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Analysis of Factors That Influence Long-Term Independent Living for Elderly Subarachnoid Hemorrhage Patients
Accepted Manuscript Analysis of factors that influence long-term independent living for elderly subarachnoid hemorrhage patients Norihito Shimamura, MD. PhD., Masato Naraoka, MD. PhD., Takeshi Katagai, MD., Kosuke Katayama, MD., Kiyohide Kakuta, MD., Naoya Matsuda, MD. PhD., Hiroki Ohkuma, MD. PhD. PII:
S1878-8750(16)00476-9
DOI:
10.1016/j.wneu.2016.03.057
Reference:
WNEU 3880
To appear in:
World Neurosurgery
Received Date: 13 February 2016 Revised Date:
17 March 2016
Accepted Date: 18 March 2016
Please cite this article as: Shimamura N, Naraoka M, Katagai T, Katayama K, Kakuta K, Matsuda N, Ohkuma H, Analysis of factors that influence long-term independent living for elderly subarachnoid hemorrhage patients, World Neurosurgery (2016), doi: 10.1016/j.wneu.2016.03.057. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title: Anal ysis of factors that influence long-term independent living for
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elderl y subarachnoid hemorrhage patients
Authors: Norihito Shimamura MD. PhD., Masato Naraoka MD. PhD., Takeshi Katagai MD., Kosuke Katayama MD., Kiyohide Kakuta MD., Nao ya Matsuda
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MD. PhD., Hiroki Ohkuma MD. PhD.
Affiliation: Department of Neurosurgery, Hirosaki Universit y School of
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Medicine
Corresponding author:
Norihito Shimamura M.D., Ph.D.
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Department of Neurosurgery
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Hirosaki Universit y School of Medicine 5-Zaihuchou, Hirosaki Aomori pref. JAPAN. 036-8562 Tel: +81-172-39-5115 Fax: +81-172-39-5116 e-mail: [email protected]
Cover Title: Long-term independent living for very elderl y SAH 1
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Itemized list: four tables and two figures
Key words: cerebral aneurysm, elderl y patient, independent living, radical
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intervention, subarachnoid hemorrhage
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Number of references: 45
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Specify the number of words: 4026
2
ACCEPTED MANUSCRIPT Abstract Background. The number of elderl y subarachnoid hemorrhage (SAH) patients
for elderl y (
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has been increasing. The aim of this study was to anal yze long-term outcome 75 y) SAH patients and to establish a treatment strategy.
Methods. From January 2005 to December 2013, 86 consecutive cases were
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treated. We used a modified Rankin scale (m-RS) at the outpatient clinic, or a
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telephone interview of patients and/or families. Kaplan-Meier plots were done for mortalit y and independent (m-RS 0 ~ 2) state. Multivariate anal ysis was done to distinguish factors that influence on outcome.
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Results. Median age was 79, Hunt-Kosnik grade 1 ~ 3 was 79 radical intervention (clipping or coiling) rate was 78
and the
. Mean follow-up
period was 28.7±3.4 se months. Half of deaths occurred during the first two
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months. The number of cases of independent living gradually decreased to
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50% at 28 months after SAH. Half of patients lived independentl y for 36 months at HK grades 1 to 3, and 3 months at HK grades 4 to 5 (p<0.05). Half of patients lived independentl y for 40 months in the radical intervention group, and 14 months in the conservative treatment group (p<0.05). Multivariate anal ysis for independent living revealed that gender, pre-morbid condition, HK grade, and postoperative complication were significant 3
ACCEPTED MANUSCRIPT (p<0.05). Conclusions. Good-grade elderl y SAH cases that were independent pre-stroke have
perioperative
radical
intervention
complications
have
performed a
aneurysm.
influence
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independent living.
positive
for
4
Avoiding
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should
on
long-term
ACCEPTED MANUSCRIPT Introduction Aneurysmal subarachnoid hemorrhage (SAH) is fatal in half of patients, but younger cases that survive can achieve useful dail y life after surgery and/or
of elderl y stroke patients is increasing 1 ,
7, 8
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rehabilitation 1 - 6 . In a societ y with progressivel y-advancing aging, the number . But outcomes for elderl y SAH
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patients treated b y clipping or coiling are poor because initial SAH grades are
organs are diseased 2 ,
9-14
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poor, the brain is vulnerable, a high rate of vasospasm exists, and other . Respectivel y, man y authors have reported that
prognostic factors for poor outcome are age and poor clinical status on 9, 10, 12, 15-17
.
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admission 2 ,
Life expectancy for elderl y persons now extends beyond that of previous decades. No doubt, elderl y SAH cases are able to live for long periods after
4, 9, 17-20
. Also, recent reports have reached the consensus that cases
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outcome
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an ictus, but qualit y of life has not been discussed in a context of long-term
of SAH less than 70 years-old have great potential to achieve favorable outcome 2 ,
18, 21-24
. Some reports recommend a treatment cutoff of 74 years 3 ,
25
.
On the other hand, selected 9 t h decade cases of SAH can achieve favorable outcome 9 ,
21, 26, 27
.
The Japanese Ministry of Health, Labor and Welfare defines a person over 5
ACCEPTED MANUSCRIPT 75 years-old as in the advanced-age category. An y controvers y over treatment strategy for very elderl y SAH cases should thus be discussed at around 75 years of age and older. Some researchers have reported mortalit y or favorable
26, 28, 29
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outcome over several months as GR and MD on the Glasgow Outcome Scale 9 , . But MD includes levels 2 and 3 of the modified Rankin scale (m-RS), 31
. Independent dail y living is
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while m-RS 3 is a partiall y-dependent state 3 0 ,
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important not onl y for patients and families but also for medico-social economics.The aim of this stud y was to reveal temporal changes in mortalit y and independent state for elderl y SAH cases. We also discuss an efficient
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treatment strategy for elderl y cases of SAH.
Material and Methods
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This stud y was approved b y the Hirosaki Universit y Ethics Committee. We
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acquired written, informed consent for this stud y from patients and/or families.
From January 2005 to December 2013, we treated 89 consecutive SAH cases at ages over 75 years. SAH was diagnosed b y computed tomograph y (CT), and aneurysms
were
diagnosed
by
digital
subtraction
angiograph y
or
three-dimensional CT angiograph y. When multiple aneurysms were found, we 6
ACCEPTED MANUSCRIPT diagnosed ruptured aneurysm based on the distribution of SAH, and the size and shape of the aneurysm. Clinical severit y of SAH was classified b y a Hunt-Kosnik (HK) grade, with grades 1 to 3 defined as good, while grades 4
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to 5 were poor 3 2 . We recommend earl y (within 72 hours after SAH onset) radical aneurysm treatment (clipping or coiling) to the patient and famil y.
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While aneurysm neck clipping is first-line at our institute for young patients, 20
. Also, an aneurysm
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we select coiling for elderl y patients just as often 1 9 ,
with posterior circulation, more than one dome, and an adequate neck ratio or large size (> 10mm) tended to be treated b y coiling. The selection of the
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treatment method was discussed b y several board-certified neurosurgeons, depending on whether the shape and route of approach were appropriate for aneurysm coiling.
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Post-operative management was as follows: We maintained normovolemia
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with intravenous administration of fasudil h ydrochloride for prevention of vasospasm. (Nimodipine has not been approved in Japan.) All patients were routinel y ambulated on the day after the operation following a determination of negative brain pathology via CT. Some patients refused ambulation due to headache, fatigue, nausea and so on. We defined ambulation according to the Hauser ambulation index 3 3 . All patients were routinel y ambulated as soon as 7
ACCEPTED MANUSCRIPT possible. Even if conservative treatment is selected, we recommend earl y ambulation to prevent muscle atroph y. When s ymptomatic vasospasm was suspected as the prime concern, triple-H therap y was also carried out,
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depending on clinical s ymptoms, biochemical examination and brain CT 1 5 . Angiograph y was performed simultaneousl y and, for etiologic spastic artery,
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intra-arterial injection of medicines (fasudil and/or nicardipine) and/or
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balloon angioplast y were carried-out. When h ydrocephalus occurred, lumbar drainage or cerebral ventricle drainage was done during the acute phase and a ventricular- or lumbo-peritoneal shunt was done for normal pressure
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h ydrocephalus.
Other organ diseases that required continuous treatment were defined as pre-morbid conditions, except for h ypertension, because almost all patients
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were taking anti-h ypertension drugs. Those organ diseases that required
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additional treatment, including infection, were defined as postoperative complications. Finally, the destination following discharge was extracted from the medical records. We evaluated m-RS at the outpatient clinic or in a telephone interview with the patient and/or famil y. The questionnaire used for the telephone interview included abilit y to walk, bathe, dress and orient. If the m-RS worsened, we 8
ACCEPTED MANUSCRIPT evaluated when and wh y the patient deteriorated. The cause of death was defined according to the clinical diagnosis, but some cases were defined as
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‘old age,’ or gradual weakening and death All patients were followed-up, and follow-up was terminated upon death. Primary outcome was mortalit y and secondary outcome was deterioration into
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dependent state. We excluded three non-aneurysm SAH cases from anal ysis of
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outcome because of non-aneurysm SAH is a disease well known for a favorable prognosis.
Blinded co-authors MN and NM independentl y assessed outcome and a
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consensus discussion was held. We defined independent living as m-RS 0 to 2. An m-RS 3 state cannot engage full y in dail y life; they need some assistance for elimination needs, bathing and dressing.
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A Kaplan-Meier curve was calculated for the survival rate or rate of
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independent dail y life (JMP 8.01, SAS Institute Inc. Cary, NC). Clinical factors that influenced outcome were anal yzed b y multivariate anal ysis (Weibull distribution). A P value of ‹0.05 was considered statisticall y significant.
Results 9
ACCEPTED MANUSCRIPT Eight y-six cases were included in this stud y. Median age was 79 years and the range was from 75 to 90 (Table 1). Gender of cases were 8 male and 78 ), with 18 cases (21%)
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female. HK grades 1 to 3 comprised 68 cases (79
given a poor grade. Pre-morbid conditions were diagnosed in 17 cases, and three cases had dual diseases (Table 1). Radical interventions were 78% (45
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clipping: 20 coiling: 2 wrapping or trapping). The other 19 cases were treated
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conservativel y, due to poor grade (n=6) or high age (n=6) and so on (Table 1). Symptomatic vasospasm occurred in 30 cases that included 4 cases before admission and 26 cases (30%) after admission. Ventricle-peritoneal shunt was
non-neurological
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done for 13 cases (15%). Eighteen cases (21%) suffered post-operative complication.
