ABSTRACT
Giant axonal neuropathy (GAN) is a rare pediatric neurodegenerative disease. It is best known for the "giant" axons caused by accumulations of intermediate filaments. The disease is progressive, with onset around age 3 years and death by the third decade of life. GAN results from recessive mutations in the GAN gene encoding gigaxonin, and our analysis of all reported mutations shows that they are distributed throughout the protein structure. Precisely how these mutations cause the disease remains to be determined. In addition to changes in peripheral nerves that are similar to those seen in neuropathies such as Charcot-Marie-Tooth type 2, GAN patients exhibit a wide range of central nervous system signs. These features, corroborated by degeneration of central tracts apparent from postmortem pathology, indicate that GAN is also a progressive neurodegenerative disease. To reflect this phenotype more precisely, we therefore propose that the disease should be more appropriately referred to as "giant axonal neurodegeneration."
Subject(s)
Giant Axonal Neuropathy/etiology , Giant Axonal Neuropathy/pathology , Animals , Cytoskeletal Proteins/metabolism , Disease Progression , Giant Axonal Neuropathy/genetics , Giant Axonal Neuropathy/physiopathology , Humans , Intermediate Filaments/pathology , Mutation/geneticsABSTRACT
Macrophage activation syndrome (MAS) is a potentially life-threatening condition that may complicate many pediatric rheumatologic diseases. Because of its similarity in presentation to other conditions with overlapping manifestations, such as flares of rheumatologic disease or systemic infection, and the fact that there exists no single pathognomonic clinical finding or laboratory parameter to aid in diagnosis, MAS presents a significant diagnostic challenge to the practicing pediatrician with limited access to consulting pediatric rheumatologists. Along with a review of the physiology and manifestations of the condition, we have included the most current consensus for diagnosing MAS. [Pediatr Ann. 2019;48(10):e395-e399.].
Subject(s)
Macrophage Activation Syndrome/diagnosis , Adolescent , Arthritis, Juvenile/complications , Female , Humans , Immunosuppressive Agents/therapeutic useSubject(s)
Blepharoptosis , Diplopia , Aged , Blepharoptosis/etiology , Diplopia/etiology , Female , HumansABSTRACT
Sleep exerts many effects on mammalian forebrain networks, including homeostatic effects on both synaptic strengths and firing rates. We used large-scale recordings to examine the activity of neurons in the frontal cortex of rats and first observed that the distribution of pyramidal cell firing rates was wide and strongly skewed toward high firing rates. Moreover, neurons from different parts of that distribution were differentially modulated by sleep substates. Periods of nonREM sleep reduced the activity of high firing rate neurons and tended to upregulate firing of slow-firing neurons. By contrast, the effect of REM was to reduce firing rates across the entire rate spectrum. Microarousals, interspersed within nonREM epochs, increased firing rates of slow-firing neurons. The net result of sleep was to homogenize the firing rate distribution. These findings are at variance with current homeostatic models and provide a novel view of sleep in adjusting network excitability.