The impact of leucoaraiosis on neurological function recovery in elderly patients with acute cerebral infarction: Clinical study involving 279 Chinese patients

Abstract

Objective

To explore the link between leucoaraiosis and recovery of neurological function in elderly patients with acute cerebral infarction.

Methods

The study included elderly patients, hospitalized with acute cerebral infarction. Magnetic resonance imaging examinations were performed before or within 5 days after admission; T1-weighted, T2-weighted, fluid-attenuated inversion recovery and diffusion-weighted imaging sequence data were collected. Using the Fazekas scale, leucoaraiosis (white matter hyperintensity [WMH]) was graded as 0 (absent), 1 (mild), 2 (moderate) or 3 (severe) for all participants.

Results

The study included 279 patients. WMH grades of 0, 1, 2 and 3 were seen in 27 (9.67%), 90 (32.26%), 104 (37.28%) and 58 cases (20.79%) respectively. Improvement on the National Institutes of Health Stroke Scale for neurological impairment was negatively associated with WMH grade. Patients with severe leucoaraiosis at hospital admission had worse neurological functional recovery and a higher rate of self-care incapability compared with those with mild or no leucoaraiosis.

Conclusions

The results suggest that severe leucoaraiosis in elderly patients with acute cerebral infarction is associated with poor prognosis and poor recovery of neurological function.

Keywords

Leucoaraiosis diffusion-weighted imaging National Institutes of Health Stroke Scale acute cerebral infarction neurological recovery outcome

Introduction

Research shows that the degree of leucoaraiosis can predict 90-day clinical outcomes in patients with acute aortic occlusion.^1–3 Furthermore, acute cerebral infarction (stroke) patients with severe leucoaraiosis in the deep white matter is associated with a high risk of brain parenchymal haematoma after mechanical embolectomy.⁴ Acute cerebral infarction patients with leucoaraiosis have a much higher incidence of haemorrhagic transformation after thrombolytic therapy compared with patients without leucoaraiosis.⁵ Leucoaraiosis has therefore been proposed as an important risk factor for a poor prognosis in stroke patients.^2,6 However, few studies have focused on the association between leucoariosis and the prognosis of cerebral infarction in elderly patients.^7,8 In the present study, associations between the degree of brain white matter hyperintensity (WMH) and clinical prognosis, neurological function recovery and self-care capability after treatment were analysed in elderly patients with acute cerebral infarction.²

Patients and methods

Patient selection and examinations

All elderly patients with acute cerebral infarction hospitalized in Beijing Military General Hospital between January and December 2007 were included in the study; those with cerebral haemorrhage, subarachnoid haemorrhage or other nonstroke-related conditions were excluded. All patients provided written informed consent prior to participation. The study was approved by the Institutional Review Board of Beijing Military General Hospital.

Patients were admitted to hospital within 7 days of symptom onset. All hospitalized patients with acute cerebral infarction met the diagnostic criteria of the 4th Chinese Cerebrovascular Diseases Conference (1995). Magnetic resonance imaging (MRI) examination was performed before or within 5 days after admission, using a Signa 1.5 T (GE Healthcare, Chalfont St Giles, UK) superconducting system. T1-weighted, T2-weighted, fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging sequences were obtained. Diffusion-weighted imaging confirmed visible fresh infarction lesions in all enrolled patients.

Within 5 days after hospital admission, MRI FLAIR images were examined by two independent neurologists (W.W. and J-J.G.) who were unfamiliar with the patient’s clinical condition. Using the Fazekas method, brain WMH was rated as 0 (none), 1 (mild), 2 (moderate) or 3 (severe).

Each patient’s scores on the National Institutes of Health Stroke Scale (NIHSS) for neurological impairment were evaluated on days 1, 7 and 14 after admission and on the day of discharge. Each patient was also evaluated for the degree of disability or dependence in their daily activities using the modified Rankin scale (mRS) on the day of discharge; each patient was recorded as having either self-care capability (mRS ≤2) or self-care incapability (mRS ≥3).

