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(Stroke. 1995;26:1000-1006.)
© 1995 American Heart Association, Inc.

Articles

Contribution of Diaschisis to the Clinical Deficit in Human Cerebral Infarction

J. V. Bowler, MD, MRCP; J. P. H. Wade, MD, FRCP; B. E. Jones, MSc; K. Nijran, PhD; R. F. Jewkes, FRCP; R. Cuming, BSc T. J. Steiner, MB, PhD

From the Regional Neurosciences Centre (J.V.B., J.P.H.W.) and the Department of Nuclear Medicine (B.E.J., K.N., R.F.J.), Charing Cross Hospital, and the Academic Unit of Neuroscience (J.V.B., J.P.H.W., T.J.S.) and the Department of Surgery (R.C.), Charing Cross and Westminster Medical School, London, UK.

	Abstract

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Background and Purpose Regions of decreased cerebral blood flow are often seen on single-photon emission computed tomography (SPECT) after stroke and have been widely reported to add to the clinical deficit. However, such reports have not distinguished between correlation and causation. We analyzed 124 serial SPECT scans performed in 50 patients to assess the role of diaschisis in the clinical deficit after stroke.

Methods SPECT with the use of ^99mTc–hexamethylpropyleneamine oxime (^99mTc-HMPAO) was performed in a prospective, unselected series of 50 patients with cerebral infarcts studied at a median of 1.1, 6.8, and 95 days after ictus. Patients were also assessed with the use of the Canadian Neurological Scale, the Barthel Index, a neuropsychological evaluation, and infarct volume measurement.

Results One hundred twenty-four serial SPECT scans were done in 50 patients. Diaschisis was identified at 168 sites. There was insufficient correlation between diaschisis and the clinical measurements to support the suggestion that diaschisis independently causes clinical deficits beyond those due to the infarct itself. Unlike the clinical status, diaschisis showed little tendency to resolve during the 3-month follow-up period of the study. Several of the instances of correlation were shown to be of a noncausal kind, with both the diaschisis and the clinical deficit being due to the lesion directly; there was no known mechanism for the diaschisis to cause the clinical deficit.

Conclusions Diaschisis does not independently add to the clinical deficit after stroke. It is more likely that it simply represents part of the damage done by the stroke.

Key Words: diaschisis • stroke outcome • tomography, emission computed

	Introduction

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Diaschisis refers to functional deactivation occurring remotely from the responsible structural lesion^{1 2 3} and was first described as an explanation for spinal shock after cord transection.¹ It has excited greater interest recently because disturbances in cerebral blood flow (CBF) or metabolism, remote from the primary lesion, have been seen on functional imaging.^{4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19} These have also been termed diaschisis. In functional imaging diaschisis may be defined as an alteration of cerebral metabolism remote from the causative lesion. It is implicit in the definition that there should be no direct cause (eg, ischemia, edema), and it is inferred that the decrease in metabolism is due to loss of afferent input. There is normally close coupling between CBF and metabolism, and therefore in the normal brain, imaging of CBF will provide a map of cerebral metabolism. ^99mTc–hexamethylpropyleneamine oxime (^99mTc-HMPAO) is a validated tracer for the imaging of CBF by single-photon emission computed tomography (SPECT)^{20 21 22 23 24} and as such can be used to detect diaschisis.

Diaschisis has been extensively reported in association with stroke^{4 13 15 25 26 27 28 29 30 31} and is most often seen in the cerebellum contralateral to supratentorial lesions (crossed cerebellar diaschisis) in approximate proportion to the degree to which they affect the pyramidal tracts. Diaschisis is also well described in the cortex overlying small deep lesions, especially those of the thalamus.^{7 14 15 16 19 30 32 33 34 35 36 37 38} It has been suggested that resolution of diaschisis may be important in recovery from stroke.^{1 3 19} A correlation has been reported between diaschisis and neuropsychological deficit after small deep lesions.^{19 28 32 39} A further correlation has been suggested between extensive cortical diaschisis and motor hemineglect³⁶ and between performance on the Token test and parietotemporal metabolism.⁸ While these reports have suggested a correlation between diaschisis and deficit, they have been unable to establish whether the association is causal or whether appropriately sited lesions produce both the clinical deficit and diaschisis, without the diaschisis adding to the deficit. Furthermore, these studies have often been poorly controlled, and it has often not been clear how the cases have been selected.

