Can a Brain Hemorrhage Happen Again

• Journal List
• J Neurol Neurosurg Psychiatry
• 5.78(8); 2007 Aug
• PMC2117741

J Neurol Neurosurg Psychiatry. 2007 Aug; 78(8): 836–840.

The gamble of recurrent stroke subsequently intracerebral bleeding

Received 2006 Sep eight; Revised 2006 Dec 21; Accepted 2007 Jan 4.

Abstract

Background and aim

The risks of recurrent intracerebral haemorrhage (ICH) vary widely (0–24%). Patients with ICH also have risk factors for ischaemic stroke (IS) and a proportion of ICH survivors re‐present with an IS. This dilemma has implications for safe treatment. This report aims to determine the risk of recurrent stroke events (both ICH and IS) following an index bleed and whether ICH recurrence gamble varies co-ordinate to location of index bleed.

Patients and methods

All patients diagnosed with an acute ICH presenting over an eight.v yr menstruation were identified. Each ICH was confirmed by reviewing all of the radiology results and, where necessary, the clinical case notes or post‐mortem data. Recurrent stroke events (ICH and IS) were identified by reappearance of these patients in our stroke database. Coronial post‐mortem results for the same period were likewise reviewed. Each recurrent effect was reviewed to confirm the diagnosis and location of the stroke.

Results

Of the 7686 stroke events recorded, 768 (x%) were ICH. In the follow‐up period, there were 19 recurrent ICH and 17 new IS in the 464 patients who survived across the index hospital stay. Recurrence rate for ICH was two.1/100 in the first year but 1.ii/100/year overall. This compares with 1.iii/100/year overall for IS. Nearly recurrences were "lobar–lobar" type.

Conclusion

The cumulative gamble of recurrent ICH in this population is like to that of IS afterward the first year.

Strokes caused by an intracerebral bleeding (ICH) are less mutual than ischaemic strokes (IS), just they take a much higher early case fatality.^{1 ,2} ICH contributes to approximately 10–15% of all strokes in Caucasians, merely this proportion is increased in some Asian and Southward American populations.^{1 ,3 ,4 ,5 ,vi} This variation in incidence may exist due to genetic influences, prevalence and handling of hypertension and medication apply (for instance, antiplatelet and anticoagulant drugs) or a combination of these factors.

Given the high bloodshed, survivors of an ICH are justifiably fearful of another event. They ask, "What are my chances of having a further stroke (ICH), medico?" Answering this with confidence is challenging. Just as incidence rates are various, the reported gamble of recurrence following an ICH also varies enormously from 0% to 24% (tabular array one​ ). This may be explained in part by pocket-size sample sizes or short follow‐up periods.^{7 ,viii ,ix ,xv ,22} Differences in the mean age and ethnicity of the populations studied, as well as location of the bleed and prevalence of hypertension, are alternative reasons.

Table 1 Risk of recurrence of intracerebral haemorrhage

Country	Reference	n	Mean historic period (y)	Maximum duration of follow‐up (y)	Crude cumulative recurrence rate (%)
Italy	Fieschi 1988vii	104	61	one	0
USA	Douglas 1982viii	70	–	(median two.5)	0
Kingdom of denmark	Helwig‐Larsen 1984nine	53	54	9	0
South Korea	Lee 199010	518	54	three	2.7
Finland	Fogelholm 199211	158	68	5	iv
Germany	Buhl 200312	968	63.seven	11	4.nine
Canada	Colina 200013	172	65	11	4.nine
India	Misra 1995xiv	105	43.5	–	5
Taiwan	Chen 199515	892	59	two	five.three
South Korea	Bae 199916	989	58	seven	5.iv
Japan	Maruishi 199617	406	62.9	viii	5.9
Mexico	Gonzalez‐Duarte 1998eighteen	359	60	viii.v	six.0
French republic	Neau 199719	375	64.seven	10	6.4
Nippon	Inagawa 200520	279	63.iii	7	7
Commonwealth of australia	Hankey 199821	36	–	v	8
Japan	Arakawa 199822	74	threescore.8	v	11
Republic of finland	Fogelholm 200523	203	66.vi	16	xi.3
Netherlands	Vermeer 20022	243	–	ten	12.ane
Italy	Passero 199524	112	63.7	(hateful seven)	24

