‘‘Invisible’’ Brain Stem Infarction at the First Day Yohei Tsuyusaki, MD,* Ryuji Sakakibara, MD, PhD,* Masahiko Kishi, MD, PhD,* Fuyuki Tateno, MD,* Yosuke Aiba, MD,* Tsuyoshi Ogata, BSc,* Takeki Nagao, MD, PhD,† Hitoshi Terada, MD, PhD,‡ and Tsutomu Inaoka, MD, PhD‡
Background: In specific stroke cases, serial diffusion-weighted magnetic resonance imaging (DW MRI) on day 1 was unable to show a lesion, whereas that on day 4 and later clearly revealed a lesion. However, clinical features of this phenomenon (‘‘invisible’’ brain stem infarction [IBI] at the first day) have not been fully delineated. Methods: We retrospectively recruited 212 stroke patients in the Emergency Unit and Neurology Department. Among these, we studied patients with IBI. Definition of IBI is that acute and clear brain stem symptoms/signs on arrival were ameliorated at discharge and appearance of high signal intensity on serial DW images with low apparent diffusion coefficient (ADC) by 1.5 T MRI with 2-mm slices. Results: IBI were found in only 6 patients. Day 1 invisible stroke was found only in the brain stem (17%, 6 of 35) but none (0 of 177) in the hemispheric infarction (P , .05). In most patients with IBI, DW MRI turned out visible at the third/fourth day. Before the fourth day, DW/ADC signal changes in patients with IBI were minimal. In IBI, lesion size (mean 2.7 mm2) was smaller than that of visible cases (mean 7.3 mm2). In IBI, lesion location was mostly at the dorsolateral medulla. In IBI, sensory disturbance was significantly more common (67%) than visible cases (24%; P , .05), whereas dysarthria was less common (0%; P , .01) than visible cases (66%; P ,.01). Conclusions: It is likely that patients with smaller stroke volume, sensory disturbance, and medullary location are prone to develop IBI. When evaluating stroke using MRI criteria, recognition of IBI is important to start early management. Key Words: Stroke—brain stem—magnetic resonance imaging— diffusion-weighted image. Ó 2014 by National Stroke Association
From the *Department of Neurology, Internal Medicine, Sakura Medical Center, Toho University, Sakura; †Department of Neurosurgery, Sakura Medical Center, Toho University, Sakura; and ‡Department of Radiology, Sakura Medical Center, Toho University, Sakura, Japan. Received January 25, 2014; revision received February 3, 2014; accepted February 11, 2014. Author contributions: Y.T. has a role in acquisition of subjects and/or data analysis and interpretation of data. R.S. has a role in the study concept, design, acquisition of subjects and/or data analysis, interpretation of data, and preparation of the manuscript. M.K., F.T., T.O., T.N., H.T., and T.I. have a role in the acquisition of subjects and/or data analysis. Conflict of interest: None of the authors have conflict of interest. Funding: None declared. Address correspondence to Ryuji Sakakibara, MD, PhD, Department of Neurology, Internal Medicine, Sakura Medical Center, Toho University, 564-1 Shimoshizu, Sakura 285-8741, Japan. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2014 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.02.010
Introduction It is well recognized that diffusion-weighted magnetic resonance imaging (DW MRI) is a sensitive and specific technique for imaging acute hemispheric infarction. In contrast, its utility in the diagnosis of acute brain stem infarction has not been fully established.1,2 This is because in specific cases, serial DW MRI on day 1 was unable to show a lesion, whereas that on day 4 and later clearly revealed a lesion. This phenomenon (‘‘invisible’’ brain stem infarction [IBI] at the first day) occurs with a discrete lesion at dorsolateral medulla (presenting isolated vertigo,3 isolated hemiataxia,4 Wallenberg syndrome,5-9 or Avellis syndrome8), dorsal pons (isolated internuclear ophthalmoplegia,10 or Millard–Gubler syndrome8), and basal midbrain (Weber syndrome8). Recognition of IBI in clinical practice is extremely important
Journal of Stroke and Cerebrovascular Diseases, Vol. -, No. - (---), 2014: pp 1-5
1
Y. TSUYUSAKI ET AL.
2
Figure 1. Frequency of day 1 invisible stroke on diffusion-weighted magnetic resonance imaging (DW MRI) among hemispheric and brain stem stroke. Frequency of day 1 invisible stroke on DW MRI in brain stem stroke was 17%, which was significantly higher than none in the hemispheric stroke (P , .05).
because anticoagulation and neuroprotection should start as early as possible. However, it remains unclear whether specific neurologic symptom, lesion location, or lesion size is related with IBI and what is the putative mechanism of IBI. Here, we systematically investigated IBI in our neurologic emergency cases.
