Teaching Case

A 47-year-old woman with a 3-week history of headache and progressive cognitive dysfunction was admitted to the hospital. The patient underwent a brain MRI including spectroscopy and DSC perfusion imaging. Diagnosis was made 3 days after MRI on the basis of biopsy including cortex and subcortical white matter for histological analysis.

Figures 1-2: confluent hyperintensities involving white matter of both hemispheres.
Figures 3-6: Contrast-enhanced T1WI and FLAIR sequences show leptomeningeal enhancement and both punctate and linear gadolinium enhancing lesions in the brain parenchyma of both hemispheres. Images show a clear right hemisphere predilection.
Figures 7-8 demonstrates mild restricted diffusion in the right white matter.
Figure 9-10: there is no lactate peak. White matter lesions show an elevated Cho signal and decreased NAA.
Figure 11: DSC perfusion imaging shows absence of elevated cerebral blood volume in the white matter disease.
Findings at histopathological analysis: inflammatory infiltrates with angiocentric distribution in leptomeningeal, cortical and white matter vessels. Small and medium-size vessels are affected. The infiltrates are composed of lymphocyte predominant cells and are accompanied of epithelioid macrophages and multinucleated cells forming non-necrotizing granulomas.

Primary angiitis of the central nervous system (PACNS) is a rare disorder that comprises a broad spectrum of disorders that result in inflammation and destruction of the blood vessels of the brain, spinal cord and meninges [1]. The only population-based study of PACNS estimated an incidence of 2.4 cases per 100, 000 person-years in Olmstead County, Minnesota [2]. The median age at diagnosis in adults is approximately 50 years [1].
Neurologic manifestations of CNS vasculitis are a consequence of ischaemia and infarction or intracranial haemorrhage. Ischaemia and infarction are thought to result from a combination of vessel narrowing and obstruction caused by wall inflammation, increased coagulability provoked by inflammatory cytokines, and vasomotor tone dysfunction. Inflammation may also result in haemorrhage by debilitating the vascular wall [1].
PACNS affects medium-sized arteries and small vessels, including arterioles, capillaries and venules of the brain parenchyma and the leptomeninges [3].
Its presentation is nonspecific, likely related to the patchy distribution of the vascular lesions, and includes headache, cognitive dysfunction and focal neurological signs [4]. These 3 manifestations have been reported as the initial symptoms in approximately 65% of cases [5].
The possibility of CNS vasculitis is usually considered in 2 clinical settings: starting with either a constellation of symptoms or an abnormal angiogram.
CSF analysis is crucial for the assessment of patients with suspected PACNS, in order to address a broad differential diagnosis that includes infection and malignancy, and because normal CSF makes a diagnosis of PACNS less likely [1].
MRI has a sensitivity of 90% to 100%, although poor specificity, for the work-up of patients with suspected PACNS [6]. The typical MRI abnormalities consist of changes in the subcortical white matter, deep grey and white matter, and the cerebral cortex. Infarcts are the most common lesions, reported in 53% of patients in the largest series [2].
Laboratory studies, neuroimaging and angiography are neither sufficiently sensitive nor specific for diagnosis, and a definitive diagnosis requires brain biopsy [1].
The majority of patients respond to therapy with glucocorticoids alone or in conjunction with cyclophosphamide [7]. The treatment response and the outcomes appear primarily related to the size of the vessels involved in the inflammatory process. The involvement of small cortical/leptomeningeal vessels is associated with a more benign course, whereas the involvement of larger/proximal cerebral vessels is related to a less favourable prognosis and identifies cases that should be treated more aggressively [7].