Tc99m-HMPAO Neuro--SPECT Assessment of Ischemic Penumbra in Acute
Brain Infarct: Control of Intra-arterial Thrombolysis Treatment.
Article N° AJ26-1
[1]Mena, Francisco J. M.D; [2]Mena, Ismael M.D; [3]Ducci, Hector M.D; [4]Soto, Francisco M.D; [4]Pedraza, Luis M.D; [4]Contreras, Andrea M.D; [4]Miranda, Marcelo M.D;[4],Basaez, Esteban MD;[4],Fruns, Manuel M.D.
[1] Interventional Neuroradiology, Clínica Las Condes, Santiago, Chile; [2]Nuclear Medicine Department, Clínica Las Condes, Santiago, Chile; [3] Interventional Cardiology, Clínica Las Condes, Santiago, Chile; [4], Neurology Department, Clínica Las Condes, Santiago, Chile. All members of the Stroke Unit, Clínica Las Condes, Santiago, Chile
Correspondence:
F. Mena, M. D.,
Dept. of Radiology, Clínica Las Condes
Lo Fontecilla 441 Santiago Chile
CP 668 2157.
Fax 562 210 4568
E-mail: fmena@clinicalascondes.cl
Cita/Reference:
Mena, Francisco J.; Mena, Ismael; Ducci, Hector. et al. Tc99m-HMPAO Neuro--SPECT Assessment of Ischemic Penumbra in Acute Brain Infarct: Control of Intra-arterial Thrombolysis Treatment. Alasbimn Journal 7(26): October 2004. Article N° AJ26-1.
Abstract
Acute brain infarct is a medical emergency potentially reversible if treated with thrombolysis, an approved therapy, if performed in the first 3 to 6 hours of evolution. Thrombolysis has many benefits, but it also has associated risks, mainly development of intracranial hemorrhage. The selection of which patient should receive this type of treatment had been an important research topic over the last decade. As a consequence neuroimaging of brain infarct has significantly improved during the last few years. A variety of diagnostic studies are now available in the evaluation of brain infarct and in particular of potentially reversible brain ischemia, including magnetic resonance imaging (MRI) diffusion-perfusion, perfusion computed tomography (CT) and functional neuroimaging techniques includes positron emission tomography (PET) and single-photon emission tomography (SPECT). The aim of this study is to present our experience with a group of patients that presented with acute brain ischemia and had a NeuroSPECT evaluation before and after intra-arterial thrombolysis and/or possible stent placement, in the treatment of acute brain infarct.
METHODS: 16 patients were treated acutely for a significant ischemic stroke with the following protocol. 1) Admission, and complete neurological evaluation. 2) Brain CT scan performed to rule out hemorrhage or established infarct. 3) IV injection of 1100MBq Tc99m HMPAO (Ceretectm) 4) Conventional cerebral angiography and intra-arterial thrombolysis with tPA and /or angioplasty/stent if necessary. 5) NeuroSPECT assessment of ischemic penumbra (Pre-therapy results). 6) 14 of 16 patients received a NeuroSPECT (Post-therapy results) control at 24 hours.
NeuroSPECT image acquisition was performed immediately following arterial thrombolysis with a dual Head Camera, Siemens ECAM, SHR collimators and conventional protocol. Image processing was performed using the Neurogam, Segami Corp. Software as previously reported in Alasbimn Journal 2(7): April 2000. http://www.alasbimnjournal.cl. The analysis consists of 1) Talairach brain volume normalization. 2) Voxel by voxel comparison of the individual brain cortex uptake normalized to the maximum in the cortex with a normal database of 24 age-matched controls.
RESULTS: The results were expressed in standard deviations (SD) below the normal mean. Normal mean is 72 ± 5 % of maximum in the brain cortex. Thrombolysis significantly reduced the brain hypoperfusion of the studied patients. Overall, 7 of 16 patients made good clinical recovery (mR 0-1) after the thrombolysis treatment. 7 of 16 patients made a moderate to poor clinical recovery (mR 2-4) and 2 of 16 patients died. The best clinical outcomes were found when successful recanalization of the occluded vessel was achieved in the presence of only moderate or superficial cerebral hypoperfusion. Patients that presented with large areas of severe brain hypoperfusion tended to have a worse outcome.
CONCLUSIONS: NeuroSPECT examination 1) Provides useful information of infarct/penumbra during the first hours of evolution. 2) Evaluates the efficacy of thrombolysis and also angioplasty and stenting therapy. 3) Helps anticipate post therapy evolution.
El infarto cerebral agudo representa una emergencia clínica, potencialmente reversible si se trata con trombolisis durante las primeras 3 a 6 horas de evolución. La trombolisis tiene muchas ventajas para el paciente, pero también representa algunos riesgos como el desarrollo de una hemorragia intracerebral. Como consecuencia de un intenso trabajo de investigación contamos hoy dia con importantes avances en diferentes técnicas de neuro-imágenes para evaluar la isquemia cerebral potencialmente reversible, incluyendo la resonancia magnética (RM) con difusión-perfusión, la tomografía computada (CT) con perfusión y estudios neurofuncionales como el PET y el SPECT cerebral. Este trabajo comunica los resultados en la evaluación pre y post tratamiento endovascular en una serie de pacientes que presentaron isquemia cerebral aguda y luego fueron tratados con trombolisis intra-arterial cerebral.
