We searched the Cochrane Library, Medline, and Embase with the search terms “vasculitis”, “angiitis”, or “angiopathy” in combination with the terms “central nervous system”, “cerebral”, or “intracranial”. We selected articles mostly in English from the past 5 years, without excluding older articles that we thought were highly relevant to this Seminar. We searched the reference lists of articles identified by this search and selected those that we judged relevant. We included some reviews
SeminarAdult primary central nervous system vasculitis
Introduction
Primary CNS vasculitis is an uncommon and poorly understood vasculitis restricted to brain and spinal cord. Recognition of this disorder as a distinct nosological entity dates back to the mid-1950s when Cravioto and Feigin1 described several cases of non-infectious granulomatous angiitis associated with the nervous system.2 Since then, primary CNS vasculitis has been referred to as granulomatous angiitis of the CNS,3, 4 or more specifically, non-infectious5 or idiopathic6 granulomatous angiitis of the CNS, and giant-cell arteritis of the CNS,7 isolated angiitis of the CNS,8 primary angiitis of the CNS,9 and benign angiopathy of the CNS.10 Outcome in early reports was frequently fatal, and diagnosis was often made at autopsy.1, 2, 3, 5, 7, 11 By contrast, in later studies outcomes were more favourable, and biopsy and angiography were used for diagnosis.8, 9, 12 Primary CNS vasculitis needs to be differentiated from disorders that closely resemble it so that appropriate treatment can be provided.10, 13
Section snippets
Diagnostic criteria
Calabrese and Mallek9 proposed criteria for diagnosis of primary CNS vasculitis on the basis of clinical experience and evidence from published work. Diagnosis is made if all three of the following criteria are met: history or clinical findings of an acquired neurological deficit of unknown origin after a thorough initial basic assessment; cerebral angiogram with classic features of vasculitis, or a CNS biopsy sample showing vasculitis; and no evidence of systemic vasculitis or any other
Epidemiology
In the Mayo Clinic series,15 the incidence of primary CNS vasculitis in Olmsted County, MI, USA, was estimated to be 2·4 cases per 1 000 000 person-years, which is the only incidence information available. Primary CNS vasculitis occurs at the same frequency in men as in women.15, 25 The median age at diagnosis is about 50 years, and 50% of patients were between 37 and 59 years of age at diagnosis. Long-term survival is reduced in primary CNS vasculitis.15 Increased mortality has been linked to
Pathophysiology
The cause and pathogenesis of primary CNS vasculitis are unknown. Infectious agents have been proposed as triggers because of the well known association of cerebral vasculitis with infections—in particular varicella zoster virus (VZV).26 In fact, a wide array of infectious agents have been linked to vasculitis of CNS (panel).
Inoculation of turkeys intravenously with Mycoplasma gallisepticum induced cerebral vasculitis similar to primary CNS vasculitis,27 and in two cases of primary CNS
Histopathology
Primary CNS vasculitis is a vasculitis histologically affecting small and medium-sized leptomeningeal and parenchymal arterial vessels. Three main histopathological patterns are seen:23, 34 granulomatous, lymphocytic, and necrotising vasculitis. Granulomatous vasculitis is the most common (58%), showing vasculocentric mononuclear inflammation and well formed granulomas with multinucleated cells (figure 1A). β4 amyloid deposition is seen in almost 50% of biopsy specimens with this pattern (
Clinical manifestations
Clinical manifestations at diagnosis are non-specific, and many symptoms are usually present (table 1).12, 15, 25 The onset of disease can be acute, but it is more frequently insidious and slowly progressive. Diagnosis is made in 75% of patients within 6 months of the onset of symptoms. Headache, the most common symptom, can be generalised or localised, it often slowly worsens, can spontaneously remit for periods, and varies in severity. Cognitive impairment is also often insidious in onset,
Special subsets
Several subsets of primary CNS vasculitis have been identified that can differ in terms of prognosis and optimum management. Spinal cord abnormalities are implicated in about 5% of patients but are rarely the only manifestation.35 The thoracic cord is predominantly affected. Careful medical assessment should be undertaken to verify diagnosis of primary CNS vasculitis and to exclude other disorders associated with acute or subacute transverse myelitis.
Angiography-negative, biopsy-positive
Laboratory findings, electroencephalography, and imaging
Results of blood tests in patients with primary CNS vasculitis are usually normal, and consist of tests for acute-phase reactants, antinuclear antibodies, antineutrophil cytoplasm antibodies, and antiphospholipid antibodies.15, 25
CSF analysis is abnormal in 80–90% of patients.15 Changes consist of a mildly increased leucocyte count and total protein concentration. Patients with angiography-negative primary CNS vasculitis often have greatly raised protein concentrations.20 CSF analysis should be
Differential diagnosis
Primary CNS vasculitis should be differentiated from other similar disorders to avoid therapeutic and prognostic errors. The most common mimicker of primary CNS vasculitis is reversible cerebral vasoconstriction syndrome.
In 2007, reversible cerebral vasoconstriction syndrome was proposed as a collective name for various disorders that are characterised by brain vasoconstriction rather than by vasculitis13 (ie, Call-Fleming syndrome, post-partum angiopathy, migrainous vasospasm, drug-induced
Treatment and course
No randomised clinical trials of medical management in primary CNS vasculitis exist; therefore, treatment for primary CNS vasculitis has been derived from therapeutic strategies used in other vasculitides, from anecdotal reports, and from cohort studies. Earliest reports suggested a poor outlook with fatal outcome in most patients, and transient or doubtful effectiveness of glucocorticoids.4, 12, 100 Studies, including those by Cupps and colleagues,8 reported the effectiveness of
Future directions
Our understanding of primary CNS vasculitis and the delineation of its range and subsets has advanced, but we still need to clarify methods of diagnosis and optimum management. Biomarker and outcome investigations might identify risk factors for an aggressive course leading to treatment tailored to disease severity. Effectiveness and safety profiles of intravenous pulse and oral cyclophosphamide treatment, and clarification of which patients need cyclophosphamide at disease onset, need to be
Search strategy and selection criteria
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