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Table of Contents    
CORRESPONDENCE
Year : 2019  |  Volume : 67  |  Issue : 3  |  Page : 942-944

Primary angiitis of the central nervous system (PACNS) – a rare and serious, but treatable entity


Department of Neurology, University Hospitals Birmingham and Honorary Reader in Neuroimmunology, Institute of Immunology and Immunotherapeutics, University of Birmingham, UK

Date of Web Publication23-Jul-2019

Correspondence Address:
Dr. Saiju Jacob
Department of Neurology, University Hospitals Birmingham, B15 2TH
UK
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.263180

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How to cite this article:
Jacob S. Primary angiitis of the central nervous system (PACNS) – a rare and serious, but treatable entity. Neurol India 2019;67:942-4

How to cite this URL:
Jacob S. Primary angiitis of the central nervous system (PACNS) – a rare and serious, but treatable entity. Neurol India [serial online] 2019 [cited 2019 Nov 20];67:942-4. Available from: http://www.neurologyindia.com/text.asp?2019/67/3/942/263180




Isolated vasculitis of the central nervous system (CNS) is an extremely rare condition affecting approximately 2.4 patients per one million patient years, as described in a US study.[1] It is described commonly as primary angiitis of the CNS (PACNS) or primary CNS vasculitis. Although PACNS can occur at any age and in both sexes, the incidence is usually higher in males in their 50s.[1],[2] Until the introduction of the diagnostic criteria,[3] PACNS has very rarely been described and was probably under-diagnosed and rarely reported. Large case series are very rarely published except from a handful of centers.

Patients with PACNS often present with a combination of headache, encephalopathy (confusion, seizures, etc), or with unexplained strokes. Careful consideration should be given to exclude secondary causes for these symptoms [Figure 1], before contemplating a diagnosis of PACNS. This is paramount because the immunosuppressive treatments used for PACNS can potentially worsen (e.g., infection) or mask (e.g., lymphoma) an alternative diagnosis. In general, systemic markers of inflammation are rarely present, but the CSF examination often shows mild lymphocytic leucocytosis and modestly elevated cerebrospinal fluid (CSF) protein.
Figure 1: Algorithm for the diagnosis and management of primary angiitis of the central nervous system (PACNS). (ADEM – Acute disseminated encephalomyelitis, CSF – Cerebrospinal fluid, DSA – Digital subtraction angiography, DWI – Diffusion weighted imaging, FLAIR – Fluid-attenuation inversion recovery, MS – Multiple sclerosis)

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MRI scan of the brain is almost always abnormal with the usual findings including multi-focal ischemic changes not following a particular vascular territory and white matter T2W/FLAIR hyperintensities. Varying levels of contrast uptake, including meningeal enhancement and rarely tumefactive parenchymal lesions (in both brain and spinal cord), have been described. Modern MRI studies have shown that the medium/larger vessel vasculitides are more likely to show ischemic lesions and vessel wall enhancement compared to the small vessel CNS vasculitis.[4] High-resolution 3Tesla MRI scanning has been found to be useful for demonstrating vessel wall inflammation,[5] thus helpng in distinguishing PACNS from reversible cerebral vasoconstriction syndrome (RCVS).

The diagnosis is often confirmed by the angiographic appearance of “beading” owing to alternate stenosis and dilatation of intracranial blood vessels, which is often multi-segmental and bilateral.[2] A digital subtraction angiogram (DSA) is considered to have a better resolution than an MRA in identifying these changes. Other angiographic changes include occlusion of blood vessels, aneurysmal dilatation, or delayed contrast enhancement and washout. A definite diagnosis can only be made after a brain biopsy showing lymphocytic infiltration of the vessel wall with patients either showing a granulomatous, lymphocytic, or necrotizing pattern.[6]

In a previous edition of this journal, Sundaram S et al.,[7] describe the largest series of angiographically or biopsy-proven primary CNS vasculitis from India. The authors have carefully applied the diagnostic criteria [3] and have made all efforts to exclude reasonable alternative diagnoses such as infection or systemic inflammation, which may cause secondary vasculitis. Forty-five PACNS patients were retrospectively analyzed with a mean follow-up of 33 months. As expected with a rare diagnosis, there was a substantial delay before the diagnosis was made (mean – 103, range 12–1893 days), which was longer (mean – 212 days) if the DSA was negative, and a brain biopsy was required as the confirmatory test. Strokes (42.2%), headaches (24.4%), seizures (17.8%), and cognitive impairment (11.1%) were the most common presenting symptoms.

More than 90% of patients had MRI features consistent with single or multi-vessel infarcts with a third of patients showing multiple microbleeds on gradient echo sequences. More than two-thirds of patients who underwent DSA had vascular changes (alternate stenosis and dilatation, the so-called “beading”) in either the small, medium, or large intracranial blood vessels. However, 65% patients who underwent brain biopsy (n = 29) showed positive evidence of blood vessel inflammation with the lymphocytic pattern being the most common (11/19). The yield of a positive biopsy was approximately 90% when the target was radiologically guided, compared to a blinded biopsy of the non-dominant frontal or temporal lobe.