MÉTODO: 16 pacientes fueron tratados de forma aguda por un infarto cerebral agudo siguiendo el siguiente protocolo: 1) Admisión y evaluación completa neurológica. 2) TAC cerebral para descartar presencia de hemorragia cerebral o de un infarto cerebral establecido. 3) Inyección endovenosa de 1100MBq Tc99mm HMPAO (Ceretecmr) 4) Angiografía cerebral convencional y trombolisis intra-arterial cerebral con tPA y posible angioplastía y colocación de stent. 5) Adquisición de imágenes de NeuroSPECT para evaluar penumbra isquémica (resultados pre-terapia) 6) 14 de 16 pacientes recibieron NeuroSPECT de control a las 24 horas (resultados post-terapia).
La adquisición de imágenes de NeuroSPECT fue inmediatamente después de la trombolisis utilizando una cámara de doble cabezal, Siemens ECAM, SHR colimador utilizando protocolo habitual. Las imágenes fueron procesadas utilizando un software Neurogam de Segami Corp. previamente reportado en Alasbimn Journal 2(7):Abril 2000. http://www.alasbimnjournal.cl El análisis estadístico consistió en 1) normalización del volumen cerebral de acuerdo al mapa de Talairach. 2) comparación voxel por voxel del cerebro individual contra una base de datos normal ajustado por la edad.
RESULTADOS: Los resultados son expresados en desviaciones standard (DS) debajo del promedio. El promedio normal de captación del Tc99m HMPAO es 72 ± 5 % del máximo en el cerebro. Sólo voxels que tuvieron captación entre menos 2 y menos 8 DS representaron isquemia cerebral potencialmente reversible y por lo tanto fue considerado como penumbra isquémica. 7 de 16 pacientes tuvieron una buena recuperación clínica (mR 0-1) luego del tratamiento con trombolisis. 7 de 16 pacientes tuvieron una moderada o mala recuperación clínica (mR 2-4) y 2 de 16 pacientes fallecieron. Los mejores resultados clínicos se obtuvieron en pacientes en que se consiguió una buena recanalización del vaso ocluido en presencia de solo hipoperfusión superficial o moderada. Pacientes que presentaron severa hipoperfusión tuvieron en general peores resultados clínicos.
CONCLUSIONES: El estudio de NeuroSPECT en evaluación de pacientes con un accidente vascular isquémico agudo proporcionó 1) información útil sobre la presencia de penumbra isquémica/infarto durante las primeras horas de evolución. 2) Evaluó la eficacia del tratamiento de trombolisis y/o angioplastía. 3) Ayudó a anticipar la evolución del paciente posterior al tratamiento endovascular.
Brain infarct is the most common cause of incapacity in adults, the second cause of dementia and the second or third cause of death in developed countries. Acute brain infarct is a medical emergency potentially reversible if treated with thrombolysis in the first hours of evolution. Thrombolysis is now an approved and efficacious method of treatment for acute ischemic stroke[1] to reduce the final infarct size and improve the clinical outcome. During the first 3 hours of evolution, intravenous and/or local intra-arterial administration of plasminogen activator (tPA) can be performed. The window of time of treatment is expanded to 6 hours only with the intra-arterial super-selective route of local thrombolysis. The potentially recoverable brain tissue affected by reversible brain ischemia is known as brain penumbra. A variety of diagnostic studies are now available in the evaluation of brain infarct and in particular of potentially reversible brain ischemia, including perfusion computed tomography (CT)[2-4], magnetic resonance imaging (MRI) diffusion-perfusion[5-6], and functional neuroimaging techniques including positron emission tomography (PET)[7-8] and single-photon emission tomography (SPECT)[9-10]. Relative to the other techniques, not us much has been reported about the utility of SPECT in the evaluation of the acutely ischemic brain. The aim of this study is to report our experience with a group of patients that presented with acute brain ischemia that had a NeuroSPECT evaluation before and after intra-arterial thrombolysis and/or possible stent placement in the treatment of acute brain infarct.
Materials and methods
Subjects:
16 patients were studied, 9 were males and 7 females, with a mean age of 60 ± 13 years. 14 had SPECT imaging before and after thrombolysis and 2 patients had SPECT imaging only before thrombolysis because their poor clinical outcome did not allow control examination. All patients with anterior circulation ischemia were treated before 6 hours of onset of symptoms while in the posterior circulation the time to treat was variable and depended mostly on the clinical status of the patient. Nine presented with MCA (Middle Cerebral Artery) occlusion, while 4 had basilar artery occlusion and 1 had PCA (Posterior Cerebral Artery) and 2 had carotid artery occlusion. 11 patients presented with right hemisphere lesions and 5 with left hemisphere arterial occlusions. Other variables reported included the NIH scores at admission, discharge, 3 months, Time To Treat (TTT), TIMI recanalization score among others (Please see Table 1).
Table 1 NIH score on admission, on discharge and at three month post Thrombolysis. (Please see Appendix). back
-
NIHAdm
NIHDisch
NIH3ms
mR3ms
TTT
Locat.
