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1.  Intracerebral haemorrhage after the neonatal period. 
Archives of Disease in Childhood  1986;61(6):538-544.
Intracerebral haemorrhage is rare in childhood. We have reviewed the last 10 years' experience, in our referral area, of parenchymatous intracerebral haemorrhage in children from 1 month to 16 years of age. There were 27 cases, five of which were intracerebellar and two predominantly intraventricular. The commonest aetiology was vascular malformation (10), followed by haemorrhage into tumour (four), and coagulopathies (five). Clinical features were non-specific, but altered consciousness, headache, vomiting, and focal signs were the most common. Focal signs were, however, rare in the patients with intracerebellar haemorrhage. There was an overall mortality of 54% (14 out of 27). Nine patients were handicapped on follow up, but none severely so. For the diagnosis of intracerebral haemorrhage a high level of clinical suspicion is needed with early use of computed tomography. Maintenance of homeostasis, relief of raised intracranial pressure, and evacuation of haematoma are the aims of management.
PMCID: PMC1777854  PMID: 3729521
2.  Subarachnoid haemorrhage (spontaneous aneurysmal) 
Clinical Evidence  2009;2009:1213.
Introduction
Subarachnoid haemorrhage (SAH) may arise spontaneously or as a result of trauma. Spontaneous SAH accounts for about 5% of all strokes. Ruptured aneurysms are the cause of 85% of spontaneous SAH. The most characteristic clinical feature is sudden-onset severe headache. Other features include vomiting, photophobia, and focal neurological deficit or seizures, or both. As the headache may have insidious onset in some cases, or may even be absent, a high degree of suspicion is required to diagnose SAH with less typical presentations.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of surgical treatments for people with confirmed aneurysmal subarachnoid haemorrhage? What are the effects of medical treatments to prevent delayed cerebral ischaemia in people with confirmed aneurysmal subarachnoid haemorrhage? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 6 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: endovascular coiling; surgical clipping; timing of surgery; and oral and intravenous nimodipine.
Key Points
Subarachnoid haemorrhage (SAH) may arise spontaneously or as a result of trauma. Spontaneous SAH accounts for about 5% of all strokes. Ruptured aneurysms are the cause of 85% of spontaneous SAH. This review deals with only spontaneous aneurysmal SAH. Without treatment, mortality rates of about 50% at 1 month after spontaneous aneurysmal SAH have been reported.
Treatment is aimed at prevention of re-bleeding from the same aneurysm. This can be performed by surgical clipping or by endovascular coiling. In people suitable for either procedure, endovascular coiling has lower rates of poor functional outcome compared with surgical clipping, but it is also associated with increased rate of recurrent haemorrhage from the treated aneurysm and a higher rate of re-treatment for the same aneurysm. Most evidence is in small (<11 mm) aneurysms of the anterior circulation. Therefore, the conclusions cannot be applied to all aneurysms (particularly large and giant aneurysms, and aneurysms with broad necks).Factors that should be considered when deciding on the method of treatment include the morphology of the aneurysm, the age and clinical condition of the person, and the presence or absence of a space-occupying intracranial haematoma.
We do not know the optimal timeframe for carrying out surgical clipping or endovascular coiling after aneurysmal SAH. However, early surgery will prevent re-bleeding from the aneurysm, and is preferred in most people.
Oral nimodipine reduces poor outcome (death or dependence), secondary ischaemia, and CT/MRI evidence of infarction after aneurysmal SAH.
We found no evidence on the effects of intravenous nimodipine alone.
PMCID: PMC2907802  PMID: 21726472
3.  Spontaneous upper limb monoplegia secondary to probable cerebral amyloid angiopathy 
Cerebral amyloid angiopathy is a clinicopathological disorder characterised by vascular amyloid deposition initially in leptomeningeal and neocortical vessels, and later affecting cortical and subcortical regions. The presence of amyloid within the walls of these vessels leads to a propensity for primary intracerebral haemorrhage. We report the unusual case of a 77-year-old female who presented to our emergency department with sudden onset isolated hypoaesthesia and right upper limb monoplegia. A CT scan demonstrated a peripheral acute haematoma involving the left perirolandic cortices. Subsequent magnetic resonance imaging demonstrated previous superficial haemorrhagic events. One week following discharge the patient re-attended with multiple short-lived episodes of aphasia and jerking of the right upper limb. Further imaging demonstrated oedematous changes around the previous haemorrhagic insult. Cerebral amyloid angiopathy is an overlooked cause of intracerebral haemorrhage; the isolated nature of the neurological deficit in this case illustrates the many guises in which it can present.
