Accepted Manuscript SMART syndrome with cerebral angiographic abnormalities - A case report
Ji-Hyung Park, Moo-seok Park, Gyeong-Moon Kim PII: DOI: Reference:
S0022-510X(17)33732-2 doi: 10.1016/j.jns.2017.08.3234 JNS 15512
To appear in:
Journal of the Neurological Sciences
Received date: Revised date: Accepted date:
18 June 2017 18 August 2017 21 August 2017
Please cite this article as: Ji-Hyung Park, Moo-seok Park, Gyeong-Moon Kim , SMART syndrome with cerebral angiographic abnormalities - A case report. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Jns(2017), doi: 10.1016/j.jns.2017.08.3234
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
SMART Syndrome with Cerebral Angiographic Abnormalities - A Case Report
Department of Neurology, and
2
Radiology, Samsung Medical Center, Sungkyunkwan
Corresponding author
ED
MA
NU
SC
University School of Medicine, Seoul, Republic of Korea
RI
1
PT
Ji-Hyung Park, M.D1 ., Moo-seok Park, M.D.2 , Gyeong-Moon Kim, M.D., Ph.D.1
EP T
Gyeong-Moon Kim, M.D., Ph.D.
Department of Neurology, Samsung Medical Center
AC C
Sungkyunkwan University School of Medicine 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea Tel: +82-2-3410-3598, Fax: +82-2-3410-0052, E-mail: [email protected]
Keywords SMART syndrome 1 ; digital subtraction angiography; reversible cerebral vasoconstriction syndrome; posterior reversible encephalopathy syndrome
1
stroke-like migraine attacks after radiation therapy syndrome
ACCEPTED MANUSCRIPT
Dear Editor,
Black et al. first used the terminology ‘stroke- like migraine attacks after radiation therapy (SMART) syndrome’ and proposed diagnostic criteria in 2006 [1]. Proposed diagnostic
PT
criteria are remote history of cerebral radiotherapy, prolonged but reversible signs and symptoms referable to a unilateral cortical region and nearly reversible diffuse gyral and
RI
leptomeningeal enhancement within the symptomatic area [2]. However, these criteria do not
SC
include angiographic features. To the best of our knowledge, our case is the first report to show vascular change by means of digital subtraction angiography. Moreover, it is the first
NU
report of SMART syndrome in Korea.
MA
A 59-year-old male presented to emergency department. He had headache of moderate intensity in right parieto-occipital area, which began the night before. The time to peak
ED
intensity was about 10 minutes. Early in the next morning, he had disorientation to time and place. Initial blood pressure was 187/88, and moderate fever up to 38.8℃ was present.
EP T
Neurologic examination revealed left homonymous hemianopsia, left-sided weakness, hypesthesia and anosognosia.
AC C
He had cerebellar medulloblastoma treated with surgical removal and whole-brain radiotherapy 17 years ago. It did not recur afterward. He also suffered uncontrolled hypertension and chronic otitis media. Two years ago, he had a similar event of confusion and visuospatial dysfunction. Brain magnetic resonance image (MRI) showed leptomeningeal enhancement and prominent stenosis of right posterior cerebral artery. He had full recovery in 2 weeks. Brain MRI on the day of admission showed leptomeningeal enhancement which was most prominent in right temporo-occipital lobe but also in other areas of right hemisphere and left parieto-occipital lobe. (Fig. 1-A, 1-B and 1-C, left panel). There were also mild cortical
ACCEPTED MANUSCRIPT
hyperintensity and swelling in right parieto-temporal lobe on fluid-attenuated inversion recovery image. Diffusion weighted image showed multiple acute infarctions in subcortical area of right parietal lobe (Fig. 1-D, left panel). Perfusion weighted image showed delayed perfusion in a larger area surrounding the infarction. Magnetic resonance angiography (MRA)
PT
showed multiple stenoses of distal vasculature on both sides. Of note among them, there was a focal stenosis of a M2 branch of left middle cerebral artery (Fig. 1-E and 1-F, left panel). In
RI
addition, a severe stenosis of right posterior cerebral artery distal to P2 segment, which was
engorgement within sulci of right parietal lobe.
