Stroke in young adults

Prognosis and complications
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By Bartlomiej Piechowski-Jozwiak MD, Jorge Moncayo-Gaete MD, and Julien Bogousslavsky MD

The prognosis and complications of stroke in young patients are highly dependent on the underlying cause of stroke, as well as the amount and location of CNS damage. The 30-day case fatality is low, particularly in ischemic stroke (0% to 6%), whereas it ranges from 20% to 36% for cerebral hemorrhage (Jacobs et al 2002; Spengos and Vemmos 2010; Groppo et al 2012). The NOMASS data showed that 30-day case fatality rates were higher in blacks and Hispanics than in whites (Jacobs et al 2002). Nedeltchev and colleagues found that higher admission NIH Stroke Scale scores, total anterior circulation stroke syndrome, and diabetes mellitus were independent predictors of unfavorable outcome; in their study, 68% achieved a modified Rankin score (mRS) of 0 to 1, 26% had a mRS score of 2 to 5, and 3% were dead by 3 months (Nedeltchev et al 2005). In a large prospective cohort of 968 patients aged 15 to 49 years, outcome at 3 months after first-ever cerebral infarct was found to be favorable (mRS 0-1) in approximately half of the patients, and 80% were functionally independent (mRS 0-2) (Putaala et al 2013). Increasing age, stroke severity, and size of infarct were directly related to unfavorable outcome in this cohort. Moreover, high-density lipoprotein (HDL) levels were inversely correlated with adverse functional outcome (Putaala et al 2013).

In a French study of 287 young adult stroke patients by Leys and colleagues, the mortality rate was 4.5%, and the recurrence rate was 1.4% during the first year, dropping to 1.6% and 1% in the subsequent 2 years, respectively. Myocardial infarction occurred in 0.2% and seizures in 6.6% (Leys et al 2002). Another study found a rate of recurrence of 7.4%, with nearly 90% having a moderate to excellent outcome (Musolino et al 2003). In the Iowa Stroke Registry, mortality was associated with age greater than 25 years and large-artery stroke etiology. In the Iowa study 7% of patients died from the initial stroke, 14% died over a follow-up period of 6 years, 9% had recurrent strokes, 0.4% had subsequent myocardial infarction, and only 49% of young stroke patients were still alive, were not disabled, were without recurrent vascular events, or had not undergone major vascular surgery by the end of the mean 6-year follow-up (Kappelle et al 1994). In a Spanish study of 240 young adult stroke patients (Varona et al 2004), 88% were alive after a mean follow-up of 12.3 years. The average mortality rate was 4.9% in the first year and 0.9% in subsequent years. Recurrent stroke occurred in 3.6% in the first year and 1.7% in subsequent years. Age greater than 35 years, male gender, carotid artery stenosis and the presence of cardiovascular risk factors was associated with worse outcome.

A 4.5% annual rate of symptomatic recurrent cerebral ischemic events (TIA or cerebral infarction) was found in 94 young patients with a follow-up of 48 months, most often in patients with an index cardioembolic infarct, followed by patients with an undetermined cause of infarct and a nonatherosclerotic vasculopathy. A neuroradiological (brain MRI) follow-up was performed 48 months after the index event in all 94 patients. Silent cerebral infarcts (lacunes) were documented in 9.5% of patients, mostly in patients with embolism from a cardiac source and undetermined cause of stroke (Patella et al 2011).

In a cohort of 250 young patients with cerebral infarct with a mean follow-up period of 52 months, the estimated 10-year survival rate was 86% and the probability of composite vascular events (recurrent stroke, vascular death, and myocardial infarction) was 30.4%. Heart failure and initial stroke severity were the leading independent predictors of mortality. Men tended to have a lower survival rate and higher risk of composite vascular events than women (Spengos and Vemmos 2010).

