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(Stroke. 1995;26:90-95.)
© 1995 American Heart Association, Inc.

Articles

Crossed Cerebellar Diaschisis and Brain Recovery After Stroke

Presented in part at the 19th International Joint Conference on Stroke and Cerebral Circulation, San Diego, Calif, February 17-19, 1994, and at the Third European Stroke Conference, Stockholm, Sweden, May 26-28, 1994.

Bernard Infeld, MB, BS, FRACP; Stephen M. Davis, MD, FRACP; Meir Lichtenstein, MB, BS, FRACP; Peter J. Mitchell, MB, BS, FRACR John L. Hopper, PhD

From the Departments of Neurology (B.I., S.M.D.), Nuclear Medicine (M.L.), and Radiology (P.J.M.), Clinical Neuroscience Centre, the Royal Melbourne Hospital, and the Department of Epidemiology (J.L.H.), University of Melbourne, Parkville, Victoria, Australia.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose Although crossed cerebellar diaschisis is well recognized after stroke, there is controversy concerning its clinical correlations and serial changes, and little is known about its prognostic value.

Methods We studied crossed cerebellar diaschisis and cerebral hypoperfusion in 47 patients with acute middle cerebral cortical infarction using ^99mTc-hexamethylpropyleneamine oxime and single-photon emission computed tomography within 72 hours of stroke onset. Thirty-one of these patients had outcome studies at 3 months; 15 of the 31 underwent an additional scan after acetazolamide injection. Tissue loss was determined with computed tomography, performed at outcome in 28 patients. Clinical stroke severity was assessed with the Canadian Neurological Scale and Barthel Index. Cerebellar blood flow asymmetry was studied in 22 healthy, age-matched control subjects.

Results Cerebellar blood flow asymmetry was significant in patients (mean±SE, 9.76±0.78%; P<.001) but not in control subjects (-0.22±0.56%). Crossed cerebellar diaschisis was strongly associated with infarct hypoperfusion volume at both acute (regression coefficient±SE_b, b=6.76±0.65; P<.001) and outcome stages (b=6.13±0.63; P<.001). Cross-sectionally over the first 72 hours, infarct hypoperfusion volume decreased by 2% for each hour from onset (P<.05), while crossed cerebellar diaschisis remained unchanged. Canadian Neurological Scale score at the acute stage was negatively associated with acute crossed cerebellar diaschisis (b=-0.10±0.05; P<.05) after allowing for infarct hypoperfusion volume. Crossed cerebellar diaschisis did not change between acute-stage, outcome, and postacetazolamide scans. Acute-stage crossed cerebellar diaschisis predicted outcome Barthel Index score (b=-0.28±0.14; P=.05) and tissue loss (b=3.81±0.96; P<.001) but was no longer an independent prognostic factor after allowing for acute-stage infarct hypoperfusion volume.

Conclusions This study shows that crossed cerebellar diaschisis is a functional phenomenon that correlates with both stroke severity and infarct hypoperfusion volume and persists despite neurological recovery. Although acute-stage crossed cerebellar diaschisis has no prognostic value independent of acute-stage hypoperfusion volume, it might indicate the proportion of nutritional to nonnutritional perfusion at the infarct site and hence be useful in the evaluation of reperfusion therapies in the acute stage.

Key Words: cerebellum • tomography • emission computed • diaschisis • reperfusion • cerebral infarction

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Crossed cerebellar diaschisis (CCD) is a matched depression of blood flow and metabolism in the cerebellar hemisphere contralateral to a focal, supratentorial lesion and is a well-recognized phenomenon following cerebral infarction.^{1 2 3 4 5 6 7 8} The most likely mechanism underlying CCD is the interruption of the corticopontocerebellar connections by the infarct causing deafferentation and transneural metabolic depression of the contralateral cerebellar hemisphere.^{1 3 4 6 9 10 11 12 13 14}

Although CCD has been studied in stroke patients with both positron emission tomography (PET)^{1 2 3 4 6 9} and single-photon emission computed tomography (SPECT),^{5 7 8} the relationships between the degree of CCD and size of the infarct, neurological severity of stroke, and time elapsed since stroke onset all remain controversial. Although some investigators have found that CCD is greater with larger infarcts,^{5 6 7 15} others have not found any relation to infarct size.^{3 4 8} Similarly, there is no consensus whether the degree of CCD correlates with clinical stroke severity. Some authors have reported that the degree of CCD is greater in patients with severe hemiparesis,^{1 6 7 8} whereas others have not found any relation to the degree of motor deficit.^{2 3 4 15}

There is also no agreement concerning the serial changes in CCD with clinical recovery. Although most investigators have reported that CCD does not resolve,^{3 5 6} others have suggested that CCD is an acute phenomenon that diminishes with time.^{1 4 7} In contrast, another study suggested that the degree of CCD increases as the time from stroke ictus increases.²

It is unclear whether CCD is merely an epiphenomenon, as its clinical significance remains uncertain. Although some authors have reported that CCD may be associated with ipsilateral ataxia¹⁶ or prolonged hypotonia¹⁵ after stroke, the evidence is not convincing. One study exploring the prognostic value of CCD measured by early PET¹⁷ found that the degree of CCD is not predictive of either neurological outcome or recovery. No study has yet used SPECT to evaluate this relation. Recent studies have emphasized the importance of early luxury perfusion after acute stroke.^{18 19 20 21 22 23 24} Because the depression of cerebellar blood flow (CbBF) and of cerebellar metabolic rate for oxygen (CbMRO₂) are matched in CCD,^{1 2} measurement of CCD could be indicative of the degree of metabolic derangement at the infarct site and hence give a guide to the proportion of nonnutritional flow. This has not been previously addressed.