SC
present two years ago, was partially reversed. Gradient-echo image showed venous
NU
On the day of admission, mild leukocytosis was present, but erythrocyte sedimentation
MA
rate, C-reactive protein and procalcitonin levels were within normal limits. Opening pressure of cerebrospinal fluid was 15 cmH2 O. Analysis of cerebrospinal fluid showed leukocyte
ED
count of 2/μL and protein concentration of 48.3 mg/dL. Because of the venous engorgement, we suspected venous infarction caused by cerebral
EP T
venous thrombosis. On digital subtraction angiography (DSA), however, multifocal arterial stenoses with ‘string-of-beads’ patterns in distal branches of bilateral middle cerebral arteries
AC C
and vertebrobasilar arteries were demonstrated (Fig. 2). We made a diagnosis of SMART syndrome and assumed that the similar clinical event 2 years prior was also an attack of SMART syndrome. We maintained conservative treatment, and the patient showed complete clinical improvement 10 days after symptom onset. On follow-up MRI taken 1 month later, leptomeningeal enhancement and venous engorgement were partially resolved (Fig. 1-A, 1-B and 1-C, right panel). Focal enhancement in areas of the previous infarction was present (Fig. 1-D, right panel), compatible with subacute infarction. The focal stenosis on M2 branch of left middle cerebral artery was incompletely resolved (Fig. 1-E and 1-F, right panel). Perfusion delay in the right parietal lobe improved,
ACCEPTED MANUSCRIPT
but did not resolve completely. On discharge, we prescribed an antihypertensive medication to control hypertension. Pathophysiologic mechanism of SMART syndrome is poorly understood yet. As suggested by Kerklaan et al., it might be a reversible radiation vasculopathy, which is
PT
comparable to posterior reversible encephalopathy syndrome (PRES) [2]. However, no imaging evidence of reversible vasculopathy in SMART syndrome has been published, to the
RI
best of our knowledge.
SC
DSA of the patient in our case showed alternating stenosis and dilatation of distal vessels, which was similar to but somewhat different from the ‘string-of-beads’ sign of reversible
NU
cerebral vasoconstriction syndrome (RCVS) [3]. This finding could suggest possible overlap
MA
with RCVS. However, since the follow-up image was lacking, it could also suggest a persistent change such as radiation vasculopathy.
ED
The two MRAs over 1-month interval showed partial reversal of a focal stenosis of a M2 branch of left middle cerebral artery which was seen on the initial MRA. In addition to these
EP T
angiographic features, perfusion delay in right parietal area was partially improved. Leptomeningeal enhancement, which might also be representative of dilated surface arteries,
AC C
was again partially improved. These findings, suggestive of partial reversibility, could represent the nature of vascular pathology of the SMART syndrome itself. Another possibility is that the MRA findings could be an inter-scan variability, since the changes were not very prominent. Most important of all, though of less certainty, is that it could suggest an overlap with RCVS, and there might be overlapping pathophysiology between SMART syndrome and RCVS. Transient dysregulation of cerebral arterial tone with sympathetic hyperactivity was proposed as the pathophysiologic mechanism of RCVS [4,5]. It is believed that endothelial dysfunction of any etiology can cause unstable autoregulation of cerebral arterial tone and
ACCEPTED MANUSCRIPT
trigger vasoconstriction [6]. Delayed radiation- induced cerebral endothelial damage has been proposed as a mechanism of late onset radiation- induced brain injury and was demonstrated in an animal experiment [7]. Therefore, it seems plausible that a similar pathophysiologic mechanism might underlie SMART syndrome. This case report is meaningful because it
PT
presents an angiographic support, though weak, for this hypothesis. We believed that blood pressure surge was a triggering factor for an attack, as two attacks
RI
were accompanied by abnormally high blood pressure relative to baseline. In order to prevent
SC
recurrence, we started antihypertensive medication on discharge. As a treatment plan for disorders with alleged endothelial dysfunction such as SMART syndrome, we suggest
NU
removing triggering factors of RCVS, such as straining, physical exertion, sudden bending
MA
down, and hypertension. Moreover, calcium channel blockers, which is commonly used in
AC C
EP T
ED
RCVS, might be tried for treatment of acute phase of SMART syndrome.
