Increased risk of trigeminal neuralgia after hypertension

A population-based study

S.-L. Pan, MD, PhD M.-F. Yen, PhD Y.-H. Chiu, PhD L.-S. Chen, PhD H.-H. Chen, DDS, PhD

ABSTRACT

Objective: Very few studies have explored the temporal relationship between hypertension and trigeminal neuralgia (TN). The aim of this population-based follow-up study was to investigate whether hypertension is associated with a higher risk of developing TN. Methods: A total of 138,492 persons with at least 2 ambulatory visits with the principal diagnosis
of hypertension in 2001 were enrolled in the hypertension group. The nonhypertension group consisted of 276,984 age- and sex-matched, randomly sampled subjects without hypertension. The 3-year TN-free survival rate and the cumulative incidence of TN were calculated using the Kaplan-Meier method. Cox proportional hazard regression was used to estimate the hazard ratio of TN.

Address correspondence and reprint requests to Dr. Shin-Liang Pan, Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan., No.7, Chung Shan S. Rd., Taipei 100, Taiwan panslcb@gmail.com

Results: In the hypertension group, 121 patients developed TN during follow-up, while, in the
nonhypertension group, 167 subjects developed TN. The crude hazard ratio for the hypertension group was 1.52 (95% confidence interval [CI] 1.201.92; p 0.0005), while, after adjustment for demographic characteristics and medical comorbidities, the adjusted hazard ratio was 1.51 (95% CI 1.191.90; p 0.0006).

Conclusions: This study shows a significantly increased risk of developing TN after hypertension.
Further studies are needed to elucidate the underlying mechanism of the association between hypertension and TN. Neurology 2011;77:16051610
GLOSSARY
aHR adjusted hazard ratio; CI confidence interval; HFS hemifacial spasm; HR hazard ratio; ICD-9-CM International Classification of Diseases, ninth revision, Clinical Modification; IQR interquartile range; MS multiple sclerosis; NHI National Health Insurance; TN trigeminal neuralgia.

Trigeminal neuralgia (TN) is an uncommon disorder characterized by recurrent, paroxysmal, lancinating, or electric shocklike pain within the trigeminal nerve distribution,1 with an estimated annual incidence of 4 27 per 100,000 person-years.2 4 Most cases are classic TN, which lacks objective evidence of motor or sensory deficit and is not attributed to another disorder,5 while a minority of cases are symptomatic TN, which is related to underlying causes, such as multiple sclerosis6 8 or nerve compression by a tumor.9,10 The exact pathophysiology of classic TN is unknown, but increasing evidence suggests that it may be related to compression of the trigeminal nerve entry zone close to the brainstem by a tortuous vessel, which leads to demyelination, resulting in ectopic excitation and ephaptic transmission.10 12 Because cerebral vascular tortuosity has been associated with hypertension,13 it was of interest whether the occurrence of hypertension is associated with increased risk of developing TN. However, pilot studies have given inconsistent results on the relationship between hypertension and TN, with 2 supporting a positive association between TN and hypertension3,14 and 1 being unable to show a signifi-

From the Department of Physical Medicine and Rehabilitation (S.-L.P.), National Taiwan University Hospital and National Taiwan University College of Medicine (S.-L.P.), Taipei; School of Oral Hygiene (M.F.-Y., L.-S.C.), College of Oral Medicine, Taipei Medical University, Taipei; Department and Graduate Institute of Health Care Management (Y.-H.C.), Chang Gung University, Tao-Yuan; and Centre of Biostatistics Consultation (H.-H.C.) and Division of Biostatistics, Graduate Institute of Epidemiology (H.-H.C.), College of Public Health, National Taiwan University, Taipei, Taiwan. Study funding: Supported by the Department of Health (DOH), Executive Yuan, Republic of China (DOH93-TD-M-113-030, DOH94-TD-M-113-004, DOH95-TD-M-113-002). Disclosure: Author disclosures are provided at the end of the article. Copyright 2011 by AAN Enterprises, Inc. 1605