Many previous studies have been compromised by the small numbers of patients,^{9 25} the grouping together of diverse stroke subtypes affecting different vascular territories,^{6 7 12 25} and the inclusion of patients with either cerebral hemorrhage^{8 12 16 25} or tumor.⁴ Quantitative data on either stroke size^{1 6 7} or neurological severity^{1 2 4 5 6 7 9} have often been lacking, as have serial scans at standardized intervals after the stroke ictus.^{1 2 3 4 6 7 8 9 15 25} Furthermore, little is known about the range of CbBF asymmetry in healthy control subjects, as some studies have either not examined or not published control data.^{1 7} Others have either used control subjects who were younger than stroke patients^{4 5 8 12} or have included control subjects with psychiatric illness.³

We aimed to study CCD in a group of stroke patients with acute middle cerebral territory cortical infarction within 72 hours of onset and to examine its relations to infarct hypoperfusion (HP), clinical severity, and time using prospective data obtained using a standardized protocol. We also planned to explore whether measurements of CCD at the acute stage would aid in the identification of nutritional versus nonnutritional reperfusion at the infarct site. This could have implications for the evaluation of acute stroke intervention.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
We prospectively studied 47 sequential patients (31 men and 16 women, aged 30 to 91 years; mean±SD, 69±11 years) with acute middle cerebral territory cortical infarction within 72 hours of stroke onset. In 26 patients, the cerebral infarction involved the left hemisphere, and in 21 it was right-sided. Middle cerebral cortical infarction was defined clinically by (1) the presence of one or more cortical deficits such as dysphasia, visual or sensory inattention, anosognosia, visuospatial apraxia, or parietal sensory deficit or (2) the finding of acute cortical infarction on the early computed tomographic (CT) scan.

Exclusion criteria were previous cerebral pathology (infarction, hemorrhage, or tumor) interfering with the assessment of cerebral blood flow (CBF) and either neurological or functional assessments; previous stroke in the vertebrobasilar territory; and the presence of neurological, psychiatric, or systemic illness. Cerebral hemorrhage and nonvascular pathology such as tumor were excluded by CT scan.

These 47 patients were studied with ^99mTc-hexamethylpropyleneamine oxime (HMPAO) SPECT within 72 hours of the ictus. The acute SPECT scan was performed within 24 hours of symptom onset in 20 patients (mean±SD, 11.5±7.9 hours), between 24 to 48 hours in 18 patients (38.0±7.1 hours), and between 48 to 72 hours in 9 patients (59.4±12.7 hours). Five patients who underwent acute SPECT scan within 6 hours of stroke onset (2.9±2.0 hours) had a repeat scan 24 hours later (23.3±2.5 hours). Outcome SPECT scans were obtained in 31 of the 47 patients at or after 3 months from ictus (6.5±4.0 months) when neurological recovery had reached a plateau. Fifteen of these 31 patients underwent a further scan after intravenous injection of 1 g acetazolamide. All SPECT scans were performed as previously described²⁶ using a GE400AC Starcam gamma camera. Of the 16 patients who did not have outcome SPECT scans, 5 died at the acute stage of stroke complications, one died at 2 months of peritonitis secondary to mesenteric infarction, and 10 refused to undergo further scanning. No patients were lost to follow-up.

A control group of 22 subjects (10 men and 12 women) with a similar age distribution to the stroke patients (range, 55 to 88 years; mean, 72±11 years) also underwent one SPECT scan each. They had been selected from a series of healthy volunteers and healthy spouses of patients with Alzheimer's disease. All control subjects had no history of any neurological disorders, dementia, or depressive illness as determined on the basis of normal Mini-Mental State Examination scores²⁷ and a score of <5 on the Hamilton Depression Rating Scale.²⁸

Measurement of CCD was performed in all SPECT studies in which the cerebellar hemispheres were adequately visualized. Multiple contiguous posterior fossa slices were analyzed to eliminate any variations that may have been caused by patient head tilt. A slice was selected for analysis if both cerebellar hemispheres were well visualized and excluded the overlying occipital lobes. Using a video display and computer software specifically written for cerebellar analysis, two regions of interest (ROIs), 272 pixels in area, were symmetrically located over the cerebellar hemispheres. To allow an objective but comprehensive cerebellar analysis, the size and shape of the ROIs were designed to include the whole of each respective cerebellar hemisphere and were predefined using the outline of a normal cerebellar hemisphere. The ROI template was first positioned over the right cerebellar hemisphere and then mirrored over onto the left side. Total, maximum, and minimum count values for each cerebellar hemisphere were then obtained. The cerebellar analysis was performed blinded to the supratentorial images and clinical details of each patient studied.

