LETTERS TO THE EDITOR
OCTOBER 2014–VOL. 62, NO. 10
SYMPTOMS DURING CAROTID SINUS MASSAGE, NOT HEMODYNAMIC CHANGE, ARE ASSOCIATED WITH WHITE MATTER HYPERINTENSITY VOLUME ON MAGNETIC RESONANCE IMAGING To the Editor: White matter hyperintensities (WMHs) on magnetic resonance imaging (MRI), common in older people, are associated with cognitive impairment, falls, and depression.1 They are believed to represent cerebrovascular small vessel disease, but because frank infarction is not always seen, it is suggested that WMHs represent anoxic damage due to recurrent cerebral hypoperfusion.2 Under normal conditions, cerebral autoregulation ensures that cerebral perfusion is maintained over a range of systemic blood pressures, typically 60 to 150 mmHg.3 If systemic blood pressure falls below the lower limit of cerebral autoregulation, cerebral perfusion cannot be maintained, and dizziness, presyncope, and syncope ensue.4 Carotid sinus hypersensitivity (CSH) is an exaggerated fall in blood pressure (BP) or heart rate (HR) in response to stimulation of the carotid sinus. It is defined as a 50mmHg drop or more in systolic blood pressure or a 3-s or longer asystole in response to carotid sinus massage (CSM).5 CSH is associated with many of the clinical correlates of WMH, including cognitive impairment, depression, and falls.6–8 It is a common cause of dizziness, presyncope, and syncope in older people, although 35% of individuals with CSH do not report symptoms.9 It was hypothesized that symptoms in association with CSH indicate cerebral hypoperfusion and that individuals with symptomatic CSH are at greater risk of WMH than individuals with asymptomatic CSH or individuals without CSH. Between 2002 and 2003, 272 community-dwelling people aged 65 and older took part in a study examining the prevalence of CSH and its association with symptoms such as falls, dizziness and syncope. Full details of recruitment and how CSM was performed have been previously described in detail.8 In 2012, all surviving study participants were invited to take part in a 10-year follow-up and undergo MRI of the brain if they did not have a contraindication to MRI at 3T. Scans were performed on a 3T MRI scanner (Intera Achieva, Philips, Eindhoven, the Netherlands). WMHs were identified using a validated automated segmentation
method.10 WMH volumes are expressed as a percentage of total brain volume and are log transformed to normalize the distribution. Differences between groups were compared using one-way analysis of variation. Sidak correction was used for post hoc comparisons. The local research ethics committee provided ethical approval for the study. Of the 272 participants undergoing CSM in 2002– 2003, 88 participated in the 10-years follow-up, 44 (50%) of whom underwent MRI. Participants who underwent MRI did not significantly differ in age from those who did not (median age at baseline (interquartile range) 69 (67– 73) vs 70 (68–74), P = .19). Prevalence of cardiovascular disease, CSH, CSH subtypes, and hemodynamic response to CSM did not differ significantly between groups. Of the 44 individuals who underwent MRI at followup, 17 met criteria for CSH at baseline, eight of whom were symptomatic during CSM. Of the 27 participants who did not have CSH, two reported symptoms—dizziness in both cases. WMH volume of three groups was compared: CSH negative, asymptomatic CSH positive, and symptomatic CSH positive. CSH-positive participants who reported symptoms during CSM had significantly greater volumes of WMH than controls in all regions except the frontal lobe (Table 1). WMH volumes for asymptomatic CSH participants did not differ significantly from those of controls. Hemodynamic response to CSM of symptomatic and asymptomatic CSH-positive participants was compared. Systolic vasodepression after CSM was significantly greater for the symptomatic CSH group than the asymptomatic CSH group (median vasodepression 69 mmHg vs 57 mmHg, P = .03). The RR interval after CSM did not differ significantly (3.3 vs 3.1 s, P = .96). Age-adjusted partial correlations failed to show any significant associations between WMH volume and RR interval after CSM or vasodepression. Linear regression was performed to examine whether WMH volume was associated with symptomatic CSH, independent of age, history of hypertension (recognized risk factors for CSH and WMH), and degree of vasodepression. Symptomatic CSH at baseline was independently associated with total and periventricular WMH volume at 10 years and volume of WMH in the parietal, occipital, and temporal lobes.