In only one article has the question of correlation and causation been specifically addressed,³² and it was conceded that the distinction could not be made from the data available. Even so, recovery from diaschisis has been suggested as one mechanism of recovery from stroke^{1 3} and metabolic enhancement therapy proposed as a treatment.¹⁹

Several associations between diaschisis and measures of outcome might be expected if diaschisis added to the clinical deficit. First, the degree and extent of diaschisis should increase with infarct volume because with increasing infarct volume more pathways would be damaged.^{26 40} Second, clinical outcome should correlate with diaschisis if diaschisis added to the clinical deficit. Third, diaschisis would be expected to resolve as the clinical deficit resolves.

During a prospective study investigating the role of ^99mTc-HMPAO SPECT in the assessment of acute human cerebral infarction, much evidence of diaschisis was seen. As detailed clinical and neuropsychological data were accumulated in serial studies up to 3 months from the time of the stroke, we analyzed the data to examine the correlations between diaschisis and the clinical deficits. We have previously reported the findings related to small deep infarcts.³⁰ We now report the findings in our complete series.

	Subjects and Methods

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All patients over the age of 18 years admitted to our district general hospital with first stroke were eligible for the study. Exclusions to entry or continuation in the study were pregnancy, previous stroke or cranial neurosurgery, primary intracerebral hemorrhage, inability to speak English, current severe psychiatric illness, epilepsy, dementia, alcohol abuse, drug abuse, severe intercurrent illness, or any other factors that might interfere with the appearance of the ^99mTc-HMPAO SPECT scans or result in a high risk of the patient defaulting from follow-up.

On each occasion a full neurological examination and SPECT scanning were performed within 2 hours of each other. The first clinical examination and SPECT were performed as soon as possible after the infarct, and subsequent studies, including SPECT and clinical examination, were done at approximately 1 week and 3 months after ictus. CT scanning was usually done between 3 and 7 days after ictus. The clinical examination included an assessment for the Canadian Neurological Scale⁴¹ and a functional evaluation, the Barthel Index.⁴² A detailed psychological evaluation was done at the time of the second SPECT scan or as soon as the patient was fit enough, and again at the time of the third SPECT scan. Details of the neuropsychological evaluation have been published elsewhere.^{43 44} Most of the tests were selected from the Wechsler Adult Intelligence Scale (WAIS),⁴⁵ the Wechsler Memory Scale (WMS),⁴⁶ the Adult Memory and Information Processing Battery (AMIPB),⁴⁷ and the Boston Diagnostic Aphasia Inventory (BDAI).⁴⁸ The precise tests were the abbreviated mental scale^{49 50} ; line division; clock drawing; house drawing; unusual and usual views⁵¹ ; digit span; arithmetic (from the WAIS); design reproduction,⁴⁶ ; logical memory (from the AMIPB); left-right discrimination; body part identification; verbal fluency; word, phrase, and nonword repetition; information processing (from the AMIPB); and the test for the reception of grammar.⁵² The study had the consent of the hospital ethics committee.

SPECT scanning began 15 to 30 minutes after the injection of 750 MBq of ^99mTc-HMPAO (Ceretec, Amersham International). Scanning was started 30 mm below the infraorbitomeatal line, with slices 10 mm apart and each of 8 to 12 slices covering the whole brain collected for 5 minutes by means of the NOVO 810 scanner, which is a dedicated multidetector tomographic head scanner with a resolution of 9 mm full width at half maximum in the plane of the scan and 19 mm axially, full width at half maximum.⁵³ The attenuation correction is a linear correction operating with circular symmetry from the center of the field.⁵³ Because this can cause substantial artifactual right-left differences if the patient's head is not exactly centered, all analyses were performed on data reconstructed with no attenuation correction.

