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ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 3  |  Page : 1082-1087

Predictive value of fractional anisotropy changes of the corticospinal tract in the acute phase of ischemic stroke


1 Department of Neuropsychiatry, Faculty of Medicine, National Liver Institute, Menoufia University, Menoufia, Egypt
2 Department of Radiology, National Liver Institute, Menoufia University, Menoufia, Egypt
3 Department of Neuropsychiatry, Shebin Elkom Teaching Hospital, Menoufia, Egypt

Date of Submission01-Mar-2020
Date of Decision12-Apr-2020
Date of Acceptance14-Apr-2020
Date of Web Publication30-Sep-2020

Correspondence Address:
Aya M Elkordy
Department of Neuropsychiatry, Shebin Elkom Teaching Hospital, Menouf, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_55_20

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  Abstract 


Objective
To evaluate the role of reduction in fractional anisotropy (FA) of the ipsilesional corticospinal tract detected by diffusion tensor imaging (DTI) as a prognostic tool to predict the outcome following an acute ischemic stroke.
Background
There are high costs and concerns about postischemic stroke disability worldwide. DTI is an emerging neuroimaging technique that allows us to measure the integrity of white matter tracts. The reduction of FA value detected by DTI can predict residual neurological deficit in the acute phase of ischemic stroke after 3 months.
Patients and methods
A nonrandomized, retrospective cohort study was conducted on 40 patients with acute ischemic stroke for the first time and 40 controls of healthy individuals. We assessed our patients according to the size of the infarction, stroke severity using the National Institute of Health and Stroke Scale (NIHSS), and degree of reduction of FA detected by DTI. Patients were followed up clinically using NIHSS after 3 months for residual neurological deficits.
Results
We observed a good association between reduction of FA value measured by DTI and clinical findings of acute ischemic stroke assessed by NIHSS at the time of onset and after 3 months (P = 0.004, 0.007), respectively. The reduction of FA value was measured by DTI, which is also correlated with the size of the infarction of ischemic stroke (P < 0.001).
Conclusion
Reduction of FA of the corticospinal tract was measured by DTI. The image could be used as a useful tool for predicting long-term poststroke disability after 3 months.

Keywords: acute ischemic stroke, corticospinal tract, diffusion tensor imaging, fractional anisotropy, National Institute of Health and Stroke Scale


How to cite this article:
Elkabany RA, Al-Ahmer IE, Afifi KH, Abdelsamea ME, Elkordy AM. Predictive value of fractional anisotropy changes of the corticospinal tract in the acute phase of ischemic stroke. Menoufia Med J 2020;33:1082-7

How to cite this URL:
Elkabany RA, Al-Ahmer IE, Afifi KH, Abdelsamea ME, Elkordy AM. Predictive value of fractional anisotropy changes of the corticospinal tract in the acute phase of ischemic stroke. Menoufia Med J [serial online] 2020 [cited 2020 Oct 22];33:1082-7. Available from: http://www.mmj.eg.net/text.asp?2020/33/3/1082/296704




  Introduction Top


Stroke is one of the leading causes of death worldwide. It can be further divided into ischemic or hemorrhagic [1]. Multiple risk factors may lead to stroke such as age, sex, smoking, hypertension, hyperlipidemia, diabetes mellitus, genetics, and hereditary blood disorders [2].

Stroke can affect people physically, mentally, emotionally, or a combination of the three. The results of stroke vary widely depending on the size and location of the lesion. Dysfunctions correspond to areas in the brain that have been damaged [3].

Because of the importance to predict the outcome following a stroke, many authors were relying on the size of the infarction on MRI, but recently with the emergence of MRI tractography, many suggest that the location of infarction rather than its size predict the prognosis following stroke [4].

The advantage of MR tractography lies in the fact that it gives direct and superior visualization of the involved white matter tracts in vivo, which is currently not possible by conventional imaging. With diffusion tensor imaging (DTI), microstructural organization of white matter tracts can be obtained and provide important information about their integrity as well as orientation. The information so obtained may prove more sensitive to assess tract damage than the volume estimation of signal abnormality on conventional imaging [5].

Based on the principle of anisotropic water molecular diffusion, DTI provides quantitative analysis of the magnitude and directionality of water molecules in a three-dimensional space and reflects the microstructural and functional abnormality of tissues.

Fractional anisotropy (FA) value which could be measured by DTI will be affected by the disruption of the brain microstructural environment in various neurologic conditions [6].

The ability to identify white matter tract disruption in acute stroke may be a useful index of stroke severity and may allow insight into likely recovery and long-term disability [7].

