Neurology
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Emerging evidence from animal models of neuropathic pain suggests that many pathophysiologic and biochemical changes occur in the peripheral and central nervous system. Similarities between the pathophysiologic phenomena observed in some epilepsy models and in neuropathic pain models justify the use of anticonvulsants in the symptomatic management of neuropathic pain. Positive results from laboratory and clinical trials further support such use. ⋯ Anecdotal experience provides support for studies with oxcarbazepine and levetiracetam for treating neuropathic pain. Evidence supporting the efficacy of anticonvulsants in treatment of such pain is evolving. Additional clinical trials should provide information that will better define their role in neuropathic pain.
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Chronic daily headache (CDH) affects approximately 4 to 5% of the population and encompasses a number of different diagnoses, including transformed migraine, chronic tension-type headache (TTH), new-onset daily persistent headache, and hemicrania continua. Although the pathophysiology of CDH is still poorly understood, some research has suggested that each of the various subtypes of CDH may have a different pathogenesis. ⋯ Several pharmacologic treatment options exist, including antidepressants, anticonvulsants, muscle relaxants, serotonin agonists, ergots, serotonin antagonists, antianxiety agents, and other miscellaneous drugs. Tizanidine, an alpha(2)-adrenergic agonist, has recently emerged as a promising prophylactic adjunct for CDH, which implicates a central alpha(2)-adrenergic mechanism as an important factor in the pathophysiology of CDH.
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Intraspinal drug delivery represents an important treatment option for the management of chronic pain. Selection of candidates for this type of therapy requires careful evaluation of the patient, possibly including psychological screening. ⋯ Such agents include opioids, alpha(2)-agonists, sodium channel antagonists, and gamma-aminobutyric acid agonists. In addition, combinations of agents with distinct mechanisms of action may be therapeutically advantageous because many clinical pain states result from more than one mechanism.
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Clinical Trial
Sustained cholinesterase inhibition in AD patients receiving rivastigmine for 12 months.
To study the long-term dual inhibitory effects of rivastigmine on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in patients with AD. ⋯ Rivastigmine causes persistent inhibition of AChE and BuChE in CSF as well as plasma. The persistent CSF inhibition contrasts with earlier findings after long-term treatment by the reversible ChE inhibitor tacrine, which demonstrated increased AChE activity in the CSF but not in the blood. Rivastigmine's effects on the preferential up-regulation of the AChE-R isoform may have a favorable effect on disease stabilization.
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In this longitudinal study of 77 patients with mild cognitive impairment (MCI), the authors analyzed whether levels of tau protein phosphorylated at threonine 231 (p-tau(231)) in CSF correlate with progression of cognitive decline. High CSF p-tau(231) levels at baseline, but not total tau protein levels, correlated with cognitive decline and conversion from MCI to AD. Independently, old age and APOE-epsilon 4 carrier status were predictive as well. Our data indicate that an increased p-tau(231) level is a potential risk factor for cognitive decline in patients with MCI.