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Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy without Anterior Temporal Pole Involvement: A Case Report
Case Report
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy without Anterior Temporal Pole Involvement: A Case Report Junpei Kobayashi, MD,* Shoichiro Sato, MD,* Kosuke Okumura, MD,*† Fumio Miyashita, MD,* Akihiko Ueda, MD,† Yukio Ando, MD,† and Kazunori Toyoda, MD*
The location of white matter lesions, especially in the anterior temporal poles (ATP), is helpful in the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We report a 49-yearold man with CADASIL who developed migraine with atypical aura, silent lacunar infarcts, and leukoencephalopathy without involvement of the ATP. The prevalence of migraine with aura in subjects with CADASIL is several times greater than that in the general population. Particularly in patients with CADASIL, the aura is often atypical (hemiplegic, basilar, or prolonged). A diagnosis of CADASIL should be considered in patients with lacunar infarcts, leukoencephalopathy, and migraine with atypical aura, even in the absence of white matter lesion in the ATPs. Key Words: Leukoencephalopathy—Notch3—migraine—lacunar infarcts. Ó 2014 by National Stroke Association
Introduction Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by migraine, subcortical infarcts, white matter lesions, mood disturbance, and progressive cogni-
From the *Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka; and †Department of Neurology, Kumamoto University, Kumamoto, Japan. Received October 1, 2013; accepted October 12, 2013. Sources of funding: This study was supported by a grant-in-aid (H23-Junkanki-Ippan-010) from the Ministry of Health, Labour and Welfare of Japan. Competing interests: None declared. Address correspondence to Shoichiro Sato, MD, Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2014 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.10.013
tive impairment. Recently, the disease spectrum has been expanded to those with milder forms including an isolated symptom of migraine or lacunar infarction.1,2 The location of white matter lesions, especially in the anterior temporal poles (ATP), is helpful in the diagnosis of CADASIL.3–5 We report a patient with CADASIL who developed migraine with atypical aura, silent lacunar infarcts, and leukoencephalopathy without involvement of the ATP.
Case Report A 49-year-old man with a 3-year history of headache visited our clinic. He described episodes of unilateral throbbing headache, lasting a few hours, which occurred approximately twice a month. His attacks were preceded by dizziness, right-sided weakness, sensory symptoms, or dysarthria. None of his relatives had a history of juvenile stroke or dementia. His neurologic and cognitive examinations were normal. Brain magnetic resonance imaging performed at the ages of 46 and 49 years showed
Journal of Stroke and Cerebrovascular Diseases, Vol. 23, No. 3 (March), 2014: pp e241-e242
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Figure 1. Brain magnetic resonance imaging at the ages of 46 (A-C) and 49 (D-F) years. Axial fluid-attenuated inversion recovery images revealed no white matter lesions in the anterior temporal poles (A and D), an increase in the number of lacunar infarcts at the level of the basal ganglia (B and E), and progression of white matter lesions at the level of the corona radiate (C and F).
progressive leukoencephalopathy without involvement of ATP and an increasing number of silent lacunar infarcts (Fig 1). A few microbleeds were present in the basal ganglia and cerebellum (data not shown). A diagnosis of CADASIL was confirmed by point mutation (C222S) in exon 4 of the Notch3 gene.
Discussion It was unusual that our CADASIL patient, who was in his late 40s, had no white matter lesions in the ATP because white matter lesions in the ATP have been previously observed in approximately 90% of patients with CADASIL.3,4 Leukoencephalopathy might be gradually enlarged in the ATP during the course of the disease in our patient because it has been reported that white matter lesions can increase over time.5 Similar to our patient, a previously reported case of CADASIL caused by a point mutation (C222S) in exon 4 of the Notch3 had no white matter lesions in the ATP.6 However, genotype– phenotype correlations in patients with CADASIL have yet to be fully elucidated.7 The prevalence of migraine with aura in patients with CADASIL is several times greater than the general population.8 Particularly in patients with CADASIL, the aura is often atypical (hemiplegic, basilar, or prolonged).8 A diagnosis of CADASIL should be considered in patients with lacunar infarcts, leukoencephalopathy, and migraine
with atypical aura, even in the absence of white matter lesion in the ATP.
References 1. Monteiro C, Barros J, Taipa R, et al. Sporadic hemiplegic migraine with normal imaging as the initial manifestation of CADASIL. Cephalalgia 2012;32:255-257. 2. Carra-Dalliere C, Ayrignac X, Renard D, et al. Isolated lacunar infarct: an early clinical presentation of CADASIL? Cerebrovasc Dis 2013;35:298-299. 3. Markus HS, Martin RJ, Simpson MA, et al. Diagnostic strategies in CADASIL. Neurology 2002;59:1134-1138. 4. O’Sullivan M, Jarosz JM, Martin RJ, et al. MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology 2001;56:628-634. 5. Singhal S, Rich P, Markus HS. The spatial distribution of MR imaging abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their relationship to age and clinical features. AJNR Am J Neuroradiol 2005;26:2481-2487. 6. Wang Z, Yuan Y, Zhang W, et al. NOTCH3 mutations and clinical features in 33 Mainland Chinese families with CADASIL. J Neurol Neurosurg Psychiatry 2011; 82:534-539. 7. Opherk C, Peters N, Herzog J, et al. Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients. Brain 2004;127:2533-2539. 8. Chabriat H, Vahedi K, Iba-Zizen MT, et al. Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Lancet 1995;346:934-939.