To be able to define regions affected by diaschisis in a way that would permit comparison between patients and between repeated studies in the same patient, the analysis was limited to regions that could be identified on high-resolution SPECT. In practice this meant each of the lobes, the basal ganglia, the thalamus, and the cerebellum. For each study available, areas consistent with diaschisis were initially identified by visual inspection of images. Initial analysis has shown that diaschisis cannot be shown to exist on single scans by analysis that uses regions of interest (ROIs) if changes compatible with diaschisis are not detectable on inspection. The converse is not the case in that suspicious regions may not be confirmed as outside the 95% limits for that volume when examined with ROIs. To confirm and quantify the severity of diaschisis in a region, ROIs 18 mm in diameter (twice the resolution of the scanner) were placed over the appropriate area on the affected side and symmetrically over the contralateral side. To avoid incorporating ischemic regions into these ROIs and to decrease partial volume effects, no ROI was placed within 2 ROI diameters (36 mm) of the edge of an infarct. For comparison of sequential scans the same regions were used in each study on the same patient. In each region, diaschisis was confirmed only if the right-left ratio fell outside the 95% confidence interval for that region when data obtained from stroke-free control subjects were used (n=11; mean age, 42.7 years; 95% confidence intervals as percent right-left difference by region: basal ganglia, 8.9%; cerebellum, 7.4%; frontal lobe, 7.2%; occipital lobe, 7.3%; parietal lobe, 4.2%; thalamus, 10.7%; temporal lobe, 7.6%⁴³ ). If any study on a patient revealed a suspect volume, the same volume was studied on all the scans on that patient to obtain information about the evolution of diaschisis. When necessary the ratios were redefined as abnormal-normal to make their distribution unidirectional.

Infarct volumes were usually measured from CT scans by planimetry with the use of the CT scan nearest in timing to 5 days after ictus. In one patient the lesion was not seen on CT, and the volume was taken from the MRI. In five other patients an appropriately timed CT scan was not available, and the infarct volumes were taken from the first ^99mTc-HMPAO SPECT scans with the use of the volume estimation facility provided in the graphical analysis package ANALYZE (Biodynamics Research Unit, Mayo Clinic). The volume of the scan, typically consisting of 160 000 voxels (from the scan format, 128 x128 pixelsx10 slices) with an individual real volume of 26 mm³, was seeded with 10 000 randomly distributed points. Those within the lesion were interactively selected on a two-dimensional slice-by-slice basis. Because the borders of the lesions were generally very sharp, there was rarely any difficulty in deciding the location of a seed. When there was any doubt, the location of the seed was examined in three dimensions; if doubt persisted, the seed was included as within the lesion. The infarct volume was calculated from the number of seeds selected. The relationship between infarct volume and the degree of diaschisis was analyzed by Kendall rank correlation.

To establish whether diaschisis had any association with the clinical condition of the patient, the data were grouped by time interval, and the severity of diaschisis at each site was compared with the clinical score on the Canadian Neurological and Barthel scales by Kendall rank correlation. In addition, for the 33 subjects in whom data were available for both the first and last studies, the rates of change with time for diaschisis for each region and for the Canadian Neurological Scale and Barthel Index were calculated and analyzed by linear regression.

Diaschisis at each site was related to the deficits in higher cerebral function (such as dysphasia or hemianopia) by means of the ² test, with diaschisis dichotomized as present or absent. For the neuropsychological evaluation, the relation to the degree of diaschisis was examined with the use of the Kendall rank correlation.

