A retrospective examination of adjunctive L-methylfolate in children and adolescents with unipolar depression.

BACKGROUND: Adjunctive l-methylfolate is commonly prescribed for children and adolescents with treatment-resistant mood disorders; however, the relationship between l-methylfolate augmentation across methylenetetrahydrofolate reductase (MTHFR) genotypes in youths with depressive symptoms is unclear. METHODS: We retrospectively examined the electronic health records of patients (N = 412) with depressive symptoms associated with unipolar depressive disorders and their MTHFR C677T genotypes from 2013 to 2019. Patients were ≤18 years of age at the time of MTHFR pharmacogenetic testing. Treatment response was assessed with Clinical Global Impression-Improvement (CGI-I) score reported in the medical record. RESULTS: Patients with an MTHFR C677T C/T or T/T genotype were more likely to be prescribed l-methylfolate when the clinician knew their MTHFR genotype (p < 0.0001, OR: 15.1, 95 % CI: [5.1, 44.2]), but not when the clinician did not know their genotype (p = 0.4, OR: 2.1, 95 % CI: [0.4, 11.4]). Change in baseline and endpoint CGI-I scores between patients with an MTHFR C677T variant who were prescribed and not prescribed l-methylfolate did not significantly differ (p = 0.39). Response rate was not associated with l-methylfolate prescription (p = 0.17) or l-methylfolate dose (p = 0.69). LIMITATIONS: This was a retrospective study, which yielded a heterogeneous patient population and limited data availability (e.g., adherence). Patients are severely ill and may have a refractory illness that limits response to adjunctive l-methylfolate. CONCLUSION: Clinicians prescribe l-methylfolate to children and adolescents with depressive symptoms associated with unipolar depressive disorders who have an MTHFR C677T variant, although augmentation may not be associated with treatment response, regardless of MTHFR genotype or dose.

Association between poor tolerability of antidepressant treatment and brain functional activation in youth at risk for bipolar disorder

Objective: To investigate whether poor antidepressant tolerability is associated with functional brain changes in children and adolescents of parents with bipolar I disorder (at-risk youth). Methods: Seventy-three at-risk youth (ages 9-20 years old) who participated in a prospective study and had an available baseline functional magnetic resonance imaging (fMRI) scan were included. Research records were reviewed for the incidence of adverse reactions related to antidepressant exposure during follow-up. The sample was divided among at-risk youth without antidepressant exposure (n=21), at-risk youth with antidepressant exposure and no adverse reaction (n=12), at-risk youth with antidepressant-related adverse reaction (n=21), and healthy controls (n=20). The fMRI task was a continuous performance test with emotional distracters. Region-of-interest mean activation in brain areas of the fronto-limbic emotional circuit was compared among groups. Results: Right amygdala activation in response to emotional distracters significantly differed among groups (F3,66 = 3.1, p = 0.03). At-risk youth with an antidepressant-related adverse reaction had the lowest amygdala activation, while at-risk youth without antidepressant exposure had the highest activation (p = 0.004). Conclusions: Decreased right amygdala activation in response to emotional distracters is associated with experiencing an antidepressant-related adverse reaction in at-risk youth. Further studies to determine whether amygdala activation is a useful biomarker for antidepressant-related adverse events are needed.

Association between poor tolerability of antidepressant treatment and brain functional activation in youth at risk for bipolar disorder.

OBJECTIVE: To investigate whether poor antidepressant tolerability is associated with functional brain changes in children and adolescents of parents with bipolar I disorder (at-risk youth). METHODS: Seventy-three at-risk youth (ages 9-20 years old) who participated in a prospective study and had an available baseline functional magnetic resonance imaging (fMRI) scan were included. Research records were reviewed for the incidence of adverse reactions related to antidepressant exposure during follow-up. The sample was divided among at-risk youth without antidepressant exposure (n=21), at-risk youth with antidepressant exposure and no adverse reaction (n=12), at-risk youth with antidepressant-related adverse reaction (n=21), and healthy controls (n=20). The fMRI task was a continuous performance test with emotional distracters. Region-of-interest mean activation in brain areas of the fronto-limbic emotional circuit was compared among groups. RESULTS: Right amygdala activation in response to emotional distracters significantly differed among groups (F3,66 = 3.1, p = 0.03). At-risk youth with an antidepressant-related adverse reaction had the lowest amygdala activation, while at-risk youth without antidepressant exposure had the highest activation (p = 0.004). CONCLUSIONS: Decreased right amygdala activation in response to emotional distracters is associated with experiencing an antidepressant-related adverse reaction in at-risk youth. Further studies to determine whether amygdala activation is a useful biomarker for antidepressant-related adverse events are needed.