doi:10.1186/1865-1380-5-1
PMCID: PMC3287112  PMID: 22214197
4.  Spectrum of primary intracerebral haemorrhage in Perth, Western Australia, 1989-90: incidence and outcome. 
In a population based register of stroke (n = 536) compiled in Perth, Western Australia during an 18 month period in 1989-90, 60 cases (11%) of primary intracerebral haemorrhage were identified among 56 persons (52% men). The mean age of these patients was 68 (range 23-93) and 46 (77%) events were first ever strokes. The crude annual incidence was 35 per 100,000, with a peak in the eighth decade, and a male predominance. Deep and lobar haemorrhages each accounted for almost one third of all cases. The clinical presentations included sudden coma (12%), headache (8%), seizures (8%), and pure sensory-motor stroke (3%). Primary intracerebral haemorrhage was the first presentation of leukaemia in two cases (both fatal) and it followed an alcoholic binge in four cases. 55% had a history of hypertension. 16 (27%) patients, half of whom had a history of hypertension, were taking antiplatelet agents, and one patient was taking warfarin. There were only two confirmed cases of amyloid angiopathy. The overall 28 day case fatality was 35%, but this varied from 100% for haemorrhages in the brainstem to 22% for those in the basal ganglionic or thalamic region. Other predictors of early death were intraventricular extension of blood, volume of haematoma, mass effect, and coma and severe paresis at onset. Although based on small numbers, these data confirm the heterogeneous nature of primary intracerebral haemorrhage, but they also suggest a different clinical spectrum of this type of stroke in the community compared with the experience of specialist neurological units.
PMCID: PMC1073077  PMID: 8057117
5.  Surgical Trial in Lobar Intracerebral Haemorrhage (STICH II) Protocol 
Trials  2011;12:124.
Background
Within the spectrum of spontaneous intracerebral haemorrhage there are some patients with large or space occupying haemorrhage who require surgery for neurological deterioration and others with small haematomas who should be managed conservatively. There is equipoise about the management of patients between these two extremes. In particular there is some evidence that patients with lobar haematomas and no intraventricular haemorrhage might benefit from haematoma evacuation. The STICH II study will establish whether a policy of earlier surgical evacuation of the haematoma in selected patients will improve outcome compared to a policy of initial conservative treatment.
Methods/Design
an international multicentre randomised parallel group trial. Only patients for whom the treating neurosurgeon is in equipoise about the benefits of early craniotomy compared to initial conservative treatment are eligible. All patients must have a CT scan confirming spontaneous lobar intracerebral haemorrhage (≤1 cm from the cortex surface of the brain and 10-100 ml in volume). Any clotting or coagulation problems must be corrected and randomisation must take place within 48 hours of ictus. With 600 patients, the study will be able to demonstrate a 12% benefit from surgery (2p < 0.05) with 80% power.
Stratified randomisation is undertaken using a central 24 hour randomisation service accessed by telephone or web. Patients randomised to early surgery should have the operation within 12 hours. Information about the status (Glasgow Coma Score and focal signs) of all patients through the first five days of their trial progress is also collected in addition to another CT scan at about five days (+/- 2 days). Outcome is measured at six months via a postal questionnaire to the patient. Primary outcome is death or severe disability defined using a prognosis based 8 point Glasgow Outcome Scale. Secondary outcomes include: Mortality, Rankin, Barthel, EuroQol, and Survival.
Trial Registration
ISRCTN: ISRCTN22153967
doi:10.1186/1745-6215-12-124
PMCID: PMC3107158  PMID: 21586127
6.  Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial 
Lancet  2013;382(9890):397-408.
Summary
Background
The balance of risk and benefit from early neurosurgical intervention for conscious patients with superficial lobar intracerebral haemorrhage of 10–100 mL and no intraventricular haemorrhage admitted within 48 h of ictus is unclear. We therefore tested the hypothesis that early surgery compared with initial conservative treatment could improve outcome in these patients.
Methods
In this international, parallel-group trial undertaken in 78 centres in 27 countries, we compared early surgical haematoma evacuation within 12 h of randomisation plus medical treatment with initial medical treatment alone (later evacuation was allowed if judged necessary). An automatic telephone and internet-based randomisation service was used to assign patients to surgery and initial conservative treatment in a 1:1 ratio. The trial was not masked. The primary outcome was a prognosis-based dichotomised (favourable or unfavourable) outcome of the 8 point Extended Glasgow Outcome Scale (GOSE) obtained by questionnaires posted to patients at 6 months. Analysis was by intention to treat. This trial is registered, number ISRCTN22153967.
Findings
307 of 601 patients were randomly assigned to early surgery and 294 to initial conservative treatment; 298 and 291 were followed up at 6 months, respectively; and 297 and 286 were included in the analysis, respectively. 174 (59%) of 297 patients in the early surgery group had an unfavourable outcome versus 178 (62%) of 286 patients in the initial conservative treatment group (absolute difference 3·7% [95% CI −4·3 to 11·6], odds ratio 0·86 [0·62 to 1·20]; p=0·367).
Interpretation
The STICH II results confirm that early surgery does not increase the rate of death or disability at 6 months and might have a small but clinically relevant survival advantage for patients with spontaneous superficial intracerebral haemorrhage without intraventricular haemorrhage.
Funding
UK Medical Research Council.
doi:10.1016/S0140-6736(13)60986-1
PMCID: PMC3906609  PMID: 23726393
7.  Location characteristics of early perihaematomal oedema 
Background
The natural history and triggers of perihaematomal oedema (PHO) remain poorly understood. Cerebral amyloid angiopathy (a common cause of lobar haemorrhage) has localised anticoagulant and thrombolytic properties, which may influence PHO. We hypothesised that early (within 24 hours) oedema to haematoma volume ratios are smaller in patients with lobar intracerebral haemorrhage (ICH) than in patients with deep ICH.
