Rostrocaudal Thickness on Sagittal Diffusion-weighted Imaging as a Predictor of Motor Deficits in an Acute Isolated Pontine Infarction Hidetaka Kato, MD,*† Takahiro Takeda, MD, PhD,*† Kuniko Ohara, MD, PhD,* Hideaki Tei, MD, PhD,* and Etsuko Nishizawa, MD, PhD*
Background: The relationship between infarct dimensions and neurologic severity in patients with acute pontine infarctions remains unclear. This study aimed to clarify the morphometric predictive value of magnetic resonance imaging for motor deficits in pontine infarction. Methods: Nineteen patients with an acute pontine infarction (12 males and 7 females, 70.6 6 13.5 years [mean age 6 SD]) had ventrodorsal length and rostrocaudal thickness and width retrospectively measured as parameters of infarct size on axial and sagittal diffusion-weighted imaging (DWI). Each patient’s functional score (FS) based on Brunnstrom scale (upper limb, hand, and lower limb) was assessed. The functional score of bulbar symptoms was coded as follows: 2, none; 1, dysarthria or dysphasia; and 0, both. The mean FS was compared with each infarct size parameter and the patients’ clinical features. Results: Rostrocaudal thickness on sagittal DWI was the parameter most closely correlated with FS (Spearman rank correlation coefficient (rs) 5 2.474, P 5 .040). However, there is apparently no association between FS and infarct size with correction for age. FS was most severe in patients with an atherothrombotic infarction; it was mildest in patients with a lacunar infarction (value of K [Kruskal–Wallis] 5 9.0, P 5 .015). Conclusions: The branch orifices of the pontine paramedian arteries could be narrowed by atheromatous plaques within the basilar artery. These atheromatous lesions involving multiple branching paramedian arteries probably cause rostrocaudally thick infarctions. A pontine infarction extending rostrocaudally along the corticospinal tract may cause severe motor impairments. Key Words: Branch atheromatous disease—diffusion-weighted image—pontine infarction—predictive value. Ó 2015 by National Stroke Association
From the *Department of Neurology, Todachuo General Hospital, Toda-shi; and †Department of Neurology, Tokyo Women’s Medical University, Tokyo, Japan. Received July 2, 2014; revision received October 20, 2014; accepted October 23, 2014. This study was not supported by grant funding. The authors report no competing interests. This study was approved by the Ethical Committee of Todachuo General Hospital. Informed consents were provided by the patients themselves or by their families. H.K and T.T. equally contributed to this work. Address correspondence to Takahiro Takeda, MD, PhD, Department of Neurology, Todachuo General Hospital, 1-19-3, Hon-cho, Toda-shi, Saitama 335-8555, Japan. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2015 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.10.012
622
Atherothrombotic infarctions (ATIs), branch atheromatous disease (BAD), and lacunar infarctions (LIs) are the most common subtypes of isolated pontine infarction.1-3 ATIs and BAD sometimes aggravate neurologic manifestations, whereas LI patients’ manifestations are usually not severe.4-8 A sophisticated previous report revealed that atherosclerotic pontine infarctions, including ATIs and BAD, are characterized by volume changes in the infarction’s subacute phase.9 However, the relationship between infarct size and neurologic severity has not been fully elucidated; it is difficult to predict neurologic severity from infarct size using conventional magnetic resonance imaging (MRI).9 To clarify, which parameters are predictive for motor deficits in patients with acute pontine infarctions, the
Journal of Stroke and Cerebrovascular Diseases, Vol. 24, No. 3 (March), 2015: pp 622-628
Location
Age Number Gender (y) 1
F
86
2
M
80
3
M
73
4
M
68
5
F
90
6
M
66
7
M
88
8
F
68
9 10
M M
63 92
11 12 13
F M M
70 77 54
14
M
64
15
F
57
Symptoms
Functional score
Duration Sagittal view Axial view Brunnstrom score from onset Rostrocaudal Ventrodorsal Ventrodorsal Rostrocaudal Ventrodorsal Upper Lower (days) Side level level Classification length thickness length Width limb Hand limb Bulbar Mean 1
Rt
Middle
V
ATI
16.2
8.8
14.7
7.4
2
2
2
0
1.5
1
Lt
Lower
VD
BAD
21.6
7.9
14.7
4.5
3
2
1
1
1.8
1
Rt
Lower
V
BAD
17.3
8.8
13.6
7.1
2
2
3
1
2.0
2
Rt
Middle
V
ATI
12.9