The incidence of ICH increases with age¹ and it is important to know the recurrence adventure for all patients, including the very quondam. However, the average age of patients in these recurrence studies ranges from 54 to 66 years.^{10 ,thirteen ,nineteen} This is much lower than expected for our stroke population,²⁵ suggesting some bias against inclusion of older patients with ICH. The predominant location of the index bleed varies from almost all deep to by and large lobar.^{17 ,19} Location may alter the take chances of recurrence.²⁴ Lobar bleeds take been reported to have a higher recurrence risk in some studies.^{two ,13 ,19} This may exist because of the college prevalence of cerebral amyloid angiopathy (CAA), ApoE genotype or that anticoagulant related bleeds are more ordinarily associated with lobar location.^{26 ,27 ,28} Hypertension is a chance factor for both the incidence of ICH and recurrent bleeds,^{one ,29} but in epidemiological studies control of hypertension is difficult to mensurate, and therefore may contribute to the large variation in take chances of recurrence.²² As with incidence data, ethnicity may explain some of the differences.

Some of the risk factors for ischaemic stroke are similar to those for ICH. These include hypertension, male sex, increasing historic period and possibly diabetes and smoking.³⁰ It is not uncommon for clinicians to take patients who accept had both an ischaemic and a haemorrhagic stroke.^{29 ,31} This presents a challenge when deciding what the most appropriate secondary prevention strategies are. For case, should aspirin be stopped, started or connected? These dilemmas take been eloquently debated in recent papers,^{32 ,33} but cannot be answered confidently without further information. This includes knowing the risks of recurrence of both ICH and ischaemic type strokes, as well as the gamble of an ischaemic effect in an ICH population (and vice versa).

Therefore, this report has the following aims

1. to determine the risk of recurrence of an ICH following an index bleed in a predominantly Caucasian population;

2. to determine whether this recurrence take a chance varies co-ordinate to location of the index drain;

3. to make up one's mind the take a chance of ischaemic stroke following an index bleed.

Methods

Christchurch city and the surrounding N Canterbury surface area (denominator population 450 000) are served by a unmarried acute general hospital (includes the regional neurosurgical unit of measurement) and two subacute or rehabilitation hospitals. Nigh all patients with an acute disabling stroke are admitted to the astute infirmary and over 95% receive a CT scan within the first day.³⁴ MRI is available on the acute site, but is not routine as the first investigation for a suspected stroke. Patients are transferred to the subacute hospitals if farther inpatient rehabilitation is required.

In New Zealand, patients are allocated a unique national health identifier (NHI) number, which is used for any subsequent health events. This NHI enables tracking of patients between dissimilar hospitals (eg, between acute and subacute hospitals for the same index event) and for subsequent hospitalisation or death.

At discharge from hospital, all patients have their diagnoses coded using the International Classification of Diseases‐10 (or ICD ix previously) nomenclature. These belch coding data from each of the 3 hospitals were used to identify all patients who had an acute stroke (I60‐I67 for ICD‐ten and 430–437 for ICD‐nine) for the 8.v year menses from 1 January 1996 to 30 June 2004. From these extracted data, a subgroup of all patients diagnosed with an acute ICH (I61 (inclusive of all 161 codes) and I62.9 for ICD 10, or 431 (inclusive of all 431 codes) and 432.9 for ICD nine) was identified. All radiology data (and where necessary the clinical case notes) of each of these ICH patients was reviewed to confirm the diagnosis, location and volume of the drain. Location was broadly categorised into the post-obit types: lobar, deep, intraventricular, cerebellar and brainstem. Volume was calculated using a grid (for earlier scans)³⁵ and latterly the ABC/2 method.³⁶

In New Zealand, all sudden unexplained deaths are referred to the coroner. The coronial records for the same menses were reviewed for any additional patients who may have died because of ICH before reaching hospital. In these cases, the autopsy reports were reviewed to confirm the diagnosis.

Exclusions from the study were subarachnoid haemorrhage, ICH from arteriovenous malformation, neoplasm, trauma, surgery and/or thrombolysis likewise equally when the patient usually resided outside of the North Canterbury region.

