More supporting evidence of the interneuron hypothesis of Dravet syndrome arose this summer after researchers found decreased sodium currents and action potential firing in inhibitory patient-derived Dravet iPSC neurons, but normal function in excitatory Dravet neurons (Sun, et. al. 2016). (What is the inhibitory interneuron hypothesis? It is the prevailing belief that many SCN1A mutations render inhibitory interneurons defective compared to those without SCN1A mutations, and this decrease in inhibition results in the seizures seen in Dravet syndrome. This hypothesis helps explain why sodium channel blockers such as lamotrigine are found to exacerbate seizures in Dravet syndrome despite the fact that one would think that less active sodium ion channels would help reduce seizures.)

References

  1. Takaori, T., et. al. (2016). Two mild cases of Dravet syndrome with truncating mutation of SCN1A. Brain & Development. Published online August 17, 2016 (doi: 10.1016/j.braindev.2016.07.006)
  2. Daverio, M., et. al. (2016). Supraventricular tachycardia during status epilepticus in Dravet syndrome: A link between brain and heart? Pediatric Neurology, March 2016 vol56:69-71.http://www.pedneur.com/article/S0887-8994(15)30030-8/fulltext
  1. Dlouhy, B.J., et. al. (2016). Palliative epilepsy surgery in Dravet syndrome – case series and review of the literature. Child’s Nervous System. Published online July 27, 2016 (doi: 10.1007/s00381-016-3201-4)http://link.springer.com/article/10.1007%2Fs00381-016-3201-4
  1. Djemie, T., et. al. (2016). Pitfalls in genetic testing: the story of missed SCN1A mutations.Molecular Genetics & Genomic Medicine. Jul; 4(4): 457-464.
  2. Sun, Y., et. al. (2016). A deleterious Nav1 mutation selectively impairs telencephalic inhibitory neurons derived from Dravet Syndrome patients. eLife. Published online July 26, 2016 (doi: 10.7554/eLife.13073) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961470/
  3. Trivisano, M., et. al. (2016). PCDH19-related epilepsy and Dravet syndrome: Face-off between two early-onset epilepsies with fever sensitivity. Epilepsy Research Sep; 125:32-6.http://www.epires-journal.com/article/S0920-1211(16)30086-9/abstract
  4. Hsiao, J., et. al. (2016). Upregulation of haploinsufficient gene expression in the brain by targeting a long non-coding RNA improves seizure phenotype in a model of Dravet syndrome. EBioMedicine, July;9:257077. http://www.ebiomedicine.com/article/S2352-3964(16)30194-3/abstract
  5. Gitiaux, C., et. al. (2016). Motor neuropathy contributes to crouching in patients with Dravet syndrome. Neurology Jul 19;87(3):277-81.
  6. El Fotoh, A., et. al. (2016). The potential implication of SCN1A and CYPA5 genetic variants on antiepileptic drug resistance among Egyptian epileptic children. Seizure. Vol 41: 75-80. http://www.seizure-journal.com/article/S1059-1311(16)30092-9/abstract
  7. Daoud, H., et. al. (2016). Next-generation sequencing for diagnosis of rare diseases in the neonatal intensive care unit. Canadian Medical Association Journal vol188(11): E254-E260. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978597/