The document describes various types of vasculitis that can affect the nervous system. It discusses several systemic necrotizing arteritis conditions like polyarteritis nodosa, Churg-Strauss syndrome, and microscopic polyangiitis. It also covers hypersensitivity vasculitis conditions, systemic granulomatous vasculitis like Wegener's granulomatosis, and vasculitis associated with connective tissue disorders or infections. For each condition, it provides details on pathology, clinical manifestations, neurological involvement, and diagnostic criteria.

1. Dr. Parag Moon
Senior resident,
Dept. of Neurology,
GMC, Kota.

2.  Spectrum of clinicopathological disorders
characterized by inflammation of blood
vessels, including arteries and veins of
varying caliber
 Result in variety of clinical neurological
manifestations related to ischemic injury of
central nervous system (CNS) and peripheral
nervous system (PNS).

3.  Systemic necrotizing arteritis
◦ Polyarteritis nodosa
◦ Churg–Strauss syndrome
◦ Microscopic polyangiitis
 Hypersensitivity vasculitis
◦ Henoch–Schonlein purpura
◦ Hypocomplementemic vasculitis
◦ Cryoglobulinemia
 Systemic granulomatous
vasculitis
◦ Wegener granulomatosis
◦ Lymphomatoid granulomatosis
◦ Lethal midline granuloma
 Giant cell arteritis
◦ Temporal arteritis
◦ Takayasu arteritis
 Connective tissue disorders
associated with vasculitis
◦ Systemic lupus erythematosus
◦ Scleroderma
◦ Rheumatoid arthritis
◦ Sjogren syndrome
◦ Mixed connective tissue disease
◦ Behcet disease
 Inflammatory diabetic
vasculopathy
 Isolated peripheral nervous
system vasculitis
 Granulomatous angiitis of the
nervous system

4.  Vasculitis associated with
infection
◦ Varicella zoster virus
◦ Spirochetes
◦ Treponema pallidum
◦ Borrelia burgdorferi
◦ Fungi
◦ Rickettsia
◦ Bacterial meningitis
◦ Mycobacterium tuberculosis
◦ HIV-1
 Central nervous system
vasculitis associated with
amphetamine abuse
 Paraneoplastic vasculitis

5.  Polyarteritis nodosa
 Necrotizing arteritis and nodules in small-
and medium-sized vessels of heart, liver,
kidney, pancreas, testicles, brain, nerves,
skeletal muscles sparing lungs and spleen.
 Dominant neurological picture-peripheral
neuritis with predilection for legs in 50 %
 Three quarters-lesions in arteriae nervorum
in post mortem studies.
 Clinically apparent brain infarcts-10%

6.  Histological lesions-mononuclear cell infiltration,
necrosis of internal and external elastic lamina of
media, fibrin deposition, perivascular
inflammation of adventitia, and intimal
proliferation ->narrowing of arterial lumina.
 Focal deposition of perivascular connective
tissue, vascular necrosis, and denuding of
endothelium occur
 Followed by vascular thrombosis, ischemia,
aneurysm formation, rupture, and hemorrhage.

7. Multiple small cortical and subcortical
regions of increased signal-infarcts in
distribution of small arteries.
Third, or proliferative-chronic inflammatory cells
replacing neutrophils of second phase; evidence
of necrosis of media, early intimal proliferation
(arrowheads), and fibrosis. Lumen is
almost completely occluded.

8.  Microscopic polyangiitis
 Differs from PAN in affliction of small arterioles,
capillaries, and venules of lungs and kidney with
necrotizing glomerulonephritis.
 Circulating antinuclear cytoplasmic
autoantibodies (ANCA), usually myeloperoxidase
or perinuclear ANCA (p-ANCA)-80%
 Epineurial arteries involvement-polyneuropathy
mononeuritis multiplex (MNM) type in 1/4th
 Skin nodules and purpura in majority.

9.  Churg-Strauss syndrome
 Syndrome of asthma, eosinophilia, extravascular
granulomas, and necrotizing vasculitis of small
and medium arteries, arterioles, capillaries, and
veins.
 Angiitis and extravascular necrotizing
granulomas with eosinophilic infiltrates.
 Granulomas located near small arteries and veins
 Characterized by palisading epithelioid
histiocytes arranged around central necrotic
zones in which eosinophils predominate.

10.  Three phases.
1. Prodromal period of constitutional symptoms
(rhinitis and asthma).
2. Peripheral blood and tissue eosinophilia
3. Systemic vasculitis
 Three fourths have neurological involvement
similar to PAN
 Typically peripheral neuropathy of MNM type,
stroke, and hemorrhage.
 Laboratory diagnosis-myeloperoxidase or p-
ANCA seropositivity, and tissue biopsy.