Methods In total, 212 patients with acute cerebral infarction including IBI were enrolled who visited our neurologic emergency room during a 4-year period. The inclusion diagnostic criteria of IBI were (1) acute and clear brain stem symptoms/signs on arrival that were ameliorated at discharge, even though they were subtle (isolated vertigo,3 isolated hemiataxia,4 etc.), and (2) appearance of high signal intensity on serial DW images with low
apparent diffusion coefficient (ADC), in addition to further appearance of high signal intensity on serial T2weighted/fluid-attenuated inversion recovery images. The exclusion criteria were (1) diffuse CNS diseases, such as encephalitis or systemic diseases (hypoxia, hyperglycemic coma, extreme hypertension, etc.), (2) drug abuse, and (3) focal central nervous system diseases other than stroke, etc. In all patients, we performed brain MRI and a laboratory test on arrival. To augment neurologic diagnosis, we performed additional electrophysiologic tests (auditory/somatosensory evoked potentials, etc.), neuro-otological tests (eye-tracking/visual suppression tests, etc.), and neuro-ophthalmological tests (Hess/binocular tests, etc.) to the extent possible. All 212 patients underwent MRI examinations on a 1.5 T Gyroscan (Philips, Best, The Netherlands). In addition to DW images with 2-mm-thick slices and .5 mm gap for infratentorial and
Figure 2. (A) Time course of diffusion-weighted magnetic resonance imaging (DW MRI) of day 1 invisible brain stem stroke. Typical case of DW MRI of day 1 invisible brain stem stroke (upper panel, day 1, lower panel, day 4). (B) Time course of DW MRI of day 1 invisible brain stem stroke. In 4 of 6 cases (67%), DW image became visible at the third/fourth day; in 1 case, it became visible at 18 hours; in 1 case, it became visible at a certain time between the 3rd day and the 19th day. Invisible, open square; visible, closed square.
INVISIBLE BRAIN STEM INFARCTION
3
Figure 3. Time course of DW MRI of day 1 invisible brain stem stroke. In comparison with differences (with that in the contralateral lesion side) in signal intensity of the DW image (high) and ADC (low) of day 1 visible cases (bars at the right side), differences in signal intensity of the DW image and ADC of day 1 invisible cases were smaller particularly at the first day of stroke onset (not statistically significant). Abbreviations: ADC, apparent diffusion coefficient; DW MRI, diffusion-weighted magnetic resonance imaging.
4-mm-thick slices for supratentorial structures, we obtained T1-weighted, T2-weighted, fluid-attenuated inversion recovery and T2* images, MR angiography, and arterial spin labeling perfusion images. All subjects provided informed consent to participate. The study was conducted according to the principles of the Declaration of Helsinki.
Results All 235 patients included 146 men and 89 women (age, 70.5 6 12.2 years [mean 6 standard deviation]). IBI were found in only 6 patients, slightly younger age (53.8 6 17.8 years) and male predominance (5 men and 1 women; not statistically significant). Only in the brain stem (17%, 6 of 35) but none (0 of 177) in the hemispheric, in any type of lacunar, atherosclerotic, and cardioembolic strokes (P , .05; Fig 1). In most patients with IBI, DW MR image turned out visible at the third or fourth day (Fig 2). Before the fourth day, DW/ADC signal changes in patients with IBI were minimal (Fig 3). In IBI, lesion size (mean 2.7 mm2) was smaller than that of visible cases (mean 7.3 mm2; not statistically significant; Fig 4). In IBI, lesion location was mostly at the dorsolateral medulla (Fig 5). This is in contrast to common pontine lesion in visible cases. In IBI, sensory disturbance was significantly more common (67%) than visible cases (24%; P , .05), whereas dysarthria was less common (0%; P , .01) than visible cases (66%; P , .01).