Aarnio and colleagues studied long-term mortality and stroke recurrence in first-ever ischemic stroke for patients aged 15 to 49 years adults (mean follow-up of 10.2 ± 4.3 years) (Aarnio et al 2014). They found a 15.7% mortality rate (cumulative risk, 23.0%; 95% CI;19.1-26.9) and a 13.6% recurrent stroke rate. The most important risk factor for mortality after first-ever ischemic stroke was recurrent stroke (hazard ratio, 16.68; 2.33-119.56). Observed mortality was 7-fold higher than the expected mortality (standardized mortality ratio, 6.94; 95% confidence interval, 5.84-8.04) and particularly high among patients who experienced a recurrent stroke (standardized mortality ratio, 14.43; 95% confidence interval, 10.11-18.74) (Aarnio et al 2014).

Young adult patients with stroke remain at substantial risk of vascular recurrence in the long-term after an index event. After a mean follow-up of 9.1 years, one fifth of 724 consecutive patients with a first-ever transient ischemic attack, cerebral infarct, or intracerebral hemorrhage experienced at least 1 incident vascular event (stroke, myocardial infarction, or cardiac or peripheral arterial revascularization procedures) (Rutten-Jacobs et al 2013). The risk of any vascular recurrence was highest in the year following the index transient ischemic attack or cerebral infarct. In young adult patients with a cerebral infarct as index event, the 20-year cumulative stroke risk (19%) or any vascular event (33%) was higher compared with those patients with an initial transient ischemic attack or intracerebral hemorrhage. According to subgroups of TOAST criteria, the higher 20-year cumulative stroke recurrence risk was observed in patients with initial lacunar infarct (30%), whereas the atherothrombotic and cardioembolic stroke subgroups each had a 20-year cumulative stroke recurrence risk of 24%, and in patients with infarct of undetermined etiology the 20-year cumulative stroke recurrence risk was 12% (Rutten-Jacobs et al 2013).

Pezzini and associates followed 1867 patients with first-ever ischemic stroke (18 to 45 years of age) for a median of 40 months (Pezzini et al 2014). They found 163 patients to have recurrent thrombotic events (average rate, 2.26 per 100 person-years at risk). The 10 year cumulative risk of these events was estimated at the level of 14.7% (95% CI; 12.2%-17.9%). The cumulative risk for brain ischemia was 14.0% (95%CI; 11.4%-17.1%) and 0.7% (95% CI; 0.4%-1.3%) for myocardial infarction or other arterial events. The independent predictors of recurrent thromobotic events were familial history of stroke, migraine with aura, circulating antiphospholipid antibodies, discontinuation of antiplatelet and antihypertensive medications, and any increase of 1 traditional vascular risk factor (Pezzini et al 2014). Young adults with a previous transient ischemic attack have a 20-year cumulative risk of stroke of 17% and a 28% risk of any vascular event. Young adults with intracerebral hemorrhage exhibited the lowest risk of stroke recurrence (10%) and of any vascular event (11.6%) (Rutten-Jacobs et al 2013).

Data about mortality after intracerebral hemorrhage is scarce. In a Finnish retrospective cohort, the mortality rate in 325 patients from the ages of 16 to 49 years with a first-ever nontraumatic intracerebral hemorrhage was 17% at 3 months. A higher 3-month mortality rate was associated with higher National Institutes of Health Stroke Scale scores, infratentorial hematoma location, and multiple hemorrhages. This observational study showed a lower mortality rate for patients undergoing surgical evacuation of hematoma than for those receiving conservative treatment (Koivunen et al 2014).

Although the incidence of stroke in young adults is low and the outcome and prognosis generally favorable as compared to the older population, the impact of stroke is much higher in the former with even minor residual deficits resulting in substantial loss of economic productivity and severe emotional or social sequelae that impair quality of life. In the Iowa study, only 42% of patients were able to resume work, and the majority reported emotional, social, or physical residuals that impacted quality of life (Kappelle et al 1994). In the study by Leys and colleagues, favorable outcome (mRS 0-2) was observed in 94%; however, 4.2% lost their job despite achieving a mRS score of 0 to 1. The emotional, social, and physical problems affecting young stroke patients have also been emphasized by another study (Neau et al 1998). Patients with strokes of unknown cause, however, do seem to have the lowest risk of stroke recurrence, with a relative risk of 0.1 compared to those with known cause (Kappelle et al 1994).