	Results

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Sixty patients were recruited prospectively and serially into the study; of these, 50 were found to have had ischemic stroke. These 50 patients (mean age, 68 years; 28 women, 22 men) are the subject of this report. One hundred twenty-four ^99mTc-HMPAO SPECT scans were done in these subjects. The first SPECT scan (n=50) was done at a median of 1.1 days (interquartile range, 0.8 to 1.7 days), the second (n=41) at 6.8 days (range, 6.0 to 7.9 days), and the third (n=33) at 95 days (range, 91 to 111 days) after stroke. Five subjects withdrew because they were intolerant of the scanning, 1 because of transfer to a remote nursing home, and 1 for no known reason, although this patient had a frontal infarct and had remained notably apathetic while an inpatient. Ten subjects died: 4 as a result of cerebral edema, 3 from additional strokes, and 1 each from pneumonia, pulmonary embolism, and incidental malignancy. Complete data were obtained in 31 subjects because 2 subjects missed their second studies. The sites and sizes of the lesions are given in the Table.

View this table: [in this window] [in a new window]   Table 1. Size and Site of Infarcts in 50 Patients With Ischemic Stroke

One hundred sixty-eight instances of diaschisis were identified. The contralateral cerebellum was affected in 28 cases, the ipsilateral thalamus in 22, the frontal cortex in 9, the parietal cortex in 9, the temporal cortex in 2, the occipital cortex in 5, the basal ganglia (consisting of the lentiform nucleus and part of the caudate nucleus) in 2, and an additional cortical volume termed the overlying cortex in 13. Overlying cortex refers to the cortex laterally overlying a lesion. This was usually parietal and frontal, with diaschisis extending in continuity over the central sulcus. Further analyses for the temporal and occipital cortices and basal ganglia were not done because of their low frequency.

The severity of the diaschisis tended not to evolve within a given region during the period of the study. In the parietal cortex the degree of diaschisis fell from 11.1% to 5.0% (P=.049) between the first and last study and in the cortex overlying a lesion fell from 11.9% to 5.9% (P=.02) from the first to the second study. There were no other significant changes, and in the cerebellum and frontal cortex not even a trend to improvement was noted.

The Canadian Neurological Scale scores for the three assessments in turn were 5.74, 6.54, and 7.73, respectively (P=.0002, first to third examination, Mann-Whitney U test). The Barthel Index scores were 11.65 and 14.64 at the second and third examinations, respectively (P=.0182).

The correlation between the infarct volume and the degree of diaschisis at each of the available sites (parietal, cerebellum, thalamus, frontal, overlying cortex) was examined by means of Kendall rank correlation. At the first examination, crossed cerebellar diaschisis correlated weakly with the infarct volume (coefficient, .382; P=.0003), as did thalamic diaschisis (coefficient, .276; P=.011), but there was no correlation at any other site. At the second examination, the correlations with cerebellar diaschisis (coefficient, .48; P<.0001) and thalamic diaschisis (coefficient, .276; P=.011) were maintained, and a significant correlation between infarct volume and occipital diaschisis was attained (coefficient, .258; P=.05), but no other correlations reached significance. A similar pattern was maintained at the third examination (cerebellar diaschisis coefficient, .467; P=.0003; thalamus coefficient, .429; P=.0012; occipital coefficient, .29; P=.05), and again no new significant correlations emerged.

The relationships between the Canadian Neurological Scale scores and Barthel Index scores and the degree of diaschisis were analyzed by rank correlation for each site, grouping together the data for all the cases at each study time. At the first examination, the Canadian Neurological Scale score correlated with the degree of diaschisis in the contralateral cerebellum (coefficient, -.365; P=.0007), thalamus (coefficient, -.427; P=.0001), and occipital cortex (coefficient, -.258; P=.031) but no other sites. At the second examination the correlations with cerebellar diaschisis (coefficient, -.281; P=.018) and thalamic diaschisis remained significant (coefficient, -.373; P=.004). The correlation with frontal diaschisis, which had previously been marginal, became significant (coefficient, -.289; P=.035), while that for the occipital cortex ceased to be significant. At the third examination only cerebellar and thalamic diaschisis remained significantly correlated with the Canadian Neurological Scale score (coefficients, -.387 and -.273; P=.004 and P=.044, respectively). For the Barthel Index, significant correlations were identified between the index and both cerebellar and thalamic diaschisis at the second examination (cerebellar coefficient, -.284; P=.017; thalamus, -.324; P=.011) and third examination (cerebellar coefficient, -.341; P=.015; thalamus, -.299; P=.037), but no other correlations attained significance.