Table 1. White Matter Hyperintensity Volume as a Percentage of Total Brain Volume According to Carotid Sinus Hypersensitivity (CSH) and Symptom Status No CSH, n = 27 Area of the Brain
Total Periventricular Frontal Parietal Occipital Temporal
0.73 0.52 0.37 0.10 0.87 0.05
(2.48) (2.25) (2.57) (4.51) (2.45) (3.38)
CSH + Symptoms, n=8
Asymptomatic CSH, n = 9
0.55 0.44 0.29 0.08 0.51 0.03
(2.22) (2.28) (2.22) (3.57) (2.72) (3.11)
1.94 1.52 0.79 0.47 2.59 0.17
(2.44) (2.41) (2.99) (4.00) (1.59) (2.80)
Analysis of Variance F, P-Value
4.91, 6.19, 2.64, 4.33, 7.95, 4.57,
.012 .004 .083 .020 .001 .016
Asymptomatic CSH vs No CSH
Symptomatic CSH vs No CSH
.80 .94 .87 .95 .31 .67
.03 .007 .16 .03 .009 .047
OCTOBER 2014–VOL. 62, NO. 10
This study showed that symptomatic CSH but not degree of hemodynamic change in response to CSM is associated with greater WMH volume. Symptoms such as dizziness, presyncope, and syncope are thought to result from low cerebral blood flow. It may be that, in asymptomatic CSH-positive individuals, cerebral autoregulation maintains cerebral blood flow despite large changes in systemic blood pressure, whereas in symptomatic individuals, systemic BP falls below the lower limit of cerebral autoregulation, or cerebral autoregulation fails, causing symptoms and anoxic white matter damage. Claire McDonald, MBBS Institute for Ageing and Health, Newcastle University, Newcastle, UK NIHR Newcastle Biomedical Research Centre in Ageing & Chronic Disease, UK Michael Firbank, PhD Institute for Ageing and Health, Newcastle University, Newcastle, UK
LETTERS TO THE EDITOR
2. Pantoni L, Garcia JH. Pathogenesis of leukoaraiosis: A review. Stroke 1997;28:652–659. 3. Panerai RB. Cerebral autoregulation: From models to clinical applications. Cardiovasc Eng 2008;8:42–59. 4. Kenny RAM, Kalaria R, Ballard C. Neurocardiovascular instability in cognitive impairment and dementia. NY Acad Sci 2002;977:183–195. 5. Brignole M, Auricchio A, Baron-Esquivias G et al. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: The Task Force on Cardiac Pacing and Resynchronization Therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J 2013;34:2281–2329. 6. Davies AJ, Steen N, Kenny RA. Carotid sinus hypersensitivity is common in older patients presenting to an accident and emergency department with unexplained falls. Age Ageing 2001;30:289–293. 7. Richardson DA, Bexton RS, Shaw FE et al. Prevalence of cardioinhibitory carotid sinus hypersensitivity in patients 50 years or over presenting to the accident and emergency department with “unexplained” or “recurrent” falls. Pacing Clin Electrophysiol 1997;20:820–823. 8. Pearce R, Ballard C, Hampton J et al. Prevalence and profile of cognitive impairment and dementia in patients with carotid sinus syndrome (CSH). Poster Abstracts. J Am Geriatr Soc 2005;53:s69–s69. 9. Kerr SR, Pearce MS, Brayne C et al. Carotid sinus hypersensitivity in asymptomatic older persons: Implications for diagnosis of syncope and falls. Arch Intern Med 2006;166:515–520. 10. Firbank MJ, Lloyd AJ, Ferrier N et al. A volumetric study of MRI signal hyperintensities in late-life depression. Am J Geriatr Psychiatry 2004;12:606–612.
Mark Pearce, PhD Institute of Health and Society, Newcastle University, Newcastle, UK Andrew M. Blamire, PhD Institute of Cellular Medicine, Newcastle University, Newcastle, UK Julia L. Newton, PhD Institute for Ageing and Health, Newcastle University, Newcastle, UK NIHR Newcastle Biomedical Research Centre in Ageing & Chronic Disease, UK Simon Kerr, PhD Institute for Ageing and Health, Newcastle University, Newcastle, UK
ACKNOWLEDGMENTS We thank Jessie Pairman and Katherine Wilton for their help with participant recruitment. This research was funded by the Research into Ageing Fund, a fund set up and managed by Age UK, the British Geriatric Society, and the National Institute for Health Research Newcastle Biomedical Research Centre in Ageing & Chronic Disease. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: All authors contributed to this paper. Sponsor’s Role: None.
REFERENCES 1. The LSG, Poggesi A, Pantoni L et al. 2001–2011: A decade of the LADIS (Leukoaraiosis aAnd DISability) Study: What have we learned about white matter changes and small-vessel disease? Cerebrovasc Dis 2011;32: 577–588.
DOES MOUNT VESUVIUS INDICATE AN OUTBREAK OF ALZHEIMER’S DISEASE? To the Editor: Because of an early semantic dysfunction,1,2 individuals with Alzheimer’s disease (AD) often have deficits in naming tasks3,4 such as the Boston Naming Test (BNT).5 In addition, the authors of the current study have observed a specific response bias; if asked to name the picture of a volcano, many individuals give responses such as Mount Vesuvius or Mount Etna, which are the bestknown volcanoes in Europe. Others give fire- (e.g., campfire) or weather-associated (e.g., rain) answers, which led to the assumption that not only a quantitative analysis of the BNT might be useful to indicate the beginning of an AD-related semantic dysfunction, but also a qualitative analysis of single BNT items. To confirm this assumption, neuropsychological data of 40 individuals with AD (meeting criteria of probable AD6) and 40 healthy controls matched with respect to age (with AD: 75.2 5.8; controls: 73.2 5.0), sex (with AD: 24 female, 16 male; controls: 21 female, 19 male), and education (with AD: 8.8 1.4 years; controls: 9.0 1.5 years) were analyzed. Groups were compared with respect to their neuropsychological performance on the Mini-Mental State Examination (MMSE),7 a category fluency test,8 and a 15-item German version of the BNT.5 Moreover, answers that participants gave on the volcano item of the BNT were recorded verbatim and classified into four categories with descending semantic proximity. The first category was the correct answer (volcano), the second category was prototypical answers such as Mount Vesuvius and Mount Etna, the third category was fire-associated answers with close semantic proximity to the target object (e.g., fire, campfire, bonfire), and the fourth category was weather-associated answers with no or low semantic relationship to the target object (e.g., water, rain, cloud). Hardly any other answers
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