For each study, a CCD value was calculated as follows: for each posterior fossa slice, a diaschisis value was calculated as the percentage difference between the normal and affected cerebellar hemispheres: diaschisis=(I-C)/Ix100%, where I refers to the maximum cerebellar count value on the side ipsilateral to the cerebral infarction, and C refers to the maximum cerebellar count value on the contralateral side. The study CCD value was the average of the diaschisis values from all slices analyzed. The maximum count values were used instead of the total count values because they were less subject to variation if the ROI was shifted by one pixel in a given direction; values were therefore not dependent on a subjective choice of ROI placement. Previous SPECT studies quantifying CCD have used total counts,^{7 8 14 15 29} and accordingly we found a high correlation between CCD values obtained from maximum and total counts ([regression coefficient±SE_b] b=0.90±0.06, P<.0001).

To enable comparison with the normal control subjects, asymmetry of CbBF in each study was measured by the asymmetry index (AI), calculated as the difference between hemispheres as a percentage of the mean: AI=(I-C)/(I+C)x200% in stroke patients and AI=(R-L)/(R+L)x200% in control subjects, where R and L refer to the maximum count values of the right and left cerebellar hemispheres, respectively.

Cerebral HP on SPECT was volumetrically quantified as previously described,²⁴ giving an infarct HP volume in cubic centimeters. Volumetric analysis was performed in all studies by a nuclear medicine technologist with knowledge of the radiological localization of the infarct but blinded to the clinical scores and associated CCD analysis.

Neurological stroke severity was assessed at the time of the acute and outcome SPECT scans using a modified Canadian Neurological Scale (CNS; scored from 0 to 11.5),³⁰ and functional assessment at both 7 to 10 days from stroke onset and at the time of the outcome SPECT scan was carried out using the Barthel Index (BI; scored from 0 to 20).³¹ In 4 surviving patients, outcome CNS score could not be obtained because of refusal to undergo further examination, whereas outcome BI score was determined by telephone interview with the patient or caregivers, which is a validated technique.³¹ For the 5 patients who died at the acute stage, outcome CNS and BI were scored as 0 on the basis that these patients were severely neurologically disabled and functionally dependent before death and that 0 was their best antemortem score.²⁴ For the patient whose death was not stroke-related, no outcome score could be allocated.

Outcome tissue loss was measured on CT scan, performed at the same follow-up visit as the outcome SPECT scan in 28 of the 31 patients. All CT scans were performed using a General Electric 9800 high-resolution CT scanner. Volumetric analysis of the infarct images (cubic centimeters) was performed as previously described³² by a neuroradiologist blinded to the CBF data and the clinical scores.

The difference in CbBF asymmetry between patients and control subjects was assessed by Student's t test. The relationship between CCD and infarct HP volume was evaluated by linear regression through the origin. Because the infarct HP volume had a skewed distribution, it was logarithmically transformed for analysis to reduce the influence of extreme values. Other relationships between CCD and CNS score and between CCD and BI score, at the acute and chronic stages, were evaluated using linear regression. For the 5 patients with two acute SPECT studies, earlier data were used where possible. Multivariate linear regression was used to assess whether acute stroke severity was independently associated with acute CCD and acute infarct HP volume. Similarly, multivariate analysis was used to determine if stroke outcome, as measured by outcome infarct HP volume, outcome tissue loss, and outcome CNS and BI scores, was predicted independently by acute CCD and acute infarct HP volume. To test if the predictions of outcome scores of CNS and BI were influenced by inclusion of deaths (scored as 0), these analyses were repeated with deaths excluded. Changes in CCD between acute-stage and outcome studies, and after acetazolamide, were assessed by Student's t test.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Of a total of 98 SPECT scans performed in 47 stroke patients, CCD and HP volume measurements were possible in 93 and 96 scans, respectively. At the acute stage, the cerebellum was not adequately visualized in 1 of the 42 patients having one SPECT scan and in 2 of the 5 patients scanned twice (the initial scans). This left 46 patients with at least one acute-stage CCD measurement and 3 with two acute-stage CCD measurements. Of the 31 patients studied at outcome, the cerebellum was not adequately visualized in 2, leaving 29 patients with outcome CCD measurements. Infarct HP volume could not be analyzed in one acute-stage study (the initial study of 1 of the 5 patients scanned twice) and in one outcome study. This left 46 patients with at least one acute-stage infarct HP volume and 4 patients with two acute-stage HP volume measurements, and 30 patients with outcome HP volume measurements.

