Saturday, July 29, 2017

FSHD inheritance

 2012 Mar;131(3):325-40. doi: 10.1007/s00439-011-1100-z. Epub 2011 Oct 9.

Facioscapulohumeral muscular dystrophy (FSHD): an enigma unravelled?



Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy after the dystrophinopathies and myotonic dystrophy and is associated with a typical pattern of muscle weakness. Most patients with FSHD carry a large deletion in the polymorphic D4Z4 macrosatellite repeat array at 4q35 and present with 1-10 repeats whereas non-affected individuals possess 11-150 repeats. An almost identical repeat array is present at 10q26 and the high sequence identity between these two arrays can cause difficulties in molecular diagnosis. Each 3.3-kb D4Z4 unit contains a DUX4 (double homeobox 4) gene that, among others, is activated upon contraction of the 4q35 repeat array due to the induction of chromatin remodelling of the 4qter region. A number of 4q subtelomeric sequence variants are now recognised, although FSHD only occurs in association with three 'permissive' haplotypes, each of which is associated with a polyadenylation signal located immediately distal of the last D4Z4 unit. The resulting poly-A tail appears to stabilise DUX4 mRNAs transcribed from this most distal D4Z4 unit in FSHD muscle cells. Synthesis of both the DUX4 transcripts and protein in FSHD muscle cells induces significant cell toxicity. DUX4 is a transcription factor that may target several genes which results in a deregulation cascade which inhibits myogenesis, sensitises cells to oxidative stress and induces muscle atrophy, thus recapitulating many of the key molecular features of FSHD.


Wednesday, March 22, 2017

Hypoglycorrhachia

The maintenance of CSF glucose levels is controlled by several mechanisms, including glucose transport into and out of the CSF as well as glucose utilization by cells. Glucose enters the CSF through the blood-brain barrier at the choroid plexus with the help of glucose transport proteins (such as GLUT1) and can either be used by cells or exit through the arachnoid villi into the venous system 119. The pathophysiology behind hypoglycorrhachia is not fully understood but is likely multifactorial. Possible contributors include decreased glucose delivery to the choroid plexus because of reduced blood flow, decreased transport across the blood-brain barrier, increased metabolism in the brain, and increased glucose transport out of the CSF into the venous system 1. While it was once thought that an increased rate of glycolysis by bacterial or immune cells was the primary cause of hypoglycorrhachia, this is no longer conventional thought12021

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065645/#__ffn_sectitle

Friday, January 13, 2017

When was the term SRSE first used?

Super-refractory status epilepticus is defined as status epilepticus that continues or recurs 24 h or more after the onset of anaesthetic therapy, including those cases that recur on the reduction or withdrawal of anaesthesia. It was a term used first in the Third London-Innsbruck Colloquium on status epilepticus held in Oxford on 7–9th April 2011 (Shorvon and Trinka, 2011)
Shorvon SD, Trinka E. Proceedings of the 3rd London-Innsbruck Colloquium on Status Epilepticus. Epilepsia 2011;52 Suppl 5.