Recurrence of a stroke event was adamant past a subsequent appearance of a person from the original dataset. For each possible recurrence, all relevant neuroimaging (and where necessary the clinical notes) were reviewed to confirm the presence of either a new (distinct from index) ICH or cerebral infarct, as well as the location and book of bleed for ICH patients. Patients were followed until 31 December 2004 (follow‐upwardly catamenia varied from six months to 9 years) or until death. Deaths were ascertained from overlapping sources including: (a) coronial records, (b) Canterbury Commune Health Board patient management systems and (c) New Zealand Wellness Information Service. The latter uses the NHI number and records date of death, irrespective of where in the state the death occurred. This source was used as a double check for local data and picked up patients who had subsequently died in the customs without re‐inbound hospital. Date of death and, where possible, cause of death, were recorded.

Kaplan–Meier survival statistics were used to compare survival rates and recurrence rates. Cox'southward proportional hazards analysis was used to decide any association with recurrence from age, sex or site of bleed.

The written report was approved past the regional Canterbury Ethics Committee (CTR/0407/127).

Results

There were 7686 stroke events recorded during the viii.v yr catamenia, of which 915 were coded as an ICH. A total of 768 patients had the ICH confirmed (ten% of all strokes) while 147 patients were excluded. Reasons for exclusion are shown in table two​ .

Table two Reasons for exclusion from the report

Reason for exclusion	n
Miscoding
Haemorrhagic transformation of infarct	36
Ischaemic infarct	27
Subdural haemorrhage	one
No stroke identified	three
Secondary crusade for ICH
Malignancy	22
Arteriovenous malformation	11
Subarachnoid bleeding	5
Trauma	5
Thrombocytopenia	2
Radiotherapy	one
Miscellaneous reasons
Lives outside of catchment surface area	xi
Notes or radiology unable to be located	7
Age <xvi years	1
ICH suspected but non confirmed earlier expiry*
Died before neuroimaging or no neuroimaging washed and no autopsy done	15

The hateful age of ICH patients was 72.4 years (range sixteen–95), and 33.6% of the sample were 80 years or older. Fifty‐two per cent were female. The grouping were predominantly Caucasian (92%) with smaller numbers of Asian (2.4%), Maori (two.4%), Pacific Isle (2.2%) and Indian (0.5%) which mirrors the ethnicity of the older people in Canterbury.³⁷ The principal imaging was CT scan in 742 patients and MRI in 26. Volume of bleed varied from <1 ml to 300 ml, with a mean of 36 ml.

Almost half the alphabetize bleeds were lobar (table 3​ ).

Table 3 Location of alphabetize bleed

Location of alphabetize ICH	No (% of all ICH)	No (%) who died in start 24 h	No (%) who died within 28 days	No (%) surviving until discharge from hospital
Lobar*	373 (49%)	66 (18%)	152 (41%)	218 (58%)
Deep	273 (36%)	41 (fifteen%)	98 (36%)	172 (63%)
Intraventricular	24 (3%)	4 (17%)	12 (l%)	11 (46%)
Brainstem	31 (4%)	9 (29%)	17 (55%)	fourteen (45%)
Cerebellar†	67 (ix%)	14 (21%)	29 (43%)	38 (58%)
Full	768 (100%)	134 (17.5%)	308 (40%)	453 (59%)

A total of 240 deaths (52% of all deaths) occurred within the outset calendar week (fig one​ ) and 315 deaths occurred in the index hospital admission. The cause of expiry for those dying in the community (146) was ascertained in 80/146 (55%). 10 of these community deaths were stroke related (7 ICH, three IS). The majority of patients, for whom the crusade of death is non known, died in long term intendance hospitals (long term case facilities or nursing homes) (47/62, 76%).

Effigy 1 Survival bend for all index intracerebral haemorrhages.

A recurrent ICH occurred in 19 patients (2.5% of all index ICH) with 3 of these patients sustaining a third drain (all lobar). This equated to a recurrence charge per unit of 1.2/100/twelvemonth for those who survived across their index hospital admission. However, the charge per unit was higher in the outset year at ii.1/100. There was a trend towards a lower charge per unit of recurrence for those with deep bleeds (tabular array 4​ ) but these differences according to location of bleed were not statistically significant. Using a proportional hazards model, increased historic period (p = 0.049), but non sex (p = 0.66) or site of bleed (p = 0.47), was associated with risk of recurrence.