5.2
12.0
6.3
3
3
3
0
2.3
0
Lt
Middle
V
ATI
13.7
12.6
13.4
4.9
3
4
4
1
3.0
5
Lt
Lower
VD
BAD
17.8
8.2
15.9
4.4
3
3
5
1
3.0
3
Rt
Lower
VD
ATI
20.2
14.2
19.9
6.8
4
5
4
0
3.3
1
Rt
Lower
VD
LI
14.7
9.9
13.7
6.9
3
5
6
1
3.8
1 5
Lt Rt
Lower Upper
V V
LI BAD
12.7 17.9
8.8 11.4
8.6 14.5
5.1 13.2
4 4
5 5
5 5
2 2
4.0 4.0
2 0 4
Rt Lt Lt
Middle Upper Upper
VD V V
Unclassified LI BAD
22.0 12.8 15.4
8.5 6.0 7.9
12.0 7.4 15.0
6.5 4.4 7.1
5 6 6
5 5 5
4 5 6
2 2 1
4.0 4.5 4.5
0
Rt
Middle
VD
BAD
18.0
12.2
20.8
9.0
6
6
6
1
4.8
2
Lt
Lower
D
LI
13.1
5.5
13.7
3.8
6
6
6
1
4.8 623
Dysarthria, dysphagia, hemiparesis Dysarthria, hemiparesis Dysarthria, hemiparesis Dysarthria, dysphagia, hemiparesis, dysesthesia Dysarthria, hemiparesis Dysarthria, hemiparesis, dysesthesia Dysarthria, dysphagia, hemiparesis Dysarthria, hemiparesis, ataxia, dysesthesia Hemiparesis Hemiparesis, ataxia Hemiparesis Hemiparesis Hemiparesis, dysesthesia Dysarthria, hemiparesis, dysesthesia Dysarthria, dysesthesia
Infarct size (mm)
SAGITTAL DWI IN ACUTE PONTINE INFARCTION
Table 1. Clinical profile
H. KATO ET AL.
1.6 1.7 70.6 13.5 Mean S.D.
54 M 19
42 79 F F 17 18
Abbreviations: ATI, atherothrombotic infarction; BAD, branch atheromatous disease; D, dorsal; F, female; LI, lacunar infarction; Lt, left; M, male; Rt, right; V, ventral; VD, ventrodorsal.
3.7 1.2 4.6 1.5 4.6 1.5 15.7 3.8
8.2 2.8
13.5 3.9
6.4 2.6
4.4 1.5
1.3 .7
5.0 6 6 3
Lt
Lower
D
LI
12.0
4.8
9.8
3.3
6
2
5.0 5.0 2 2 6 6 6 6 0 0
Rt Lt
Middle Lower
D D
LI LI
7.7 12.8
4.7 5.6
7.1 9.8
4.6 3.8
6 6
5 M 16
70
Hemiparesis, dysesthesia, ataxia Dysesthesia Ataxia, dysesthesia Hemiparesis, dysesthesia
0
Lt
Middle
VD
BAD
20.4
5.6
19.5
11.7
6
6
2
4.8
624
ventrodorsal length, and rostrocaudal thickness and width, based on both axial and sagittal diffusionweighted imaging (DWI), were retrospectively measured and compared with the motor functional score (FS). The possible relationship of each parameter with motor severity was then examined.
Materials and Methods Patients diagnosed within 5 days of onset as having an acute isolated pontine infarction at Todachuo General Hospital from 2011 to 2014 were enrolled in this study. These criteria identified 12 men and 7 women (70.6 6 13.5 years) (Table 1). All 19 patients were free from motor impairments before the pontine infarction. The motor function of the upper limb, hand, and lower limb was scored in all participants using Brunnstrom scale.10 Bulbar symptoms were also scored as follows: 2, none; 1, dysarthria or dysphagia; and 0, both. These scores were evaluated within 5 days of onset. The mean FS was calculated from these scores. The classification, location, and size of the infarction were retrospectively surveyed. According to the Trial of Org 10172 in Acute Stroke Treatment classification and diagnostic criteria for BAD by Caplan,1,3,11 the pontine infarctions were classified into 4 subtypes: (1) ATI, defined as vertebrobasilar stenosis of more than 50% proximal to the DWI lesion; (2) BAD, defined as a DWI lesion extending to the pontine base surface; (3) LI, defined as a DWI lesion of less than 15 mm in the pons; and (4) an unclassified infarction. Cardiogenic embolisms were excluded. The pons was divided into 3 sections in the rostrocaudal direction (upper, middle, and lower pons; Fig 1, A) and 2 sections in the ventrodorsal direction (ventral and dorsal pons; Fig 1, B). The ventrodorsal length (maximum dimension in a direction perpendicular to the rostrocaudal axis) and rostrocaudal thickness (maximum dimension along the rostrocaudal axis) of each infarction were measured on sagittal DWI (Fig 1, C). The ventrodorsal length (maximum dimension along the ventrodorsal axis) and width (maximum dimension in a direction perpendicular to the ventrodorsal axis) of each infarction were measured on axial DWI (Fig 1, D). MRI was performed with a 1.5-T MR unit (MAGNE TOM Avanto; Siemens, Berlin and Munich, Germany) with echo planar capabilities. The parameters of the DWI were as follows: repetition time 5 3100 ms, echo time 5 79 ms, and a b-value of 1000 seconds/mm2. The slice thickness of the sagittal and axial DWI was 3 and 7 mm, respectively. The interslice gap was .45 mm and 1.05 mm, respectively (Fig 2). The reference plane for axial imaging was based on the orbitomeatal line and that for sagittal imaging was on the midline of the brain.