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy without Anterior Temporal Pole Involvement: A Case Report Junpei Kobayashi, MD,* Shoichiro Sato, MD,* Kosuke Okumura, MD,*† Fumio Miyashita, MD,* Akihiko Ueda, MD,† Yukio Ando, MD,† and Kazunori Toyoda, MD*
The location of white matter lesions, especially in the anterior temporal poles (ATP), is helpful in the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We report a 49-yearold man with CADASIL who developed migraine with atypical aura, silent lacunar infarcts, and leukoencephalopathy without involvement of the ATP. The prevalence of migraine with aura in subjects with CADASIL is several times greater than that in the general population. Particularly in patients with CADASIL, the aura is often atypical (hemiplegic, basilar, or prolonged). A diagnosis of CADASIL should be considered in patients with lacunar infarcts, leukoencephalopathy, and migraine with atypical aura, even in the absence of white matter lesion in the ATPs. Key Words: Leukoencephalopathy—Notch3—migraine—lacunar infarcts. Ó 2014 by National Stroke Association
Introduction Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by migraine, subcortical infarcts, white matter lesions, mood disturbance, and progressive cogni-
From the *Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka; and †Department of Neurology, Kumamoto University, Kumamoto, Japan. Received October 1, 2013; accepted October 12, 2013. Sources of funding: This study was supported by a grant-in-aid (H23-Junkanki-Ippan-010) from the Ministry of Health, Labour and Welfare of Japan. Competing interests: None declared. Address correspondence to Shoichiro Sato, MD, Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2014 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.10.013
tive impairment. Recently, the disease spectrum has been expanded to those with milder forms including an isolated symptom of migraine or lacunar infarction.1,2 The location of white matter lesions, especially in the anterior temporal poles (ATP), is helpful in the diagnosis of CADASIL.3–5 We report a patient with CADASIL who developed migraine with atypical aura, silent lacunar infarcts, and leukoencephalopathy without involvement of the ATP.
Case Report A 49-year-old man with a 3-year history of headache visited our clinic. He described episodes of unilateral throbbing headache, lasting a few hours, which occurred approximately twice a month. His attacks were preceded by dizziness, right-sided weakness, sensory symptoms, or dysarthria. None of his relatives had a history of juvenile stroke or dementia. His neurologic and cognitive examinations were normal. Brain magnetic resonance imaging performed at the ages of 46 and 49 years showed
Journal of Stroke and Cerebrovascular Diseases, Vol. 23, No. 3 (March), 2014: pp e241-e242
e241
J. KOBAYASHI ET AL.
e242
Figure 1. Brain magnetic resonance imaging at the ages of 46 (A-C) and 49 (D-F) years. Axial fluid-attenuated inversion recovery images revealed no white matter lesions in the anterior temporal poles (A and D), an increase in the number of lacunar infarcts at the level of the basal ganglia (B and E), and progression of white matter lesions at the level of the corona radiate (C and F).
progressive leukoencephalopathy without involvement of ATP and an increasing number of silent lacunar infarcts (Fig 1). A few microbleeds were present in the basal ganglia and cerebellum (data not shown). A diagnosis of CADASIL was confirmed by point mutation (C222S) in exon 4 of the Notch3 gene.
Discussion It was unusual that our CADASIL patient, who was in his late 40s, had no white matter lesions in the ATP because white matter lesions in the ATP have been previously observed in approximately 90% of patients with CADASIL.3,4 Leukoencephalopathy might be gradually enlarged in the ATP during the course of the disease in our patient because it has been reported that white matter lesions can increase over time.5 Similar to our patient, a previously reported case of CADASIL caused by a point mutation (C222S) in exon 4 of the Notch3 had no white matter lesions in the ATP.6 However, genotype– phenotype correlations in patients with CADASIL have yet to be fully elucidated.7 The prevalence of migraine with aura in patients with CADASIL is several times greater than the general population.8 Particularly in patients with CADASIL, the aura is often atypical (hemiplegic, basilar, or prolonged).8 A diagnosis of CADASIL should be considered in patients with lacunar infarcts, leukoencephalopathy, and migraine
with atypical aura, even in the absence of white matter lesion in the ATP.
References 1. Monteiro C, Barros J, Taipa R, et al. Sporadic hemiplegic migraine with normal imaging as the initial manifestation of CADASIL. Cephalalgia 2012;32:255-257. 2. Carra-Dalliere C, Ayrignac X, Renard D, et al. Isolated lacunar infarct: an early clinical presentation of CADASIL? Cerebrovasc Dis 2013;35:298-299. 3. Markus HS, Martin RJ, Simpson MA, et al. Diagnostic strategies in CADASIL. Neurology 2002;59:1134-1138. 4. O’Sullivan M, Jarosz JM, Martin RJ, et al. MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology 2001;56:628-634. 5. Singhal S, Rich P, Markus HS. The spatial distribution of MR imaging abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their relationship to age and clinical features. AJNR Am J Neuroradiol 2005;26:2481-2487. 6. Wang Z, Yuan Y, Zhang W, et al. NOTCH3 mutations and clinical features in 33 Mainland Chinese families with CADASIL. J Neurol Neurosurg Psychiatry 2011; 82:534-539. 7. Opherk C, Peters N, Herzog J, et al. Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients. Brain 2004;127:2533-2539. 8. Chabriat H, Vahedi K, Iba-Zizen MT, et al. Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Lancet 1995;346:934-939.