Expert review of neurotherapeutics
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Expert Rev Neurother · May 2009
ReviewSecretase inhibitors and modulators for Alzheimer's disease treatment.
Genetic and biological studies provide strong evidence that the deposition of amyloid-beta peptide (Abeta) contributes to the etiology of Alzheimer's disease (AD). Abeta is generated from amyloid-beta precursor protein by beta- and gamma-secretases, which are plausible molecular targets for AD treatment. Thus, drugs that regulate the production of Abeta by inhibiting or modulating secretase activity could provide effective therapeutics for AD. ⋯ Moreover, extensive drug screening and development have enabled some secretase inhibitors and modulators to advance into late-Phase clinical trials. This review focuses on recent progresses in beta- and gamma-secretase biology, including the proteolytic mechanism, regulation and composition of these enzymes. Moreover, this review discusses the recent development of inhibitors, and provides a direction for the effective treatment of AD through inhibition/modulation of beta- and gamma-secretase activities.
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Cerebral venous thrombosis (CVT) was formerly considered a rare disorder, associated with an unfavorable outcome. More recent data based on modern imaging techniques, however, have changed our perception of this disorder. The use of angiography and, especially, MRI have allowed an early diagnosis and have proved that the incidence of CVT is, in fact, higher than previously thought, approximately 3-4 cases per million people per year, and that the majority of patients have a favorable outcome. ⋯ The clinical presentation of CVT is highly variable and includes patients with just a mild headache, others with focal neurological deficits and a few with a dramatic syndrome with coma; seizures are a frequent presenting symptom. The best radiological examination to confirm the suspicion of CVT is MRI of the brain, which can both demonstrate parenchymal lesions and directly show evidence of sinus occlusions. The available evidence suggests that anticoagulants are effective in reducing mortality and dependency in CVT patients; the possible role of systemic or localized thrombolysis is still to be established.
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'Sinus headache' is a term used by many patients and primary-care physicians and, contrary to popular belief, sinus headaches are uncommon. Headaches that are due to sinusitis are confined to a minority of patients who have acute frontal sinusitis or sphenoiditis. The International Headache Society classification is robust in qualifying the term sinus headache and says that "chronic sinusitis is not validated as a cause of headache and facial pain unless relapsing into an acute stage". ⋯ First, acute sphenoid sinusitis is rare and second, most of these patients respond to antibiotics. Batotrauma can cause short-lived pain in the sinus involved but there is always a clear history associated with diving or flying and, as the pressure within the sinus equalizes, the pain resolves within a few hours. Headaches are rarely due to sinusitis.
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Combined oral contraceptives are a safe and highly effective method of birth control, but they can also raise problems of clinical tolerability and/or safety in migraine patients. It is now commonly accepted that, in migraine with aura, the use of combined oral contraceptives is always contraindicated, and that their intake must also be suspended by patients suffering from migraine without aura if aura symptoms appear. ⋯ Other risk factors (tobacco use, hypertension, hyperlipidemia, obesity and diabetes) must be carefully considered when prescribing combined oral contraceptives in migraine without aura patients, in particular in women aged over 35 years. Furthermore, the exclusion of a hereditary thrombophilia and of alterations of coagulative parameters should precede any decision of combined oral contraceptive prescription in migraine patients.
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Expert Rev Neurother · Mar 2009
ReviewAllodynia in migraine: frequent random association or unavoidable consequence?
Allodynia, the perception of pain induced by a non-painful stimulus, is frequently associated with migraine, especially when chronic, and mainly in the aura subtype. Among migraineurs, allodynia is thought to be caused by the headache and the activation of nociceptors with the development of central sensitization in subjects with an altered regulation of the central nociceptive pathway. The persistence of pain sensation seems to be able to induce central sensitization in the caudal nucleus of the trigeminal nerve by lowering the neuronal pain threshold. ⋯ This symptom must be carefully assessed because it may be as annoying and limiting in daily activities as pain itself, and because its presence seems to reduce the efficacy of drugs used for migraine attacks. Instrumental measures may be applied, and clinical questionnaires to assess the presence of allodynic symptoms have also been developed and validated. All these aspects will be discussed.