SAGITTAL DWI IN ACUTE PONTINE INFARCTION
625
Figure 1. Schematic representation of sagittal and axial views of the pons. The pons was longitudinally divided into 3 sections: upper, middle, and lower (A). The pons was also divided into 2 parts, dorsal and ventral, by a horizontal line located at the mid-distance between 2 tangents to the ventral and dorsal limits of the pons, respectively (B). The ventrodorsal length (a) and rostrocaudal diameter (thickness; b) were calculated on a sagittal view (C). The ventrodorsal length (c) and width (d) were also calculated on an axial view (D).
Three-dimensional time-of-flight magnetic resonance angiography at the level of the circle of Willis was performed with a repetition time 5 29 ms and echo time 5 7.15 ms. The parameters included a flip angle of 20 , matrix size of 320 3 320, and field of view of 160 mm (Fig 2). Statistical analyses were performed with the statistical program Ekuseru-Toukei 2012 (Social Survey Research Information Co, Ltd, Tokyo, Japan) and Microsoft Excel (Microsoft Corporation, Redmond, WA). Mann–Whitney and Kruskal–Wallis rank analyses were performed when comparing quantitative measures. The correlation was analyzed with Spearman rank correlation test. A partial correlation analysis for infarct size parameters and mean FS was performed with elimination of age as a factor. The impact of sex on infarct size was evaluated by multinominal logistic regression analysis. P less than .05 was regarded as significant.
Results The mean FS was significantly correlated with the rostrocaudal thickness of the pontine infarction (Spearman rank correlation coefficient (rs) 5 2.474, P 5 .040; Fig 3, B). The FS was not correlated with any other infarct size parameters (Fig 3, A,C,D). There was a significant correlation between age and mean FS (rs 5 2.527, P 5 .020; Fig 4, A). When age was eliminated as a factor, there was no remarkable statistical correlation between infarct size parameters and FS (sagittal ventrodorsal length versus mean FS: rs 5 2.152, P 5 .171; sagittal rostrocaudal thickness versus mean FS: rs 5 .005, P 5 .268; axial ventrodor-
sal length versus mean FS: rs 5 2.057, P 5 .458; axial width: rs 5 .191, P 5 .959). There were no differences in infarct size between sexes (sagittal ventrodorsal length: odds ratio, 1.117; 2-sided 95% confidence interval, .744-1.677), P 5 .593; sagittal rostrocaudal thickness: odds ratio, .837 (.495-1.412), P 5 .503; axial ventrodorsal length: odds ratio, 1.109 (.699-1.758), P 5.485; axial width: odds ratio, 1.239 (.679-2.259), P 5 .307. The duration from the onset to examination was not correlated with FS (rs 5 2.229, P 5 .346; Fig 4, B). In comparisons between the rostrocaudal levels of the infarction (upper, middle, and lower pons), there were no significant differences in mean FS (Fig 4, C). However, the mean FS was significantly higher in patients with a dorsally localized infarction than in those with the ventrally localized or ventrodorsal infarctions (value of K [Kruskal– Wallis] 5 8.5, P 5 .036, P 5 .025, respectively; Fig 4, D). The mean FS was higher in patients with LIs than in those with ATIs (K 5 9.0, P 5 .015; Fig 4, E). There were no significant differences in the mean FS between patients with BAD and those with LI and ATI (Fig 4, E).
