ro-16-0154 and Stroke

Neuronal cells are susceptible to cerebral ischaemia. As gamma-aminobutyric acid(A) (GABA(A)) receptors are specific for neurones, functional receptor imaging using I-iomazenil (IMZ), a ligand to the GABA benzodiazepine receptor, has been proposed as an imaging modality for the assessment of neuronal integrity. However, there is only limited experience with IMZ in patients with acute cerebral infarction. Therefore, the aim of this study was to evaluate IMZ single photon emission computed tomography (SPECT) in patients with acute cerebral ischaemia. IMZ SPECT was performed in 21 patients with acute cerebral infarction 7-10 days after stroke onset. Eleven patients underwent systemic thrombolysis within 6 h after symptom onset (group 1), whereas 10 patients were treated conservatively (group 2). IMZ (150-200 MBq) was injected intravenously and imaging was performed using a dedicated four-head SPECT camera at 5 min (perfusion) and 90 min (receptor distribution) post-injection, with an acquisition time of 50 min each. Images were analysed by visual inspection. Four patients showed normal IMZ distribution, and 17 patients showed abnormalities of IMZ uptake on both early and late images. In six patients with regional uptake deficits, a crossed cerebellar diaschisis was observed on early images. Cerebellar inhomogeneity of tracer uptake was absent at the time of late images in all six patients. In eight patients, areas of hypoperfusion corresponded exactly to the regions of receptor deficiency (match). In five patients, preserved neuronal integrity was present in hypoperfused areas (mismatch). In four patients, normally or even hyperperfused areas exhibited regional receptor deficiency (inverse mismatch). In conclusion, IMZ SPECT demonstrated differences between regional perfusion and receptor distribution in about one-half of patients 7-10 days after acute cerebral ischaemia. Interesting patterns between the early phase (perfusion) and the late phase (receptor distribution) were found. These patterns are indicative of the heterogeneous development of cerebral ischaemia where, even days after stroke onset, areas of hypoperfusion but preserved neuronal integrity may be present. However, the evaluation of the potential clinical and therapeutic impact of individual IMZ distribution patterns requires further investigation.

Topics: Adult; Aged; Aged, 80 and over; Cerebral Infarction; Data Interpretation, Statistical; Female; Flumazenil; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Radiopharmaceuticals; Receptors, GABA-A; Sterilization, Reproductive; Stroke; Thrombolytic Therapy; Tomography, Emission-Computed, Single-Photon

Reduced cortical benzodiazepine receptor binding potential in late images of I-iomazenil SPECT indicates neuronal damage in the cortex. We present the case of a 31-year-old woman with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) who had focal seizures in the right hand. FLAIR imaging in the ictal state revealed a high-intensity lesion in the left post-central gyrus, while I-iomazenil SPECT showed decreased tracer uptake in this lesion. The lesion completely disappeared on FLAIR imaging performed 1 month after the focal seizures; in contrast, I-iomazenil SPECT still revealed a significant decrease in tracer uptake in this lesion.

Topics: Adult; Female; Flumazenil; Humans; Iodine Radioisotopes; MELAS Syndrome; Stroke; Tomography, Emission-Computed, Single-Photon

The mismatch of hypoperfused tissue on perfusion imaging and ischemic tissue on diffusion-weighted imaging is used as a surrogate marker for thrombolytic therapy in the extended time window. Mismatch tissue may recover completely, progress toward infarction, or proceed toward incomplete infarction with selective loss of cortical neurons. We used [(123)I]iomazenil-single-photon emission computed tomography (IMZ-SPECT) to characterize the neuronal integrity of reperfused "tissue at risk of infarction" that appeared morphologically intact on follow-up magnetic resonance imaging (MRI).. Twelve patients with acute stroke with striatocapsular (SC) infarctions were examined with multimodal MRI at days 0, 1, and 7; IMZ-SPECT was performed at days 5 to 15. The PI at day 0, fluid-attenuated inversion recovery (FLAIR) image at day 7, and IMZ-SPECT were coregistered and stereotactically normalized. The mismatch volume of interest (VOI) was defined as the initial PI lesion subtracted by the FLAIR lesion at day 7. An asymmetry ratio (AR) was computed by dividing the mean IMZ uptake of the mismatch VOI by the unaffected mirror VOI. The same AR was computed for signal intensity on FLAIR images at day 7. Three patients with cortical infarctions were included for calibration of the AR. In this group, the VOI consisted of the FLAIR lesion at day 7.. All patients with SC infarctions had a large mismatch of initially hypoperfused (112+/-31 mL; mean+/-SD) and finally infarcted tissue (19+/-14 mL). Mean AR of cortical IMZ uptake was 0.85+/-0.01 in cortical infarctions and 0.95+/-0.03 in SC infarctions; thereby AR showed a continuous distribution from clearly reduced (0.89) to normal (1.01) in SC infarctions. Mean AR for FLAIR signal intensity was 1.84+/-0.14 for cortical infarctions and normal (1.01+0.03) for SC infarctions.. IMZ-SPECT detected a selective loss of cortical neurons in patients with SC infarctions in transient hypoperfused tissue, which was morphologically intact on MRI.

Topics: Adult; Aged; Cell Count; Cerebral Infarction; Female; Flumazenil; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neurons; Stroke; Tomography, Emission-Computed, Single-Photon