TIMI
1
17
2
-
-
2
M1
3
2
23
11
5
1
4
CI/M1
3
3
16
12
8
-
72
Basilar
2
4
10
1
1
-
1,5
M1left
2
5
9
3
0
0
3
M1
2
6
18
5
1
2
6
Basilar
3
7
5
3
2
2
5
P2
1
8
4
1
1
-
3
M1
1
9
22
10
-
-
3
M2
3
10
17
10
8
2
2,5
M1
1
11
10
23
-
--
-
Basilar
3
12
14
0
-
0
2
M2 left
2
13
10
9
7
3
6
M2
0
14
14
3
1
0
4
M1
1
Imaging Protocol:
Prior to angiography the patient's antecubital vein was cannulated and an HMPAO dose of 30 mCi (1 100 MBq) was administered intravenously. The intravenous injection was given in an approximate volume of 2 ml. followed by a bolus of normal saline of 10 ml. All subjects were maintained in a low ambient light and low noise environment during the intravenous injection and brain uptake phase (2 minutes after injection). After the arterial thrombolysis was completed, imaging of HMPAO distribution in the cerebral cortex was performed utilizing a Dual Head Siemens ECAM SPECT System with Ultra High Resolution collimation and conventional acquisition protocol. The matrix is 64 x 64 with a circular orbit and Step&Shoot motion with 64 steps and 360 degrees rotation. The time of acquisition per projection was 30 seconds with a zoom factor of 1.66 and at the end of acquisition we verified the possibility of a motion artifact in a Cine mode and the Sinogram would demonstrate the existence of patient motion. The subjects laid in supine position, with the head fastened and positioned carefully in order to obtain an optimal orbito-meatal line angle and a vertical midline.
Data analysis:
All studies had the same post acquisition image processing which was performed at Clinica Las Condes. The acquisition was three-dimensionally (3D) reconstructed by back projection by means of a Butterworth filter 4.25 delimiting non-useful information by means of an elliptic region of interest (ROI). We perform oblique reorientation for transaxial, coronal, and sagittal planes with a volume zoom of 35%.
The reconstructed 3D raw images are transferred in an Interfile format to a Personal Computer (PC) in order to reprocess, quantify and normalize their volume.
The computer performed an analysis voxel by voxel of the brain uptake of HMPAO, and the results were normalized and expressed as percentage of maximal uptake observed in the brain for cortical analysis and for basal ganglia analysis. The results were displayed by means of a color scale that defined normal values in a range of 72 ± 5 % of maximum cortical uptake in red color, values above the normal mean above 82%,, in silver color and values below 60% (larger than 2 standard deviations below normal mean) expressed in color yellow, 50% of maximum in color green and below 40% in color blue. Fig.1.
Figure 1
Right MCA Stroke, 53 years old male. Notice extensive and deep hypoperfusion in territory of RMCA. In the projection of temporal lobe there are areas of deep hypoperfusion,< 40 % of maximum in brain cortex. (Color black), with extension into the convexity of parietal lobe. Notice also small focal areas of hypoperfusion in the left hemisphere suggestive of embolism. (Please see Method).
automated cortical gray-matter edge detection technique defined 64 ROIs per transaxial image. The data was normalized to the maximal brain activity and the results were expressed as maximal, minimal and average percentage uptake of each ROI. We applied Chang's attenuation correction with an attenuation coefficient µ= 0.1cm-1. Three criticaltransaxial images were analyzed including images located at the orbito-meatal plane and + 70 mm above it and also - 40mm below it. The results were displayed in an Excel table and a program was build to determine areas of interest with Minimal values < 2 standard deviations (SD), < 4 SD and < 8 SD below the mean uptake of HMPAO. Fig. 4.
Figure 4
Transaxial plane same patient, at 3 mm above AC-Post Commissural plane. Edge detection is performed by second derivative analysis and a band with a width of 30% of the distance to the center of the brain is defined. On this band 64 identical size ROIS are automatically determined for quantitative analysis. Maximal, minimal and average activity is reported for each ROI. (Please see Method section). Notice hypoperfusion of Caudate, Lentiforme Nucleus and a segment of Thalamus in Right Hemisphere, denoting ischemia of deep structures. Deepest ischemia appears in the cortex of right frontal-temporal lobes.
Furthermore, the Talairach technique normalized the brain volume and allowed a voxel by voxel comparison of the HMPAO uptake in the brain cortex with a normal elderly data base, corrected also volumetrically. In this 3D image, we define a new color scale that represents in color gray values above and below 2 SD of the normal mean, and two standard deviations above the normal mean in color red, also 3 and 4 SD above the normal mean in colors pink and white respectively. Colors light blue, dark blue and green defined areas at 2, 3 and 4 SD below the normal mean (Segami Corp., Maryland, USA). Fig. 2 and 3.
Figure 2
Same study of Figure 1. (Table 1 pt. 1) compared against Normal Older than 45 years Data Base. The territory of right MCA appears with deep hypoperfusion )< 5 SD below the Normal mean (black color). There is a relative small volume of superficial penumbra, color blue 2 and 3 SD below the Normal mean. In the left hemisphere there are small focal areas of superficial hypoperfusion, at 2 SD below the Normal mean.