ACCEPTED MANUSCRIPT
Conflicts of interest: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
PT
Funding The authors received no financial support for the research, authorship and/or publication of
SC
RI
this article.
Clinical Implications
NU
Angiographic study in SMART syndrome may show partially reversible stenosis.
MA
SMART syndrome may share some pathophysiologic mechanism with reversible cerebral vasoconstriction syndrome.
ED
Same preventive strategies used in reversible cerebral vasoconstriction syndrome might
AC C
EP T
be applied in SMART syndrome such as calcium channel blockers.
ACCEPTED MANUSCRIPT
References
[1]
D.F. Black, J.D. Bartleson, M.L. Bell, D.H. Lachance, SMART: stroke- like migraine attacks after radiation therapy, Cephalalgia : an international journal of headache 26
[2]
PT
(2006) 1137-1142. J.P. Kerklaan, G.J. Lycklama a Nijeholt, R.G. Wiggenraad, B. Berghuis, T.J. Postma,
RI
M.J. Taphoorn, SMART syndrome: a late reversible complication after radiation
[3]
SC
therapy for brain tumours, Journal of neurology 258 (2011) 1098-1104. A. Ducros, Reversible cerebral vasoconstriction syndrome, The Lancet. Neurology 11
L.H. Calabrese, D.W. Dodick, T.J. Schwedt, A.B. Singhal, Narrative review: reversible
MA
[4]
NU
(2012) 906-917.
cerebral vasoconstriction syndromes, Annals of internal medicine 146 (2007) 34-44. D.W. Dodick, R.D. Brown, Jr., J.W. Britton, J. Huston, 3rd, Nonaneurysmal
ED
[5]
thunderclap headache with diffuse, multifocal, segmental, and reversible vasospasm,
[6]
EP T
Cephalalgia : an international journal of headache 19 (1999) 118-123. D. Staykov, S. Schwab, Posterior reversible encephalopathy syndrome, Journal of
[7]
AC C
intensive care medicine 27 (2012) 11-24. D. Greene-Schloesser, M.E. Robbins, A.M. Peiffer, E.G. Shaw, K.T. Wheeler, M.D. Chan, Radiation- induced brain injury: A review, Frontiers in oncology 2 (2012) 73.
ACCEPTED MANUSCRIPT
AC C
EP T
ED
MA
NU
SC
RI
PT
Figure 1.
ACCEPTED MANUSCRIPT
AC C
EP T
ED
MA
NU
SC
RI
PT
Figure 2.
ACCEPTED MANUSCRIPT
Figure legends
Fig. 1. Comparison of initial images and 1- month follow- up. (A-C) Fluid-attenuated inversion recovery images with gadolinium enhancement at initial presentation (left panel)
PT
and 1 month later (right panel), showing bilateral multifocal leptomeningeal enhancement which is most prominent at right temporo-occipital lobe. (D) Diffusion-weighted image at
RI
initial presentation showing acute infarction of right parietal lobe (left panel) and T1-
SC
weighted image with gadolinium enhancement 1 month later showing enhancement of old infarction (right panel). (E-F) MR angiogram at initial presentation (left panel) and 1 month
MA
NU
later (right panel) showing reversed stenosis of M2 branch of left middle cerebral artery.
Fig. 2. Images showing alternating stenosis and dilatation of distal vessels. (A) Right internal carotid artery angiogram, oblique view. (B) Right internal carotid artery angiogram, lateral
ED
view. (C) Left internal carotid artery angiogram, lateral view. (D) Left internal carotid artery
AC C
EP T
angiogram, anteroposterior view.
