotransmitters that are co-localised with GHB. After exogenous administration, most of the observed behavioural effects appear to be mediated via the activity of GHB at GABA(B) receptors, as long as the concentration is sufficient to elicit binding, which does not happen at endogenous concentrations. Endogenous and exogenous GHB is rapidly and completely converted into CO(2) and H(2)O through the tricarboxylic acid cycle (Krebs cycle). Sodium oxybate has been observed to modulate sleep in nonclinical study participants, and sleep and wakefulness in clinical populations, including groups with insomnia, fibromyalgia and narcolepsy. In narcolepsy, sodium oxybate has shown dose-related effects on various properties of sleep, including increases in slow-wave sleep duration and delta power, and a reduced number of night-time awakenings. Furthermore, multiple measures of daytime sleepiness and cataplexy demonstrated consistent short- and long-term improvement in response to night-time sodium oxybate therapy. The most common reported adverse events include dose-related headache, nausea, dizziness and somnolence.
 ...
PMID:gamma-Hydroxybutyrate/sodium oxybate: neurobiology, and impact on sleep and wakefulness. 1714 Feb 79

Restless legs syndrome (RLS) has proven to often have both a difficult differential diagnosis and also problems with assessing severity. These problems contribute to some of the confusion about medication effects on RLS and also to the large placebo effect seen in clinical trials. We need to find better diagnostic and evaluative methods. The following three promising methods for better diagnosis and evaluation have been somewhat overlooked. (1) The polysomnogram with a preceding suggested immobilization test offers objective measures of the motor sign of RLS, the periodic leg movements in sleep (PLMS) under standard conditions of sleep and during quiet resting, both of which provoke RLS symptoms. The diagnostic sensitivity and specificity for these measures is about the same as that for MSLT diagnosis of narcolepsy and the use of these tests deserves to be reconsidered. (2) Leg activity measures provide an attractive less costly and more accessible alternative to the polysomnogram and can be used on repeated nights, reducing measurement problems occurring because of the well-recognized variability in symptom expression across days. (3) RLS-logs provide a more concurrent assessment of RLS symptom occurrence that provide a more direct measure of severity than questionnaires completed at clinic visits. Similar logs have been found useful in evaluating other sensory disorders such as headache. These methods need to be developed and evaluated in both our research and clinical trials of RLS because they may enhance accuracy of diagnosis and reduce the placebo response to treatments.
 ...
PMID:Improving RLS diagnosis and severity assessment: polysomnography, actigraphy and RLS-sleep log. 1756 34

(1) Narcolepsy is characterised by sudden, overwhelming daytime drowsiness, sometimes associated with cataplexy (more or less complete loss of muscle tone during an emotional reaction). (2) Modafinil moderately reduces daytime drowsiness but has no effect on cataplexy. Methylphenidate, an amphetamine psychostimulant, seems to act on both drowsiness and cataplexy, although its clinical evaluation is limited to observational series. (3) Oxybic acid, long used in general anaesthesia, but also misused for recreational and criminal purposes (chemical or drug-induced submission), has been approved to treat adults with both narcolepsy and cataplexy, in the form of an oral solution of sodium oxybate. (4) The rationale behind the use of sodium oxybate is to re-establish a near-normal pattern of the different phases of sleep. Because of its short-lasting action, sodium oxybate has to be taken once at bedtime and then again 2.5 to 4 hours later. (5) Clinical evaluation mainly consists of 4 double-blind placebo-controlled trials of sodium oxybate. Three short-term trials, involving 136 patients treated for 4 weeks and 228 and 270 patients treated for 8 weeks, showed that sodium oxybate at a dose of 4.5 g to 9 g a day reduced the number of cataplexy attacks but that a dose of at least 6 g was needed to reduce daytime drowsiness. A trial involving 56 patients who had been taking sodium oxybate for nearly 2 years, assessed the effects of stopping versus continuing treatment. The results suggest that sodium oxybate is effective in the long term. (6) During clinical trials, 61% of patients had adverse effects attributed to sodium oxybate. These included gastrointestinal disorders (nausea (18%)), neurological disorders (dizziness (15%), headache (6%)), confusion (3%), and enuresis (7%). (7) Altered consciousness and respiratory depression occurred after a single intake of a dose two or three times higher than the recommended dose. (8) Misuse, especially to obtain chemical or drug-induced submission (i.e. as a 'date rape' drug), is facilitated by the odourless and colourless nature of the oral solution. (9) In practice, for some patients who are seriously affected by persistent episodes of cataplexy or drowsiness, despite treatment of narcolepsy, sodium oxybate is preferable to methylphenidate, which has been less thoroughly evaluated. However, the risks of misuse and overdose mean that this drug should only be proposed to patients in whom the benefits are likely to outweigh the risks.
 ...
PMID:Sodium oxybate: new drug. Fewer attacks of cataplexy in some patients. 1758 23

(1) The first-line treatment for patients with troublesome obstructive sleep apnoea syndrome is night-time nasal continuous positive airway pressure, which reduces daytime drowsiness and improves cognitive performance. (2) Modafinil, a non amphetamine psychostimulant already marketed for idiopathic narcolepsy and hypersomnia, is the first drug to be approved in France for the treatment of patients with residual daytime drowsiness despite nasal continuous positive airway pressure treatment. (3) Clinical evaluation of modafinil for this indication consists of two short-term double-blind placebo-controlled trials, lasting 4 and 12 weeks, and including a total of about 500 patients. At a dose of 400 mg/day, 68% of patients experienced an improvement in their daytime drowsiness (usually partial), compared to 37% of patients on placebo. It is not known how many patients no longer had any daytime drowsiness. A major improvement occurred in about 14% of patients (7% on placebo). (4) The main adverse effects of modafinil are neuropsychological (headache, nervousness, insomnia, anxiety, nausea). (5) In short, modafinil is an option to consider when continuous positive airway pressure is not sufficiently effective and when drowsiness continues to significantly interfere with daily activities. However, it only appears to provide a major benefit to about 10% of patients. The only important improvement is in daytime drowsiness, and this is often offset by adverse effects such as headache. Effects of long-term treatment are not known.
 ...
PMID:Modafinil: new indication. For a minority of patients with sleep apnoea. 1758 24


<< Previous 1 2 3 4 5 6 Next >>