Primary central nervous system vasculitis (PACNS) is a rare disorder characterized by inflammation of blood vessels within the brain and spinal cord. It can be classified as granulomatous or atypical based on biopsy findings. Common symptoms include headache, seizures, strokes, and cognitive or neurological deficits. Diagnosis involves neuroimaging showing vessel inflammation or infarction, and ruling out other causes. Treatment is typically high-dose corticosteroids. Other CNS vasculitides can be secondary to infections like varicella zoster virus or systemic conditions like giant cell arteritis that affect larger vessels. Reversible cerebral vasoconstriction syndrome is a related disorder of reversible cerebral artery constriction causing similar symptoms.

1. CNS VASCULITIS
Dr Sankalp Mohan
Senior Resident
Neurology
GMC, Kota

2. VASCULITIS
 The vasculitides are defined by the presence
of inflammatory leukocytes in vessel walls
with reactive damage to mural structures.
 Compromise of the lumen leads to
downstream tissue ischemia and necrosis
 Pathogenetic mechanisms – immune
complex deposition , invasion of endothelial
cells by microorganisms , autoantibodies
,granuloma formation

3. CLASSIFICATION OF VASCULITIS
• Takayasu
• Giant Cell ArteritisLarge vessel
• PAN
• Kawasaki s disease
• Primary CNS vasculitis
Medium vessel
• Microscopic Polyangiitis
• Churg Strauss Syndrome
• Wegner s Granulomatosis
Small Vessel

4. CNS VASCULITIS

5. CLASSIFICATION
Primary angiitis of the CNS
(PACNS) when it is confined to
the CNS.
Secondary when associated
with various other disorders.
Reversible cerebral
vasoconstriction syndromes

6. PRIMARY CENTRAL NERVOUS SYSTEM
VASCULITIS (PACNS)
 . Defined as inflammation of the cerebral
vasculature without angiitis in other organs
 affects small- and medium-sized arteries of
the brain parenchyma, spinal cord, and
leptomeninges
 1. Granulomatous angiitis of the CNS
(GACNS)
 2. Atypical PACNS

7. GRANULOMATOUS ANGIITIS OF THE CENTRAL
NERVOUS SYSTEM
 20% of all patients with PACNS
 male-predominant (2:1)
 at any age mean age at diagnosis is 42
years,
 long prodromal period insidious onset of
symptoms

8. PATHOLOGY
 Langerhans or foreign body giant cells,
necrotizing vasculitis, or lymphocytic
vasculitis
 Atypical PACNS –biopsy is not
granulomatous , only lymphocytic infiltrate
 vessels to become narrowed, occluded and
thrombosed – ischemia
 In contrast to systemic vasculitides, the
finding of aneurysms in the cerebral arteries
is rare

9. PATHOGENESIS
 The cause of PACNS is unknown
 Infection — Infectious agents, particularly
mycoplasma and viruses
 varicella zoster virus, West Nile virus
 HIV infection can cause both a CNS
vasculitis and a CNS vasculopathy that is
associated with aneurysm formation
 Amyloid angiopathy

10. CLINICAL MANIFESTATIONS
 characterized by a long prodromal period
 Signs and symptoms of systemic vasculitis,
such as, fever, weight loss, or rash, are
usually lacking.
 highly variable and nonspecific
 PACNS should be suspected when strokes,
more often recurrent, occur in young patients
& unexplained diffuse neurologic dysfunction

11.  Decreased cognition — 83 percent
 Headache — 56 percent
 Seizure — 30 percent
 Stroke — 14 percent
 Cerebral hemorrhage — 12 percent
 Angiitis affecting the spinal cord usually
presents as a myelopathy /spinal cord
infarction

12. PROPOSED THE CRITERIA FOR THE DIAGNOSIS
OF PACNS.
 The presence of an acquired and otherwise
unexplained neurologic deficit and with
 (a) the presence of either classic angiographic or
histopathologic features of angiitis within the
CNS, and
 (b) no evidence of systemic vasculitis or any
condition that could elicit the angiographic or
pathologic features

13. DIAGNOSTIC TESTS
 erythrocyte sedimentation rate (ESR) and C-
reactive protein (CRP) are usually normal
 Serologic evaluation
 Antinuclear antibodies
 Rheumatoid factor
 Antibodies to the Ro/SSA, La/SSB, Sm, and RNP
antigens
 Antibodies to double-stranded DNA
 Antineutrophil cytoplasmic antibodies (ANCA)
 Serum C3 and C4
 Serum cryoglobulins

