Inflammatory vascular disease
- Giant-cell arteritis
- Takayasu's disease
- Systemic lupus erythematosus (SLE)
- Antiphospholipid antibody syndrome
- Primary systemic vasculitis
- Rheumatoid disease
- Sjögren's syndrome
- Relapsing polychondritis
- Progressive systemic sclerosis
- Sarcoid angiitis
- Isolated angiitis of the CNS
- Malignant atrophic papulosis (Degos' disease)
- Acute posterior multifocal placoid pigment epitheliopathy
- Buerger's disease
There are a number of acute, subacute and chronic inflammatory disorders of the arterial (or venous) wall which may cause cerebral ischaemia and haemorrhage. The inflammation may provoke enough cellular proliferation, necrosis, and fibrosis in the vessel wall to occlude the lumen; to precipitate thrombosis and then embolism; or promote aneurysm formation, dissection, and even rupture of the vessel. These "vasculitic" disorders may present with, or be complicated during their course by: ischaemic stroke, intracranial haemorrhage, intracranial venous thrombosis, and, more often, by a generalized encephalopathy (Sigal 1987; Berlit et al. 1993; Charles and Maini 1993; Futrell 1995; Ostrov and Barron 1995; Jennette and Falk 1997).
There is no sensitive or specific angiographic appearance and the diagnosis is made on the basis of the clinical syndrome, systemic features (usually a raised ESR and anaemia), backed up by antibody tests and, if necessary, biopsy (skin, kidney, brain, etc.). The CSF is either normal or shows non-specific inflammatory changes.
Giant-cell arteritis is the most common vasculitic cause of stroke. Medium and large arteries are affected, particularly branches of the external carotid artery, the ophthalmic artery, and the vertebral artery. The patients are elderly. Malaise, polymyalgia, and other systemic symptoms are almost invariable and the ESR is usually raised, often to over 100 mm in the first hour (Wilkinson and Ross Russell 1972; Huston and Hunder 1980; Caselli et al. 1988).
Takayasu's disease is a chronic vasculitis, histologically identical to giant-cell arteritis, but affecting only the aorta and large arteries arising from it, mainly in young Oriental women. Systemic features are common (e.g. malaise, weight loss, arthralgia, fever). The neurological complications reflect progressive narrowing and eventual occlusion of the large arteries in the neck: claudication of the jaw muscles, ischaemic oculopathy, syncope, epileptic seizures, confusion, boundary zone infarction, and rather rarely focal ischaemic stroke or TIAs. In addition, there may be ischaemia of the arms, and of the kidneys to cause hypertension, as well as ischaemic necrosis of the lips, nasal septum, and palate (Lupi-Herrera et al. 1977; Hall et al. 1985).
Other causes of a similar aortic arch syndrome include advanced atheroma, giant-cell arteritis, syphilis, subintimal fibrosis, arterial dissection, trauma, and coarctation (Ross and McKusick 1953; Dalal et al. 1971).
Systemic lupus erythematosus (SLE)
Systemic lupus erythematosus (SLE) is more likely to cause a subacute or chronic generalized encephalopathy than symptomatic focal ischaemia. Surprisingly, the underlying vascular pathology, if any is found, appears to be mostly intimal proliferation rather than a vasculitis (Bennett et al. 1972; Kitagawa et al. 1990; Mills 1994; Hama and Boumpas 1995).
The extracranial arteries do not often seem to be affected, but embolism from heart-valve vegetations may be quite common, particularly when there are circulating antiphospholipid antibodies (Haas 1982; Devinski et al. 1988; Khamashta et al. 1990; Mitsias and Levine 1994; Roldan et al. 1996). Intracranial venous thrombosis is rare (Vidailhet et al. 1990).
In some patients with little clinical evidence of SLE there is prominent livedo reticularis which, when associated with stroke, is referred to as Sneddon's syndrome, in which antiphospholipid antibodies are particularly common (Burton 1988; Stockhammer et al. 1993; Kalashnikova et al. 1994; Geschwind et al. 1995).