After admission, all patients received standardized treatment regimens based on the Chinese guidelines for cerebrovascular disease prevention and treatment for stroke.^9,10

All clinical investigations were conducted according to the principles of the Declaration of Helsinki.

Statistical analyses

Statistical analyses were performed using SPSS® version 13.0 (SPSS®, Chicago, IL, USA). All quantitative values were expressed as mean ± SD. Because patients’ NIHSS scores were not normally distributed, the Kruskal–Wallis method for nonparametric testing was used to analyse the associations between WMH grade and neurological function. χ²-test or Fisher’s exact test were used to analyse differences between groups in risk-factor frequencies. Student’s t-test was used to analyse differences between groups in quantitative variables. Unconditional logistic analyses were performed to investigate risk factors associated with clinical outcome; patients’ living skills (measured as the mRS score), age, sex, WMH grade, admission NIHSS score and improvement in NIHSS score were included as independent variables. A P-value of <0.05 was considered to indicate statistical significance.

Results

The study enrolled 279 patients (191 male and 88 female; age range 65–94 [mean 73.11 ± 10.32]) years. WMH grade 0 was seen in 27 (9.67%), grade 1 in 90 (32.26%), grade 2 in 104 (37.28%) and grade 3 in 58 patients (20.79%). No significant correlations between NIHSS score and brain white matter change were found in patients with different WMH grades on days 1, 7 and 14 after admission or on the day of discharge (Table 1).

Table 1.

Association between National Institutes of Health Stroke Scale (NIHSS) score and white matter hyperintensity (WMH) grade in elderly acute cerebral infarction patients at different timepoints.

Timepoint	WMH grade				Statistical significance^a
Timepoint	0	1	2	3	Statistical significance^a
NIHSS score
Admission	7.15 ± 2.75	7.62 ± 4.30	8.14 ± 4.79	8.77 ± 4.37	NS
7 days after admission	4.95 ± 2.72	6.14 ± 4.43	6.94 ± 4.86	7.31 ± 4.58	NS
14 days after admission	3.70 ± 2.95	5.65 ± 3.96	5.91 ± 4.45	6.73 ± 4.63	NS
Day of discharge	2.95 ± 2.04	4.43 ± 3.26	5.10 ± 3.97	5.74 ± 3.67	NS
NHSS score improvement
Baseline to 7 days after admission^a	−2.35 ± 1.43	−1.27 ± 1.49	−1.38 ± 1.24^Δ	−1.13 ± 1.20^a	P = 0.024
Baseline to 14 days after admission^a	−3.37 ± 1.98	−2.73 ± 1.93	−2.47 ± 2.17	−2.54 ± 2.10^a	P = 0.047
Baseline to discharge^a	−3.24 ± 2.14	−2.71 ± 1.91	−2.16 ± 1.76	−1.94 ± 2.01^ab	P = 0.021

Data presented as mean ± SD. NS, not statistically significant.

Data were analysed using Kruskal‐Wallis test.

P < 0.05 compared with WMH grade 0 group; ^bP < 0.05 compared with WMH grade 1 group.

The NIHSS score improvements between baseline (before admission) and 7 days after admission (P = 0.024) and between baseline and discharge (P = 0.021) were negatively associated with WMH grade. The NIHSS score improvements between baseline and 14 days after admission showed a similar trend, but the P-value was slightly higher (P = 0.047). Pairwise comparison showed that the NIHSS score improvement between different timepoints after admission in the group with a WMH grade of 3 was smaller than that in the group with a WMH grade of 0 (P < 0.05) (Table 1).

At the time of discharge, stroke patients who had severe leucoaraiosis on admission (WMH grade ≥2) had a high probability of self-care incapability (P < 0.05). The mortality rate tended to increase with increasing WMH grade, but no significant difference was observed (Table 2).

Table 2.