Discussion Previous reports have shown that atherothrombotic pontine infarctions that occasionally cause deterioration of motor deficits are characterized by sequential infarction volume changes, but that their size is not necessarily linked to motor severity.9,12 Our approach using sagittal DWI methods demonstrated that the rostrocaudal thickness of a pontine infarction is most closely correlated with motor severity in the
626
H. KATO ET AL.
Figure 2. Sagittal and axial views on magnetic resonance imaging. Atherothrombotic infarction (ATI; A: case 4), lacunar infarction (LI; B: case 12), and branch atheromatous disease (BAD; C: case 16). Abbreviation: MRA, magnetic resonance angiography.
acute phase. A rostrocaudally thick infarction could damage the long segments of the corticospinal tract, which run through the pontine base in a rostrocaudal direction; motor severity is probably related to the length of damage along the corticospinal tract.13,14 The reason why the ventrodorsal length and width of the infarction was not necessarily correlated with FS was probably that the
corticospinal fibers run less densely through the pontine base.15 Long atherosclerotic changes in the basilar artery could involve multiple orifices of the perforating arteries branching from it. ATI and BAD occasionally involve long atherosclerotic changes and have a possibility of developing deteriorating neurologic manifestations.3 The present study also clarified that age is a facilitating factor
Figure 3. Plots of infarct diameter and mean functional scores (FSs). Ventrodorsal lengths (A, C) and width (D) were not significantly correlated with mean FS. Rostrocaudal length (thickness; B) and mean FS were significantly correlated (Spearman rank correlation coefficient (rs) 5 2.474, P 5 .040).*significant at P , .05
SAGITTAL DWI IN ACUTE PONTINE INFARCTION
627
Figure 4. Relationship between mean functional score (FS) and age, duration from onset, location, and classification. The mean FS was significantly correlated with age (rs 5 2.527, P 5.020; A) but not duration from onset (rs 5 2.229, P 5.346; B). There was no significant difference in mean FS by the longitudinal level of the infarct (C). The mean FS of the dorsally localized type (D) was higher than that of the ventrally localized type (V) and ventrodorsal type (VD) (value of K [Kruskal–Wallis] 5 8.5, P 5 .036, P 5 .025, respectively; D). The mean FS of lacunar infarcts was much higher than that of atherothrombotic infarcts (K 5 9.0, P 5 .015; E). *significant at P,.05
for motor deficits. It is probable that older patients have complications including silent, old, cerebral infarctions and/or cerebral atrophy. These complications possibly accelerate the deterioration of motor function in patients with pontine infarctions.16 Age is one of the greatest factors of functional disability in many neurologic diseases or conditions.17-19 Especially, small vessel disease more typically affects the aged persons.20 The present study revealed that infarct size parameters (including rostrocaudal thickness) were not significantly correlated with mean FS when age was eliminated as a factor. Further examination on a large scale should be performed to determine relationships between these factors.7,9 Conventional MRI on an axial cross-section can be useful for evaluating the whole brain. However, it is sometimes inadequate for the accurate evaluation of brainstem lesions because of the following: (1) the axis of the axial cross-section is not consistent in the brainstem and (2) the slice of an axial section is sometimes too thick to measure down to the appropriate resolution. It seems that an additional thinly sliced sagittal MRI is helpful for more accurate measurement or identification of brainstem infarctions (ie, their size and location). In conclusion, the present study clarified the relationship between rostrocaudal thickness of infarctions, measured by sagittal DWI, and motor impairments. How-
ever, the relationship with long-term prognosis of motor impairments could not be uncovered. It also remains unclear whether age influences infarction size parameters and motor severity. Further prospective investigations on a large scale are needed to identify more useful morphometric values for predicting the long-term prognosis of motor impairments with elimination of age as a factor. Awareness of these predictive values could be helpful for the identification of patients who need intensive treatment in the initial phase of pontine infarction.21 Acknowledgments: We are grateful to the radiological team of Todachuo General Hospital for their excellent technical assistance.
References 1. Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35-41. 2. Fisher CM, Caplan LR. Basilar artery branch occlusion: a cause of pontine infarction. Neurology 1971; 21:900-905. 3. Caplan LR. Intracranial branch atheromatous disease: a neglected, understudied, and underused concept. Neurology 1989;39:1246-1250.
628 4. Vemmos KN, Spengos K, Tsivgoulis G, et al. Aetiopathogenesis and long-term outcome of isolated pontine infarcts. J Neurol 2005;252:212-217. 5. Field TS, Benavente OR. Penetrating artery territory pontine infarction. Rev Neurol Dis 2011;8:30-38. 6. Kumral E, Bayulkem G, Evyapan D. Clinical spectrum of pontine infarction. Clinical-MRI correlations. J Neurol 2002;249:1659-1670. 7. Toyoda K, Saku Y, Ibayashi S, et al. Pontine infarction extending to the basal surface. Stroke 1994;25:2171-2178. 8. Hallevi H, Chernyshev OY, El Khoury R, et al. Intracranial atherosclerosis is associated with progression of neurological deficit in subcortical stroke. Cerebrovasc Dis 2012;33:64-68. 9. Kim JS, Cho KH, Kang DW, et al. Basilar artery atherosclerotic disease is related to subacute lesion volume increase in pontine base infarction. Acta Neurol Scand 2009;120:88-93. 10. Brunnstrom S. Recovery stages and evaluation procedures. In: Brunnstrom S, ed. Movement therapy in hemiplegia: a neurophysiological approach. New York: Harper & Row 1970:34-55. 11. Lee LJ, Kidwell CS, Alger J, et al. Impact on stroke subtype diagnosis of early diffusion-weighted magnetic resonance imaging and magnetic resonance angiography. Stroke 2000;31:1081-1089. 12. Saia V, Pantoni L. Progressive stroke in pontine infarction. Acta Neurol Scand 2009;120:213-215.
