Longitudinal dysphagia assessment in adult patients with nephropathic cystinosis using the Modified Barium Swallow Impairment Profile.

INTRODUCTION/AIMS: Nephropathic cystinosis is a lysosomal storage disorder with known myopathic features, including dysphagia. Evaluation of oropharyngeal swallowing physiology can be standardized using the Modified Barium Swallow Impairment Profile (MBSImP), a validated assessment tool used to analyze and rate swallowing across 17 distinct physiologic domains. Our objective was to better characterize swallowing impairments in nephropathic cystinosis using MBSImP analysis. METHODS: We retrospectively evaluated 40 video fluoroscopic swallowing studies performed at two time points over 1 y in patients with nephropathic cystinosis with various levels of oral and pharyngeal stage dysphagia. Patients completed two self-administered dysphagia outcome measures (the M. D. Anderson Dysphagia Inventory [MDADI] and the 10-item Eating Assessment Tool [EAT-10]). RESULTS: We demonstrated oral stage and pharyngeal stage dysphagia across domains that impacted bolus control, transit, and clearance through both the oral cavity and pharyngeal lumen. Also captured were deficits related to onset and completeness of laryngeal closure that impact airway protection during swallow. There were significant correlations between pharyngeal total score and EAT-10 (r = 0.5, p < 0.001) and between oral total score and EAT-10 (r = 0.7, p < 0.001), MDADI-e (r = -0.6, p < 0.001), MDADI-p (r = -0.5, p < 0.001) and MDADI-c (r = -0.6, p < 0.001). There were no differences in oral or pharyngeal total scores across the 1-y time span. DISCUSSION: This study identifies oral and pharyngeal stage dysphagia as crucial to patients with nephropathic cystinosis and paves the path for future studies of treatment targets.

Clinical trial readiness study of distal myopathy and dysphagia in nephropathic cystinosis.

BACKGROUND: Nephropathic cystinosis is a lysosomal storage disorder with late-onset systemic complications, such as myopathy and dysphagia. Currently employed outcome measures lack sensitivity and responsiveness for dysphagia and myopathy, a limitation to clinical trial readiness. METHODS: We evaluated 20 patients with nephropathic cystinosis in two visits over the course of a year to identify outcomes sensitive to detect changes over time. Patients also underwent an expiratory muscle strength training program to assess any effects on aspiration and dysphagia. RESULTS: There were significant differences in the Timed Up and Go Test (TUG) and Timed 25-Foot Walk (25-FW) between baseline and 1-y follow-up (P < .05). Maximum expiratory pressure (MEP) and peak cough flow (PCF) significantly improved following respiratory training (P < .05). CONCLUSIONS: Improved respiratory outcomes may enhance patients ability to expel aspirated material from the airway, stave off pulmonary sequelae associated with chronic aspiration, and yield an overall improvement in physical health and well-being.

Clinical myopathy in patients with nephropathic cystinosis.

BACKGROUND: Nephropathic cystinosis is a lysosomal storage disorder. Patient survival years after renal transplantation has revealed systemic complications including distal myopathy and dysphagia. METHODS: We evaluated 20 adult patients with nephropathic cystinosis using patient-reported and clinical outcome measures. Standard motor measures, video fluoroscopy swallow studies, and tests of respiratory function were performed. We also used Rasch analysis of an initial survey to design a 16-item survey focused on upper and lower extremity function, which was completed by 31 additional patients. RESULTS: Distal myopathy and dysphagia were common in patients with nephropathic cystinosis. Muscle weakness ranges from mild involvement of intrinsic hand muscles to prominent distal greater than proximal weakness and contractures. CONCLUSIONS: In addition to further characterization of underlying dysphagia and muscle weakness, we propose a new psychometrically devised, disease specific, functional outcome measures for distal myopathy in patients with nephropathic cystinosis.

Brain swelling and death in children with cerebral malaria.

