Primary Angiitis of the CNS

Updated: Nov 03, 2016
  • Author: Mazen Noufal, MD; Chief Editor: Helmi L Lutsep, MD  more...
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Overview

Practice Essentials

Primary angiitis of the central nervous system (PACNS) is frequently considered in the differential diagnosis in patients with cryptogenic neurologic illness or in young subjects with ischemic stroke. The absence of characteristic clinical, laboratory, or radiographic features of this rare disease make the diagnosis very difficult, and has contaminated the literature with unproven cases in which alternative diagnoses are plausible.

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Background

Vasculitis is inflammation of blood vessel walls leading to disruption of the normal structural and physiologic characteristics of the affected vessels, which in turn results in vascular occlusion and/or formation of aneurysms with consequent ischemia and hemorrhage.

Numerous forms of vasculitis can affect the central nervous system (CNS). This review focuses on primary angiitis of the central nervous system (PACNS), a rare form of vasculitis restricted to the brain and spinal cord. Only biopsy-proved case series are referenced in this report.

See Vasculitis: Case Presentations, a Critical Images slideshow, for more information on clinical, histologic, and radiographic imaging findings in various forms of vasculitis.

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Pathophysiology

The etiology and pathogenesis of PACNS are unknown. The fundamental mechanism of all vasculitides is immunologic; Crowe discussed 4 different mechanisms of tissue injury that might apply to the pathogenesis of vasculitis: immune complexes, direct antibody-mediated damage, delayed hypersensitivity, and cytotoxic T lymphocytes. [1] With the limited knowledge we have about PACNS, no strong evidence supports any of these mechanisms in the pathogenesis of this disease, although the granulomatous nature of inflammation suggests a role of cell-mediated immunity. [2]

As in other autoimmune disorders, T cells that become sensitized in the course of systemic illness or viral infection probably later contribute to a cellular immune response directed against cross-reacting epitopes in CNS vessels. [3] Other authors propose that, in the setting of altered host defense mechanisms, a virus or other pathogen may lead directly or indirectly to diffuse cerebral vasculitis. [4]

The latter hypothesis is supported by the rare condition in which vasculitis involving mainly the ipsilateral anterior circulation with consequent infarcts occurs days to weeks following varicella-zoster infection of the first division of the trigeminal nerve. The mechanism seems to be retrograde spread of the virus from Gasserian ganglion to the arteries of the anterior circle of Willis. [5]

Pathologically confirmed cases of PACNS have been reported in patients with Hodgkin disease, amyloid angiopathy, and graft-versus-host disease. However, available information in these cases does not allow any conclusion about the causal relation between these diseases and PACNS. [2]

Regardless of the etiology of PACNS, the main mechanism of neurologic damage in these patients is ischemic. This results from 3 consequences of inflammation in the vascular wall: obstruction of the vessel lumen, increased local coagulation from the effects of proinflammatory cytokines on the endothelial surface, and alteration in vasomotor tone. [6]

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Epidemiology

Frequency

United States

The rarity of PACNS and the lack of consensus on diagnostic criteria make incidence and prevalence of the disease difficult to estimate.

International

PACNS is reported more frequently in North America, Europe, Australia, and New Zealand. Whether the disease has a higher incidence in these regions or it has just been more successfully diagnosed and reported there is unclear.

Mortality/Morbidity

Mortality and morbidity of PACNS are hard to determine due to the variability in diagnosis means and treatment among published series. However, treatment with steroids and immunosuppressants has improved the outcomes of the disease, which used to be fatal. In a recent report, 14% of 29 patients with biopsy-proven PACNS died or had severe morbidity (Modified Rankin Scale of 5) at follow-up of 1.14 years. [7]

Sex

Men are more commonly affected by PACNS than women; the male-to-female ratio is about 7:3. [4]

Age

In most reported cases, patients were in the fourth to sixth decades of life at time of diagnosis. However, patients aged 7 months to 78 years have been described. [8, 9, 10]

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