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Nocturnal blood pressure dip in CADASIL
Journal of the Neurological Sciences 193 Ž2001. 13–16 www.elsevier.comrlocaterjns
Nocturnal blood pressure dip in CADASIL Y. Manabe a,) , T. Murakami a , K. Iwatsuki a , H. Narai a , H. Warita a , T. Hayashi a , M. Shoji a , Y. Imai b, K. Abe a b
a Department of Neurology, Graduate School of Medicine and Dentistry, Okayama UniÕersity, 2-5-1 Shikata-cho, Okayama 700-8558, Japan Department of Clinical Pharmacology and Therapeutics, Tohoku UniÕersity Graduate School of Pharmaceutical Science and Medicine, 1-1 Aobaku, Seiryocho, Sendai 980-8574, Japan
Received 1 June 2001; received in revised form 6 August 2001; accepted 22 August 2001
Abstract The influence of a nocturnal blood pressure dip on cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ŽCADASIL. has not yet been clarified. We attempted to examine a correlation with the nocturnal blood pressure dip and CADASIL. We monitored circadian blood pressure patterns by the use of a portable blood pressure monitoring device in five patients with CADASIL and 10 age- and sex-matched control subjects. Based on nocturnal fall in mean arterial blood pressure ŽMABP., we classified patients into extreme dippers Žnocturnal reduction of MABP P 20%., dippers ŽP 10% but - 20%., nondippers Ž- 10% but P 0%., and inverted dippers Ž- 0%.. Three patients revealed non-dipper and two inverted dipper. Nighttime MABP fall was significantly lower in patients compared with control subjects Ž P - 0.01.. This study suggests that a lower nocturnal blood pressure fall may be partly associated with incidence andror worsening of deep white matter lesions in CADASIL. q 2001 Elsevier Science B.V. All rights reserved. Keywords: CADASIL; Ambulatory blood pressure monitoring; Non-dipper; Inverted dipper
1. Introduction Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ŽCADASIL. is a hereditary microangiopathic disease of the brain caused by mutations of the notch 3 gene on chromosome 19p13.1 w1,2x. The most frequent clinical presentations are transient ischemic attacks ŽTIAs. and strokes, vascular dementia, migraine with aura, and psychiatric disturbances w3,4x. On brain magnetic resonance imaging ŽMRI., there are varying degrees of diffuse white matter signal abnormalities and small circumscribed areas of abnormal signal Ždecreased on T1-weighted and increased on T2-weighted images. in the periventricular white matter, internal capsule, basal ganglia, thalamus, and the pons w5–7x. Vascular
risk factors such as hypertension ŽHT., diabetes mellitus ŽDM., hyperlipidemia, obesity, or smoking are notably absent. Periventricular white matter signal abnormalities Žleukoaraiosis. are associated with intracerebral pathology, including demyelinating diseases, hydrocephalus, subcortical arteriosclerotic encephalopathy ŽBinswanger’s disease., and CADASIL w8,9x. It has been reported that nighttime blood pressure ŽBP. fall was absent in the patients with Binswanger’s and lacunar-type dementia w10x. However, nocturnal BP dip has never been reported in CADASIL. Using a noninvasive portable BP recorder, we examined 24-h variations in the BP of patients with CADASIL.
2. Methods and results AbbreÕiations: ABP, ambulatory blood pressure; BP, blood pressure; CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; DBP, diastolic blood pressure; DM, diabetes mellitus; HT, hypertension; MABP, mean arterial blood pressure; MRI, magnetic resonance imaging; SBP, systolic blood pressure; TIA, transient ischemic attack. ) Corresponding author. Tel.: q81-86-235-7365; fax: q81-86-2357368. E-mail address: [email protected] ŽY. Manabe..