H. KATO ET AL. 13. Jang SH, Bai D, Son SM, et al. Motor outcome prediction using diffusion tensor tractography in pontine infarct. Ann Neurol 2008;64:460-465. 14. Groisser BN, Copen WA, Singhal AB, et al. Corticospinal tract diffusion abnormalities early after stroke predict motor outcome. Neurorehabil Neural Repair 2014; 28:751-760. 15. Seo JP, Jang SH. Characteristics of corticospinal tract area according to pontine level. Yonsei Med J 2013;54:785-787. 16. Gauthier LV, Taub E, Mark VW, et al. Atrophy of spared gray matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke. Stroke 2012; 43:453-457. 17. Lenehan B, Street J, O’Toole P, et al. Central cord syndrome in Ireland: the effect of age on clinical outcome. Eur Spine J 2009;18:1458-1463. 18. Weier K, Penner IK, Magon S, et al. Cerebellar abnormalities contribute to disability including cognitive impairment in multiple sclerosis. PLoS One 2014;9:e86916. 19. Grueter BE, Schulz UG. Age-related cerebral white matter disease (leukoaraiosis): a review. Postgrad Med J 2012;88:79-87. 20. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010;9:689-701. 21. Deguchi I, Hayashi T, Kato Y, et al. Treatment outcomes of tissue plasminogen activator infusion for branch atheromatous disease. J Stroke Cerebrovasc Dis 2013;22:e168-172.
Background: The relationship between infarct dimensions and neurologic severity in patients with acute pontine infarctions remains unclear. This study aimed to clarify the morphometric predictive value of magnetic resonance imaging for motor deficits in pontine infarction. Methods: Nineteen patients with an acute pontine infarction (12 males and 7 females, 70.6 6 13.5 years [mean age 6 SD]) had ventrodorsal length and rostrocaudal thickness and width retrospectively measured as parameters of infarct size on axial and sagittal diffusion-weighted imaging (DWI). Each patient’s functional score (FS) based on Brunnstrom scale (upper limb, hand, and lower limb) was assessed. The functional score of bulbar symptoms was coded as follows: 2, none; 1, dysarthria or dysphasia; and 0, both. The mean FS was compared with each infarct size parameter and the patients’ clinical features. Results: Rostrocaudal thickness on sagittal DWI was the parameter most closely correlated with FS (Spearman rank correlation coefficient (rs) 5 2.474, P 5 .040). However, there is apparently no association between FS and infarct size with correction for age. FS was most severe in patients with an atherothrombotic infarction; it was mildest in patients with a lacunar infarction (value of K [Kruskal–Wallis] 5 9.0, P 5 .015). Conclusions: The branch orifices of the pontine paramedian arteries could be narrowed by atheromatous plaques within the basilar artery. These atheromatous lesions involving multiple branching paramedian arteries probably cause rostrocaudally thick infarctions. A pontine infarction extending rostrocaudally along the corticospinal tract may cause severe motor impairments. Key Words: Branch atheromatous disease—diffusion-weighted image—pontine infarction—predictive value. Ó 2015 by National Stroke Association
From the *Department of Neurology, Todachuo General Hospital, Toda-shi; and †Department of Neurology, Tokyo Women’s Medical University, Tokyo, Japan. Received July 2, 2014; revision received October 20, 2014; accepted October 23, 2014. This study was not supported by grant funding. The authors report no competing interests. This study was approved by the Ethical Committee of Todachuo General Hospital. Informed consents were provided by the patients themselves or by their families. H.K and T.T. equally contributed to this work. Address correspondence to Takahiro Takeda, MD, PhD, Department of Neurology, Todachuo General Hospital, 1-19-3, Hon-cho, Toda-shi, Saitama 335-8555, Japan. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2015 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.10.012