An additional analysis was performed in the 33 subjects for whom data were available for the first and third studies to compare changes in clinical status and degree of diaschisis within subjects. For each subject, the rate of change with time between the first and third studies for the Barthel Index score, Canadian Neurological Scale score, and the degree of diaschisis at each site was calculated and the clinical evolution and the evolution of diaschisis compared by linear regression, since these data were largely normally distributed. Thalamic diaschisis decreased as the Canadian Neurological Scale score increased (F ratio, 9.74; P=.0041; R²=25.14%), but this was the only site for which a positive result was obtained. The Barthel Index score tended to improve as thalamic diaschisis decreased, but this did not reach significance, and at no other site was a positive result identified for the Barthel Index.

As part of the clinical examination, several specific neurological deficits were sought, ie, anosognosia, asomatognosia, dysphasia, gaze paresis, and visual field defects.⁴³ However, only visual field defects and dysphasia, which were both assessed clinically at the bedside, occurred sufficiently frequently to permit further analysis. There was an association between crossed cerebellar diaschisis and dysphasia at the second examination (²=5.55, P=.018 with Yates' correction). All three patients with occipital diaschisis had visual loss. However, 18 patients on the first examination had visual loss without occipital diaschisis. Analysis of visual loss against diaschisis at other sites showed significant associations only with crossed cerebellar diaschisis and thalamic diaschisis. The relationship with crossed cerebellar diaschisis was significant at the first examination (²=4.7, P=.030) and the final examination (²=5.93, P=.015) but not at the second examination. For thalamic diaschisis a similar pattern was seen (first examination, ²=10.04, P=.0015; final examination, ²=8.5, P=.0036).

The relationship between diaschisis at each site and the scores for the tests used in the neuropsychological assessment were examined by Kendall rank correlation. Thirty-nine of these achieved a value of P<.05. However, for each site and time of diaschisis analyzed, correlations were sought for 25 psychological test scores. A Bonferroni correction adjusted the value for significance to P=.002 for each time and site. No correlations reached this value.

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The criteria used here for the detection of diaschisis were made specific by the use of large volumes and by the requirement that a region had to be both visible on at least one scan in a series and confirmable with ROIs before diaschisis was confirmed. The use of large volumes reduces the risk of small areas of change producing spuriously positive results, although this may be at the price of lowered sensitivity. On only two occasions did the technique produce statistically significant results that were internally inconsistent, ie, in which putative diaschisis altered from side to side within the same patient over time. In view of the very large number of measurements made, this is a modest error rate and suggests that the criteria produced specific results with few spurious regions of diaschisis identified.

The sensitivity of the technique is more difficult to evaluate because no data exist to suggest how much diaschisis should be seen. Indeed, it has been shown that diaschisis may persist even when not visible on a resting scan and may require activation to show it.⁵⁴ This considerably expands the potential extent of diaschisis. Whether undetected and latent diaschisis is important remains unknown. Transcallosal diaschisis, by reducing the CBF on the side contralateral to the lesion and thereby increasing the abnormal-normal ratio, may have prevented confirmation of diaschisis in some instances. Because of the difficulty of establishing a reference value other than by using the contralateral side, we did not look for transcallosal diaschisis. This is a common problem with proportionate measures of CBF.²¹ We do not know the amount of data that is lost by the combination of these two problems. The amount of contralateral supratentorial diaschisis expected after stroke is a matter of dispute. Some evidence suggests that this is common,^{55 56} but other work attributes the fall in contralateral CBF to the fact that the subjects had some degree of bilateral cerebrovascular disease because control subjects with similar disease but no acute events showed the same decrease in cortical CBF compared with disease-free normal subjects as did subjects with acute stroke.⁵⁷ However, diaschisis was detected in our study with a frequency comparable to that in the literature, which suggests that our methods are valid. For example, we detected crossed cerebellar diaschisis in 28 of 50 subjects, and other reports have yielded figures in the range of 50% to 70%.^{4 10 26 27 29 40 58} In addition, the CBF decrease seen in our subjects corresponds to that reported in the literature.¹⁵ The decrease reached a maximum of 45.7%, although the vast majority was below 25% compared with the opposite side.