These
comprised
mostl y
infections
by
methicillin-resistant Staph ylococcus aureus; Six cases of pneumonia and one
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of wound infection are included (Table 1). Fort y-nine percent of cases
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achieved favorable outcome at 30 days after the ictus (Table 1), sixt y-nine percent of cases were discharged to another hospital for rehabilitation, and 22% of patients were discharged to their own homes (Table 1). Mean follow-up period was 28.7 ± 3.4 se months. The end of stud y mortalit y rate was 22
, rate of independent living was 41
, rate of
dependent living was 37%(Table 1). Half of deaths occurred during the first 10
ACCEPTED MANUSCRIPT two months after SAH and the reason of death were medical complications (Table 1, Figure 1A). Major reasons for death after the discharge were old age
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(Table 2). The number of cases of independent living gradually decreased to 52% at 19 months after SAH (Figure 1B). Thereafter, the decrease in independence slowed. Half of patients lived independentl y for 36 months at
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HK grades 1 to 3, and 3 months at poor grades (p<0.05, Figure 2A). Half of
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patients lived independentl y for 36 months in the radical intervention group, and 13 months in the conservative treatment group (p<0.05, Figure 2B). Multivariate anal ysis for death revealed that high age, male gender and
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postoperative complication correlated positivel y with mortalit y (p<0.05, Table 3). Also multivariate anal ysis for independent living revealed that male gender, pre-morbid condition, poor HK grade and postoperative complication
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correlated negativel y with independent living (p<0.05, Table 4).
Discussion
We evaluated long-term temporal changes in survival and independent living in elderl y SAH cases. The survival rate for elderl y SAH patients abruptl y decreased after the ictus but stabilized after four years. But the rate of independent living graduall y decreased and half of patients could not enjo y 11
ACCEPTED MANUSCRIPT their lives independentl y three years after SAH onset. Ninet y percent of patients were refereed to our department, and our patient
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cohort had a smaller than usual number of poor HK grades. Some poor-grade SAH cases were not transferred to our department, due to rejection of radical treatment b y the famil y or due to poor surgical indications. As in previous
.
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34-36
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reports, poor initial HK grade cases rapidl y drop into the dependent state 2 9 ,
Also, our cases had been transferred to our department for surgery, leading to a high number of surgicall y-treated cases. Our strategy is to do radical intervention of an aneurysm for patients who functioned independentl y
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preoperativel y, even in cases of advanced age 1 9 . Age limitation for SAH radical intervention is controversial. In 1995 Fridriksson SM et al. reported
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outcome for 8th and 9th decade SAH cases in Sweden 2 1 . Two-thirds of 70 ~
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74 year-old patients returned to independent living, but they did not recommend surgery for cases over 80 years old. After two decades in 2014, Park J et al. reported a 1-year functional outcome for cases of SAH over 70 years old, even with WFNS grades 1 ~ 3, while onl y 54.8% of cases over 75 years old could achieve an m-RS of 0 ~ 3. They concluded that 75 was the critical age for the radical operation 3 . In 2006 Nieuwkamp DJ anal yzed 170 12
ACCEPTED MANUSCRIPT SAH cases over 75 years old, with onl y 25% treated surgically and onl y 15% independent at discharge 1 8 . Follow up outcome at 2 ~ 4 months after ictus showed that 18% of cases were independent. Age was not related to outcome
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in their elderl y cohort, while good initial grade related to good outcome 2 9 . Several reports on one-year follow up of 9 t h decade, surgically-treated SAH 27, 34
. The rate of favorable outcome was 20 ~
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cases have been published 2 6 ,
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54% and the WFNS grade was determined as a significant factor. From an elderl y subgroup anal ysis of ISAT, endovascular treatment allowed quicker mobilization in these patients, and prolonged bed rest could therefore be
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avoided 1 3 . Incidences of infections and pulmonary complications were reduced in the endovascular treated patient group. Of course, we selected interventional coiling of ruptured aneurysm for elderl y SAH cases. But the
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majorit y of aneurys ms were not suitable for coiling because of aneurysm
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shape and/or access route.
Our treatment strategy is to radicall y treat pre-SAH independent patients at HK grades of 1 to 3 during the acute phase and ambulate earl y to avoid muscle atroph y and dementia. Brain-derived neurotrophic factor is secreted b y skeletal muscle, and muscle atroph y induces dementia, depression, diabetes and malignancies 3 7 - 3 9 . Age is not a major limitation in an 13
ACCEPTED MANUSCRIPT advanced-age society. Even if the patient was not treated radicall y, we recommended and did earl y ambulation. Our previous studies reveal earl y 20
.
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ambulation produce ph ysical and ps ychological favorable outcome 1 9 ,
Elderl y stroke patients lose their ph ysical abilities abruptl y d uring the acute phase. At the same time, full recovery of ph ysical and ps ychological function
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is difficult for elderly patients; aging diminishes tissue stem cell functions
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that regenerate the central nervous s ystem, muscle and other organs 4 0 . Favorable outcome of our series at discharge was 49%, but the discharge to their own homes was 22%. Sixt y-nine percent of patients were transferred to a
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rehabilitation hospital. This discrepancy is a function of medico social problems in Japan; intensive rehabilitation is available within three months after the ictus and for those who live alone or for aged couples in need. After
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discharge from the acute-care hospital, elderl y SAH patients have little
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chance to improve their activities in daily life 2 2 ,
35, 41-43
. Anal ysis of SAH
cases over 65 years revealed that 40 ~ 60% of cases achieved favorable outcome after 6 to 20 months 1 0 ,
11, 24, 44, 45
. In 2009 Nieuwkamp DJ et al.
reported that the mean age of patients with SAH increased from 52 to 62 years, but case-fatalit y rates decreased b y 17% between 1973 and 2002 8 . Birinjikji W et al. anal yzed SAH mortalit y in a data-base from 2001 to 2009, with aging 14
ACCEPTED MANUSCRIPT an independent risk for mortalit y, but the outcomes for SAH at all ages has been improving 1 . Very elderl y SAH cases have a high rate of mortalit y, but
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extending life is not the onl y purpose of SAH treatment. All patients and families strongl y desire qualit y of life and independent living. We need to focus on how we can bring independent living to very elderl y SAH patients.
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The pre-morbid condition for our cohort is onl y 20% because we eliminate
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h ypertension from the pre-morbid condition. Nearl y all cases were medicated with anti-h ypertension drugs, so we did not include h ypertension in the pre-morbid condition. In our result, pre-morbid condition did not influence
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mortalit y but influenced independent living negativel y. And post-operative complication was negativel y related mortalit y and dependent living. While the pre-morbid condition cannot be prevented b y our surgeons, post-operative
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complications are preventable. Elderl y patients have a high likelihood of 35, 42
.
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mortalit y and cardiovascular events compared to a health y population 2 2 ,
From our results, half of patients drop into a dependent state within three years after ictus, and a long-term treatment strategy for very elderl y SAH patients is vitall y important for the future. There are several limitations to this stud y. We do not have age- and gender matched health y controls and thus cannot objectivel y measure the influence 15
ACCEPTED MANUSCRIPT of age progression on mortalit y or decrease in functional independence. A randomized control trial is difficult due to ethical problems: absence of
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treatment produces a fatal prognosis for the patient.
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Conclusions
pre-stroke Avoiding
should
have
perioperative
radical
intervention
complications
have
performed
a
positive
for
aneurysm.
influence
on
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independent living.
Acknowledgement
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Good-grade SAH cases over 75 years of age that were independent
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We thank Markus In glin (Universit y of Basel) for his editorial assistance.
Sources of Funding
This stud y was supported b y a Grant-in-Aid for Scientific Research of the Japan Societ y for the Promotion of Science (No: 40312491) to NS.
Conflict of interest 16
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We do not have an y conflict of interest.
17
ACCEPTED MANUSCRIPT Ref er e nc e L is t
1.
Br i nj ik j i W , Lan zi n o G , Ra b ins t ei n A A , K al lm e s DF , C l of t HJ . A g e- r e l at e d tr e nds i n th e tr ea tm ent an d o utc om es of r u pt ur e d c er e br a l a ne ur ys m s : a s tu d y of th e na t io n wi d e i n pa t ie nt s am pl e 2 00 1- 20 0 9. AJ N R Am J N e ur or a d io l 2 0 13 ;
2.
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34( 5) :1 0 22 - 1 0 27 . La n zi n o G , Ka s s e l l NF , G er m ans on T P e t a l. A ge a n d o utc om e af t er
an e ur ys m al s u b ar ac h n o id h em or r h a ge : wh y d o o ld er p a ti e nts f ar e w or s e ? J Ne ur os ur g 1 9 96 ; 8 5( 3 ) :4 1 0- 4 1 8.
P ar k J , W oo H, K a ng DH , K im Y. C r i t ic a l a g e af f ec t i ng 1- ye a r f unc ti o na l
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3.
ou tc om e i n e l der l y p a t i en ts a ge d > / = 7 0 ye a r s wit h a n eur ys m a l s u b ar ac h n oi d
4.
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hem or r ha g e. Ac t a Ne u r oc h ir (W ien ) 2 01 4; 1 56( 9) :1 6 55 - 1 6 61 . Ho p JW , Rink e l G J , A l gr a A, v an G J . C h an g e s i n f unc t io n a l ou tc om e a nd qu a l it y of l if e in p a ti e n ts an d c ar e g i ver s af t er a n eur ys m a l s ub ar ac h no i d hem or r ha g e. J Ne ur os ur g 20 0 1; 9 5( 6) : 9 57 - 9 63 . 5.
Ho p JW , Rink e l G J , A l gr a A, v an G J . Q ua l i t y of l if e i n p at i e nts a n d par t ner s af ter an e ur ys m al s u b a r ac h n o id hem or r ha g e. Str ok e 1 99 8 ; 29 ( 4) :7 9 8- 8 0 4. Ho p JW , Rink e l G J , A l gr a A, v an G J . C as e- f at a l it y r a tes an d f unc t i on a l
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6.
ou tc om e af t er s u ba r ac hn o i d hem or r ha g e: a s ys t em at ic r e v i e w. S tr o k e 1 99 7; 28( 3) :6 6 0- 66 4.
J oh a ns s o n M , C es ar i n i K G , C on t an t CF , P er s s on L, E n b la d P . C ha n ges in
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7.
i nt er ve n t io n a nd ou tc o m e in el d er l y p at i en ts wi t h s ub ar ac hn o id he m or r ha ge .
8.