Ji-Hyung Park, Moo-seok Park, Gyeong-Moon Kim PII: DOI: Reference:
S0022-510X(17)33732-2 doi: 10.1016/j.jns.2017.08.3234 JNS 15512
To appear in:
Journal of the Neurological Sciences
Received date: Revised date: Accepted date:
18 June 2017 18 August 2017 21 August 2017
Please cite this article as: Ji-Hyung Park, Moo-seok Park, Gyeong-Moon Kim , SMART syndrome with cerebral angiographic abnormalities - A case report. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Jns(2017), doi: 10.1016/j.jns.2017.08.3234
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
SMART Syndrome with Cerebral Angiographic Abnormalities - A Case Report
Department of Neurology, and
2
Radiology, Samsung Medical Center, Sungkyunkwan
Corresponding author
ED
MA
NU
SC
University School of Medicine, Seoul, Republic of Korea
RI
1
PT
Ji-Hyung Park, M.D1 ., Moo-seok Park, M.D.2 , Gyeong-Moon Kim, M.D., Ph.D.1
EP T
Gyeong-Moon Kim, M.D., Ph.D.
Department of Neurology, Samsung Medical Center
AC C
Sungkyunkwan University School of Medicine 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea Tel: +82-2-3410-3598, Fax: +82-2-3410-0052, E-mail: [email protected]
Keywords SMART syndrome 1 ; digital subtraction angiography; reversible cerebral vasoconstriction syndrome; posterior reversible encephalopathy syndrome
1
stroke-like migraine attacks after radiation therapy syndrome
ACCEPTED MANUSCRIPT
Dear Editor,
Black et al. first used the terminology ‘stroke- like migraine attacks after radiation therapy (SMART) syndrome’ and proposed diagnostic criteria in 2006 [1]. Proposed diagnostic
PT
criteria are remote history of cerebral radiotherapy, prolonged but reversible signs and symptoms referable to a unilateral cortical region and nearly reversible diffuse gyral and
RI
leptomeningeal enhancement within the symptomatic area [2]. However, these criteria do not
SC
include angiographic features. To the best of our knowledge, our case is the first report to show vascular change by means of digital subtraction angiography. Moreover, it is the first
NU
report of SMART syndrome in Korea.
MA
A 59-year-old male presented to emergency department. He had headache of moderate intensity in right parieto-occipital area, which began the night before. The time to peak
ED
intensity was about 10 minutes. Early in the next morning, he had disorientation to time and place. Initial blood pressure was 187/88, and moderate fever up to 38.8℃ was present.
EP T
Neurologic examination revealed left homonymous hemianopsia, left-sided weakness, hypesthesia and anosognosia.
AC C
He had cerebellar medulloblastoma treated with surgical removal and whole-brain radiotherapy 17 years ago. It did not recur afterward. He also suffered uncontrolled hypertension and chronic otitis media. Two years ago, he had a similar event of confusion and visuospatial dysfunction. Brain magnetic resonance image (MRI) showed leptomeningeal enhancement and prominent stenosis of right posterior cerebral artery. He had full recovery in 2 weeks. Brain MRI on the day of admission showed leptomeningeal enhancement which was most prominent in right temporo-occipital lobe but also in other areas of right hemisphere and left parieto-occipital lobe. (Fig. 1-A, 1-B and 1-C, left panel). There were also mild cortical
ACCEPTED MANUSCRIPT
hyperintensity and swelling in right parieto-temporal lobe on fluid-attenuated inversion recovery image. Diffusion weighted image showed multiple acute infarctions in subcortical area of right parietal lobe (Fig. 1-D, left panel). Perfusion weighted image showed delayed perfusion in a larger area surrounding the infarction. Magnetic resonance angiography (MRA)
PT
showed multiple stenoses of distal vasculature on both sides. Of note among them, there was a focal stenosis of a M2 branch of left middle cerebral artery (Fig. 1-E and 1-F, left panel). In
RI
addition, a severe stenosis of right posterior cerebral artery distal to P2 segment, which was
engorgement within sulci of right parietal lobe.