Magnetic Resonance Imaging of Non-ischemic Cardiomyopathies: A Pictorial Essay.

Non-ischemic cardiomyopathies are defined as either primary or secondary diseases of the myocardium resulting in cardiac dysfunction. While primary cardiomyopathies are confined to the heart and can be genetic or acquired, secondary cardiomyopathies show involvement of the heart as a manifestation of an underlying systemic disease including metabolic, inflammatory, granulomatous, infectious, or autoimmune entities. Non-ischemic cardiomyopathies are currently classified as hypertrophic, dilated, restrictive, or unclassifiable, including left ventricular non-compaction. Cardiovascular Magnetic Resonance Imaging (CMRI) not only has the capability to assess cardiac morphology and function, but also the ability to detect edema, hemorrhage, fibrosis, and intramyocardial deposits, providing a valuable imaging tool in the characterization of non-ischemic cardiomyopathies. This pictorial essay shows some of the most important non-ischemic cardiomyopathies with an emphasis on magnetic resonance imaging features.

Leukoencephalopathic changes on magnetic resonance imaging associated with a thermogenic dietary supplement (Thermatrim).

Acute toxic leukoencephalopathy can be caused by exposure to many compounds. Reversibility has been described in some cases with prompt recognition and withdrawal of the offending agent. Its association with a thermogenic supplement has never been reported. We describe two such cases in young women taking a commercially available thermogenic dietary supplement who presented with acute neurologic deficits and a common magnetic resonance imaging pattern.

Assessment of Ischemic Cardiomyopathy Using Cardiovascular Magnetic Resonance Imaging: A Pictorial Review.

Ischemic heart disease is the leading cause of death worldwide. In the last two decades, cardiovascular magnetic resonance imaging (CMRI) has emerged as the primary imaging tool in the detection and prognostic assessment of ischemic heart disease. In a single study, CMRI allows evaluation of not only myocardial wall perfusion, but also the presence, acuity, and extent of myocardial ischemia and infarction complications. Also, rest and stress perfusion imaging can accurately depict inducible ischemia secondary to significant coronary artery stenosis. We present a pictorial review of the assessment of ischemic cardiomyopathy with an emphasis on CMRI features.

Glomus jugulare presenting with isolated facial nerve palsy.

Glomus jugulare is a rare slow growing tumor occurring within the jugular foramen that rarely presents with isolated symptoms. Although histologically benign, these tumors are locally destructive because of their proximity to the petrous bone, the lower cranial nerves, and the major vascular structures (Miller et al. (2009) and Silverstone (1973)). We wish to report a glomus jugulare tumor eroding the petrous bone and producing an ipsilateral peripheral facial weakness. The mechanism of this erosion is discussed.

Design of a set of probes with high potential for influenza virus epidemiological surveillance.

An Influenza Probe Set (IPS) consisting in 1,249 9-mer probes for genomic fingerprinting of closely and distantly related Influenza Virus strains was designed and tested in silico. The IPS was derived from alignments of Influenza genomes. The RNA segments of 5,133 influenza strains having diverse degree of relatedness were concatenated and aligned. After alignment, 9-mer sites having high Shannon entropy were searched. Additional criteria such as: G+C content between 35 to 65%, absence of dimer or trimer consecutive repeats, a minimum of 2 differences between 9mers and selecting only sequences with Tm values between 34.5 and 36.5oC were applied for selecting probes with high sequential entropy. Virtual Hybridization was used to predict Genomic Fingerprints to assess the capability of the IPS to discriminate between influenza and related strains. Distance scores between pairs of Influenza Genomic Fingerprints were calculated, and used for estimating Taxonomic Trees. Visual examination of both Genomic Fingerprints and Taxonomic Trees suggest that the IPS is able to discriminate between distant and closely related Influenza strains. It is proposed that the IPS can be used to investigate, by virtual or experimental hybridization, any new, and potentially virulent, strain.

Current contrast media delivery strategies for cardiac and pulmonary multidetector-row computed tomography angiography.

Recent advances in multidetector-row computed tomography (MDCT) have led to substantial improvements in coverage area, acquisition speed, and temporal/spatial resolution, which have strengthened the performance of thoracic and cardiac MDCT angiography but have also imposed new challenges for optimization of contrast medium enhancement and scan acquisition strategies. Understanding contrast media dynamics is fundamental for the design of scan acquisition and injection protocols. This article examines the fundamentals of the physiological and contrast delivery factors that determine the quality of contrast enhancement, emphasizing the modifications required in contrast delivery protocols for optimizing cardiothoracic MDCT angiography with modern-era MDCT scanners.