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Stroke Research and Treatment
Volume 2011 (2011), Article ID 879817, 5 pages
Long-Term Prognosis of Ischemic Stroke in Young Adults
Department of Internal Medicine, University Hospital “Madrid Montepríncipe”, CEU-San Pablo University School of Medicine and Institute of Applied Molecular Medicine (IMMA), Avenida Montepríncipe 25, Boadilla del Monte, 28660 Madrid, Spain
Received 19 August 2010; Revised 7 October 2010; Accepted 8 November 2010
Academic Editor: Janika Kõrv
Copyright © 2011 Jose F. Varona. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
There is limited information about long-term prognosis of ischemic stroke in young adults. Giving the potentially negative impact in physical, social, and emotional aspects of an ischemic stroke in young people, providing early accurate long-term prognostic information is very important in this clinical setting. Moreover, detection of factors associated with bad outcomes (death, recurrence, moderate-to-severe disability) help physicians in optimizing secondary prevention strategies. The present paper reviews the most relevant published information concerning long-term prognosis and predictors of unfavorable outcomes of ischemic stroke affecting young adults. As a summary, we can conclude that, in the long term, stroke in the young adult increases slightly the risk of mortality, implies higher risk of future cardiovascular events, and determines functional limitations in a significant percentage of patients. Nevertheless, in every individual case the prognosis has to be considered depending on several factors (stroke subtype, initial severity, cardiovascular risk factors) that determine the long-term outcomes.
Ischemic stroke in young adults (15–45 years) is not exceptional and accounts for up to 12% of all first ischemic strokes, with a wide diversity of etiologies [1–8]. Moreover, the impact on years of potential life lost and on socioeconomic cost is very important in this range of ages.
Many series have reported a favorable prognosis, but only the short-term prognosis has been widely evaluated and there are few investigations about long-term functional recovery of young adults with first-ever ischemic stroke.
Most of the investigations in long-term prognosis have described good functional recovery in young adults with ischemic stroke, since most patients are independent and at least 50% return to work [8–12]. Moreover, some predictive factors for mortality, recurrence, and good/poor functional recovery have been identified .
In the main series, the mean followup after the initial episode ranges between 1 and 16 years (Table 1) [9–33]. The most important methodological limitations in most of these studies are the retrospective design, but it is not so important to evaluate the long-term consequences of stroke, since events as recurrence, death, and disability can be easyly and accurately evaluated with this methodology. The review of the clinical records (including periodic outpatient reviews) complemented with telephone interviews is the main tools for obtaining information about the patients’ functional status after the stroke in the main studies about consequences of stroke in the young [9–14], including prospective series [10, 11].
The prognosis of ischemic stroke in the young is much better than in the elderly, with lower mortality and recurrence and better functional recovery . Thus, prognosis of stroke in young as a whole has been described as favorable in most of the series [12, 17–21], but the long-term prognosis is notably worse when compared with the general population of the same age, with higher death rate, higher risk of cardiovascular events, and significant limitations in quality of life . Moreover, in our series (with a mean followup of almost 12 years and mean age of 36 years old), only 57% of the patients followed for more than 3 years are alive, free of significant disability, stroke recurrence or other vascular event .
The overall risk of long-term death after an acute ischemic stroke in young adults is low. The reported cumulative risk of mortality is about 2% (95% confidence interval [CI], 1.5% to 3.9%) at 1 month, about 5% (3.1% to 6.5%) at 1 year, 9%-10% (8.5% to 11.5%) at 5 years, and 12% (11.2% to 13.0%) at 10 years [12, 31] (Table 2).
The mortality rate is higher in the first year (about 4%-5%; 95% CI: 1.8% to 6.0%) and decreases in following years (about 1.0% annually; 95% CI: 0.3% to 1.7%) [10–12, 21, 34]. Also the risk of vascular mortality is higher in the first year after stroke and then falls to lower risk in subsequent years. Thus, the mean vascular mortality rate is lower as longer is the followup.
The cumulative risk of mortality at 10 years in young adults with ischemic stroke is about almost 10 times higher than in the general population of the same age [12, 34], as shown in Figure 1, which compares the survival of young patients with ischemic stroke in our series against the survival of persons between 15–45 years in the Madrid Community [35, 36], indicating the negative impact on survival for suffering from ischemic stroke in the young .
However, the mortality of young adults with ischemic stroke is much lower than in older patients, since survival at five years is more than 90% in the young and only 40% in the elderly .
Among the survivors after a first-ever ischemic stroke, the main causes of death are stroke recurrence (20%–30%), other cardiovascular events (20%–50%), malignancies (15%–35%), and infections (10%) [9, 12, 31].