Antiphospholipid antibody syndrome
Antiphospholipid antibody syndrome is a constellation of various recurrent clinical events as well as specific immunological features: recurrent ischaemic stroke/TIA, intracranial venous thrombosis, arterial and venous thrombi elsewhere in the body, migraine-like episodes, recurrent miscarriage, livedo reticularis, cardiac valvular vegetations, thrombocytopenia, false-positive syphilis serology and—the defining feature—persistently and substantially raised (>20 units) circulating IgG anticardiolipin antibodies and/or the circulating lupus anticoagulant, usually detected by prolongation of the activated partial thromboplastin time. It overlaps with SLE but falls short of the whole syndrome. The same antibodies are found in some normal people, and in SLE (Levine et al. 1987; Bick 1993; Hughes 1993; Dahle et al. 1995; Feldmann and Levine 1995; Levine et al. 1995).
Primary systemic vasculitis
Primary systemic vasculitis is a group of related disorders, including polyarteritis nodosa, Wegener's granulomatosis, the Churg–Strauss syndrome, and various hypersensitivity vasculitides, which have very rare cerebrovascular consequences, similar to those of SLE (Savage et al. 1997). However, unlike SLE, it is more common to find underlying vascular pathology (i.e. a necrotizing vasculitis affecting medium and small arteries) while the circulating antibodies so frequently found in SLE are usually absent. More common are haematuria, eosinophilia, and circulating antineutrophil cytoplasmic antibodies (ANCA) (Ford and Siekert 1965; Moore and Fauci 1981; Nishino et al. 1993).
Rheumatoid disease is rarely complicated by a systemic vasculitis which can involve the brain (see above) (Watson et al. 1977; Beck and Corbett 1983). Occasionally atlanto-axial dislocation causes symptomatic vertebral artery compression (Howell and Molyneux 1988).
Sjögren's syndrome is occasionally complicated by systemic vasculitis (see above) causing focal cerebral ischaemia, global encephalopathy, and aseptic meningitis (Alexander et al. 1982; de la Monte et al. 1983; Bragoni et al. 1994). Neurological complications are well described in Behçet's disease, usually with or after the onset of the mucocutaneous manifestations. The vasculitis may affect cerebral arteries, particularly to the brainstem, to cause ischaemic stroke, and possibly intracranial haemorrhage. Intracranial venous thrombosis is another complication (Kawakita et al. 1967; Iragui and Maravi 1986; Altinors et al. 1987; Wechsler et al. 1993; Devlin et al. 1995; Akman-Demir et al. 1996; Farah et al. 1998)
Relapsing polychondritis may be complicated by a generalized encephalopathy, stroke-like episodes, and ischaemic optic neuropathy as a result of systemic vasculitis (Stewart et al. 1988).
Progressive systemic sclerosis
Progressive systemic sclerosis is hardly ever complicated directly by stroke, although a carotid and cerebral vasculopathy has been described (Gordon and Silverstein 1970; Heron et al. 1998).
Sarcoid angiitis affects the brain rarely, usually causing a generalized encephalopathy rather than focal features due to ischaemia or haemorrhage (Matthews 1979; Stern et al. 1985; Libman et al. 1997).
Isolated angiitis of the CNS
Isolated angiitis of the central nervous system is a very rare disorder which affects leptomeningeal, cortical, and sometimes spinal cord blood vessels . It is ‘isolated’ in the sense that it is confined to the central nervous system. Histologically it is similar to sarcoid angiitis and it can occur in association with herpes zoster and lymphoma. The course is subacute, usually leading to death in weeks or months, with mental confusion and impairment, headache, vomiting, stroke-like episodes, and myelopathy. Systemic symptoms are very uncommon. Diagnosis is only really possible from meningeal/cortical biopsy (Hankey 1991; Vollmer et al. 1993).
Malignant atrophic papulosis (Degos' disease)
Malignant atrophic papulosis (Degos' disease) is a very rare syndrome consisting of crops of painless pinkish papules on the trunk and limbs which heal as distinctive circular porcelain-white scars. It may be complicated by ischaemic gut, brain, spinal cord, and root lesions as a result of endothelial proliferation in small arteries (Sotrel et al. 1983; Subbiah et al. 1996).
Acute posterior multifocal placoid pigment epitheliopathy
Acute posterior multifocal placoid pigment epitheliopathy is a rare and usually benign and self-limiting chorioretinal disorder with rapidly deteriorating central vision. However, it can be complicated by systemic vasculitis, aseptic meningitis, and stroke (Manto et al. 1995; Comu et al. 1996)
Buerger's disease (thromboangiitis obliterans) is a rare inflammatory disorder of small and medium-sized arteries and veins, chiefly of the limbs and almost never of the cerebral circulation, much more common in men than women, and in smokers (Drake 1982; Spittell 1983; Berlit et al. 1984; Lie 1986).