We first compared CbBF asymmetry in the control subjects with that in the stroke patients. The mean CbBF asymmetry (±SE) was -0.22±0.56% in control subjects (n=22; range, -6.82% to 3.74%) and 10.15±0.90% in stroke patients (n=78: 49 acute, 29 outcome; range, -7.61% to 35.62%). Therefore, in stroke patients, CbBF asymmetry was significant (P<.001) and was greater than CbBF asymmetry in control subjects (P<.001).

We then examined the relationship between CCD and infarct HP volume (Fig 1). Acute-stage CCD was strongly associated with acute-stage infarct HP volume ([regression coefficient±SE_b] b=6.76±0.65; n=46; P<.001), and outcome CCD was similarly associated with outcome infarct HP volume (b=6.13±0.63; n=29; P<.001).

View larger version (15K): [in this window] [in a new window]   Figure 1. Graphs show linear regression of crossed cerebellar diaschisis (CCD) as a function of infarct hypoperfusion (HP) volume (n=46, P<.001) measured at acute stroke stage (top) and CCD as a function of infarct HP volume (n=29, P<.001) measured at outcome (bottom).

The effect of time of the scan from stroke onset on infarct HP volume, CCD, and CNS score at the acute stage was cross-sectionally analyzed over the first 72 hours. Acute-stage infarct HP volume decreased by 2.1±1.01% for each hour after stroke onset (P<.05), whereas both CCD and CNS score remained unchanged. Similar results were found in 3 patients who had acute-stage and 24-hour measurements of both infarct HP volume and CCD. Mean infarct HP volume (±SD) significantly decreased from 42.02±7.24 cm³ at acute stage to 9.59±5.07 cm³ (P=.04) 24 hours later. In contrast, there was no significant difference between mean acute-stage CCD (5.28±4.60%) and 24-hour CCD (7.80±4.62%) or between mean acute-stage CNS score (4.3±0.3) and 24-hour CNS score (4.8±1.0).

The severity of neurological deficit and of functional disability were both strongly associated with CCD. Acute-stage CCD correlated well with both acute-stage CNS (b=-1.31±0.44; n=46; P<.01) and 7- to 10-day BI (b=-0.56±0.15; n=46; P<.001) scores. Similarly, outcome CCD correlated well with both outcome CNS (b= -1.42±0.42; n=29; P<.01) and outcome BI (b=-0.56±0.21; n=29; P<.01) scores.

We used multivariate analysis to determine if both CCD and infarct HP volume were independently associated with clinical severity. At the acute stage, CNS score was associated with CCD (b=-0.099±0.045, P<.05), but only marginally with infarct HP volume (b=-0.013±0.007, P=.07). The 7- to 10-day BI score was independently associated with both CCD (b=-0.32±0.12, P<.01) and infarct HP volume (b=-0.054±0.018, P<.01). Conversely, at outcome, CNS and BI scores were independently associated with infarct HP volume only (b=-0.026±0.012, P<.05 for CNS; b=-0.056±0.027, P<.05 for BI).

In evaluating serial changes in CCD with brain recovery, there were 28 patients who had both acute-stage and outcome CCD measurements (Fig 2). Mean outcome CCD (±SE) of 9.19±1.24% was unchanged from mean acute-stage CCD of 10.21±1.46%. Mean infarct HP volume increased from 36.08±6.32 cm³ at the acute stage to 50.00±7.46 cm³ (P<.01) at outcome, contrasting with mean CNS score, which improved from 5.27±0.45 at acute stage to 8.50±0.44 at outcome (P<.001), and mean BI, which improved from 9.18±1.12 to 16.50±1.00 (P<.001). To test if patients who had both acute-stage and outcome SPECT scans differed from those who only had an acute-stage CBF study, we compared mean acute-stage CNS, infarct HP volume, and CCD between the 28 patients who had both studies and the 18 who had only one study and found no significant differences.

View larger version (8K): [in this window] [in a new window]   Figure 2. Graphs show changes in mean crossed cerebellar diaschisis (CCD) and mean infarct hypoperfusion (HP) volume with recovery. Mean HP volume increased between acute and outcome stages (P<.01), while mean CCD remained unchanged despite clinical recovery.

In the 15 patients who had CBF studies before and after acetazolamide at outcome, the mean CCD before acetazolamide was 9.87±1.79%. After acetazolamide, the mean CCD value was 7.68±1.18%. This suggests a tendency for CCD to diminish with cerebral vasodilatation, although the significance was marginal (P=.06).

Acute-stage CCD was a significant predictor of outcome BI (b=-0.28±0.14, n=45, P=.05) and outcome CNS (b=-0.14±0.07, n=41, P<.05) scores, outcome tissue loss (b=3.81±0.96, n=28, P<.001), and outcome infarct HP volume (b=3.83±0.65, n=29, P<.001). After excluding deaths, there was no significant change in the relationships between acute-stage CCD and outcome BI (b=-0.20±0.11, n=40, P=.1) and outcome CNS (b=-0.10±0.05, n=36, P=.04). All patients who had acute-stage CCD 3.23% had outcome BI scores >12, a standard measure of favorable stroke outcome.³³ However, in multivariate analyses comparing the predictive abilities of acute-stage CCD and HP volume, only the acute-stage infarct HP volume independently predicted outcome BI score (b=-0.088±0.020, P<.001), outcome CNS score (b=-0.044±0.009, P<.001), outcome tissue loss (b=1.24±0.29, P<.001), and outcome infarct HP volume (b=1.05±0.13, P<.001).

