Brain Haemorrhage AK Mahapatra, PS Chandra, Raj Kumar
Chapter Notes

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A. K. Mahapatra
and P. S. Chandra
Spontaneous intracerebral haemorrhage (SICH) is a blood clot that arises in the brain parenchyma in the absence of trauma or surgery. This is responsible for about 10–15 per cent of all strokes and has higher mortality than the other types of strokes. The common causes include hypertension, amyloid angiopathy, coagulopathy, vascular anomalies, tumours, and various drugs. Hypertension, is the single greatest modifiable risk factor for SICH. Primary ICH is most common occurring in about 70–80 per cent of cases and is due to spontaneous rupture of small vessels damaged by hypertension. Secondary ICH occurs due to pre-existing developmental and acquired conditions such as vascular anomalies, coagulopathies, tumours, and various drug therapies. The most frequent sites are the basal ganglia, thalamus, subcortical white matter of the cerebral lobes, cerebellum, and brainstem.
Table 1.1 provides an outline of the major causes of SICH.
Cerebrovascular damage to small arteries and arterioles due to chronic hypertension is recognised as the most significant cause of primary SICH1. Racial differences in hypertension and socio-economic factors may explain the high incidence of SICH in certain ethnic groups.
Vascular anomalies are the second most common cause of SICH, which include aneu-rysms, AVMs, cavernomas, dural arteriovenous fistulas, and venous malformations.
Spontaneous ICH is not uncommon due to an underlying unsuspected brain tumour. Haemorrhage resulting from brain tumours can occur in up to 10 per cent of all primary or metastatic tumours. Haemorrhage is more likely with certain types of tumours, including glioblastoma, haemangioblastoma, oligoden-droglioma, and metastatic tumours. Metastatic tumours with a high incidence to bleed are malignant melanoma, renal cell, prostate, and lung cancer. Contrast-enhanced CT scanning or contrast-enhanced MR imaging usually identifies the tumour, although small areas of contrast enhancement can be obscured by haemorrhage. In young patients without hypertension, follow-up imaging is warranted, if initial studies are not very conclusive for the underlying pathology2.
Patients with liver failure or coagulopathy from any cause are at higher risk for SICH3. The liver is responsible for synthesis of most clotting factors and fibrinogen, as well as playing a major role in metabolism of platelets.
Excluding neonatal intraventricular haemorrhage, structural vascular lesions are the most common cause of SICH in children. Haematological disorders and coagulopathies, as well as brain tumours, are also important causes. An underlying structural lesion should be sought in all paediatric patients.
Moyamoya disease is a rare disorder characterised by progressive occlusive changes in the anterior circulation of the circle of Willis and the abnormal development of collateral moyamoya vessels in the basal ganglia. Although cerebral ischaemia is usually the initial symptom in children with the disease, SICH is the most common initial presentation in adults4.2
Abuse of sympathomimetic drugs such as cocaine, amphetamine, or ecstasy has been reported in association with SICH. Drug abuse may represent the most common cause of stroke in young adults. These drugs may also predispose unsuspected vascular anomalies to haemorrhage. The most commonly implicated sympathomimetic medication related to SICH is phenylpropanolamine. Ephedrine, pseu-doephedrine, and phencyclidine have also been described in association with SICH. Ginkgo bi-loba is an over-the-counter herbal extract used by many people in the US and Europe as a ‘memory aid’, several case reports have described an association between its use and ICH.
Pregnancy and the puerperium can be associated with SICH due to dural venous sinus thrombosis and eclampsia.
There are numerous other rare causes of SICH including cerebral artery dissection, infections, and a host of unusual bleeding diatheses.
The classic presentation of SICH is sudden onset of focal neurological deficit progressing over hours with accompanying headache, nausea, vomiting, altered consciousness, and elevated blood pressure. The symptoms are sudden, catastrophic and progresses rapidly, thus the nomenclature ‘brain attack’ is not illogical to describe its ominous nature. Supratentorial haemorrhage is commonly accompanied by vomiting and altered consciousness but is rare in ischaemic stroke. Elevation in blood pressure occurs in as many as 90 per cent of patients with SICH. Seizures occur in approximately 10 per cent of patients4.
The type of focal neurological deficit, of course, depends on haematoma location. Patients with supratentorial haemorrhage often present with contralateral sensory or motor deficits, aphasia, neglect, gaze deviation, and hemianopia. Infratentorial haemorrhages manifest with signs of brainstem dysfunction, cranial nerve abnormalities, ataxia, nystagmus, and dysmetria.
