Therapeutic effects and safety of olcegepant and telcagepant for migraine A meta-analysis

OBJECTIVE： To evaluate the therapeutic effects and adverse reactions of olcegepant and telcagepant for the treatment of migraine. DATA RETRIEVAL： We identified studies using Medline （1966-01/2012-06）, PubMed （1966-01/2012-06）, Scopus （1980-01/2012-06）, Cochrane Central Register of Controlled Trials （1980-01/2012-06） and China National Knowledge Infrastructure （1980-01/2012-06）. SELECTION CRITERIA： The included studies were double-blind, randomized and placebo-controlled trials of olcegepant or telcagepant for the treatment of single acute migraine in patients with or without aura. Adverse reaction data were also included. Two independent investigators performed quality evaluation and data extraction using Jadad scoring. Meta-analyses were undertaken using RevMan 5.0.25 software. MAIN OUTCOME MEASURES： Pain relief rate, pain-free rate, and incidence of adverse reactions were measured in patients 2 and 24 hours after injection of olcegepant and oral teicagepant. RESULTS： Six randomized, controlled trials were included. Meta-analysis demonstrated that compared with placebo, the pain relief rate （odds ratio, OR = 5.21, 95% confidence interval, CI： 1.91-14.2, P 〈 0.01） and pain-free rate （OR = 31.11, 95% Ch 3.80-254.98, P 〈 0.01） significantly increased 2 hours after 2.5 mg/d olcegepant treatment. Pain relief rate and pain-free rate 2 and 24 hours after treatment with telcagepant 150 mg/d and 300 mg/d were superior to placebo （P 〈 0.01）. Moreover, the remission rate of unrelenting headache was higher after 24 hours of 300 mg/d telcagepant treatment compared with 150 mg/d （OR = 0.78, 95% Ch 0.62-0.97, P 〈 0.05）. The incidence of adverse reactions with olcegepant was not significantly greater than placebo （P = 0.28） but within 48 hours of administration of telcagepant 300 mg/d, the incidence of adverse reactions was higher than placebo （OR = 1.21,95% Ch 1.04-1.42, P 〈 0.01）. Few studies have compared the therapeutic effects of olcegepant and telcagepant. CONCLUSION： The calcitonin-gene-related peptide receptor antagonists olcegepant and telcagepant have shown good therapeutic effects in the treatment of migraine. Moreover, the incidence of adverse reactions compares favorably with placebo, although liver transaminases may become elevated after long-term use.

Tumor necrosis factor-alpha in experimental autoimmune neuritis

Tumor necrosis factor-α （TNF-α） plays a key role in the pathogenesis of experimental autoimmune neuritis （EAN） as well as Guillain-Barre syndrome. The proposed pathogenesis of TNF-α associated neuropathies involves immune-mediated attack to blood-nerve barrier, aggravated production of pro-inflammatory cytokines, and the induction of Schwann cells apoptosis. TNF-α may play a regulatory role by increasing production of interleukin-1 in macrophages, attenuating T cell receptor signaling and regulating apoptosis of potentially autoreactive T cells in EAN. The data suggest that antagonizing TNF-α functions or suppressing TNF-α production may be useful in the acute phase of EAN treatment, but further studies are required.

A case of thalamic hemorrhage-induced diaschisis

Diaschisis refers to a disturbance （inhibition or facilitation） of function in an area remote from the site of a primary brain lesion. Previous studies have confirmed that regional cerebral blood flow and metabolism are noticeably decreased in an infarct region. Transient excessive perfusion appears in the ischemic penumbra, and diaschisis occurs in an area remote from the lesion site, showing decreased regional cerebral blood flow and metabolism. Mirror diaschisis refers to a decrease in oxygen metabolism and blood flow in the ＂mirror image area＂ to the infarct regions in the contralateral hemisphere. In this study, a patient with right thalamic hemorrhage was affected with right arm and leg numbness. At 4 months before onset, magnetic resonance imaging of the head demonstrated lacunar infarcts in the left thalamus; therefore the right arm and leg numbness was not associated with lacunar infarcts in the left thalamus. At 8 days following onset, magnetic resonance imaging reexamination did not reveal the focus that could induce right arm and leg numbness and weakness. Thus, it is suggested in this study that the onset of this disease can be explained by mirror diaschisis. That is, right thalamic hemorrhage leads to decreased blood flow and metabolic disturbance in the contralateral thalamus, resulting in right arm and leg numbness.