BACKGROUND: Case fatality rates among African children with cerebral malaria remain in the range of 15 to 25%. The key pathogenetic processes and causes of death are unknown, but a combination of clinical observations and pathological findings suggests that increased brain volume leading to raised intracranial pressure may play a role. Magnetic resonance imaging (MRI) became available in Malawi in 2009, and we used it to investigate the role of brain swelling in the pathogenesis of fatal cerebral malaria in African children. METHODS: We enrolled children who met a stringent definition of cerebral malaria (one that included the presence of retinopathy), characterized them in detail clinically, and obtained MRI scans on admission and daily thereafter while coma persisted. RESULTS: Of 348 children admitted with cerebral malaria (as defined by the World Health Organization), 168 met the inclusion criteria, underwent all investigations, and were included in the analysis. A total of 25 children (15%) died, 21 of whom (84%) had evidence of severe brain swelling on MRI at admission. In contrast, evidence of severe brain swelling was seen on MRI in 39 of 143 survivors (27%). Serial MRI scans showed evidence of decreasing brain volume in the survivors who had had brain swelling initially. CONCLUSIONS: Increased brain volume was seen in children who died from cerebral malaria but was uncommon in those who did not die from the disease, a finding that suggests that raised intracranial pressure may contribute to a fatal outcome. The natural history indicates that increased intracranial pressure is transient in survivors. (Funded by the National Institutes of Health and Wellcome Trust U.K.).

Protocol for a magnetic resonance imaging study of participants in the fever RCT: Does fever control prevent brain injury in malaria?

BACKGROUND: Despite eradication efforts, ~135,000 African children sustained brain injuries as a result of central nervous system (CNS) malaria in 2021. Newer antimalarial medications rapidly clear peripheral parasitemia and improve survival, but mortality remains high with no associated decline in post-malaria neurologic injury. A randomized controlled trial of aggressive antipyretic therapy with acetaminophen and ibuprofen (Fever RCT) for malarial fevers being conducted in Malawi and Zambia began enrollment in 2019. We propose to use neuroimaging in the context of the RCT to further evaluate neuroprotective effects of aggressive antipyretic therapy. METHODS: This observational magnetic resonance imaging (MRI) ancillary study will obtain neuroimaging and neurodevelopmental and behavioral outcomes in children previously enrolled in the Fever RCT at 1- and 12-months post discharge. Analysis will compare the odds of any brain injury between the aggressive antipyretic therapy and usual care groups based upon MRI structural abnormalities. For children unable to undergo imaging without deep sedation, neurodevelopmental and behavioral outcomes will be used to identify brain injury. DISCUSSION: Neuroimaging is a well-established, valid proxy for neurological outcomes after brain injury in pediatric CNS malaria. This MRI ancillary study will add value to the Fever RCT by determining if treatment with aggressive antipyretic therapy is neuroprotective in CNS malaria. It may also help elucidate the underlying mechanism(s) of neuroprotection and expand upon FEVER RCT safety assessments.

Protocol for a Magnetic Resonance Imaging (MRI) Study of Participants in the Fever Randomized Controlled Trial: Does fever control prevent brain injury in malaria?

Background: Despite eradication efforts, ~135,000 African children sustained brain injuries as a result of central nervous system (CNS) malaria in 2021. Newer antimalarial medications rapidly clear peripheral parasitemia and improve survival, but mortality remains high with no associated decline in post-malaria neurologic injury. A randomized controlled trial of aggressive antipyretic therapy with acetaminophen and ibuprofen (Fever RCT) for malarial fevers being conducted in Malawi and Zambia began enrollment in 2019. We propose to use neuroimaging in the context of the RCT to further evaluate neuroprotective effects of aggressive antipyretic therapy. Methods: This observational magnetic resonance imaging (MRI) ancillary study will obtain neuroimaging and neurodevelopmental and behavioral outcomes in children previously enrolled in the Fever RCT at 1- and 12-months post discharge. Analysis will compare the odds of any brain injury between the aggressive antipyretic therapy and usual care groups based upon MRI structural abnormalities. For children unable to undergo imaging without deep sedation, neurodevelopmental and behavioral outcomes will be used to identify brain injury. Discussion: Neuroimaging is a well-established, valid proxy for neurological outcomes after brain injury in pediatric CNS malaria. This MRI ancillary study will add value to the Fever RCT by determining if treatment with aggressive antipyretic therapy is neuroprotective in CNS malaria. It may also help elucidate the underlying mechanism(s) of neuroprotection and expand upon FEVER RCT safety assessments.