Risk of Haematoma Enlargement
In nearly one quarter of initially alert patients presenting with SICH, secondary deterioration in level of consciousness occurs within the first 24 hours after onset. Haematoma expansion and oedema formation are believed to be the major factors involved which occurs in about half of the cases.
Despite advances in neurocritical care and neurosurgery, the prognosis for patients with SICH remains bad, if not dismal. Apart from the high mortality, this pathology creates havoc in terms of severe disability, financial and emotional stress to the patient and his/her attendants. The volume of ICH, initial GCS score, and intraventricular extension of the haemorrhage are powerful predictors of 30-day mortality and morbidity rates in patients with SICH6,7.
Treatment of SICH
Macewan reported the first successful surgery for SICH in 1883. In general, there has been a pessimistic attitude among many medical professionals, including neurosurgeons, regarding treatment of SICH. The American Heart Association formed a task force that published practice guidelines in 1999 for the management of SICH and emphasized the desperate need for future randomised controlled trials.
Medical Treatment
Critical Care Because the risk of clinical deterioration after SICH is greatest during the first day, patients in whom this entity has been diagnosed should be monitored in an intensive care unit for a minimum of 24 hours. The goal of fluid status is to maintain euvolemia with the use of isotonic crystalloid intravenous solutions. Enteral nutrition, via a feeding tube, if necessary, should begin as soon as possible. Pneumatic sequential compression devices and elastic stockings decrease the risk of venous thrombosis and pulmonary embolism. Gastric cytoprotection should also be considered. Physical therapy, occupational therapy, speech therapy, and rehabilitation services should be consulted as soon as medically feasible.3
Seizure Prophylaxis Most of the studies have shown the high risk of seizures in SICH as compared with other strokes and the deleterious effect it can have on the patient in presence of a large blood clot. Most seizures occur within the first 24 hours after SICH.
Hence it is strongly recommended to provide anticonvulsant therapy in all patients who present with supratentorial SICH. Phenytoin sodium is preferred as it is widely available, comes in injectable forms, and the therapeutic levels are proportionate to the blood levels. No consensus exists on when anticon-vulsant therapy can be discontinued following SICH, but most medications can be withdrawn after the first month in patients in whom no further seizure activity occurs. Those with late onset seizures may require long-term anticon-vulsant prophylaxis upto three to five years.
Blood Pressure Management Hypertension is common in patients who suffer SICH and in the early clinical course. There is disagreement as to the mechanism of this acute hypertensive state; however, major factors appear to be catechola-mine release and the Cushing response.
Proponents of lowering blood pressure argue that doing so reduces secondary injury due to rebleeding and oedema formation8,9. Opponents, who favour leaving hypertension untreated, argue that preserving CPP is paramount to areas in the ischaemic penumbra. Although induced hypertension can increase oedema in experimental models, hypertension following SICH is not clearly related to the development of oedema. Because of these complex issues, the management of hyper-tension in SICH remains controversial.
The changes that occur in CBF in the setting of SICH are complex. Autoregulation can become deranged after a number of cerebral insults including ischaemia, SAH, traumatic brain injury, and SICH. When CPP decreases below the lower limit of autoregulation, oxygen extraction increases in a compensatory fashion. After oxygen extraction is maximised, ischaemia occurs. In most patients with chronic hypertension, the autoregulatory curve is at higher pressures, which may increase the risk of cerebral ischaemia if blood pressure is normalised.
Data acquired in clinical studies of patients with SICH are limited, but most vasodilators have the potential to raise ICP by increasing intracerebral blood volume. Short-acting, mixed á- and â- blockers such as labetalol should be used as first-line agents. Nitroprusside, the most commonly used agent for severe hypertension, is a vasodilator with the potential to raise CBF and ICP, although this effect has not been demonstrated in a clinical study. Arterial vasodilators, such as hydralazine or angiotensin-converting enzyme inhibitors, as well as calcium channel blockers may have less of a tendency to raise ICP and maintain CBF9. Venodilators, diazoxide, and ganglionic blockers should not be used in patients with SICH and elevated ICP.