Status of elderly acute cerebral infarction patients with different white matter hyperintensity (WMH) grades at the time of discharge.

Patient status	WMH grade				Statistical significance
Patient status	0	1	2	3	Statistical significance
Self-care capable	21/27 (77.78)	66/87 (75.86)	59/98 (60.20)	31/54 (57.41)	P = 0.033
Self-care incapable	6/27 (22.22)	21/87 (24.14)	39/98 (39.80)	23/54 (42.59)	P = 0.033
Alive	27/27 (100.00)	87/90 (96.67)	98/104 (94.23)	54/58 (93.10)	NS
Dead	0/27 (0.00)	3/90 (3.33)	6/104 (5.77)	4/58 (6.90)	NS

Data presented as n (%) of patients. NS, not statistically significant.

Data were analysed using Fisher’s exact test.

Results of the logistic regression analysis showed that the NIHSS score on the day of admission (odds ratio [OR] 3.517, 95% confidence interval [CI] 2.782, 6.443) and WMH grade on the day of admission (OR 3.702, 95% CI 2.639, 5.445) were independent factors predicting the patient’s self-care incapability on the day of discharge.

Discussion

In the present study we found that elderly stroke patients with severe leucoaraiosis at the time of admission (WMH grade ≥2) had a high probability of self-care incapability after treatment (P < 0.05). The NIHSS score improvement was also negatively associated with the patients’ leucoaraiosis severity (P < 0.05). Mortality tended to increase with WMH grade, but not significantly. Thus, we suggest that severe leucoaraiosis was associated with poor prognosis in elderly stroke patients.

Leucoaraiosis is an independent prediction factor for stroke.^2,11 After the first infarct, patients with severe leucoaraiosis had a higher risk of recurrence of stroke than those without leucoaraiosis or with mild leucoaraiosis.^2,11 However, few studies have focused on the association between brain leucoaraiosis and prognosis in stroke patients; results are inconclusive.¹² Thus, we suggest that severe leucoaraiosis is associated with poor prognosis in elderly stroke patients. Furthermore, the NIHSS score and WMH grade on the day of admission were independent risk factors for clinical outcome in elderly stroke patients.

Among patients with transient ischaemic attack and lacunar infarction, the stroke recurrence rate in those with leucoaraiosis was 60% higher than in those without leucoaraiosis.¹³ Leucoaraiosis is known to be associated with cognitive impairment,¹⁴ gait and balance impairment,¹⁵ mood changes and depression, urinary incontinence, decline in daily living capability¹⁶ and other clinical manifestations. Podgorska et al.¹² studied 370 patients with acute stroke and analysed the association between patient prognosis and leucoaraiosis severity. They found that the 1-year mortality rate was significantly higher in patients with, than in those without, leucoaraiosis.¹² However, no significant difference in mortality was observed 30 days after clinical onset.¹²

In the present study, no significant difference was observed in mortality in patients with or without leucoaraiosis during the period of hospitalization. These results are consistent with those of Podgorska et al.¹² However, in the present study stroke patients with leucoaraiosis had a higher rate of self-care incapability than patients without leucoaraiosis, so the difference in mortality between our study and that of Podgorska et al.¹² may be related to a difference in the methods used to evaluate self-care incapability.¹²

Leucoaraiosis had a substantial impact on the patients’ neurological functional recovery and self-care capability in the present study. Studies have shown that leucoaraiosis volume is an independent predictor of infarct size in stroke patients.¹⁷ This is probably one reason why acute infarction patients who also have leucoaraiosis have a poor prognosis. In addition, patients with severe leucoaraiosis often also have cerebrovascular disease and cognitive dysfunction, which may affect functional recovery.¹⁸ It has been shown that long-term mortality and the incidence of pneumonia are greater in neurology outpatients who have leucoaraiosis than in those without leucoaraiosis.¹⁹ Furthermore, patients with leucoaraiosis are susceptible to lung and urinary tract infections, which might also be linked to their poor prognosis.¹⁹

In conclusion, Chinese elderly patients with acute infarction and severe leucoaraiosis had a poorer prognosis than those without leucoaraiosis or with minor leucoaraiosis, in the present study. Dufouil et al.²⁰ showed that positive blood-pressure control can reverse or slow the progress of leucoaraiosis; their study²⁰ has brought new hope for the prevention and treatment of leucoaraiosis.