So, this study aimed to evaluate the role of reduction in FA of the ipsilesional corticospinal tract (CST) detected by DTI as a prognostic tool to predict outcome following acute ischemic stroke.


  Patients and Methods Top


This study was a nonrandomized retrospective cohort, conducted on 40 patients with acute ischemic stroke for the first time and 40 healthy individuals matched for age and sex. The patients were recruited from the Neurology Department, Menoufia University Hospital and were referred to the Radiology Department, National Liver Institute, Menoufia University. This occurred during the period from December 2017 to November 2018 after approval from the Research and Ethics Committee of Faculty of Medicine, Menoufia University. Written informed consent was obtained from all participants and patients' confidentiality was assured. All patients were subjected to complete history taking, including assessment of initial stroke severity using the National Institute of Health and Stroke Scale (NIHSS). All patients were also subjected to MRI and were assessed according to infarction size obtained from fluid-attenuated inversion recovery (FLAIR) and degree of reduction of FA detected by DTI.

Sample size: based on previous studies, Elkholy et al. [8] reported that the percentage of disrupted tractography in mild NIHSS patients was 3.3%, while in the nondisrupted one it was 43.8%. Minimum sample needed is 80 patients, according to the following formula:



where n: sample size, Z1-α: Z score for 95% confidence interval and equals 1.96, Z1-β: Z score for power of the study, 80% and equals 0.84, P 1: 0.033, P 2: 0.438.

Patients were followed up clinically using NIHSS after 3 months for residual neurological deficits [9].

MRI was done without prior preparation or anesthesia and after the exclusion of MRI contraindications as a cardiac pacemaker, prosthetic valve, and claustrophobia. All MRI were performed with GE optima MR 450 1.5 T (General Electric USA, Arizona, USA). All images were revised and reported by an expert radiologist at the Radiology Department, National Liver Institute, Menoufia University.

The acquisition was done using a standard head coil. The sequences were obtained by Axial T2-weighted spin-echo, T1-weighted spin-echo, FLAIR, echo-planar diffusion-weighted sequences, and DTI.

All images were postprocessed using the Philips IntelliSpace portal software version 6.0.620039 (Amsterdam, the Netherlands).

Size of infarction was obtained from FLAIR sequence and measured manually in three diameters, anteroposterior, transverse, and craniocaudal using the ruler tool. We considered the longest diameter for comparison.

Anisotropy was measured in several ways. One way was by a ratio called FA. An FA of 0 corresponded to a perfect sphere, whereas 1 was an ideal linear diffusion.

The interpretation was done by the analysis of the reduction of FA value. DTI data of the involved white matter tracts were compared with the corresponding tracts of the corresponding hemisphere in the control group. FA, which was the most widely used scalar in DTI, was calculated by dividing the square root of the sum of squares of the diffusivity differences by the square root of the sum of squares of the diffusivities [10]. The FA represented the amount of diffusional asymmetry in a voxel. FA values of 0 and 1 correspond to infinite isotropy (i.e., the ellipsoid was a sphere) and infinite anisotropy (i.e., the ellipsoid was highly elongated), respectively. FA was a marker of axonal integrity that presumes degeneration could change the shape of the diffusion ellipsoid, and this made it highly sensitive to the microstructural integrity of fibers [11].

Patients included in this study were categorized by radiological assessment. As regards the reduction in FA value detected by DTI, they were classified into mild (0.4), moderate (0.2–0.3), and severe (0.1). They were also classified according to the size of infarction (based on the longest diameter) into small (<3 cm), medium-sized (3–8 cm), and large (>8 cm) [1],[8].

On the other hand, all patients were categorized clinically according to the NIHSS patients into mild (0–5), moderate (6–11), severe (12–18), and very severe (>19) [9].

Results were collected, tabulated, and statistically analyzed by IBM personal computer and Statistical Package for Social Science, version 22 (2013; IBM Corp., Armonk, New York, USA).

Two types of statistics were done descriptive statistics, e.g. percentage (%), mean, and SD, and analytic statistics, for example, c2 test: used to study the association between two qualitative variables and Student's t test: a test of significance used for comparison between two groups having quantitative variables. A P value of less than 0.05 was considered statistically significant. An odds ratio (OR) is a measure of association between an exposure and an outcome. where a is the number of exposed cases, b the number of exposed noncases, c the number of unexposed cases, and d is the number of unexposed noncases.