In keeping with the current recommendations,[7],[8] all patients were treated with oral prednisolone (1 mg/kg), and a smaller proportion (14 patients) were given other immunosuppressive medications, mainly cyclophosphamide. Three-quarters of patients (33/45) had a favorable outcome, as defined by a modified Rankin scale ≤2. A higher National Institute of Health Stroke Scale (NIHSS ≥5), cognitive dysfunction and an abnormal electroencephalogram (EEG) were more likely to lead to a poorer prognosis. Patients with normal DSA were found to fare poorly, but this was likely to be secondary to the delay in diagnosis and subsequent initiation of treatment.

RCVS remains one of the most important differential diagnoses, and patients often present with either a single episode of headache or of recurrent thunderclap headaches, with a recent study suggesting that patients are often female with a history of migraine usually manifesting in the postpartum period, or with a history of the usage of vasoactive substances.[9] In this prospective study involving 110 PACNS and 173 RCVS patients, all PACNS patients had an abnormal MRI as opposed to only 30% in the RCVS group. Ischemic stroke and intracerebral hemorrhage were much more likely to be seen in the PACNS patients, and RCVS was more likely to cause sub-arachnoid hemorrhage and vasogenic edema. Multiple deep white matter lesions, tumefactive changes, and extensive gadolinium enhancement were seen almost exclusively in the PACNS patients. None of the patients in the current study had a presentation with a thunderclap headache.[7]

In our neuroscience center, most patients are worked up systematically with MRI and DSA, and where possible, a brain biopsy before a diagnosis is established. Patients are classified as having definite PACNS only if there is histopathological confirmation. All patients with suspected PACNS receive steroids (intravenous, especially in the more severely affected individuals, followed by oral prednisolone) and a good proportion of them also receive pulsed intravenous cyclophosphamide [Figure 1]. Most patients require only 12–18 months of therapy and generally lead an independent life. Rituximab and infliximab are very rarely needed in the vast majority of patients.

Primary CNS vasculitis remains a rare diagnosis, but with the advancement of imaging technology (invasive and non-invasive), more patients are being diagnosed and treated. An early recognition with a high index of suspicion is crucial in initiating appropriate immunosuppressive therapies and most patients have a favorable outcome. Prognostic factors as identified by Sundaram et al.,[7] may help in targeting more aggressive immunotherapies in a timely fashion.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Salvarani C, Brown RDJr, Calamia KT, Christianson TJ, Weigand SD, Miller DV, et al. Primary central nervous system vasculitis: Analysis of 101 patients. Ann Neurol 2007;62:442e51.  Back to cited text no. 1
    
2.
Hajj-Ali RA, Calabrese LH. Diagnosis and classification of central nervous system vasculitis. J Autoimmun 2014;48-9:149-52.  Back to cited text no. 2
    
3.
Calabrese LH, Mallek JA. Primary angiitis of the central nervous system. Report of 8 new cases, review of the literature, and proposal for diagnostic criteria. Medicine (Baltimore) 1988;67:20-39.  Back to cited text no. 3
    
4.
Thaler C, Kaufmann-Bühler AK, Gansukh T, Gansukh A, Schuster S, Bachmann H, et al. Neuroradiologic characteristics of primary angiitis of the central nervous system according to the affected vessel size. Clin Neuroradiol 2017:27:37-44.  Back to cited text no. 4
    
5.
Obusez EC, Hui F, Hajj-Ali RA, Cerejo R, Calabrese LH, Hammad T, et al. High-resolution MRI vessel wall imaging: Spatial and temporal patterns of reversible cerebral vasoconstriction syndrome and central nervous system vasculitis. AJNR Am J Neuroradiol 2014;35:1527-32.  Back to cited text no. 5
    
6.
Miller DV, Salvarani C, Hunder GG, Brown RD, Parisi JE, Christianson TJ, et al. Biopsy findings in primary angiitis of the central nervous system. Am J Surg Pathol 2009;33:35-43.  Back to cited text no. 6
    
7.
Sundaram S, Menon D, Khatri P, Sreedharan SE, Jayadevan ER, Sarma P, et al. Primary angiitis of the central nervous system: Clinical profiles and outcomes of 45 patients. Neurol India 2019;67:105-12.  Back to cited text no. 7
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8.
Salvarani C, Brown RD Jr, Hunder GG. Adult primary central nervous system vasculitis. Lancet 2012;380:767-77.  Back to cited text no. 8
    
9.
de Boysson H, Parienti JJ, Mawet J, Arquizan C, Boulouis G, Burcin C, et al. Primary angiitis of the CNS and reversible cerebral vasoconstriction syndrome: A comparative study. Neurology 2018;91:e1468-78.  Back to cited text no. 9
    


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