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Str ok e 2 00 1 ; 32 ( 1 2) : 2 84 5- 2 94 9. Ni e u wk am p DJ , Se t z L E, A lg r a A, Li n n F H , d e R oo ij N K, Ri nk e l G J . C h an g es i n c as e f at a l it y of a n eur ys m al s u b ar ac h no i d ha em or r h ag e o v er t im e, ac c or d i ng t o ag e , s ex , a n d r e g io n: a m et a- an a l ys is . L a nc et N e ur o l 2 0 09 ; 8( 7) : 6 35- 6 4 2. 9.
As an o S , W atan ab e T , S h i no h ar a T e t a l. Im por t anc e of th e i n it i a l gr a d e of s ub ar ac hn o id hem or r h ag e i n t he pa t ie nts wi t h th e a g e of 8 0 ye ar s an d o l de r f r om a s in g le c en te r a na l ys is . Ac t a N e ur o l B e lg 2 0 11 ; 1 11 ( 3) :2 1 3- 21 6 .
10 . Br au n V, R at h S, An t o n ia d is G , R ic ht er H P , B or m W . T r eatm en t a n d o utc om e of an e ur ys m al s u b ar ac h n o id h a em or r h ag e i n t h e e ld er l y p at i e nt . Ne ur or a d i o lo g y 20 0 5; 4 7( 3) : 2 15 - 2 2 1.
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ACCEPTED MANUSCRIPT 11 . Lu b ic z B , Lec l er c X , G au vr i t J Y, Lej eu n e J P , Pr u vo J P. E n do v as c u l ar tr e a tm ent of r u p tur e d i ntr ac r an i a l a ne ur ys m s i n e l der l y pe o p le . AJ NR Am J N eur or a di o l 20 0 4; 2 5( 4) : 5 92 - 5 9 5. 12 . Ros e ng ar t AJ , Sc hu l th e is s K E, T o le nt i n o J , Mac d on a l d RL . Pr o gn o s tic f ac t or s f or o u tc om e i n p at i en t s wit h a n eur ys m a l s u b ar ac h n oi d h em or r h a ge . Str ok e
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20 0 7; 3 8( 8) : 2 31 5- 2 32 1 . 13 . R yt tl ef or s M, E n b la d P , K er r R S, M o l yn e ux A J . I n ter n at i on a l s u b ar a c hn o i d an e ur ys m tr i al of n e ur os ur g ic a l c l i p pi n g ver s us e n do v as c u lar c o i l in g: s ub gr o up an a l ys is of 27 8 e l der l y p at i e nts . St r ok e 2 00 8 ; 39( 1 0) : 2 72 0- 2 72 6.
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14 . S u zuk i A, Ya s u i N, H a de is h i H , Sa yam a I, As ak ur a K, N ag as him a M . [C a us es of po or r es u lts of e ar l y s ur g er y i n r up tur e d i ntr ac r a n i a l an e ur ys m s i n e ld er l y
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pa t ie n ts ] . Ne ur o l Me d Ch ir ( T ok yo) 19 8 8; 2 8( 12) : 11 5 7- 1 1 62 .
15 . B ed er s on J B , Co n no l l y E S, J r . , Ba tj e r H H e t a l. G u i d el i n es f or th e m an a gem e nt of a n eur ys m a l s u bar ac hn o i d hem or r ha g e: a s ta tem en t f or h ea l thc ar e pr of es s i o n als f r om a s pec i a l wr it i ng gr o u p of t he Str ok e Co u nc il , A m er ic a n He ar t As s oc i a ti o n. Str ok e 20 0 9; 4 0( 3) : 9 94- 1 02 5 .
16 . G o n za l e z NR , Dus ic k J R, D uc k wi l er G et a l . E nd o v as c u l ar c o i l in g o f
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i ntr ac r an i a l an e ur ys m s i n e l der l y p a t ie nts : r e por t of 20 5 tr e at ed an eur ys m s . Ne ur os ur g er y 2 01 0 ; 6 6( 4 ) : 71 4- 7 20 .
17 . Hor i uc hi T , Ho n go K. Cl i p pi n g s ur ge r y f or a ne ur ys m al s ub ar ac h n o i d
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hem or r ha g e i n p at i en t s a g ed 7 5 ye ar s or o l d er . N e ur o l R es 2 01 1 ; 33( 8) :8 5 3- 85 7.
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18 . Ni e u wk am p DJ , R ink e l G J , Si l v a R, G r e eb e P, Sc hok k ing D A , F er r o J M. S ub ar ac h n o id ha em or r ha g e i n p at i en ts > o r = 7 5 ye a r s : c li n ic a l c ou r s e, tr e atm e nt a n d ou tc om e. J Ne ur o l Ne ur os u r g Ps yc hi a tr y 2 00 6; 77( 8) :9 3 3- 9 3 7. 19 . S him am ur a N , M ats ud a N, Sa to u J , N ak an o T , O hk um a H . E ar l y a m bul at i on pr o d uc es f a v or ab l e o u tc om e an d n o nd em en t i a l s ta te in an e ur ys m al s ub ar ac hn o id hem or r h ag e p at i e nts o l de r th a n 7 0 ye ar s of a g e. W or l d Ne ur os ur g 2 0 14 ; 8 1( 2 ) :3 3 0- 3 3 4. 20 . S him am ur a N , M un ak a ta A, O hk um a H. C ur r e nt m ana g em ent of s u b ar ac h n oi d hem or r ha g e i n a d va nc ed ag e. Ac t a N eur oc h i r S u p pl 20 1 1; 1 1 0( Pt 2 ) :1 5 1- 1 5 5.
19
ACCEPTED MANUSCRIPT 21 . F r i dr ik s s on SM , H i llm a n J , S a ve l a nd H , Br a n dt L . In tr ac r an i a l an e u r ys m s ur g er y i n t h e 8t h a nd 9t h d ec a d es of l if e: im pac t o n p op u la t io n- b a s ed m anag em en t o utc om e. N eur os ur ger y 1 9 9 5; 3 7( 4 ) : 62 7- 6 31 . 22 . Ni e u wk am p DJ , d e W A, W erm er MJ , A l gr a A , R i nk el G J . L o ng - t er m ou tc om e af ter an e ur ys m al s u b a r ac h n o id hem or r ha g e- r is k s of v as c u l ar e v e nt s , de a th
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f r om c anc er a nd a l l- c a us e de at h . J N eu r o l 2 0 14 ; 2 61( 2) :3 0 9- 31 5. 23 . Ro we J G , Mo l yn e ux A J , B yr ne J V, R e no wd e n S , A zi z T Z . En d o vas c u lar
tr e atm e nt of i ntr ac r an i a l an e ur ys m s : a m in im a ll y i n v as i v e ap pr o ac h wit h ad v a nt a ges f or e l de r l y p at i e nts . A ge Ag e i ng 19 9 6; 2 5( 5) : 3 72 - 3 7 6.
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24 . S ed at J , D i b M, L onj o n M et a l . E nd o v as c u l ar tr e atm e nt of r up tur e d i ntr ac r an i a l an e ur ys m s i n pa t ie n ts ag e d 6 5 ye ar s a nd o l d er : f o l l o w- u p of 5 2 pa t i en ts af t er 1
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ye ar . S tr ok e 2 0 0 2; 3 3( 11) : 26 2 0- 2 6 25 .
25 . S hi r a o S , Yo n e d a H, K un i ts u g u I, Su e h ir o E, K oi zum i H, Su zuk i M . A ge lim i t f or s ur g ic a l tr ea tm ent of p oor - gr a de pa t ie nts wi t h s u bar ac hn o i d hem or r ha g e: A pr oj ec t of t he C h u gok u - S h ik ok u d i v is io n of th e J a pa n n eu r os ur g ic a l s oc i et y. S ur g N e ur ol I n t 20 1 2; 3: 1 43 .
26 . Ham ad a J , M or i ok a M , M i ur a M, F uj i ok a S , M ar u b a ya s h i T , Us h io Y .
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Ma n ag em en t o utc om e f or r up tur e d a nt er io r c i r c u la t io n a n eur ys m s wit h a H u nt an d H es s c l i nic a l gr a d e of I II in p a t ie nts in t he 9t h d ec a d e of lif e. S ur g N e ur ol 20 0 1; 5 6( 5) : 2 94 - 3 0 0.
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27 . Ya n o S, H am ad a J , K ai Y e t a l. S ur gic a l in d ic at i ons to m ai n ta i n q u al it y of l if e in e ld er l y p at i en ts wi t h r up t ur e d i n tr ac r a n ia l a n eur ys m s . Ne ur os ur g er y 2 0 0 3 ;
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52( 5) :1 0 10 - 1 0 15 .
28 . B ar k er F G , m i n- H a nj a n i S, B ut l er W E et a l. A ge- d ep e nd e nt dif f er e nc es in s hor t- ter m o utc om e af t er s ur g ic a l or en d o vas c u lar tr e atm en t of unr up t ur e d i ntr ac r an i a l an e ur ys m s i n t he U n it e d S ta t es , 19 9 6- 20 0 0. N eu r os ur g er y 2 00 4; 54( 1) :1 8- 2 8.
29 . Mo n t' al v er n e F , M us ac c h io M , T o l e nt i no V, R i qu e lm e C , T o ur na d e A. E nd o v as c u l ar m a na g e m ent f or in tr ac r a n i al r up t ur e d a n eur ys m s i n e ld er l y pa t ie n ts : o utc om e an d tec h nic a l as pec ts . N e u r or ad i o lo g y 2 00 5 ; 47 ( 6 ) :4 4 6- 4 5 7. 30 . Ra nk in J . C er e br a l va s c u lar ac c i d en ts i n p at i en ts o v er th e a g e of 6 0. I I. Pr og n os is . S c o tt M e d J 1 9 57 ; 2( 5) : 2 00- 2 15 .
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ACCEPTED MANUSCRIPT 31 . v an S wi et en J C , K ou d s ta a l PJ , Vis s er M C, S c ho u te n HJ , v a n G J . In ter o bs er v er agr e em ent f or t h e as s es s m ent of h a nd ic ap i n s tr ok e p at i e nts . S tr o k e 1 98 8; 19( 5) :6 0 4- 60 7. 32 . Hu nt W E, Kos n ik EJ . T im in g a nd per i o per at i v e c ar e i n i ntr ac r an i a l a ne ur ys m s ur g er y. C li n N eu r os ur g 1 97 4; 21 :7 9- 8 9.
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33 . Ha us er S L, D a ws o n D M, L e hr ic h J R et a l . In te ns i ve im m unos u ppr e s s i on in pr o gr es s i ve m ul t ip l e s c l er os is . A r a n dom i ze d, t hr ee- ar m s t ud y of h ig h- dos e i ntr a ve n o us c yc l op h os ph am id e , p las m a ex c h an g e, a n d A CT H. N E n g l J M e d 19 8 3; 3 0 8( 4) : 17 3- 1 80 .