cant association.15 This inconsistency may be partly due to insufficient statistical power, and partly due to the cross-sectional design adopted in the majority of studies which makes it impossible to identify a temporal relationship between hypertension and TN. The present population-based follow-up study aimed to investigate whether hypertension is associated with an increased risk of developing TN using a large population insurance-based database.
METHODS Data source. The data used in this study were from the complete National Health Insurance (NHI) claim database in Taiwan for the period 2000 to 2003. The NHI program has been implemented in Taiwan since 1995, and the coverage rate was 96% of the whole population in 2000 and 97% at the end of 2003, at which time more than 21.9 million inhabitants were enrolled. It should be noted that the rationale for using the NHI database after 2000 is that from January 1, 2000, according to the rules of the Bureau of NHI, NHI claim data were all encoded using the standardized International Classification of Diseases, ninth revision, Clinical Modification (ICD-9-CM). To determine the date and cause of death, the claim database was linked to the national mortality registry.

2000 (n 816,437) to increase the likelihood of identifying only new incident hypertension cases in 2001; 3) a previous diagnosis of TN (ICD-9-CM codes 350.1) (n 2,899) before the index visit; and 4) a diagnosis of multiple sclerosis (MS) (ICD9-CM code 340, n 363) or benign or malignant neoplasm of the nervous system (ICD-9-CM code 191, 192, 225, n 6,097) before their index ambulatory visit or within 2 years after the index visit, in order to reduce the possibility of developing symptomatic TN. A total of 138,492 subjects were included in the final hypertension group. The nonhypertension group was taken from the remaining subjects without a diagnosis of hypertension in the same 2001 NHI claim database. The first ambulatory medical care visit during 2001 was assigned as the index visit. The exclusion criteria for recruiting subjects into the nonhypertension group were 1) a previous diagnosis of hypertension before the index visit; 2) a previous diagnosis of TN before the index visit; and 3) a diagnosis of MS or benign or malignant neoplasm of the nervous system before the index visit or within 2 years after the index visit. We randomly selected 2 age- and sex-matched subjects for each subject in the hypertension group. A total of 276,984 subjects was included in the nonhypertension group.

Standard protocol approvals, registrations, and patient consents. To keep individual information confidential in order
to satisfy regulations on personal privacy in Taiwan, all personal identification numbers in the data were encrypted by converting the personal identification numbers into scrambled numbers before data processing. Because the database used in this study consists of deidentified secondary data released for research purposes, this principle meets the Personal Information Protection Act in Taiwan, and this study was exempt from full review by the Institutional Review Board.

Study subjects and design. We used a prospective age- and sex-matched cohort design to examine whether patients with hypertension are at increased risk for developing subsequent TN. The study cohort included a hypertension group and a nonhypertension group, both of which were selected from Taiwanese residents in the complete NHI claims database for 2001. Note that, in 2001, more than 21.6 million persons were registered in the NHI, accounting for approximately 97% of the total population in Taiwan. This large-scale population-based NHI database provides a unique opportunity for investigating the temporal relationship between hypertension and the occurrence of TN. The hypertension group consisted of subjects who had received a principal diagnosis of hypertension (ICD-9-CM code 401) in ambulatory medical care visits between January 1, 2001, and December 31, 2001. To maximize case ascertainment, only patients with at least 2 ambulatory visits with the principal diagnosis of hypertension in this period were considered for inclusion in the hypertension group (n 956,525). The index visit was defined as the first ambulatory visit during which the principal diagnosis of hypertension was made. The exclusion criteria for the recruitment of subjects into the hypertension group were as follows: 1) age less than 18 years (n 41) or greater than 100 years (n 493) to restrict the research sample to the general adult population; 2) a previous diagnosis of hypertension during
1606 Neurology 77 October 25, 2011