Methods
Haematoma and PHO volumes were measured in consecutive patients admitted to an acute stroke unit with a diagnosis of spontaneous supratentorial ICH proven by computed tomography. The oedema to haematoma volume ratios were calculated and compared in patients with lobar ICH and deep ICH.
Results
In total, 44 patients with ICH were studied: 19 patients had deep ICH, median haematoma volume 8.4 ml (interquartile range (IQR) 4.8 to 20.8), median PHO 8.2 ml (2.8 to 16), and 25 had lobar ICHs, median haematoma volume 17.6 ml (6.6 to 33.1) and median oedema volume 10.2 ml (3.4 to 24.2). Patients with lobar ICH were older than those with deep ICH (65.7 v 57.4 years, p = 0.009) but ICH location did not differ by sex or race. There was no evidence that haematoma or oedema volumes were related to type of ICH (p = 0.23, p = 0.39 respectively). The median oedema to haematoma volume ratios were similar in patients with lobar and deep ICH (0.67 v 0.58, p = 0.71). Controlling for age, sex, and race made little difference to these comparisons.
Conclusions
There are no major location specific differences in PHO volumes within 24 hours of ICH onset. Deep and lobar ICH may have common therapeutic targets to reduce early PHO.
doi:10.1136/jnnp.2005.070714
PMCID: PMC2077688  PMID: 16484648
Intracerebral haemorrhage; perihaematomal oedema
8.  Is family history an independent risk factor for stroke? 
OBJECTIVE: To estimate the influence of family history on the occurrence of stroke. METHODS: A case-control study was carried out from August 1992 to January 1994. The study population comprised 502 patients with a first stroke, aged between 20 and 70 years, who were treated at 48 affiliated hospitals. The same number of age and sex matched controls were selected from outpatients. Diagnoses were based on CT findings and clinical signs. There were 155 case-control pairs for subarachnoid haemorrhage, 158 for intracerebral haematoma, and 159 for cerebral infarction. Information about the patients and their families was obtained from a questionnaire which included the family histories of each subtype of stroke and other potential risk factors for stroke. The data were analysed focusing on the role of the family histories in the occurrence of stroke. RESULTS: In univariate analysis, the family histories of subarachnoid haemorrhage and intracerebral haematoma were positively associated with each of the subtypes of stroke (odds ratios 11.24 for subarachnoid haemorrhage, 2.39 for intracerebral haematoma), whereas family history of cerebral infarction was not a significant risk factor for its occurrence (odds ratio 1.41). Family history of intracerebral haematoma was correlated with a personal history of hypertension and habitual alcohol consumption. After adjustment for potential risk factors (hypertension, diabetes, hyperlipidaemia, obesity, alcohol consumption, and regular smoking), family history of subarachnoid haemorrhage still remained the most powerful risk factor for subarachnoid haemorrhage, whereas family history of intracerebral haematoma no longer showed a significant association with haematoma. CONCLUSION: Genetic factors play a major part in the pathogenesis of subarachnoid haemorrhage, and family history of subarachnoid haemorrhage is the strongest independent risk factor for the disease. On the other hand, family history of intracerebral haematoma was not an independent risk factor for haematoma, but it might be a good predictor, which indirectly influences the pathogenesis of intracerebral haematoma via certain hereditary components such as hypertension, and even lifestyle factors such as alcohol consumption. In cerebral infarction, genetic factors play a minor part in its pathogenesis.
PMCID: PMC486697  PMID: 9010402
9.  Amyloid angiopathy and lobar cerebral haemorrhage. 
Seven cases of lobar cerebral haemorrhage due to amyloid angiopathy were found among 60 necropsy cases of intracerebral haemorrhage. Clinically five patients were demented and two had hypertension. Immediately after the onset of stroke there was a high incidence of headache and vomiting, followed by nuchal rigidity. Amyloid angiopathy was most prominent in the cerebral cortex and the leptomeninges. Senile plaques were noted in all cases. One should suspect that a haemorrhage may be due to amyloid angiopathy, when lobar cerebral haemorrhage occurs in an aged, normotensive patient with or without dementia. Surgical evacuation of the haematoma is inadvisable, because of the diffuse nature of amyloid angiopathy, high recurrence rate and less tendency to cause brain stem compression.
Images
PMCID: PMC1028087  PMID: 6502178
10.  Simultaneous intracerebral haemorrhages; which came first, the supra-tentoral or the infra-tentorial one? 
BMJ Case Reports  2010;2010:bcr0320102805.
The occurrence of simultaneous spontaneous non-traumatic hypertensive intracerebral haemorrhages (ICHs) is a rare event that carries a considerable morbidity and mortality. These haematomas constitute 0.7–2% of all hypertensive ICHs. We report a 42-year-old man with ischaemic heart disease who presented with sudden severe pancephalic headache, repeated vomiting and left-sided weakness. His work-up revealed two right-sided ICHs: putamenal and cerebellar.
doi:10.1136/bcr.03.2010.2805
PMCID: PMC3029376  PMID: 22766571
11.  Subdural haemorrhages in infants: population based study 
BMJ : British Medical Journal  1998;317(7172):1558-1561.
Objectives
To identify the incidence, clinical outcome, and associated factors of subdural haemorrhage in children under 2 years of age, and to determine how such cases were investigated and how many were due to child abuse.