14.  Testing for infections appropriate to the
clinical circumstances
 Lumbar puncture –
 CSF is abnormal in 80 to 90 percent of
patients with pathologically documented
disease. There are no specific abnormalities
of the CSF in PACNS.
 excluding any infectious or malignant
process
 RCVS – CSF normal

15. NEUROIMAGING
 MR imaging =
 single or multiple, may include infarcts (both
white and gray matter) and hemorrhage, and
may be tumor-like
 Nonspecific high-intensity T2WI/FLAIR lesions
in white matter present in 42 percent of
Secondary vasculitis (low specificity )
 MR angiography — The resolution of MR
angiography (MRA) remains inadequate for the
demonstration of vasculitic changes

16. NEUROIMAGING
 Angiography
 positive findings if focal or diffuse areas of
arterial stenosis, occlusion, dilatation, or
beading were detected
 findings of ectasia and stenosis referred to as
"beading", usually in the small arteries
 sensitivity of angiography in biopsy proven
PACNS cases was only 60 percent
 Thus, a negative angiogram cannot be used to
exclude the diagnosis of PACNS.

17.  Brain and leptomeningeal biopsy

21. REVERSIBLE CEREBRAL VASOCONSTRICTION
SYNDROMES
 group of disorders linked by prolonged but
reversible vasoconstriction of the cerebral
arteries
 severe, acute-onset headaches
 Ischemic stroke and/or hemorrhage associated
with reperfusion may occur in the setting of
RCVS.
 pheochromocytoma and poorly-controlled
hypertension can also be associated with
cerebral vasospasm and clinical presentations
that mimic PACNS.

22. RCVS AND PACNS
 Symptom onset
 Clinical setting
 Reversibility of angiographic findings
 Cerebral spinal fluid (CSF)

23. SYSTEMIC VASCULITIS INVOLVING THE BRAIN
 systemic vasculitides,
 connective tissue disease (CTD),
sarcoidosis,
 infections,
 and lymphoproliferative diseases.

24. INFECTIOUS CAUSES
1. VZV -associated cerebral angiitis
 affects older age groups
 disease tends to be more localized
 Cerebral angiographic findings of segmental,
unilateral involvement of the vessels in the
distribution of the middle cerebral artery/ICA
 Diagnosis -higher antibodies levels of VZV in
the CSF than in the serum
 positive VZV PCR in the CSF

25.  (35%) of pathologic findings of AIDS-
associated CNS disease demonstrate
encephalitis, leptomeningitis, and/or
vasculitis,
Treponema pallidum – neurosyphilis
 most common in patients with HIV infections
 Meningitis and meningovascular disease are
the usual manifestation.
 May present as stroke

26.  CNS vasculitis associated with hepatitis C
virus (HCV) without underlying
cryoglobulinemia

27. SYSTEMIC VASCULITIDES AFFECTING CNS
 Temporal Arteritis
 Takayasu s Arteritis
 Wegener Granulomatosis
 Henoch Scholein Purpura
 Polyarteritis Nodosa

28. TEMPORAL ARTERITIS
 >50 years age .Women >men
 Transmural inflammation of arteries .intimal
hyperplasia
 Branches of ECA – sup temporal most common
 ICA ,Subclavian ,coronary and intracranial
 Systemic features fatigue, weight loss , anorexia
- Headche (new onset )unilateral localised to
areas of scalp ,Jaw claudication,scalp
tenderness
- -Neuropathy – Median nerve
- ,TIA and stroke

29.  Cranial neuropathies – AION .23 % of cases
 Temporary or permanent blindness
 Posterior ciliary arteritis
 Diagnosis – anemia ,High Esr ,CRP
 Angiography – stenotic segments or complet
occlusions
 Biopsy – Transmural inflammation,occlusion
 Sensitivity – 70 %
 Treatment – Prednisolone -40 -80 mg /day >high
dose for a month then taper .50% by one
month.1mg/month

