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.

Pathophysiology

The etiology and pathogenesis of primary angiitis of the central nervous system (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]

Frequency

The rarity of primary angiitis of the central nervous system (PACNS) and the lack of consensus on diagnostic criteria make incidence and prevalence of the disease difficult to estimate.

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]}

Prognosis

Prognosis of primary angiitis of the central nervous system (PACNS) is usually guarded, even with appropriate therapy. Prognosis is good in benign angiopathy of the CNS and postpartum CNS angiopathy, but these diagnoses are usually confirmed only in retrospect.

Patient Education

Primary angiitis of the central nervous system (PACNS) patients should be educated about the chronic nature of the disease, and about the potential toxic side effects of steroids and immunosuppressants.

Patients should also be educated about the importance of controlling other cerebrovascular risk factors, such as hypertension, diabetes, hyperlipidemia, and smoking.

Clinical Presentation

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Media Gallery

Lateral right internal carotid angiogram shows beading of anterior cerebral arteries (arrowheads) and beading (straight arrows), segmental dilatation (curved arrow), and narrowing of middle cerebral arteries (open arrow).
Low power view of inflamed vessel in the subarachnoid space shows fibrinoid necrosis (pink areas) superiorly.
Higher power view of small inflamed vessel in the medulla, with fibrinoid necrosis in the wall and chronic transmural inflammation.
(a) T1-weighted left parasagittal MRI showing hypointense lesions in the cortical and subcortical white matter of the left superior temporal gyrus and frontal and frontoparietal operculum with sulcal obliteration. (b) The postgadolinium MRI at this level showing nodular parenchymal and linear pial enhancement.
(a) T2-weighted axial MRI showing hyperintense lesions in the lentiform nuclei, head of the caudate nuclei and frontoparietal subcortical white matter. (b) On T1-weighted (postgadolinium) axial image, the lentiform nuclei and head of caudate nuclei are heterogeneously hypointense, while subcortical white matter lesions are isointense. Linear areas of pial enhancement are seen bilaterally.
(a) T2-weighted axial MRI showing large, well-defined hyperintense lesions in the left frontal and parietal lobes. (b) Postgadolinium T1-weighted axial MRI showing nodular parenchymal and cortical-pial enhancement of the lesion. A follow up (after 3 mo) T2-weighted axial (c) and postgadolinium (d) T1-weighted axial MRIs showing significant reduction of the lesion size and nodular enhancing areas.