SC
present two years ago, was partially reversed. Gradient-echo image showed venous
NU
On the day of admission, mild leukocytosis was present, but erythrocyte sedimentation
MA
rate, C-reactive protein and procalcitonin levels were within normal limits. Opening pressure of cerebrospinal fluid was 15 cmH2 O. Analysis of cerebrospinal fluid showed leukocyte
ED
count of 2/μL and protein concentration of 48.3 mg/dL. Because of the venous engorgement, we suspected venous infarction caused by cerebral
EP T
venous thrombosis. On digital subtraction angiography (DSA), however, multifocal arterial stenoses with ‘string-of-beads’ patterns in distal branches of bilateral middle cerebral arteries
AC C
and vertebrobasilar arteries were demonstrated (Fig. 2). We made a diagnosis of SMART syndrome and assumed that the similar clinical event 2 years prior was also an attack of SMART syndrome. We maintained conservative treatment, and the patient showed complete clinical improvement 10 days after symptom onset. On follow-up MRI taken 1 month later, leptomeningeal enhancement and venous engorgement were partially resolved (Fig. 1-A, 1-B and 1-C, right panel). Focal enhancement in areas of the previous infarction was present (Fig. 1-D, right panel), compatible with subacute infarction. The focal stenosis on M2 branch of left middle cerebral artery was incompletely resolved (Fig. 1-E and 1-F, right panel). Perfusion delay in the right parietal lobe improved,
ACCEPTED MANUSCRIPT
but did not resolve completely. On discharge, we prescribed an antihypertensive medication to control hypertension. Pathophysiologic mechanism of SMART syndrome is poorly understood yet. As suggested by Kerklaan et al., it might be a reversible radiation vasculopathy, which is
PT
comparable to posterior reversible encephalopathy syndrome (PRES) [2]. However, no imaging evidence of reversible vasculopathy in SMART syndrome has been published, to the
RI
best of our knowledge.
SC
DSA of the patient in our case showed alternating stenosis and dilatation of distal vessels, which was similar to but somewhat different from the ‘string-of-beads’ sign of reversible
NU
cerebral vasoconstriction syndrome (RCVS) [3]. This finding could suggest possible overlap
MA
with RCVS. However, since the follow-up image was lacking, it could also suggest a persistent change such as radiation vasculopathy.
ED
The two MRAs over 1-month interval showed partial reversal of a focal stenosis of a M2 branch of left middle cerebral artery which was seen on the initial MRA. In addition to these
EP T
angiographic features, perfusion delay in right parietal area was partially improved. Leptomeningeal enhancement, which might also be representative of dilated surface arteries,
AC C
was again partially improved. These findings, suggestive of partial reversibility, could represent the nature of vascular pathology of the SMART syndrome itself. Another possibility is that the MRA findings could be an inter-scan variability, since the changes were not very prominent. Most important of all, though of less certainty, is that it could suggest an overlap with RCVS, and there might be overlapping pathophysiology between SMART syndrome and RCVS. Transient dysregulation of cerebral arterial tone with sympathetic hyperactivity was proposed as the pathophysiologic mechanism of RCVS [4,5]. It is believed that endothelial dysfunction of any etiology can cause unstable autoregulation of cerebral arterial tone and
ACCEPTED MANUSCRIPT
trigger vasoconstriction [6]. Delayed radiation- induced cerebral endothelial damage has been proposed as a mechanism of late onset radiation- induced brain injury and was demonstrated in an animal experiment [7]. Therefore, it seems plausible that a similar pathophysiologic mechanism might underlie SMART syndrome. This case report is meaningful because it
PT
presents an angiographic support, though weak, for this hypothesis. We believed that blood pressure surge was a triggering factor for an attack, as two attacks
RI
were accompanied by abnormally high blood pressure relative to baseline. In order to prevent
SC
recurrence, we started antihypertensive medication on discharge. As a treatment plan for disorders with alleged endothelial dysfunction such as SMART syndrome, we suggest
NU
removing triggering factors of RCVS, such as straining, physical exertion, sudden bending
MA
down, and hypertension. Moreover, calcium channel blockers, which is commonly used in
AC C
EP T
ED
RCVS, might be tried for treatment of acute phase of SMART syndrome.