A potential source of error is the misidentification of mild ischemia as diaschisis. This is unlikely to be a major source of error because infarcts were usually sharply demarcated from adjacent normal tissue, with little evidence of partial ischemia. The use of a gap equivalent to twice the resolution of the scanner between the infarct and any areas of diaschisis should abolish partial volume effects within the plane of the scan as a source of error. Partial volume errors between scan planes remain theoretically possible, but most of the structures of interest do not overlie each other vertically. Only the temporal and parietal lobes may have been affected in this way, but neither of these regions was often affected by diaschisis, and it seems unlikely that partial volume errors in the vertical direction are an important source of error.

Diaschisis usually recovers over time,^{1 2} although not always.^{26 27 35} We identified recovery on only two occasions, and these were at low levels of significance. In the cerebellum, which is the area in which the most valid results might be expected because of its remoteness from supratentorial lesions and numerous observations, there was not even a trend toward resolution. The most obvious explanation for the failure to observe resolution is that the period of follow-up was too short. Although there is some evidence to support the notion that diaschisis resolves quickly,^{4 12} there is much evidence that it does not always do so, even as long as 6 months after the ictus.^{26 40} Failure of resolution may be due to the development of irreversible structural changes that can appear rapidly, within the time course applicable here.^{27 59 60 61 62} Structural changes, such as transneuronal degeneration, are not included within the definition of diaschisis³ but may be difficult to separate from it on functional imaging alone. In practical terms some degree of transneuronal degeneration is likely in all but the earliest scans. While the effect is probably small,³ it may interfere with the correlation between diaschisis and clinical deficits after prolonged intervals after stroke.¹⁹

The general lack of correlation between diaschisis and infarct volume was surprising. The most likely explanation for this is that small deep lesions may be as effective as large cortical lesions in producing diaschisis because of their effect on tightly packed pathways. This is particularly likely to be the case with crossed cerebellar diaschisis, which is known to be correlated with the degree to which the lesion affects the corticopontocerebellar tract.^{27 31 63} The thalamus, because of its numerous inputs, might also be readily affected by stroke. Conversely, most cortical regions receive numerous inputs, and only close subcortical infarcts or very strategically placed infarcts (eg, in the thalamus) would be expected to cause cortical diaschisis. This would produce a low frequency of cortical diaschisis in stroke in general, combined with a poor correlation with size because of the effects of strategic, potentially small, lesions.

The consistent association between cerebellar diaschisis and clinical status measured by the Canadian Neurological Scale and Barthel Index can readily be explained by lesions that affect the descending motor tracts, including the corticopontocerebellar tract, thereby producing crossed cerebellar diaschisis and motor impairment, which would profoundly affect the scores on both rating scales. Although significant, the coefficient of the correlation is weak, and it would be difficult to extrapolate causation from such a weak association. Similar comments apply to the thalamus, although in this case the association is likely to be due to involvement of several of the many circuits in which the thalamus is involved.

Clinical improvement in the absence of a decrease in the amount of diaschisis may be due to the resolution of edema. However, because the resolution of edema presumably causes clinical improvement by the return of function to impaired neurons, it would be expected to affect the amount of diaschisis as well if diaschisis was closely related to clinical recovery. Thus, while edema may have had an independent effect, this does not detract from our conclusions.

