NUBPL mitochondrial disease: new patients and review of the genetic and clinical spectrum

Background: The nucleotide binding protein-like (NUBPL) gene was first reported as a cause of mitochondrial complex I deficiency (MIM 613621, 618242) in 2010. To date, only eight patients have been reported with this mitochondrial disorder. Five other patients were recently reported to have NUBPL disease but their clinical picture was different from the first eight patients. Here, we report clinical and genetic findings in five additional patients (four families).  Methods: Whole exome sequencing was used to identify patients with compound heterozygous NUBPL variants. Functional studies included RNA-Seq transcript analyses, missense variant biochemical analyses in a yeast model (Yarrowia lipolytica) and mitochondrial respiration experiments on patient fibroblasts.  Results: The previously reported c.815-27T>C branch-site mutation was found in all four families. In prior patients, c.166G>A [p.G56R] was always found in cis with c.815-27T>C, but only two of four families had both variants. The second variant found in trans with c.815-27T>C in each family was: C.311T>C [p.L104P] in three patients, c.693+1G>A in one patient and c.545T>C [p.V182A] in one patient. Complex I function in the yeast model was impacted by p.L104P but not p.V182A. Clinical features include onset of neurological symptoms at 3-18 months, global developmental delay, cerebellar dysfunction (including ataxia, dysarthria, nystagmus and tremor) and spasticity. Brain MRI showed cerebellar atrophy. Mitochondrial function studies on patient fibroblasts showed significantly reduced spare respiratory capacity.  Conclusion: We report on five new patients with NUBPL disease, adding to the number and phenotypic variability of patients diagnosed worldwide, and review prior reported patients with pathogenic NUBPL variants

PACS Used While On-Call: A National Survey of Radiology Program Directors and Chief Residents

The aim of this study was to determine the prevalence of different diagnostic image viewing platforms used by radiologists while on-call, and to assess the opinions and preferences of radiology program directors and chief residents regarding their use. An online survey was sent electronically to radiology residency program directors and chief residents via the Association of University Radiologists. Forty-two radiology program directors and 25 chief residents completed the survey, yielding response rates of 24.9 and 8.5 %, respectively. From the survey results, 10 different Picture Archiving Communications Systems (PACS) were identified; GE (25 %), Philips (17 %), and Agfa Impax (15 %) were the most prevalent. Interestingly, only 5 % of all respondents use a secondary "Digital Imaging and Communications in Medicine" viewer for on-call studies. Perceptions of PACS functionality were generally neutral to weakly positive. Most respondents strongly agreed that it is important to have a single integrated PACS for viewing on-call studies and agreed that the PACS should be integrated into the Electronic Medical Records (EMR). The overwhelming majority of respondents use their institution's PACS while on-call. The results show there is still a wide variety of PACS platforms used by different institutions; however, GE, Phillips, and Agfa were some of the most prevalent. Most radiologists surveyed have neutral to slightly positive perceptions about the functionality and ease of use of their PACS. Finally, while radiologists agree that PACS should be integrated with EMR, only 53 % of respondents currently have this arrangement

Acute hemorrhagic leukoencephalitis: neuroimaging features and neuropathologic diagnosis

A case of biopsy-proven acute hemorrhagic leukoencephalitis is reported. The early computed tomography scans showed extensive bilateral hypodensities with mass effects and foci of microhemorrhages. Bilateral asymmetric hyperintensities in the mesiotemporal and frontal lobes and massive edema were found on T2-weighted and fluid-attenuated inversion recovery magnetic resonance images in a pattern classic for herpes simplex encephalitis. This fulminant demyelinating disease progresses to coma and death within days. Early diagnosis with neuroimaging studies and rapid correlation with the clinical findings of this disease are vital for the institution of potentially lifesaving treatments