30. POLYARTERITIS NODOSA
 Medium vessel vasculitis
 40 -60 yrs . Asso - Hep B,C ,cryoglobulinemia
 Inflammation of PMN, Monocytes – Fibrinoid necrosis
 Most common neurologic manifestation –
Mononeuritis multiplex
 CNS- 20 % - 40 %.diffuse encephalopathy ,focal
..infarcts in spinal cord ,brainstem.Rarely ICH,
 Optic neuropathy (AION)
 CNS abnormalities are late -after systemic signs and
PN

31.  Diagnosis – Clinical
 Multisystem involvement –Skin ,PN, Renal
,GIT
 Fever ,weight loss ,anemia raised ESR
 Angiography – may show saccular or
fusiform aneurysms
 Treatment – Systemic steroids with cytotoxic
agents – cyclophosphamide azthioprine

32. TAKAYASU S ARTERITIS
 10 -30 yrs of age .women more commonr ,fatigue ,anoreixa
 Aorta and its branches innominate,common carotid ,subclavian
,abdominal aorta ,celiac ,mesentric
Symptoms –
 Acute stage – low grade fever
 Stage of acute inflammation – Vascular Bruits ,diminished
pulses,hypertension
 Chronic phase- Claudication ,ischemic ulcers
Neurologic – Headche ,syncope blurred vision .
DIAGNOSIS –Arteriography – occlusion or dilatation/Stenosis
aneurysm of entire aorta or its primary branches
 TREATMENT – Prednisolone 1mg/kg /d for 3 months –taper
In unsuccesful cases cyclophosphamide ,MTX

33. WEGNER S GRANULOMATOSIS
 More in men 40 yrs
 Small and medium sized vessels
 Necrotizing granulomatous lesion in upper ,lower
respiratory tract , Kidneys
 50 % develop neurologic involvement
 Most have recurrent mononeuropathies,mononeuritis
multiplex, Cranial neuropathies II,VI,VII
 Ischemic stroke ,encephalopathy ,granulomatous
basilar meningitis , pachnymenigitis – less frequently

34.  Diagnosis –Clinical picture with c-ANCA
 Radiographically confirmed vasculitis of the
CNS in Wegener’s granulomatosis is rare,
because the small vessel
 MR findings – Dural thickening and
enhancement hyperintense brainstem
signals
 Treatment – corticosteroids plus
cyclophosphamide/azathioprine

35. BEHCET S DISEASE
 Oral ulcers ,Genital ulcers and Uveitis,Skin
finding ,(folliculitis and erythema nodosum
),Thrombophlebitis
 Neurologic involvement occurs in 6-10 %

36. CONNECTIVE TISSUE DISORDERS
 CTDs that can involve the CNS include
 Sjogren’s syndrome, rheumatoid arthritis,
mixed CTDs,
 and dermatomyositis

37. NEUROLOGIC MANIFESTATIONS OF SYSTEMIC
LUPUS ERYTHEMATOSUS
 seen in 10 to 80 percent of patients
 Direct involvement of CNS
 Secondary to complications of disease
/Treatment

38.  PATHOPHYSIOLOGY
 initially thought to be due to vasculitis.
 vasculopathy is characterized by a small to
moderate perivascular accumulation of
mononuclear cells, without destruction
 Accelerated atherosclerosis may contribute
to the risk of stroke
 Autoantibodies — The demonstration of a
number of autoantibodies including APLA

39.  Secondary factors — Prospective studies
suggest that from 50 to 78 percent of neurologic
episodes are caused by secondary factors
[ 2,35 ], including:
 Infections associated with immunosuppressive
therapy
 Metabolic complications of other organ system
failure, such as uremia
 Hypertension
 Toxic effects of therapy (particularly
corticosteroids)

40. COMMON CLINICAL SYNDROMES

41. REFERENCES
 CNS Vasculitis in Autoimmune Disease: MR Imaging
Findings and Correlation with Angiography --
AJNR 1999 20: 75-85
 Central nervous system vasculitis - Rula A. Hajj-Alia and
Leonard H. Calabreseb -, Cleveland Clinic, Cleveland, Ohio,
USA ; Current Opinion in Rheumatology 2009, 21:10–18
 Neurology Clinics –Neurology and systemic Disease . Feb
2010,vol28
 Caplan’s – Stroke –A clinical approach 4th edition ,Chapter
11-Non atherosclerotic vasculopathies
 www.uptodate.com