Overview of CNS Manifestations of Systemic Vasculitis
Vasculitis is a systemic inflammatory condition affecting blood vessels. The resulting disruption in blood flow can result in organ damage. Different insults, such as bacterial or viral infection, drugs, food (the additive tartrazine, for instance), impaired circulation, and autoimmune disease, can trigger inflammation within the blood vessel structure. The term vasculitis is used in clinical medicine to designate a heterogeneous group of diseases, each characterized on the basis of the vessels’ size and anatomical location as well as the histopathological features of the inflammation and laboratory tests. Typical manifestations of inflammation (fever, swelling, pain) are usually present, alongside the specific symptoms and signs associated to a given vasculitis, which are functions of the organ affected, the magnitude of the damage and abnormal results of ancillary tests. Vasculitis may be primary in origin, in which the cause is unknown, or it may occur secondary to an underlying autoimmune disease, such as rheumatoid arthritis and Crohn’s disease, in conjunction with an infection, or in association with drug therapy.9363
Central nervous system (CNS) manifestations may occur in patients with systemic vasculitis, resulting in stroke, cerebral hemorrhage, encephalopathy, and seizures, but generally occur later in the disease course as a result of an accumulation of inflammatory changes.9364
The potential severity of CNS manifestations in systemic vasculitis is of special concern. The 1-year mortality rate for patients with any type of systemic vasculitis admitted to an intensive care unit is about 29%, and CNS involvement may further decrease survival.
Large-Vessel Vasculitides
Two primary types of large-vessel vasculitides that affect the CNS are giant-cell arteritis (GCA) and Takayasu’s arteritis (TA). They both affect the large arteries, and CNS involvement is typically related to ischemia.
Giant-cell arteritis is the most prevalent form of primary vasculitis in the world with 2-20 cases per 100,000 annually in people aged older than 50 years.12000, 12001 It is a granulomatous arteritis of the aorta and its major branches with a tendency to affect the extracranial branches of the carotid artery, including the superficial temporal artery, facial and lingual artery, occipital artery and the intraorbital branches.12000, 12001 The symptoms seen in GCA are due to ischemia of the supplied territories, usually including headache, visual disturbances, fever, scalp tenderness, jaw or tongue claudication, and increased acute phase reactants.12000 Neurological complications are caused by involvement of vessels supplying blood to the CNS or to cranial and peripheral nerves and may include ischemic optic neuropathy, visual symptoms related to retinal ischemia, and diplopia secondary to ischemia of extraocular muscles.12000, 12001 Stroke is observed in 1%-3% of cases, and is secondary to involvement of the arteries responsible for posterior intracranial circulation.12000, 12001 Half of untreated patients develop unilateral vision loss or ocular motor paresis. Visual loss results from retinal or optic nerve ischemia. Following unilateral visual loss, one-third of patients lose vision in the other eye within 3 weeks if untreated.12001 Polymyalgia rheumatica is often associated with the onset of GCA. Symptoms may include weight loss, fever, backache, and proximal muscle or periarticular pain.12001
Takayasu’s arteritis is also a granulomatous arteritis of the aorta and its major branches but involves the pulmonary arteries as well.12001 TA more frequently occurs in those younger than 50 years, female, and of Asian descent.12001 CNS involvement is seen in as many as one-third of cases.12001 This involvement is related to ischemia of the supplied territories and may include angina abdominis, claudication of the upper or lower limbs, renovascular hypertension, and symptoms related to ischemia of the CNS.12000 Stroke is the most threatening manifestation of TA, but the rate of incidence is unknown.12000
Medium-Vessel Vasculitides
Two types of vasculitis that affect medium-sized vessels are polyarteritis nodosa (PAN) and Kawasaki’s disease (KD).
Polyarteritis nodosa is an extremely rare condition characterized by inflammation that leads to microaneurysm. The organs that are usually affected are the skin, kidneys, and peripheral nervous system (PNS). The inflammatory process in PAN has a tendency towards bifurcations, leading to thrombosis which causes ischemia of the supplied territories.12000 CNS involvement occurs in as many as 40% of cases. Involvement most commonly occurs late in the disease as a result of accumulation of vascular inflammatory changes.12001 Common CNS manifestations include diffuse encephalopathy, focal deficits, seizures, stroke-like episodes, and intracerebral or subarachnoid hemorrhages.12000, 12001
Kawasaki’s disease (KD) is an acute febrile vasculitis predominantly involving medium-sized arteries, but large and small vessels may also be affected. It is one of the most common childhood vasculitides, generally affecting infants and young children.12001 Although KD is a self-limited disease that lasts approximately 12 days without treatment, it may be complicated by myocardial ischemia, artery aneurysms, depressed contractility or arrhythmias, and vascular obstruction in peripheral arteries.12000 KD has occurred in epidemic forms which suggests an infectious pathology.12001 The same vasculitic process affecting coronary arteries may also be responsible for CNS involvement. Inflammatory changes in brain vasculature have included leptomeningeal thickening, mild endarteritis, and periarteritis.12000 Neurological symptoms have included seizures, facial palsy, and rarely, cerebral infarction.12001
Small-Vessel Vasculitides
Small-vessel vasculitides are a group of disorders characterized by the presence of necrotizing leukocytoclastic inflammation in the wall of small, and less commonly, medium-sized vessels. Leukocytoclasia refers to the presence of debris of dead neutrophils in the vessel wall and is related to a defect in their clearance. Wegener’s granulomatosis (WG) and Churg-Strauss syndrome (CSS) are 2 examples of small-vessel vasculitides.
