Primary central nervous system vasculitis (PACNS) is a rare disorder characterized by inflammation of blood vessels in the brain and spinal cord. It presents with non-specific symptoms like headache, cognitive impairment, and focal neurological deficits. Diagnosis involves neuroimaging showing multifocal lesions, angiography revealing vessel narrowing and dilation, and brain biopsy detecting immune cell infiltration of vessel walls. While the cause is unknown, infectious agents may trigger PACNS. Treatment involves immunosuppression but prognosis depends on disease severity and response to treatment.

1. PRIMARY CNS
VASCULITIS
(PACNS)
By/ Lobna Ahmed

2. • Primary angiitis of the central nervous system (PACNS) is a rare inflammatory disorder of the blood
vessels affects the blood vessels supplying the brain parenchyma, spinal cord and leptomeninges,
and less frequently veins and venules, occurring in the absence of any evidence of systemic
vasculitis.
• Clinical manifestations are non-specific with various presenting symptoms.
• Headache is the most common presenting symptom in the majority of the PACNS cases.
• The exact etiology and pathogenesis of PACNS are unknown, but infectious agents have been
postulated as one of the triggers (VZV, HIV, HCV, Bacterial).
• There is also a notable association between PACNS and cerebral amyloid angiopathy. The amyloid
deposition has been identified as a possible trigger for PACNS in animal models.

3. The exact epidemiology of this rare
disorder have not been done (some data
shows an annual incidence rate of 2.4
cases per 1 million person-years).
Equal distribution among both sexes
and the median age of diagnosis of
about 50 years.
Epidemiology
PACNS mainly
affects younger
stroke patients
lacking CVS risk
factors.
Approximately 3-5%
of CVS in patients
<50 years are
caused by PACNS.

4.  Pathological findings can affect both
small and large vessels of the CNS.
 Specific activation of the immune system
(especially T-cells) by various cause
inflammation of blood vessels in the CNS.
 Immunohistochemical staining of biopsy
samples in PACNS showed an extensive
infiltration around the small cerebral arteries
by CD45R0+ T cells.
Infiltration of
immune cells
within vessels wall
destruction of the
vessels walls
Thickening of
vessels walls with
alternating
segments of
stenosis
Poor blood
circulation
Pathophysiology
On the other hand,
weak vessels walls can
rupture leading to
hemorrhage.

5.  Affection of parenchymal and leptomeningeal
arteries.
 Three different types of vasculitis patterns
have been described in PACNS
(granulomatous type, necrotizing type, and
lymphocytic type).
 The most common type, granulomatous,
shows numerous granulomas with
multinucleated cells.
 The necrotizing type presents with fibrinoid
necrosis, and lymphocytic type shows
extensive lymphocytic inflammation with
plasma cells.
Granulomatous
Necrotizing
Lymphocytic
Histopathology

6. The onset of PACNS is usually insidious, and the course
is slowly progressive. Acute presentations have also
been reported but are, however, less common.
Clinical
presentation
Non-specific
Multiple
symptoms
Headache is the most
common presenting
symptom
•Cognitive dysfunction
•Stroke
•Transient ischemic attack (TIA)
•Aphasia
•Visual symptoms including visual field
deficits, blurred vision, and double
vision
•Seizures
•Ataxia
•Papilledema
•Intracranial bleeding
•Amnestic syndrome
The presenting symptoms and signs from the
most common to the least common include:

7. Headache 60%
Cognitive
impairment 50%
Focal neurological
deficits
Marked constitutional symptoms
such as fever, weight loss and night
sweats are less frequent and can be
indicative of systemic vasculitides.
In about 5% of patients primary CNS
vasculitis can affect the spinal cord
and isolated vasculitic myelopathies
have also been reported.

8. A combination of symptoms is
usually present in most patients.
PACNS should always be
considered as a possibility in
cases of rapidly progressive
cognitive decline and personality
changes of unknown etiology.

9. Diagnostic
criteria
1- A history of
clinical findings of
an acquired
otherwise
unexplained
neurologic deficit.
2- Presence of
classic
angiographic or
histopathologic
features of angiitis
within the CNS.
3- No evidence of
systemic vasculitis
or of any other
disorder that could
cause or mimic the
angiographic or
pathologic features.

