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Journal of the Belgian Society of... 2021The main differential diagnosis of leukodystrophy associated with macrocephaly consists of Alexander disease, Canavan disease, and megalencephalic leukodystrophy with...
The main differential diagnosis of leukodystrophy associated with macrocephaly consists of Alexander disease, Canavan disease, and megalencephalic leukodystrophy with subcortical cysts. Distinguishing imaging characteristics of Alexander disease are an apicoposterior gradient of white matter involvement and a periventricular T2-hypointense rim.
PubMed: 34723085
DOI: 10.5334/jbsr.2588 -
Science Translational Medicine Apr 2022Intracellular accumulation of TAU aggregates is a hallmark of several neurodegenerative diseases. However, global genetic reduction of TAU is beneficial also in models...
Intracellular accumulation of TAU aggregates is a hallmark of several neurodegenerative diseases. However, global genetic reduction of TAU is beneficial also in models of other brain disorders that lack such TAU pathology, suggesting a pathogenic role of nonaggregated TAU. Here, conditional ablation of TAU in excitatory, but not inhibitory, neurons reduced epilepsy, sudden unexpected death in epilepsy, overactivation of the phosphoinositide 3-kinase-AKT-mammalian target of rapamycin pathway, brain overgrowth (megalencephaly), and autism-like behaviors in a mouse model of Dravet syndrome, a severe epileptic encephalopathy of early childhood. Furthermore, treatment with a TAU-lowering antisense oligonucleotide, initiated on postnatal day 10, had similar therapeutic effects in this mouse model. Our findings suggest that excitatory neurons are the critical cell type in which TAU has to be reduced to counteract brain dysfunctions associated with Dravet syndrome and that overall cerebral TAU reduction could have similar benefits, even when initiated postnatally.
Topics: Animals; Autistic Disorder; Disease Models, Animal; Epilepsies, Myoclonic; Epilepsy; Epileptic Syndromes; Humans; Infant; Mice; Neurons; Phosphatidylinositol 3-Kinases; Spasms, Infantile; Sudden Unexpected Death in Epilepsy; tau Proteins
PubMed: 35476595
DOI: 10.1126/scitranslmed.abm5527 -
International Journal of Molecular... May 2024Macrocephaly, characterized by an abnormally large head circumference, often co-occurs with distinctive finger changes, presenting a diagnostic challenge for clinicians.... (Review)
Review
Macrocephaly, characterized by an abnormally large head circumference, often co-occurs with distinctive finger changes, presenting a diagnostic challenge for clinicians. This review aims to provide a current synthetic overview of the main acquired and genetic etiologies associated with macrocephaly and finger changes. The genetic cause encompasses several categories of diseases, including bone marrow expansion disorders, skeletal dysplasias, ciliopathies, inherited metabolic diseases, RASopathies, and overgrowth syndromes. Furthermore, autoimmune and autoinflammatory diseases are also explored for their potential involvement in macrocephaly and finger changes. The intricate genetic mechanisms involved in the formation of cranial bones and extremities are multifaceted. An excess in growth may stem from disruptions in the intricate interplays among the genetic, epigenetic, and hormonal factors that regulate human growth. Understanding the underlying cellular and molecular mechanisms is important for elucidating the developmental pathways and biological processes that contribute to the observed clinical phenotypes. The review provides a practical approach to delineate causes of macrocephaly and finger changes, facilitate differential diagnosis and guide for the appropriate etiological framework. Early recognition contributes to timely intervention and improved outcomes for affected individuals.
Topics: Humans; Megalencephaly; Fingers
PubMed: 38791606
DOI: 10.3390/ijms25105567 -
Child's Nervous System : ChNS :... Nov 2021Multiple names within the literature refer to a clinical picture affecting infants and consisting of a large or fast growing head circumference with enlarged cortical... (Review)
Review
PURPOSE
Multiple names within the literature refer to a clinical picture affecting infants and consisting of a large or fast growing head circumference with enlarged cortical subarachnoid spaces (CSAS) while cranial sutures are open. This myriad of terms demonstrates the confusion about the entity, that may even group together different etiological processes. In this review, we aim to shed light on this matter in an effort to restate the defining features of the clinical picture and sum the evidence and current understanding of its pathophysiology and related imaging findings.
METHODS
Extensive and updated review of the literature with special focus on defining features, clinical history with long term evaluation and pathophysiological process.
RESULTS
Functional and molecular CSF studies as well as clinical evidence challenges the common pathophysiological theory based on non-functional arachnoid villi. Conversely, there is increasing evidence supporting cerebro-venous system abnormalities as the main pathophysiological factor. Additionally, long term cohorts studies show that it may have subtle but irreversible neurodevelopmental consequences.
CONCLUSION
Subarachnomegaly is an age-related condition of the infancy with radiological enlargement of CSAS and often self limiting course. However, considering the evidence on pathophysiology as outlined herein and long term outcome reports, further research effort is needed to assess the consequences of venous outflow impairment and enlarged CSAS and how this relates to imaging findings and neurodevelopment test results later in life.
Topics: Humans; Hyperemia; Infant; Subarachnoid Space
PubMed: 34687332
DOI: 10.1007/s00381-021-05328-z