Magnetic resonance imaging research in sub-Saharan Africa: challenges and satellite-based networking implementation.

As part of an NIH-funded study of malaria pathogenesis, a magnetic resonance (MR) imaging research facility was established in Blantyre, Malawi to enhance the clinical characterization of pediatric patients with cerebral malaria through application of neurological MR methods. The research program requires daily transmission of MR studies to Michigan State University (MSU) for clinical research interpretation and quantitative post-processing. An intercontinental satellite-based network was implemented for transmission of MR image data in Digital Imaging and Communications in Medicine (DICOM) format, research data collection, project communications, and remote systems administration. Satellite Internet service costs limited the bandwidth to symmetrical 384 kbit/s. DICOM routers deployed at both the Malawi MRI facility and MSU manage the end-to-end encrypted compressed data transmission. Network performance between DICOM routers was measured while transmitting both mixed clinical MR studies and synthetic studies. Effective network latency averaged 715 ms. Within a mix of clinical MR studies, the average transmission time for a 256 × 256 image was ~2.25 and ~6.25 s for a 512 × 512 image. Using synthetic studies of 1,000 duplicate images, the interquartile range for 256 × 256 images was [2.30, 2.36] s and [5.94, 6.05] s for 512 × 512 images. Transmission of clinical MRI studies between the DICOM routers averaged 9.35 images per minute, representing an effective channel utilization of ~137% of the 384-kbit/s satellite service as computed using uncompressed image file sizes (including the effects of image compression, protocol overhead, channel latency, etc.). Power unreliability was the primary cause of interrupted operations in the first year, including an outage exceeding 10 days.

Nursing care for pediatric patients with autism spectrum disorders: A cross-sectional survey of perceptions and strategies.

PURPOSE: The purpose of this study is to describe nursing staff perspectives about caring for children with autism spectrum disorders (ASD) in the hospital, strategies they use to support care, and relationships between these factors. DESIGN AND METHODS: A descriptive, cross-sectional survey design with nursing staff at a large pediatric hospital system in the United States was employed. The researcher-designed, pilot-tested survey assessed participant demographics, knowledge about ASD, perceived effectiveness caring for children with ASD, previous training, and current strategy use. Data analysis involved descriptive statistics, correlations, and group comparisons based on interaction frequency with the population and previous training. RESULTS: The participants involved 90 pediatric hospital nursing staff members providing direct care. Respondents demonstrated 90% accurate knowledge of the characteristics of ASD. Self-reported effectiveness in caring for children with ASD did not correlate with knowledge and significantly correlated with an increased number of strategies. Nursing staff with frequent interaction with people with ASD or those with previous training reported significantly more strategies to care for children with ASD. Only 35% of participants reported that they have adequate strategies to care for children with ASD in the hospital. PRACTICE IMPLICATIONS: Having more strategies was the factor associated with higher self-efficacy, so training for nursing staff should focus on increasing the number of strategies to use with children with ASD in the hospital and provide mechanisms to collaborate with other professionals to individualize strategies to meet each child's needs.

Noninvasive measures of brain edema predict outcome in pediatric cerebral malaria.

BACKGROUND: Increased brain volume (BV) and subsequent herniation are strongly associated with death in pediatric cerebral malaria (PCM), a leading killer of children in developing countries. Accurate noninvasive measures of BV are needed for optimal clinical trial design. Our objectives were to examine the performance of six different magnetic resonance imaging (MRI) BV quantification measures for predicting mortality in PCM and to review the advantages and disadvantages of each method. METHODS: Receiver operator characteristics were generated from BV measures of MRIs of children admitted to an ongoing research project with PCM between 2009 and 2014. Fatal cases were matched to the next available survivor. A total of 78 MRIs of children aged 5 months to 13 years (mean 4.0 years), of which 45% were males, were included. RESULTS: Areas under the curve (AUC) with 95% confidence interval on measures from the initial MRIs were: Radiologist-derived score = 0.69 (0.58-0.79; P = 0.0037); prepontine cistern anteroposterior (AP) dimension = 0.70 (0.56-0.78; P = 0.0133); SamKam ratio [Rt. parietal lobe height/(prepontine AP dimension + fourth ventricle AP dimension)] = 0.74 (0.63-0.83; P = 0.0002); and global cerebrospinal fluid (CSF) space ascertained by ClearCanvas = 0.67 (0.55-0.77; P = 0.0137). For patients with serial MRIs (n = 37), the day 2 global CSF space AUC was 0.87 (0.71-0.96; P < 0.001) and the recovery factor (CSF volume day 2/CSF volume day 1) was 0.91 (0.76-0.98; P < 0.0001). Poor prognosis is associated with radiologist score of ≥7; prepontine cistern dimension ≤3 mm; cisternal CSF volume ≤7.5 ml; SamKam ratio ≥6.5; and recovery factor ≤0.75. CONCLUSION: All noninvasive measures of BV performed well in predicting death and providing a proxy measure for brain volume. Initial MRI assessment may inform future clinical trials for subject selection, risk adjustment, or stratification. Measures of temporal change may be used to stage PCM.