11.  Unique predilection for dermis
 Inflammatory infiltrates-extravasation of
erythrocytes, pronounced endothelial swelling,
andinfiltration by PMN and later mononuclear
cells, with resultant fibrosis.
 Involves arterioles, capillaries and postcapillary
venules.
 Resultant nuclear fragments or leukocytoclasia
and fibrinoid necrosis (termed leukocytoclastic
vasculitis [LCV]) and circulating immune
complexes deposit in skin and vasculitic lesions.
 Lesions-same stage of evolution.

12. Leucocytoclastic vasculitis- Entire vessel and perivascular tissue
are infiltrated with polymorphonuclear leukocytes and some
chronic inflammatory cells with necrosis and nuclear debris with
vascular lumen nearly obliterated

13.  Drug-related vasculitis
 20% of dermal vasculitis cases.
 Clinical spectrum varies from urticaria,
wheezing, and rhinitis; variable serum
sickness to laryngeal edema; and
hypotension.
 Rash mostly maculopapular or vesicular—less
often palpable purpura— along arms and legs
 More severe drug reactions-multiple organ
involvement.

14.  Results from focal deposition of immune
complexes developed from covalent binding
of offending drug or its metabolites with
native or foreign proteins to produce hapten
molecules.

15.  Serum sickness
 Varying degrees of infiltration of arterioles,
capillaries, and venules with interstitial
inflammation by PMN cells, eosinophils, and
mononuclear cells.
 Urticaria followed by erythematous or
maculopapular rash, petechiae, palpable
purpura, and lymphadenopathy
 Accompanied by arthralgia, edema, headache,
and lethargy.

16.  Nervous system-
◦ brachial plexus neuritis,
◦ mononeuritis simplex and multiplex,
◦ Guillain-Barre´ syndrome,
◦ cranial nerve palsies,
◦ blurring of vision,
◦ retinal and palpebral hemorrhages,
◦ meningismus,
◦ stroke,
◦ myelopathy.
 Immune complex disease

17.  Henoch-Schonlein purpura
 Nonthrombocytopenic purpura, arthralgia,
abdominal pain, leukocytoclastic vasculitis of
skin lesions
 Affected child-fever, headache, anorexia.
 Palpable purpuric lesions-extensor surfaces
of lower extremities and buttocks
 Associated with migratory angioneurotic
edema of hands, scalp, face, lower legs, and
genitalia.
 Deposits of immunoglobulins particularly IgA
and C3-kidney and blood vessel walls

18.  Hypocomplementemic vasculitis
 Urticaria, migratory arthralgia, and persistent
or intermittent hypocomplementemia.
 Sometimes severe angioneurotic edema and
life-threatening laryngeal edema
 Conjunctivitis, episcleritis, uveitis, mild renal
disease, pericarditis, abdominal pain,
splenomegaly.

19.  Pseudotumor cerebri-most common
neurological manifestation.
 Immunological-binding of IgG antibody to
C1q along basement membranes with
complement activation.

20.  Cryoglobulinemia
 Reversibly precipitate at below 37degree
 Composed of IgG and IgM, complement,
lipoprotein and antigenic protein moieties.
◦ Type I-single monoclonal IgM or IgG antibody
◦ Type II-mixed, has monoclonal IgM possessing
activity against polyclonal IgG
◦ Type III-mixed polyclonal and non-immunoglobulin
 Types I and II-lymphoproliferative diseases,
particularly multiple myeloma and
Waldenstrom macroglobulinemia.
 Type III-infection and collagen vascular
diseases

21.  Four vascular lesions
 (1) occlusion of small and large vessels in type I or II;
 (2) bland thrombosis of small arteries and arterioles
 (3) endothelial swelling, proliferation, and basement
membrane thickening
 (4) LCV.
 Peripheral nerves-chronic axonopathy of
large myelinated fibers.
 Dermatitis, palpable purpura heralded by a
sharp or burning sensation.
 PNS and CNS-more common with types II and
III.

22.  Cryoprecipitation-cause of ischemia of arterioles
and capillaries due to hyperviscosity and direct
plugging of small vessels.
 CNS manifestations-vascular occlusion with or
without vasculitis.
 Peripheral neuropathy-epineurial vasculitis,
cryoprecipitate deposition, microvascular
ischemia with resultant secondary axonopathy.
 Inflammatory cell infiltrate-mainly T cell with
lesser numbers of B lymphocytes

23.  Isolation of HCV RNA in peripheral nerve
biopsies-unsuccessful.
 Presence of cryoglobulinemia, bone marrow
studies, nerve biopsy, studies for HCV, HIV,
occult cancer, infection, plasma cell
dyscrasia, CVD

24.  Wegener granulomatosis.
 Triad-necrotizing granulomatous lesions of
sinuses and lower respiratory tract, systemic
necrotizing vasculitis of small arteries and
veins, and glomerulonephritis
 WG lesions begin as minute foci of granular
necrosis and fibrinoid degeneration with PMN
cells followed by histiocytes and giant cells
along margins of granulomas

25.  One fourth- CNS involvement
 Direct destruction of nerve or brain tissue by
necrotizing granulomas
 Necrotizing arteritis of cerebral and arteriae
nervorum of peripheral nerves.
 Multifocal pain, sensory loss, and weakness
due to MNM
 Circulating c-ANCA directed against
proteinase 3.

