A Positive or a Negative Brain SPECT Clinical Trial
Official title:
Evaluation of Blood Brain Barrier Permeability in Chronic Stroke
In this study the investigators intend to explore the long term significance of BBB disruption on the clinical course and the rate of significant recurrent ischemic events in patients with a chronic stroke.
Evaluation of Blood Brain Barrier Permeability in Chronic Stroke
Mordechai Lorberboym, M.D.1, Yair Lampl, M.D.2, Ronit Gilad, M.D.2.
From the Department of Nuclear Medicine1 and the department of Neurology2 of the Edith
Wolfson Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Introduction
The blood brain barrier (BBB) is a highly selective barrier of brain microvascular
endothelial cells that shields the brain from toxic substances in the blood, supplies brain
tissues with nutrients, and filters harmful compounds from the brain back to the bloodstream
(1). Transport across the BBB is strictly limited through both physical (tight junctions)
and metabolic barriers (enzymes, diverse transport systems). BBB breakdown or alterations in
transport systems play an important role in the pathogenesis of many CNS diseases (HIV-1
encephalitis, Alzheimer's disease, ischemia, tumors, multiple sclerosis, and Parkinson's
disease).
Cerebral ischemia leads to disruption of blood flow, increased BBB permeability, and is
associated with rapid depletion of essential nutrients and oxygen (2-3). Only a few studies
were designed in humans in order to compare the degree of BBB changes and the neurological
outcome after a stroke. The most significant stage of BBB breakdown occurs in humans within
48-72 hours post infarction and is accompanied by increased brain edema volume.
The investigators performed a study on thirty patients with acute stroke of the middle
cerebral artery using technetium-99m-DTPA brain SPECT (4). Tc-99m-DTPA (Diethylenetriamine-
pentacetic acid) brain scintigraphy is a useful technique for the assessment of BBB
disruption. Is has been used in the past to localize areas within the cranium which had been
disrupted by infection, neoplasms, trauma or stroke. The study showed that the magnitude of
disruption of the BBB was negatively correlated with the change in neurological status with
a sensitivity of 95% and a specificity of 89%. Interestingly, a significant proportion of
patients with stroke (23%) had no gross evidence of BBB disruption, all of them with very
good prognosis.
It is unclear for how long the BBB remains disrupted after a stroke, and whether there is
any correlation between the BBB permeability and recurrent ischemic events or delayed
functional and neurological outcome after a stroke.
Aim of the study
In this study the investigators intend to explore the long term significance of BBB
disruption on the clinical course and the rate of significant recurrent ischemic events in
patients with a chronic stroke.
Patients and methods Inclusion criteria
Male and female patients at any age with a history of a large stroke in the territory of the
middle cerebral artery, occurring 1-2 years ago or between 2-5 years ago.
Exlusion criteria
Methods:
40 patients will be recruited from the Neurological Outpatient Clinic of the Edith Wolfson
Medical Center and from the Neurological Department.
For the SPECT study each patient will receive 740 MBq Tc-99m-DTPA and a SPECT study will be
performed 60-90- minutes later. A dual head or a triple head gamma camera is usually used,
equipped with high resolution collimators.
References
1. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD. Blood-brain barrier: structural
components and function under physiologic and pathologic conditions. J Neuroimmune
Pharmacol 2006;1:223-236.
2. del Zoppo GJ, Hallenbeck JM (2000) Advances in the vascular pathophysiology of ischemic
stroke. Thromb Res 98:73-81
3. Petty MA, Wettstein JG (2001) Elements of cerebral microvascular ischaemia. Brain Res
Rev 36:23-34
4. 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;44:1898-1904.
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Time Perspective: Retrospective