Patient Perceptions of Exertion and Dyspnea With Interleukin-1 Blockade in Patients With Recently Decompensated Systolic Heart Failure.

Interleukin-1 (IL-1) blockade is an anti-inflammatory treatment that may affect exercise capacity in heart failure (HF). We evaluated patient-reported perceptions of exertion and dyspnea at submaximal exercise during cardiopulmonary exercise testing (CPET) in a double-blind, placebo-controlled, randomized clinical trial of IL-1 blockade in patients with systolic HF (REDHART [Recently Decompensated Heart Failure Anakinra Response Trial]). Patients underwent maximal CPET at baseline, 2, 4, and 12 weeks and rated their perceived level of exertion (RPE, on a scale from 6 to 20) and dyspnea on exertion (DOE, on a scale from 0 to 10) every 3 minutes throughout exercise. Patients also answered 2 questionnaires to assess HF-related quality of life: the Duke Activity Status Index and the Minnesota Living with Heart Failure Questionnaire. From baseline to the 12-week follow-up, IL-1 blockade significantly reduced RPE and DOE at 3- and 6-minutes during CPET without changing values for heart rate, oxygen consumption, and cardiac workload at 3- and 6-minutes. Linear regression identified 6-minute RPE to be a strong independent predictor of both physical symptoms (Minnesota Living with Heart Failure Questionnaire; ß = 0.474, p = 0.002) and perceived exercise capacity (Duke Activity Status Index; ß = -0.443, p = 0.008). In conclusion, patient perceptions of exertion and dyspnea at submaximal exercise may be valuable surrogates for quality of life and markers of response to IL-1 blockade in patients with HF.

Pediatric cochlear implantation of children with eighth nerve deficiency.

OBJECTIVE: To evaluate the auditory outcomes of children implanted in an ear with eighth nerve hypoplasia or aplasia and to determine whether preoperative characteristics are predictive of auditory performance achieved. STUDY DESIGN: retrospective case review. SETTING: tertiary care medical center. PATIENTS: ten children implanted in an ear with eighth nerve hypoplasia or aplasia, as determined by high resolution magnetic resonance imaging. MAIN OUTCOME MEASURES: Neural response test measurements, detection and speech awareness thresholds, Meaningful Auditory Integration Scale scores, as well as speech perception level achieved. RESULTS: Post-implantation, three children demonstrated little to no detection of sound, three had improved detection and awareness of environmental sounds, one developed closed-set speech perception and spoken language, and three developed open-set speech perception and spoken language. No imaging findings appeared related to outcomes. Significantly better implant detection thresholds and Meaningful Auditory Integration Scale scores were found in children who had preoperative aided auditory detection (p's ≤ 0.02-0.05). CONCLUSION: Some children with eighth nerve hypoplasia or aplasia may derive significant benefit from a cochlear implant. In our study high resolution magnetic resonance imaging was more sensitive than high resolution computer tomography in detecting neural deficiency. However, no imaging findings were predictive of auditory performance level achieved post-implantation.

Abnormal neuroimaging is associated with early in-hospital seizures in pediatric abusive head trauma.

BACKGROUND: Abusive head trauma (AHT) is a common condition in children. Little is known in this condition regarding the frequency of seizures, the factors associated with increased risk of seizures, or the association of seizures with outcome. We sought to determine frequency and risks for in-hospital seizures after AHT. METHODS: This was a single-center, retrospective chart review study at a 270 bed tertiary care referral pediatric hospital. RESULTS: A total of 54 cases of AHT were identified during the study period. During the first week following hospital admission, 33% of patients were observed to have clinical seizures. The occurrence of clinical seizures after admission was associated with findings on initial CT including midline shift, cerebral edema, and loss of gray white differentiation. MRI findings associated with clinical seizures after admission included midline shift, cerebral edema, infarction, and restricted diffusion. The presenting complaint of seizures or acute mental status changes well as a variety of abnormal imaging findings including gray white blurring, infarction, and edema were associated with short-term outcomes. CONCLUSIONS: Specific neuroradiologic findings identify children at greater risk for seizures, both clinical and subclinical, following AHT. Clinical and subclinical seizures are common in the initial hospitalization for AHT.