Outcome and follow-up. All the medical care records for each subject in the above 2 groups were tracked from their index visit until the end of 2003 and the mortality data for the subjects who died during the follow-up were obtained from the mortality registry. The date of the first principal diagnosis of TN (ICD9-CM codes 350.1) within the follow-up period was defined as the primary endpoint. The case ascertainment for TN required at least 2 ambulatory medical care visits with the principal diagnosis of TN. All subjects were followed from the index visit to the first occurrence of TN, death, or end of follow-up. We analyzed the influence of hypertension on TN-free survival, adjusting for demographic factors, including age, sex, and comorbid chronic diseases, including diabetes mellitus (ICD-9-CM code 250) and hyperlipidemia (ICD-9-CM code 272). The data for these preexisting comorbid medical disorders were acquired by tracking all the ambulatory medical care and inpatient records in the NHI database in the year before the index visit. Statistical analysis. The 2 test and Student t test were used
to examine differences in demographic variables and comorbid medical disorders between the hypertension and nonhypertension groups. Incidence rates of TN during the follow-up period by hypertension status were calculated by number of incident cases divided by the person-years of TN-free. We used the Poisson test to examine the difference of risk of developing TN between the hypertension and nonhypertension groups. The TN-free survival curves for the 2 groups were estimated using the Kaplan-Meier method. The cumulative incidence was then calculated as 1 minus the TN-free survival probability, and the differences in cumulative incidence rates between the 2 groups were tested with the log-rank test. We used the Cox proportional hazards regression analysis to estimate the effect of hypertension on TN-free survival after adjusting for the above demographic and clinical variables. Univariate analysis was performed for each variable, and then the best subsets selection method was used to develop the final multiple regression model. Age and sex were considered as basic elements and were always included in the multiple regression analysis. An level of 0.05 was considered statistically significant. The analyses were performed using SAS 9.2 software (SAS Institute, Cary, NC).

Table 1

Demographic features and comorbid chronic diseases of the hypertension and nonhypertension groupa
Total study population (n 415,476) Hypertension group (n 138,492) 57.5 13.7 68,614 (49.5) 12,079 (8.7) 13,446 (9.7) Nonhypertension group (n 276,984) 57.3 13.7 137,228 (49.5) 24,224 (8.8) 20,372 (7.4)

hypertension group than the nonhypertension group (figure, p 0.0005).

Results of Cox regression analysis. The results of the Cox proportional hazards regression analysis are listed in table 2. The left panel shows the unadjusted hazard ratio for each variable based on univariate analysis. The covariates with a p value less than 0.05 were hypertension and age. Compared to the nonhypertension group, the unadjusted hazard ratio (HR) for the hypertension group was 1.52 (95% CI 1.20 1.92; p 0.0005). The middle panel shows the full multivariate model including all variables from the univariate analysis. The significant prognostic factors were hypertension and age. Using the best subsets selection method, the final multiple regression model was developed, as shown in the right panel of table 2. Age and sex were considered as basic elements and were always included in the analysis. The variables included in final model were hypertension, age, and sex. The adjusted hazard ratio (aHR) of developing incident TN cases during the 3-year follow-up was 1.51 (95% CI 1.19 1.90; p 0.0006) for the hypertension group compared to the nonhypertension group. Older subjects were at greater risk of developing TN, with an increased risk of 3% (aHR 1.03; 95% CI 1.021.04, p 0.0001) per year of age.

Variables Age, y Female Diabetes Hyperlipidemia

a

p Value 0.8352 1.0000 0.7976 0.0001

Values are mean SD or n (%).

RESULTS Descriptive findings.

Table 1 shows the distribution of demographic characteristics and comorbid chronic diseases for the hypertension and nonhypertension groups. The mean age and gender proportion were identical in the 2 groups. The hypertension group had a higher prevalence of hyperlipidemia ( p 0.0001) than the nonhypertension group. There was no difference ( p 0.7976) in the prevalence of diabetes between the 2 groups. median follow-up time was 31.8 months (interquartile range [IQR] 7.1 months). In the total study cohort, the risk of developing incident TN cases during the follow-up period was 0.07% (288/415,476) and the corresponding risks for the hypertension group and nonhypertension group were 0.09% (121/ 138,492) and 0.06% (167/276,984), respectively. The hypertension group had a higher incidence rate of TN than the nonhypertension group (35.2 vs 23.2 per 100,000 person-years, p 0.0005). The cumulative incidence rate of TN over time was higher in the

Cumulative incidence of trigeminal neuralgia. The

Figure

Cumulative risk of developing trigeminal neuralgia

Cumulative risk of developing trigeminal neuralgia over time for the hypertension group (red line) and nonhypertension group (black line).