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
This study has shown that CCD after middle cerebral territory cortical infarction correlates with infarct HP volume as well as with neurological severity and degree of disability. We have also demonstrated that although CCD is a functional phenomenon, it persists despite clinical recovery. The severity of CCD at the acute stage has prognostic value but is not an independent determinant of outcome when the acute-stage infarct HP volume is considered.

The lack of a significant correlation between CCD and infarct size found by some previous investigators^{3 4 8} could be accounted for by the inclusion of patients studied at various subacute stages. Consequently, nonnutritional flow (luxury perfusion) around the infarct core might have confounded the assessment of the relationship between infarct size and CCD. Meneghetti et al⁵ measured CBF within 72 hours of stroke onset in 12 patients and reported similar findings to ours. Other studies^{6 7 15} have demonstrated a significant correlation between CCD and infarct size measured on CT. We have shown that CCD correlates strongly with infarct HP at both acute and chronic stages. Our results support the previously proposed mechanism,¹ whereby CCD is thought to arise secondarily to interruption of the cerebrocerebellar pathway by destruction of the supratentorial portion of the cerebropontine connections.^{1 3 4 6 9 10 11 12 13 14 15 34}

We have also shown a strong correlation between CCD and clinical measurements of stroke severity. Most previous studies examining this relationship have not used validated, quantitative clinical scoring methods.^{1 3 4 6 7} Perani et al⁸ quantified motor weakness using the CNS and found that CCD was more severe in hemiplegic patients than in both hemiparetic and asymptomatic patients. However, Serrati et al,¹⁷ using the Mathew and Orgogozo scales, found stronger correlations 1 month after stroke onset than at the acute stage.

Few studies have included serial measurements of CbBF at acute and outcome stages after stroke.^{5 7} Meneghetti et al⁵ serially measured CCD four to six times during the acute phase, and again at 2 and 6 months in the chronic phase. They found that CCD persisted at 6 months. Our results concur with those of Meneghetti et al⁵ and confirm that CCD remains essentially unchanged over the first 3 months despite clinical recovery.

Our results have shown that in CCD, vasoreactivity in the affected cerebellar hemisphere is preserved. If CCD were associated with underlying structural cerebellar abnormalities, one would expect the degree of CCD to increase after the administration of acetazolamide. Similar findings have been reported by other investigators.^{35 36} This supports the hypothesis that the pathophysiology of CCD is regional vasoconstriction associated with local metabolic depression due to functional deactivation.¹² Whether chronic cerebellar hypometabolism associated with cerebral infarction leads to transneural degeneration and morphological changes has been addressed in only two small magnetic resonance imaging (MRI) studies,^{25 34} which found no evidence of cerebellar atrophy. In contrast, crossed cerebellar atrophy on MRI has been noted in patients with long-standing cerebral hemispheric atrophy associated with intractable seizures and onset at birth or childhood.³⁴

Our observation that infarct HP volume decreased over the first 72 hours after stroke onset is consistent with progressive infarct reperfusion in patients studied at later intervals after onset. Although we compared acute-stage infarct HP volumes among different patients, we found a similar pattern in the small number of patients who had two acute-stage SPECT scans (Fig 3). This was not associated with significant clinical improvement, suggesting that this reperfusion was substantially nonnutritional and reflected postischemic hyperemia or the luxury-perfusion syndrome, as originally described by Lassen.³⁷ Although the exact time of onset of postischemic luxury perfusion has not been clearly established, it has been seen within the first 1 to 2 days after stroke^{2 19} and becomes more prevalent thereafter.^{19 21 38 39} Acute-stage luxury perfusion would also explain our finding of an increase in the mean HP volume between acute and outcome stages despite significant clinical recovery. Similar reductions of infarct HP during the subacute phase without an accompanying clinical gain, increasing again at outcome, have been reported by our group²⁴ and other authors.^{18 22 33 40} This acute-stage nonnutritional reperfusion requires confirmation by serial studies in a larger number of patients.

View larger version (0K): [in this window] [in a new window]   Figure 3. Serial single-photon emission computed tomographic scans of a patient with a left middle cerebral cortical infarction. The scans were performed 4 hours, 2 weeks, and 6 months after stroke onset. The transverse slices through the cerebral hemispheres (upper images) show nonnutritional reperfusion at 2 weeks, not maintained at 6 months. The lower cerebellar images show persistent crossed cerebellar diaschisis. (The 24-hour study was technically unsatisfactory.)