622
Atherothrombotic infarctions (ATIs), branch atheromatous disease (BAD), and lacunar infarctions (LIs) are the most common subtypes of isolated pontine infarction.1-3 ATIs and BAD sometimes aggravate neurologic manifestations, whereas LI patients’ manifestations are usually not severe.4-8 A sophisticated previous report revealed that atherosclerotic pontine infarctions, including ATIs and BAD, are characterized by volume changes in the infarction’s subacute phase.9 However, the relationship between infarct size and neurologic severity has not been fully elucidated; it is difficult to predict neurologic severity from infarct size using conventional magnetic resonance imaging (MRI).9 To clarify, which parameters are predictive for motor deficits in patients with acute pontine infarctions, the
Journal of Stroke and Cerebrovascular Diseases, Vol. 24, No. 3 (March), 2015: pp 622-628
Location
Age Number Gender (y) 1
F
86
2
M
80
3
M
73
4
M
68
5
F
90
6
M
66
7
M
88
8
F
68
9 10
M M
63 92
11 12 13
F M M
70 77 54
14
M
64
15
F
57
Symptoms
Functional score
Duration Sagittal view Axial view Brunnstrom score from onset Rostrocaudal Ventrodorsal Ventrodorsal Rostrocaudal Ventrodorsal Upper Lower (days) Side level level Classification length thickness length Width limb Hand limb Bulbar Mean 1
Rt
Middle
V
ATI
16.2
8.8
14.7
7.4
2
2
2
0
1.5
1
Lt
Lower
VD
BAD
21.6
7.9
14.7
4.5
3
2
1
1
1.8
1
Rt
Lower
V
BAD
17.3
8.8
13.6
7.1
2
2
3
1
2.0
2
Rt
Middle
V
ATI
12.9
5.2
12.0
6.3
3
3
3
0
2.3
0
Lt
Middle
V
ATI
13.7
12.6
13.4
4.9
3
4
4
1
3.0
5
Lt
Lower
VD
BAD
17.8
8.2
15.9
4.4
3
3
5
1
3.0
3
Rt
Lower
VD
ATI
20.2
14.2
19.9
6.8
4
5
4
0
3.3
1
Rt
Lower
VD
LI
14.7
9.9
13.7
6.9
3
5
6
1
3.8
1 5
Lt Rt
Lower Upper
V V
LI BAD
12.7 17.9
8.8 11.4
8.6 14.5
5.1 13.2
4 4
5 5
5 5
2 2
4.0 4.0
2 0 4
Rt Lt Lt
Middle Upper Upper
VD V V
Unclassified LI BAD
22.0 12.8 15.4
8.5 6.0 7.9
12.0 7.4 15.0
6.5 4.4 7.1
5 6 6
5 5 5
4 5 6
2 2 1
4.0 4.5 4.5
0
Rt
Middle
VD
BAD
18.0
12.2
20.8
9.0
6
6
6
1
4.8
2
Lt
Lower
D
LI
13.1
5.5
13.7
3.8
6
6
6
1
4.8 623
Dysarthria, dysphagia, hemiparesis Dysarthria, hemiparesis Dysarthria, hemiparesis Dysarthria, dysphagia, hemiparesis, dysesthesia Dysarthria, hemiparesis Dysarthria, hemiparesis, dysesthesia Dysarthria, dysphagia, hemiparesis Dysarthria, hemiparesis, ataxia, dysesthesia Hemiparesis Hemiparesis, ataxia Hemiparesis Hemiparesis Hemiparesis, dysesthesia Dysarthria, hemiparesis, dysesthesia Dysarthria, dysesthesia
Infarct size (mm)
SAGITTAL DWI IN ACUTE PONTINE INFARCTION
Table 1. Clinical profile
H. KATO ET AL.
1.6 1.7 70.6 13.5 Mean S.D.
54 M 19
42 79 F F 17 18
Abbreviations: ATI, atherothrombotic infarction; BAD, branch atheromatous disease; D, dorsal; F, female; LI, lacunar infarction; Lt, left; M, male; Rt, right; V, ventral; VD, ventrodorsal.
3.7 1.2 4.6 1.5 4.6 1.5 15.7 3.8
8.2 2.8
13.5 3.9
6.4 2.6
4.4 1.5
1.3 .7
5.0 6 6 3
Lt
Lower
D
LI
12.0
4.8
9.8
3.3
6
2
5.0 5.0 2 2 6 6 6 6 0 0
Rt Lt
Middle Lower
D D
LI LI
7.7 12.8
4.7 5.6
7.1 9.8
4.6 3.8
6 6
5 M 16
70
Hemiparesis, dysesthesia, ataxia Dysesthesia Ataxia, dysesthesia Hemiparesis, dysesthesia
0
Lt
Middle
VD
BAD
20.4
5.6
19.5
11.7
6
6
2
4.8
624
ventrodorsal length, and rostrocaudal thickness and width, based on both axial and sagittal diffusionweighted imaging (DWI), were retrospectively measured and compared with the motor functional score (FS). The possible relationship of each parameter with motor severity was then examined.