  Results Top


This study involved 80 individuals: 40 patients had acute ischemic stroke for the first time, had no contraindication to MRI, and 40 healthy individuals. They had a mean age of 58.4 ± 11.3 with male predominance of 55%. There was no statistically significant difference between patients and control regarding age and sex (P = 0.895). Diabetes mellitus was the most prevalent risk factor (65%) followed by hypertension (62.5%), dyslipidemia (52.5%), and current smoking (47.5%) [Table 1].
Table 1: Age, sex distribution, and vascular risk factors

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Initially, at the onset of acute ischemic stroke, we assessed the association between the NIHSS on admission and degree of FA reduction at the site of infarction. There was a significant statistical correlation (P = 0.004) between NIHSS and FA. Among four patients with very severe NIHSS on admission, three patients had severe FA, and one patient had moderate FA value [Table 2].
Table 2: Association between the National Institute of Health and Stroke Scale on admission and degree of fractional anisotropy reduction at the site of infraction

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On follow-up after 3 months, we also found a significant statistical correlation (P = 0.007) between NIHSS after 3 months and FA. All patients (N = 2) with very severe NIHSS found to have a severe reduction of FA value and so we could rely on FA value to predict long-term disability after 3 months [Table 2], [Figure 1] and [Figure 2].
Figure 1: (a) Axial diffusion weighed images in a 58-year-old woman presented with left side weakness and dysarthria shows right post limb of internal capsule of restricted diffusion (acute infarct) measuring 2 cm according to the longest diameter. (b) Axial FA map overlaid over axial FLAIR image showing FA value = 0.3. Patient shows minimal residual sensory neurological deficit (NIHSS after 3 months). FA, fractional anisotropy; FLAIR, fluid-attenuated inversion recovery; NIHSS, National Institute of Health and Stroke Scale.

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Figure 2: (a) Axial FLAIR in 65-year-old female HTN and DM presented with right side hemiplegia shows left infraction at postlimb of internal capsule measuring 4 cm according to the longest diameter. (b) Axial FA map overlaid over axial FLAIR image showing FA value (2). Patient showed mild clinical improvement with residual neurological deficit (NIHSS after 3 months was 5). DM, diabetes mellitus; FA, fractional anisotropy; FLAIR, fluid-attenuated inversion recovery; HTN, hypertension; NIHSS, National Institute of Health and Stroke Scale.

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On the other hand, there was significant statistical (P < 0.001) association between the size of infarction and reduction in FA value measured by DTI. The larger the infraction was, the more reduction the FA [Table 3].
Table 3: Relation between size of infraction in patients group of acute ischemic stroke and fractional anisotropy detected by diffusion tensor imaging

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On conducting linear regression analysis FA (P ≤ 0.001), it remained correlated with NIHSS 3 months with a negative correlation that increasing FA value was of a good predictive value while increasing NIHSS value was that of poor predictive value [Table 4].
Table 4: Linear regression analysis between fractional anisotropy and National Institute of Health and Stroke Scale 3 months

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  Discussion Top


DTI is an advanced MRI neuroimaging method that is useful for investigating motor tract integrity following stroke. With DTI, the microstructural organization of white matter tracts can be obtained and provide important information about their integrity as well as orientation. The information so obtained may prove more sensitive to assess tract damage than the volume estimation of signal abnormality on conventional imaging [12].

Based on the principle of anisotropic water molecular diffusion, DTI provides the quantitative analysis of the magnitude and directionality of water molecules in a three-dimensional space and reflects the microstructural and functional abnormality of tissues. FA value which could be measured by DTI will be affected by the disruption of the brain microstructural environment in various neurological conditions [6].

Our study was performed to assess the role of reduction in FA of the ipsilesional CST as a prognostic tool to predict outcome following acute ischemic stroke.

In the current study, we found a significant association between reduction of FA value and stroke severity assessed by the NIHSS at the time of onset as well as the patient's clinical recovery on the follow-up after 3 months assessed by NIHSS. All the patients with severe reduction of FA value measured by DTI had residual deficits on clinical follow-up after 3 months, whereas mild reduction had a near-complete neurological recovery. This indicates that reduction in FA value of CST is well correlated with the clinical presentation of stroke patients, i.e., the more the reduction of FA value of CST detected by DTI, the more severe the clinical presentation and worse clinical recovery on the follow-up after 3 months.

Inconsistent with our results, Ali and Elhameed [13] showed that concerning the pyramidal tract involvement, all infarction lesions were divided into three subgroups, and the degree of pyramidal tract involvement was correlated with the severity of the patients' motor deficits outcome according to NIHSS scores and also with FA values and ratios. This agreed with the study done by Elkholy et al. [8], Lai et al. [14], and Puig et al.[15].

