Primary central nervous system vasculitis and its mimicking diseases – clinical features, outcome, comorbidities and diagnostic results – A case control study

Highlights

• Symptoms do not discriminate between PCNSV and its differential diagnoses.

• Contrast enhancement is typical for vasculitis.

• Tumor-like mass lesion in magnetic resonance imaging is a feature of vasculitis.

• Normal Duplex findings are characteristic for vasculitis.

Abstract

Objectives

To compare clinical features and outcome, imaging characteristics, biopsy results and laboratory findings in a cohort of 69 patients with suspected or diagnosed primary central nervous system vasculitis (PCNSV) in adults; to identify risk factors and predictive features for PCNSV.

Patients and methods

We performed a case-control-study including 69 patients referred with suspected PCNSV from whom 25 were confirmed by predetermined diagnostic criteria based on biopsy (72%) or angiography (28%). Forty-four patients turned out to have 15 distinct other diagnoses. Clinical and diagnostic data were compared between PCNSV and Non-PCNSV cohorts.

Results

Clinical presentation was not able to discriminate between PCNSV and its differential diagnoses. However, a worse clinical outcome was associated with PCNSV (p = 0.005). Biopsy (p = 0.004), contrast enhancement (p = 0.000) or tumour-like mass lesion (p = 0.008) in magnetic resonance imaging (MRI), intrathecal IgG increase (p = 0.020), normal Duplex findings of cerebral arteries (p = 0.022) and conventional angiography (p = 0.010) were able to distinguish between the two cohorts.

Conclusion

In a cohort of 69 patients with suspected PCNSV, a large number (64%) was misdiagnosed and partly received treatment, since mimicking diseases are very difficult to discriminate. Clinical presentation at manifestation does not help to differentiate PCNSV from its mimicking diseases. MRI and cerebrospinal fluid analysis are unlikely to be normal in PCNSV, though unspecific if pathological. Cerebral angiography and biopsy must complement other diagnostics when establishing the diagnosis in order to avoid misdiagnosis and mistreatment.

Clinical trial registration

German clinical trials register: http://drks-neu.uniklinik-freiburg.de/drks_web/, Unique identifier: DRKS00005347.

Introduction

Primary central nervous system vasculitis (PCNSV), also known as isolated angiitis of the CNS, represents a very rare and poorly understood disease that manifests exclusively in the central nervous system (CNS) [1] and that is potentially fatal. Numerous differential diagnoses have to be considered that can mimic either clinical features and/or diagnostic results, which make PCNSV a diagnostic challenge for clinicians [2], [3]. According to its rarity and the diagnostic difficulties reliable registry and epidemiologic data still are lacking [4].

PCNSV is an inflammatory disease affecting medium- to small-sized vessels; the inflammation and necrosis of the vessel walls affects arterial and venous vessels most frequently in a segmental pattern [5]. Morphological lesions are stenosis and vessel occlusions leading to ischemic tissue damage, or micro-aneurysmal expansions with the risk of rupture and bleedings. The angiographic picture of segmental narrowing, occlusion or dilatation in multiple cerebral arteries is regarded as typical [5] (Fig. 1).

In 1988 Calabrese and Mallek implemented diagnostic criteria for PCNSV [6], extended in 2009 by Birnbaum and Hellmann [7]. Thus, definite PCNSV can be diagnosed histopathologically. In order to diagnose a probable PCNSV corresponding results in magnetic resonance imaging (MRI), conventional angiography of intracranial vessels and cerebrospinal fluid (CSF) are required. In addition, competing causes have to be excluded furthermore by clinical history, whole body examination and peripheral blood laboratory tests [2].

Exclusion of the more frequent differential diagnoses is one key element of the diagnostic work up [2]. Non-inflammatory vascular diseases like reversible cerebral vasoconstriction syndrome (RCVS)[8], Moyamoya angiopathy [9], Divry-van Bogaert syndrome [10] or Sneddon’s syndrome [10] which can mimic PCNSV [2] have to be excluded, as well as other autoimmune diseases such as multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), or infection-associated conditions [11], [12]. In spite of the dilemma of angiography-negative vasculitis and false-negative brain biopsies it is essential to strictly pay attention to the diagnostic criteria, which include the procedure of angiography and brain biopsy in order to avoid hasty immunosuppressive therapy in unrecognized non-inflammatory differential diagnoses [4], [13] (Fig. 2, Fig. 3).