An Open-Label Study Evaluating the Pharmacokinetics and Safety of Diclofenac Potassium for Oral Solution for the Acute Treatment of MWA or MWoA in Pediatric Participants.

OBJECTIVE: To evaluate the pharmacokinetics, safety, and tolerability of a single 50-mg oral dose of diclofenac potassium for oral solution (OS) in a pediatric cohort with a diagnosis of episodic migraine; the 3-month safety trial following an outpatient dosing period was also evaluated. BACKGROUND: Children and adolescents often experience migraine pain that is poorly controlled, which may affect their emotional and psychological well-being. Diclofenac potassium for OS is approved for the treatment of migraine with aura (MWA) or migraine without aura (MWoA) in adults 18 years of age or older. It is formulated in a soluble buffered powder that provides more rapid absorption than the tablet formulations of diclofenac potassium. In a randomized, double-blind, crossover trial, more adult patients were pain-free at 2 hours post-dose following treatment with diclofenac potassium for OS than those who received the diclofenac tablet formulation or placebo. METHODS: This was a Phase 4 open-label study that took place at 2 US sites. Participants 12-17 years of age with a diagnosis of episodic MWA or MWoA for ≥3 months and ≤14 headaches per month were enrolled in the study. Participants received one 50-mg dose of diclofenac potassium for OS under fasted conditions on day 1. Blood samples were collected for PK analysis within 15 minutes pre-dose and at 5, 10, 15, 20, 30, 40, and 60 minutes post-dose, and at 2, 4, and 6 hours post-dose. Safety evaluations were performed after the initial dose and at the end of study on day 90; adverse events were monitored throughout the study. After completing the PK assessments, participants were given a 3-month supply (27 packets) of diclofenac potassium for OS (50-mg doses) for their migraine attacks. Participants were advised to take diclofenac potassium for OS at the onset of a migraine. They were told to take no more than 2 doses daily and not to use it more than 3 days/week. RESULTS: Twenty-five participants completed the study; 84% were females and 96% were white or Caucasian, with a mean age of 15.5 years and a mean weight of 63.1 kg. Diclofenac was rapidly absorbed with a median time to maximum concentration of 15 minutes and a mean peak plasma concentration of 1412 (±846.2) ng/mL. Diclofenac had a half-life of 66.8 (±9.2) minutes. The mean area under the concentration-time curve from zero to the last measurable time point was 82,920.0 (±25,327.6) minutes × ng/mL, and the mean area under the concentration-time curve from time zero to infinity was 84,388.8 (±25,993.6) minutes × ng/mL. Participants took the study drug an average of 10 times over 79 days, with an overall total drug exposure of 506 mg. No deaths or discontinuations due to an AE were reported during the study. The most frequently reported treatment emergent adverse events were arthralgia and motion sickness, each of which occurred in 2 (8%) of the participants. CONCLUSIONS: Diclofenac potassium for OS exhibited a favorable pharmacokinetic and safety profile in 12- to 17-year-old patients with a diagnosis of episodic MWA or MWoA.

Neuroimaging During Pregnancy and the Postpartum Period.

New onset or exacerbation of preexisting neurologic symptoms during pregnancy often necessitates brain or spinal cord imaging. Magnetic resonance techniques are preferred imaging modalities during pregnancy and the postpartum period. Ionizing radiation with computed tomography and intravenous contrast material with magnetic resonance or computed tomography should be avoided during pregnancy. New onset of headaches in the last trimester or in the postpartum period may indicate cerebrovascular disease or a mass lesion, for which brain imaging is necessary. The continuum of cerebrovascular complications of pregnancy and enlarging lesions may produce neurologic symptoms later in pregnancy and after delivery, necessitating imaging.

Imaging of Neurologic Disorders in Pregnancy.

Pregnant women may have exacerbation of preexisting neurologic disorders or new-onset neurologic symptoms for which brain or spinal cord imaging is appropriate. Primary headaches in early pregnancy can be diagnosed and treated without imaging. Headaches later in pregnancy or in the peripartum period may need to be evaluated by brain and/or vascular imaging. Cerebrovascular complications have distinctive imaging but overlapping presentations. Mass lesions can enlarge, producing neurologic symptoms, late in pregnancy. Imaging may be necessary to diagnose neurologic disorders in pregnancy and the peripartum period. MRI is preferred during pregnancy; imaging involving ionizing radiation and/or contrast should be avoided.

Imaging of Congenital Malformations.

PURPOSE OF REVIEW: Intracranial congenital malformations are anomalies of brain development caused by genetic and environmental influences. This article discusses common intracranial congenital malformations, presents the associated neuroimaging findings, and discusses how appropriate identification of intracranial anomalies can impact diagnosis and treatment. RECENT FINDINGS: Advances in neuroimaging techniques and genetic research have led to a better understanding of the pathogenesis of many congenital malformations, adding insight into their clinical relevance and the intricate relationship between critical periods of development, genetic predisposition, and environmental insults. When one malformation is discovered, a high likelihood of more malformations exists. In some instances, the intracranial anomalies will lead to the diagnosis of a particular neurologic syndrome, which may, in turn, lead to modification of a plan of care. SUMMARY: Knowledge of congenital malformations and their appearance on imaging sequences is essential to improve clinical outcomes and quality of life for patients.

Imaging of Chiari type I malformation and syringohydromyelia.

Chiari malformations are anatomic anomalies that comprise a broad spectrum of neurologic conditions. The most common malformation, a Chiari type I malformation, can present with a variety of signs and symptoms, most frequently an occipital Valsalva-induced headache. Cranial and spinal magnetic resonance (MR) imaging is used to identify the degree of tonsillar descent and document the presence of syringohydromyelia. The advent of cine-MR flow imaging (cine as in "cinema") has provided new insight as to the dynamic process involved in the evolution of this pathophysiology. This article reviews the neuroimaging of this fascinating disorder.