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34 . Hor i uc hi T , T s uts um i K, I t o K, H o n go K. R es u lts of c l i pp i ng s ur g er y f or
an e ur ys m al s u ba r ac h n o id h em or r h ag e i n th e n in th a n d t e nt h d ec a d es of l if e . J
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Cl i n N eur os c i 2 01 4 ; 2 1( 9 ) : 15 6 7- 15 6 9.
35 . Sc ho l l er K , M as s m an n M, Mar k l G et a l . A n eu r ys m al s ub ar ac hn o id h em or r h ag e i n e ld er l y p at i en ts : lo n g- t er m o utc om e a n d pr og n os t ic f ac t or s i n a n i nt er d is c i p l in ar y tr ea t m ent ap pr o ac h . J N e ur o l 20 1 2.
36 . T ak i W , Sak ai N , S u zu k i H. D e ter m i na nts of po or o utc om e af te r an eur ys m a l s ub ar ac hn o id hem or r h ag e whe n b ot h c l i p p in g a nd c o i l i ng a r e a v a i l ab l e:
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Pr os p ec ti v e R eg is tr y o f S ub ar ac h n o id An e ur ys m s T r eatm e nt ( PR E S AT ) in J ap a n. W or ld N eur os u r g 2 01 1; 76( 5) :4 3 7- 44 5. 37 . P ed er s en B K, P ed er s e n M , Kr a bb e K S, Br uu n s ga ar d H , M at th e ws V B, F e bb r a i o
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M A. R o le of ex er c is e- i nd uc ed br a i n- der i v e d ne ur otr o ph ic f ac t or pr od uc ti o n i n th e r e gu l a ti o n of en er g y h om eos t as is i n m a m m als . Ex p P h ys io l 2 0 09 ;
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94( 1 2) : 1 15 3- 1 16 0.
38 . P ed er s en B K , F e b br a i o M A . M us c les , ex er c i s e a n d o bes i t y: s k e le t a l m us c le as a s ec r et or y or g an . Na t R e v E nd oc r i no l 2 0 1 2; 8( 8) :4 5 7- 4 6 5. 39 . T ole a M I, G a l vi n J E . S ar c o p e ni a a n d im pa ir m en t i n c o gn i t i ve a n d p h ys ic a l per f or m anc e. C l in I n te r v Ag i ng 20 1 5; 1 0: 6 6 3 - 67 1 . 40 . S ig n er R A, Mor r is o n S J . Mec h an is m s t ha t r e gu l at e s t em c e ll ag i ng an d l if e s pa n . Ce l l S t em Ce l l 2 01 3 ; 12( 2) :1 5 2- 16 5. 41 . G r e eb e P , R ink e l G J , A lg r a A. L o ng- t er m ou t c om e of p at i en ts d is c h ar g e d to a nur s i n g h om e af t er a n eur ys m a l s u bar ac hn o i d h em or r h ag e. Ar c h P h ys M ed
21
ACCEPTED MANUSCRIPT Re h ab i l 2 01 0 ; 9 1( 2) : 2 47- 2 5 1. 42 . Ni e u wk am p DJ , A l gr a A, B lom q v is t P e t a l. E x c es s m or t a li t y a nd c a r d io v as c u lar e ve n ts i n pa t ie n ts s ur v i v in g s u b ar ac h no i d h e m or r ha ge : a n at i o n wi d e s tu d y i n S we de n . S tr ok e 2 0 11 ; 42( 4) :9 0 2- 90 7. 43 . S an ds t r om N, Ya n B, Do wl i n g R, L a i d la w J , M itc he l l P. C om par is o n of
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m ic r os ur g er y an d e n d o vas c u l ar tr e a tm ent o n c l i nic a l o utc om e f o l l o wi ng
po or - gr ad e s u b ar ac h n o id h em or r h a ge . J Cl i n N eu r os c i 2 0 13 ; 2 0( 9 ) : 12 1 3- 12 1 8. 44 . J oh a ns s o n M, N or bac k O , G a l G et a l. C l i n ic a l o utc om e af t er e nd o v a s c u lar c o il
Ne ur or a d i ol o g y 2 00 4 ; 46( 5) :3 8 5- 39 1.
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em bo l i za t io n i n e l der l y p at i e nts wit h s u b ar ac hn o i d hem or r ha g e.
45 . St ur i a le C L, Br inj ik j i W , Mur a d M H, L a n zi n o G . En d o vas c u l ar tr e a t m ent of
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i ntr ac r an i a l an e ur ys m s i n e l der l y p a t ie nts : a s ys tem at ic r e v i e w a n d
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m eta- a n a l ys is . S tr ok e 20 1 3; 4 4( 7) : 1 89 7- 1 90 2 .
22
ACCEPTED MANUSCRIPT Figure legend Figure 1. Kaplan-Meier curves of survival rate (A) and independent living rate (B) Figure 2. Kaplan-Meier curves of independent living rate.
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A: Good (black line) or poor (gray line) Hunt-Kosnik grade. Difference between these groups is statisticall y significant. B: Radical- (black line) or conservative intervention (gray line) treatment.
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Difference between these groups is statisticall y significant.
23
ACCEPTED MANUSCRIPT
Content
Result
Median age (Range)
79 year old (75 - 90)
Gender (Male/Female)
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Table 1. Outline of anal yzed cases
Hunt-Kosnik grade 1 : 2 : 3 : 4 : 5
8 : 33 : 27 : 13 : 5 (79%: 21%)
3 : 17 : 51 : 15
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Fisher group 1 : 2 : 3 : 4
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(1~3: 4,5)
8 / 78
Arthritis
5
Renal failure
3
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Dementia, Heart failure, Cancer, Liver cirrhosis, Pre-morbid
2 each
Cerebral infarction
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conditions
Abdominal aortic aneurysm
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Acute myocardial infarction,
1 each
Internal carotid artery occlusion (Three cases had dual diseases.)
Radical intervention (clip/coil/other) : 78% (45/20/2): 22% conservative
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Poor HK grade, High age
6 each (32%)
Reason for Perforator involved, conservative Multiple aneurysms treatment Fusiform, Heart failure,
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2 each (11%)
Renal failure Yes (before
30 (4, 26): 51: 5
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Symptomatic vasospasm
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1 each (5.3%)
(35%: 59%: 5.8%)
Ventricle peritoneal shunt
13: 66: 7
Yes: No : N/A
(15%: 77%: 8%)
m-RS @ 30 days
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admission, after admission) : No : N/A
0: 1: 2: 3: 4: 5: 6
(Independent: Dependent: Death)
13: 10: 4: 15: 27: 11: 6 (31%: 62%: 7%)
Discharge
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Rehabilitation hospital: Home: 59: 19: 1: 1
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Nursing home: Change to
destination
(69%: 22%: 1.2%: 1.2%)
another department
Mean follow up periods
28.7 ± 3.4 se months
(Range)
(1 ~ 110 months)
m-RS @ final follow up: 0: 1: 2: 3: 4: 5: 6
20: 3: 10: 7: 11: 14: 19
(Independent: Dependent: Death)
(41 ％ : 37 ％ : 22 ％ )
ACCEPTED MANUSCRIPT
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Values without units are given in a number of cases. N/A: not available.
ACCEPTED MANUSCRIPT Table 2. Post-operative complications and reason for mortalit y Number of cases
MRSA infection*
7 (39%)
Cardiogenic cerebral embolization
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Diagnosis
2 (11%)
Heart failure
complications
Cerebral infarction not due to vasospasm
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AMI, ICH, lung edema,
2 (11%) 2 (11%)
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Post-operative
1 each (5.6%)
Reason for mortality
Old age
5 (26%)
Aneurysm rupture
4 (21%)
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TAA rupture, drug eruption
3 (16%)
Pneumonia
Heart failure/ Renal failure/ Lung 1 each (5.2%)
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cancer/ Abdominal aneurysm rupture 3 (16%)
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Undefined
MRSA: methicillin-resistant staph ylococcus aureus, AM I: acute m yocardial infarction, ICH: intra cerebral hemorrhage, TAA: thoracic aortic aneurysm. * Six pneumonia cases and one wound infection case are included.
ACCEPTED MANUSCRIPT Table 3. Multivariate anal ysis for death Likelihood-ratio
p-value
chi-square test
(Prob>ChiSq)
Factors
5.997 ( 75~79 : 80~84 : 85~ ) Gender
(Yes : No) Hunt-Kosnik grade
Treatment
1.737
0.1875
3.237
0.0720
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(1~3 : 4, 5)
<.0001*
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(Male : Female) Pre-morbid conditions
0.0499*
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19.56
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Age
1.099
0.2946
4.084
0.2526
24.40
<.0001*
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(Surgery : Conservative)
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Symptomatic vasospasm (Yes : No : N/A)
Postoperative complication (Yes : No)
N/A: not available
ACCEPTED MANUSCRIPT Table 4. Multivariate anal ysis for independent living Likelihood-ratio
p-value
chi-square test
(Prob>ChiSq)
Factors
4.618 ( 75~79 : 80~84 : 85~ ) Gender
(Yes : No) Hunt-Kosnik grade
Treatment
5.239
0.0221*
11.09
0.0009*
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(1~3 : 4, 5)
0.0184*
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(Male : Female) Pre-morbid conditions
0.0994
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5.553
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Age
0.1421
0.7062
5.756
0.1241
11.36
0.0034*
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(Surgery : Conservative)
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Symptomatic vasospasm (Yes : No : N/A)
Postoperative complication (Yes : No)
N/A: not available
ACCEPTED MANUSCRIPT
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SC
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Survival rate
A
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Rate of independent
B
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Follow-up periods (month)
Follow-up periods (month) Figure 1
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A
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Rate of independent
(p<0.05)
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HK grade 1~3
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HK grade 4, 5
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(p<0.05)
Radical intervention
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Rate of independent
B
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Follow-up periods (month)
Conservative treat
Follow-up periods (month) Figure 2
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Abbreviations
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m-RS: modified Rankin scale HK grade: Hunt-Kosnik grade
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EP
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SAH: subarachnoid hemorrhage
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Conflict of interest This study was supported by a Grant-in-Aid for Scientific Research of the Japan Society for
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the Promotion of Science (No: 40312491) to Norihito Shimamura. We do not have any other
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conflict of interest.
ACCEPTED MANUSCRIPT
Highlights
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Good grade independent elderly SAH cases should have radical intervention performed. Half of patients lived independently for 40 months in the radical intervention group.
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Post-operative complication strongly influence to poor outcome.
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Age is not important factor for independent living in elderly cohort.