This population insurance-based cohort study showed that occurrence of hypertension was associated with a higher risk of developing TN. The 3-year cumulative incidence of TN for the subjects with hypertension was significantly higher than that for the nonhypertension group. In our longitudinal study, we followed patients with hypertension from the time of the diagnosis of hypertension for 3 years to examine the temporal relationship between hypertension and the development of subsequent TN and found that the adjusted HR for the hypertension group relative to the nonhypertension group was 1.51 (95% CI 1.19 1.90). These findings are compatible with the results of a previous population-based study of TN in Rochester, MN,3 which showed that 25% (19 out of 75) of patients with TN had a history of hypertension and that the OR for hypertension in patients with TN was 1.96 (95% CI 1.23.1).3 It has been suggested that TN is usually caused by vascular compression of the trigeminal nerve root at the brainstem by a tortuous vessel.10 This compression results in demyelination of the nerve root entry zone, leading to ectopic impulse generation, ephaptic transmission of impulses, and the symptoms of TN.10,16 Similarly, neurovascular compression of the facial and glossopharyngeal nerves is thought to be responsible for most cases of hemifacial spasm (HFS)
DISCUSSION
Neurology 77 October 25, 2011 1607

Table 2

Unadjusted and adjusted hazard ratios for the occurrence of trigeminal neuralgia during the 3-year follow-up period in the hypertension and nonhypertension groups
Occurrence of trigeminal neuralgia Full multivariate model, adjusted HR (95% CI) 1.50 (1.191.90) 1.03 (1.021.04) 1.04 (0.821.31) 0.84 (0.501.40) 1.24 (0.702.19) Best subset selected model, adjusted HR (95% CI)a 1.51 (1.191.90) 1.03 (1.021.04) 1.04 (0.821.31) NA NA

Variable Hypertension (vs nonhypertension) Age (year) Sex (female vs male) Diabetes mellitus (yes vs no) Hyperlipidemia (yes vs no)

Unadjusted HR (95% CI) 1.52 (1.201.92) 1.03 (1.021.04) 1.09 (0.871.38) 1.06 (0.711.58) 1.27 (0.871.86)

p Value 0.0005 0.0001 0.4509 0.7875 0.2211

p Value 0.0007 0.0001 0.7517 0.4975 0.4695

p Value 0.0006 0.0001 0.7471 NA NA

Abbreviations: CI confidence interval; HR hazard ratio; NA not applicable. a The variables of age and sex were always retained in the multiple regression analysis in the best subset selection procedure.

and glossopharyngeal neuralgia, respectively.12,16 Previous case-control studies have suggested that hypertension was associated with HFS,17,18 and hypertension was related to vascular tortuosity in the cerebello-pontine angle.18 These findings suggest that hypertension may accelerate the development of arterial tortuosity, which leads to compression and demyelination of the facial nerve, resulting in ectopic excitation and ephaptic transmission in the facial nerve.18 Hypertension has been suggested to be a predisposing factor for arterial tortuosity,19 23 which may increase the chance of developing neurovascular compression at the brainstem. From this perspective, a possible mechanism underpinning the temporal relationship between hypertension and TN seen in our study is that hypertension may exacerbate the arterial tortuosity at the brainstem and increase the chance of developing neurovascular compression, which, in turn, contributes to a higher risk for TN. Conversely, some studies have suggested that vascular compression of the ventrolateral medulla is associated with a subgroup of patients with essential hypertension.24 26 It raises a possibility that the link between hypertension and TN seen in our study may be attributed to a common etiology, namely, neurovascular compression at the brainstem. However, various epidemiologic, neuroimaging, and histopathologic studies2730 have provided evidence against a major role of neurovascular compression at the brainstem in the pathogenesis for most cases with essential hypertension. These conflicting findings suggest that the association between neurovascular compression at the brainstem and essential hypertension is still uncertain, and neurovascular compression appears to be a rare cause for essential hypertension, which is thought to have a multifactorial etiology involving interactions between various environmental and genetic factors.31 Therefore, it would be more plausible that the primary pathophysiologic mechanism underlying the association between hyperten1608 Neurology 77 October 25, 2011