10. Definite • Confirmed by tissue biopsy.
Probable
• High probability finding on an angiogram with
abnormal findings on MRI and a CSF profile
consistent with PACNS (in the absence of tissue
confirmation).
Diagnostic
certainty

11. Subtypes of PACNS
Small vessels
Large/medium
vessels
According to the size
of affected vessel
In contrast, LV-PACNS is
more likely to present with
focal deficits and acute
ischemia on MRI.
Isolated SV-PACNS is associated with:
-A more severe encephalopathic
presentation with cognitive impairment
and seizures.
-A more abnormal CSF analysis and
more diffuse gad enhanced lesions on
MRI.
-More relapses.

12. CAROLIN BEUKE. (N.D.). PRIMARY ANGIITIS OF THE CENTRAL NERVOUS SYSTEM: DIAGNOSIS AND TREATMENT.
THER ADV NEUROL DISORD. HTTPS://DOI.ORG/ 10.1177/1756286418785071

13. Evaluation
Laboratory
• Detection of ANA, RF, ANCA, antiphospholipid Ab,
bacterial or viral Ag is usually suggestive of systemic
vasculitis or auto-immune disease.
• Elevated ESR and CRP neither sensitive nor specific.
• Serological tests are needed to exclude infection
including varicella, mycobacteria, syphilis, human HIV,
and fungi.
• No specific marker for PACNS.

14. CSF
The only useful laboratory investigation is CSF examination
which shows an abnormality in more than 90% of the cases.
Should be performed in all patients.
Inflammatory
findings:
lymphocytic
pleocytosis,
elevated
protein.

15. Normal CSF (cell count
<5 cells /μl or total
protein concentration
<45 mg/dl) >> search for
DD.
OCB and IgG are only
found occasionally.
Increased interleukin
(IL)17-producing CD41
cells in CSF can
differentiate PACNS
from ischemic stroke.
Values more than 250
cells/μl are indicative for
infection.
Malignant vasculitis can
be detected with CSF
cytology and flow
cytometry.
CSF

16. The cornerstone for establishing the
diagnosis of PACNS.
Imaging
Cerebral
angiography
MRI, MRA
CT,CTA
vessel beading
Intracranial
vessels
Narrowing
and dilatation
Fusiform
arterial
dilation
Delayed
contrast
enhancement
Development
of collateral
circulation
Multilocular
occlusions

17. Vessel beading is not
a specific feature for
PACNS
It is also seen in:
• Noninflammatory vasculopathies.
• Non-vasculitis conditions such as
atherosclerosis.
• After radiation.
• Neurofibromatosis.
• Atrial myxomas.
• Infections.
• Vasospasm.

18. DSA is the gold
standard imaging.
It’s not 100% specific.
Possibly due to the
waxing and waning
pattern of stenosis.
VALERIE L JEWELLS. (N.D.). CNS VASCULITIS; AN OVERVIEW OF THIS M ULTIPLE SCLEROSIS MIMIC; CLINICAL AND MRI
IMPLICATIONS. SEMINARS IN ULTRASOUND CT AND MRI. HTTPS://DOI.ORG /HTTPS://DOI.ORG/10.1053/J.SULT.2020.02.004

19.  MRI of the brain is abnormal in more than 90%
of patients, but the pattern of abnormal findings
is not specific.
 MRI should include T1, T2, FLAIR, DWI, ADC,
GRE, with and without gadolinium
administration.
Multifocal bilateral
T2, FLAIR lesions
in cortical,
subcortical, DWM
and gray matter.
New and old
coexisting ischemic
lesions.
Lesions can be
accompanied by
subarachnoid and
ICH.
Mass lesions that
can mimic a tumors
or abscess.
Gd enhancement of
parenchymal
lesions and the
leptomeninges.
Imaging
Cerebral
angiography
MRI, MRA
CT,CTA

20. MRI/MRA is the first
diagnostic test of choice.
VALERIE L JEWELLS. (N.D.). CNS VASCULITIS; AN OVERVIEW OF THIS M ULTIPLE SCLEROSIS MIMIC; CLINICAL AND MRI
IMPLICATIONS. SEMINARS IN ULTRASOUND CT AND MRI. HTTPS://DOI.ORG /HTTPS://DOI.ORG/10.1053/J.SULT.2020.02.004
MRA is a less invasive imaging modality and therefore can be used to monitor the
disease course, however, in comparison with DSA, MRA is less sensitive in the
detection of both lesions localized in the posterior circulation and in distal arteries.