In contrast to nonnutritional reperfusion at the infarct site, we found that the severity of CCD remained unchanged both over the first 72 hours and between acute and outcome stages. This indicates that CCD is unaffected by nonnutritional reperfusion (Fig 3). Unlike the characteristic mismatch between CBF and metabolism (CMRO₂) at the infarct site, the depression of CbBF and CbMRO₂ are matched in CCD.^{1 2 3 4 5 6 7 8} As the degree of CCD reflects the severity of corticocerebellar deafferentation, CCD measured by ^99mTc-HMPAO SPECT might provide an indirect index of metabolic derangement at the infarct site. Two previous studies of CCD using PET have advanced a similar hypothesis.^{17 41}

It has been established that the acute-stage HP volume deficit, measured within 72 hours, is a good predictor of functional outcome^{22 24 42} but is less strong than clinical stroke prognosis models such as Allen's prognostic score.^{24 32} There has been only one previous report of the prognostic value of CCD after stroke.¹⁷ Serrati et al¹⁷ found that the degree of acute-stage CCD measured by PET within 30 hours of stroke onset was not predictive of neurological outcome or recovery, although their data indicated that lack of significant CCD was associated with favorable outcome. We found that acute-stage CCD was a significant predictor of stroke outcome and, as Serrati et al¹⁷ found, that its absence was associated with favorable outcome. However, acute-stage CCD did not add independent prognostic value to the acute-stage infarct HP volume.

The finding that acute-stage CCD was not an independent predictor of outcome was unexpected given that it appears to be a useful indicator of acute metabolic derangement at the infarct site. A possible explanation is that CCD may be applicable only to the motor component of infarction because the corticopontine projections probably arise mainly from the frontoparietal motor cortex.⁴³ This is supported by Pantano et al,⁶ who reported that the temporal lobes do not contribute significantly to the magnitude of CCD.

While SPECT has an important role in evaluating new therapeutic interventions aimed at improving perfusion after stroke,^{33 44} controversy exists as to whether the degree of infarct reperfusion after therapy correlates with clinical gains.^{18 22 33 44 45} The lack of correlation in some studies^{18 22 33 45} could be explained by varying proportions of nutritional and nonnutritional infarct reperfusion induced by therapy. Our results show that at the acute stage, neurological severity was more strongly correlated with CCD than with infarct HP volume, a trend which was reversed at outcome, probably reflecting acute luxury perfusion. This suggests that early serial changes in acute-stage CCD after therapeutic intervention might correlate with clinical improvement. For example, if infarct reperfusion was largely nonnutritional without clinical improvement, CCD should remain unchanged, as seen in our study. On the other hand, nutritional reperfusion should be associated with reduced CCD. Although we have insufficient data to draw conclusions from this study, it seems likely that changes in CCD accompanying infarct reperfusion in trials of acute stroke therapy will better predict outcome than the degree of reperfusion alone. This potential clinical role of CCD measurements deserves further investigation.

	Acknowledgments

 
This research was supported by grants from the National Health and Medical Research Council and the Australian Stroke and Neuroscience Institute.

	Footnotes

 
Reprint requests to Stephen M. Davis, MD, FRACP, Department of Neurology, Royal Melbourne Hospital, Victoria 3050, Australia.