Figure 3
Same study of Figure 1. Color Scale for Deep hypoperfusion, color black = < 8 SD. Demonstrates large area of deep penumbra colors dark blue (4 and 5 SD below Normal) and very deep penumbra color, green (6 and 7 SD below Normal), while there a a peripherical superficial large penumbra color light blue (2 and 3 SD below Normal).
Table 2 depicts in column 1 the ROIs that were analyzed in 3 adjacent transaxial images, numbers 0-32 in the right hemisphere progressing counterclockwise from the frontal lobe and numbers 33-64 in the left hemisphere progressing from occipital to frontal lobe.
Statistical analysis of the data: We considered that the absolute SD was a continuous variable, and therefore we applied an unpaired Student t test for the intra-comparison of pairs of before and after thrombolysis in each study group.
Results
Overall, 7 of 16 patients made good clinical recovery (mR 0-1) after the thrombolysis treatment. 7 of 16 patients made a moderate to poor clinical recovery (mR 2-4) and 2 of 16 patients died.Table 1.
There was a significant reduction of hypoperfusion with the treatment of thrombolysis as depicted by the results of the pre and post treatment examinations. There were three different level of hypoperfusion analyzed. Normal perfusion was defined at 72% +/-6% of maximal brain cortical uptake. "Superficial hypoperfusion", defined as areas with perfusion < 60% of maximum in the brain, < 2 SD below normal, was found on average in 41 voxels per patients before thrombolysis and remained unchanged after thrombolysis. "Moderate hypoperfusion", defined as uptake < 50% of maximum in the brain, < 4 SD below normal, was found on average in 34 voxels per patient and was reduced to an average 9 voxels after thrombolysis p < 0.006. "Severe hypoperfusion", namely < 30% uptake, < 8 SD below the normal mean, occupied an average 15 voxels before the thrombolysis and was reduced to 5 voxels after thrombolysis. Table 2. Figures 6, 7,8, 9.
Table 2 NeuroESPECT results. Notice all but three patients diminished the number
of voxels in very deep penumbra, namely < 8 SD, or < 30% of maximun
Basal
Post Trom
Basal
Post Trom
Basal
Post Trom
ROIS
1
2 - 28
75
39
16
69
0
0
76
57
0
0
2
5 - 25
63
39
43
63
30
30
57
36
30
12
3
14 - 27
42
7
71
42
0
0
28
12
0
0
4
40 - 60
59
35
61
36
0
0
0
0
0
0
5
5 - 30
78
58
23
75
10
6
73
57
0
0
6
20-y 22
9
6
100
9
0
0
-
0
0
0
7
29 - 31
30
15
83
28
60
12
10
3
20
3
8
2- 18
39
33
69
36
0
0
23
9
0
0
9
39 - 55
22
42
18
4
5
2
0
0
0
0
10
4 - 16
39
39
8
3
18
7
-
0
0
0
11
24 - 30
21
19
90
19
31
6
0
0
0
0
12
41 - 48
24
24
33
8
50
12
-
0
0
0
13
38 - 50
39
39
38
39
39
7
61
24
92
36
14
13 - 26
45
42
73
45
47
42
26
12
43
18
-
-
--
---
-
-
-
-
-
-
---
-
Mean
41,78
31,21
34
8,85
15
4,92
St
Dev
-
-
20,65
14,92
-
23,83
-
12,48
-
20,75
-
10,20
p Value
-
-
-0,13
--
-
0,0067
-
-
-
0,11
-
-
-
-
--
- ---
-
-
---
--
-
-
---
-
15
35 - 61
100
--
100
100
-
-
100
100
--
--
16
9 - 28
60
-
60
90
-
-
6
10
-
-
---
GOOD Clinical Outcome 9/14
Figure 6
Pt # 1 (Please see Table 1) after arterial thrombolysis 2 hrs after onset of symptoms. Notices residual superficial ischemia at 60% of maximum in right temporal lobe, orbitofrontal are and left medial temporal lobe.
Figure 7
Residual ischemia at 2, 3 and 4 St Dev below normal in right lateral temporal lobe. Notice one focus suspicious of infarction: color black < 5 SD.
Figure 8
Residual ischemia in same patient at 8 SD demonstrates penumbra at 2-3 and 4-5 SD below the Normal without infarction.
Figure 9
Transaxial plane same patient, at 3 mm above AC-Post Commissural plane, after TPA arterial thrombolysis. Notice normalization of perfusion of cortical and subcortical structures.
Figure 10
Pre and Post arterial Thrombolysis NeuroSPECT images demonstrating the extent of damage recovery. (Pt.# 1 Table 1).
The relationship between of recovery of severe hypoperfusion, degree of recanalization and clinical outcome are as follows. 4 of 10 patients that presented with severe hypoperfusion had their uptake values normalized after a successful recanalization of the occluded vessel (TIMI 2-3), Fig. 5. 3 of which had a good clinical outcome (mR 0-1) and 1 had a moderate outcome (mR 2). 1 of 10 patients had only a partial reduction of the severe hypoperfusion after successful thrombolysis (TIMI 3) and this patient also had a good clinical recovery (mR 1). Now 5 of 10 patients either did not improve their severe hypoperfusion post-thrombolysis or didn't have a control examination[2] due to their poor clinical state. 2 of these patients died and the other 3 only made moderate recoveries (mR 2). 4 of these 5 patients had a poor o no recanalization post thrombolysis (TIMI 0-1). 1 patient had a successful recanalization (TIMI 3) but had a subsequent massive hemorrhage.
