Clinical Review & Education
Images in Neurology
Massive Pontine Microbleeds in a Patient With CADASIL Seong-il Oh, MD; Seung Hyun Kim, MD; Hee-Jin Kim, MD
A 46-year-old woman developed dysarthria for 2 weeks. She also manifested headaches for several years. Her blood pressure was 140/99 mm Hg. The results of a neurologic examination showed right hemiparesis with a power grade of 3/5 in the right upper limb and lower limb, but her cognitive function and deep tendon reflexes were normal, and pathologic reflex was absent. Her Korean Mini-Mental State Examination score was 30, and her Clinical Dementia Rating score was 0. Initial laboratory results were unremarkable. Magnetic resonance imaging of her brain showed confluent microbleeds in the basal pons (Figure) and high–signal intensity lesions with inherent microbleeds in the bilateral periventricular white matter, basal ganglia, and thalamus. The woman’s family history showed that her mother presented with dementia and that her brother had a stroke. Analysis of the NOTCH3 gene in the patient revealed a novel mutation (P1008S), and the patient then received a diagnosis of cerebral autosomal
dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); however, DNA samples from family members were not available.
Discussion Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is a hereditary disease of the small blood vessels caused by mutations in the NOTCH3 gene.1 The abnormalities detected by magnetic resonance imaging in patients with CADASIL are severe white matter hyperintensities, typically extending to the anterior temporal region and external capsules, and subcortical lacunar lesions, and cerebral microbleeds have also been found in 31% to 69% of patients with CADASIL and have been localized in various locations. Their preferential localization included cortical-subcortical regions, white matter, and the thalamus.2-4 Microbleeds in patients with CADASIL and with a few small lesions in
Figure. Axial Magnetic Resonance Imaging of the Brain A
B
C
D
Axial, gradient-echo–weighted (A) and susceptibility-weighted (B) scans reveal confluent microbleeds in the pons (arrowhead). Fluid-attenuated inversion recovery (C) and high-resolution magnetic resonance imaging proton-density weighted (D) scans showing the heterogeneous signal intensity suggest the temporally unpredictable development of microbleeds. 1048
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the brainstem are observed less frequently; moreover, pontine involvement presenting with massive confluent microbleeds has not been reported. In this case, we report massive pontine microbleeds in the patient with CADASIL, which would be one of the causal ARTICLE INFORMATION Author Affiliations: Department of Neurology, College of Medicine, Hanyang University, Seoul, Republic of Korea. Corresponding Author: Hee-Jin Kim, MD, Department of Neurology, College of Medicine, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Republic of Korea ([email protected]). Published Online: June 9, 2014. doi:10.1001/jamaneurol.2014.45. Conflict of Interest Disclosures: None reported. Funding/Support: This study was supported by a grant from the Korea Healthcare Technology R and
risk factors. As an aspect of novel mutation in the NOTCH3 gene, it is not entirely clear whether atypical findings of massive confluent microbleeds in the patient could be ascribed to chance or whether the P1008S mutation of the gene is responsible.
D Project, Ministry for Health, Welfare, and Family Affairs, Republic of Korea (A120182). Role of the Sponsor: The funding agencies had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. REFERENCES 1. Lesnik Oberstein SA, van den Boom R, van Buchem MA, et al; Dutch CADASIL Research Group. Cerebral microbleeds in CADASIL. Neurology. 2001; 57(6):1066-1070.
jamaneurology.com
2. Dichgans M, Holtmannspötter M, Herzog J, Peters N, Bergmann M, Yousry TA. Cerebral microbleeds in CADASIL: a gradient-echo magnetic resonance imaging and autopsy study. Stroke. 2002;33(1):67-71. 3. Rinnoci V, Nannucci S, Valenti R, et al. Cerebral hemorrhages in CADASIL: report of four cases and a brief review. J Neurol Sci. 2013;330(1-2):45-51. 4. Lesnik Oberstein SA, van den Boom R, Middelkoop HA, et al. Incipient CADASIL. Arch Neurol. 2003;60(5):707-712.
JAMA Neurology August 2014 Volume 71, Number 8
Copyright 2014 American Medical Association. All rights reserved.