Footnotes

Declaration of conflicting interest

The authors declare that there are no conflicts of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

References

Henninger

Lin

Baker

. Leukoaraiosis predicts poor 90-day outcome after acute large cerebral artery occlusion. Cerebrovasc Dis 2012; 33: 525–531.

Neumann-Haefelin

Hoelig

Berkefeld

. Leukoaraiosis is a risk factor for symptomatic intracerebral hemorrhage after thrombolysis for acute stroke. Stroke 2006; 37: 2463–2466.

Demchuk

Khan

Hill

. Importance of leukoaraiosis on CT for tissue plasminogen activator decision making: evaluation of the NINDS rt-PA Stroke Study. Cerebrovasc Dis 2008; 26: 120–125.

Shi

Loh

Liebeskind

. Leukoaraiosis predicts parenchymal hematoma after mechanical thrombectomy in acute ischemic stroke. Stroke 2012; 43: 1806–1811.

Palumbo

Boulanger

Hill

. Leukoaraiosis and intracerebral hemorrhage after thrombolysis in acute stroke. Neurology 2007; 68: 1020–1024.

Pantoni

. Leukoaraiosis: from an ancient term to an actual marker of poor prognosis. Stroke 2008; 39: 1401–1403.

Hénon

Godefroy

Lucas

. Risk factors and leukoaraiosis in stroke patients. Acta Neurol Scand 1996; 94: 137–144.

Karsidag

Ozer

Karsidag

. Relationship of leukoaraiosis to vascular risk factors and lesion type in stroke patients. Ann Saudi Med 1995; 15: 107–109.

Liu

Wang

. Stroke in China: epidemiology, prevention, and management strategies. Lancet Neurol 2007; 6: 456–464.

10.

Zhao

Liu

Wang

. Epidemiological transition of stroke in China: twenty-one-year observational study from the Sino-MONICA-Beijing Project. Stroke 2008; 39: 1668–1674.

11.

Hong

. Extent of white matter lesions is related to acute subcortical infarcts and predicts further stroke risk in patients with first ever ischaemic stroke. J Neurol Neurosurg Psychiatry 2005; 76: 793–796.

12.

Podgorska

Hier

Pytlewski

. Leukoaraiosis and stroke outcome. J Stroke Cerebrovasc Dis 2002; 11: 336–340.

13.

Inzitari

. Leukoaraiosis: an independent risk factor for stroke? Stroke 2003; 34: 2067–2071.

14.

Schmidt

Petrovic

Ropele

. Progression of leukoaraiosis and cognition. Stroke 2007; 38: 2619–2625.

15.

Baezner

Blahak

Poggesi

. Association of gait and balance disorders with age-related white matter changes: the LADIS study. Neurology 2008; 70: 935–942.

16.

Inzitari

Simoni

Pracucci

. Risk of rapid global functional decline in elderly patients with severe cerebral age-related white matter changes: the LADIS study. Arch Intern Med 2007; 167: 81–88.

17.

Arsava

Rosand

. Severity of leukoaraiosis and susceptibility to infarct growth in acute stroke. Stroke 2008; 39: 1409–1413.

18.

Werring

Frazer

Coward

. Cognitive dysfunction in patients with cerebral microbleeds on T2*-weighted gradient-echo MRI. Brain 2004; 127: 2265–2275.

19.

Briley

Haroon

Sergent

. Does leukoaraiosis predict morbidity and mortality? Neurology 2000; 54: 90–94.

20.

Dufouil

Chalmers

Coskun

. Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging Substudy. Circulation 2005; 112: 1644–1650.