S1878-8750(16)00476-9
DOI:
10.1016/j.wneu.2016.03.057
Reference:
WNEU 3880
To appear in:
World Neurosurgery
Received Date: 13 February 2016 Revised Date:
17 March 2016
Accepted Date: 18 March 2016
Please cite this article as: Shimamura N, Naraoka M, Katagai T, Katayama K, Kakuta K, Matsuda N, Ohkuma H, Analysis of factors that influence long-term independent living for elderly subarachnoid hemorrhage patients, World Neurosurgery (2016), doi: 10.1016/j.wneu.2016.03.057. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title: Anal ysis of factors that influence long-term independent living for
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elderl y subarachnoid hemorrhage patients
Authors: Norihito Shimamura MD. PhD., Masato Naraoka MD. PhD., Takeshi Katagai MD., Kosuke Katayama MD., Kiyohide Kakuta MD., Nao ya Matsuda
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MD. PhD., Hiroki Ohkuma MD. PhD.
Affiliation: Department of Neurosurgery, Hirosaki Universit y School of
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Medicine
Corresponding author:
Norihito Shimamura M.D., Ph.D.
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Department of Neurosurgery
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Hirosaki Universit y School of Medicine 5-Zaihuchou, Hirosaki Aomori pref. JAPAN. 036-8562 Tel: +81-172-39-5115 Fax: +81-172-39-5116 e-mail: [email protected]
Cover Title: Long-term independent living for very elderl y SAH 1
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Itemized list: four tables and two figures
Key words: cerebral aneurysm, elderl y patient, independent living, radical
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intervention, subarachnoid hemorrhage
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Number of references: 45
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Specify the number of words: 4026
2
ACCEPTED MANUSCRIPT Abstract Background. The number of elderl y subarachnoid hemorrhage (SAH) patients
for elderl y (
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has been increasing. The aim of this study was to anal yze long-term outcome 75 y) SAH patients and to establish a treatment strategy.
Methods. From January 2005 to December 2013, 86 consecutive cases were
SC
treated. We used a modified Rankin scale (m-RS) at the outpatient clinic, or a
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telephone interview of patients and/or families. Kaplan-Meier plots were done for mortalit y and independent (m-RS 0 ~ 2) state. Multivariate anal ysis was done to distinguish factors that influence on outcome.
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Results. Median age was 79, Hunt-Kosnik grade 1 ~ 3 was 79 radical intervention (clipping or coiling) rate was 78
and the
. Mean follow-up
period was 28.7±3.4 se months. Half of deaths occurred during the first two
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months. The number of cases of independent living gradually decreased to
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50% at 28 months after SAH. Half of patients lived independentl y for 36 months at HK grades 1 to 3, and 3 months at HK grades 4 to 5 (p<0.05). Half of patients lived independentl y for 40 months in the radical intervention group, and 14 months in the conservative treatment group (p<0.05). Multivariate anal ysis for independent living revealed that gender, pre-morbid condition, HK grade, and postoperative complication were significant 3
ACCEPTED MANUSCRIPT (p<0.05). Conclusions. Good-grade elderl y SAH cases that were independent pre-stroke have
perioperative
radical
intervention
complications
have
performed a
aneurysm.
influence
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SC
independent living.
positive
for
4
Avoiding
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should
on
long-term
ACCEPTED MANUSCRIPT Introduction Aneurysmal subarachnoid hemorrhage (SAH) is fatal in half of patients, but younger cases that survive can achieve useful dail y life after surgery and/or
of elderl y stroke patients is increasing 1 ,
7, 8
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rehabilitation 1 - 6 . In a societ y with progressivel y-advancing aging, the number . But outcomes for elderl y SAH
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patients treated b y clipping or coiling are poor because initial SAH grades are
organs are diseased 2 ,
9-14
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poor, the brain is vulnerable, a high rate of vasospasm exists, and other . Respectivel y, man y authors have reported that
prognostic factors for poor outcome are age and poor clinical status on 9, 10, 12, 15-17
.
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admission 2 ,
Life expectancy for elderl y persons now extends beyond that of previous decades. No doubt, elderl y SAH cases are able to live for long periods after
4, 9, 17-20
. Also, recent reports have reached the consensus that cases
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outcome
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an ictus, but qualit y of life has not been discussed in a context of long-term
of SAH less than 70 years-old have great potential to achieve favorable outcome 2 ,
18, 21-24
. Some reports recommend a treatment cutoff of 74 years 3 ,
25
.
On the other hand, selected 9 t h decade cases of SAH can achieve favorable outcome 9 ,
21, 26, 27
.
The Japanese Ministry of Health, Labor and Welfare defines a person over 5
ACCEPTED MANUSCRIPT 75 years-old as in the advanced-age category. An y controvers y over treatment strategy for very elderl y SAH cases should thus be discussed at around 75 years of age and older. Some researchers have reported mortalit y or favorable
26, 28, 29
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outcome over several months as GR and MD on the Glasgow Outcome Scale 9 , . But MD includes levels 2 and 3 of the modified Rankin scale (m-RS), 31
. Independent dail y living is
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while m-RS 3 is a partiall y-dependent state 3 0 ,
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important not onl y for patients and families but also for medico-social economics.The aim of this stud y was to reveal temporal changes in mortalit y and independent state for elderl y SAH cases. We also discuss an efficient
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treatment strategy for elderl y cases of SAH.
Material and Methods
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This stud y was approved b y the Hirosaki Universit y Ethics Committee. We
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acquired written, informed consent for this stud y from patients and/or families.
From January 2005 to December 2013, we treated 89 consecutive SAH cases at ages over 75 years. SAH was diagnosed b y computed tomograph y (CT), and aneurysms
were
diagnosed
by
digital
subtraction
angiograph y
or
three-dimensional CT angiograph y. When multiple aneurysms were found, we 6
ACCEPTED MANUSCRIPT diagnosed ruptured aneurysm based on the distribution of SAH, and the size and shape of the aneurysm. Clinical severit y of SAH was classified b y a Hunt-Kosnik (HK) grade, with grades 1 to 3 defined as good, while grades 4
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to 5 were poor 3 2 . We recommend earl y (within 72 hours after SAH onset) radical aneurysm treatment (clipping or coiling) to the patient and famil y.
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While aneurysm neck clipping is first-line at our institute for young patients, 20
. Also, an aneurysm
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we select coiling for elderl y patients just as often 1 9 ,
with posterior circulation, more than one dome, and an adequate neck ratio or large size (> 10mm) tended to be treated b y coiling. The selection of the
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treatment method was discussed b y several board-certified neurosurgeons, depending on whether the shape and route of approach were appropriate for aneurysm coiling.
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Post-operative management was as follows: We maintained normovolemia
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with intravenous administration of fasudil h ydrochloride for prevention of vasospasm. (Nimodipine has not been approved in Japan.) All patients were routinel y ambulated on the day after the operation following a determination of negative brain pathology via CT. Some patients refused ambulation due to headache, fatigue, nausea and so on. We defined ambulation according to the Hauser ambulation index 3 3 . All patients were routinel y ambulated as soon as 7
ACCEPTED MANUSCRIPT possible. Even if conservative treatment is selected, we recommend earl y ambulation to prevent muscle atroph y. When s ymptomatic vasospasm was suspected as the prime concern, triple-H therap y was also carried out,
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depending on clinical s ymptoms, biochemical examination and brain CT 1 5 . Angiograph y was performed simultaneousl y and, for etiologic spastic artery,
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intra-arterial injection of medicines (fasudil and/or nicardipine) and/or
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balloon angioplast y were carried-out. When h ydrocephalus occurred, lumbar drainage or cerebral ventricle drainage was done during the acute phase and a ventricular- or lumbo-peritoneal shunt was done for normal pressure
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h ydrocephalus.
Other organ diseases that required continuous treatment were defined as pre-morbid conditions, except for h ypertension, because almost all patients
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were taking anti-h ypertension drugs. Those organ diseases that required
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additional treatment, including infection, were defined as postoperative complications. Finally, the destination following discharge was extracted from the medical records. We evaluated m-RS at the outpatient clinic or in a telephone interview with the patient and/or famil y. The questionnaire used for the telephone interview included abilit y to walk, bathe, dress and orient. If the m-RS worsened, we 8
ACCEPTED MANUSCRIPT evaluated when and wh y the patient deteriorated. The cause of death was defined according to the clinical diagnosis, but some cases were defined as
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‘old age,’ or gradual weakening and death All patients were followed-up, and follow-up was terminated upon death. Primary outcome was mortalit y and secondary outcome was deterioration into
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dependent state. We excluded three non-aneurysm SAH cases from anal ysis of
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outcome because of non-aneurysm SAH is a disease well known for a favorable prognosis.
Blinded co-authors MN and NM independentl y assessed outcome and a
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consensus discussion was held. We defined independent living as m-RS 0 to 2. An m-RS 3 state cannot engage full y in dail y life; they need some assistance for elimination needs, bathing and dressing.
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A Kaplan-Meier curve was calculated for the survival rate or rate of
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independent dail y life (JMP 8.01, SAS Institute Inc. Cary, NC). Clinical factors that influenced outcome were anal yzed b y multivariate anal ysis (Weibull distribution). A P value of ‹0.05 was considered statisticall y significant.
Results 9
ACCEPTED MANUSCRIPT Eight y-six cases were included in this stud y. Median age was 79 years and the range was from 75 to 90 (Table 1). Gender of cases were 8 male and 78 ), with 18 cases (21%)
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female. HK grades 1 to 3 comprised 68 cases (79
given a poor grade. Pre-morbid conditions were diagnosed in 17 cases, and three cases had dual diseases (Table 1). Radical interventions were 78% (45
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clipping: 20 coiling: 2 wrapping or trapping). The other 19 cases were treated
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conservativel y, due to poor grade (n=6) or high age (n=6) and so on (Table 1). Symptomatic vasospasm occurred in 30 cases that included 4 cases before admission and 26 cases (30%) after admission. Ventricle-peritoneal shunt was
non-neurological
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done for 13 cases (15%). Eighteen cases (21%) suffered post-operative complication.
