| Revised: 5 January 2019 | Accepted: 6 January 2019

DOI: 10.1111/1440-1681.13067  

ORIGINAL ARTICLE

Successful intravenous Alteplase for a centenarian woman with
acute ischaemic stroke
Chaoming He1 | Yanyan Sun2 | Bo Yan1 | Haiyun Chen1 | Yu Zheng1

| Ying Tang2

1
Third People's Hospital of Hainan Province,
Sanya, Hainan, China

Summary

2

Department of Neurology, The First
Affiliated Hospital of Harbin Medical
University, Harbin, China

We report a case of a 105‐year‐old woman who was treated with Alteplase for acute

Correspondence
Ying Tang, Department of Neurology, The
First Affiliated Hospital of Harbin Medical
University, Harbin, Heilongjiang Province,
China.
Email: [email-masked]

(NIHSS) score was 21. An acute noncontrast brain CT scan showed only mild white

ischaemic stroke (AIS). On arrival, this centenarian woman had sudden‐onset aphasia
and right‐sided hemiparesis, her baseline National Institutes of Health Stroke Scale

Funding information
This study was supported by National
Natural Science Foundation of China (Grant
# 81771508).

matter disease. After assessing the patient's risk‐benefit ratio, the patient was admin‐
istered intravenous Alteplase (0.9 mg/kg) 2.5 hours after symptom onset. Her right
hemiparesis and aphasia eased within 24 hours after Alteplase treatment. At dis‐
charge, her NIHSS score had decreased to 1, leaving only mild right facial palsy unre‐
solved. Few clinical data are available on centenarian patients with AIS who undergo
intravenous thrombolysis. There are no data on what is the best method to use to
manage centenarians. Our successful thrombolysis case indicates that biologically
young centenarians may profit from thrombolysis, despite the very high age.
KEYWORDS

acute ischaemic stroke, centenarian, intravenous thrombolysis, tissue‐type plasminogen
activator

1 | I NTRO D U C TI O N

who were ≥90 years old is very small, and the benefit of IV r‐tPA

Recombinant tissue plasminogen activator (r‐tPA) is a thrombolytic

tively high age, centenarians display clinical characteristics different

drug that remains the only medication proven to improve outcomes

from those of younger elderly populations (patients aged less than

in selected patients with acute ischaemic stroke (AIS) when given

100 years old). Here, we report and discuss a case of a 105‐year‐old

in patients ≥90 years of age is not clear. Among patients with rela‐

1,2

within 4.5 hours of symptom onset.

Alteplase‐associated symp‐

tomatic intracranial haemorrhage (sICH) is a clinically feared com‐

woman with AIS who has undergone successful intravenous r‐tPA
thrombolysis.

plication. Because high age itself is a widely acknowledged high risk
factor associated with bad outcomes and sICH after treatment with
intravenous IV r‐tPA, patients with extreme chronological age are

2 | C A S E D E S C R I P TI O N

often excluded from clinical practice or trials of IV r‐tPA for AIS.3
The safety and efficacy of intravenous thrombolysis with r‐tPA in

The patient, a 105‐year‐old right‐handed female with a history of

the elderly population with AIS have always been two main problems

hypertension and chronic bronchitis, was admitted to the Third

for clinicians. Many randomized trials have provided evidence of the

People's Hospital of Hainan Province emergency room with main

benefits of r‐tPA in stroke patients ≥80 years old. 2,4,5 Administration

symptoms of sudden‐onset aphasia and right‐sided hemiparesis. She

of IV r‐tPA within 3 hours or between 3 and 4.5 hours has been of‐

had no history of diabetes mellitus, dyslipidaemia or cardiac prob‐

ficially recommended for the treatment of this special elderly sub‐

lems, liver or kidney disease or blood disease. On arrival, the patient

6

group AIS patients. However, the number of patients in these trials

Clin Exp Pharmacol Physiol. 2019;46:423–426.

was sober, and the baseline National Institutes of Health Stroke Scale

wileyonlinelibrary.com/journal/cep 
© 2019 John Wiley & Sons Australia, Ltd

|

423

424

|

HE et al.

