Anger recall mental stress decreases 123I-metaiodobenzylguanidine (123I-MIBG) uptake and increases heterogeneity of cardiac sympathetic activity in the myocardium in patients with ischemic cardiomyopathy.

BACKGROUND: Acute psychological stressors such as anger can precipitate ventricular arrhythmias, but the mechanism is incompletely understood. Quantification of regional myocardial sympathetic activity with 123I-metaiodobenzylguanidine (123I-mIBG) SPECT imaging in conjunction with perfusion imaging during mental stress may identify a mismatch between perfusion and sympathetic activity that may exacerbate a mismatch between perfusion and sympathetic activity that could create a milieu of increased vulnerability to ventricular arrhythmia. METHODS: Five men with ischemic cardiomyopathy (ICM), and five age-matched healthy male controls underwent serial 123I-mIBG and 99mTc-Tetrofosmin SPECT/CT imaging during an anger recall mental stress task and dual isotope imaging was repeated approximately 1 week later during rest. Images were reconstructed using an iterative reconstruction algorithm with CT-based attenuation correction. The mismatch of left ventricular myocardial 123I-mIBG and 99mTc-Tetrofosmin was assessed along with radiotracer heterogeneity and the 123I-mIBG heart-to-mediastinal ratios (HMR) were calculated using custom software developed at Yale. RESULTS: The hemodynamic response to mental stress was similar in both groups. The resting-HMR was greater in healthy control subjects (3.67 ± 0.95) than those with ICM (3.18 ± 0.68, P = .04). Anger recall significantly decreased the HMR in ICM patients (2.62 ± 0.3, P = .04), but not in normal subjects. The heterogeneity of 123I-mIBG uptake in the myocardium was significantly increased in ICM patients during mental stress (26% ± 8.23% vs. rest: 19.62% ± 9.56%; P = .01), whereas the 99mTc-Tetrofosmin uptake pattern was unchanged. CONCLUSION: Mental stress decreased the 123I-mIBG HMR, increased mismatch between sympathetic activity and myocardial perfusion, and increased the heterogeneity of 123I-mIBG uptake in ICM patients, while there was no significant change in myocardial defect size or the heterogeneity of 99mTc-Tetrofosmin perfusion. The changes observed in this proof-of-concept study may provide valuable information about the trigger-substrate interaction and the potential vulnerability for ventricular arrhythmias.

Novel Mutations in a Lethal Case of Lymphomatous Adult T Cell Lymphoma with Cryptic Myocardial Involvement.

The autopsy of a 65-year-old diabetic African American male revealed significant left myocardial involvement by adult T-cell leukemia/lymphoma (ATLL) despite normal pre-mortem fluorodeoxyglucose (FDG) uptake by positron emission tomography/computed tomography (PET/CT). Due to pre-existing diabetic cardiomyopathy with reduced ejection fraction (EF) and compatible imaging studies, cardiac lymphomatous involvement was not suspected. While peripheral blood was negative for leukemia, next-generation sequencing of a lymph node revealed at least eight novel mutations (AXIN1, R712Q, BARD1 R749K, CTNNB1 I315V, CUX1 P102T, DNMT3A S199R, FGFR2 S431L, LRP1B Y2560C and STAG2 I771M). These findings underscore a diagnostic pitfall in a rare lymphomatous variant of ATLL infiltrating myocardium and contribute to its molecular characterization.

A blind deconvolution method incorporated with anatomical-based filtering for partial volume correction: Validations with 123 I-mIBG cardiac SPECT/CT.