sion and TN is hypertension-related arterial tortuosity, which in turn predisposes the development of neurovascular compression of the brainstem, resulting in an increased risk of TN. In the present study, the estimated incidence rate of TN for the nonhypertension group was 23.2 (95% CI 19.8 27.0) per 100,000 person-years, and carbamazepine was prescribed as the initial therapy in 54.2% (156 out of 288) of the patients with TN. These findings are consistent with the results from a large-scale observational study of neuropathic pain in the United Kingdom which used the diagnostic information collected routinely from UK primary care records (the General Practice Research Database) from January 1992 to April 2002.2 In that study, the estimated incidence rate of TN was 27 per 100,000 person-years and carbamazepine was prescribed as the initial therapy to 58% of patients with TN.2 Since the present study is a large population insurance-based cohort study and the temporal sequence between hypertension and TN is ordered, the observed significant association seems unlikely to be due to artificial phenomenon, such as selection bias and information bias (e.g., patients with hypertension would be more likely to be diagnosed with TN than those without hypertension). In addition, the temporal sequence, i.e., hypertension preceding TN, in our prospective study might also eliminate the possible differential misclassification of hypertension that might occur in a retrospective study. Our findings therefore provide evidence for a temporal association between hypertension and TN. Such a temporal relationship is essential for establishing a causal connection. Nevertheless, several limitations in our study need to be addressed. First, the diagnosis of hypertension, TN, diabetes, and hyperlipidemia in our study was entirely determined by the ICD codes from the NHI claim database. One may be concerned over the diagnostic accuracy of the database. However, the Bureau

of NHI has formed different audit committees that make it a rule to randomly sample the claim data from every hospital and review charts on a regular basis to verify the diagnostic validity and quality of care. Accordingly, the NHI claim database is an established research database and has been applied to various biomedical research fields.32,33 In the NHI research database, each ambulatory visit has its own individual record which includes 3 ICD codes: 1 principal diagnosis code and 2 secondary diagnosis codes. The principal diagnosis is defined as the condition chiefly responsible for the visit. In addition, we further adopted a case ascertainment algorithm that required at least 2 ambulatory medical care visits with a principal diagnosis code of hypertension or trigeminal neuralgia to further validate the diagnosis; such case definition may be expected to provide adequate diagnostic accuracy. Moreover, the estimated incidence rate of TN and the pattern of the initial pharmacologic therapy are similar between our study and a large-scale study of neuropathic pain which used the routinely collected primary care records in the United Kingdom.2 Such consistency may also support an acceptable pattern of diagnosis or drug use for TN in our study. Second, the NHI database lacks some information regarding the risk assessment of hypertension, such as smoking, alcohol use, body mass index, physical activity, or detailed blood pressure values, which may affect the interpretation of our results. Third, the follow-up time was only 3 years and the longterm effects of hypertension on the development of TN cannot therefore be evaluated. Fourth, most of the inhabitants in Taiwan are of Chinese ethnicity; it is uncertain whether our findings can be generalized to other ethnic groups. This population insurance-based cohort study demonstrates that hypertension leads to a higher risk of TN. Further long-term follow-up study would be required to validate our findings and to investigate the underlying pathophysiologic mechanism for the positive association between hypertension and TN.
AUTHOR CONTRIBUTIONS
Dr. Pan: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, statistical analysis. Dr. Yen: drafting/revising the manuscript, analysis or interpretation of data. Dr. Chiu: study concept or design, analysis or interpretation of data, statistical analysis. Dr. L.-S. Chen: analysis or interpretation of data, acquisition of data. Dr. T.H.-H. Chen: drafting/revising the manuscript, study concept or design, analysis or interpretation of data.