F I G U R E 1 A 105‐year‐old female
patient presented with right hemiparesis
and aphasia. A, On admission, a CT scan
showed only mild white matter disease.
B, On day 3, there were acute small left
middle cerebral artery (MCA); infarcts on
diffusion weighted imaging (DWI). C, On
day 3, magnetic resonance angiography
(MRA) showed a fully re‐canalized MCA
(NIHSS) score was 21. Her blood pressure was 155/100 mm Hg. An

intracranial bleeding was found for those ≥80 years of age.7 The

acute noncontrast brain computed tomography (CT) scan showed

older patients were not only less likely to achieve good outcomes

only a slight atrophy and a mild white matter disease (no hyperden‐

but also more likely to end with a larger infarct volume and to die

stiy of the left middle cerebral artery (MCA); no hypoattenuation

in‐hospital than was found in younger individuals regardless of r‐

was detected in the left caudate, the lenticular nucleus or the insula,

tPA administration.7-10

and no grey‐white matter differentiation was detected in the adja‐
cent cortex), as shown in Figure 1A. A 0.9 mg/kg dose of intrave‐
nous r‐tPA was given 2.5 hours after symptom onset, and the patient

3.2 | The significance of this centenarian case

was transferred to our stroke unit. The results of screening serum

Among the advanced age population, evidence for thrombolytic safety

chemistry were all unremarkable and had no signs of kidney insuf‐

and efficacy in the nonagenarian (90‐ to 99‐ years) and centenarian

ficiency. The total blood cell count and blood clotting checks were

(≥100 years) population is rare. Centenarians and nonagenarians have

normal. Electrocardiography (ECG) at onset in the emergency room

clinical characteristics different from those observed in younger elderly

showed a sinus rhythm. Continuous ECG monitoring in stroke unit,

patients: the older elderly (≥90 years) are less likely to have traditional

which lasted for 7 days, did not find any paroxysmal atrial fibrillation.

coronary artery disease risk factors such as diabetes, smoking and obe‐

Transthoracic echocardiography was performed and did not show

sity.11 This has been proposed as one of the main reasons that the old

signs of heart insufficiency or other pathology. Magnetic resonance

successfully get older. A stroke registry investigation suggested that

imaging (MRI) performed on day 3 revealed a small restricted diffu‐

the risk of post‐thrombolytic sICH in nonagenarians and centenarians

sion lesion on diffusion weighted imaging (DWI) in the left frontal

was not higher than that in 66‐ to 89‐year‐olds; however, mortality was

and temporal lobe (Figure 1B). Brain magnetic resonance angiog‐

higher, and functional outcomes were lower.12 Another retrospective

raphy (MRA) was normal and demonstrated successful recanaliza‐

study that included patients older than 90 years old who were admitted

tion of the entire left MCA and intracranial internal carotid artery

for AIS showed that patients who received thrombolysis did not have

(Figure 1C). No plaque or stenosis of the cervical or vertebral artery

a better functional prognosis than was found in non‐thrombolysed pa‐

was detected with Doppler ultrasound. Neurologically, the patient

tients.13 Moreover, haemorrhagic transformations were more frequent

presented with progressive improvement: her right hemiparesis

and the duration of hospitalization was longer in the thrombolysed

subsided within 24 hours after r‐tPA treatment. At 24 hours after

group.13 In this study, computed tomography perfusion‐imaging (CTP)

thrombolysis, she had an NIHSS of 4, and at discharge, her NIHSS

was performed, but even with the favourable perfusion profile, the

was 1 (mild right facial palsy), her modified Rankin scale (mRS) was 0,

response to thrombolysis in terms of safety and efficacy was not im‐

and her Barthel was 100.

proved in very old patients.13 Swallowing disorders, altered awareness
and pulmonary infections occurring after AIS might be more frequent
in thrombolysed very elderly patients.13 Age is the critical determinant