Five CADASIL individuals Žone man, four women; mean age, 56.0 " 2.6 years, mean " SD; range, 53 to 60 years. and 10 age- and sex-matched control subjects Žthree men, seven women; mean age, 55.5 " 1.8 years; range, 53 to 59 years. were enrolled into this study. CADASIL individuals were derived from three families. In all CADASIL cases, the diagnosis had been confirmed by the
0022-510Xr01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S 0 0 2 2 - 5 1 0 X Ž 0 1 . 0 0 6 3 6 - 0
14
Y. Manabe et al.r Journal of the Neurological Sciences 193 (2001) 13–16
identification of a mutation in the Notch 3 gene Ž n s 4. or by skin biopsy Ž n s 1.. Signs and symptoms included at least leukoencephalopathy on MRI, a history of stroke or dementia, and no causative vascular risk factors such as HT, DM, hyperlipidemia, cardiac disease, obesity, or smoking. Ten age- and sex-matched control subjects had also no causative vascular risk factors such as HT, DM, hyperlipidemia, cardiac disease, obesity, or smoking. All patients had the classic manifestations of CADASIL. The Arg141™ Cys mutation in exon 4 was detected in four patients. Blood pressure was monitored using a noninvasive portable recorder ŽABPM-630, Colin Medical, Komaki, Japan.. The subjects were free to move during the recording. Systolic and diastolic blood pressure ŽSBP and DBP, respectively., and heart rate were recorded at 1-h intervals Ži.e., 24 times a day.. The accuracy of this device was validated previously w11x. From the data thus obtained, averages of the mean arterial blood pressure ŽMABP. were calculated for daytime ŽMABP-d; 6:00 AM to 11:00 PM. and for nighttime ŽMABP-n; 11:00 PM to 6:00 AM.. MABP was computed with the formula MABPs ŽSBP y DBP.r3 q DBP. Nighttime MABP fall was calculated as ŽMABP-dy MABP-n.rMABP-d. Based on nocturnal fall in MABP, we classified patients into extreme dippers
Fig. 2. Nighttime MABP fall in CADASIL individuals and age- and sex-matched control subjects. Nighttime MABP fall was significantly lower in patients compared with control subjects Ž ) ) P - 0.01..
Žnocturnal reduction of MABP P 20%., dippers ŽP 10% but - 20%., nondippers Ž- 10% but P 0%., and inverted dippers Ž- 0%.. All patients included in the study had recordings of good technical quality. Data are expressed as means" SD. Statistical analysis was performed using oneway analysis of variance ŽANOVA. followed by Student’s t-test. Significance was set at p - 0.05. Three patients revealed non-dipper and two inverted dipper. Two control subjects revealed non-dipper, six dipper, and two extreme dipper. Individual curves for a patient and a control subject are presented in Fig. 1. Nighttime MABP fall was significantly lower in patients compared with control subjects Ž5.0 " 2.2% versus 15.3 "
Table 1 Blood pressure values in patients with CADASIL and control subjects
Fig. 1. Examples of 24-h MABP from a 57-year-old female CADASIL patient and a 58-year-old female control subject. Note only a small dip of BP in the night time for CADASIL patient Žfrom 11:00 PM to 6:00 AM..
Case
Control
CADASIL
n Age Žyears. Daytime SBP Žmm Hg. Daytime MABP Žmm Hg. Daytime DBP Žmm Hg. Nighttime SBP Žmm Hg. Nighttime MABP Žmm Hg. Nighttime DBP Žmm Hg. 24-h SBP Žmm Hg. 24-h MBP Žmm Hg. 24-h DBP Žmm Hg. 24-h HR Nighttime MABP fall Ž%.
10 55.5"1.8 120"4 91"5 72"4 104"7 77"5 61"5 116"4 87"4 69"3 68"7 15.3"7.1
5 56.0"2.6 111"15 86"10 73"9 108"14 84"14 71"13 110"15 85"11 71"10 79"18 5.0"2.2 ) )
Data are expressed as mean"SD. DBP, diastolic blood pressure; HR, heart rate; MABP, mean arterial blood pressure; SBP, systolic blood pressure. )) P - 0.01.
Y. Manabe et al.r Journal of the Neurological Sciences 193 (2001) 13–16
7.1%; P - 0.01; Fig. 2.. Table 1 shows blood pressure values in patients with CADASIL and control subjects.
