Impaired intracortical inhibition demonstrated in vivo in people with Dravet syndrome.

Abstract:

OBJECTIVE:Dravet syndrome is a rare neurodevelopmental disorder characterized by seizures and other neurologic problems. SCN1A mutations account for ∼80% of cases. Animal studies have implicated mutation-related dysregulated cortical inhibitory networks in its pathophysiology. We investigated such networks in people with the condition. METHODS:Transcranial magnetic stimulation using single and paired pulse paradigms was applied to people with Dravet syndrome and to 2 control groups to study motor cortex excitability. RESULTS:Short interval intracortical inhibition (SICI), which measures GABAergic inhibitory network behavior, was undetectable in Dravet syndrome, but detectable in all controls. Other paradigms, including those testing excitatory networks, showed no difference between Dravet and control groups. CONCLUSIONS:There were marked differences in inhibitory networks, detected using SICI paradigms, while other inhibitory and excitatory paradigms yielded normal results. These human data showing reduced GABAergic inhibition in vivo in people with Dravet syndrome support established animal models.

journal_name

Neurology

journal_title

Neurology

authors

Stern WM,Sander JW,Rothwell JC,Sisodiya SM

doi

10.1212/WNL.0000000000003868

subject

Has Abstract

pub_date

2017-04-25 00:00:00

pages

1659-1665

issue

17

eissn

0028-3878

issn

1526-632X

pii

WNL.0000000000003868

journal_volume

88

pub_type

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