Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures.

BACKGROUND: Pregabalin is an alpha(2)-delta ligand that has anxiolytic, analgesic, and anticonvulsant properties. OBJECTIVE: To establish the efficacy, safety, and tolerability of pregabalin administered twice-daily (BID) without dose titration as adjunctive treatment in patients with partial seizures and to confirm the dose-response relationship. METHODS: This 76-center, double-blind, randomized, placebo-controlled, parallel-group study consisted of an 8-week baseline and a 12-week double-blind phase. Patients with refractory partial seizures on one to three antiepileptic drugs were randomly assigned to one of five treatment groups (placebo or 50, 150, 300, and 600 mg/d pregabalin, all administered BID). Efficacy was assessed using seizure frequency reduction and responder rate (> or =50% seizure reduction from baseline). Pharmacokinetic parameters were estimated. RESULTS: A total of 453 patients were included in the intent-to-treat analysis. The median baseline seizure rate was 10 per month. Seizure frequency reductions from baseline were 7% (placebo; n = 100), 12% (50 mg/d; n = 88), 34% (150 mg/d; n = 86), 44% (300 mg/d; n = 90), and 54% (600 mg/d; n = 89). Responder rates (> or =50% seizure reduction) were 14% (placebo), 15% (50 mg/d), 31% (150 mg/d), 40% (300 mg/d), and 51% (600 mg/d). Discontinuation rates due to adverse events were 5% (placebo), 7% (50 mg/d), 1% (150 mg/d), 14% (300 mg/d), and 24% (600 mg/d). The 150-, 300-, and 600-mg/d pregabalin groups were associated with greater reductions in seizures (p < or = 0.0001) and greater responder rates compared with the placebo group (p < or = 0.006). There was a favorable dose-response trend for both seizure reductions (p < or = 0.0001) and responder rate (p < or = 0.001). CONCLUSION: Adjunctive therapy with pregabalin 150, 300, and 600 mg/d, given in twice-daily doses without titration, is significantly effective and well tolerated in the treatment of patients with partial seizures as demonstrated in patients with refractory partial seizures.

Is cyclic vomiting syndrome related to migraine?

OBJECTIVE: To examine the overlap between cyclic vomiting syndrome (CVS) and migraine by comparing 2 subsets of children with migraine-associated and non-migraine-associated CVS. METHODS: We studied all children <18 years of age who met the consensus criteria for CVS after presentation to our pediatric gastroenterology service from 1986 to 1998. The clinical patterns and responses to treatment were obtained from a combination of chart reviews and structured interviews. RESULTS: Among 214 children identified as having CVS, 82% were classified as having migraine-associated CVS based on 1 of 2 criteria either a family history of migraines or subsequent development of migraine headaches. Compared with the non-migraine CVS subgroup, the migraine subset had milder episodes (20.7 27.3 SD vs 39.5 66.5 emeses/episode, P =.006); more symptoms of abdominal pain (83% vs 66%), headache (41% vs 24%), social withdrawal (40% vs 22%), photophobia (36% vs 16%, all P <.05); more frequent triggering events (70% vs 49%, P =.013) including psychologic stress (39% vs 22%), physical exhaustion (23% vs 3%), and motion sickness (10% vs 0%); and a higher positive response rate to anti-migraine therapy (79% vs 36%, P =.002). CONCLUSIONS: The majority of children with CVS were subclassified as having migraine-associated CVS. The migraine-associated subgroup had less severe vomiting, manifested symptoms typical of migraine headaches, and had higher response rates to anti-migraine therapy. These findings strengthen the relationship between migraine and CVS.

Heterogeneity of diagnoses presenting as cyclic vomiting.

OBJECTIVE: To establish the diagnostic profile in children who present with cyclic vomiting. METHODS: We studied 225 children < 18 years of age who presented to our pediatric gastroenterology service from 1986 to 1997 with at least three discrete episodes of vomiting between which they were well. To determine the diagnoses in those presenting with a pattern of cyclic vomiting, the results of diagnostic testing and responses to various treatments were obtained from a combination of chart review and structured telephone interviews. RESULTS: The largest diagnostic category included idiopathic cyclic vomiting syndrome (88%). Extraintestinal disorders (7%) and gastrointestinal disorders (5%) constituting the probable cause of vomiting were established in those having complete cessation of episodes after therapy. In 12%, serious surgical disorders of the gastrointestinal (malrotation), renal (acute hydronephrosis), and central nervous systems (neoplasm) were found. In 2%, serious endocrine (Addison's disease) and metabolic disorders (disorder of fatty acid oxidation) were found. Among those with idiopathic cyclic vomiting syndrome, 41% had associated disorders (gastroesophageal reflux and chronic sinusitis) that could contribute to the vomiting, but, based on a partial response to therapy, were not deemed to be the main cause. Altogether 49% had an identified disorder that probably caused or could contribute to the vomiting. CONCLUSIONS: The cyclic pattern of vomiting is a symptom complex that can be induced by heterogeneous disorders that either cause or contribute to the vomiting. Once the cyclic vomiting pattern is identified, systematic diagnostic testing is warranted to look for these underlying disorders.

An unusual complication of minidose heparin therapy.

A 50-year-old woman developed a massive hematoma of the superficial abdominal wall following subcutaneous heparin therapy. The lesion was located above the fasica, became infected, and was associated with epithelial necrosis over the right lower quadrant of the abdominal wall. Operative excision of the entire affected area with primary closure was successful 4 weeks following the injection. The etiology of this problem was attributed to accidental laceration of the superficial epigastric vessels. This extensive local complication of subcutaneous minidose heparin injection seems not to have been previously reported.

The prevalence of farmer's lung in an agricultural population.

Four hundred seventy-one persons associated with farming or dairy production were surveyed by means of a questionnaire for evidence of hypersensitivity lung disease due to inhalation of moldy hay or grain (farmer's lung). Of these, 172 were evaluated with spirometry, serologic studies, and chest roentgenographs. A history typical of the farmer's lung syndrome was given by 14 of the 471 subjects (3.9 per cent). Precipitating antibodies to Micropolyspora faeni were identified in sera from 2 of these 14 subjects (14 per cent), and spirograms were abnormal in 4 (28 per cent). The prevalence of farmer's lung in this community (i.e., 3 per cent) is comparable to that found in epidemiologic studies in Britain and Scotland. Farmer's lung disease may be an important occupational illness of dairy and cattlemen in this country, but the diagnosis may be overlooked frequently because of the lack of patient and/or physician awareness.