These
comprised
mostl y
infections
by
methicillin-resistant Staph ylococcus aureus; Six cases of pneumonia and one
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of wound infection are included (Table 1). Fort y-nine percent of cases
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achieved favorable outcome at 30 days after the ictus (Table 1), sixt y-nine percent of cases were discharged to another hospital for rehabilitation, and 22% of patients were discharged to their own homes (Table 1). Mean follow-up period was 28.7 ± 3.4 se months. The end of stud y mortalit y rate was 22
, rate of independent living was 41
, rate of
dependent living was 37%(Table 1). Half of deaths occurred during the first 10
ACCEPTED MANUSCRIPT two months after SAH and the reason of death were medical complications (Table 1, Figure 1A). Major reasons for death after the discharge were old age
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(Table 2). The number of cases of independent living gradually decreased to 52% at 19 months after SAH (Figure 1B). Thereafter, the decrease in independence slowed. Half of patients lived independentl y for 36 months at
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HK grades 1 to 3, and 3 months at poor grades (p<0.05, Figure 2A). Half of
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patients lived independentl y for 36 months in the radical intervention group, and 13 months in the conservative treatment group (p<0.05, Figure 2B). Multivariate anal ysis for death revealed that high age, male gender and
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postoperative complication correlated positivel y with mortalit y (p<0.05, Table 3). Also multivariate anal ysis for independent living revealed that male gender, pre-morbid condition, poor HK grade and postoperative complication
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correlated negativel y with independent living (p<0.05, Table 4).
Discussion
We evaluated long-term temporal changes in survival and independent living in elderl y SAH cases. The survival rate for elderl y SAH patients abruptl y decreased after the ictus but stabilized after four years. But the rate of independent living graduall y decreased and half of patients could not enjo y 11
ACCEPTED MANUSCRIPT their lives independentl y three years after SAH onset. Ninet y percent of patients were refereed to our department, and our patient
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cohort had a smaller than usual number of poor HK grades. Some poor-grade SAH cases were not transferred to our department, due to rejection of radical treatment b y the famil y or due to poor surgical indications. As in previous
.
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34-36
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reports, poor initial HK grade cases rapidl y drop into the dependent state 2 9 ,
Also, our cases had been transferred to our department for surgery, leading to a high number of surgicall y-treated cases. Our strategy is to do radical intervention of an aneurysm for patients who functioned independentl y
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preoperativel y, even in cases of advanced age 1 9 . Age limitation for SAH radical intervention is controversial. In 1995 Fridriksson SM et al. reported
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outcome for 8th and 9th decade SAH cases in Sweden 2 1 . Two-thirds of 70 ~
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74 year-old patients returned to independent living, but they did not recommend surgery for cases over 80 years old. After two decades in 2014, Park J et al. reported a 1-year functional outcome for cases of SAH over 70 years old, even with WFNS grades 1 ~ 3, while onl y 54.8% of cases over 75 years old could achieve an m-RS of 0 ~ 3. They concluded that 75 was the critical age for the radical operation 3 . In 2006 Nieuwkamp DJ anal yzed 170 12
ACCEPTED MANUSCRIPT SAH cases over 75 years old, with onl y 25% treated surgically and onl y 15% independent at discharge 1 8 . Follow up outcome at 2 ~ 4 months after ictus showed that 18% of cases were independent. Age was not related to outcome
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in their elderl y cohort, while good initial grade related to good outcome 2 9 . Several reports on one-year follow up of 9 t h decade, surgically-treated SAH 27, 34
. The rate of favorable outcome was 20 ~
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cases have been published 2 6 ,
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54% and the WFNS grade was determined as a significant factor. From an elderl y subgroup anal ysis of ISAT, endovascular treatment allowed quicker mobilization in these patients, and prolonged bed rest could therefore be
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avoided 1 3 . Incidences of infections and pulmonary complications were reduced in the endovascular treated patient group. Of course, we selected interventional coiling of ruptured aneurysm for elderl y SAH cases. But the
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majorit y of aneurys ms were not suitable for coiling because of aneurysm
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shape and/or access route.
Our treatment strategy is to radicall y treat pre-SAH independent patients at HK grades of 1 to 3 during the acute phase and ambulate earl y to avoid muscle atroph y and dementia. Brain-derived neurotrophic factor is secreted b y skeletal muscle, and muscle atroph y induces dementia, depression, diabetes and malignancies 3 7 - 3 9 . Age is not a major limitation in an 13
ACCEPTED MANUSCRIPT advanced-age society. Even if the patient was not treated radicall y, we recommended and did earl y ambulation. Our previous studies reveal earl y 20
.
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ambulation produce ph ysical and ps ychological favorable outcome 1 9 ,
Elderl y stroke patients lose their ph ysical abilities abruptl y d uring the acute phase. At the same time, full recovery of ph ysical and ps ychological function
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is difficult for elderly patients; aging diminishes tissue stem cell functions
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that regenerate the central nervous s ystem, muscle and other organs 4 0 . Favorable outcome of our series at discharge was 49%, but the discharge to their own homes was 22%. Sixt y-nine percent of patients were transferred to a
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rehabilitation hospital. This discrepancy is a function of medico social problems in Japan; intensive rehabilitation is available within three months after the ictus and for those who live alone or for aged couples in need. After
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discharge from the acute-care hospital, elderl y SAH patients have little
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chance to improve their activities in daily life 2 2 ,
35, 41-43
. Anal ysis of SAH
cases over 65 years revealed that 40 ~ 60% of cases achieved favorable outcome after 6 to 20 months 1 0 ,
11, 24, 44, 45
. In 2009 Nieuwkamp DJ et al.
reported that the mean age of patients with SAH increased from 52 to 62 years, but case-fatalit y rates decreased b y 17% between 1973 and 2002 8 . Birinjikji W et al. anal yzed SAH mortalit y in a data-base from 2001 to 2009, with aging 14
ACCEPTED MANUSCRIPT an independent risk for mortalit y, but the outcomes for SAH at all ages has been improving 1 . Very elderl y SAH cases have a high rate of mortalit y, but
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extending life is not the onl y purpose of SAH treatment. All patients and families strongl y desire qualit y of life and independent living. We need to focus on how we can bring independent living to very elderl y SAH patients.
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The pre-morbid condition for our cohort is onl y 20% because we eliminate
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h ypertension from the pre-morbid condition. Nearl y all cases were medicated with anti-h ypertension drugs, so we did not include h ypertension in the pre-morbid condition. In our result, pre-morbid condition did not influence
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mortalit y but influenced independent living negativel y. And post-operative complication was negativel y related mortalit y and dependent living. While the pre-morbid condition cannot be prevented b y our surgeons, post-operative
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complications are preventable. Elderl y patients have a high likelihood of 35, 42
.
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mortalit y and cardiovascular events compared to a health y population 2 2 ,
From our results, half of patients drop into a dependent state within three years after ictus, and a long-term treatment strategy for very elderl y SAH patients is vitall y important for the future. There are several limitations to this stud y. We do not have age- and gender matched health y controls and thus cannot objectivel y measure the influence 15
ACCEPTED MANUSCRIPT of age progression on mortalit y or decrease in functional independence. A randomized control trial is difficult due to ethical problems: absence of
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treatment produces a fatal prognosis for the patient.
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Conclusions
pre-stroke Avoiding
should
have
perioperative
radical
intervention
complications
have
performed
a
positive
for
aneurysm.
influence
on
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independent living.
Acknowledgement
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Good-grade SAH cases over 75 years of age that were independent
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We thank Markus In glin (Universit y of Basel) for his editorial assistance.
Sources of Funding
This stud y was supported b y a Grant-in-Aid for Scientific Research of the Japan Societ y for the Promotion of Science (No: 40312491) to NS.
Conflict of interest 16
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We do not have an y conflict of interest.
17
ACCEPTED MANUSCRIPT Ref er e nc e L is t
1.
Br i nj ik j i W , Lan zi n o G , Ra b ins t ei n A A , K al lm e s DF , C l of t HJ . A g e- r e l at e d tr e nds i n th e tr ea tm ent an d o utc om es of r u pt ur e d c er e br a l a ne ur ys m s : a s tu d y of th e na t io n wi d e i n pa t ie nt s am pl e 2 00 1- 20 0 9. AJ N R Am J N e ur or a d io l 2 0 13 ;
2.
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34( 5) :1 0 22 - 1 0 27 . La n zi n o G , Ka s s e l l NF , G er m ans on T P e t a l. A ge a n d o utc om e af t er
an e ur ys m al s u b ar ac h n o id h em or r h a ge : wh y d o o ld er p a ti e nts f ar e w or s e ? J Ne ur os ur g 1 9 96 ; 8 5( 3 ) :4 1 0- 4 1 8.
P ar k J , W oo H, K a ng DH , K im Y. C r i t ic a l a g e af f ec t i ng 1- ye a r f unc ti o na l
SC
3.
ou tc om e i n e l der l y p a t i en ts a ge d > / = 7 0 ye a r s wit h a n eur ys m a l s u b ar ac h n oi d
4.
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hem or r ha g e. Ac t a Ne u r oc h ir (W ien ) 2 01 4; 1 56( 9) :1 6 55 - 1 6 61 . Ho p JW , Rink e l G J , A l gr a A, v an G J . C h an g e s i n f unc t io n a l ou tc om e a nd qu a l it y of l if e in p a ti e n ts an d c ar e g i ver s af t er a n eur ys m a l s ub ar ac h no i d hem or r ha g e. J Ne ur os ur g 20 0 1; 9 5( 6) : 9 57 - 9 63 . 5.
Ho p JW , Rink e l G J , A l gr a A, v an G J . Q ua l i t y of l if e i n p at i e nts a n d par t ner s af ter an e ur ys m al s u b a r ac h n o id hem or r ha g e. Str ok e 1 99 8 ; 29 ( 4) :7 9 8- 8 0 4. Ho p JW , Rink e l G J , A l gr a A, v an G J . C as e- f at a l it y r a tes an d f unc t i on a l
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6.
ou tc om e af t er s u ba r ac hn o i d hem or r ha g e: a s ys t em at ic r e v i e w. S tr o k e 1 99 7; 28( 3) :6 6 0- 66 4.
J oh a ns s o n M , C es ar i n i K G , C on t an t CF , P er s s on L, E n b la d P . C ha n ges in
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7.
i nt er ve n t io n a nd ou tc o m e in el d er l y p at i en ts wi t h s ub ar ac hn o id he m or r ha ge .
8.
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Str ok e 2 00 1 ; 32 ( 1 2) : 2 84 5- 2 94 9. Ni e u wk am p DJ , Se t z L E, A lg r a A, Li n n F H , d e R oo ij N K, Ri nk e l G J . C h an g es i n c as e f at a l it y of a n eur ys m al s u b ar ac h no i d ha em or r h ag e o v er t im e, ac c or d i ng t o ag e , s ex , a n d r e g io n: a m et a- an a l ys is . L a nc et N e ur o l 2 0 09 ; 8( 7) : 6 35- 6 4 2. 9.
As an o S , W atan ab e T , S h i no h ar a T e t a l. Im por t anc e of th e i n it i a l gr a d e of s ub ar ac hn o id hem or r h ag e i n t he pa t ie nts wi t h th e a g e of 8 0 ye ar s an d o l de r f r om a s in g le c en te r a na l ys is . Ac t a N e ur o l B e lg 2 0 11 ; 1 11 ( 3) :2 1 3- 21 6 .
