Specific causes of intracranial haemorrhage
Chronic hypertension causes thickening and disruption of the walls of the small arteries which perforate the base of the brain, particularly in the region of the basal ganglia (lenticulostriate arteries), along with microaneurysm formation (Charcot- Bouchard aneurysms) (Ross Russell 1975). It is the rupture of these abnormal vessels which is thought to cause hypertensive primary intracerebral haemorrhage (PICH), although it is almost impossible to prove a cause and effect relationship in individuals because the haemorrhage destroys the exact site of the bleeding (Takebayashi and Kaneko 1983). More recently, the very existence of microaneurysms has been challenged as a post-mortem artefact (Challa et al. 1992).
In practice, the clinical diagnosis of ‘hypertensive’ PICH is based on the lack of any alternative explanation (bearing in mind angiography is seldom done in elderly patients and those in poor clinical condition) in a patient known to have had hypertension, or clearly has evidence of hypertensive organ damage (e.g. left ventricular hypertrophy, retinopathy, etc.), not just high blood pressure as a consequence of the stroke. However, it seems very likely that other factors, such as cerebral amyloid angiopathy, interact with hypertension to cause PICH in a particular individual. After all, hypertension is neither necessary nor sufficient to explain every case of PICH.
Saccular aneurysms vary from a few millimetres to several centimetres in diameter, can enlarge with time, but not necessarily, and almost certainly are much more often acquired than congenital. Associations for aneurysmal haemorrhage, which may or may not be causal, include polycystic kidney disease, hypertension, smoking, alcohol, oral contraceptives, and possibly coronary heart disease (Longstreth et al. 1985; Teunissen et al. 1996; Johnston et al. 1998; Uehara et al. 1998). Sometimes aneurysms are familial (ter Berg et al. 1992; Bromberg et al. 1995; Ronkainen et al. 1998).
Saccular aneurysms tend to occur at branching points on the circle of Willis and proximal cerebral arteries; about 40 per cent on the anterior communicating artery complex, 30 per cent on the posterior communicating artery or distal internal carotid artery (ICA), 20 per cent on the middle cerebral artery, and 10 per cent in the posterior circulation (basilar, posterior cerebral artery, etc.). About 25 per cent occur at multiple sites. Aneurysms are an incidental finding in about 6 per cent of cerebral angiograms done for various reasons in adults, an almost certain overestimate of the true rate, which may be about 2 per cent (Rinkel et al. 1998). They present most commonly in middle life with subarachnoid haemorrhage.
Other presentations include primary intracerebral haemorrhage; compression of adjacent structures (e.g. optic nerve from an anterior communicating artery aneurysm; optic chiasm, third, fourth, and fifth cranial nerves from a distal ICA or posterior communicating artery aneurysm; brainstem from a basilar artery aneurysm); seizures due to pressure on adjacent brain; TIA or ischaemic stroke due to embolism of intra-aneurysmal thrombus; and carotico-cavernous fistula from rupture of an intracavernous carotid aneurysm (Raps et al. 1993).
Associations of intracranial saccular aneurysms
- Polycystic kidney disease
- Fibromuscular dysplasia
- Cervical artery dissection
- Coarctation of the aorta
- Intracranial arteriovenous malformations
- Marfan's syndrome
- Ehlers–Danlos syndrome
- Pseudoxanthoma elasticum
- Neurofibromatosis type 1
- α1-Antitrypsin deficiency
- Hereditary haemorrhagic telangiectasia
- Moyamoya syndrome
- Klinefelter's syndrome
Cerebral amyloid angiopathy
Cerebral amyloid angiopathy (CAA) is an organ-specific form of amyloid deposition in small and medium arteries, less commonly veins, of the cerebral cortex and meninges, particularly in the elderly. Very often there is additional subcortical small vessel disease and demyelination, very reminiscent of Binswanger's disease. CAA can be associated with Alzheimer's disease, Down's syndrome, cerebral vasculitis, cerebral irradiation, and dementia pugilistica (Venters 1987). It is increasingly presumed—but seldom biopsy or post-mortem proven—to be the cause of lobar haemorrhages in the elderly, often multiple and recurrent, and perhaps very rarely of subarachnoid haemorrhage. Fibrinoid necrosis seems to be a common accompaniment but could be secondary to, rather than the cause of, the haemorrhage (Vonsattel et al. 1991).
Patients, with or without primary intracerebral haemorrhage (PICH), may also have a progressive dementia and a history of minor stroke-like episodes and TIAs, and even focal epileptic seizures, possibly due to small PICHs undetectable except perhaps by MRI (Greenberg et al. 1993). Dominantly inherited forms of CAA cause PICH in young adults in Iceland (Jensson et al. 1987) and in middle-aged adults in Holland (Bornebroek et al. 1997), and a syndrome of progressive dementia, ataxia, and spasticity associated sometimes with stroke in the UK (Plant et al. 1990).