Design
Population based case series.
Setting
South Wales and south west England.
Subjects
Children under 2 years of age who had a subdural haemorrhage. We excluded neonates who developed subdural haemorrhage during their stay on a neonatal unit and infants who developed a subdural haemorrhage after infection or neurosurgical intervention.
Main outcome measures
Incidence and clinical outcome of subdural haemorrhage in infants, the number of cases caused by child abuse, the investigations such children received, and associated risk factors.
Results
Thirty three children (23 boys and 10 girls) were identified with subdural haemorrhage. The incidence was 12.8/100 000 children/year (95% confidence interval 5.4 to 20.2). Twenty eight cases (85%) were under 1 year of age. The incidence of subdural haemorrhage in children under 1 year of age was 21.0/100 000 children/year and was therefore higher than in the older children. The clinical outcome was poor: nine infants died and 15 had profound disability. Only 22 infants had the basic investigations of a full blood count, coagulation screen, computed tomography or magnetic resonance imaging, skeletal survey or bone scan, and ophthalmological examination. In retrospect, 27 cases (82%) were highly suggestive of abuse.
Conclusion
Subdural haemorrhage is common in infancy and carries a poor prognosis; three quarters of such infants die or have profound disability. Most cases are due to child abuse, but in a few the cause is unknown. Some children with subdural haemorrhage do not undergo appropriate investigations. We believe the clinical investigation of such children should include a full multidisciplinary social assessment, an ophthalmic examination, a skeletal survey supplemented with a bone scan or a skeletal survey repeated at around 10 days, a coagulation screen, and computed tomography or magentic resonance imaging. Previous physical abuse in an infant is a significant risk factor for subdural haemorrhage and must be taken seriously by child protection agencies.
Key messagesSubdural haemorrhage in children under 2 years of age is a relatively common occurrence. The majority are due to child abuseThe mortality and morbidity of this condition are both high and seriousThe high probability of child abuse in cases is still not being recognised, and cases are not being investigated fullyThe clinical investigation of subdural haemorrhage must include a full series of basic investigationsPrevious child abuse in an infant is a strong risk factor for subdural haemorrhage, and social services must be aware of this in the future care plans for that child and family
PMCID: PMC28734  PMID: 9836654
12.  Thalamic haemorrhage vs internal capsule-basal ganglia haemorrhage: clinical profile and predictors of in-hospital mortality 
BMC Neurology  2007;7:32.
Background
There is a paucity of clinical studies focused specifically on intracerebral haemorrhages of subcortical topography, a subject matter of interest to clinicians involved in stroke management. This single centre, retrospective study was conducted with the following objectives: a) to describe the aetiological, clinical and prognostic characteristics of patients with thalamic haemorrhage as compared with that of patients with internal capsule-basal ganglia haemorrhage, and b) to identify predictors of in-hospital mortality in patients with thalamic haemorrhage.
Methods
Forty-seven patients with thalamic haemorrhage were included in the "Sagrat Cor Hospital of Barcelona Stroke Registry" during a period of 17 years. Data from stroke patients are entered in the stroke registry following a standardized protocol with 161 items regarding demographics, risk factors, clinical features, laboratory and neuroimaging data, complications and outcome. The region of the intracranial haemorrhage was identified on computerized tomographic (CT) scans and/or magnetic resonance imaging (MRI) of the brain.
Results
Thalamic haemorrhage accounted for 1.4% of all cases of stroke (n = 3420) and 13% of intracerebral haemorrhage (n = 364). Hypertension (53.2%), vascular malformations (6.4%), haematological conditions (4.3%) and anticoagulation (2.1%) were the main causes of thalamic haemorrhage. In-hospital mortality was 19% (n = 9). Sensory deficit, speech disturbances and lacunar syndrome were significantly associated with thalamic haemorrhage, whereas altered consciousness (odds ratio [OR] = 39.56), intraventricular involvement (OR = 24.74) and age (OR = 1.23), were independent predictors of in-hospital mortality.
Conclusion
One in 8 patients with acute intracerebral haemorrhage had a thalamic hematoma. Altered consciousness, intraventricular extension of the hematoma and advanced age were determinants of a poor early outcome.
doi:10.1186/1471-2377-7-32
PMCID: PMC2169250  PMID: 17919332
13.  Patch: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial 
BMC Neurology  2010;10:19.
Background
Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect.
Methods/Design
The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included.
Discussion
To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.
Trial registration
The Netherlands National Trial Register (NTR1303)
doi:10.1186/1471-2377-10-19
PMCID: PMC2851678  PMID: 20298539
14.  Cerebellar haematomas caused by angiomas in children1 
Spontaneous cerebellar haematomas in previously well children are most often caused by haemorrhage from small angiomas. Eight such cases in children 12 years of age or younger have been reported previously. Their clinical course was usually not as acute as the course most commonly seen in adults, and four of the children survived after evacuation of the haematoma. Two additional cases are presented. Both children were admitted in a comatose state, but survived after surgical intervention. Cerebellar haematomas in children seem to have a better prognosis than in adults and should be considered in the evaluation of children with subarachnoid haemorrhage or the rapid onset of coma. Even if admitted in extremis, recovery is possible after prompt diagnosis and surgical evacuation of the haematoma.