Tabular array iv Crude recurrence for survivors compared with location of the index bleed

Alphabetize bleed		Recurrent bleed
Location	northward	Lobar	Deep	Intraventricular	Cerebellar	Brainstem	Unknown*	Total	Unadjusted % recurrence
Lobar	218	8	2	ane				11	5.0%
Deep	172	1	2				1	4	2.3%
Intraventricular	11	1						ane	9.ane%
Cerebellar	38	1			1			2	7.ane%
Brainstem	14	1						i	5.3%
Total	453	12	4	i	1	0	ane	nineteen	4.two%

Seventeen patients who had an index ICH too had an ischaemic stroke during follow‐up. These infarcts were diagnosed past acute CT head scans in 16 and MRI in one. All were in a different location to the alphabetize bleed. The charge per unit of new ischaemic events over the follow‐up menstruation was 1.three/100/twelvemonth. Unlike ICH recurrence rates, the IS rate was not higher in the get-go yr after the ICH (for patients who survived beyond the alphabetize hospital stay). Using a proportional hazards model, neither historic period, sex or site of bleed was associated with the risk of a subsequent IS.

2 people had both a new infarct and a recurrent bleed after the initial ICH.

Discussion

The primary findings of this study are that the adventure of ICH recurrence in survivors of an ICH is highest in the first year at 2.1/100/yr but after that the overall rate of 1.ii/100/yr is comparable with the risk of an IS at 1.iii/100/yr. Increasing age, but not location of the index bleed, is associated with a higher recurrence rate. Almost half of the index bleeds were lobar and the majority of the recurrences were of a "lobar–lobar" type.

At that place are some considerations in relation to completeness of data collection. The risks of recurrence of IS in our study represent a lower estimate of risk as some events may have been missed. Very early recurrences may have been missed in dying patients who did non have a second CT scan and the deterioration attributed to the index ICH. Even so, clinical deterioration in all other patients would prompt a repeat scan. Secondly, while there was a reliance on CT rather than MRI scans, we believe that this has non resulted in any meaning nether counting of recurrence, equally CT is sensitive for detecting acute ICH. Even so, modest microbleeds (detectable on MRI) may have been missed.³⁸ Finally, the cause of out‐of‐infirmary deaths was unable to exist ascertained in 66 people (14% of all deaths). All the same, all sudden unexplained deaths in our community are referred to the coroner and well-nigh ICH patients who survive the initial ictus are symptomatic then present to the unmarried acute hospital. Disabled patients already residing in an establishment were less likely to re‐present to the astute hospital and constituted 75% of those in whom cause of death was not ascertained. Either ICH or IS could have occurred in some of these patients. Some IS may have been missed in patients who presented with neurological signs similar to their index ICH and the CT scan did not show either a new ICH or definite IS. These were not counted as definite IS and so our figures for IS should be regarded as a lower estimate of risk.

Some other potential weakness of our written report is that medication use at the time of recurrence (eg, antiplatelet agents) and the presence (and command) of hypertension were not known. The adequacy of control of hypertension afterwards an ICH is known to influence chance of recurrence.^{15 ,22 ,29} Nonetheless, control of hypertension, and other cardiovascular risk factors, in our general community population has recently been shown to be expert.³⁹

Counterbalanced against these are pregnant strengths of the study. The denominator population was well defined and of a reasonable size, a large cohort of ICH patients (n = 768) was followed and the cohort included a large grouping of older patients (including the "one-time‐old"). Mean historic period was considerably older than other reported ICH recurrence series^{7 ,ten ,13 ,15 ,18 ,19 ,22} and is comparable with the recent Auckland (NZ) Stroke Study.⁴⁰ Thus this accomplice is representative of all patients presenting with ICH, including the very old and those with comorbidities. Unique national identifiers allowed tracing of all recurrent events to be more complete and enabled local survival data to be cross checked confronting national survival data and there was a long follow‐up catamenia (up to 9 years).