3. Discussion The present results first reported a change of nocturnal BP in CADASIL patients, showing that a lower nocturnal BP fall was frequent among the patients with CADASIL. It has been reported that non-dippers, inverted dippers, and extreme dippers have greater cardiac, cerebral, and renal damage than dippers w12–14x. Leukoaraiosis is characteristic in demyelinating diseases, hydrocephalus, and Binswanger’s disease. Tohgi et al. w10x have reported that nighttime BP fall seen in the controls was absent in the patients with Binswanger and lacunar-type dementia Žboth related to hypertensive cerebrovascular disease.. Shimada et al. w15x have documented that hypertension-related silent cerebrovascular damage such as lacunar and periventricular white matter abnormalities was more frequent in nondippers than in dippers. A commonly accepted explanation for the nocturnal BP decline is a diminution of sympathetic nervous system activity paralleling the change in wakefulness. Many barometers of sympathetic nervous system activity, such as plasma catecholamine level, cardiac output, and peripheral resistance, are lower at night. Nocturnal BP decline is diminished in such diseases as autonomic failure, Shy– Drager syndrome, and diabetic neuropathy w16–18x. Multiple lacunar infarction involves deep and specific cerebral regions including the striatum, diencephalon, frontal operculum, cingulate gyrus, and their connections. Although the exact relation between leukoaraiosis and nocturnal BP dip is still not clear, diminished nocturnal BP decline may be caused by specific injury to the central autonomic nervous system such as the striatum, diencephalon, midbrain, and pontine tegmentum and their connecting fibers w19x. Non-dippers, inverted dippers, and extreme dippers were closely associated with leukoaraiosis caused by the lesion of central autonomic nervous system. Leukoaraiosis is also a major characteristic feature of CADASIL. Our data showed that the patients with CADASIL were non-dippers and an inverted dipper. The main mechanism of leukoaraiosis in CADASIL is microangiopathy by the Notch 3 gene mutation with pathologic features of splitting of the internal elastic lamina and stenosis of the vessel secondary to concentric deposition of granular material within the media w20,21x. Previous studies have suggested that the loss of nocturnal decrease in BP in stroke patients may be responsible for stroke in hypertensive patients w14,15x. The patients with CADASIL do not have HT, making it more likely that the loss of autonomic reflex is secondary to the stroke, it may contribute to further stroke. Although it is not fully understood whether non-dipper is a consequence
15
or a cause of leukoaraiosis, a lower nocturnal BP fall may be partly associated with incidence andror worsening of deep white matter lesions in CADASIL.
Acknowledgements This work was partly supported by Grant-in-Aid for Scientific Research ŽB. 12470141, ŽC. 13670649 and ŽHoga. 12877211 from the Ministry of Education, Science, Culture and Sports of Japan, and by grants ŽTashiro K., Itoyama Y., and Tsuji S.. and Comprehensive Research on Aging and Health ŽH11-Choju-010, No.207, Koizumi A. from the Ministry of Health and Welfare of Japan.
References w1x Tournier-Lasserve E, Joutel A, Melki J, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps on chromosome 19q12. Nat Genet 1993;3:256–9. w2x Joutel A, Corpechot C, Ducros A, et al. Notch 3 mutation in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996;383:707–10. w3x Chariat H, Vahedi K, Iba-Zizen MT, et al. Clinical spectrum of CADASIL: a study of 7 families. Lancet 1995;346:934–9. w4x Desmond DW, Moreney JT, Lynch T, et al. CADSIL in a north American family: clinical, pathologic, and radiologic findings. Neurology 1998;58:844–9. w5x Dichgans M, Filippi M, Bruming R, et al. Quantitative MRI in ¨ CADASIL: correlation with disability and cognitive performance Neurology 1999;52:1361–7. w6x Chabriat H, Mrissa R, Levy C, et al. Brain stem MRI signal abnormalities in CADASIL. Stroke 1999;30:457–9. w7x Yousry TA, Seelos K, Mayer M, et al. Characteristic MR lesion pattern and correlation of T1 and T2 lesion volume with neurologic and neuropsychological findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leurkoencephalopathy ŽCADASIL.. AJNR Am J Neuroradiol 1999;20:91–100. w8x Zimmerman RD, Fleming CA, Lee BCP, et al. Preventricular hyperintensity as seen by magnetic resonance: prevalence and significance. AJNR Am J Neuroradiol 1986;7:13–20. w9x Kertesz A, Black SE, Tokar G, et al. Periventricular and subcortical hyperintensities on magnetic resonance imaging: Arims, caps, and unidentified bright objectsB. Arch Neurol 1988;45:404–8. w10x Tohgi H, Chiba K, Kimura M. Twenty-four-hour variation of blood pressure in vascular dementia of the Binswanger type. Stroke 1991;22:603–8. w11x White WB, Lund-Johansen P, McCabe EJ. Clinical evaluation of the Colin ABPM 630 at rest and during exercise: an ambulatory blood pressure monitor with gas-powered cuff inflation. J Hypertens 1989;7:477–83. w12x O’Brien E, Sheridan J, O’Malley K. Dippers and non-dippers. Lancet 1988;ii:397. w13x Shimada K, Kawamoto A, Matsubayashi K, Ozawa T. Silent cerebrovascular disease in the elderly: correlation with ambulation pressure. Hypertension 1990;16:692–9. w14x Verdecchia P, Schillaci G, Guerrieri M, et al. Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension. Circulation 1990;81:528–36. w15x Shimada K, Kawamoto A, Matsubayashi K, et al. Diurnal blood pressure variations and silent cerebrovascular damage in elderly patients with hypertension. J Hypertens 1992;10:875–8.