There was good correlation between the location of the lesion, the degree of pyramidal tract involvement, and the patient's motor deficit on the day of discharge and correlated also with FA values where significant reduction correlated well with pyramidal tract interruption and loss of anatomical continuity on the DTT colored images [16]. These results were also in agreement with other results given by previous studies [16],[17].

Another study by Mahmoud et al. [18] showed that five patients in the mild FA group were all belonging to the moderate NIHSS group. Among the 36 patients in the moderate FA group, two (5.5%) patients fall in the mild NIHSS group, 24 (66.7%) patients in the moderate group, and 10 (27.8%) patients in the severe group. In the severe FA group, eight (42.2%) patients were in the mild NIHSS group and 11 (57.8%) patients were in the moderate group. The results were statistically significant denoting that the more the degree of FA reduction, the more the brain damage and the higher the clinical severity.

Among the 38 patients with disrupted white matter tracts, one (2.6%) patient fall in the mild NIHSS group, 29 (76.3%) patients in the moderate group, and eight (21.1%) patients in the severe group, whereas from the 22 patients in the nondisrupted group, nine (40.9%) patients were in the mild NIHSS group, and 11 (50%) patients were in the moderate group and two (9.1%) in the severe group. The results were highly statistically significant. Regarding the correlation between the degree of FA reduction and the NIHSS after 3 months, all the five patients in the mild FA group belonged to the mild NIHSS group.

Among the 36 patients in the moderate FA group, 15 (41.6%) patients fall in the mild NIHSS group and 21 (58.4%) patients in the moderate group, whereas in the severe FA group, six (31.6%) patients were in the mild NIHSS group and 13 (68.4%) were in the moderate group. The results were statistically significant (P = 0.01) denoting that the more the degree of FA reduction and brain damage, the more the residual neurological deficits observed in the patients.

Some studies used the motor subindex score of the NIHSS to evaluate functional outcomes following stroke and reached a conclusion similar to our study. Puig et al. [15]evaluated 60 patients at admission (within 12 h of stroke onset), on day 3 and day 30. They assessed the severity of limb weakness and established three groups: groups I (m-NIHSS scores of 0), II (m-NIHSS: 1–4), and III (m-NIHSS: 5–8). FA values and FA ratio were measured on the affected and the unaffected CSTs. They found that FA values for the CST were significantly lower on the affected side compared with the unaffected side only on day 30, and the FA ratio was significantly correlated with motor deficit on day 30.

However, our results were in contrast with Elkholy et al. [8], who found an insignificant statistical correlation between the degree of FA reduction and the NIHSS score. This could be explained by the different methodologies between the two studies, as they included some cases with chronic infarcts [8].

We also found that there was a statistically significant association between the size of the infraction and the reduction of FA and NIHSS, which means that the larger the size of infraction was, the more the affection of the CST detected by fiber tractography and unfavorable the clinical outcome and according to Schiemanck et al. [19] the size of acute infarction on neuroimaging studies may be used to estimate stroke outcome.

Also, a study of Alemam [20] confirmed that the larger the size of the ischemic cerebral stroke, the more the unfavorable outcome. Our result agreed also with Baird et al. [21] and Vogt et al. [22].

On the other hand, the results of Puig et al. [23] found no correlation between infarct volume and motor outcome and stated that motor deficit was present only when critical motor regions were involved, suggesting that large lesions do not necessarily predict poor outcome and that location of the lesion might be more predictive than its size. This could be explained by different methodologies and different sample sizes.

Limitations

Our study design has limitations. First, the main obstacle in this study was the small sample size and lack of resources. Second, we chose to use a short DTI sequence in order to minimize movement artifacts in the sample of moderately to severely impaired patients and to test the predictive value of DTI parameters acquired with a sequence that could be easily implemented in standard clinical settings (4:20 min scanning time). Third, the limited number of diffusion directions may hinder an appropriate modeling of multiple fibers per voxels (crossing fibers) at last DTI parameters used in the current study may be appropriate for clinical applications. Studies with higher resolution and isotropic voxels as well as greater number of diffusion directions would be needed to more accurately test the predictive value of tract-specific diffusivity measures [8].


  Conclusion Top


Reduction in FA value detected by DTI which affected acute ischemic stroke could help us visualize microstructural changes of CST fibers, not found in conventional MRI. We also noticed that most of the patients with good clinical recovery after 3 months had mild to moderate reduction in FA value.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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