A nearly 12-year follow-up of a retrospectively selected cohort of patients with brain infarction at a young age (mean age of 41 at index event) showed the worst prognosis compared with matched controls by sex and age. Thus, 77% of 187 young stroke patients had a two-fold higher rate of depression, anxiety, and sleeping problems compared to a control population, whereas memory deficit was 8 times higher in stroke patients as compared with controls. Also, young stroke patients were less able to handle full-time work compared with controls (Waje-Andreassen et al 2013).

Furthermore, in the last year, data of cognitive performance after a longer follow-up has been reported in a prospective cohort of 277 young patients with a mean age of 40 at index infarct (56% women, mostly with a good outcome according to the Barthel Index at follow-up) having a first-ever ischemic stroke, compared with a matched stroke-free population (146 controls) (Schaapsmeerders et al 2013). The median follow-up was 11 years and almost half the patients had a follow-up of over 10 years. Compared with matched controls, up to 50% of young stroke patients exhibited below-average cognitive performance or impairment in processing speed, executive functioning, attention, working, and immediate and delayed memory. Regarding the location of index stroke, patients with supratentorial infarct on the left side had the worst cognitive outcome (Schaapsmeerders et al 2013).

Long-term cognitive outcomes in young ischemic stroke patients (n = 96; median age at index event 43.0 years; 45.8% male) were studied by de Bruijn and colleagues (de Bruijn et al 2014). This study excluded patients with severe aphasia or preexistent cognitive impairment. Visual perception, visual and verbal memory, mental speed, and executive functioning were assessed and compared to controls with adjustment for education level. The authors found that the patients performed significantly worse than controls in mental speed tests (Stroop Color-Word Test Part 1 and Symbol-Digit Substitution Task), and verbal memory assessments (Word Pair test). These data confirm long-term cognitive impairment in this patient population (de Bruijn et al 2014).

Seizures within 7 days of ischemic stroke (acute symptomatic seizures) occurred in 3.5% of 995 young patients (ranging in age from 15 to 49 years) with a first-ever ischemic stroke included in a retrospective observational cohort (Roivainen et al 2013). Nearly 60% of seizures occurred in the first 24 hours after stroke onset. Anxiolytic use, moderate stroke severity, cortical involvement, and hyponatremia at the time of index stroke were independently associated with a higher risk of acute symptomatic seizures. In addition, in the same cohort at 5 years after index infarct, 1 out of 10 young ischemic stroke patients developed late poststroke seizures (7 days from brain infarct; patients with previous epilepsy were excluded). Total or partial anterior circulation infarct (Bamford criteria), history of acute symptomatic seizures, hemorrhagic infarction, antidepressant use at the time of late poststroke seizures, male gender, and hyperglycemia were independently associated with a higher risk for late poststroke seizures (Roivainen et al 2013).

The risk of poststroke epilepsy (7 days after the initial event) was reported in another recent cohort of around 700 young adult stroke patients (mean age of 40.5, ranging from 18 to 50), 60% with cerebral infarct, 10% with intracerebral hemorrhage, and the remainder with a transient ischemic attack (Arntz et al 2013). In this series, 11% developed epilepsy after a mean follow-up of 9 years and 6% developed epilepsy with recurrent seizures, mainly within the first 12 months after the stroke. The first poststroke seizure was tonic-clonic generalized in one third of patients and simple partial in another third of patients. The highest risk of epilepsy was observed in patients with intracerebral hemorrhage (17%), followed by patients with cerebral infarct (14%), and the lowest risk was observed in patients with transient ischemic attack (3%). Cumulative risk of both poststroke epilepsy and epilepsy with recurrent seizures was higher in patients with intracerebral hemorrhage as compared to the other stroke subtypes. A high NIHSS score at admission was found to be a predictor of poststroke epilepsy and epilepsy with recurrent seizures (Arntz et al 2013).

In This Article

Historical note and nomenclature
Clinical manifestations
Clinical vignette
Pathogenesis and pathophysiology
Differential diagnosis
Diagnostic workup
Prognosis and complications
References cited