Intracranial vascular malformations
Intracranial vascular malformations (IVMs) are uncommon, probably congenital, and sometimes familial. Those in the dura, draining into the sinuses rather than cerebral veins, can be caused by skull fracture, craniotomy, or dural sinus thrombosis (Nabors et al. 1987). The overall IVM detection rate is about 3 per 100 000 population per annum and the prevalence is about 20 per 100 000 (Brown et al. 1996b). There are four main types (Stein and Mohr 1988), as follows:
Arteriovenous malformations (AVMs) are the most common clinically and consist of an abnormal fistulous connection(s) between one or more hypertrophied feeding arteries and dilated draining veins. The blood supply is derived from one or, more often, several cerebral arteries, perhaps with a contribution from branches of the external carotid artery. AVMs vary from a few millimetres to several centimetres in diameter. About 15 per cent are associated with aneurysms on their feeding arteries. Some grow during life but a few shrink or even disappear, and some are multiple (Mendelow et al. 1987; Reddy et al. 1987).
These fistulae occur in or on the brain, or in the dura of the intracranial sinuses. They present at almost any age, with partial or secondary generalized epileptic seizures due to a cerebral AVM; intracerebral more often than subarachnoid or subdural haemorrhage from the AVM itself or associated aneurysm; as a mass lesion; with a carotico-cavernous fistula due to a dural AVM (see below); with TIA-like episodes, perhaps due to vascular steal or venous thrombosis; or with an audible bruit to the patient, particularly if a dural AVM is near the transverse/ sigmoid sinus and petrous bone (Lasjaunias et al. 1986); with the syndrome of benign intracranial hypertension due to increased pressure in cerebral draining veins or sinuses (Chimowitz et al. 1990; or with high-output cardiac failure in neonates and infants (Davidson and Falconer 1973). Headache, although common, is not by itself diagnostically helpful and may well be a coincidence. Rather rarely, a bruit can be heard over the skull or orbits. A brainstem AVM can present like multiple sclerosis, with fluctuating symptoms and signs of brainstem dysfunction, perhaps due to recurrent haemorrhage (Stahl et al. 1980).
The diagnosis can be suspected on CT; a plain scan may show calcification and rather non-specific hypo- or hyperdensity, while an enhanced scan is likely to show the dilated vessels of large malformations. MRI is more sensitive, showing evidence of old haemorrhage and vascular flow voids. Angiography is the definitive investigation but can be normal with small malformations. It is crucial to display all the possible feeding vessels, not forgetting branches from the external carotid artery feeding dural AVMs (Tsitsopoulos et al. 1987; Abe et al. 1989).
Venous malformations consist of collections of venous channels and a large draining vein. Most are asymptomatic but they can possibly present with haemorrhage into the ventricles, or seizures. On contrast CT the draining vein may appear as a linear enhancing streak, but a flow void on MRI is more sensitive. The definitive diagnosis is made on the venous phase of a cerebral angiogram.
Cavernous malformations (cavernomas) are sharply circumscribed collections of thin-walled sinusoidal vessels lined with a single layer of endothelium without intervening brain parenchyma or identifiable mature vessel wall elements. They are sometimes multiple and occasionally familial. Most are asymptomatic and picked up on MRI being done for an unrelated problem. But they can present with seizures, recurrent subacute brainstem syndromes, or even as a mass lesion, but rather seldom with haemorrhage. The angiogram is usually normal but CT can show a hypo- or hyperdense area which may enhance, and perhaps calcification, usually without surrounding oedema or mass effect. The most sensitive imaging is with MRI, revealing sharply circumscribed lesions, typically with evidence of haemosiderin as a result of old but asymptomatic haemorrhage. However, they cannot always be distinguished from small AVMs by imaging (Requena et al. 1991; Kattapong et al. 1995).
Telangiectasias are collections of dilated capillaries which are usually of no clinical significance (Milandre et al. 1987). They may be associated with hereditary haemorrhagic telangiectasia (Osler–Weber–Rendu syndrome) but this is more likely to be associated with neurological complications from a pulmonary AVM with right-to-left shunting (cerebral hypoxia, brain abscess, paradoxical and septic embolism), or from an associated intracranial AVM or aneurysm (Roman et al. 1978; Guttmacher et al. 1995; McDonald et al. 1998).
Carotico-cavernous fistula is an abnormal connection between the carotid arterial system and the cavernous sinus. It occurs as a result of a ruptured dural AVM or intracavernous internal carotid artery aneurysm, closed or penetrating head injury, Ehlers–Danlos syndrome, or pseudoxanthoma elasticum. More often, it seems to be spontaneous, particularly in the elderly. With high-flow, direct fistulae from the carotid artery itself, the onset is dramatic, with unilateral pulsating exophthalmos and an orbital bruit, often audible to the patient. In addition, there may be orbital pain, papilloedema, dilated conjunctival veins and chemosis, glaucoma, monocular visual loss, and involvement of the third, fourth, sixth, and the first and perhaps second sensory division of the trigeminal nerve. The ophthalmoplegia may also be due to hypoxia and swelling within the extraocular muscles. Dural fistulae present more insidiously because the blood flow is lower from small meningeal branches of the internal or external carotid arteries in the cavernous sinus (Barrow et al. 1985). If there is no spontaneous resolution, it may be possible to obliterate the fistula with balloon catheterization.