PMCID: PMC494070  PMID: 5035308
15.  Stroke management 
Clinical Evidence  2010;2010:0201.
Introduction
Stroke is the third most common cause of death in most developed countries. It is a worldwide problem; about 4.5 million people die from stroke each year. Stroke can occur at any age, but half of all strokes occur in people aged over 70 years. About 80% of all acute strokes are ischaemic, usually resulting from thrombotic or embolic occlusion of a cerebral artery. The remainder are caused either by intracerebral or subarachnoid haemorrhage.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of specialised care in people with acute stroke? What are the effects of medical treatment in people with acute ischaemic stroke? What are the effects of decompressive hemicraniectomy in acute ischaemic stroke? What are the effects of surgical evacuation for intracerebral haematomas? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 44 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acute reduction in blood pressure, aspirin, evacuation (early surgical evacuation, or conservative treatment), decompressive hemicraniectomy, neuroprotective agents (calcium channel blockers, citicoline, gamma-aminobutyric acid agonists, glycine antagonists, lubeluzole, magnesium, N-methyl-D-aspartate antagonists), specialised stroke care, systemic anticoagulation (heparinoids, low or specific thrombin inhibitors, low molecular weight heparin, oral anticoagulants, unfractionated heparin), and thrombolysis.
Key Points
Stroke is characterised by rapidly developing clinical symptoms and signs of focal, and at times global, loss of cerebral function lasting over 24 hours or leading to death, with no apparent cause other than that of vascular origin. Ischaemic stroke (which accounts for about 80% of all acute strokes) is caused by vascular insufficiency (such as cerebrovascular thromboembolism) rather than haemorrhage.It is the third most common cause of death in most developing countries, with about 4.5 million people worldwide dying from stroke each year.About 10% of all people with acute ischaemic strokes will die within 30 days of onset, and, of those who survive the acute event, about 50% will still experience some level of disability after 6 months.
Specialised stroke rehabilitation seems more effective than conventional care at reducing death and dependency after 1 year.
Aspirin effectively reduces death or dependency at 6 months when given within 48 hours of ischaemic stroke. Aspirin has a similar effectiveness as anticoagulants (unfractionated or low molecular weight heparin), but a lower risk of intra- and extracranial haemorrhage.
Thrombolysis (given within 3 hours of symptom onset) reduces death or dependency at 6 months in people with confirmed ischaemic stroke, but increases the risk of symptomatic haemorrhage. The reduction in death or dependency may not apply to streptokinase treatment.
While there does seem to be a direct link between blood pressure and risk of recurrent stroke, acute blood pressure lowering in acute ischaemic stroke may actually lead to increased cerebral ischaemia.
Neuroprotective drugs do not seem to significantly reduce the risk of poor outcome (including death) or to improve outcome in people with ischaemic stroke.
In young people with malignant middle cerebral artery (MCA) infarction, decompressive hemicraniectomy is an effective life-saving treatment.
In people with primary supratentorial haematomas, surgical evacuation may be more effective at reducing death or dependency. We found no evidence examining the effects of evacuation in people with infratentorial haematoma whose consciousness level is declining.
PMCID: PMC2907612
16.  Stroke management 
Clinical Evidence  2011;2011:0201.
Introduction
Stroke is the third most common cause of death in most developed countries. It is a worldwide problem; about 4.5 million people die from stroke each year. Stroke can occur at any age, but half of all strokes occur in people aged over 70 years. About 80% of all acute strokes are ischaemic, usually resulting from thrombotic or embolic occlusion of a cerebral artery. The remainder are caused either by intracerebral or subarachnoid haemorrhage.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of specialised care in people with acute stroke? What are the effects of medical treatment in people with acute ischaemic stroke? What are the effects of decompressive hemicraniectomy in acute ischaemic stroke? What are the effects of surgical evacuation for intracerebral haematomas? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 41 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acute reduction in blood pressure, aspirin, evacuation (early surgical evacuation, or conservative treatment), decompressive hemicraniectomy, neuroprotective agents (calcium channel blockers, citicoline, gamma-aminobutyric acid agonists, glycine antagonists, lubeluzole, magnesium, N-methyl-D-aspartate antagonists), specialised stroke care, systemic anticoagulation (heparinoids, specific thrombin inhibitors, low molecular weight heparin, oral anticoagulants, unfractionated heparin), and thrombolysis.
Key Points
Stroke is characterised by rapidly developing clinical symptoms and signs of focal, and at times global, loss of cerebral function lasting over 24 hours or leading to death, with no apparent cause other than that of vascular origin. Ischaemic stroke (which accounts for about 80% of all acute strokes) is caused by vascular insufficiency (such as cerebrovascular thromboembolism) rather than haemorrhage.Stroke is the third most common cause of death in most developing countries, with about 4.5 million people worldwide dying from stroke each year.About 10% of all people with acute ischaemic strokes will die within 30 days of onset, and, of those who survive the acute event, about 50% will still experience some level of disability after 6 months.
Specialised stroke rehabilitation seems more effective than conventional care at reducing death and dependency after 1 year.