Discussion Figure 4. Lesion size of day 1 visible/invisible brain stem stroke on diffusion-weighted magnetic resonance imaging. Among brain stem strokes, final area of lesion of day 1 invisible cases was smaller than that of day 1 visible cases (not statistically significant).
As shown earlier, as compared with visible cases, patients with IBI presented with distinct clinical imaging abnormalities. It is striking that day 1 invisible infarction was found only in the brain stem (17%) but none in the
4
Y. TSUYUSAKI ET AL.
Figure 5. Lesion location and symptom of day 1 visible/invisible brain stem stroke on DW MRI. (Upper panel) Among brain stem strokes, lesion location of day 1 invisible cases was mostly dorsolateral medulla. This is in contrast to common pontine lesion in day 1 visible cases. (Lower panel) Among brain stem strokes, looking at the neurologic symptoms, sensory disturbance in day 1 invisible cases was significantly more common (67%) than that in day 1 visible cases (24%; P , .05). Speech disturbance in day 1 invisible cases was less common (0%; P , .01) than that in day 1 visible cases (66%; P , .01). Abbreviations: DW MRI, diffusion-weighted magnetic resonance imaging; ns, not significant.
hemispheric (P ,.05) in the present study. Previous study results5-9 are the same with ours in that brain stem alone may present with invisible infarction. The frequency of IBI among brain stem infarction in the study was 17% (6 of 35). This is lower than 33% (10 of 30) by Krasnianski et al.8 The exact reason of difference remains unclear, but it may depend on different signal sequences and MRI machine we used. Axer et al11 described relative DW image and ADC time course in a longer window than ours. Alteration of relative DW image and ADC in brain stem infarction had their peak at around day 4, which is delayed as compared with those in the hemispheric infarction. Among brain stem infarctions, as expected, lesion size in IBI was smaller than that of visible cases (around 3 mm2). Among IBI lesion sites, dorsolateral medulla was the most common, which was in accordance with the previous studies. Clinically, dorsolateral medullary lesion may present with isolated vertigo,3 isolated hemiataxia,4 and Wallenberg syndrome as the full neurologic syndrome.5-9 According to this, in IBI, sensory disturbance
was more common (67%; P , .05), whereas dysarthria was less common (0%; P , .01) than that in visible cases. Therefore, particularly in patients with acute sensory disturbance, forme fruste of Wallenberg syndrome should always be explored by MRI. The exact reason why invisible stroke at the first day preferentially occurs in the brain stem, particularly in the dorsolateral medulla, remains unclear. One explanation is that because nuclei and fibers are dense within the brain stem, even smaller lesion presents with distinct neurologic dysfunction that brought patients to clinic. Another explanation is that small infarct volume as seen in IBI might be sensitive to partial volume effects and also affected by the skull base.11 Other explanation is that IBI may reflect a slower metabolic and perfusion change in watershed brain stem infarcts compared with thromboembolic hemispheric infarcts.12 Previously different ischemic tolerance between brain stem and hemisphere has not fully been explored. However, it is reported that in mouse brain, immunostaining of neuroglobin, an endogenous ischemia-protecting substance, is
INVISIBLE BRAIN STEM INFARCTION
weak in the cerebral cortex, whereas strong labeling is observed in the brain stem nuclei.13 Furthermore, better vascular collateralization, early reperfusion, and smaller lesion size in IBI may relate to situations of delayed cell death that occur in areas of milder ischemic injury for days after the initial ischemic event.14 Limitations of this study include that MRI we used is 1.5 T with a 2-mm-thick slice; therefore, using higher magnetic fields (3-4 T) with thinner slices, frequency of IBI among brain stem infarction may become smaller. However, even though, when evaluating stroke using MRI criteria, recognition of IBI is extremely important because early administration of antithrombotic/neuroprotective therapy are necessary to maximize stroke outcome.
Conclusion In conclusion, using 1.5 T MRI, the frequency of IBI at the first day was 17%, which was significantly higher than hemispheric infarction. It is likely that patients with smaller stroke volume, sensory disturbance, and medullary location are prone to develop IBI. When evaluating stroke using MRI criteria, recognition of IBI is extremely important to start early management.