PURPOSE: Segmentation of contrast-enhanced CT and measurement of SPECT point spread function (PSF) are usually required for conventional partial volume correction (PVC). This study was to develop a segmentation-free method with blind deconvolution (BD) and anatomical-based filtering for SPECT PVC. METHODS: The proposed method was implemented using an iterative BD algorithm to estimate the restored image and the PSF simultaneously. An anatomical-based filtering was implemented at each iteration to reduce Gibbs artifact and suppress noise amplification in the deconvolution process. The proposed method was validated with 123 I-metaiodobenzylguanidine (123 I-mIBG) SPECT/CT imaging of NCAT phantoms with and without myocardial perfusion defect and a physical cardiac phantom. Fifteen heart-to-mediastinum ratios (HMRs) were configured in the NCAT and physical phantoms. Correlations between SPECT-quantified and true HMRs were calculated from images without PVC as well as from BD restored images. The proposed method was also performed on a human 123 I-mIBG study. RESULTS: Relative bias and standard deviation images of NCAT phantoms showed that the proposed method reduced both bias and noise. Mean relative bias in the simulated normal myocardium was markedly improved (-16.8% ± 0.4% versus -0.8% ± 0.6% for low noise level; -16.7% ± 0.7% versus -2.3% ± 0.9% for high noise level). Mean relative bias in the simulated myocardial defect was also noticeably improved (-12.7% ± 1.2% versus 1.2% ± 1.6% for low noise level; -13.5% ± 2.4% versus -0.9% ± 2.8% for high noise level). The signal to noise ratio (SNR) of the defect was improved from 2.95 ± 0.09 to 4.07 ± 0.16 for low noise level (38% increase of mean), and from 2.56 ± 0.15 to 3.62 ± 0.22 for high noise level (41% increase of mean). For both NCAT and physical phantoms, HMRs calculated from images without PVC were underestimated (correlations between SPECT-quantified and true HMRs: y = 0.81x + 0.1 for NCAT phantom; y = 0.82x + 0.14 for physical phantom). HMRs from BD restored images were markedly improved (correlations between SPECT-quantified and true HMRs: y = x + 0.05 for NCAT phantom; y = 0.97x - 0.12 for physical phantom). After applying the proposed PVC method, the estimation error between the SPECT-quantified and true HMRs was significantly reduced from -0.75 ± 0.57 to 0.04 ± 0.17 for NCAT phantom (P = 8e-05), and from -0.68 ± 0.67 to -0.26 ± 0.42 for physical phantom (P = 0.005). The human study demonstrated that the HMR increased by 8% with PVC. CONCLUSIONS: The proposed segmentation-free PVC method has the potential of improving SPECT quantification accuracy and reducing noise without the need for premeasuring the image PSF.

Botulinum Toxin Treatment of Spasticity in Adults and Children.

Spasticity is a frequent symptom in stroke, multiple sclerosis, cerebral or spinal trauma, and cerebral palsy that affects and disables a large number of adults and children. In this review, we discuss the pathophysiology and nonpharmacologic and pharmacologic treatments of spasticity with emphasis on the role of botulinum neurotoxins (BoNTs). The world literature is reviewed on double-blind and placebo-controlled clinical trials reporting safety and efficacy of BoNT treatment in adult spasticity and spasticity of children with cerebral palsy. The evidence for efficacy is presented from recommendations of the Assessment and Therapeutics subcommittee of the American Academy of Neurology. A technical section describes the techniques and recommended doses of BoNTs in spasticity.

Congenital cardiac anomalies in myelomeningocele patients.

OBJECTIVE: Myelomeningocele may be isolated but more frequently is associated with other anomalies. Congenital heart disease occurs with different incidence rate in myelomeningocele which is observed more frequently with skeletal malformations. METHODS: This study was undertaken in the Children's Hospital Medical Center between 2010 to 2012 to evaluate 75 myelomeningocele patients for cardiac anomalies, with electrocardiography and echocardiography in addition to clinical examination of the cardiopulmonary system. Demographic information, myelomeningocele location and characteristics, orthopedic deformities, neurological deficits and radiographic findings were studied besides cardiologic assessments. RESULTS: The ages of the patients ranged from 1 day to 4 years. The myelomeningocele locations were lumbosacral, lumbar and sacral area in most cases. Physical examination of the heart was abnormal in 6 children, but echocardiography revealed cardiac anomalies in only two children. Both children were female patients with severe scoliosis, multiple rib deficiencies and associated vertebral anomalies. CONCLUSION: Congenital heart defects are not very common in MMC patients. Female patients with suspicious clinical examinations for cardiac anomalies and associated rib and vertebral anomalies are advised to be investigated by echocardiography to rule out associated cardiac anomalies.