3 | D I S CU S S I O N

of the efficacy of collateral vessels; thus, advanced age indicates poor

3.1 | Reasons that elderly individuals are often
excluded from intravenous thrombolysis in clinical
practice
Although advanced age is not a contraindication for IV r‐tPA

collateral blood flow. Some reports have suggested that the Stroke
Prognostication using Age and NIHSS Scale (SPAN) index “SPAN‐100
(patient age + NIHSS at baseline ≥100)” predicts no significant benefit
for thrombolysis.14 To our knowledge, this case presents the first suc‐
cessful IV r‐tPA lytic therapy in a Chinese centenarian patient with AIS.

thrombolysis in patients with AIS, age is undoubtedly a highly
important unmodifiable risk factor that might lead to adverse
clinical outcomes after stroke. Many multicentre and randomized
clinical trials have indicated the benefits of r‐tPA in stroke pa‐
tients ≥80 years of age with AIS.

4,5

However, an increased risk of

3.3 | About our patient
The elderly usually have several comorbidities, such as diabetes,
hypertension and coronary heart disease (CHD). Long exposure

| 425

HE et al.

to these vascular risk factors could result in impaired cerebral
15

vessels, especially collateral vessels.

These can explain the high

mortality and poor functional outcomes observed among the el‐

AC K N OW L E D G E M E N T S
Thanks to my colleagues for their valuable contribution.

derly. Our patient did have hypertension, but she did not have
dyslipidaemia, diabetes, cerebral vascular disease or cardiac prob‐
lems. Her lipid profiles at admission were normal, and her body
mass index was only 18.7 kg/m2 . She never used any lipid‐lower‐

C O N FL I C T O F I N T E R E S T
The authors have no conflicts of interest to declare.

ing drugs or antiplatelet medication. Our patient had a history of
chronic bronchitis, which occurred 2 years before. She had a his‐
tory of hypertension and used an angiotensin‐converting enzyme
inhibitor but did not monitor blood pressure regularly. Considering

ORCID
Yu Zheng

http://orcid.org/0000-0002-9088-3016

this woman in a high age, but biological young and in a healthy
condition, in order to maintain her still very good quality of life,
we treated her with r‐tPA. We gave her antiplatelet and statin for
secondary stroke prevention. Our case showed that if we selected
a suitable patient for IV‐tPA, revascularization therapy could still
stop the vicious cycle of post‐stroke complications, thus providing
a benefit.
In this patient, the baseline brain CT image showed leukoarai‐
osis, which is defined as a diffuse white matter abnormality (with
a low density on brain CT images). Leukoaraiosis is common in the
elderly and a neuroimaging marker of small cerebral vessel disease
related to ageing and hypertension.16 The presence of eukoaraio‐
sis is independently associated with the risk of spontaneous sICH.17
Moreover, pre‐existing leukoaraiosis on brain CT scans might be
associated with a higher risk of thrombolysis‐related sICH.17 The
successful thrombolytic case reported for our centenarian stroke
patient suggests that there is no reason to withhold IV t‐PA from
the oldest elderly patients solely because leukoaraiosis is present
on brain CT.
The aetiology of this stroke patient is unknown. Radiographic
profiles showed scattered lesions in the left hemisphere, indicat‐
ing that it was an embolic stroke. However, Doppler ultrasound and
MRA did not reveal any stenosis or plaque in the intracranial and
extracranial arteries. Additionally, no cardiac arrhythmias or struc‐
tural abnormalities were revealed. In order to detect the source of
the emboli, we propose that this elderly patient could undergo mi‐
crobubble test using transcranial Doppler, an extension of the ECG
monitoring time, and an examination via aortic arch computed to‐
mography angiography (CTA).

4 | CO N C LU S I O N S
Extremely high age is an important independent risk factor for
IV‐tPA. In practice, the oldest elderly are more likely to undergo
conservative medical therapy than thrombolysis, especially in
centenarians. Our successful thrombolysis case indicates that
the preponderance of t‐PA‐eligible centenarians could be treated
with intravenous thrombolysis. However, further clinical study is
needed to prove the benefit of t‐PA in the oldest elderly Chinese
patients.