References 1. Querol-Pascual MR. Clinical approach to brainstem lesions. Semin Ultrasound CT MRI 2010;31:220-229. 2. Alvarez-Linera J. Magnetic resonance techniques for the brainstem. Semin Ultrasound CT MRI 2010;31: 230-245.
5 3. Kishi M, Sakakibara R, Nomura T, et al. Lateral medullary infarction presenting as isolated vertigo and unilateral loss of visual suppression. Neurol Sci 2012; 33:129-132. 4. Kishi M, Sakakibara R, Nagao T, et al. Isolated hemiataxia and cerebellar diaschisis after a small dorsolateral medullary infarct. Case Rep Neurol 2009;1:41-46. 5. Begemann M, Silvers A, Tang C, et al. Delayed signal detection by diffusion-weighted imaging in brainstem infarction. J Stroke Cerebrovasc Dis 2001;10:284-289. 6. Frey LC, Sung GY, Tanabe J. Early false-negative diffusion-weighted imaging in brainstem infarction. J Stroke Cerebrovasc Dis 2002;11:51-53. 7. K€ uker W, Weise J, Krapf H, et al. MRI characteristics of acute and subacute brainstem and thalamic infarctions: value of T2- and diffusion-weighted sequences. J Neurol 2002;249:33-42. 8. Krasnianski M, Lindner A, Zierz S. Brainstem infarctions with normal MRI. Eur J Med Res 2002;7:125-127. 9. Kitis O, Calli C, Yunten N, et al. Wallenberg’s lateral medullary syndrome: diffusion-weighted imaging findings. Acta Radiol 2004;45:78-84. 10. Ogawa E, Sakakibara R, Kishi M, et al. Pure isolated internuclear ophthalmoplegia. Intern Med 2011;50:1785. 11. Axer H, Grael D, Bramer D, et al. Time course of diffusion imaging in acute brainstem infarcts. J Magn Reson Imaging 2007;26:905-912. 12. Huang I-J, Chen C-Y, Chang D-C, et al. Time course of cerebral infarction in the middle arterial territory: deep watershed versus territorial subtypes on diffusionweighted MR images. Radiology 2001;221:35-42. 13. Wystub S, Laufs T, Schmidt M, et al. Localization of neuroglobin protein in the mouse brain. Neurosci Lett 2003; 346:114-116. 14. Pulera MR, Adams LM, Liu H, et al. Apoptosis in a neonatal rat model of cerebral hypoxia-ischemia. Stroke 1998;29:2622-2630.
Background: In specific stroke cases, serial diffusion-weighted magnetic resonance imaging (DW MRI) on day 1 was unable to show a lesion, whereas that on day 4 and later clearly revealed a lesion. However, clinical features of this phenomenon (‘‘invisible’’ brain stem infarction [IBI] at the first day) have not been fully delineated. Methods: We retrospectively recruited 212 stroke patients in the Emergency Unit and Neurology Department. Among these, we studied patients with IBI. Definition of IBI is that acute and clear brain stem symptoms/signs on arrival were ameliorated at discharge and appearance of high signal intensity on serial DW images with low apparent diffusion coefficient (ADC) by 1.5 T MRI with 2-mm slices. Results: IBI were found in only 6 patients. Day 1 invisible stroke was found only in the brain stem (17%, 6 of 35) but none (0 of 177) in the hemispheric infarction (P , .05). In most patients with IBI, DW MRI turned out visible at the third/fourth day. Before the fourth day, DW/ADC signal changes in patients with IBI were minimal. In IBI, lesion size (mean 2.7 mm2) was smaller than that of visible cases (mean 7.3 mm2). In IBI, lesion location was mostly at the dorsolateral medulla. In IBI, sensory disturbance was significantly more common (67%) than visible cases (24%; P , .05), whereas dysarthria was less common (0%; P , .01) than visible cases (66%; P ,.01). Conclusions: It is likely that patients with smaller stroke volume, sensory disturbance, and medullary location are prone to develop IBI. When evaluating stroke using MRI criteria, recognition of IBI is important to start early management. Key Words: Stroke—brain stem—magnetic resonance imaging— diffusion-weighted image. Ó 2014 by National Stroke Association