Aspirin effectively reduces death or dependency at 6 months when given within 48 hours of ischaemic stroke. Aspirin has a similar effectiveness to anticoagulants (unfractionated or low molecular weight heparin) in acute stroke, but a lower risk of intracranial and extracranial haemorrhage.
Thrombolysis (given within 3 hours of symptom onset) reduces death or dependency at 6 months in people with confirmed ischaemic stroke, but increases the risk of symptomatic haemorrhage. The reduction in death or dependency may not apply to streptokinase treatment.
Although there seems to be a direct link between blood pressure and risk of recurrent stroke, acute blood pressure lowering in acute ischaemic stroke may actually lead to increased cerebral ischaemia.
Neuroprotective drugs do not seem to be effective in reducing death or dependency in people with ischaemic stroke.
In younger people with malignant middle cerebral artery infarction, decompressive hemicraniectomy is an effective life-saving treatment.
In people with primary supratentorial haematomas, surgical evacuation may be more effective at reducing death or dependency. We found no high-quality evidence examining the effects of evacuation in people with infratentorial haematoma whose consciousness level is declining.
PMCID: PMC3217648  PMID: 21658301
17.  Alcohol consumption as a risk factor for poor outcome after aneurysmal subarachnoid haemorrhage. 
BMJ : British Medical Journal  1992;304(6843):1663-1667.
OBJECTIVE--To evaluate the effect of factors existing before aneurysmal subarachnoid haemorrhage on outcome of haemorrhage. DESIGN--Prospective follow up study. SETTING--Helsinki University Hospital. PATIENTS--291 consecutive patients (149 men) aged 15 to 65 years admitted within 96 hours after the bleeding. MAIN OUTCOME MEASURES--Potential risk factors (baseline characteristics, health habits, and clinical variables) for poor outcome after haemorrhage (dependent state in the activities of daily living, or death) were studied using multiple logistic regression. RESULTS--One year after haemorrhage, 179 (62%) patients were independent in the activities of daily living and 28 (10%) dependent; 84 (29%) had died. Risk of poor outcome was predicted, after adjustment for sex and age, by clinical condition at admission according to the Glasgow coma scale (p less than 0.0001); occurrence of rebleeding (relative risk 7.1, 95% confidence interval 2.8 to 18.0, p less than 0.0001) or delayed cerebral ischaemia (10.3, 4.2 to 25.4, p less than 0.0001); surgery on an aneurysm (0.13, 0.05 to 0.35, p less than 0.0001); and heavy consumption of alcohol (4.5, 1.8 to 11.0, p = 0.0014). Heavy drinking remained a significant risk factor after additional adjustment for hypertension, body mass index, and presence of intracerebral haematoma. Heavy drinkers had a more unfavourable outcome after rebleeding and delayed ischaemia than did others with rebleeding or ischaemia. Those who had salicylates in urine on admission had delayed ischaemia with fixed neurological deficits less commonly than others. CONCLUSIONS--Heavy drinking impairs outcome mainly through severe rebleeding and delayed ischaemia and to a lesser extent through a poor initial condition and presence of intracerebral haematoma.
PMCID: PMC1882384  PMID: 1633519
18.  Epileptic seizures in intracerebral haemorrhage. 
Among 1402 patients with intracerebral haemorrhage (ICH), seizures occurred in 64 (4.6%) and epilepsy in 35 (2.5%). Seizure was the first manifestation of ICH in 19 patients (30%). Status epilepticus occurred in 11 patients (17%) and it was the initial presentation of ICH in six (9%). The majority had simple partial seizures that were predominantly focal and motor. There were 38 patients with early seizure and 26 patients with late seizure. Ninety per cent of seizures occurred within one year after ICH. Eleven patients (29%) with early seizure developed epilepsy, whereas 24 patients (93%) with late seizure developed recurrent seizures. The incidence of seizure was 32% for lobar haematoma, 2% respectively for putaminal, thalamic and pontine haemorrhages and 1% for cerebellar haemorrhage. Twenty-six (62%) out of 42 patients with lobar haematomas developed epilepsy. Thirteen patients (34%) with early seizure died within three months after the onset of seizures whereas three patients (12%) with late seizure died within the same period. The majority of patients who died had deep-seated haematomas.
PMCID: PMC1031636  PMID: 2512371
19.  Update in Intracerebral Hemorrhage 
The Neurohospitalist  2011;1(3):148-159.
Spontaneous, nontraumatic intracerebral hemorrhage (ICH) is defined as bleeding within the brain parenchyma. Intracranial hemorrhage includes bleeding within the cranial vault and encompasses ICH, subdural hematoma, epidural bleeds, and subarachnoid hemorrhage (SAH). This review will focus only on ICH. This stroke subtype accounts for about 10% of all strokes. The hematoma locations are deep or ganglionic, lobar, cerebellar, and brain stem in descending order of frequency. Intracerebral hemorrhage occurs twice as common as SAH and is equally as deadly. Risk factors for ICH include hypertension, cerebral amyloid angiopathy, advanced age, antithrombotic therapy and history of cerebrovascular disease. The clinical presentation is “stroke like” with sudden onset of focal neurological deficits. Noncontrast head computerized tomography (CT) scan is the standard diagnostic tool. However, newer neuroimaging techniques have improved the diagnostic yield in terms of underlying pathophysiology and may aid in prognosis. Intracerebral hemorrhage is a neurological emergency. Medical care begins with stabilization of airway, breathing function, and circulation (ABCs), followed by specific measures aimed to decrease secondary neurological damage and to prevent both medical and neurological complications. Reversal of coagulopathy when present is of the essence. Blood pressure management can be key and continues as an area of debate and ongoing research. Surgical evacuation of ICH is of unproven benefit though a subset of well-selected patients may have improved outcomes. Ventriculostomy and intracranial pressure (ICP) monitoring are interventions also used in this patient population. To date, hemostatic medications and neuroprotectants have failed to result in clinical improvement. A multidisciplinary approach is recommended, with participation of vascular neurology, vascular neurosurgery, critical care, and rehabilitation medicine as the main players.