21. Occipital
Temporal
Parietal
Frontal
WM lesions
distribution
2/3rd of CNSV cases
have WM involvement.
MCA>PCA>ACA
MRI
protocol
 Standard protocol is 3D T1, T2, FLAIR, and post contrast imaging
with MRA, perfusion and SWI (for depicting hemosiderin from
intraparenchymal hemorrhages and hemosiderosis).
 Recently, vessel wall imaging can be used as a part of the protocol
to detect vessel wall inflammation, preferentially performed at 3T
via black blood sequences using T2 TSE or T2* weighted-GRE
sequences with FLAIR and TOF MRI as well as fat sat T1 images.
VALERIE L JEWELLS. (N.D.). CNS VASCULITIS; AN OVERVIEW OF THIS M ULTIPLE SCLEROSIS MIMIC; CLINICAL AND MRI
IMPLICATIONS. SEMINARS IN ULTRASOUND CT AND MRI. HTTPS://DOI.ORG /HTTPS://DOI.ORG/10.1053/J.SULT.2020.02.004

22.  Vessel wall imaging uses different techniques to
suppress the signal of intraluminal blood (“black
blood imaging”), thus allowing evaluation of the
vessel wall and possibly the detection of
inflammatory changes within the vessel wall.
 Vessel wall contrast enhancement has been
reported as a potential sign of CNS vasculitis
 In particular, differentiating between inflammation,
intracranial atherosclerotic plaques, and other wall
abnormalities based on the typical enhancement
patterns was reported.
High resolution
contrast-enhanced
MRI
(HR-MRI)
“Black Blood MRI”
PATZIG, M., FORBRIG, R., KÜPPER, C. ET AL. DIAGNOSIS AND FOLLOW-UP EVALUATION OF CENTRAL NERVOUS SYSTEM
VASCULITIS: AN EVALUATION OF VESSEL-WALL MRI FINDINGS. J NEUROL 269, 982–996 (2022). HTTPS://DOI.ORG/10.1007/S00415-
021-10683-7

23.  CT /CTA may demonstrate occlusion, stenosis,
and wall thickening of large vessels.
 It’s limitations are insensitivity for WM
assessment, leptomeningeal enhancement or
depiction of small vessels.
Imaging
Cerebral
angiography
MRI, MRA
CT,CTA

24. PRIMARY ANGIITIS OF THE CENTRAL NERVOUS SYSTEM MAGNETIC RESONANC E IMAGING
SPECTRUM OF PARENCHYMAL, MENINGEAL, AND VASCULAR LESIONS AT BASE LINE.
(N.D.). STROKE. DOI:10.1161/STROKEAHA.116.016194
Multiple ischemic
lesions (A-B), post-
contrast
leptomeningeal
enhancement (C),
multiple focal stenosis
of bilateral MCA on TOF
MRI (D).

25. PRIMARY ANGIITIS OF THE CENTRAL NERVOUS SYSTEM MAGNETIC RESONANC E IMAGING
SPECTRUM OF PARENCHYMAL, MENINGEAL, AND VASCULAR LESIONS AT BASE LINE.
(N.D.). STROKE. DOI:10.1161/STROKEAHA.116.016194
Right frontal acute
intraparenchymal
hemorrhage (A), 3 months
later on (B-C) showing post
contrast enhancement.

26. PRIMARY ANGIITIS OF THE CENTRAL NERVOUS SYSTEM MAGNETIC RESONANC E IMAGING
SPECTRUM OF PARENCHYMAL, MENINGEAL, AND VASCULAR LESIONS AT BASE LINE.
(N.D.). STROKE. DOI:10.1161/STROKEAHA.116.016194
Patterns of contrast
enhancement in PACNS,
punctate (A), incomplete
sub centimetric (B),
leptomeningeal (C),
parenchymal
enhancement (D).