16
Y. Manabe et al.r Journal of the Neurological Sciences 193 (2001) 13–16
w16x Martinelli P, Coccagna G, Rizzuto N, Lugaresi E. Change in systemic arterial pressure during sleep in Shy–Drager syndrome. Sleep 1981;4:139–46. w17x Mann S, Altman DG, Raftery EB, Bannister R. Circadian variation of blood pressure in autonomic failure. Circulation 1983;3:477–83. w18x Torffvit O, Agardh CD. Day and night variation in ambulatory blood pressure in type 1 diabetes mellitus with neuropathy and autonomic neuropathy. J Intern Med 1993;233:131–7. w19x Yamamoto Y, Akiguchi I, Oiwa K, et al. Diminished nocturnal
blood pressure decline and lesion site in cerebrovascular disease. Stroke 1995;26:829–33. w20x Baudrimont M, Dubas F, Joutel A, et al. Autosomal dominant leukoencephalopathy and subcortical ischemic stroke: a clinicopathological study. Stroke 1993;24:122–5. w21x Ragno M, Tournier-Lasserve E, Fiori MG, et al. An Italian kindred with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ŽCADSIL.. Ann Neurol 1995;38: 231–6.
Nocturnal blood pressure dip in CADASIL Y. Manabe a,) , T. Murakami a , K. Iwatsuki a , H. Narai a , H. Warita a , T. Hayashi a , M. Shoji a , Y. Imai b, K. Abe a b
a Department of Neurology, Graduate School of Medicine and Dentistry, Okayama UniÕersity, 2-5-1 Shikata-cho, Okayama 700-8558, Japan Department of Clinical Pharmacology and Therapeutics, Tohoku UniÕersity Graduate School of Pharmaceutical Science and Medicine, 1-1 Aobaku, Seiryocho, Sendai 980-8574, Japan
Received 1 June 2001; received in revised form 6 August 2001; accepted 22 August 2001
Abstract The influence of a nocturnal blood pressure dip on cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ŽCADASIL. has not yet been clarified. We attempted to examine a correlation with the nocturnal blood pressure dip and CADASIL. We monitored circadian blood pressure patterns by the use of a portable blood pressure monitoring device in five patients with CADASIL and 10 age- and sex-matched control subjects. Based on nocturnal fall in mean arterial blood pressure ŽMABP., we classified patients into extreme dippers Žnocturnal reduction of MABP P 20%., dippers ŽP 10% but - 20%., nondippers Ž- 10% but P 0%., and inverted dippers Ž- 0%.. Three patients revealed non-dipper and two inverted dipper. Nighttime MABP fall was significantly lower in patients compared with control subjects Ž P - 0.01.. This study suggests that a lower nocturnal blood pressure fall may be partly associated with incidence andror worsening of deep white matter lesions in CADASIL. q 2001 Elsevier Science B.V. All rights reserved. Keywords: CADASIL; Ambulatory blood pressure monitoring; Non-dipper; Inverted dipper
1. Introduction Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ŽCADASIL. is a hereditary microangiopathic disease of the brain caused by mutations of the notch 3 gene on chromosome 19p13.1 w1,2x. The most frequent clinical presentations are transient ischemic attacks ŽTIAs. and strokes, vascular dementia, migraine with aura, and psychiatric disturbances w3,4x. On brain magnetic resonance imaging ŽMRI., there are varying degrees of diffuse white matter signal abnormalities and small circumscribed areas of abnormal signal Ždecreased on T1-weighted and increased on T2-weighted images. in the periventricular white matter, internal capsule, basal ganglia, thalamus, and the pons w5–7x. Vascular
risk factors such as hypertension ŽHT., diabetes mellitus ŽDM., hyperlipidemia, obesity, or smoking are notably absent. Periventricular white matter signal abnormalities Žleukoaraiosis. are associated with intracerebral pathology, including demyelinating diseases, hydrocephalus, subcortical arteriosclerotic encephalopathy ŽBinswanger’s disease., and CADASIL w8,9x. It has been reported that nighttime blood pressure ŽBP. fall was absent in the patients with Binswanger’s and lacunar-type dementia w10x. However, nocturnal BP dip has never been reported in CADASIL. Using a noninvasive portable BP recorder, we examined 24-h variations in the BP of patients with CADASIL.