Figure 5
Right MCA angiography demonstrates complete occlusion of M1 segment completely corrected after thrombolysis with tPA. Notice immediate visualization of arterial branches previously ischemic. (Pt. 1. Table 1)
The two patients that were not tested after thrombolysis were as follows. The first had a large left MCA infarct with voxels in the infarct zone registering < 30% uptake, and died shortly after the thrombolysis. The second patient presented with a right MCA occlusion, had 10 voxels in the < 30% range, was successfully treated with the thrombolysis but expired shortly after due to a large intracerebral hemorrhage.
The 6 patients that presented with only superficial to moderate hypoperfusion, 3 patients made an excellent recovery (mR 0) associated with a complete satisfactory recanalization (TIMI 2-3), 2 only a moderate recovery (mR 2) related to one patient having a poor recanalization of the occluded vessel (TIMI 1) and the other had a good recanalization (TIMI 3) but suffered a brainstem infarct. Finally the last 1 patient a poor recovery (mR 4) due to also a brainstem infarct.
The clinical outcome related to the recanalization results of the thrombolysis were as follows. 10 of 16 patients had successful recanalization of the occluded vessel (TIMI 2-3) and of these patients, 6 patients had good clinical recovery (mR 0-1), 3 patients had a moderate to poor recovery (mR 2-4) secondary to brainstem infarcts and 1 patient died secondary to a intracranial hemorrhage. 6 of 16 patients had a poor recanalization results post thrombolysis (TIMI 0-1) and of these 1 made a good recovery (mR 0), 4 patients made a moderate to poor recovery (mR 2-3) and 1 patient died.
Discussion
Analysis of our results of intra-arterial thrombolysis in patients of acute brain ischemia revealed the good outcomes were ssociated with less severe hypoperfusion on presentation, successful recanalization and early treatment of the occlusion. These observations support Warach´s et al[11] recently presented 4-factor model of tissue viability thresholds in acute stroke which include: 1) Time (duration of hemodynamic changes from onset), 2) Hemodynamic factor (degree of changes of cerebral blood flow (CBF), cerebral blood volume (CBV) or mean transit time (MTT), 3) Tissue factor (local metabolic, genetic, vascular or structural changes), 4) Intervention factor (type to reperfusion or neuroprotective therapies). Our data support the fact that the best clinical results were obtained when
1. The Time factor was at a minimum, best if revascularization was achieved in less than three hours of the onset on the ischemia. Fig. 10.
Figura 10
Pre and Post arterial Thrombolysis NeuroSPECT images demonstrating the extent of damage recovery. (Pt.# 1 Table 1).
2. The Hemodynamic factor, the degree of hypoperfussion was not as severe, between 2 and 4 SD below the mean uptake.
3. The Intervencional factor achieve satisfactory revascularization of the occluded vessel.
Based on these three parameters, we were able to anticipate the evolution of our patients.
There are a variety of known predictors of poor clinical outcome and increased risk of parenchymal hematoma, including hyperglycemia, stroke severity, elevated pretreatment blood pressure, very early and extensive hypodensity on brain CT that exceeds on third of the middle cerebral artery (MCA) territory[12-14]. We present another possible predictor of poor outcome, namely severe cerebral hypoperfusion as defined as below 8 SD of the mean uptake of HMPAO in the Neuro-SPECT scan.
Furthermore, to the authors knowledge this paper represents the first published report of cerebral blood flow (CBF) changes studied by NeuroSPECT in response to intra-arterial thrombolysis treatment of an ischemic stroke. The changes in CBF depicted on the before and after endovascular therapy scans confirms that thrombolysis positively alters the natural history and outcome of a significant ischemic brain lesion. Recently Parson et al reported the MRI Diffusion-Perfusion changes in studies performed before and after thrombolysis in patients with acute ischemic stroke[16].
We believe that Tc99m-HMPAO SPECT brain cortical uptake examination is an underutilized and extremely useful method for evaluating ischemic cerebrovascular disease. Its infrastructure requirements include a standard gamma camara, already present in many hospitals, and much less expensive than the new MRI or Multislice CT machines. The radiopharmaceutical HMPAO labeled with Tc99mm is widely available, and is much less expensive than the cyclotron labeled PET isotopes. Furthermore, the Tc99m-HMPAO isotope can be quickly prepared and administered in time before the initiation of therapy. The therapeutic intervention was not delayed by the HMPAO injection, and imaging was deliberately performed after the completion of the thrombolysis treatment as to not delay the treatment of the patient. This is impossible to achieve with the cyclotron labeling of the isotope in the PET examination. Furthermore, the post-processing of the NeuroSPECT data is also relatively simple, performed by an automated Neurogam program available at in many laboratories.