From the *Department of Neurology, Internal Medicine, Sakura Medical Center, Toho University, Sakura; †Department of Neurosurgery, Sakura Medical Center, Toho University, Sakura; and ‡Department of Radiology, Sakura Medical Center, Toho University, Sakura, Japan. Received January 25, 2014; revision received February 3, 2014; accepted February 11, 2014. Author contributions: Y.T. has a role in acquisition of subjects and/or data analysis and interpretation of data. R.S. has a role in the study concept, design, acquisition of subjects and/or data analysis, interpretation of data, and preparation of the manuscript. M.K., F.T., T.O., T.N., H.T., and T.I. have a role in the acquisition of subjects and/or data analysis. Conflict of interest: None of the authors have conflict of interest. Funding: None declared. Address correspondence to Ryuji Sakakibara, MD, PhD, Department of Neurology, Internal Medicine, Sakura Medical Center, Toho University, 564-1 Shimoshizu, Sakura 285-8741, Japan. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2014 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.02.010
Introduction It is well recognized that diffusion-weighted magnetic resonance imaging (DW MRI) is a sensitive and specific technique for imaging acute hemispheric infarction. In contrast, its utility in the diagnosis of acute brain stem infarction has not been fully established.1,2 This is because in specific cases, serial DW MRI on day 1 was unable to show a lesion, whereas that on day 4 and later clearly revealed a lesion. This phenomenon (‘‘invisible’’ brain stem infarction [IBI] at the first day) occurs with a discrete lesion at dorsolateral medulla (presenting isolated vertigo,3 isolated hemiataxia,4 Wallenberg syndrome,5-9 or Avellis syndrome8), dorsal pons (isolated internuclear ophthalmoplegia,10 or Millard–Gubler syndrome8), and basal midbrain (Weber syndrome8). Recognition of IBI in clinical practice is extremely important
Journal of Stroke and Cerebrovascular Diseases, Vol. -, No. - (---), 2014: pp 1-5
1
Y. TSUYUSAKI ET AL.
2
Figure 1. Frequency of day 1 invisible stroke on diffusion-weighted magnetic resonance imaging (DW MRI) among hemispheric and brain stem stroke. Frequency of day 1 invisible stroke on DW MRI in brain stem stroke was 17%, which was significantly higher than none in the hemispheric stroke (P , .05).
because anticoagulation and neuroprotection should start as early as possible. However, it remains unclear whether specific neurologic symptom, lesion location, or lesion size is related with IBI and what is the putative mechanism of IBI. Here, we systematically investigated IBI in our neurologic emergency cases.
Methods In total, 212 patients with acute cerebral infarction including IBI were enrolled who visited our neurologic emergency room during a 4-year period. The inclusion diagnostic criteria of IBI were (1) acute and clear brain stem symptoms/signs on arrival that were ameliorated at discharge, even though they were subtle (isolated vertigo,3 isolated hemiataxia,4 etc.), and (2) appearance of high signal intensity on serial DW images with low
apparent diffusion coefficient (ADC), in addition to further appearance of high signal intensity on serial T2weighted/fluid-attenuated inversion recovery images. The exclusion criteria were (1) diffuse CNS diseases, such as encephalitis or systemic diseases (hypoxia, hyperglycemic coma, extreme hypertension, etc.), (2) drug abuse, and (3) focal central nervous system diseases other than stroke, etc. In all patients, we performed brain MRI and a laboratory test on arrival. To augment neurologic diagnosis, we performed additional electrophysiologic tests (auditory/somatosensory evoked potentials, etc.), neuro-otological tests (eye-tracking/visual suppression tests, etc.), and neuro-ophthalmological tests (Hess/binocular tests, etc.) to the extent possible. All 212 patients underwent MRI examinations on a 1.5 T Gyroscan (Philips, Best, The Netherlands). In addition to DW images with 2-mm-thick slices and .5 mm gap for infratentorial and
Figure 2. (A) Time course of diffusion-weighted magnetic resonance imaging (DW MRI) of day 1 invisible brain stem stroke. Typical case of DW MRI of day 1 invisible brain stem stroke (upper panel, day 1, lower panel, day 4). (B) Time course of DW MRI of day 1 invisible brain stem stroke. In 4 of 6 cases (67%), DW image became visible at the third/fourth day; in 1 case, it became visible at 18 hours; in 1 case, it became visible at a certain time between the 3rd day and the 19th day. Invisible, open square; visible, closed square.