2. Methods and results AbbreÕiations: ABP, ambulatory blood pressure; BP, blood pressure; CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; DBP, diastolic blood pressure; DM, diabetes mellitus; HT, hypertension; MABP, mean arterial blood pressure; MRI, magnetic resonance imaging; SBP, systolic blood pressure; TIA, transient ischemic attack. ) Corresponding author. Tel.: q81-86-235-7365; fax: q81-86-2357368. E-mail address: [email protected] ŽY. Manabe..
Five CADASIL individuals Žone man, four women; mean age, 56.0 " 2.6 years, mean " SD; range, 53 to 60 years. and 10 age- and sex-matched control subjects Žthree men, seven women; mean age, 55.5 " 1.8 years; range, 53 to 59 years. were enrolled into this study. CADASIL individuals were derived from three families. In all CADASIL cases, the diagnosis had been confirmed by the
0022-510Xr01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S 0 0 2 2 - 5 1 0 X Ž 0 1 . 0 0 6 3 6 - 0
14
Y. Manabe et al.r Journal of the Neurological Sciences 193 (2001) 13–16
identification of a mutation in the Notch 3 gene Ž n s 4. or by skin biopsy Ž n s 1.. Signs and symptoms included at least leukoencephalopathy on MRI, a history of stroke or dementia, and no causative vascular risk factors such as HT, DM, hyperlipidemia, cardiac disease, obesity, or smoking. Ten age- and sex-matched control subjects had also no causative vascular risk factors such as HT, DM, hyperlipidemia, cardiac disease, obesity, or smoking. All patients had the classic manifestations of CADASIL. The Arg141™ Cys mutation in exon 4 was detected in four patients. Blood pressure was monitored using a noninvasive portable recorder ŽABPM-630, Colin Medical, Komaki, Japan.. The subjects were free to move during the recording. Systolic and diastolic blood pressure ŽSBP and DBP, respectively., and heart rate were recorded at 1-h intervals Ži.e., 24 times a day.. The accuracy of this device was validated previously w11x. From the data thus obtained, averages of the mean arterial blood pressure ŽMABP. were calculated for daytime ŽMABP-d; 6:00 AM to 11:00 PM. and for nighttime ŽMABP-n; 11:00 PM to 6:00 AM.. MABP was computed with the formula MABPs ŽSBP y DBP.r3 q DBP. Nighttime MABP fall was calculated as ŽMABP-dy MABP-n.rMABP-d. Based on nocturnal fall in MABP, we classified patients into extreme dippers
Fig. 2. Nighttime MABP fall in CADASIL individuals and age- and sex-matched control subjects. Nighttime MABP fall was significantly lower in patients compared with control subjects Ž ) ) P - 0.01..
Žnocturnal reduction of MABP P 20%., dippers ŽP 10% but - 20%., nondippers Ž- 10% but P 0%., and inverted dippers Ž- 0%.. All patients included in the study had recordings of good technical quality. Data are expressed as means" SD. Statistical analysis was performed using oneway analysis of variance ŽANOVA. followed by Student’s t-test. Significance was set at p - 0.05. Three patients revealed non-dipper and two inverted dipper. Two control subjects revealed non-dipper, six dipper, and two extreme dipper. Individual curves for a patient and a control subject are presented in Fig. 1. Nighttime MABP fall was significantly lower in patients compared with control subjects Ž5.0 " 2.2% versus 15.3 "
Table 1 Blood pressure values in patients with CADASIL and control subjects
Fig. 1. Examples of 24-h MABP from a 57-year-old female CADASIL patient and a 58-year-old female control subject. Note only a small dip of BP in the night time for CADASIL patient Žfrom 11:00 PM to 6:00 AM..
