Diagnosing and managing headache in children

Opinion statement Once the correct diagnosis of migraine in a child is established, a treatment plan can be developed. This often entails a combination of acute therapies, preventive therapies, and biobehavioral interventions. Goals of treatment should be clearly established for the patients and parents, and realistic time courses discussed. Overall outcome in terms of disability and quality of life also may need to be addressed and included within the evaluation and management scheme.     

Genetics of headache in children: Where are we headed?

A history of headaches in a family is very frequently noted when evaluating a child for recurrent, episodic headaches. Oftentimes, these headaches have migraine features, although the family may deny a history of migraine. This positive family history implies an inherited or genetic basis as a component to the underlying pathophysiology of primary headaches. A variety of methodology has begun to elucidate this contribution, including historical observation, population-based studies of families and twins, gene polymorphism association studies, and specific gene identification for isolated migraine subtypes. This line of investigation should progress in the future to a better understanding of migraine and clarification of the diagnostic subtypes for a genotype-phenotype association.     

Validation of a fiducial-based atlas localization method for deep brain stimulation contacts in the area of the subthalamic nucleus

Differences in the location of active contacts with respect to the subthalamic nucleus (STN) may account for much variability in motor, psychiatric and cognitive responses to deep brain stimulation (DBS) in Parkinson disease (PD) patients. Because localization of STN based on hypointensity in T2-weighted MR images is unreliable and further limited by artifacts from the metal electrodes, we developed and validated a method to transform brain images into stereotactic space [Mai JK, Assheuer J, Paxinos G. Atlas of the Human Brain, 2nd ed. San Diego: Elsevier Academic; 2004] using reliably-identified anatomic fiducials identified in high-resolution T2-weighted pre-operative MR images. Average intraclass correlation between two raters for 29 PD patients was 0.93 for those fiducials used to define the atlas. Accuracy of the registration was tested by comparing the rater-identified centers of the red nuclei with their predicted locations from the fiducial-based atlas transformation. Mean discrepancies were 0.1, 0.9, and 0.0mm (x, y, z) with standard deviations of 0.9, 0.7 and 1.1mm, respectively. Because post-operative determination of contact location with respect to the STN is necessary due to possible shifting of electrodes during surgical placement, we identified active contacts on post-operative CT images and transformed their locations into stereotactic space. This method provides an accurate and reliable means for STN DBS contact localization.     

Treatment of Acute Migraine in the Pediatric Population

The recognition of the diagnosis of migraine in the pediatric population is increasing. Early and aggressive treatment of migraine in children and adolescents with the use of over-the-counter medications has proven effective. In addition, the off-label use of many migraine-specific medications is often accepted in the absence of sufficient evidence-based trials. Mild to severe cases of migraine should be treated with NSAIDs, with triptans used for moderate to severe headaches that are unresponsive to over-the-counter therapy. Rescue medication including dihydroergotamine (DHE) should be used for intractable migraines, preferably in the hospital setting. In patients with associated symptoms of nausea and vomiting, antiemetics with antidopaminergic properties can be helpful through their action on central migraine generation. Furthermore, patients and families should be educated about nonpharmacologic aspects of management such as preventing episodic migraine through lifestyle modification and avoidance of triggers.     

Transfection screening for primary defects in the pyruvate dehydrogenase E1alpha subunit gene

In a significant number of patients with biochemical evidence of a defect in the E1 (pyruvate dehydrogenase) component of the pyruvate dehydrogenase complex, it has not proved possible to identify a mutation in the gene coding regions. To assess the need for more extensive genetic analysis in these patients and to establish a test system in which to study the biochemical consequences of mutations in the E1alpha subunit gene (which is responsible for the great majority of defined cases of pyruvate dehydrogenase deficiency), we have developed a method to screen for E1alpha gene defects based on complementation of the enzyme deficiency in transformed fibroblast cell lines following transfection and expression of the normal cDNA. Using this system, cell lines from patients with a variety of different defined mutations in the E1alpha gene show restoration of enzyme activity. A number of patients have been identified in whom deficient enzyme activity is not restored by expression of the normal cDNA indicating that an alternative explanation for the enzyme defect must be sought.      