INVISIBLE BRAIN STEM INFARCTION
3
Figure 3. Time course of DW MRI of day 1 invisible brain stem stroke. In comparison with differences (with that in the contralateral lesion side) in signal intensity of the DW image (high) and ADC (low) of day 1 visible cases (bars at the right side), differences in signal intensity of the DW image and ADC of day 1 invisible cases were smaller particularly at the first day of stroke onset (not statistically significant). Abbreviations: ADC, apparent diffusion coefficient; DW MRI, diffusion-weighted magnetic resonance imaging.
4-mm-thick slices for supratentorial structures, we obtained T1-weighted, T2-weighted, fluid-attenuated inversion recovery and T2* images, MR angiography, and arterial spin labeling perfusion images. All subjects provided informed consent to participate. The study was conducted according to the principles of the Declaration of Helsinki.
Results All 235 patients included 146 men and 89 women (age, 70.5 6 12.2 years [mean 6 standard deviation]). IBI were found in only 6 patients, slightly younger age (53.8 6 17.8 years) and male predominance (5 men and 1 women; not statistically significant). Only in the brain stem (17%, 6 of 35) but none (0 of 177) in the hemispheric, in any type of lacunar, atherosclerotic, and cardioembolic strokes (P , .05; Fig 1). In most patients with IBI, DW MR image turned out visible at the third or fourth day (Fig 2). Before the fourth day, DW/ADC signal changes in patients with IBI were minimal (Fig 3). In IBI, lesion size (mean 2.7 mm2) was smaller than that of visible cases (mean 7.3 mm2; not statistically significant; Fig 4). In IBI, lesion location was mostly at the dorsolateral medulla (Fig 5). This is in contrast to common pontine lesion in visible cases. In IBI, sensory disturbance was significantly more common (67%) than visible cases (24%; P , .05), whereas dysarthria was less common (0%; P , .01) than visible cases (66%; P , .01).
Discussion Figure 4. Lesion size of day 1 visible/invisible brain stem stroke on diffusion-weighted magnetic resonance imaging. Among brain stem strokes, final area of lesion of day 1 invisible cases was smaller than that of day 1 visible cases (not statistically significant).
As shown earlier, as compared with visible cases, patients with IBI presented with distinct clinical imaging abnormalities. It is striking that day 1 invisible infarction was found only in the brain stem (17%) but none in the
4
Y. TSUYUSAKI ET AL.
Figure 5. Lesion location and symptom of day 1 visible/invisible brain stem stroke on DW MRI. (Upper panel) Among brain stem strokes, lesion location of day 1 invisible cases was mostly dorsolateral medulla. This is in contrast to common pontine lesion in day 1 visible cases. (Lower panel) Among brain stem strokes, looking at the neurologic symptoms, sensory disturbance in day 1 invisible cases was significantly more common (67%) than that in day 1 visible cases (24%; P , .05). Speech disturbance in day 1 invisible cases was less common (0%; P , .01) than that in day 1 visible cases (66%; P , .01). Abbreviations: DW MRI, diffusion-weighted magnetic resonance imaging; ns, not significant.