Neuroimaging findings in children with rare or novel de novo chromosomal anomalies.

BACKGROUND: De novo constitutional chromosomal anomalies provide important insights into the genetic loci responsible for congenital neurological disorders. However, most phenotypic descriptions of patients with rare chromosomal abnormalities are published as individual case reports or small group studies, making genotype-phenotype correlations unclear. Moreover, many clinical genetic reports do not include neuroimaging. METHODS: We conducted a retrospective case series study of all children who had genetic testing done at Children's Memorial Hospital in Chicago, Illinois between 1985 and 2006. The case series was selected from a database containing all chromosomal testing results, clinical data, and neuroimaging. Clinical examination results were assigned by board certified geneticists and/or neurologists and neuroimages were reviewed by both a neurologist or neuroradiologist and a blinded neurologist. RESULTS: Of the 28,108 children in the series, we identified 34 children with novel or apparently novel de novo chromosomal abnormalities. Several of the cases represent potentially new genetic loci for neurological malformations and novel syndromic conditions. CONCLUSIONS: This study demonstrates the utility of large clinical databases in assessing genotype-phenotype correlations and mapping loci for congenital neurological disorders. We describe a case-series strategy to analyze existing databases to reveal new genotype-phenotype correlations.

A new complication of stem cell transplantation: measles inclusion body encephalitis.

Measles inclusion body encephalitis (MIBE) is a disease of the immunocompromised host and typically occurs within 1 year of acute measles infection or vaccination. We report a 13-year-old boy who had chronic granulomatous disease and presented 38 days after stem cell transplantation with afebrile focal seizures that progressed despite multiple anticonvulsants. After an extensive diagnostic evaluation, brain biopsy was performed, revealing numerous intranuclear inclusion bodies consistent with paramyxovirus nucleocapsids. Measles studies including reverse transcriptase-polymerase chain reaction and viral growth confirmed measles virus, genotype D3. Immunohistochemistry was positive for measles nucleoprotein. Despite intravenous ribavirin therapy, the patient died. MIBE has not been described in stem cell recipients but is a disease of immunocompromised hosts and typically occurs within 1 year of measles infection, exposure, or vaccination. Our case is unusual as neither the patient nor the stem cell donor had apparent recent measles exposure or vaccination, and neither had recent travel to measles-endemic regions. The patient had an erythematous rash several weeks before the neurologic symptoms; however, skin biopsy was consistent with graft-versus-host disease, and immunohistochemistry studies for measles nucleoprotein were negative. As measles genotype D3 has not been seen in areas where the child lived since his early childhood, the possibility of an unusually long latency period between initial measles infection and MIBE is raised. In addition, this case demonstrates the utility of brain biopsy in the diagnosis of encephalitis of unknown cause in the immunocompromised host.

MRI volumetric analysis in rasmussen encephalitis: a longitudinal study.

PURPOSE: Rasmussen encephalitis is a progressive inflammatory process with difficult-to-control focal or lateralized seizure activity, leading to hemispheric dysfunction and atrophy in advanced stages. Anatomic changes of atrophy may be subtle in earlier phases of the disease, and progressive changes on serial scans may be difficult to detect. We report a case of early-stage Rasmussen encephalitis with a relatively stable clinical course in whom we performed magnetic resonance imaging (MRI)-based volumetric analysis over an interval of 1 year, to assess for volumetric changes. METHODS: Volumetric analysis was performed on two successive MRI scans obtained at age 5 and 6 years, by using the CARDVIEWS program (J Cogn Neurosci, 1996). The images were segmented into gray- and white-matter structures according to signal intensity of their borders semiautomatically, with manual corrections. The cerebral cortex was further subdivided into smaller parcellation units according to anatomic landmarks identifiable on MRI. RESULTS: Stable left cerebral hemispheric atrophy and progressive atrophy in the left precentral gyrus, left inferior frontal gyrus, and left cerebellar atrophy were detected over the 1-year interval. CONCLUSIONS: Volumetric analysis enables early detection and quantification of anatomic changes, identification of focal involvement, and assists in determining the severity of disease and timing for surgical interventions such as hemispherectomy.