doi: 10.1161/01.STR.0000019049.33669.E3
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(Stroke. 2002;33:1456.)
© 2002 American Heart Association, Inc.
Letters to the Editor |
When Is a Stroke Actually "Stable"?
V Chair of Neurology, Department of Neurological Sciences, University "La Sapienza", Rome, Italy
To the Editor:
Lazar et al1 recently published an interesting study on the possibility of midazolam to transiently unmask focal deficits in patients with a good recovery after a stroke. The authors pointed to a direct 
-aminobutyric acid (GABA)A–mediated inhibition of neural activity, thus suggesting a possible role for this neurochemical mechanism in poststroke recovery.
We would like to stress an additional effect of benzodiazepine (BDZ) on cerebral blood flow (CBF). It is known that BDZ causes a global reduction of CBF in normal subjects.2–4 A state of chronic hypoperfusion, which in turn could affect particularly the peri-infarct areas, has been demonstrated in stroke patients in the acute as well as in the chronic phase.5–7 These findings suggest the role of transient cerebral hypoperfusion in unmasking an otherwise clinically silent tissue with a reduced "perfusional reserve."
Therefore, in addition to a direct GABAA-mediated action, we suggest that a global reduction of CBF, linked to BDZ administration, should also be considered. This raises the possibility that a drug-induced critical hypoperfusion of peri-infarct tissue might contribute to the reemergence of previous symptoms.
Lazar et al1 brilliantly demonstrated that a stroke lesion is never "stable," even in the later stages. If a contribution to the reappearance of the old symptoms might be also ascribed to CBF reduction, the latter factor should shed a new light on the complex interaction between drugs and poststroke recovery.
References
1.
Lazar RM, Fitzsimmons BF, Marshall RS, Berman MF, Bustillo MA, Young WL, Mohr JP, Shah J, Robinson JV. Reemergence of stroke deficits with midazolam challenge. Stroke. 2002; 33: 283–285.
2.
Matthew E, Andreason P, Pettigrew K, Carson RE, Herscovitch P, Cohen R, King C, Johanson CE, Greenblatt DJ, Paul SM. Benzodiazepine receptors mediate regional blood flow changes in the living human brain. Proc Natl Acad Sci U S A. 1995; 92: 2775–2779.
3. Reinsel RA, Veselis RA, Dnistrian AM, Feshchenko VA, Beattie BJ, Duff MR. Midazolam decreases cerebral blood flow in the left prefrontal cortex in a dose-dependent fashion. Int J Neuropsychopharmacol. 2000; 3: 117–127.[CrossRef][Medline] [Order article via Infotrieve]
4. Di Piero V, Ferracuti S, Sabatini U, Tombari D, Di Legge S, Pantano P, Cruccu G, Lenzi GL. Diazepam effects on the cerebral responses to tonic pain: a SPET study. Psychopharmacology (Berl). 2001; 158: 252–258.[CrossRef][Medline] [Order article via Infotrieve]
5. De Reuck JL. Evidence for chronic ischaemia in the pathogenesis of vascular dementia: from neuroPATH to neuroPET. Acta Neurol Belg. 1996; 96: 228–231.[Medline] [Order article via Infotrieve]
6. Baron JC. Mapping the ischaemic penumbra with PET: a new approach. Brain. 2001; 124(pt 1): 2–4.
7. Labelle M, Khiat A, Durocher A, Boulanger Y. Comparison of metabolite levels and water diffusion between cortical and subcortical strokes as monitored by MRI and MRS. Invest Radiol. 2001; 36: 155–163.[CrossRef][Medline] [Order article via Infotrieve]
Response
Department of Neurology, Columbia University College of Physicians & Surgeons, New York, NY
We thank Dr Di Piero and his colleagues for bringing to our attention the relevance of recent findings that benzodiazepines produce changes in cerebral blood flow. It is certainly possible that, in addition to direct GABAA-mediated inhibition of compensatory mechanisms, midazolam-induced global hypoperfusion could be reducing the ability of perilesional brain regions to carry out new functions. Although there could be a lowered perfusional threshold in a chronically hypoperfused area adjacent to the infarct, an alternative explanation might be that there are fewer neurons in the compensatory zone that participate in the target function, making them vulnerable to lowered cerebral blood flow. Experimental observations support the notion that compensatory networks after stroke consist of a markedly smaller neural pool than the original system.1 Research using transcranial magnetic stimulation in patients after stroke reveals smaller motor evoked potentials in the affected limbs after stroke as compared with normal, suggesting fewer descending neurons responsible for the generation of movement in these limbs.2 More important, however, is that Di Piero and his colleagues assume that the perilesional area is the region solely responsible for the restitution of function. Investigations with positron-emission tomography and functional MRI to study motor recovery have suggested the importance of the contralateral and ipsilateral cortex in studies of recovery after hemiparesis,3 even as soon as 24 hours after the stroke onset.4 The roles of the contralateral hemisphere and preserved ipsilateral regions have been similarly implicated in the restitution of language,5,6 with recent work indicating that poststroke patients with bilateral language networks have better functional recovery.7 The manner in which the contralesional hemisphere gains such control and may be vulnerable to targeted pharmacological challenge remains to be determined.
References
1. Villablanca JR, Hovda DA. Developmental neuroplasticity in a model of cerebral hemispherectomy and stroke. Neuroscience. 2000; 95: 625–637.[CrossRef][Medline] [Order article via Infotrieve]
2. Traversa R, Cicinelli P, Oliveri M, Giuseppina Palmieri M, Filippi MM, Pasqualetti P, Rossini PM. Neurophysiological follow-up of motor cortical output in stroke patients. Clin Neurophysiol. 2000; 111: 1695–1703.[CrossRef][Medline] [Order article via Infotrieve]
3.
Cramer SC, Nelles G, Benson RR, Kaplan JD, Parker RA, Kwong KK, Kennedy DN, Finkelstein SP, Rosen BR. A functional MRI study of subjects recovered from hemiparetic stroke. Stroke. 1997; 28: 2518–2527.
4.
Marshall RS, Perera GM, Lazar RM, Krakauer JW, Constantine RC, DeLaPaz RL. Evolution of cortical activation during recovery from corticospinal tract infarction. Stroke. 2000; 31: 656–661.
5. Cappa SF, Perani D, Grassi F, Bressi S, Alberoni M, Franceschi M, Bettinardi V, Todde S, Fazio F. A PET follow-up study of recovery after stroke in acute aphasics. Brain Lang. 1997; 56: 55–67.[CrossRef][Medline] [Order article via Infotrieve]
6. Weiller C, Isensee C, Rijntjes M, Huber W, Muller S, Bier D, Dutschka K, Woods RP, Noth J, Diener HC. Recovery from Wernicke’s aphasia: a positron emission tomographic study. Ann Neurol. 1995; 37: 723–732.[CrossRef][Medline] [Order article via Infotrieve]
7.
Thulborn KR, Carpenter PA, Just MA. Plasticity of language-related brain function during recovery from stroke. Stroke. 1999; 30: 749–754.
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