27. PRIMARY ANGIITIS OF THE CENTRAL NERVOUS SYSTEM MAGNETIC RESONANC E IMAGING
SPECTRUM OF PARENCHYMAL, MENINGEAL, AND VASCULAR LESIONS AT BASE LINE.
(N.D.). STROKE. DOI:10.1161/STROKEAHA.116.016194
Post circulation
CVS with bilateral
PCA stenosis.
Chronic infarct
and proximal
stenosis of left
MCA.

28. Multifocal segmental
narrowing (A),
multiple DWI lesions in
different vascular
territories(B),
concentric enhancement of
the M1-segment of the left
middle cerebral artery on
black blood MRI(C),
vessel beading on MRI-
TOF-angiography(D),
bilateral infarctions of
variable size (E),
and intracerebral
hemorrhage (F).
CAROLIN BEUKE. (N.D.). PRIMARY ANGIITIS OF THE CENTRAL NERVOUS SYSTEM: DIAGNOSIS AND TREATMENT.
THER ADV NEUROL DISORD. HTTPS://DOI.ORG/ 10.1177/1756286418785071

29. -Vessel wall contrast enhancement of
the right distal M1 segment is seen at
initial presentation on vessel wall
imaging (A), which remains unchanged
at two-months follow-up (B) despite
immunosuppressive therapy.
-Correlating TOF-MRA findings (C, D),
showing unchanged high-grade
stenosis of the affected segment.
PATZIG, M., FORBRIG, R., KÜPPER, C. ET AL. DIAGNOSIS AND FOLLOW-UP EVALUATION OF CENTRAL NERVOUS SYSTEM
VASCULITIS: AN EVALUATION OF VESSEL-WALL MRI FINDINGS. J NEUROL 269, 982–996 (2022). HTTPS://DOI.ORG/10.1007/S00415-
021-10683-7

30. -At initial presentation (A, C), there is marked
vessel wall contrast enhancement of the
posterior circulation, including the basilar
artery (arrow) and left PCOM (arrowhead).
-Follow-up vessel wall imaging after ten years
(B, D) shows complete resolution of vessel
wall contrast enhancement of the PCOM and
regressive but still persistent vessel wall
contrast enhancement of the basilar artery.
-Correlating TOF-MRA images (E, F)
demonstrate resolution of a high-grade
stenosis of the left PCOM.
PATZIG, M., FORBRIG, R., KÜPPER, C. ET AL. DIAGNOSIS AND FOLLOW-UP EVALUATION OF CENTRAL NERVOUS SYSTEM
VASCULITIS: AN EVALUATION OF VESSEL-WALL MRI FINDINGS. J NEUROL 269, 982–996 (2022). HTTPS://DOI.ORG/10.1007/S00415-
021-10683-7

31. Angio
Positive
• In large/ proximal
vessel affection.
Angio
Normal
• In small vessel (<500
μm in diameter)
affection.
In case of negative
angiographic findings >>
brain biopsy should be
considered as an important
step towards diagnosing
PACNS.

32. Biopsy
• Due to the focal and segmental distribution of the disease,
the sensitivity of brain biopsy is as a result of sampling
errors between 53–74%.
• The diagnostic yield can be increased by 80% by targeting
areas of imaging abnormalities.
• If affected lesions are not accessible for surgery, a biopsy
from the right (nondominant) frontal lobe with its overlying
leptomeninges tissue is recommended.
• Negative biopsy cannot rule out the diagnosis of cerebral
vasculitis, but histopathological examination often results
in alternative diagnoses (special attention is paid to PACNS
mimics like infections, neoplasms especially lymphoma,
and degenerative disease.
Biopsy
is safe! Brain biopsies are associated with rather low morbidity and
mortality rates; therefore, a biopsy should be obtained, if the
diagnosis is uncertain.

33. CAROLIN BEUKE. (N.D.). PRIMARY ANGIITIS OF THE CENTRAL NERVOUS SYSTEM: DIAGNOSIS AND TREATMENT.
THER ADV NEUROL DISORD. HTTPS://DOI.ORG/ 10.1177/1756286418785071

34. Differential
diagnosis
Non-
inflammatory
vascular
diseases.
Malignancy.
Systemic
inflammatory
diseases.
Infection.

35. RCVS
Formerly RCVS
was described as
a subtype of
PACNS, called
benign angiopathy
of the CNS.
Typical clinical features are sudden and
recurrent attacks of severe (usually
thunderclap) HEADACHE with or without
focal neurological deficits or seizures.
More in
Females.
Mean age of
onset 42
yrs.
The most
important non-
inflammatory
DD to PACNS.
Headache
RCVS is more often detected in patients
with exposure to vasoactive drugs,
migraine, hypertension, eclampsia or in
the postpartum period.