In summary, there is no convincing evidence that lowering blood pressure in the acute period after SICH alters the course or prognosis. Modest reductions in SBP may be well tolerated, especially in patients with systemic hypertension complications or those at greater risk for haemorrhage expansion (such as, in coagulopathic patients). To balance the two theoretical risks of haemorrhage extension compared with worsening ischaemia, the American Heart Association recommended maintaining MABP below 130 mm Hg in patients with pre-existing hypertension and CPP above 70 mm Hg10.
Elevated ICP can have deleterious effects on CPP and, therefore, global CBF. Reduction in CPP and perihaematoma ischaemia may occur locally even in the absence of globally increased ICP. The impact of ICP treatment and haematoma evacuation on CBF has not been well studied, but some evidence exists that surgical evacuation and elevated ICP treatment can improve CBF9,10.
Common strategies for managing elevated ICP include elevation of the head of the bed, hyperventilation therapy, osmotic therapy, sedation, and cerebrospinal fluid drainage. Mannitol is often given when surgery is not considered appropriate. Mechanical ventilation parameters should be adjusted to a PCO2 goal of 430 to 35 mm Hg. Intraventricular blood is associated with a high mortality rate11. Barbiturate coma or hemicraniectomy may be necessary if all other measures fail. However, by and large surgical evacuation of the blood clot remains the most effective method to promptly reduce the ICP.
Treatment with corticosteroids, haemo-dilution and intravenous glycerol have not been found useful and should not be advocated1214.
Surgical Treatment
Despite a nihilistic attitude among clinicians regarding SICH, most neurosurgeons believe evacuation of certain intracerebral haematomas can reduce the mortality rate and improve outcome. Most of the published reports regarding surgical removal of these haemorrhages, many of which are in the Japanese literature, are non-randomised case series for which definitive recommendations or guidelines cannot be made. There is considerable international variation in the indications and rate of surgery for SICH. In part because of its high incidence in Japan, there has been an increase in the number of clinical and experimental studies being reported over the past two decades.
The Cochrane Database of Systematic Reviews published a meta-analysis of surgery for primary supratentorial ICH in 2001–15. The authors analysed the randomised and quasiran-domised trials of medical management combined with intracranial surgery compared with medical management alone. Only four surgical trials comprising 260 patients met their criteria for inclusion. No trial had blinded outcome assessment and each trial used different scales for assessing functional status. The authors of the review concluded that the available evidence to date was insufficient to make a recommendation concerning the safety and efficacy of surgical treatment.
Although evidence favouring surgical intervention is lacking, there is good theoretical rationale for early surgery. Early haematoma evacuation may decrease the toxic effects of blood and plasma products, diminish surrounding oedema and ischaemia, and prevent haematoma expansion. Liquefaction of the clot by instillation of tPA and subsequent aspiration at three hours has been shown to reduce mass effect and peri-haematomal oedema markedly at 24 hours in a pig model. Clot evacuation might be combined with pharmacological therapy targeting the inflammatory response shown to develop around the haematoma and leading to delayed cellular death in experimental animal models.
Randomised Trials of Surgical and Medical Management To date, there are nine prospective randomised controlled studies in which surgical and medical management of SICH has been compared (see chapter 21). Overall, these studies fail to demonstrate a superiority of either medical or surgical management. The results are also limited by considerable methodological differences among the trials.
The recently concluded STICH trial1618 represents an important milestone in the role of surgical treatment for ICH. The relative paucity of data from randomised trials has severely limited progress in the surgical treatment of ICH and has led to substantial variability in the management of ICH throughout the world. This trial is the largest ever randomised treatment trial of ICH. It adds substantially to what we know about surgical management of ICH and will have an impact on current treatment as well as design of future trials.
The goal of the STICH trial was to investigate the effectiveness of early surgery (within 24 hours of randomisation) as compared with initial conservative medical treatment with later evacuation, if deemed necessary, by the treating neurosurgeon. The STICH trial showed no significant difference in outcome between the early surgical and initial conservative management groups. Of the prespecified subgroups that were examined, patients with an ICH within a centimeter of the cortical surface showed a benefit for early surgery and there was a significant treatment interaction between treatment assignment and depth of the ICH from the cortical surface. However, statistical testing of this subgroup was not adjusted for the multiple subgroup comparisons as the investigators note. The STICH investigators concluded that 5“patients with spontaneous supratentorial ICH in neurosurgical units show no overall benefit for early surgery when compared with initial conservative management.”