Wegener’s granulomatosis is a multisystem inflammatory disorder characterized by necrotizing granulomas in the upper and lower respiratory tract. It can be accompanied by segmental glomerulonephritis and necrotizing systemic vasculitis.12001 Inflammation is directed against some unknown antigen, affecting the mucosa, nasal and paranasal structures, and bronchial tract.12000 Organs that are commonly affected are the skin, heart, orbits, and joints. Wegener’s granulomatosis most commonly occurs in patients who are 40-50 years of age.12001 CNS manifestations have been described in 3%-33% of cases; however, large series have shown CNS involvement in 22%-54% of cases.12000, 12001 These manifestations have included seizure, pachymeningitis, cerebritis, external ophthalmoplegia, cranial neuropathy, and cerebrovascular events.12000 Involvement of the brain and meninges has been seen in less than 10% of cases and is manifested as cerebral arterial or venous thrombosis and as intracerebral or subarachnoid hemorrhage.12001
Churg-Strauss syndrome has an inflammatory process similar to that of WG but is characterized by eosinophil-rich and granulomatous inflammation involving the respiratory tract and by necrotizing vasculitis affecting small to medium-sized vessels. Churg-Strauss syndrome may follow years of allergic disease and is associated with asthma and eosinophilia.12001 The nervous system is affected in 10%-60% of cases with neuropathies in the form of mononeuritis multiplex or polyneuropathy.12000, 12001 Peripheral nervous system involvement will be present at onset, while CNS involvement develops years after the onset of asthma and eosinophilia.12000 The CNS is affected in 25% and is usually seen as cranial neuropathies, encephalopathy, and strokelike episodes.12001
Behçet’s Disease and Neuro-Behçet’s Disease
Behçet’s disease (BD) can affect veins or arteries of any size, and depending on which size is affected, can have different outcomes. Involvement of large veins leads to superficial thrombophlebitis and deep vein thrombosis while involvement of large arteries leads to aneurysm formation. Small- to medium-sized vessels can lead to an array of clinical manifestations.12000 The major causes of morbidity and mortality in BD stem from ocular, major vascular, and neurological involvement.12001 Neuro-Behçet’s disease (NBD) is a term for BD that describes cases with CNS and PNS involvement.12000 The average age of onset for BD and NBD is 26.7 and 32.0 year, respectively.12001 The largest series of patients with NBD ever reported included 200 Turkish patients. CNS involvement affected the parenchyma in 81%, brain stem in 51%, hemispheres in 15%, and spinal cord in 14%.12000 Neuro-Behçet’s disease is subdivided into intra-axial or CNS involvement, and extra-axial or cerebral venous sinus thrombosis. Intra-axial NBD is due to small vessel disease and causes focal or multifocal CNS involvement. Extra-axial NBD is due to large vessel disease and has limited symptoms, a better prognosis, and generally an uncomplicated outcome.12001 Approximately 50% of patients with NBD are moderately to severely disabled 10 years after onset.12000, 12001
Content on this page was last reviewed on January 01, 2009.
Content on this page was last changed on December 22, 2009.
References:| 9363. | Mader R, Segol O, Adawi M, Trougoboff P, Nussinson E. Arthritis or vasculitis as presenting symptoms of Crohn’s disease. Rheumatol Intern. 2005;25(6):401-405. |
| 9364. | Guillevin L, Dörner T. Vasculitis: mechanisms involved and clinical manifestations. Arthritis Res Ther. 2007;9(Suppl 2):S9. |
| 12000. | Rossi CM, Di Comite G. The clinical spectrum of the neurological involvement in vasculitides. J Neurol Sci. 2009;285(1-2):13-21. |
| 12001. | Siva A. Vasculitis of the nervous system. J Neurol . 2001;248(6):451-468. |
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