Conclusions
NeuroSPECT examination provides 1) useful information of infarct/penumbra during the first hours of evolution. 2) Evaluates the efficacy of thrombolysis and also angioplasty and stenting therapy. 3) Helps anticipate post therapy evolution.
References
1
The National Institute of Neurological Disorders and Stroke rt-PA Study Group. Tissue plasminogen activator for acute ischaemic stroke. N Engl J Med 1995;333:1581-1587. back
2
Grond M, Von Kummer R, Sobesky J. et al. Early x-ray hypoattenuation of brain parenchyma indicates extended critical hypoperfusion in acute astoke. Stroke 2000; 31:133-139. back
3
Wintermark M, Thiran JP, Maeder P, et al. Simultaneous measurement of regional cerebral blood flow by perfusion CT and stable xenon CT: a validation study. Am J Neuroradiol 2001; 22:905-914. back
4
Wintermark M, Maeder P, Thiran JP, et al. Quantitative assessment of regional cerebral blood flow by perfusion CT studies at low injection rates: a critical review of the underlying theoretical models. Eur Radiol 2001; 11:1220-1230. back
5
Baird AE, Warach S. Magnetic resonance imaging of acute stroke. J Cereb Blood Flow Metab 1998; 18:583-609. back
6
Schlaug G, Benfield A, Baird AE, et al. The ischemic penumbra: operationally defined by diffusion and perfusion MRI. Neurology 1999; 53:1528-1537. back
7
Read SJ, Hirano T, Abbott DF, et al. The fate of hypoxic tissue on 18F-fluromisonidazole positron emission tomography after ischemic stroke. Ann Neurol 2000; 48:228-235. back
8
Baron JC. Mapping the ischemic penumbra with PET: a new approach. Brain 2001; 124:2-4. back
9
Migneco 0, Mena I, Villanueva-Meyer J. Semiquantitative HMPAO brain SPECT display: Validation of a high specificity colorscale threshold. Clin Nuc Med 1992; 17(9):767. back
10
Lassen NA. Cerebral blood flow tomography with xenon-133. Semin Nucl Med 1985; 15:347-356.Tanne D, Kasner SE, Demchuk AM, et al. Markers of increased risk of intracranial hemorrage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: the Multicenter rt-PA Stroke Survey. Circulation 2002;105:1679-1685 back
11
Warach S. Tissue viability thresholds in acute stroke: the 4-factor model. Stroke 2001; 32:2460-2461. back
12
Demchuk AM, Morgenstern LB, Krieger DW, et al. Serum glucose level and diabetes predict tissue plasminogen activator-related intracerebral hemorrhage in acute ischemic stroke. Stroke 1999; 30:34-39. back
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Von Kummer R, Bourquain H, Bastianello S, et al. Early predicton of irreversible brain damage after ischemic stroke at CT. Radiology 2001; 219:95-100. back
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Parsons MW, Barber PA, Chalk J, et al. Diffusion-and perfusion weighted MRI response to thrombolysis in stroke. Ann Neurol 2002; 51:28-37 back
Appendix 1: Modified rankin scale (MRS)
MODIFIED
RANKIN
SCALE (MRS)
Patient Name: Rater Name: Date:
Score
Description
0
No symptoms at all
1
No significant disability despite symptoms; able to carry out all usual duties and activities
2
Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
3
Moderate disability; requiring some help, but able to walk without assistance
4
Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
5
Severe disability; bedridden, incontinent and requiring constant nursing care and attention
6
Dead
TOTAL (0 -6): _________
References
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Bonita R, Beaglehole R. "Modification of Rankin Scale: Recovery of motor function after stroke." Stroke1988 Dec;19(12):1497-1500
Van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. "Interobserver agreement for the assessment of handicap in stroke patients." Stroke 1988;19(5):604-7
1 [ ] Baseline 2[ ] 2 hours post treatment 3[ ] 24 hours post onset of symptoms ±20 minutes 4[ ] 7-10 days
5 [ ] 3 months 6 [ ] Other _______________ (__ __)
Time: __:__:1 [ ]am 2[ ]pm
Administer stroke scale items in the order listed. Record performance in each category after each subscale exam. Do not go back and change scores. Follow directins provided for each exam technique. Scores should reflect what the patient do es, not what the clinician thinks the patient can do. The clinician should record answers while administering the exam and work quickly. Except where indicated, the patient should not be coached (i.e., repeated requests to patient to ma ke a special effort).
IF ANY ITEM IS LEFT UNTESTED, A DETAILED EXPLANATION MUST BE CLEARLY WRITTEN ON THE FORM. ALL UNTESTED ITEMS WILL BE REVIEWED BY THE MEDICAL MONITOR, AND DISCUSSED WITH THE EXAMINER BY TELEPHONE.
1a. Level of Consciousness: The investigator must choose a response, even if a full evaluation is prevented by such obstacles as an endotracheal tube, language barrier, orotracheal trauma/bandages. A 3 is scor ed only if the patient makes no movement (other than reflexive posturing) in response to noxious stimulation.
0=
3D Alert; keenly responsive.
1=
3D Not alert, but arousable by minor stimulation to obey, answer, or respond.
