Table 3.

Overview of (selected) differential diagnosis of PACNS.

Type of disease	Selected example	Similarities with PACNS	Differences to PACNS	Diagnostic approach
	RCVS	cerebral angiographic abnormalities (multifocal segmental cerebral artery vasoconstriction), cerebral infarctions, intracerebral haemorrhage	acute onset, monophasic course, thunderclap headache, usually normal CSF analysis, normal MRI in 20%, no vasculitis changes in cerebral biopsy, precipitating factors, reversible angiographic abnormalities	angiographic follow-up after 12 weeks shows resolution of abnormalities, nimodipine (reverse vessel narrowing in DSA?)
Non-inflammatory vasculopathies	Atherosclerosis	multiple cerebral infarctions, vessel beading, vessel wall enhancement	older age, vascular risk factors (hypertension, diabetes mellitus), hetergeneous lesions, calcifications and irregular focal stenoses of proximal arteries, normal CSF analysis, infarcts usually restricted to a single vascular territory	eccentric enhancement patterns of intracranial atherosclerotic plaques in high-resolution 3-Tesla contrast-enhanced MRI, calcified proximal cerebral arteries
	CADASIL	disease course, headache, psychiatric disturbances, sensory, motor and cognitive deficits, seizures, cerebral infarctions, diffuse white matter abnormalities on brain MRI	strokes or dementia in the history of the first-degree relatives, bilateral external capsule and anterior temporal lobe hyperintensities	genetic testing (mutation of the notch 3 gene), pathologic findings characteristic of CADASIL on brain or skin punch biopsies
	MELAS	enzephalopathy, stroke-like episodes before age 40, seizures, dementia, multiple hyperintensities on T2 and FLAIR-sequences	bilateral basal ganglia calcifications	genetic testing (point mutation A3243G), muscle biopsy (ragged-red fibers)
	Moyamoya angiopathy	cerebral infarctions, headache	younger age, normal CSF analysis, no inflammatory signs in the vessel wall, triggering of ischaemic events with hyperventilation, orthostatic stress, etc.,watershed infarctions on brain MRI, no gadolinium-enhancement, effect on extracranial or proximal intracranial cerebral arteries	angiography shows typical collateral network of small leptomeningeal and transdural vessels
	Radiation vasculopathy	vessel wall enhancement, leukoaraiosis	normal CSF analysis	history of cranial irradiation
CNS manifestations as part of a primary systemic vasculitis	Systemic vasculitis	headache, encephalopathy, seizures, cranial nerve palsies, visual symptoms, myelopathy, cerebral infarctions, intracranial haemorrhage, signs of mural inflammation on brain MRI	systemic signs and symptoms (fever, malaise, weight loss), renal insufficiency, pulmonary haemorrhage, unexplained sinusitis, abdominal pain, PNS can be affected	Elevated erythrocyte sedimentation rate or serum C reactive protein; Testing for antineutrophil cytoplasmic antibodies, antinuclear antibodies, cryoglobulins, hepatitis B/C serologies, p ANCA, c ANCA, anti-PR3, anti-MPO, extraneuronal biopsy

ANCA, Anti-neutrophil cytoplasmic antibodies; CSF, cerebrospinal fluid; DSA, digital subtraction angiography; MPO, Myeloperoxidase; MRI, magnetic resonance imaging; PACNS, primary angiitis of the central nervous system; PNS, peripheral nervous system; RCVS, reversible cerebral vasoconstriction syndrome