37. RCVS
Neuro imaging
may show infarctions (located
in the superficial border zone
or watershed regions),
cortical SAH, and lobar ICH.
Angiogram shows multifocal
segmental cerebral artery
vasoconstriction; dissection and
unruptured aneurysms occur
significantly more frequently than in
cerebral vasculitis.
Angiographic follow up
12 weeks after clinical onset
usually shows complete or
substantial resolution of
abnormalities in RCVS.
Intra-arterial nimodipine
use during convential
angiography showed reverse
of vessel narrowing in RCVS
in contrast with PACNS.

38. A-CT scan showing a small
cSAH,
B-MRI (FLAIR) showing a small
cSAH,
C- CT scan showing an
occipital intracerebral
haemorrhage,
D-MRI showing sequelae of
bilateral occipital infarcts and
left frontal-parietal infarct,
E-MRI (FLAIR) showing
hypersignals consistent with a
RPLS,
F-Control MRI in the same
patient after 28 days showing
resolution of the RPLS.

39. Diffuse intracerebral vasoconstriction on initial angiogram, after 2 wk of
headache then right hemiparesis and encephalopathy. B, Resolution of
vasoconstriction after 4 mo.

40. Systemic
vasculiti
s
CNS involvement
most often arises in
patients with:
 Bechet's disease.
 Wegener’s granulomatosis.
 Churg–Strauss syndrome.

41. Bechet’s
=
Variable vessel
size vasculitis
Large
vessel
vasculitis
 Involves >2mm size vessels, including the ICA,
M1 segment of the MCA, A1 segment of the
ACA, and P1 segment of the PCA.
 Takayasu’s arteritis (<50 yo), Giant cell arteritis
and temporal arteritis (>50 yo) are common
large vessel causes.
Medium
size vessel
vasculitis
 Most commonly Kawasaki’s
disease and polyarteritis
nodosa involve the M2, A2,
and P2 segments.
Small
vessel
vasculitis
 SLE, granulomatosis
with polyangiitis +/-
eosinophils, IgA
vasculitis, and
microscopic polyangiitis

42. Vasculitis
2nd to CT
diseases
SLE
Sjogren’s
syndrome
Dermatomyositis
Mixed CT
disease
RA

43.  Moyamoya angiopathy.
 Divry-van Bogaert syndrome.
 fibromuscular dysplasia.
 Fabry disease.
 Sneddon’s syndrome.
Non-
inflammatory
vascular
diseases

44. Malignancy
 In single cases, the occurrence of PACNS in
association with Hodgkin’s lymphoma, non- Hodgkin’s
lymphoma and angio-immuno-lympho-proliferative
lesions has been reported.
 Furthermore, intravascular lymphoma (IVL), a subtype
of extra-nodal diffuse large B-cell lymphoma, is an
important differential diagnosis of primary CNS
vasculitis characterized by intravascular proliferation
of lymphoma cells with a predilection for the CNS and
skin.

45. Infection
VZV vasculopathy:
 An infectious arteritis that causes ischemic infarction of the
brain and spinal cord, and cerebral hemorrhage, as well as
aneurysm and carotid dissection.
 Diagnosis of VZV infection can be made by detection of
anti-VZV IgG antibody in the CSF.
PACNS should be distinguished from other infectious agents
that can affect the CNS including:
Hepatitis C virus, HIV, Streptococcus pneumoniae, Neisseria
meningitidis, Bartonella spp ,Mycobacterium tuberculosis,
Borrelia burgdorferi, and Treponema pallidum.