2.1. Risk Factors for Mortality
Apart from patients with malignancies, several subgroups of patients and some factors have been identified as associated with notably higher risk of death: increasing age (above 35 years; relative risk [RR] of 2.0 and hazard ratio [HR] of 2.5), male gender (RR of 1.9; HR of 2.1), the presence of cardiovascular risk factors, in particular arterial hypertension (HR 1.3), completed stroke, with total anterior circulation involvement (HR: 3.3), heart failure (HR: 5.2), heart and/or vascular disease (HR: 1.7), heavy drinking (HR: 2.8), large artery atherosclerosis (HR: 4.4), smoking (HR: 1.4), and severe neurological deficit at presentation (RR of 5.1) have been associated with mortality in young adults with ischemic stroke [10, 12, 31, 33]. The majority of these factors are associated with an atherosclerotic risk profile, which is present in older and male patients in whom premature atherosclerosis is much more prevalent  and prognosis is worse.
As “protective” factors, the following have been reported as associated with lower long-term mortality: stroke due to dissection of extracranial arteries, stroke associated with migraine, permanent poststroke anticoagulation therapy (in patients with cardioembolic stroke or potential cardiac sources of emboli and patients with hypercoagulable states) (RR 0.3), and hypercholesterolemia (RR 0.3). The protective role of hypercholesterolemia therapy has been reported in young [10, 12] as well as in elderly . This is due to the neuroprotective effect of drugs such as statins or fibrates, which are prescribed in young adults with stroke and hypercholesterolemia.
Ischemic stroke in relation to atherothrombotic (HR: 4.4) and cardioembolic (HR: 2.8) causes has been associated in some series with a poor prognosis. Conversely, several etiologies have been associated with better prognosis and lower percentages of mortality: lacunar infarct, nonatherosclerotic vasculopathy, hypercoagulable state, and undetermined/unknown etiology [9, 10, 31, 40].
3. Long-Term Functional Deficits
With respect to functional recovery, the prognosis for young adults with stroke is good, especially compared with the elderly. Some series have reported that up to 90% of patients with a long-term followup are independent for all activities of daily living and 95% are able to walk without any assistance in spite of previous stroke (Figure 2) [9–12].
Functional recovery and residual disability outcomes are often rated with modified Rankin scale (MRS), Barthel Index (BI), and Glasgow Outcome Scale (GOS). According to these scales, in the long-term followup even more than 70%–80% of the patients report no significant problems for daily activities (; ), about 10%–20% report moderate handicaps (), and only about 10% report major handicaps and residual dependency after ischemic stroke (MRS score higher than 3 and/or BI score less than 90) [12, 30, 41].
The reported predictive factors for better long-term functional recovery have been: age below 35, transient ischemic stroke, favorable initial course without severe handicaps at discharge, and stroke associated with migraine and/or oral contraceptives [11, 12]. No etiology has been significantly associated with a better or poorer functional recovery, but lacunar infarct and unknown etiology have been associated to a slightly better prognosis.
4. Occupational Status
Ischemic stroke in the young originates limitations in the quality of life and occupational status [9, 12, 20, 21, 40, 44]. Series have reported that between 50%–70% of young adults with stroke return to work, with a time period ranging from several days after stroke to 40 months, with a mean of 8 months. However, about 25% of them need adjustments [other job or part-time employment] in their occupation due to their inability after stroke to perform the prior activity, so less than half of the patients return to their previous work (Figure 2) [9, 10, 12, 30, 40, 45].
Transient ischemia (71%), undetermined stroke (69%), and nonatherosclerotic vasculopathy (64%) had been associated with a higher probability of returning to work .
5. Other Sequelae
In the reported series, between 20%–50% of patients have poststroke depression (using DSM-IIIR criteria and/or The Montgomery Asberg Depression Rating Scale). Most of these patients need specific psychiatric assistance. Stroke localization on carotid artery territory, a severe disability, and absence of return to work have been reported as associated with poststroke depression [12, 41].
6. Quality of Life
Few studies have evaluated specifically the quality of life after ischemic stroke in young people. In a Norwegian report, stroke had only moderate effects on self-reported health-related quality of life (HRQoL) among young adults with ischemic stroke as a group (the most affected domain was physical functioning), although some factors were associated with marked reduction in HRQoL: functionally dependant status, fatigue, depression, unmarried status, and unemployment . Other series conclude that aside from residual disability (mainly rated by MRS scale and BI), other factors which affect the quality of life are unemployment, motor impairment, aphasia, dysarthria, and dysphagia .