DISCLOSURE
Dr. Pan, Dr. Yen, Dr. Chiu, and Dr. L.-S. Chen report no disclosures. Dr. H.-H. Chen serves as an Associate Editor for Journal of Epidemiology and Community Health and on the editorial advisory board of the World Journal of Gastroenterology.

Received March 7, 2011. Accepted in final form July 6, 2011.

ACKNOWLEDGMENT
This study used the complete National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health. The findings and conclusions in our study do not stand for those from the Department of Health, Executive Yuan, Republic of China.

REFERENCES 1. Bennetto L, Patel NK, Fuller G. Trigeminal neuralgia and its management. BMJ 2007;334:201205. 2. Hall GC, Carroll D, Parry D, McQuay HJ. Epidemiology and treatment of neuropathic pain: the UK primary care perspective. Pain 2006;122:156 162. 3. Katusic S, Beard CM, Bergstralh E, Kurland LT. Incidence and clinical features of trigeminal neuralgia, Rochester, Minnesota, 19451984. Ann Neurol 1990;27:89 95. 4. MacDonald BK, Cockerell OC, Sander JW, Shorvon SD. The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK. Brain 2000;123:665 676. 5. Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004; 24(suppl 1):9 160. 6. Gass A, Kitchen N, MacManus DG, Moseley IF, Hennerici MG, Miller DH. Trigeminal neuralgia in patients with multiple sclerosis: lesion localization with magnetic resonance imaging. Neurology 1997;49:11421144. 7. Meaney JF, Watt JW, Eldridge PR, Whitehouse GH, Wells JC, Miles JB. Association between trigeminal neuralgia and multiple sclerosis: role of magnetic resonance imaging. J Neurol Neurosurg Psychiatry 1995;59:253259. 8. Nurmikko TJ, Eldridge PR. Trigeminal neuralgia: pathophysiology, diagnosis and current treatment. Br J Anaesth 2001;87:117132. 9. Cheng TM, Cascino TL, Onofrio BM. Comprehensive study of diagnosis and treatment of trigeminal neuralgia secondary to tumors. Neurology 1993;43:2298 2302. 10. Love S, Coakham HB. Trigeminal neuralgia: pathology and pathogenesis. Brain 2001;124:23472360. 11. Hilton DA, Love S, Gradidge T, Coakham HB. Pathological findings associated with trigeminal neuralgia caused by vascular compression. Neurosurgery 1994;35:299 303. 12. Kobata H, Kondo A, Iwasaki K, Nishioka T. Combined hyperactive dysfunction syndrome of the cranial nerves: trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia: 11-year experience and review. Neurosurgery 1998;43:13511361. 13. Hiroki M, Miyashita K, Oda M. Tortuosity of the white matter medullary arterioles is related to the severity of hypertension. Cerebrovasc Dis 2002;13:242250. 14. Siqueira SR, Teixeira MJ, Siqueira JT. Clinical characteristics of patients with trigeminal neuralgia referred to neurosurgery. Eur J Dent 2009;3:207212. 15. Teruel A, Ram S, Kumar SK, Hariri S, Clark GT. Prevalence of hypertension in patients with trigeminal neuralgia. J Headache Pain 2009;10:199 201. 16. Jannetta PJ. Neurovascular compression in cranial nerve and systemic disease. Ann Surg 1980;192:518 525. 17. Defazio G, Berardelli A, Abbruzzese G, et al. Primary hemifacial spasm and arterial hypertension: a multicenter case-control study. Neurology 2000;54:1198 1200.
Neurology 77 October 25, 2011 1609

18. 19.

20.

21.

22. 23.

24.

25.

26.