2=
3D Not alert, requires repeated stimulation to attend, or is obtunded and requires strong or painful stimulation to make movements (not stereotyped)
3=
3D Responds only with reflex motor or autonomic effects or totally unresponsive, flaccid, areflexic.
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1 b. LOC Questions: The patient is asked the month and his/her age. The answer must be correct - there is no partial credit for being close. Aphasic and stuporous patients who do not comprehend the questions will score 2. Patients unable to speak because of endotracheal intubation, orotracheal trauma, severe dysarthria from any cause, language barrier or any other problem not secondary to aphasia are given a 1. It is important that only the initial answer be graded and that the examiner not "help" the patient with verbal or non-verbal cues.
0=
3D Answers both questions correctly.
1=
3D Answers one question correctly.
2=
3D Answers neither question correctly.
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1c. LOC Commands: The patient is asked to open and close the eyes and then to grip and release the non-paretic hand. Substitute another one step command if the hands cannot be used. Credit is given if an unequivocal attempt is made but not completed due toweakness. If the patient does not respond to command, the task should bedemonstrated to them (pantomime) and score the result (i.e.,follows none, one or two commands). Patients with trauma, amputation, or other physical impediments should be given suitable one-step commands. Only the first attempt is scored.
0=
3D Performs both tasks correctly
1=
3D Performs one task correctly
2=
3D Performs neither task correctly
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2. Best Gaze: Only horizontal eye movements will be tested. Voluntaryor reflexive (oculocephalic) eye movements will be scored but caloric testing is not done. If the patient has a conjugate deviation of the eyes that can be overcome by voluntary or reflexive activity, the score will be 1. If a patient has an isolated peripheral nerve paresis (CN III, IV or VI) score a 1. Gaze is testable in all aphasic patients.Patients with ocular trauma, bandages, pre-existing blindness or other disorder of visual acuity or fields should be tested with reflexive movements and a choice made by the investigator. Establishing eye contact and then moving about the patient from side to side will occasionally clarify the presence of a partial gaze palsy.
0=
3D Normal
1=
3D Partial gaze palsy. This score is given when gaze is abnormal in one or both eyes, but where forced deviationor total gaze paresis are not present.
2=
3D Forced deviation, or total gaze paresis not overcome by the oculocephalic maneuver.
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3. Visual: Visual fields (upper and lower quadrants) are tested by confrontation, using finger counting or visual threat as appropriate. Patient must be encouraged, but if they look at the side of the moving fingers appropriately, this can be scored as normal. If there is unilateral blindness or enucleation, visual fields in the remaining eye are scored. Score 1 onlyif a clear-cut asymmetry, including quadrantanopia is found. If patient is blind from any cause score 3. Double simultaneous stimulation is performed at this point. If there is extinction patient receives a 1 and the results are usedto answer question 11.
0=
No visual loss
1=
Partial hemianopia
2 =
Complete hemianophia
3 =
Bilateral hemianophia (blind including cortical blindness
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4. Facial Palsy: Ask, or use pantomime to encourage the patient to show teeth or raise eyebrows and close eyes. Score symmetry of grimace in response to noxious stimuli in the poorly responsive or non-comprehending patient. If facial trauma/bandages, orotracheal tube, tape or other physical barrier obscures the face, these should be removed to the extent possible.
0=
3D Normal symmetrical movement
1=
3D Minor paralysis (flattened nasolabial fold, asymmetry on smiling)
2=
3D Partial paralysis (total or near total paralysis of lower face)
3=
3D Complete paralysis of one or both sides (absence of facial movement in the upper and lower face)
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5 & 6. Motor Arm and Leg: The limb is placed in the appropriate position: extend the arms (palms down) 90 degrees (if sifting) or 45 degrees (if supine) and the leg 30 degrees (always tested supine). Drift is scored if the arm falls before 10 seconds or the leg before 5 seconds. The aphasic patient is encouraged using urgency in the voice and pantomime but not noxious stimulation. Each limb is tested in turn, beginning with the non-paretic arm. Only in the case of amputation or joint fusion at the shoulder or hip may the score be "9" and the examiner must clearly write the explanation for scoring as a "9".
0=
3D No drift, limb holds 90 (or 45) degrees for full 10 seconds.
1=
3D Drift, Limb holds 90 (or 45) degrees, but driftsdown before full 10 seconds; does not hit bed or other support.
2=
3D Some effort against gravity, limb cannot get to or maintain (if cued) 90 (or 45) degrees, drifts down to bed, but has some effort against gravity.
3=
3D No effort against gravity, limb falls.
4=
3D No movement
9=
3D Amputation, joint fusion explain: ---------------
5a.
Left Arm
5b.
Right Arm
___
___
0=
3D No drift, leg holds 30 degrees position for full 5 seconds.
1=
3D Drift, leg falls by the end of the 5 second period but does not hit bed.
2=
3D Some effort against gravity; leg falls to bed by 5 seconds, but has some effort against gravity.
3=
3D No effort against gravity, leg falls to bed immediately.
4=
3D No movement
9=
3D Amputation, joint fusion explain:____
6a.
Left Leg
6b.