Received July 20, 1994; revision received October 10, 1994; accepted October 14, 1994.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Baron JC, Bousser MG, Comar D, Castaigne P. "Crossed cerebellar diaschisis" in human supratentorial brain infarction. Trans Am Neurol Assoc. 1980;105:459-461.
2. Lenzi GL, Frackowiak RS, Jones T. Cerebral oxygen metabolism and blood flow in human cerebral ischemic infarction. J Cereb Blood Flow Metab. 1982;2:321-335. [Medline] [Order article via Infotrieve]
3. Martin WR, Raichle ME. Cerebellar blood flow and metabolism in cerebral hemisphere infarction. Ann Neurol. 1983;14:168-176. [Medline] [Order article via Infotrieve]
4. Kushner M, Alavi A, Reivich M, Dann R, Burke A, Robinson G. Contralateral cerebellar hypometabolism following cerebral insult: a positron emission tomographic study. Ann Neurol. 1984;15:425-434. [Medline] [Order article via Infotrieve]
5. Meneghetti G, Vorstrup S, Mickey B, Lindewald H, Lassen NA. Crossed cerebellar diaschisis in ischemic stroke: a study of regional cerebral blood flow by ¹³³Xe inhalation and single photon emission computerized tomography. J Cereb Blood Flow Metab. 1984;4: 235-240.
6. Pantano P, Baron JC, Samson Y, Bousser MG, Derouesne C, Comar D. Crossed cerebellar diaschisis: further studies. Brain. 1986;109:677-694. [Abstract/Free Full Text]
7. Pantano P, Lenzi GL, Guidetti B, Di Piero V, Gerundini P, Savi AR, Fazio F, Fieschi C. Crossed cerebellar diaschisis in patients with cerebral ischemia assessed by SPECT and 123I-HIPDM. Eur Neurol. 1987;27:142-148. [Medline] [Order article via Infotrieve]
8. Perani D, Di Piero V, Lucignani G, Gilardi MC, Pantano P, Rossetti C, Pozzilli C, Gerundini P, Fazio F, Lenzi GL. Remote effects of subcortical cerebrovascular lesions: a SPECT cerebral perfusion study. J Cereb Blood Flow Metab. 1988;8:560-567. [Medline] [Order article via Infotrieve]
9. Heiss WD, Pawlik G, Wagner R, Ilsen HW, Herholz K, Wienhard K. Functional hypometabolism of noninfarcted brain regions in ischemic stroke. J Cereb Blood Flow Metab. 1983;3(suppl 1):S582-S583.
10. Fukuyama H, Kameyama M, Harada K, Fujimoto N, Kobayashi A, Taki W, Ishikawa T, Handa H, Tanada S, Torizuka K. Thalamic tumours invading the brain stem produce crossed cerebellar diaschisis demonstrated by PET. J Neurol Neurosurg Psychiatry. 1986;49:524-528. [Abstract]
11. Botez MI, Leveille J, Lambert R, Botez T. Single photon emission computed tomography (SPECT) in cerebellar disease: cerebello-cerebral diaschisis. Eur Neurol. 1991;31:405-412. [Medline] [Order article via Infotrieve]
12. Yamauchi H, Fukuyama H, Kimura J. Hemodynamic and metabolic changes in crossed cerebellar hypoperfusion. Stroke. 1992;23:855-860. [Abstract/Free Full Text]
13. Fulham MJ, Brooks RA, Hallett M, Di Chiro G. Cerebellar diaschisis revisited: pontine hypometabolism and dentate sparing. Neurology. 1992;42:2267-2273. [Abstract/Free Full Text]
14. Fazekas F, Payer F, Valetitsch H, Schmidt R, Flooh E. Brain stem infarction and diaschisis: a SPECT cerebral perfusion study. Stroke. 1993;24:1162-1166. [Abstract/Free Full Text]
15. Pantano P, Formisano R, Ricci M, Barbanti P, Fiorelli M, Sabatini U, Di Piero V, Lenzi GL. Prolonged muscular flaccidity in stroke patients is associated with crossed cerebellar diaschisis. Cerebrovasc Dis. 1993;3:80-85.
16. Tanaka M, Kondo S, Hirai S, Ishiguro K, Ishihara T, Morimatsu M. Crossed cerebellar diaschisis accompanied by hemiataxia: a PET study. J Neurol Neurosurg Psychiatry. 1992;55:121-125. [Abstract]
17. Serrati C, Marchal G, Rioux P, Viader F, Petittaboue MC, Lochon P, Luet D, Derlon JM, Baron JC. Contralateral cerebellar hypometabolism: a predictor for stroke outcome. J Neurol Neurosurg Psychiatry. 1994;57:174-179. [Abstract]
18. Rango M, Candelise L, Perani D, Messa C, Scarlato G, Canal N, Franceschi M, Fazio F. Cortical pathophysiology and clinical neurologic abnormalities in acute cerebral ischemia: a serial study with single photon emission computed tomography. Arch Neurol. 1989;46:1318-1322. [Abstract]
19. Wise RJ, Bernardi S, Frackowiak RS, Legg NJ, Jones T. Serial observations on the pathophysiology of acute stroke: the transition from ischaemia to infarction as reflected in regional oxygen extraction. Brain. 1983;106:197-222. [Abstract/Free Full Text]
20. Baron JC, Frackowiak RS, Herholz K, Jones T, Lammertsma AA, Mazoyer B, Wienhard K. Use of PET methods for measurement of cerebral energy metabolism and hemodynamics in cerebrovascular disease. J Cereb Blood Flow Metab. 1989;9:723-742. [Medline] [Order article via Infotrieve]
21. Ackerman RH, Alpert NM, Correia JA, Finklestein S, Davis SM, Kelley RE, Donnan GA, D'Alton JG, Taveras JM. Positron imaging in ischemic stroke disease. Ann Neurol. 1984;15(suppl):S126-S130.
22. Limburg M, van Royen EA, Hijdra A, Verbeeten B Jr. rCBF-SPECT in brain infarction: when does it predict outcome? J Nucl Med. 1991;32:382-387. [Abstract/Free Full Text]