Materials and Methods Patients diagnosed within 5 days of onset as having an acute isolated pontine infarction at Todachuo General Hospital from 2011 to 2014 were enrolled in this study. These criteria identified 12 men and 7 women (70.6 6 13.5 years) (Table 1). All 19 patients were free from motor impairments before the pontine infarction. The motor function of the upper limb, hand, and lower limb was scored in all participants using Brunnstrom scale.10 Bulbar symptoms were also scored as follows: 2, none; 1, dysarthria or dysphagia; and 0, both. These scores were evaluated within 5 days of onset. The mean FS was calculated from these scores. The classification, location, and size of the infarction were retrospectively surveyed. According to the Trial of Org 10172 in Acute Stroke Treatment classification and diagnostic criteria for BAD by Caplan,1,3,11 the pontine infarctions were classified into 4 subtypes: (1) ATI, defined as vertebrobasilar stenosis of more than 50% proximal to the DWI lesion; (2) BAD, defined as a DWI lesion extending to the pontine base surface; (3) LI, defined as a DWI lesion of less than 15 mm in the pons; and (4) an unclassified infarction. Cardiogenic embolisms were excluded. The pons was divided into 3 sections in the rostrocaudal direction (upper, middle, and lower pons; Fig 1, A) and 2 sections in the ventrodorsal direction (ventral and dorsal pons; Fig 1, B). The ventrodorsal length (maximum dimension in a direction perpendicular to the rostrocaudal axis) and rostrocaudal thickness (maximum dimension along the rostrocaudal axis) of each infarction were measured on sagittal DWI (Fig 1, C). The ventrodorsal length (maximum dimension along the ventrodorsal axis) and width (maximum dimension in a direction perpendicular to the ventrodorsal axis) of each infarction were measured on axial DWI (Fig 1, D). MRI was performed with a 1.5-T MR unit (MAGNE TOM Avanto; Siemens, Berlin and Munich, Germany) with echo planar capabilities. The parameters of the DWI were as follows: repetition time 5 3100 ms, echo time 5 79 ms, and a b-value of 1000 seconds/mm2. The slice thickness of the sagittal and axial DWI was 3 and 7 mm, respectively. The interslice gap was .45 mm and 1.05 mm, respectively (Fig 2). The reference plane for axial imaging was based on the orbitomeatal line and that for sagittal imaging was on the midline of the brain.
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Figure 1. Schematic representation of sagittal and axial views of the pons. The pons was longitudinally divided into 3 sections: upper, middle, and lower (A). The pons was also divided into 2 parts, dorsal and ventral, by a horizontal line located at the mid-distance between 2 tangents to the ventral and dorsal limits of the pons, respectively (B). The ventrodorsal length (a) and rostrocaudal diameter (thickness; b) were calculated on a sagittal view (C). The ventrodorsal length (c) and width (d) were also calculated on an axial view (D).
Three-dimensional time-of-flight magnetic resonance angiography at the level of the circle of Willis was performed with a repetition time 5 29 ms and echo time 5 7.15 ms. The parameters included a flip angle of 20 , matrix size of 320 3 320, and field of view of 160 mm (Fig 2). Statistical analyses were performed with the statistical program Ekuseru-Toukei 2012 (Social Survey Research Information Co, Ltd, Tokyo, Japan) and Microsoft Excel (Microsoft Corporation, Redmond, WA). Mann–Whitney and Kruskal–Wallis rank analyses were performed when comparing quantitative measures. The correlation was analyzed with Spearman rank correlation test. A partial correlation analysis for infarct size parameters and mean FS was performed with elimination of age as a factor. The impact of sex on infarct size was evaluated by multinominal logistic regression analysis. P less than .05 was regarded as significant.
Results The mean FS was significantly correlated with the rostrocaudal thickness of the pontine infarction (Spearman rank correlation coefficient (rs) 5 2.474, P 5 .040; Fig 3, B). The FS was not correlated with any other infarct size parameters (Fig 3, A,C,D). There was a significant correlation between age and mean FS (rs 5 2.527, P 5 .020; Fig 4, A). When age was eliminated as a factor, there was no remarkable statistical correlation between infarct size parameters and FS (sagittal ventrodorsal length versus mean FS: rs 5 2.152, P 5 .171; sagittal rostrocaudal thickness versus mean FS: rs 5 .005, P 5 .268; axial ventrodor-
sal length versus mean FS: rs 5 2.057, P 5 .458; axial width: rs 5 .191, P 5 .959). There were no differences in infarct size between sexes (sagittal ventrodorsal length: odds ratio, 1.117; 2-sided 95% confidence interval, .744-1.677), P 5 .593; sagittal rostrocaudal thickness: odds ratio, .837 (.495-1.412), P 5 .503; axial ventrodorsal length: odds ratio, 1.109 (.699-1.758), P 5.485; axial width: odds ratio, 1.239 (.679-2.259), P 5 .307. The duration from the onset to examination was not correlated with FS (rs 5 2.229, P 5 .346; Fig 4, B). In comparisons between the rostrocaudal levels of the infarction (upper, middle, and lower pons), there were no significant differences in mean FS (Fig 4, C). However, the mean FS was significantly higher in patients with a dorsally localized infarction than in those with the ventrally localized or ventrodorsal infarctions (value of K [Kruskal– Wallis] 5 8.5, P 5 .036, P 5 .025, respectively; Fig 4, D). The mean FS was higher in patients with LIs than in those with ATIs (K 5 9.0, P 5 .015; Fig 4, E). There were no significant differences in the mean FS between patients with BAD and those with LI and ATI (Fig 4, E).