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Images in Neurology
Massive Pontine Microbleeds in a Patient With CADASIL Seong-il Oh, MD; Seung Hyun Kim, MD; Hee-Jin Kim, MD
A 46-year-old woman developed dysarthria for 2 weeks. She also manifested headaches for several years. Her blood pressure was 140/99 mm Hg. The results of a neurologic examination showed right hemiparesis with a power grade of 3/5 in the right upper limb and lower limb, but her cognitive function and deep tendon reflexes were normal, and pathologic reflex was absent. Her Korean Mini-Mental State Examination score was 30, and her Clinical Dementia Rating score was 0. Initial laboratory results were unremarkable. Magnetic resonance imaging of her brain showed confluent microbleeds in the basal pons (Figure) and high–signal intensity lesions with inherent microbleeds in the bilateral periventricular white matter, basal ganglia, and thalamus. The woman’s family history showed that her mother presented with dementia and that her brother had a stroke. Analysis of the NOTCH3 gene in the patient revealed a novel mutation (P1008S), and the patient then received a diagnosis of cerebral autosomal
dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); however, DNA samples from family members were not available.
Discussion Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is a hereditary disease of the small blood vessels caused by mutations in the NOTCH3 gene.1 The abnormalities detected by magnetic resonance imaging in patients with CADASIL are severe white matter hyperintensities, typically extending to the anterior temporal region and external capsules, and subcortical lacunar lesions, and cerebral microbleeds have also been found in 31% to 69% of patients with CADASIL and have been localized in various locations. Their preferential localization included cortical-subcortical regions, white matter, and the thalamus.2-4 Microbleeds in patients with CADASIL and with a few small lesions in
Figure. Axial Magnetic Resonance Imaging of the Brain A
B
C
D
Axial, gradient-echo–weighted (A) and susceptibility-weighted (B) scans reveal confluent microbleeds in the pons (arrowhead). Fluid-attenuated inversion recovery (C) and high-resolution magnetic resonance imaging proton-density weighted (D) scans showing the heterogeneous signal intensity suggest the temporally unpredictable development of microbleeds. 1048
JAMA Neurology August 2014 Volume 71, Number 8
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a University of Georgia User on 06/04/2015
jamaneurology.com
Images in Neurology Clinical Review & Education
the brainstem are observed less frequently; moreover, pontine involvement presenting with massive confluent microbleeds has not been reported. In this case, we report massive pontine microbleeds in the patient with CADASIL, which would be one of the causal ARTICLE INFORMATION Author Affiliations: Department of Neurology, College of Medicine, Hanyang University, Seoul, Republic of Korea. Corresponding Author: Hee-Jin Kim, MD, Department of Neurology, College of Medicine, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Republic of Korea ([email protected]). Published Online: June 9, 2014. doi:10.1001/jamaneurol.2014.45. Conflict of Interest Disclosures: None reported. Funding/Support: This study was supported by a grant from the Korea Healthcare Technology R and
risk factors. As an aspect of novel mutation in the NOTCH3 gene, it is not entirely clear whether atypical findings of massive confluent microbleeds in the patient could be ascribed to chance or whether the P1008S mutation of the gene is responsible.
D Project, Ministry for Health, Welfare, and Family Affairs, Republic of Korea (A120182). Role of the Sponsor: The funding agencies had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. REFERENCES 1. Lesnik Oberstein SA, van den Boom R, van Buchem MA, et al; Dutch CADASIL Research Group. Cerebral microbleeds in CADASIL. Neurology. 2001; 57(6):1066-1070.
jamaneurology.com
2. Dichgans M, Holtmannspötter M, Herzog J, Peters N, Bergmann M, Yousry TA. Cerebral microbleeds in CADASIL: a gradient-echo magnetic resonance imaging and autopsy study. Stroke. 2002;33(1):67-71. 3. Rinnoci V, Nannucci S, Valenti R, et al. Cerebral hemorrhages in CADASIL: report of four cases and a brief review. J Neurol Sci. 2013;330(1-2):45-51. 4. Lesnik Oberstein SA, van den Boom R, Middelkoop HA, et al. Incipient CADASIL. Arch Neurol. 2003;60(5):707-712.
JAMA Neurology August 2014 Volume 71, Number 8
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a University of Georgia User on 06/04/2015
1049