46. Other
mimics
CADASIL
• An AD arteriopathy with
manifestation in early
adulthood.
• Clinical symptoms include:
migraine, recurrent
transient ischemic
attacks or strokes,
psychiatric disorders,
cognitive impairment,
and epilepsy.
• Brian MRI typically shows
large or small white matter
abnormalities.
• The most typical findings
are white matter
hyperintensities in the
anterior temporal lobe
(temporal pole) seen on T2
sequence.
Susac syndrome
• Autoimmune-mediated
endotheliopathy
characterized by the
clinical triad of:
Branch retinal artery
occlusions.
Encephalopathy.
Neurosensorial hearing
loss.
• It causes microangiopathic
occlusion of precapillary
arterioles in the brain,
retina, and inner ear.
Anti-phospholipid syndrome
• Present by diverse
neurologic manifestations
including: stroke, TIA,
seizures, movement
disorders,
neuropsychiatric
manifestations, and
cognitive decline.
• Angiography shows
intracranial abnormalities
suggestive of vasculitis.

47. ALIAGA FREDERIK BARKHOF, E. S. (N.D.). CHAPTER 13 - MRI MIMICS OF MULTIPLE SCLEROSIS. IN HANDBOOK OF
CLINICAL NEUROLOGY (PP. 291–316). ELSEVIER.

48. ADEM
Other
mimics

49. ALIAGA FREDERIK BARKHOF, E. S. (N.D.). CHAPTER 13 - MRI MIMICS OF MULTIPLE SCLEROSIS. IN HANDBOOK OF
CLINICAL NEUROLOGY (PP. 291–316). ELSEVIER.

50. ALIAGA FREDERIK BARKHOF, E. S. (N.D.). CHAPTER 13 - MRI MIMICS OF MULTIPLE SCLEROSIS. IN HANDBOOK OF
CLINICAL NEUROLOGY (PP. 291–316). ELSEVIER.

51. Treatment
Induction
therapy
Maintenance
therapy
Corticosteroids Immunosuppressants Biologics

52. Induction
therapy
Combination
therapy
Steroids Cyclophosphamide
High-dose of IV CST (1000 mg daily for
3–5 days),
or oral prednisone (1 mg/kg per day) are
currently the most frequently used
therapies.
IV is not more
effective than
oral!
Given either as an oral dose
(2 mg/kg/day) for 3–6 months,
or as IV pulse (750 mg/m2/
month) for 6 months.
Monitor:
 Leukocyte nadir and disease course.
 Side effects (infection, especially
bladder, cancer and infertility).
 It is contraindicated during pregnancy.

53. In patients who are intolerant to conventional immunosuppressive
therapeutic regimens ..
or in patients failing to respond to cyclophosphamide therapy ..
Biological
agents
Rituximab
TNF-α blockers
(infliximab and
etanercept)

54. Maintenance
therapy
Goal:
Limiting the
risk of relapses and
preventing long-term
disabilities.
Started 4–6 months
after initiation of the
induction therapy.
Corticosteroid-sparing low-
risk immunosuppressive
agents
Azathioprine Methotrexate
Mycophenolate
mofetil
1-2 mg/kg/day
1-2 g/day
20-25 mg/week

55. CAROLIN BEUKE. (N.D.). PRIMARY ANGIITIS OF THE CENTRAL NERVOUS SYSTEM: DIAGNOSIS AND TREATMENT.
THER ADV NEUROL DISORD. HTTPS://DOI.ORG/ 10.1177/1756286418785071

56. Duration of
treatment
• Validated data are lacking. In principle, induction
therapy should be administered for 6–12 months
based on individual response to treatment.
• Decisions on de-escalation of induction therapy
should depend on the achievement of clinical
stability.

57. Prognosis
• Older patients and those with infarctions on the MRI
scan had an increased mortality rate.
• Meningeal gadolinium enhancements on MRI and
seizures were associated with an increased risk of
relapse.
• Involvement of larger or rather proximal cerebral
vessels seems to be associated with a higher mortality
rate and poorer prognosis, requiring a more
aggressive treatment.

58. Disease monitoring
• Combination of repeated neurological examinations and periodic
neuroradiological imaging (e.g. MRI and MRA) during therapy and
afterwards is recommended for assessing disease activity.
• MRI should be performed 4–6 weeks after the initiation of therapy and
afterwards every 3–4 months in the first year of treatment.
• CSF examinations can additionally be helpful in the follow up to
document improvement in the inflammatory response.
• In patients with severe clinical course and worsening neurological
symptoms, serial conventional angiography might be necessary.
• Color duplex sonography might be useful for follow-up examinations
in patients with cerebral artery stenoses