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Endozepine Stupor. Recurring Stupor Linked to Endozepine-4 Accumulation
Brain 121:127-133, Lugaresi,E.,et al, 1998
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Article Abstract
Recurring stupor can be caused by repeated metabolic,toxic or structural brain disturbances.Recently,cases of recurring stupor with fast EEG activity were shown to display increased endogenous benzodiazepine-like activity during the episodes of stupor.Patients with recurrent stupor underwent extensive metabolic and toxicologic screening,EEG and brain imaging.Endozepines and exogenously administered benzodiazepines were assayed in plasma and CSF by means of mass spectrometry.Flumazenil,a benzodiazepine antagonist was administered and the behavioral and EEG responses were monitored.Treatment with oral flumazenil was attempted in selected cases.Twenty patients were found with recurrent stupor.Episodes had begun between ages 18 and 67 years and in nine patients had disappeared spontaneously after 4-6 years with symptoms.Stupor lasted hours or days.Onset of the episodes and frequency were unpredictable. Patients were normal between attacks.Stupor was characterized by initial drowsiness,staggering and behavioral changes followed by deep sleep and spontaneous recovery with post-ictal amnesia.Biochemical screening and brain imaging were always normal.Ictal EEG showed fast background activity and flumazenil transiently awoke the patients and normalized the EEG.In the nine cases examined,endozepine-4 levels were increased during the stupor.Oral flumazenil reduced the frequency of the attacks in three of these nine patients.We propose the term'endozepine stupor'for such episodes.Endozepine-4 is an endogenous ligand for the benzodiazepine recognition site at the GABAA receptor with unknown molecular structure.
 
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coma
electroencephalogram
electroencephalogram,abnormalities of
endozepine
flumazenil
idiopathic recurring stupor
paroxysmal neurologic deficits
stuporous
treatment of neurologic disorder

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