ACCEPTED MANUSCRIPT
Conflicts of interest: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
PT
Funding The authors received no financial support for the research, authorship and/or publication of
SC
RI
this article.
Clinical Implications
NU
Angiographic study in SMART syndrome may show partially reversible stenosis.
MA
SMART syndrome may share some pathophysiologic mechanism with reversible cerebral vasoconstriction syndrome.
ED
Same preventive strategies used in reversible cerebral vasoconstriction syndrome might
AC C
EP T
be applied in SMART syndrome such as calcium channel blockers.
ACCEPTED MANUSCRIPT
References
[1]
D.F. Black, J.D. Bartleson, M.L. Bell, D.H. Lachance, SMART: stroke- like migraine attacks after radiation therapy, Cephalalgia : an international journal of headache 26
[2]
PT
(2006) 1137-1142. J.P. Kerklaan, G.J. Lycklama a Nijeholt, R.G. Wiggenraad, B. Berghuis, T.J. Postma,
RI
M.J. Taphoorn, SMART syndrome: a late reversible complication after radiation
[3]
SC
therapy for brain tumours, Journal of neurology 258 (2011) 1098-1104. A. Ducros, Reversible cerebral vasoconstriction syndrome, The Lancet. Neurology 11
L.H. Calabrese, D.W. Dodick, T.J. Schwedt, A.B. Singhal, Narrative review: reversible
MA
[4]
NU
(2012) 906-917.
cerebral vasoconstriction syndromes, Annals of internal medicine 146 (2007) 34-44. D.W. Dodick, R.D. Brown, Jr., J.W. Britton, J. Huston, 3rd, Nonaneurysmal
ED
[5]
thunderclap headache with diffuse, multifocal, segmental, and reversible vasospasm,
[6]
EP T
Cephalalgia : an international journal of headache 19 (1999) 118-123. D. Staykov, S. Schwab, Posterior reversible encephalopathy syndrome, Journal of
[7]
AC C
intensive care medicine 27 (2012) 11-24. D. Greene-Schloesser, M.E. Robbins, A.M. Peiffer, E.G. Shaw, K.T. Wheeler, M.D. Chan, Radiation- induced brain injury: A review, Frontiers in oncology 2 (2012) 73.
ACCEPTED MANUSCRIPT
AC C
EP T
ED
MA
NU
SC
RI
PT
Figure 1.
ACCEPTED MANUSCRIPT
AC C
EP T
ED
MA
NU
SC
RI
PT
Figure 2.
ACCEPTED MANUSCRIPT
Figure legends
Fig. 1. Comparison of initial images and 1- month follow- up. (A-C) Fluid-attenuated inversion recovery images with gadolinium enhancement at initial presentation (left panel)
PT
and 1 month later (right panel), showing bilateral multifocal leptomeningeal enhancement which is most prominent at right temporo-occipital lobe. (D) Diffusion-weighted image at
RI
initial presentation showing acute infarction of right parietal lobe (left panel) and T1-
SC
weighted image with gadolinium enhancement 1 month later showing enhancement of old infarction (right panel). (E-F) MR angiogram at initial presentation (left panel) and 1 month
MA
NU
later (right panel) showing reversed stenosis of M2 branch of left middle cerebral artery.
Fig. 2. Images showing alternating stenosis and dilatation of distal vessels. (A) Right internal carotid artery angiogram, oblique view. (B) Right internal carotid artery angiogram, lateral
ED
view. (C) Left internal carotid artery angiogram, lateral view. (D) Left internal carotid artery
AC C
EP T
angiogram, anteroposterior view.