REFERENCES
1. National Institute of Neurological Disorders and Stroke rt‐PA
Stroke Study Group. Tissue plasminogen activator for acute isch‐
emic stroke. N Engl J Med. 1995;333:1581‐1587.
2. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with al‐
teplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med.
2008;359:1317‐1329.
3. Whiteley WN, Slot KB, Fernandes P, et al. Risk factors for intra‐
cranial hemorrhage in acute ischemic stroke patients treated with
recombinant tissue plasminogen activator: a systematic review and
meta‐analysis of 55 studies. Stroke. 2012;43:2904‐2909.
4. Davis SM, Donnan GA, Parsons MW, et al. Effects of alteplase be‐
yond 3 h after stroke in the echoplanar imaging thrombolytic evalu‐
ation trial (EPITHET): a placebo‐controlled randomised trial. Lancet
Neurol. 2008;7:299‐309.
5. Sandercock P, Wardlaw JM, Lindley RI, et al. The benefits and harms
of intravenous thrombolysis with recombinant tissue plasminogen
activator within 6 h of acute ischaemic stroke (the third interna‐
tional stroke trial [IST‐3]): a randomised controlled trial. Lancet.
2012;379:2352‐2363.
6. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines
for the early management of patients with acute ischemic
stroke: a guideline for healthcare professionals from the
American heart association/American stroke association. Stroke.
2018;49:e46‐e110.
7. Bhatnagar P, Sinha D, Parker RA, et al. Intravenous thrombolysis
in acute ischaemic stroke: a systematic review and meta‐analysis
to aid decision making in patients over 80 years of age. J Neurol
Neurosurg Psychiatry. 2011;82:712‐717.
8. Fonarow GC, Reeves MJ, Zhao X, et al. Age‐related differences
in characteristics, performance measures, treatment trends,
and outcomes in patients with ischemic stroke. Circulation.
2010;121:879‐891.
9. Lindley RI, Wardlaw JM, Sandercock PA. Thrombolysis in elderly
people. Observational data insufficient to change treatment. BMJ.
2011;342:d306.
10. Al‐Khaled M, Matthis C, Eggers J. Predictors of in‐hospital mor‐
tality and the risk of symptomatic intracerebral hemorrhage
after thrombolytic therapy with recombinant tissue plasmino‐
gen activator in acute ischemic stroke. J Stroke Cerebrovasc Dis.
2014;23:7‐11.
11. Skolnick AH, Alexander KP, Chen AY, et al. Characteristics, manage‐
ment, and outcomes of 5,557 patients age > or =90 years with acute
coronary syndromes: results from the CRUSADE initiative. J Am Coll
Cardiol. 2007;49:1790‐1797.
12. Arora R, Salamon E, Katz JM, et al. Use and outcomes of intrave‐
nous thrombolysis for acute ischemic stroke in patients >/=90 years
of age. Stroke. 2016;47:2347‐2354.

426

|

13. Sagnier S, Galli P, Poli M, et al. The impact of intravenous throm‐
bolysis on outcome of patients with acute ischemic stroke after
90 years old. BMC Geriatr. 2016;16:156.
14. Saposnik G, Guzik AK, Reeves M, et al. Stroke prognostication using
age and NIH stroke scale: SPAN‐100. Neurology. 2013;80:21‐28.
15. Liebeskind DS. Collateral circulation. Stroke. 2003;34:2279‐2284.
16. Charidimou A, Pasi M, Fiorelli M, et al. Leukoaraiosis, cerebral hem‐
orrhage, and outcome after intravenous thrombolysis for acute
ischemic stroke: a meta‐analysis (v1). Stroke. 2016;47:2364‐2372.
17. Debette S, Markus HS. The clinical importance of white matter
hyperintensities on brain magnetic resonance imaging: systematic
review and meta‐analysis. BMJ. 2010;341:c3666.

HE et al.

How to cite this article: He C, Sun Y, Yan B, Chen H, Zheng Y,
Tang Y. Successful intravenous Alteplase for a centenarian
woman with acute ischaemic stroke. Clin Exp Pharmacol Physiol.
2019;46:423‐426. https://doi.org/10.1111/1440-1681.13067