Midazolam challenge reinduces neurological deficits after transient ischemic attack.
OBJECTIVE
A transient ischemic attack (TIA) in the brain is classically considered a syndrome lasting <24 hours. Having previously shown that an experimental challenge with the GABAA agonist midazolam in recovered stroke patients can reinduce the acute clinical state, we determined whether TIA patients would demonstrate a similar effect.


METHODS
Four right-handed patients participated: 3 with clinical TIA presumed to have affected the left hemisphere within the previous 24 to 72 hours and no evidence of a new lesion on diffusion-weighted and fluid-attenuated inversion recovery imaging, and 1 patient with an asymptomatic temporal arteriovenous malformation. The TIA duration ranged from 30 minutes to 3 hours. Each patient underwent baseline testing for motor function and aphasia, after which intravenous midazolam was delivered until mild drowsiness was detected. Patients were tested during the peak drug effect and again after 2 hours when sedation had dissipated.


RESULTS
No patient showed weakness or aphasia at baseline. After administration of midazolam, all 3 TIA patients demonstrated re-emergence of features that characterized their recent transient neurological syndromes (right-sided weakness and/or aphasia) but no left-sided findings. The arteriovenous malformation patient who had never been symptomatic showed no drug effect. Two hours later, all TIA patients returned to their normal clinical state.


CONCLUSIONS
Patients who had suffered recent transient cerebral ischemic episodes and were neurologically intact with negative diffusion-weighted imaging showed re-emergence of prior focal deficits after administration of a benzodiazepine in a dose that produces light sedation. These findings suggest that presumed TIA may produce neuronal dysfunction beyond the symptomatic period.
Lazar
Ronald M
RM
From the Columbia University College of Physicians and Surgeons, Columbia-Presbyterian Medical Center, New York, NY, USA. ral22@columbia.edu
Fitzsimmons
Brian-Fred
BF
Marshall
Randolph S
RS
Mohr
J P
JP
Berman
Mitchell F
MF
D000328:Adult; D000368:Aged; D001037:Aphasia / Q000139:chemically induced; D004401:Dysarthria / Q000139:chemically induced; D005260:Female; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D006801:Humans; D002546:Ischemic Attack, Transient / Q000150:complications / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging; D008297:Male; D008874:Midazolam / Q000009:adverse effects*; D008875:Middle Aged; D009422:Nervous System Diseases / Q000175:diagnosis* / Q000209:etiology; D010291:Paresis / Q000139:chemically induced; D011237:Predictive Value of Tests; D020127:Recovery of Function
D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D008874:Midazolam