In this New Zealand population, the risk of ICH recurrence in survivors of an ICH is moderate, with a cumulative run a risk of 1.ii/100/year. This is comparable with, or lower than, other predominantly Caucasian populations.^{two ,11 ,12 ,13 ,23 ,24 ,31} This is nevertheless the average historic period of our cohort (72.iv years) being older than other series (range 54–68 years). One‐third of our cohort was over 80 years sometime. Age is a recognised risk of both mortality and recurrence risk.^{1 ,2 ,11} Increased age is associated with a college prevalence of cerebral amyloid angiopathy and lobar bleeds, both of which increase recurrent events.ⁱⁱ Alternatively, an older cohort may have lower risks past reducing initial survival. However, by reporting recurrence in survivors simply, this should not exist a cistron. We believe that the historic period structure of our written report population is more reflective of all strokes and ICH presenting in our community and thus our estimate of risk tin can be generalised to all stroke survivors.^{four ,twoscore}

In Asian serial (and possibly S/Central American¹⁸), deep bleeds predominate and near recurrences are "deep–deep" type (ie, both index and recurrent bleed were deep).^{14 ,xvi ,17 ,22 ,27} In contrast, almost half of the index bleeds in this written report were lobar which is a similar or college proportion than previous reports in Caucasian populations.^{2 ,7 ,xix ,41 ,42} Furthermore, the majority of the recurrences were "lobar–lobar" type.^{11 ,19} Lobar bleeds are thought to be the result of hypertensive disease, anticoagulant utilize or CAA, either singly or in combination.⁴³ CAA is a recognised take chances factor for recurrent haemorrhages in a lobar pattern, with one report showing 30% recurrence rates for biopsy proven CAA.^{1 ,27 ,38} Lobar location of the bleed may increase the unadjusted risk of recurrence only information technology is not known whether this is independent of CAA or age.^{2 ,13 ,19 ,24 ,26} Our findings propose that it is not independent of these variables. Patients presenting with an alphabetize drain located in the brainstem, cerebellum or ventricles had a recurrence chance equal to or greater than lobar bleeds. While this has not been previously reported, it requires cautious interpretation. The numbers in each alphabetize group are much smaller than for lobar and deep bleeds, and the risk calculations are based on 1 or ii recurrent bleeds only. However, it is interesting to annotation that all just one of these recurrences occurred in a lobar distribution.

In the current written report, the IS risk in survivors was comparable to that of ICH recurrence (1.three/100/yr and 1.2/100/year, respectively) simply lower than the first yr recurrence gamble (ii.ane/100). Canadian,¹³ Dutch^two and Australian studies²¹ also found that rates of IS and ICH were similar. A Finnish study had like proportions of ICH and IS, simply a much higher absolute, but unadjusted, hazard (11.3% and 10.3%, respectively).²³ In contrast, other studies propose that recurrent ICH events are more mutual than IS past a factor of between 1.4 and ii.ix.^{29 ,31}

The findings of this study accept considerable clinical significance. While the risk of a recurrent drain appears to exist higher in the first yr after the index ICH, there is an ongoing chance that extends out for many years^{12 ,16 ,18 ,23} at a rate that is similar to IS. This finding is not surprising, as the risks of hypertension and increasing age persist. Antihypertensive treatment is very effective for both types of stroke²⁹ and so ongoing efforts to control loftier blood pressure in this grouping are appropriate. Antiplatelet or anticoagulant therapy are advisable strategies to reduce IS, but are usually contraindicated in ICH survivors.^{32 ,33} This seems reasonable in the outset year after an ICH. Yet, as some patients with an alphabetize ICH subsequently develop IS, thromboembolic prophylaxis may be appropriate in selected individuals. Aspirin both increases the relative adventure of ICH and decreases the relative risk of IS, but the accented risks in this population are non known.^{32 ,33} Therefore, thromboembolic prophylaxis should only be given if the chance of IS is loftier and after careful consideration of the risks and benefits for the given private.

Acknowledgements

Nosotros are thankful to the staff of the medical records and radiology departments for assisting with searching for the relevant archived documents and radiology. We are besides grateful to the NZ Health Information Service for confirmation of deaths. The anonymous reviewers fabricated some very helpful comments, for which we are grateful.

Abbreviations

CAA - cerebral amyloid angiopathy

ICD - International Classification of Diseases

ICH - intracerebral bleeding

IS - ischaemic stroke

NHI - national health identifier

Footnotes

Funding: Funding was provided past the Canterbury District Health Board and the Canterbury Health Care of the Elderly Education Trust. This funding supported one of the authors (NFI) as a summertime student but played no other role in the study.

Competing interests: None.

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