Blood-brain barrier integrity in a zolpidem-responder patient
N E Nyakale, R P Clauss, H W Nel, M M SathekgeN E Nyakale and M M Sathekge hail from the Nuclear Medicine Department, Steve Biko Academic Hospital, University of Pretoria. H W Nel is from the Wellco Medical Centre, Pollack Park, Springs. R P Clauss is from the Nuclear Medicine Department, Royal Surrey County Hospital, Guildford, UK.
S Afr Med J 2012;102(10):790-791.
DOI:10.7196/SAMJ.5993
Studies have documented improvements in brain-damaged patients following zolpidem treatment;1 , 2 , 3 single-photon emission computed tomography (SPECT) technetium-99m-labelled hexamethylpropylene amine oxime (99mTcHMPAO) brain scans have shown functioning in previously dormant areas of injured brain, sometimes many years post injury.3 These dormant areas have no typical location, vary from patient to patient and have slow-wave rhythmic electrical activity which desynchronises after zolpidem treatment.4 Neurotransmitter abnormalities, including γ-aminobutyric acid (GABA) depletion via chronic blood-brain barrier (BBB) dysfunction, have been proposed as the cause for dormancy. Other considerations include leakage into the cerebrospinal fluid or inadequate neurotransmitter production.2
We report for the first time a zolpidem-responder patient investigated for chronic BBB dysfunction 5 years after traumatic brain injury. The BBB was investigated using an intravenous hydrophilic radio-tracer – technetium-99m-labelled diethylene-triamine-pentacetic acid (99mTcDTPA) which is kept outside of the brain by a normally functioning BBB, but penetrates it upon disruption following acute traumatic brain injury, stroke, brain tumour or infection.5
Case description
A 27-year-old man sustained a left-sided head injury during a car accident in September 2005. Initially comatose, he regained full consciousness after 3 months, but remained neurologically disabled, walking with difficulty and a limp due to severe muscle spasms. He had poor co-ordination, short-term memory impairment, and impaired speech, especially in consonant pronunciation. He had decreased confidence in performing daily activities and withdrew socially.
In February 2011, upon initiation of treatment with 10 mg oral
zolpidem daily, the patient’s movement, coordination and gait
improved markedly. His muscle spasms decreased and only a
minimal limp remained. His speech improved, especially in the
pronunciation of ‘s’ and ‘r’. He became more confident in daily
activities and his family reported an increase in his social
participation. His Barthel index was normal before and after
zolpidem treatment. The patient’s Tinetti falls efficacy scale
improved from 21/100 to 15/100. On baseline brain SPECT scan
prior to zolpidem treatment there was a decreased uptake of
99mTcHMPAO in the left frontoparietal region, left temporal
region and left thalamus. Marked improvement within 1 hour after
zolpidem treatment was demonstrated at a follow-up scan 2 weeks
later (Fig. 1, a and b). Results of the 99mTcDTPA BBB scan
remained within normal limits before and after zolpidem
treatment (Fig. 1, c and d). The baseline 99mTcHMPAO scan showed
a focally deficient cerebral blood flow that improved after
zolpidem treatment, but the 99mTcDTPA scan remained normal.
There was therefore no evidence of a BBB leak in the patient 5
years after brain damage.
Conclusion
This case confirms previous findings of clinical and cerebral blood flow improvements with zolpidem treatment in a patient left neurologically disabled after brain damage. Long-term brain suppression and dormancy, reversible with zolpidem, was not attributed to long-term BBB dysfunction in the patient.
1. Clauss RP, Güldenpfennig WM, Nel HJ, Sathekge MM, Venkannagari RR. Extraordinary arousal from semi-comatose state on zolpidem: A case report. S Afr Med J 2000;90(1):68-72.
2. Clauss RP, Nel HW. Drug induced arousal from the permanent vegetative state. Neuro Rehab 2006;21(1):23-28.
3. Nyakale NE, Clauss RP, Nel HW, Sathekge MM. Clinical and Brain SPECT scan response to zolpidem in patients after brain damage. Arzneimittel Forschung 2010;60(4):177-181. [http://dx.doi.org/10.1016/j.clinph.2009.11.084]
4. Hall SD, Yamawaki N, Fisher AE, Clauss RP, Woodhall GL, Stanford IM. GABA(A) alpha-1 subunit mediated desynchronization of elevated low frequency oscillations alleviates specific dysfunction in stroke – a case report. Clin Neurophysiol 2010;121(4):549-555. [http://dx.doi.org/10.1016/j.clinph.2009.11.084]
5. Lorberboym M, Lampl Y, Sadeh M. Correlation of 99mTc-DTPA SPECT of the blood brain barrier with neurologic outcome after acute stroke. J Nucl Med 2003;44(12):1898-1904.
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