23. Sperling B, Lassen NA. Hyperfixation of HMPAO in subacute ischemic stroke leading to spuriously high estimates of cerebral blood flow by SPECT. Stroke. 1993;24:193-194. [Free Full Text]
24. Davis SM, Chua MG, Lichtenstein M, Rossiter SC, Binns D, Hopper JL. Cerebral hypoperfusion in stroke prognosis and brain recovery. Stroke. 1993;24:1691-1696. [Abstract/Free Full Text]
25. Pappata S, Tran Dinh S, Baron JC, Cambon H, Syrota A. Remote metabolic effects of cerebrovascular lesions: magnetic resonance and positron tomography imaging. Neuroradiology. 1987;29:1-6. [Medline] [Order article via Infotrieve]
26. Davis S, Andrews J, Lichtenstein M, Kaye A, Tress B, Rossiter S, Salehi N, Binns D. A single-photon emission computed tomography study of hypoperfusion after subarachnoid hemorrhage. Stroke. 1990;21:252-259. [Abstract/Free Full Text]
27. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189-198. [Medline] [Order article via Infotrieve]
28. Williams JB. A structured interview guide for the Hamilton Depression Rating Scale. Arch Gen Psychiatry. 1988;45:742-747. [Abstract]
29. Lindegaard MW, Skretting A, Hager B, Watne K, Lindegaard KF. Cerebral and cerebellar uptake of 99mTc-(d,1)-hexamethyl-propyleneamine oxime (HM-PAO) in patients with brain tumor studied by single photon emission computerized tomography. Eur J Nucl Med. 1986;12:417-420. [Medline] [Order article via Infotrieve]
30. Coté R, Battista RN, Wolfson C, Boucher J, Adam J, Hachinski V. The Canadian Neurological Scale: validation and reliability assessment. Neurology. 1989;39:638-643. [Abstract/Free Full Text]
31. Collin C, Wade DT, Davies S, Horne V. The Barthel ADL Index: a reliability study. Int Disabil Stud. 1988;10:61-63. [Medline] [Order article via Infotrieve]
32. Chua MG, Davis SM, Infeld B, Rossiter SC, Tress BM, Hopper JL. Prediction of functional outcome and tissue loss in acute cortical infarction. Arch Neurol. In press.
33. Hanson SK, Grotta JC, Rhoades H, Tran HD, Lamki LM, Barron BJ, Taylor WJ. Value of single-photon emission-computed tomography in acute stroke therapeutic trials. Stroke. 1993;24:1322-1329. [Abstract/Free Full Text]
34. Tien RD, Ashdown BC. Crossed cerebellar diaschisis and crossed cerebellar atrophy: correlation of MR findings, clinical symptoms, and supratentorial diseases in 26 patients. AJR. 1992;158:1155-1159. [Abstract/Free Full Text]
35. Bogsrud TV, Rootwelt K, Russell D, Nyberg-Hansen R. Acetazolamide effect on cerebellar blood flow in crossed cerebral-cerebellar diaschisis. Stroke. 1990;21:52-55. [Abstract/Free Full Text]
36. Sakashita Y, Matsuda H, Kakuda K, Takamori M. Hypoperfusion and vasoreactivity in the thalamus and cerebellum after stroke. Stroke. 1993;24:84-87. [Abstract/Free Full Text]
37. Lassen NA. The luxury perfusion syndrome and its possible relation to acute metabolic acidosis localized within the brain. Lancet. 1966;2:1113-1115. [Medline] [Order article via Infotrieve]
38. Baron JC, Bousser MG, Comar D, Soussaline F, Castaigne P. Noninvasive tomographic study of cerebral blood flow and oxygen metabolism in vivo: potentials, limitations, and clinical applications in cerebral ischemic disorders. Eur Neurol. 1981;20:273-284. [Medline] [Order article via Infotrieve]
39. Baron JC. Positron tomography in cerebral ischemia: a review. Neuroradiology. 1985;27:509-516. [Medline] [Order article via Infotrieve]
40. Companioni JM, Lassen NA, Tfelt-Hansen P, Friberg L. Delayed reflow of an ischemic infarct after spontaneous thrombolysis studied by CBF tomography using SPECT and Tc-99m HMPAO. Am J Physiol Imaging. 1991;6:167-171. [Medline] [Order article via Infotrieve]
41. Yamauchi H, Fukuyama H, Yamaguchi S, Doi T, Ogawa M, Ouchi Y, Kimura J, Sadatoh N, Yonekura Y, Tamaki N, Konishi J. Crossed cerebellar hypoperfusion in unilateral major cerebral artery occlusive disorders. J Nucl Med. 1992;33:1637-1641. [Abstract/Free Full Text]
42. Giubilei F, Lenzi GL, Di Piero V, Pozzilli C, Pantano P, Bastianello S, Argentino C, Fieschi C. Predictive value of brain perfusion single-photon emission computed tomography in acute ischemic stroke. Stroke. 1990;21:895-900. [Abstract/Free Full Text]
43. Brodal P. The corticopontine projection in the rhesus monkey: origin and principles of organization. Brain. 1978;101:251-283. [Free Full Text]
44. Baird AE, Donnan GA, Austin MC, Fitt GJ, Davis SM, McKay WJ. Reperfusion after thrombolytic therapy in ischemic stroke measured by single-photon emission computed tomography. Stroke. 1994;25:79-85. [Abstract]
45. Herderschee D, Limburg M, van Royen EA, Hijdra A, Buller HR, Koster PA. Thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke: evaluation with rCBF-SPECT. Acta Neurol Scand. 1991;83:317-322.[Medline] [Order article via Infotrieve]

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