10 . Br au n V, R at h S, An t o n ia d is G , R ic ht er H P , B or m W . T r eatm en t a n d o utc om e of an e ur ys m al s u b ar ac h n o id h a em or r h ag e i n t h e e ld er l y p at i e nt . Ne ur or a d i o lo g y 20 0 5; 4 7( 3) : 2 15 - 2 2 1.
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ACCEPTED MANUSCRIPT 11 . Lu b ic z B , Lec l er c X , G au vr i t J Y, Lej eu n e J P , Pr u vo J P. E n do v as c u l ar tr e a tm ent of r u p tur e d i ntr ac r an i a l a ne ur ys m s i n e l der l y pe o p le . AJ NR Am J N eur or a di o l 20 0 4; 2 5( 4) : 5 92 - 5 9 5. 12 . Ros e ng ar t AJ , Sc hu l th e is s K E, T o le nt i n o J , Mac d on a l d RL . Pr o gn o s tic f ac t or s f or o u tc om e i n p at i en t s wit h a n eur ys m a l s u b ar ac h n oi d h em or r h a ge . Str ok e
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20 0 7; 3 8( 8) : 2 31 5- 2 32 1 . 13 . R yt tl ef or s M, E n b la d P , K er r R S, M o l yn e ux A J . I n ter n at i on a l s u b ar a c hn o i d an e ur ys m tr i al of n e ur os ur g ic a l c l i p pi n g ver s us e n do v as c u lar c o i l in g: s ub gr o up an a l ys is of 27 8 e l der l y p at i e nts . St r ok e 2 00 8 ; 39( 1 0) : 2 72 0- 2 72 6.
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14 . S u zuk i A, Ya s u i N, H a de is h i H , Sa yam a I, As ak ur a K, N ag as him a M . [C a us es of po or r es u lts of e ar l y s ur g er y i n r up tur e d i ntr ac r a n i a l an e ur ys m s i n e ld er l y
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pa t ie n ts ] . Ne ur o l Me d Ch ir ( T ok yo) 19 8 8; 2 8( 12) : 11 5 7- 1 1 62 .
15 . B ed er s on J B , Co n no l l y E S, J r . , Ba tj e r H H e t a l. G u i d el i n es f or th e m an a gem e nt of a n eur ys m a l s u bar ac hn o i d hem or r ha g e: a s ta tem en t f or h ea l thc ar e pr of es s i o n als f r om a s pec i a l wr it i ng gr o u p of t he Str ok e Co u nc il , A m er ic a n He ar t As s oc i a ti o n. Str ok e 20 0 9; 4 0( 3) : 9 94- 1 02 5 .
16 . G o n za l e z NR , Dus ic k J R, D uc k wi l er G et a l . E nd o v as c u l ar c o i l in g o f
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i ntr ac r an i a l an e ur ys m s i n e l der l y p a t ie nts : r e por t of 20 5 tr e at ed an eur ys m s . Ne ur os ur g er y 2 01 0 ; 6 6( 4 ) : 71 4- 7 20 .
17 . Hor i uc hi T , Ho n go K. Cl i p pi n g s ur ge r y f or a ne ur ys m al s ub ar ac h n o i d
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hem or r ha g e i n p at i en t s a g ed 7 5 ye ar s or o l d er . N e ur o l R es 2 01 1 ; 33( 8) :8 5 3- 85 7.
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18 . Ni e u wk am p DJ , R ink e l G J , Si l v a R, G r e eb e P, Sc hok k ing D A , F er r o J M. S ub ar ac h n o id ha em or r ha g e i n p at i en ts > o r = 7 5 ye a r s : c li n ic a l c ou r s e, tr e atm e nt a n d ou tc om e. J Ne ur o l Ne ur os u r g Ps yc hi a tr y 2 00 6; 77( 8) :9 3 3- 9 3 7. 19 . S him am ur a N , M ats ud a N, Sa to u J , N ak an o T , O hk um a H . E ar l y a m bul at i on pr o d uc es f a v or ab l e o u tc om e an d n o nd em en t i a l s ta te in an e ur ys m al s ub ar ac hn o id hem or r h ag e p at i e nts o l de r th a n 7 0 ye ar s of a g e. W or l d Ne ur os ur g 2 0 14 ; 8 1( 2 ) :3 3 0- 3 3 4. 20 . S him am ur a N , M un ak a ta A, O hk um a H. C ur r e nt m ana g em ent of s u b ar ac h n oi d hem or r ha g e i n a d va nc ed ag e. Ac t a N eur oc h i r S u p pl 20 1 1; 1 1 0( Pt 2 ) :1 5 1- 1 5 5.
19
ACCEPTED MANUSCRIPT 21 . F r i dr ik s s on SM , H i llm a n J , S a ve l a nd H , Br a n dt L . In tr ac r an i a l an e u r ys m s ur g er y i n t h e 8t h a nd 9t h d ec a d es of l if e: im pac t o n p op u la t io n- b a s ed m anag em en t o utc om e. N eur os ur ger y 1 9 9 5; 3 7( 4 ) : 62 7- 6 31 . 22 . Ni e u wk am p DJ , d e W A, W erm er MJ , A l gr a A , R i nk el G J . L o ng - t er m ou tc om e af ter an e ur ys m al s u b a r ac h n o id hem or r ha g e- r is k s of v as c u l ar e v e nt s , de a th
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f r om c anc er a nd a l l- c a us e de at h . J N eu r o l 2 0 14 ; 2 61( 2) :3 0 9- 31 5. 23 . Ro we J G , Mo l yn e ux A J , B yr ne J V, R e no wd e n S , A zi z T Z . En d o vas c u lar
tr e atm e nt of i ntr ac r an i a l an e ur ys m s : a m in im a ll y i n v as i v e ap pr o ac h wit h ad v a nt a ges f or e l de r l y p at i e nts . A ge Ag e i ng 19 9 6; 2 5( 5) : 3 72 - 3 7 6.
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24 . S ed at J , D i b M, L onj o n M et a l . E nd o v as c u l ar tr e atm e nt of r up tur e d i ntr ac r an i a l an e ur ys m s i n pa t ie n ts ag e d 6 5 ye ar s a nd o l d er : f o l l o w- u p of 5 2 pa t i en ts af t er 1
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ye ar . S tr ok e 2 0 0 2; 3 3( 11) : 26 2 0- 2 6 25 .
25 . S hi r a o S , Yo n e d a H, K un i ts u g u I, Su e h ir o E, K oi zum i H, Su zuk i M . A ge lim i t f or s ur g ic a l tr ea tm ent of p oor - gr a de pa t ie nts wi t h s u bar ac hn o i d hem or r ha g e: A pr oj ec t of t he C h u gok u - S h ik ok u d i v is io n of th e J a pa n n eu r os ur g ic a l s oc i et y. S ur g N e ur ol I n t 20 1 2; 3: 1 43 .
26 . Ham ad a J , M or i ok a M , M i ur a M, F uj i ok a S , M ar u b a ya s h i T , Us h io Y .
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Ma n ag em en t o utc om e f or r up tur e d a nt er io r c i r c u la t io n a n eur ys m s wit h a H u nt an d H es s c l i nic a l gr a d e of I II in p a t ie nts in t he 9t h d ec a d e of lif e. S ur g N e ur ol 20 0 1; 5 6( 5) : 2 94 - 3 0 0.
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27 . Ya n o S, H am ad a J , K ai Y e t a l. S ur gic a l in d ic at i ons to m ai n ta i n q u al it y of l if e in e ld er l y p at i en ts wi t h r up t ur e d i n tr ac r a n ia l a n eur ys m s . Ne ur os ur g er y 2 0 0 3 ;
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52( 5) :1 0 10 - 1 0 15 .
28 . B ar k er F G , m i n- H a nj a n i S, B ut l er W E et a l. A ge- d ep e nd e nt dif f er e nc es in s hor t- ter m o utc om e af t er s ur g ic a l or en d o vas c u lar tr e atm en t of unr up t ur e d i ntr ac r an i a l an e ur ys m s i n t he U n it e d S ta t es , 19 9 6- 20 0 0. N eu r os ur g er y 2 00 4; 54( 1) :1 8- 2 8.
29 . Mo n t' al v er n e F , M us ac c h io M , T o l e nt i no V, R i qu e lm e C , T o ur na d e A. E nd o v as c u l ar m a na g e m ent f or in tr ac r a n i al r up t ur e d a n eur ys m s i n e ld er l y pa t ie n ts : o utc om e an d tec h nic a l as pec ts . N e u r or ad i o lo g y 2 00 5 ; 47 ( 6 ) :4 4 6- 4 5 7. 30 . Ra nk in J . C er e br a l va s c u lar ac c i d en ts i n p at i en ts o v er th e a g e of 6 0. I I. Pr og n os is . S c o tt M e d J 1 9 57 ; 2( 5) : 2 00- 2 15 .
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ACCEPTED MANUSCRIPT 31 . v an S wi et en J C , K ou d s ta a l PJ , Vis s er M C, S c ho u te n HJ , v a n G J . In ter o bs er v er agr e em ent f or t h e as s es s m ent of h a nd ic ap i n s tr ok e p at i e nts . S tr o k e 1 98 8; 19( 5) :6 0 4- 60 7. 32 . Hu nt W E, Kos n ik EJ . T im in g a nd per i o per at i v e c ar e i n i ntr ac r an i a l a ne ur ys m s ur g er y. C li n N eu r os ur g 1 97 4; 21 :7 9- 8 9.
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33 . Ha us er S L, D a ws o n D M, L e hr ic h J R et a l . In te ns i ve im m unos u ppr e s s i on in pr o gr es s i ve m ul t ip l e s c l er os is . A r a n dom i ze d, t hr ee- ar m s t ud y of h ig h- dos e i ntr a ve n o us c yc l op h os ph am id e , p las m a ex c h an g e, a n d A CT H. N E n g l J M e d 19 8 3; 3 0 8( 4) : 17 3- 1 80 .
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34 . Hor i uc hi T , T s uts um i K, I t o K, H o n go K. R es u lts of c l i pp i ng s ur g er y f or
an e ur ys m al s u ba r ac h n o id h em or r h ag e i n th e n in th a n d t e nt h d ec a d es of l if e . J
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Cl i n N eur os c i 2 01 4 ; 2 1( 9 ) : 15 6 7- 15 6 9.
