Arterioectatic Spinal Angiopathy of Childhood: Clinical, Imaging, Laboratory, Histologic, and Genetic Description of a Novel CNS Vascular Pathology.

Pediatric patients with myelopathy expressing intradural spinal vascular ectasia without arteriovenous shunting were studied at four tertiary referral neuropediatric centers. Patients were identified by retrospective review of institutional records and excluded if spinal vascular pathology could be classified into a previously described category of spinal vascular malformation. Four patients meeting the study criteria were enrolled in the study. Clinical, magnetic resonance imaging, catheter-directed angiography, laboratory, histological and genetic data were analyzed to characterize the disease process and elucidate underlying pathomechanisms. Our study revealed a highly lethal, progressive multi-segmental myelopathy associated with a unique form of non-inflammatory spinal angiopathy featuring diffuse enlargement and tortuosity of spinal cord arteries, spinal cord hyperemia, and spinal cord edema (Arterioectatic Spinal Angiopathy of Childhood). The condition was shown to mimic venous congestive myelopathy associated with pediatric spinal cord arteriovenous shunts on MRI but to have distinct pathognomonic findings on catheter-directed angiography. Clinicopathological, genetic, and neuroimaging features, which are described in detail, closely overlap with those of mitochondrial disease.

Symptoms of cutaneous sensitivity pre-treatment and post-treatment: results from the rizatriptan TAME studies.

The presence of cutaneous allodynia may predict response to triptans. Identical randomized double-blind studies were conducted comparing the efficacy of rizatriptan 10 mg or placebo administered within 1 h of headache onset, while pain was mild. The primary endpoint was freedom from pain at 2 h. Presence of symptoms suggesting cutaneous sensitivity (SCS) at baseline and at 2 h post-treatment was recorded. Before treatment, 29% of rizatriptan patients and 22% of placebo patients reported SCS. At 2 h, the percentage of patients with SCS was significantly decreased with rizatriptan. The presence of SCS pre-treatment was not predictive of response to rizatriptan. Most patients with SCS at 2 h were non-responders. Early treatment with rizatriptan significantly reduced the percentage of patients with SCS at 2 h. The presence of SCS at baseline did not predict pain-free response, but presence of SCS at 2 h correlated with lack of a 2-h pain-free response.

Rizatriptan for the acute treatment of ICHD-II proposed menstrual migraine: two prospective, randomized, placebo-controlled, double-blind studies.

These are the first prospective studies to use criteria for menstrual migraine proposed in the 2004 revision of the International Classification of Headache Disorders (ICHD-II) to examine the efficacy of rizatriptan for treatment of a menstrual attack. Two identical protocols (MM1 and MM2) were randomized, parallel, placebo-controlled, double-blind studies. Adult women with ICHD-II menstrual migraine were assigned to either rizatriptan 10-mg tablet or placebo in a 2 : 1 ratio. Patients treated a single menstrual migraine attack of moderate or severe pain intensity. The primary end-point was 2-h pain relief and the secondary end-point was 24-h sustained pain relief. A total of 707 patients (MM1 357, MM2 350) treated a menstrual migraine attack. The percentage of patients reporting 2-h pain relief was significantly greater for rizatriptan than for placebo (MM1 70% vs. 53%, MM2 73% vs. 50%), as was the percentage of patients reporting 24-h sustained pain relief (MM1 46% vs. 33%; MM2 46% vs. 33%). Rizatriptan 10 mg was effective for the treatment of ICHD-II menstrual migraine, as measured by 2-h pain relief and 24-h sustained pain relief.

Oral glycoprotein IIb/IIIa antagonism in patients with coronary artery disease.

Dose-finding studies and trials of interaction of oral glycoprotein IIb/IIIa antagonists with other antiplatelet agents have been limited. We hypothesized that these detailed assessments could be first performed in patients with stable coronary artery disease (CAD) and then extrapolated to the target population. To this end, we performed 2 sequential studies. The first study examined the dose-related effects on indexes of platelet and vascular function induced by the oral inhibitor RPR 109891, when given alone and in combination with aspirin, in patients (n = 100) with stable CAD. The second study (the Antagonism of the FIbrinogen Receptor after Myocardial Events trial) assessed the pharmacodynamics and safety of derived regimens in patients (n = 320) with unstable coronary syndromes. In patients with stable CAD, platelet aggregation was dose dependently inhibited by RPR 109891, and the dose-response relation was shifted to the right by the concomitant administration of aspirin (p = 0.0001). The degree of platelet inhibition induced by 3 doses of RPR 109891 (plus aspirin) was lower in patients with unstable than stable CAD. No drug-related major bleeding occurred in either study. RPR 109891 treatment was associated with acute and delayed thrombocytopenia. In conclusion, chronic treatment with an oral glycoprotein IIb/IIIa antagonist (1) induces antiplatelet effects that are potentiated by concomitant administration of aspirin, (2) may require dose adjustment in syndromes of platelet activation, (3) is associated with a low rate of clinically significant bleeding when doses inducing incomplete inhibition of platelet aggregation are used, and (4) requires frequent monitoring of platelet count unless reliable predictors of delayed thrombocytopenia become available.