doi:10.1177/1941875211409050
PMCID: PMC3726132  PMID: 23983850
intracerebral hemorrhage; diagnosis; treatment; prognosis; surgery
20.  Update on the Surgical Trial in Lobar Intracerebral Haemorrhage (STICH II): statistical analysis plan 
Trials  2012;13:222.
Background
Previous studies had suggested that the outcome for patients with spontaneous lobar intracerebral haemorrhage (ICH) and no intraventricular haemorrhage (IVH) might be improved with early evacuation of the haematoma. The Surgical Trial in Lobar Intracerebral Haemorrhage (STICH II) set out to establish whether a policy of earlier surgical evacuation of the haematoma in selected patients with spontaneous lobar ICH would improve outcome compared to a policy of initial conservative treatment. It is an international, multi-centre, prospective randomised parallel group trial of early surgery in patients with spontaneous lobar ICH. Outcome is measured at six months via a postal questionnaire.
Results
Recruitment to the study began on 27 November 2006 and closed on 15 August 2012 by which time 601 patients had been recruited. The protocol was published in Trials (http://www.trialsjournal.com/content/12/1/124/). This update presents the analysis plan for the study without reference to the unblinded data. The trial data will not be unblinded until after follow-up is completed in early 2013. The main trial results will be presented in spring 2013 with the aim to publish in a peer-reviewed journal at the same time.
Conclusion
The data from the trial will provide evidence on the benefits and risks of early surgery in patients with lobar ICH.
Trial registration
ISRCTN: ISRCTN22153967
doi:10.1186/1745-6215-13-222
PMCID: PMC3543336  PMID: 23171588
21.  Henoch-Schönlein purpura with intracerebral haemorrhage in an adult patient: a case report 
Introduction
Henoch-Schönlein purpura is a small vessel vasculitis that affects mainly the skin, joints, gastrointestinal tract and kidneys. The central nervous system is also occasionally affected, although the majority of patients experience only mild symptoms such as headaches and behavioural changes. Intracerebral haemorrhage is a rare complication of Henoch-Schönlein purpura that so far has mainly been described in children and young adolescence.
Case presentation
We describe a 42-year-old man with Henoch-Schönlein purpura who developed an acute intracerebral haemorrhage that coincided with a reactivation of his vasculitis and the development of renal failure following discontinuation of steroids. In this patient, both the Henoch-Schönlein purpura and his neurological symptoms were successfully treated with intravenous cyclophosphamide and methylprednisolone, followed by a short course of oral cyclophosphamide and long-term oral prednisolone. His renal function also recovered sufficiently not to require renal replacement therapy.
Conclusion
The management of Henoch-Schönlein nephritis remains unclear, especially in the presence of severe complications such as intracerebral haemorrhage. We describe a successful outcome in such a patient.
doi:10.1186/1752-1947-2-200
PMCID: PMC2430708  PMID: 18547440
22.  Angioarchitecture of Brain Arteriovenous Malformations and the Risk of Bleeding: An Analysis of Patients in Northeastern Malaysia 
Background:
Central nervous system arteriovenous malformation (AVM) is a vascular malformation of the brain and involves entanglement of veins and arteries without an intervening capillary bed. Affecting predominantly young male patients, AVM presents with different clinical manifestations namely headache, seizures, neurological deficit and intracranial haemorrhage. The patients who present acutely with intracranial bleeding have a significant morbidity and mortality. The aim is to study the angioarchitecture of brain AVM (BAVM) and determine the risk factors for intracranial bleeding. Ultimately, the goal of the study is to look for the association between volume of haematoma and architecture of BAVM.
Methods:
A cross-sectional study of 58 patients was conducted at the Hospital Universiti Sains Malaysia. Data were collected over a period of seven years (2000 to 2007) to look for the association between the angioarchitecture of brain arteriovenous malformations (BAVM), haemodynamics and the natural history and risk of intracranial haemorrhage.
Results:
BAVM was predominantly found in young male patients in 65.5%. Small nidal size (P-value=0.004), deep location (P-value=0.003) and deep venous drainage (P-value=0.006) were found to be significant factors contributing to intracranial haemorrhage. All patients with coexisting intranidal or prenidal aneurysms presented with intracranial haematoma.
Conclusion:
The angioarchitecture of BAVM like nidal size, deep location and deep venous drainage can predict the risk of intracranial bleeding and can help in the management of high risk patients without any delay. Small sized and deep seated lesions have a diffuse type of intracranial bleed which eventually need more attention to the managing team as diffuse haematoma indicates more insult to brain.