35 . Sc ho l l er K , M as s m an n M, Mar k l G et a l . A n eu r ys m al s ub ar ac hn o id h em or r h ag e i n e ld er l y p at i en ts : lo n g- t er m o utc om e a n d pr og n os t ic f ac t or s i n a n i nt er d is c i p l in ar y tr ea t m ent ap pr o ac h . J N e ur o l 20 1 2.
36 . T ak i W , Sak ai N , S u zu k i H. D e ter m i na nts of po or o utc om e af te r an eur ys m a l s ub ar ac hn o id hem or r h ag e whe n b ot h c l i p p in g a nd c o i l i ng a r e a v a i l ab l e:
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Pr os p ec ti v e R eg is tr y o f S ub ar ac h n o id An e ur ys m s T r eatm e nt ( PR E S AT ) in J ap a n. W or ld N eur os u r g 2 01 1; 76( 5) :4 3 7- 44 5. 37 . P ed er s en B K, P ed er s e n M , Kr a bb e K S, Br uu n s ga ar d H , M at th e ws V B, F e bb r a i o
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M A. R o le of ex er c is e- i nd uc ed br a i n- der i v e d ne ur otr o ph ic f ac t or pr od uc ti o n i n th e r e gu l a ti o n of en er g y h om eos t as is i n m a m m als . Ex p P h ys io l 2 0 09 ;
AC C
94( 1 2) : 1 15 3- 1 16 0.
38 . P ed er s en B K , F e b br a i o M A . M us c les , ex er c i s e a n d o bes i t y: s k e le t a l m us c le as a s ec r et or y or g an . Na t R e v E nd oc r i no l 2 0 1 2; 8( 8) :4 5 7- 4 6 5. 39 . T ole a M I, G a l vi n J E . S ar c o p e ni a a n d im pa ir m en t i n c o gn i t i ve a n d p h ys ic a l per f or m anc e. C l in I n te r v Ag i ng 20 1 5; 1 0: 6 6 3 - 67 1 . 40 . S ig n er R A, Mor r is o n S J . Mec h an is m s t ha t r e gu l at e s t em c e ll ag i ng an d l if e s pa n . Ce l l S t em Ce l l 2 01 3 ; 12( 2) :1 5 2- 16 5. 41 . G r e eb e P , R ink e l G J , A lg r a A. L o ng- t er m ou t c om e of p at i en ts d is c h ar g e d to a nur s i n g h om e af t er a n eur ys m a l s u bar ac hn o i d h em or r h ag e. Ar c h P h ys M ed
21
ACCEPTED MANUSCRIPT Re h ab i l 2 01 0 ; 9 1( 2) : 2 47- 2 5 1. 42 . Ni e u wk am p DJ , A l gr a A, B lom q v is t P e t a l. E x c es s m or t a li t y a nd c a r d io v as c u lar e ve n ts i n pa t ie n ts s ur v i v in g s u b ar ac h no i d h e m or r ha ge : a n at i o n wi d e s tu d y i n S we de n . S tr ok e 2 0 11 ; 42( 4) :9 0 2- 90 7. 43 . S an ds t r om N, Ya n B, Do wl i n g R, L a i d la w J , M itc he l l P. C om par is o n of
RI PT
m ic r os ur g er y an d e n d o vas c u l ar tr e a tm ent o n c l i nic a l o utc om e f o l l o wi ng
po or - gr ad e s u b ar ac h n o id h em or r h a ge . J Cl i n N eu r os c i 2 0 13 ; 2 0( 9 ) : 12 1 3- 12 1 8. 44 . J oh a ns s o n M, N or bac k O , G a l G et a l. C l i n ic a l o utc om e af t er e nd o v a s c u lar c o il
Ne ur or a d i ol o g y 2 00 4 ; 46( 5) :3 8 5- 39 1.
SC
em bo l i za t io n i n e l der l y p at i e nts wit h s u b ar ac hn o i d hem or r ha g e.
45 . St ur i a le C L, Br inj ik j i W , Mur a d M H, L a n zi n o G . En d o vas c u l ar tr e a t m ent of
M AN U
i ntr ac r an i a l an e ur ys m s i n e l der l y p a t ie nts : a s ys tem at ic r e v i e w a n d
AC C
EP
TE D
m eta- a n a l ys is . S tr ok e 20 1 3; 4 4( 7) : 1 89 7- 1 90 2 .
22
ACCEPTED MANUSCRIPT Figure legend Figure 1. Kaplan-Meier curves of survival rate (A) and independent living rate (B) Figure 2. Kaplan-Meier curves of independent living rate.
RI PT
A: Good (black line) or poor (gray line) Hunt-Kosnik grade. Difference between these groups is statisticall y significant. B: Radical- (black line) or conservative intervention (gray line) treatment.
AC C
EP
TE D
M AN U
SC
Difference between these groups is statisticall y significant.
23
ACCEPTED MANUSCRIPT
Content
Result
Median age (Range)
79 year old (75 - 90)
Gender (Male/Female)
RI PT
Table 1. Outline of anal yzed cases
Hunt-Kosnik grade 1 : 2 : 3 : 4 : 5
8 : 33 : 27 : 13 : 5 (79%: 21%)
3 : 17 : 51 : 15
M AN U
Fisher group 1 : 2 : 3 : 4
SC
(1~3: 4,5)
8 / 78
Arthritis
5
Renal failure
3
TE D
Dementia, Heart failure, Cancer, Liver cirrhosis, Pre-morbid
2 each
Cerebral infarction
EP
conditions
Abdominal aortic aneurysm
AC C
Acute myocardial infarction,
1 each
Internal carotid artery occlusion (Three cases had dual diseases.)
Radical intervention (clip/coil/other) : 78% (45/20/2): 22% conservative
ACCEPTED MANUSCRIPT
Poor HK grade, High age
6 each (32%)
Reason for Perforator involved, conservative Multiple aneurysms treatment Fusiform, Heart failure,
RI PT
2 each (11%)
Renal failure Yes (before
30 (4, 26): 51: 5
M AN U
Symptomatic vasospasm
SC
1 each (5.3%)
(35%: 59%: 5.8%)
Ventricle peritoneal shunt
13: 66: 7
Yes: No : N/A
(15%: 77%: 8%)
m-RS @ 30 days
TE D
admission, after admission) : No : N/A
0: 1: 2: 3: 4: 5: 6
(Independent: Dependent: Death)
13: 10: 4: 15: 27: 11: 6 (31%: 62%: 7%)
Discharge
EP
Rehabilitation hospital: Home: 59: 19: 1: 1
AC C
Nursing home: Change to
destination
(69%: 22%: 1.2%: 1.2%)
another department
Mean follow up periods
28.7 ± 3.4 se months
(Range)
(1 ~ 110 months)
m-RS @ final follow up: 0: 1: 2: 3: 4: 5: 6
20: 3: 10: 7: 11: 14: 19
(Independent: Dependent: Death)
(41 ％ : 37 ％ : 22 ％ )
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
Values without units are given in a number of cases. N/A: not available.
ACCEPTED MANUSCRIPT Table 2. Post-operative complications and reason for mortalit y Number of cases
MRSA infection*
7 (39%)
Cardiogenic cerebral embolization
RI PT
Diagnosis
2 (11%)
Heart failure
complications
Cerebral infarction not due to vasospasm
M AN U
AMI, ICH, lung edema,
2 (11%) 2 (11%)
SC
Post-operative
1 each (5.6%)
Reason for mortality
Old age
5 (26%)
Aneurysm rupture
4 (21%)
TE D
TAA rupture, drug eruption
3 (16%)
Pneumonia
Heart failure/ Renal failure/ Lung 1 each (5.2%)
EP
cancer/ Abdominal aneurysm rupture 3 (16%)
AC C
Undefined
MRSA: methicillin-resistant staph ylococcus aureus, AM I: acute m yocardial infarction, ICH: intra cerebral hemorrhage, TAA: thoracic aortic aneurysm. * Six pneumonia cases and one wound infection case are included.
ACCEPTED MANUSCRIPT Table 3. Multivariate anal ysis for death Likelihood-ratio
p-value
chi-square test
(Prob>ChiSq)
Factors
5.997 ( 75~79 : 80~84 : 85~ ) Gender
(Yes : No) Hunt-Kosnik grade
Treatment
1.737
0.1875
3.237
0.0720
TE D
(1~3 : 4, 5)
<.0001*
M AN U
(Male : Female) Pre-morbid conditions
0.0499*
SC
19.56
RI PT
Age
1.099
0.2946
4.084
0.2526
24.40
<.0001*
EP
(Surgery : Conservative)
AC C
Symptomatic vasospasm (Yes : No : N/A)
Postoperative complication (Yes : No)
N/A: not available
ACCEPTED MANUSCRIPT Table 4. Multivariate anal ysis for independent living Likelihood-ratio
p-value
chi-square test
(Prob>ChiSq)
Factors
4.618 ( 75~79 : 80~84 : 85~ ) Gender
(Yes : No) Hunt-Kosnik grade
Treatment
5.239
0.0221*
11.09
0.0009*
TE D
(1~3 : 4, 5)
0.0184*
M AN U
(Male : Female) Pre-morbid conditions
0.0994
SC
5.553
RI PT
Age
0.1421
0.7062
5.756
0.1241
11.36
0.0034*
EP
(Surgery : Conservative)
AC C
Symptomatic vasospasm (Yes : No : N/A)
Postoperative complication (Yes : No)
N/A: not available
ACCEPTED MANUSCRIPT
M AN U
SC
RI PT
Survival rate
A
EP AC C
Rate of independent
B
TE D
Follow-up periods (month)
Follow-up periods (month) Figure 1
ACCEPTED MANUSCRIPT
A
RI PT
Rate of independent
(p<0.05)
SC
HK grade 1~3
M AN U
HK grade 4, 5
EP
(p<0.05)
Radical intervention
AC C
Rate of independent
B
TE D
Follow-up periods (month)
Conservative treat
Follow-up periods (month) Figure 2
ACCEPTED MANUSCRIPT
Abbreviations
RI PT
m-RS: modified Rankin scale HK grade: Hunt-Kosnik grade
AC C
EP
TE D
M AN U
SC
SAH: subarachnoid hemorrhage
ACCEPTED MANUSCRIPT
Conflict of interest This study was supported by a Grant-in-Aid for Scientific Research of the Japan Society for
RI PT
the Promotion of Science (No: 40312491) to Norihito Shimamura. We do not have any other
AC C
EP
TE D
M AN U
SC
conflict of interest.
ACCEPTED MANUSCRIPT
Highlights
RI PT
Good grade independent elderly SAH cases should have radical intervention performed. Half of patients lived independently for 40 months in the radical intervention group.
SC
Post-operative complication strongly influence to poor outcome.
AC C
EP
TE D
M AN U
Age is not important factor for independent living in elderly cohort.