Extension of Rapid Phase-Contrast Magnetic Resonance Imaging Using BRISK in Multidirectional Flow

We developed BRISK–CON–VPS, a rapid phase-contrast cine approach that is a hybrid of the BRISK–VPS (Block Regional Interpolation Scheme for k-space) and conventional (CONV–VPS) scanning employing k-space views per segment (VPS). BRISK–CON–VPS allows data acquisition approximately four times faster than CONV–VPS imaging and has the advantage compared to BRISK–VPS that it can potentially be incorporated into real-time applications. In BRISK–CON–VPS contiguous regions of k-space are sampled using a views per segment factor that is varied as a function of distance from the k-space center. Computational fluid dynamics (CFD) data were used to simulate CONV–VPS, BRISK–VPS, and BRISK–CON–VPS. BRISK–CON–VPS was simulated by incrementing the VPS progressively with increasing distance from the k-space origin while BRISK–VPS was simulated using a uniform VPS applied to the sparse sampling scheme. Simulations showed that up to a base VPS of 5, both BRISK–CON–VPS and BRISK–VPS retained excellent axial-velocity accuracy. Secondary in-plane velocity flow fields were well represented with BRISK–CON–VPS and BRISK–VPS up to a base VPS of 3. CONV–VPS, BRISK–CON–VPS, and BRISK–VPS were applied in vivo and shown to provide comparable quantitative flow data. BRISK–CON–VPS accomplishes breath-hold acquisitions as efficiently as BRISK–VPS, but without requiring data interpolation or under-sampling k-space.     

Cellular infiltration and cytokine mRNA expression in perennial allergic rhinitis

BACKGROUND: Allergen challenge in allergic rhinitis patients leads to local eosinophilia and Th2-type cytokine expression. Natural exposure to grass pollen is additionally characterized by epithelial mast-cell infiltration. We hypothesized that perennial allergic rhinitis is also associated with T-cell and eosinophil infiltration of the nasal mucosa, local Th2-type cytokine expression, and increased numbers of nasal epithelial mast cells. METHODS: Nasal biopsies from perennial allergic rhinitis patients and controls were analysed by immunocytochemistry for different cell populations and in situ hybridization for cytokine mRNA-expressing cells. RESULTS: Perennial allergic rhinitis was associated with increased numbers of submucosal CD3+ T cells (P=0.05), EG2+ activated eosinophils (P=0.01), and CD68+ macrophages (P=0.01) compared to controls. Epithelial, but not submucosal, tryptase-positive mast cells were also elevated in rhinitics compared to controls (P=0.01). The numbers of cells expressing interleukin (IL)-5 were higher (P=0.01) and the numbers of cells expressing IL-2 were lower (P=0.04) in rhinitic patients than controls. There were no significant differences for either IL-4 or interferon-gamma between the groups. CONCLUSIONS: Perennial allergic rhinitis is characterized by mast-cell migration into the epithelium; submucosal infiltration by T cells, eosinophils, and macrophages; and an imbalance in local T-cell cytokine production in favour of enhanced IL-5 and reduced IL-2 expression.     

Mediastinal masses: MR imaging

Seventy-five patients with mediastinal masses were imaged with magnetic resonance (MR). Results were analyzed with regard to the ability of MR to demonstrate the masses, their morphology, and their encroachment or displacement of blood vessels and airways. T1 values were determined in 53 patients and T2 values in 59. Hydrogen density and percentage of contrast relative to muscle and fat were also obtained in 53 and 59 patients, respectively. MR images were compared with computed tomography (CT) scans, which were available in 45 patients. MR depicted all masses and demonstrated compromise of vessels and cardiac chambers owing to the inherent contrast between the masses and cardiovascular structures. Bronchogenic carcinoma had very long relaxation values for T1 and T2, while chronic inflammatory processes had intermediate values for T1 and T2, thus appearing less intense than bronchogenic carcinoma on T2-weighted images. Other neoplasms demonstrated T1 and T2 values between these two disease groups. Masses appeared less homogeneous on MR images than on CT scans, and vascular compromise was better assessed with MR. Thus, MR imaging is a completely noninvasive technique for the evaluation of mediastinal masses. While the anatomic information is comparable to that produced by CT, MR provides some insight into the composition of the mass.