hemispheric (P ,.05) in the present study. Previous study results5-9 are the same with ours in that brain stem alone may present with invisible infarction. The frequency of IBI among brain stem infarction in the study was 17% (6 of 35). This is lower than 33% (10 of 30) by Krasnianski et al.8 The exact reason of difference remains unclear, but it may depend on different signal sequences and MRI machine we used. Axer et al11 described relative DW image and ADC time course in a longer window than ours. Alteration of relative DW image and ADC in brain stem infarction had their peak at around day 4, which is delayed as compared with those in the hemispheric infarction. Among brain stem infarctions, as expected, lesion size in IBI was smaller than that of visible cases (around 3 mm2). Among IBI lesion sites, dorsolateral medulla was the most common, which was in accordance with the previous studies. Clinically, dorsolateral medullary lesion may present with isolated vertigo,3 isolated hemiataxia,4 and Wallenberg syndrome as the full neurologic syndrome.5-9 According to this, in IBI, sensory disturbance
was more common (67%; P , .05), whereas dysarthria was less common (0%; P , .01) than that in visible cases. Therefore, particularly in patients with acute sensory disturbance, forme fruste of Wallenberg syndrome should always be explored by MRI. The exact reason why invisible stroke at the first day preferentially occurs in the brain stem, particularly in the dorsolateral medulla, remains unclear. One explanation is that because nuclei and fibers are dense within the brain stem, even smaller lesion presents with distinct neurologic dysfunction that brought patients to clinic. Another explanation is that small infarct volume as seen in IBI might be sensitive to partial volume effects and also affected by the skull base.11 Other explanation is that IBI may reflect a slower metabolic and perfusion change in watershed brain stem infarcts compared with thromboembolic hemispheric infarcts.12 Previously different ischemic tolerance between brain stem and hemisphere has not fully been explored. However, it is reported that in mouse brain, immunostaining of neuroglobin, an endogenous ischemia-protecting substance, is
INVISIBLE BRAIN STEM INFARCTION
weak in the cerebral cortex, whereas strong labeling is observed in the brain stem nuclei.13 Furthermore, better vascular collateralization, early reperfusion, and smaller lesion size in IBI may relate to situations of delayed cell death that occur in areas of milder ischemic injury for days after the initial ischemic event.14 Limitations of this study include that MRI we used is 1.5 T with a 2-mm-thick slice; therefore, using higher magnetic fields (3-4 T) with thinner slices, frequency of IBI among brain stem infarction may become smaller. However, even though, when evaluating stroke using MRI criteria, recognition of IBI is extremely important because early administration of antithrombotic/neuroprotective therapy are necessary to maximize stroke outcome.
Conclusion In conclusion, using 1.5 T MRI, the frequency of IBI at the first day was 17%, which was significantly higher than hemispheric infarction. It is likely that patients with smaller stroke volume, sensory disturbance, and medullary location are prone to develop IBI. When evaluating stroke using MRI criteria, recognition of IBI is extremely important to start early management.
References 1. Querol-Pascual MR. Clinical approach to brainstem lesions. Semin Ultrasound CT MRI 2010;31:220-229. 2. Alvarez-Linera J. Magnetic resonance techniques for the brainstem. Semin Ultrasound CT MRI 2010;31: 230-245.
5 3. Kishi M, Sakakibara R, Nomura T, et al. Lateral medullary infarction presenting as isolated vertigo and unilateral loss of visual suppression. Neurol Sci 2012; 33:129-132. 4. Kishi M, Sakakibara R, Nagao T, et al. Isolated hemiataxia and cerebellar diaschisis after a small dorsolateral medullary infarct. Case Rep Neurol 2009;1:41-46. 5. Begemann M, Silvers A, Tang C, et al. Delayed signal detection by diffusion-weighted imaging in brainstem infarction. J Stroke Cerebrovasc Dis 2001;10:284-289. 6. Frey LC, Sung GY, Tanabe J. Early false-negative diffusion-weighted imaging in brainstem infarction. J Stroke Cerebrovasc Dis 2002;11:51-53. 7. K€ uker W, Weise J, Krapf H, et al. MRI characteristics of acute and subacute brainstem and thalamic infarctions: value of T2- and diffusion-weighted sequences. J Neurol 2002;249:33-42. 8. Krasnianski M, Lindner A, Zierz S. Brainstem infarctions with normal MRI. Eur J Med Res 2002;7:125-127. 9. Kitis O, Calli C, Yunten N, et al. Wallenberg’s lateral medullary syndrome: diffusion-weighted imaging findings. Acta Radiol 2004;45:78-84. 10. Ogawa E, Sakakibara R, Kishi M, et al. Pure isolated internuclear ophthalmoplegia. Intern Med 2011;50:1785. 11. Axer H, Grael D, Bramer D, et al. Time course of diffusion imaging in acute brainstem infarcts. J Magn Reson Imaging 2007;26:905-912. 12. Huang I-J, Chen C-Y, Chang D-C, et al. Time course of cerebral infarction in the middle arterial territory: deep watershed versus territorial subtypes on diffusionweighted MR images. Radiology 2001;221:35-42. 13. Wystub S, Laufs T, Schmidt M, et al. Localization of neuroglobin protein in the mouse brain. Neurosci Lett 2003; 346:114-116. 14. Pulera MR, Adams LM, Liu H, et al. Apoptosis in a neonatal rat model of cerebral hypoxia-ischemia. Stroke 1998;29:2622-2630.