Thus, early identification and improved therapy for conditions such depression, fatigue, and physical disability may improve quality of life among young adults with ischemic stroke .
Recurrent stroke is frequent in the young, but lower compared with older patients, so cumulative recurrence rate at 5 years is almost 2 times lower in young (15%) than in older (29.5%) patients (Table 2) [12, 48].
The recurrence rate is higher in the first year (3%–5%) and decreases in following years (2%–5%). Thus, the annual recurrence rate between the second and twentieth year after stroke is less than 2% [10–12, 21, 33, 49] (Table 2).
Recurrence is more frequent in patients with atherothrombotic stroke (about 5% annual) than in those with stroke due to non-atherosclerotic vasculopathy (about 2%) .
Recurrent stroke may result in an important limitation in vital and functional prognosis, so about 15%–20% of patients died as the result of the recurrence, 30%–40% had severe handicaps with residual dependent status, and more than 50% receive permanent disability pension as a result of the recurrent stroke. These findings underline the importance of a properly secondary prevention therapy to avoid recurrence.
The predictive factors for recurrence in most of the studies are age over 35 years (RR: 1.7), the presence of cardiovascular risk factors (especially, diabetes mellitus, RR: 2.5), previous transient ischemic attack (RR: 1.5), and atherothrombotic stroke in the carotid territory (RR: 1.7). Stroke associated with migraine, stroke due to extracranial artery dissection, and patients with an unknown etiology have been associated with lower risk of recurrence [2, 12, 13, 20, 32, 33].
Although global risk of long-term death is low, first-ever ischemic stroke in young people has severe prognostic implications. The mortality risk is higher than general population, the risk of recurrent vascular events is considerable, and only about 50% of patients recover fully (without significant disability) and return to work after first-ever ischemic stroke. Several subgroups have notably increased risk of unfavorable outcomes in the long term and therefore need special attention. Thus, while the atherosclerotic risk profile is associated with the highest risk of recurrent stroke and mortality, age under 35 years and the stroke associated with dissection, migraine and/or contraceptives are associated with a good long-term outcome. Regarding young people with a long expected life span ahead, identifying factors associated to higher mortality is essential, because we can modify some of these factors with strict pharmacological control and/or invasive cardiovascular procedures in selected patients.
- J. F. Varona, J. M. Guerra, and F. Bermejo, “Stroke in young adults,” Medicina Clinica, vol. 122, no. 2, pp. 70–74, 2004.
- J. Bogousslavsky and P. Pierre, “Ischemic stroke in patients under age 45,” Neurologic Clinics, vol. 10, no. 1, pp. 113–124, 1992.
- J. F. Varona, J. M. Guerra, F. Bermejo, J. A. Molina, and A. Gomez De La Cámara, “Causes of ischemic stroke in young adults, and evolution of the etiological diagnosis over the long term,” European Neurology, vol. 57, no. 4, pp. 212–218, 2007.
- M. E. Shriver and L. D. Prockop, “The economic approach to the stroke work-up,” Current Opinion in Neurology and Neurosurgery, vol. 6, no. 1, pp. 74–77, 1993.
- R. G. Hart and V. T. Miller, “Cerebral infarction in young adults: a practical approach,” Stroke, vol. 14, no. 1, pp. 110–114, 1983.
- O. Lidegaard, M. Soe, and M. V. N. Andersen, “Cerebral thromboembolism among young women and men in Denmark 1977–1982,” Stroke, vol. 17, no. 4, pp. 670–675, 1986.
- P. Nencini, D. Inzitari, M. C. Baruffi et al., “Incidence of stroke in young adults in Florence, Italy,” Stroke, vol. 19, no. 8, pp. 977–981, 1988.
- C. Marini, R. Totaro, F. De Santis, I. Ciancarelli, M. Baldassarre, and A. Carolei, “Stroke in young adults in the community-based L'Aquila registry: incidence and prognosis,” Stroke, vol. 32, no. 1, pp. 52–56, 2001.
- L. J. Kappelle, H. P. Adams, M. L. Heffner, J. C. Torner, F. Gomez, and J. Biller, “Prognosis of young adults with ischemic stroke: a long-term follow-up study assessing recurrent vascular events and functional outcome in the Iowa Registry of Stroke in Young Adults,” Stroke, vol. 25, no. 7, pp. 1360–1365, 1994.
- C. Marini, R. Totaro, and A. Carolei, “Long-term prognosis of cerebral ischemia in young adults,” Stroke, vol. 30, no. 11, pp. 2320–2325, 1999.
