Document Detail

Endozepine stupor. Recurring stupor linked to endozepine-4 accumulation.
MedLine Citation:
PMID:  9549493     Owner:  NLM     Status:  MEDLINE    
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 recurring 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 behavioural and EEG responses monitored. Treatment with oral flumazenil was attempted in selected cases. Twenty patients were found with recurring 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 behavioural 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. Recurring episodes of stupor may be due to increased endozepine-4. 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.
E Lugaresi; P Montagna; P Tinuper; G Plazzi; R Gallassi; T C Wang; S P Markey; J D Rothstein
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Brain : a journal of neurology     Volume:  121 ( Pt 1)     ISSN:  0006-8950     ISO Abbreviation:  Brain     Publication Date:  1998 Jan 
Date Detail:
Created Date:  1998-05-08     Completed Date:  1998-05-08     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0372537     Medline TA:  Brain     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  127-33     Citation Subset:  AIM; IM    
Institute of Clinical Neurology, University of Bologna, Italy.
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MeSH Terms
Carrier Proteins / adverse effects*,  blood*
Coma / chemically induced*,  diagnosis,  drug therapy
Diazepam Binding Inhibitor
Flumazenil / therapeutic use
Middle Aged
Treatment Outcome
Reg. No./Substance:
0/Carrier Proteins; 0/Diazepam Binding Inhibitor; 78755-81-4/Flumazenil

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