Case
Control
CADASIL
n Age Žyears. Daytime SBP Žmm Hg. Daytime MABP Žmm Hg. Daytime DBP Žmm Hg. Nighttime SBP Žmm Hg. Nighttime MABP Žmm Hg. Nighttime DBP Žmm Hg. 24-h SBP Žmm Hg. 24-h MBP Žmm Hg. 24-h DBP Žmm Hg. 24-h HR Nighttime MABP fall Ž%.
10 55.5"1.8 120"4 91"5 72"4 104"7 77"5 61"5 116"4 87"4 69"3 68"7 15.3"7.1
5 56.0"2.6 111"15 86"10 73"9 108"14 84"14 71"13 110"15 85"11 71"10 79"18 5.0"2.2 ) )
Data are expressed as mean"SD. DBP, diastolic blood pressure; HR, heart rate; MABP, mean arterial blood pressure; SBP, systolic blood pressure. )) P - 0.01.
Y. Manabe et al.r Journal of the Neurological Sciences 193 (2001) 13–16
7.1%; P - 0.01; Fig. 2.. Table 1 shows blood pressure values in patients with CADASIL and control subjects.
3. Discussion The present results first reported a change of nocturnal BP in CADASIL patients, showing that a lower nocturnal BP fall was frequent among the patients with CADASIL. It has been reported that non-dippers, inverted dippers, and extreme dippers have greater cardiac, cerebral, and renal damage than dippers w12–14x. Leukoaraiosis is characteristic in demyelinating diseases, hydrocephalus, and Binswanger’s disease. Tohgi et al. w10x have reported that nighttime BP fall seen in the controls was absent in the patients with Binswanger and lacunar-type dementia Žboth related to hypertensive cerebrovascular disease.. Shimada et al. w15x have documented that hypertension-related silent cerebrovascular damage such as lacunar and periventricular white matter abnormalities was more frequent in nondippers than in dippers. A commonly accepted explanation for the nocturnal BP decline is a diminution of sympathetic nervous system activity paralleling the change in wakefulness. Many barometers of sympathetic nervous system activity, such as plasma catecholamine level, cardiac output, and peripheral resistance, are lower at night. Nocturnal BP decline is diminished in such diseases as autonomic failure, Shy– Drager syndrome, and diabetic neuropathy w16–18x. Multiple lacunar infarction involves deep and specific cerebral regions including the striatum, diencephalon, frontal operculum, cingulate gyrus, and their connections. Although the exact relation between leukoaraiosis and nocturnal BP dip is still not clear, diminished nocturnal BP decline may be caused by specific injury to the central autonomic nervous system such as the striatum, diencephalon, midbrain, and pontine tegmentum and their connecting fibers w19x. Non-dippers, inverted dippers, and extreme dippers were closely associated with leukoaraiosis caused by the lesion of central autonomic nervous system. Leukoaraiosis is also a major characteristic feature of CADASIL. Our data showed that the patients with CADASIL were non-dippers and an inverted dipper. The main mechanism of leukoaraiosis in CADASIL is microangiopathy by the Notch 3 gene mutation with pathologic features of splitting of the internal elastic lamina and stenosis of the vessel secondary to concentric deposition of granular material within the media w20,21x. Previous studies have suggested that the loss of nocturnal decrease in BP in stroke patients may be responsible for stroke in hypertensive patients w14,15x. The patients with CADASIL do not have HT, making it more likely that the loss of autonomic reflex is secondary to the stroke, it may contribute to further stroke. Although it is not fully understood whether non-dipper is a consequence
15
or a cause of leukoaraiosis, a lower nocturnal BP fall may be partly associated with incidence andror worsening of deep white matter lesions in CADASIL.