The design and conduct of the STICH trial are keys to interpretation of the STICH trial. Inclusion criteria for STICH included computed tomographic evidence of a spontaneous supratentorial ICH that had arisen within 72 hours, uncertainty concerning the benefits of either treatment by the treating neurosurgeon, and a recommendation for a minimum haematoma diameter of two cm and a Glasgow Coma Score of five or more. Exclusion criteria included ICHs likely caused by an aneurysm or an angiograph-ically proven arteriovenous malformation, tumour or trauma; cerebellar or brainstem ICH; and inability to perform surgery within 24 hours of randomization. An important characteristic of the care plan was that patients randomised initially to conservative management could undergo evacuation of the ICH, if clinically indicated in the judgment of the treating physicians. This latter design feature reflects the clinical reality that ICH patients, on average, the most gravely ill of all stroke patients, frequently die despite the best efforts of physicians, nurses, and other healthcare personnel. In the face of marked deterioration and imminent death, holding to a course of medical management may be challenging.
The surgical approach was left to the choice of the treating neurosurgeons. In 77 per cent of cases, craniotomy was the surgical procedure and the remainder of cases had haematoma removal by burr hole, endoscopy, or stereotaxy in similar numbers. Thus, the STICH trial is primarily a trial of craniotomy for ICH removal. Interestingly, there was a borderline statistical interaction (P=0.07) between surgical method and outcome.
The fact that the investigators noted a benefit for surgical removal of superficial haematomas but saw no benefit overall, demonstrates that STICH patients with deep ICHs randomised to earlier surgery tended to do more poorly. This observation likely reflects that most patients with a deep ICH had a craniotomy rather than a less invasive approach such as endoscopy or stereotaxy. The overall result of the trial may have been different, if less invasive approaches had been used uniformly in patients with deep ICHs with subsequent minimisation of brain injury from the surgical procedure itself.
What does the STICH tell us about the role of surgical removal of ICH? A fair summary is that except for possibly those with superficial ICHs, craniotomy at one day or longer after onset is not better than initial conservative medical treatment with or without later craniotomy for patients who have deteriorated. A nonsignificant absolute benefit of five per cent in favour of early surgery (P = 0.116) in the prognosis-based Rankin Scale at six months is a hopeful finding for future surgical trials. It also illustrates the importance of adequate sample size in detecting smaller absolute clinical benefits.
What STICH leaves unanswered is the role of less invasive surgery to remove ICH, particularly at earlier time windows. Several small randomised trials of less invasive surgical approaches, particularly using stereotactic localisation, have reported positive outcomes for surgical removal as compared with medical management1921. These favourable results have stimulated pilot randomised studies of stereotactic removal of ICH using tissue plasminogen activator and drainage of blood via catheter, such as the National Institute of Neurological Disorders and Stroke-funded Minimally Invasive (stereotactic) Surgery Plus rtPA for ICH Evaluation (MISTIE) Study (Mario Zuccarello and Daniel Hanley; 2005).
We end this review with a highly optimal view that the future will unfold highly sophisticated minimal invasive surgical techniques which can be performed at bed side for a rapid and effective clot removal that hopefully will improve the outcome of this grevious illness.6
Table 1.1   Summary of primary and secondary causes of SICH
  • Hypertension
  • Amyloid angiopathy
  • Aneurysm
    • Saccular
    • Fusiform
    • Mycotic
  • Vascular malformation
    • AVM
    • Cavernous malformation
    • Venous angioma
    • Dural arteriovenous fistula
  • Neoplasm
    • Primary
    • Metastatic
  • Coagulopathy
    • Acquired
      • Anticoagulation (Coumadin, heparin)
      • Thrombolytics (tPA, urokinase)
      • Blood dyscrasias (DIC*, leukaemia, thrombocytopenia)
      • Hepatic failure
      • Platelet dysfunction (renal failure, medications)
    • Congenital
      • Haemophilia
      • Platelet disorders
  • Drugs or alcohol
    • Sympathomimetics (ephedrine, phenylpropanolamine, pseudoephedrine)
    • Cocaine, amphetamine, ecstasy
  • Haemorrhagic ischaemic stroke
  • Dural venous sinus thrombosis vasculitis vasculopathy
  • Moyamoya disease
  • Arterial dissection
  • Pregnancy
  • Eclampsia, venous sinus thrombosis
  • Other/unknown
* DIC = disseminated intravascular coagulation
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