Discussion Previous reports have shown that atherothrombotic pontine infarctions that occasionally cause deterioration of motor deficits are characterized by sequential infarction volume changes, but that their size is not necessarily linked to motor severity.9,12 Our approach using sagittal DWI methods demonstrated that the rostrocaudal thickness of a pontine infarction is most closely correlated with motor severity in the
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Figure 2. Sagittal and axial views on magnetic resonance imaging. Atherothrombotic infarction (ATI; A: case 4), lacunar infarction (LI; B: case 12), and branch atheromatous disease (BAD; C: case 16). Abbreviation: MRA, magnetic resonance angiography.
acute phase. A rostrocaudally thick infarction could damage the long segments of the corticospinal tract, which run through the pontine base in a rostrocaudal direction; motor severity is probably related to the length of damage along the corticospinal tract.13,14 The reason why the ventrodorsal length and width of the infarction was not necessarily correlated with FS was probably that the
corticospinal fibers run less densely through the pontine base.15 Long atherosclerotic changes in the basilar artery could involve multiple orifices of the perforating arteries branching from it. ATI and BAD occasionally involve long atherosclerotic changes and have a possibility of developing deteriorating neurologic manifestations.3 The present study also clarified that age is a facilitating factor
Figure 3. Plots of infarct diameter and mean functional scores (FSs). Ventrodorsal lengths (A, C) and width (D) were not significantly correlated with mean FS. Rostrocaudal length (thickness; B) and mean FS were significantly correlated (Spearman rank correlation coefficient (rs) 5 2.474, P 5 .040).*significant at P , .05
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Figure 4. Relationship between mean functional score (FS) and age, duration from onset, location, and classification. The mean FS was significantly correlated with age (rs 5 2.527, P 5.020; A) but not duration from onset (rs 5 2.229, P 5.346; B). There was no significant difference in mean FS by the longitudinal level of the infarct (C). The mean FS of the dorsally localized type (D) was higher than that of the ventrally localized type (V) and ventrodorsal type (VD) (value of K [Kruskal–Wallis] 5 8.5, P 5 .036, P 5 .025, respectively; D). The mean FS of lacunar infarcts was much higher than that of atherothrombotic infarcts (K 5 9.0, P 5 .015; E). *significant at P,.05
for motor deficits. It is probable that older patients have complications including silent, old, cerebral infarctions and/or cerebral atrophy. These complications possibly accelerate the deterioration of motor function in patients with pontine infarctions.16 Age is one of the greatest factors of functional disability in many neurologic diseases or conditions.17-19 Especially, small vessel disease more typically affects the aged persons.20 The present study revealed that infarct size parameters (including rostrocaudal thickness) were not significantly correlated with mean FS when age was eliminated as a factor. Further examination on a large scale should be performed to determine relationships between these factors.7,9 Conventional MRI on an axial cross-section can be useful for evaluating the whole brain. However, it is sometimes inadequate for the accurate evaluation of brainstem lesions because of the following: (1) the axis of the axial cross-section is not consistent in the brainstem and (2) the slice of an axial section is sometimes too thick to measure down to the appropriate resolution. It seems that an additional thinly sliced sagittal MRI is helpful for more accurate measurement or identification of brainstem infarctions (ie, their size and location). In conclusion, the present study clarified the relationship between rostrocaudal thickness of infarctions, measured by sagittal DWI, and motor impairments. How-
ever, the relationship with long-term prognosis of motor impairments could not be uncovered. It also remains unclear whether age influences infarction size parameters and motor severity. Further prospective investigations on a large scale are needed to identify more useful morphometric values for predicting the long-term prognosis of motor impairments with elimination of age as a factor. Awareness of these predictive values could be helpful for the identification of patients who need intensive treatment in the initial phase of pontine infarction.21 Acknowledgments: We are grateful to the radiological team of Todachuo General Hospital for their excellent technical assistance.
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