Acknowledgements This work was partly supported by Grant-in-Aid for Scientific Research ŽB. 12470141, ŽC. 13670649 and ŽHoga. 12877211 from the Ministry of Education, Science, Culture and Sports of Japan, and by grants ŽTashiro K., Itoyama Y., and Tsuji S.. and Comprehensive Research on Aging and Health ŽH11-Choju-010, No.207, Koizumi A. from the Ministry of Health and Welfare of Japan.
References w1x Tournier-Lasserve E, Joutel A, Melki J, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps on chromosome 19q12. Nat Genet 1993;3:256–9. w2x Joutel A, Corpechot C, Ducros A, et al. Notch 3 mutation in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996;383:707–10. w3x Chariat H, Vahedi K, Iba-Zizen MT, et al. Clinical spectrum of CADASIL: a study of 7 families. Lancet 1995;346:934–9. w4x Desmond DW, Moreney JT, Lynch T, et al. CADSIL in a north American family: clinical, pathologic, and radiologic findings. Neurology 1998;58:844–9. w5x Dichgans M, Filippi M, Bruming R, et al. Quantitative MRI in ¨ CADASIL: correlation with disability and cognitive performance Neurology 1999;52:1361–7. w6x Chabriat H, Mrissa R, Levy C, et al. Brain stem MRI signal abnormalities in CADASIL. Stroke 1999;30:457–9. w7x Yousry TA, Seelos K, Mayer M, et al. Characteristic MR lesion pattern and correlation of T1 and T2 lesion volume with neurologic and neuropsychological findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leurkoencephalopathy ŽCADASIL.. AJNR Am J Neuroradiol 1999;20:91–100. w8x Zimmerman RD, Fleming CA, Lee BCP, et al. Preventricular hyperintensity as seen by magnetic resonance: prevalence and significance. AJNR Am J Neuroradiol 1986;7:13–20. w9x Kertesz A, Black SE, Tokar G, et al. Periventricular and subcortical hyperintensities on magnetic resonance imaging: Arims, caps, and unidentified bright objectsB. Arch Neurol 1988;45:404–8. w10x Tohgi H, Chiba K, Kimura M. Twenty-four-hour variation of blood pressure in vascular dementia of the Binswanger type. Stroke 1991;22:603–8. w11x White WB, Lund-Johansen P, McCabe EJ. Clinical evaluation of the Colin ABPM 630 at rest and during exercise: an ambulatory blood pressure monitor with gas-powered cuff inflation. J Hypertens 1989;7:477–83. w12x O’Brien E, Sheridan J, O’Malley K. Dippers and non-dippers. Lancet 1988;ii:397. w13x Shimada K, Kawamoto A, Matsubayashi K, Ozawa T. Silent cerebrovascular disease in the elderly: correlation with ambulation pressure. Hypertension 1990;16:692–9. w14x Verdecchia P, Schillaci G, Guerrieri M, et al. Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension. Circulation 1990;81:528–36. w15x Shimada K, Kawamoto A, Matsubayashi K, et al. Diurnal blood pressure variations and silent cerebrovascular damage in elderly patients with hypertension. J Hypertens 1992;10:875–8.
16
Y. Manabe et al.r Journal of the Neurological Sciences 193 (2001) 13–16
w16x Martinelli P, Coccagna G, Rizzuto N, Lugaresi E. Change in systemic arterial pressure during sleep in Shy–Drager syndrome. Sleep 1981;4:139–46. w17x Mann S, Altman DG, Raftery EB, Bannister R. Circadian variation of blood pressure in autonomic failure. Circulation 1983;3:477–83. w18x Torffvit O, Agardh CD. Day and night variation in ambulatory blood pressure in type 1 diabetes mellitus with neuropathy and autonomic neuropathy. J Intern Med 1993;233:131–7. w19x Yamamoto Y, Akiguchi I, Oiwa K, et al. Diminished nocturnal
blood pressure decline and lesion site in cerebrovascular disease. Stroke 1995;26:829–33. w20x Baudrimont M, Dubas F, Joutel A, et al. Autosomal dominant leukoencephalopathy and subcortical ischemic stroke: a clinicopathological study. Stroke 1993;24:122–5. w21x Ragno M, Tournier-Lasserve E, Fiori MG, et al. An Italian kindred with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ŽCADSIL.. Ann Neurol 1995;38: 231–6.