Oliveira LD, Cardoso F, Vargas AP. Hemifacial spasm and arterial hypertension. Mov Disord 1999;14:832 835. Cha KS, Kim MH, Kim HJ. Prevalence and clinical predictors of severe tortuosity of right subclavian artery in patients undergoing transradial coronary angiography. Am J Cardiol 2003;92:1220 1222. Del Corso L, Moruzzo D, Conte B, et al. Tortuosity, kinking, and coiling of the carotid artery: expression of atherosclerosis or aging? Angiology 1998;49:361371. Dobrin PB, Schwarcz TH, Baker WH. Mechanisms of arterial and aneurysmal tortuosity. Surgery 1988;104: 568 571. Han HC. A biomechanical model of artery buckling. J Biomech 2007;40:36723678. Pickering TG. Neurovascular compression of the medulla: can it cause neurogenic hypertension? J Clin Hypertens 2007;9:63 66. Coffee RE, Nicholas JS, Egan BM, Rumboldt Z, DAgostino S, Patel SJ. Arterial compression of the retroolivary sulcus of the medulla in essential hypertension: a multivariate analysis. J Hypertens 2005;23:20272031. Kleineberg B, Becker H, Gaab MR, Naraghi R. Essential hypertension associated with neurovascular compression: angiographic findings. Neurosurgery 1992;30:834 841. Nicholas JS, DAgostino SJ, Patel SJ. Arterial compression of the retro-olivary sulcus of the ventrolateral medulla in

essential hypertension and diabetes. Hypertension 2005; 46:982985. 27. Saglitz SA, Gaab MR. Investigations using magnetic resonance imaging: is neurovascular compression present in patients with essential hypertension? J Neurosurg 2002;96: 1006 1012. 28. Zizka J, Ceral J, Elias P, et al. Vascular compression of rostral medulla oblongata: prospective MR imaging study in hypertensive and normotensive subjects. Radiology 2004;230:65 69. 29. Hohenbleicher H, Schmitz SA, Koennecke H-C, et al. Neurovascular contact of cranial nerve IX and X root-entry zone in hypertensive patients. Hypertension 2001;37: 176 181. 30. Naraghi R, Gaab MR, Walter GF, Kleineberg B. Arterial hypertension and neurovascular compression at the ventrolateral medulla: a comparative microanatomical and pathological study. J Neurosurg 1992;77:103112. 31. Carretero OA, Oparil S. Essential hypertension: part I: definition and etiology. Circulation 2000;101:329 335. 32. Wen CP, Tsai SP, Chung WS. A 10-year experience with universal health insurance in Taiwan: measuring changes in health and health disparity. Ann Intern Med 2008;148: 258 267. 33. Lin H-C, Chien C-W, Ho J-D. Herpes zoster ophthalmicus and the risk of stroke. Neurology 2010;74:792797.

Historical Abstract: June 1, 1992

DEMENTIA AFTER STROKE: BASELINE FREQUENCY, RISKS, AND CLINICAL FEATURES IN A HOSPITALIZED COHORT T.K. Tatemichi, D.W. Desmond, R. Mayeux, M. Paik, Y. Stern, M. Sano, R.H. Remien, J.B.W. Williams, J.P. Mohr, W.A. Hauser, and M. Figueroa Neurology 1992;42:1185-1193 We determined the frequency of dementia in a cohort of 251 patients aged 60 years hospitalized with acute ischemie stroke, based on examinations performed 3 months after stroke onset. Using modified DSM-III-R criteria, we found dementia in 66 patients (26.3%). Diagnostic agreement among raters was excellent (kappa 0.96). In a control sample of 249 stroke-free subjects recruited from the community and matched by age, we found dementia in eight subjects (3.2%). Using a logistic regression model to estimate the risk of dementia associated with stroke in the combined samples, the odds ratio (OR) for stroke patients compared with control subjects was 9.4 ( p 0.001). Advancing age and fewer years of education were significant, independent correlates of dementia, with a trend evident for race (non-white versus white). Confining the analysis to subjects residing in the Washington Heights-Inwood community of northern Manhattan, the OR was 10.3 ( p 0.001) with significant age and race effects. We conclude that ischemic stroke significantly increases the risk of dementia, with independent contributions by age, education, and race.
Free Access to this article at www.neurology.org/content/42/6/1185 Comment from Lalit Kalra, FRCP, PhD, Editorial Board Member: This seminal paper established the association between stroke and dementia, highlighting the contribution of ischemia to degenerative processes in the brain. It catalyzed research into the determinants and mechanisms for vascular dementias and understanding the relationships between vascular risk factors and progression of Alzheimer disease.

1610

Neurology 77

October 25, 2011