PMCID: PMC3216150  PMID: 22135525
angioarchitecture; brain arteriovenous malformation; intracranial haemorrhage; stroke; neurosciences; neuroradiology
23.  Even in Patients with a Small Hemorrhagic Volume, Stereotactic-Guided Evacuation of Spontaneous Intracerebral Hemorrhage Improves Functional Outcome 
Objective
The decision to adopt a conservative or surgical modality for a relatively small volume of spontaneous intracerebral hemorrhage (SICH) is difficult and often controversial, especially when consciousness is tolerable. The authors examined the results of stereotactic-guided evacuation of SICH for relatively small volumes with respect to functional outcome.
Methods
This prospective study was performed on 387 patients with SICH who underwent stereotactic-guided evacuation (n = 204, group A) or conservative treatment (n = 183, group B) during the past 8 years. The primary end-point was recovery of functional status, which was estimated using the Modified Barthel Index (MBI) and the modified Rankin Scale (mRS).
Results
All patients had a Glasgow coma scale (GCS) score of ≥ 13 and unilateral hemiparesis of less than motor power grade 3. Group demographic characteristics and initial neurological statuses were similar. In all cases, the volume of SICH involved was < 30 cm3 and location was limited to basal ganglia and thalamus. At 6-month follow-ups, MBI was 90.9 in group A and 62.4 in group B (p < 0.05), and MRS was 1.2 in group A and 3.0 in group B (p < 0.05). Better motor function and stereotactic-guided evacuation had a significant effect on a functional recovery in regression analyses.
Conclusion
Even in patients with a small volume of SICH, stereotactic-guided evacuation improved functional recovery in activities in daily life than conservative treatment did.
doi:10.3340/jkns.2009.46.2.109
PMCID: PMC2744019  PMID: 19763212
Cerebral hemorrhage; Treatment efficacy; Neurosurgery; Stereotaxy; Recovery of function
24.  Anticoagulation-related intracranial extracerebral haemorrhage. 
From January 1981 to June 1986 116 patients with anticoagulation-related intracranial haemorrhage were referred to hospital. Seventy six of these haemorrhages were extracerebral, 69 were in the subdural and seven in the subarachnoid space. No epidural haemorrhages were identified. Compared with non-anticoagulation-related haematomas, the risk of haemorrhage was calculated to be increased fourfold in men and thirteenfold in women. An acute subdural haematoma, mostly due to contusion, was more frequently accompanied by an additional intracerebral haematoma than a chronic subdural haematoma. Trauma was a more important factor in acute subdural haematomas than in chronic. Almost half of the patients (48%) had a history of hypertension, more than a third (35%) had heart disease and about one fifth (18%) were diabetic. Headache was the most frequent initial symptom. Later decreased level of consciousness and focal neurological signs exceeded the frequency of headache. Three patients with subarachnoid haemorrhage and nine patients with acute subdural haematomas died, while those with chronic subdural haematomas all survived and had at the most mild, non-disabling sequelae. Myocardial infarction (22%), pulmonary embolism (20%), and arterial disease (20%) were the most frequent reasons for anticoagulant treatment. Critical review based on established criteria for anticoagulation treatment suggests there was no medical reason to treat a third of these patients. The single most useful measure that could be taken to reduce the risk of anticoagulation-induced intracranial haemorrhage would be to identify patients who are being unnecessarily treated and to discontinue anticoagulants.
PMCID: PMC1031928  PMID: 2769275
25.  Use of topically applied rt-PA in the evacuation of extensive acute spinal subdural haematoma 
European Spine Journal  2003;13(4):380-383.
Spontaneous spinal subdural haematoma is a rare cause of spinal cord compression, usually confined to a few vertebral levels. When the haematoma extends over several spinal segments, surgical decompression is a major undertaking. Recombinant tissue plasminogen activator (rt-PA) has previously been used in a number of surgical procedures, but not in the setting of acute spinal subdural haematoma. A minimally invasive technique of decompression, using topical rt-PA, is presented in two patients with extensive spinal intradural haematoma. Two patients receiving long-term anticoagulation therapy presented with acute-onset back pain progressing to paraparesis. Magnetic resonance imaging of the spine demonstrated spinal subdural haematomas extending over 15 vertebral levels in one patient and 12 in the other. An angiography catheter was introduced into the subdural space through a limited laminectomy. Thrombolysis and evacuation of haematoma was then achieved by intermittent irrigation of the subdural space with rt-PA, followed by saline lavage. Postoperative imaging demonstrated satisfactory decompression in both patients. There was significant improvement of neurological function in one patient. Topical application of rt-PA for spinal subdural haematoma allows evacuation of the haematoma through a limited surgical exposure. Decompression of the subdural space by this minimally invasive technique may be advantageous over extensive surgery by minimising surgical exposure, reducing postoperative pain and risk of neuronal injury. This technique may be useful in patients presenting with compression extending over several vertebral levels or poor surgical candidates.
doi:10.1007/s00586-003-0529-8
PMCID: PMC3468042  PMID: 12920622
Spontaneous spinal subdural haematoma; Anticoagulant therapy; Topical rt-PA

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