The association between thalamic diaschisis and visual loss is curious. It was demonstrated in the first and third studies with a high degree of significance and only just failed to reach significance on the second study. The observation seems genuine. However, while the lateral geniculate body is often considered part of the thalamus and cannot be distinguished from the thalamus by SPECT, the thalamus has no other known contribution to the visual pathway. There is therefore no mechanism by which thalamic diaschisis could turn off the visual cortex. An alternative explanation is needed. The obvious explanation is that the thalamus, and hence the lateral geniculate body, was ischemic. However, care was taken not to analyze as diaschisis changes in the thalami that might be considered ischemic, and the evidence to suggest that thalamic ischemia can cause occipital diaschisis is mixed. In one study that used positron emission tomography to investigate the effect of thalamic stroke in causing cortical diaschisis, no occipital diaschisis was identified despite the identification of diaschisis in many different cortical sites except the temporal cortex. The analytical technique was very similar to that used here. However, only seven cases were studied.³⁷ Conversely, in another investigation of 11 patients with thalamic lesions studied with the use of positron emission tomography between 0.6 and 9 years after infarct, both posterior and medial thalamic lesions had an effect on the occipital cortex.³⁵ The interpretation of this report is made difficult by the lack of statistics but is supported by a single additional case study demonstrating occipital deactivation after the development of a lesion in the region of the lateral geniculate body.¹⁶

An alternative explanation is that the lesions that caused thalamic diaschisis independently affected both the thalamus and some part of the optic tract and that the association is spurious, reflecting the danger of equating causation with association. Similarly, the association between visual loss and crossed cerebellar diaschisis is likely to be due to large lesions causing both. The loss of the correlation between visual loss and crossed cerebellar diaschisis at 1 week was probably an artifact of death and withdrawal since 7 of the 8 subjects who were lost between the first and second examinations had both visual loss and crossed cerebellar diaschisis, making the association nonsignificant. Between the second and third examinations, 4 of the 6 subjects lost had visual loss but no crossed cerebellar diaschisis, thereby partially restoring the balance of the ² table. An additional example of possible spurious associations comes from the correlation between dysphasia and crossed cerebellar diaschisis. This is causally implausible and is most likely due to lesions that independently caused both the neuropsychological deficit and the crossed cerebellar diaschisis.

Despite an exhaustive treatment, it has not been possible to demonstrate more than a weak association between diaschisis and clinical deficits. Demonstrating such an association is only the first step in proving causation. Despite the reports of diaschisis and its correlation with clinical deficit,^{19 28 33} the material published to date has not been able to distinguish between correlation and causation. Where correlations between diaschisis and clinical deficit have been shown, the relationships are sufficiently weak to lead to doubt as to whether the diaschisis could be causative. Furthermore, unlike the series reported here, the series previously reported usually have not been unselected prospective studies. Series that select cases on the basis of the presence of diaschisis or because they have lesions that often lead to diaschisis¹⁹ run the risk of identifying false-positive correlations.

We cannot exclude the possibility that diaschisis has effects that are too subtle to detect by the methods we used. However, we used a battery of clinical and neuropsychological tests. Thus, even if this is so, it would not detract from our conclusion that diaschisis does not independently add to the clinical deficit in stroke because deficits that are so minor that they require specially developed tests beyond those used here would not affect recovery.

We conclude that diaschisis is simply due to deactivation of areas that no longer receive the normal level of input, ie, it is simply a consequence of the lesion itself.

	Acknowledgments

 
This study was supported by the Stroke Association (Dr Bowler).

	Footnotes

 
Reprint requests to Dr J.V. Bowler, Department of Clinical Neurological Sciences, University Hospital, London, Ontario N6A 5A5, Canada. E-mail jbowler@biostats.uwo.ca.

Received September 15, 1994; revision received February 28, 1995; accepted February 28, 1995.

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Top Abstract Introduction Subjects and Methods Results Discussion References

 

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