Right Leg
___
___
7. Limb Ataxia: This item is aimed at finding evidence of a unilateral cerebellar lesion. Test with eyes open. In case of visual defect, insure testing is done in intact visual field. The finger-nose-finger and heelshin tests are performed on both sides, and ataxia is scored only if present out of proportion to weakness. Ataxia is absent in the patient who cannot understand or is paralyzed. Only in the case of amputation or joint fusion may the item be scored "9", and the examiner must clearly write the explanation for not scoring. In case of blindness test by touching nose from extended arm position.
0=
3D Absent
1=
3D Present in one limb
2=
3D Present in two limbs
If present, is ataxia in
Right arm 1 = Yes 2 = No
9 = amputation or joint fusion, explain
Left arm 1 = Yes 2 = No
9 = amputation or joint fusion, explain
Right leg 1 = Yes 2 = No
9 = amputation or joint fusion,
Left leg 1 = Yes 2 = No
9 = amputation or joint fusion,
___
___
___
___
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8. Sensory: Sensation or grimace to pin prick when tested, or withdrawal from noxious stimulus in the obtunded or aphasic patient. Only sensory loss attributed to stroke is scored as abnormal and the examiner should test as many body areas [arms (not hands), legs, trunk, face] as needed to accurately check for hemisensory loss. A score of 2, "severe or total," should only be given when a severe or total loss of sensation can be clearly demonstrated. Stuporous and aphasic patients will therefore probably score 1 or O. The patient with brain stem stroke who has bilateral loss of sensation is scored 2. If the patient does not respond and is quadriplegic score 2. Patients in coma (item l a=3D3) are arbitrarily given a 2 on this item.
0=
Normal; no sensory loss.
1=
Mild to moderate sensory loss; patient feels pinprick is less sharp or is dull on the affected side; or there is a loss of superficial pain with pinprick but patient is aware he/she is being touched.
2=
Severe to total sensory loss; patient is not aware of being touched in the face, arm, and leg.
___
9. Best Language: A great deal of information about comprehension will be obtained during the preceding sections of the examination. The patient is asked to describe what is happening in the attached picture, to name the items on the attached naming sheet, and to read from the attached list of sentences. Comprehension is judged from responses here as well as to all of the commands in the preceding general neurological exam. If visual loss interferes with the tests, ask the patient to identify objects placed in the hand, repeat, and produce speech. The intubated patient should be asked to write. The patient in coma (question 1a=3D3) will arbitrarily score 3 on this item. The examiner must choose a score in the patient with stupor or limited cooperation but a score of 3 should be used only if the patient is mute and follows no one step commands.
0=
No aphasia, normal
1=
Mild to moderate aphasia; some obvious loss of fluency or facility of comprehension, without significant limitation on ideas expressed or form of expression. Reduction of speech and/or comprehension, however, makes conversation about provided material difficult or impossible. For example in conversation about provided materials examiner can identify picture or naming card from patient's response.
2=
Severe aphasia; all communication is through fragmentary expression; great need for inference, questioning, and guessing by the listener. Range of information that can be exchanged is limited; listener carries burden of communication. Examiner cannot identify materials provided from patient response.
3=
Mute, global aphasia; no usable speech or auditory comprehension.
___
10. Dysarthria: If patient is thought to be normal an adequate sample of speech must be obtained by asking patient to read or repeat words from the attached list. If the patient has severe aphasia, the clarity of articulation of spontaneous speech can be rated. Only if the patient is intubated or has other physical barrier to producing speech, may the item be scored "9", and the examiner must clearly write an explanation for not scoring. Do not tell the patient why he/she is being tested.
0=
Normal
1=
Mild to moderate; patient slurs at least some words and, at worst, can be understood with some difficulty.
2=
Severe; patient's speech is so slurred as to be unintelligible in the absence of or out of proportion to any dysphasia, or is mute/anarthric.
9=
Intubated or other physical barrier,explain___
___
11. Extintion and inattention (formerly Neglect): Sufficient informatin to identify neglect may be obtained during the prior testing. If the pacient has a severe visual loss preventing visual double simultaneous stimulation, and the cutaneous stimuli are normal, the score is normal. If the patient has aphasia but does appear to attend to both sides, the score is normal. The presence of visual spatial neglect or anosagnosia may also be taken as evidence of abnormality. Since the abnormality is scored only if present, the item is never untestable
0=
No abnormality.
1=
Visual, tactile, auditory, spatial, or personal inattention or extinction to bilateral simultaneous stimulation in one of the sensory modalities.
2=
Profound hemi-inattention or hemi-inattention to more than one modality. Does not recognize own hand or orients to only one side of space.
___
Additional item, not a part of the NIH Stroke Scale score.
A. Distal Motor Function: The patient's hand is held up at the forearm by the examiner and patient is asked to extend his/her fingers as much as possible. If the patient can't or doesn't extend the fingers the examiner places the fingers in full extension and observes for any flexion movement for 5 seconds. The patient's first attempts only are graded. Repetition of the instructions or of the testing is prohibited.
0=
Normal (No flexion after 5 seconds)
1=
At least some extension after 5 seconds, but not fully extended. Any movement of the fingers which is not command is not scored.
2=
No voluntary extension after 5 seconds. Movements of the fingers at another time are not scored.