1.5 Tesla Magnetic Resonance Imaging to Investigate Potential Etiologies of Brain Swelling in Pediatric Cerebral Malaria.

The hallmark of pediatric cerebral malaria (CM) is sequestration of parasitized red blood cells in the cerebral microvasculature. Malawi-based research using 0.35 Tesla (T) magnetic resonance imaging (MRI) established that severe brain swelling is associated with fatal CM, but swelling etiology remains unclear. Autopsy and clinical studies suggest several potential etiologies, but limitations of 0.35 T MRI precluded optimal investigations into swelling pathophysiology. A 1.5 T MRI in Zambia allowed for further investigations including susceptibility-weighted imaging (SWI). SWI is an ideal sequence for identifying regions of sequestration and microhemorrhages given the ferromagnetic properties of hemozoin and blood. Using 1.5 T MRI, Zambian children with retinopathy-confirmed CM underwent imaging with SWI, T2, T1 pre- and post-gadolinium, diffusion-weighted imaging (DWI) with apparent diffusion coefficients and T2/fluid attenuated inversion recovery sequences. Sixteen children including two with moderate/severe edema were imaged; all survived. Gadolinium extravasation was not seen. DWI abnormalities spared the gray matter suggesting vasogenic edema with viable tissue rather than cytotoxic edema. SWI findings consistent with microhemorrhages and parasite sequestration co-occurred in white matter regions where DWI changes consistent with vascular congestion were seen. Imaging findings consistent with posterior reversible encephalopathy syndrome were seen in children who subsequently had a rapid clinical recovery. High field MRI indicates that vascular congestion associated with parasite sequestration, local inflammation from microhemorrhages and autoregulatory dysfunction likely contribute to brain swelling in CM. No gross radiological blood brain barrier breakdown or focal cortical DWI abnormalities were evident in these children with nonfatal CM.

Alternative oblique head CT scanning technique reduces bone artifact and improves interpretability of brainstem anatomy.

Brainstem pathology due to infections, infarcts and tumors are common in developing countries, but neuroimaging technology in these resource-poor settings is often limited to single slice, and occasionally spiral, CT. Unlike multislice CT and MRI, single slice and spiral CT are compromised by bone artifacts in the posterior fossa due to the dense petrous bones, often making imaging of the brainstem non-diagnostic. With appropriate head positioning, the petrous ridges can be avoided with 40° sagittal oblique scans parallel to either petrous ridge. We describe an alternative sagittal oblique scanning technique that significantly reduces brainstem CT artifacts thereby improving clarity of anatomy. With Institutional Ethical approval, 13 adult patients were enrolled (5 males; 39%). All patients had routine axial brain CT and sagittal oblique scans with no lesions found. Images were read by 2 readers who gave a score for amount of artefact and clarity of structures in the posterior fossa. The mean artifact score was higher for routine axial images compared to sagittal oblique (2.92 vs. 1.23; P<0.0001). The mean anatomical certainty scores for the brainstem were significantly better in the sagittal oblique views compared to routine axial (1.23 vs. 2.77; P<0.0001). No difference was found between the two techniques with respect to the fourth ventricle or the cerebellum (axial vs. sag oblique: 1.15 vs. 1.27; P=0.37). When using single slice CT, the sagittal oblique scanning technique is valuable in improving clarity of anatomy in the brainstem if axial images are non-diagnostic due to bone artifacts.