- D. Leys, L. Bandu, H. Hénon et al., “Clinical outcome in 287 consecutive young adults (15 to 45 years) with ischemic stroke,” Neurology, vol. 59, no. 1, pp. 26–33, 2002.
- J. F. Varona, F. Bermejo, J. M. Guerra, and J. A. Molina, “Long-term prognosis of ischemic stroke in young adults: study of 272 cases,” Journal of Neurology, vol. 251, no. 12, pp. 1507–1514, 2004.
- B. Hindfelt and O. Nilsson, “The prognosis of ischemic stroke in young adults,” Acta Neurologica Scandinavica, vol. 55, no. 2, pp. 123–130, 1977.
- J. M. Ferro and M. Crespo, “Prognosis after transient ischemic attack and ischemic stroke in young adults,” Stroke, vol. 25, no. 8, pp. 1611–1616, 1994.
- C. Leno, J. Berciano, O. Combarros et al., “A prospective study of stroke in young adults in Cantabria, Spain,” Stroke, vol. 24, no. 6, pp. 792–795, 1993.
- N. Rozenthul-Sorokin, R. Ronen, A. Tamir, H. Geva, and R. Eldar, “Stroke in the young in Israel: incidence and outcomes,” Stroke, vol. 27, no. 5, pp. 838–841, 1996.
- A. I. Qureshi, K. Safdar, M. Patel, R. S. Janssen, and M. R. Frankel, “Stroke in young black patients: risk factors, subtypes, and prognosis,” Stroke, vol. 26, no. 11, pp. 1995–1998, 1995.
- J. Bogousslavsky and F. Regli, “Ischemic stroke in adults younger than 30 years of age. Cause and prognosis,” Archives of Neurology, vol. 44, no. 5, pp. 479–482, 1987.
- J. Marshall, “The cause and prognosis of strokes in people under 50 years,” Journal of the Neurological Sciences, vol. 53, no. 3, pp. 473–488, 1982.
- G. Lanzino, A. Andreoli, G. Di Pasquale et al., “Etiopathogenesis and prognosis of cerebral ischemia in young adults. A survey of 155 treated patients,” Acta Neurologica Scandinavica, vol. 84, no. 4, pp. 321–325, 1991.
- M. Camerlingo, L. Casto, B. Censori et al., “Recurrence after first cerebral infarction in young adults,” Acta Neurologica Scandinavica, vol. 102, no. 2, pp. 87–93, 2000.
- J. Matias-Guiu, J. Alvarez-Sabin, R. Falip, et al., “Prognosis of ischaemic stroke in young adults,” in Proceedings of the ECST Collaborators Meeting, Edimburg, Scotland, September 1991.
- J. Abraham, G. Sheety, and C. J. Jose, “Strokes in the young,” Stroke, vol. 2, no. 3, pp. 258–267, 1971.
- A. F. Haerer and R. R. Smith, “Cerebrovascular disease of young adults in a Mississippi teaching hospital,” Stroke, vol. 1, no. 6, pp. 466–476, 1970.
- C. E. Wells and R. J. Timberger, “Cerebral thrombosis in patients under fifty years of age,” Archives of Neurology, vol. 4, pp. 268–271, 1961.
- A. B. Grindal, R. J. Cohen, R. F. Saul, and J. R. Taylor, “Cerebral infarction in young adults,” Stroke, vol. 9, no. 1, pp. 39–42, 1978.
- B. D. Snyder and M. Ramirez Lassepas, “Cerebral infarction in young adults. Long term prognosis,” Stroke, vol. 11, no. 2, pp. 149–153, 1980.
- K. Srinivasan, “Ischemic cerebrovascular disease in the young. Two common causes in India,” Stroke, vol. 15, no. 4, pp. 733–735, 1984.
- A. M. Chancellor, G. L. Glasgow, P. A. Ockelford, A. Johns, and J. Smith, “Etiology, prognosis, and hemostatic function after cerebral infarction in young adults,” Stroke, vol. 20, no. 4, pp. 477–482, 1989.
- R. Musolino, P. La Spina, A. Granata et al., “Ischaemic stroke in young people: a prospective and long-term follow-up study,” Cerebrovascular Diseases, vol. 15, no. 1-2, pp. 121–128, 2003.
- J. Putaala, S. Curtze, S. Hiltunen, H. Tolppanen, M. Kaste, and T. Tatlisumak, “Causes of death and predictors of 5-year mortality in young adults after first-ever ischemic stroke: the Helsinki young stroke registry,” Stroke, vol. 40, no. 8, pp. 2698–2703, 2009.
- K. Nedeltchev, T. A. Der Maur, D. Georgiadis et al., “Ischaemic stroke in young adults: predictors of outcome and recurrence,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 76, no. 2, pp. 191–195, 2005.
- H. Naess, H. I. Nyland, L. Thomassen, J. Aarseth, and K. M. Myhr, “Long-term outcome of cerebral infarction in young adults,” Acta Neurologica Scandinavica, vol. 110, no. 2, pp. 107–112, 2004.
- U. Waje-Andreassen, H. Naess, L. Thomassen, G. E. Eide, and C. A. Vedeler, “Long-term mortality among young ischemic stroke patients in western Norway,” Acta Neurologica Scandinavica, vol. 116, no. 3, pp. 150–156, 2007.
- Instituto de Estadística. Consejería de Economía e Innovación Tecnológica. Comunidad de Madrid, “Estadísticas del movimiento natural de la población de la Comunidad de Madrid 1999. III,” Defunciones. 3, 3105, 178 pages.
- Censo de población. INE [MINECO], “Padrón Municipal de habitantes,” INE [MINECO], May 2003, http://www.copmadrid.es/.
- G. J. Hankey, K. Jamrozik, R. J. Broadhurst et al., “Five-year survival after first-ever stroke and related prognostic factors in the Perth Community Stroke Study,” Stroke, vol. 31, no. 9, pp. 2080–2086, 2000.
- A. Carolei, L. Candelise, M. Fiorelli, et al., “Long-term prognosis of transient ischemic attacks and reversible ischemic neurological deficits: a hospital-based study,” Cerebrovascular Diseases, vol. 2, pp. 266–272, 1992.
- C. Vauthey, G. R. De Freitas, G. Van Melle, G. Devuyst, and J. Bogousslavsky, “Better outcome after stroke with higher serum cholesterol levels,” Neurology, vol. 54, no. 10, pp. 1944–1948, 2000.
- J. Biller, H. P. Adams, A. Bruno, B. B. Love, and E. E. Marsh, “Mortality in acute cerebral infarction in young adults—a ten-year experience,” Angiology, vol. 42, no. 3, pp. 224–230, 1991.
- J. P. Neau, P. Ingrand, C. Mouille-Brachet et al., “Functional recovery and social outcome after cerebral infarction in young adults,” Cerebrovascular Diseases, vol. 8, no. 5, pp. 296–302, 1998.
- H. M. Dewey, J. Sturm, G. A. Donnan, R. A. L. Macdonell, J. J. McNeil, and A. G. Thrift, “Incidence and outcome of subtypes of ischaemic stroke: initial results from the North East Melbourne Stroke Incidence Study (NEMESIS),” Cerebrovascular Diseases, vol. 15, no. 1-2, pp. 133–139, 2003.
- P. M. W. Bath and K. R. Lees, “Acute stroke,” British Medical Journal, vol. 320, no. 7239, pp. 920–923, 2000.
- A. Adunsky, M. Hershkowitz, R. Rabbi, L. Asher-Sivron, and A. Ohry, “Functional recovery in young stroke patients,” Archives of Physical Medicine and Rehabilitation, vol. 73, no. 9, pp. 859–862, 1992.
- J. Rodríquez García, J. A. Expósito Tirado, J. S. Camacho, P. Ferrand Ferri, J. C. Pérez Herrera, and R. Del Pino Algarrada, “Functional recovery and return to work in the young patient after a stroke,” Neurologia, vol. 19, no. 4, pp. 160–167, 2004.
- H. Naess, U. Waje-Andreassen, L. Thomassen, H. Nyland, and K. M. Myhr, “Health-related quality of life among young adults with ischemic stroke on long-term follow-up,” Stroke, vol. 37, no. 5, pp. 1232–1236, 2006.
- J. S. Kim, S. Choi-Kwon, S. U. Kwon, et al., “Factors affecting the quality of life after ischemic stroke: young versus old patients,” The Journal of Clinical Neurology, vol. 1, pp. 59–68, 2005.
- J. Burn, M. Dennis, J. Bamford, P. Sandercock, D. Wade, and C. Warlow, “Long-term risk of recurrent stroke after a first-ever stroke: the Oxfordshire community stroke project,” Stroke, vol. 25, no. 2, pp. 333–337, 1994.
- T. C. D. Rettig, B. J. Bouma, and R. B. A. Van Den Brink, “Influence of transoesophageal echocardiography on therapy and prognosis in young patients with TIA or ischaemic stroke,” Netherlands Heart Journal, vol. 17, no. 10, pp. 373–377, 2009.