26.  Stroke, intracerebral and subarachnoid
hemorrhage, optic neuritis
 Contiguous extension from nasal and
paranasal sinus cavity granulomas-
pseudotumor with exophthalmos, extraocular
muscles, optic nerve involvement
 Extension through temporal bone-middle ear.

27. Muscular artery nearly completely destroyed. A large confluent area of fibrinoid
degradation is surrounded by neutrophils, palisading histiocytes, lymphocytes,
plasma cells, and some giant cells

28.  Lymphomatoid granulomatosis.
 Malignant lymphoreticular disorder with
strong predilection for CNS.
 Present with constitutional symptoms and
skin lesions resembling erythema nodosum.
 Focal neurological-MNM, unilateral cranial
nerve palsies, hemiparesis, ataxia, seizures,
spinal and radicular syndromes, myopathy.

29.  CNS-invasion of unifocal and multifocal necrotizing
angiocentric and angiodestructive lesions of small-
and medium-sized muscular arteries and their
endothelia by masses of T cells, plasma cells,
histiocytes, and atypical lymphoreticular cells
 Immunoblast formation-cerebrum, brain stem,
cerebellar parenchyma, meninges

30.  Lethal midline granuloma.
 Relentlessly invasive necrotizing process of
nose and palate that causes destruction of
sinuses and all major midline structures of
head
 Producing grotesque facial mutilation and
ultimately death.
 CNS complications-direct invasion of orbit
and face, jugular vein, and sigmoid and
cavernous sinuses leading to vascular
thrombosis, sepsis, meningitis.

31.  Temporal arteritis-older adult whites of either
gender and involves medium and large
arteries.
 Headache, scalp tenderness, thickened
nodular and pulseless superficial temporal
artery, unilateral visual loss, jaw claudication
 Along branches of external carotid artery and
arteritis of vertebral and carotid arteries
typically at end points of dural investment.
 Biopsy of temporal artery

32.  Takayasu arteritis-aorta and its branches in
young Asian women.
 Obliterative lesions in large arteries such
aorta and its major branches.
 Dizziness, syncope, subclavian steal, carotid
sinus syndrome, stroke, amaurosis fugax,
corneal opacification, cataracts, claudication
and gangrene of limbs, chest and abdomen
angina.

33. A, Early lesion of a arge muscular artery, necrosis, inflammation, and giant cell formation (single arrow) seen immediately
adjacent to internal elastic lamina (arrowhead), which is undergoing degenerative changes, some intimal proliferation (double
arrows)
B, More advanced lesion-complete segmental destruction of internal elastic lamina and virtually the entire media (arrows).
Marked intimal proliferation has nearly occluded lumen, and few inflammatory cells remain.

34.  Granulomatous angiitis of the nervous system
 Nearly exclusive neurological manifestations
 Headache, mental change, pleocytosis and
elevated protein content in CSF with signs of
angiographic beading that precede focal seizure
and stroke
 Untreated-coma and death.
 Can occur in association with cell arteritis,
sarcoidosis, varicella-zoster virus, lymphoma,
amyloid angiopathy,HIV infection.
 Diagnostic biopsy of brain and overlying
meninges
 From named cerebral vessels to medium and
small leptomeningeal vessels

35. A, Media and adventitia of this small leptomeningeal artery completely replaced by multinucleated giant cells (arrowheads). Intimal
proliferation with obliteration of vascular lumen and a dense, perivascular, mononuclear inflammatory infiltrate
B, Larger leptomeningeal vessel-necrosis of media and internal elastic lamina with multinucleated giant cell formation (arrows),
intimal proliferation (arrowhead), lymphocytic infiltration of the adventitia and neighboring meninges

36.  Systemic lupus erythematosus.
 True vasculitis-present in only 10%
 Atinuclear antibody (ANA) screen-
homogenous pattern in majority
 Antibodies to native double- stranded DNA
(anti-dsDNA) and reactivity to the Smith (Sm)
and ribonucleoprotein (RNP)
 Antiphospholipid antibodies (APA) (lupus
anticoagulant (LAC) and anticardiolipin (aCL)
antibody)-prothrombotic events

37. Small vessel within brain parenchyma-largely necrotic. Abundant fibrin
(darkly stained) is evident in vessel walls and surrounding tissues. A few
chronic inflammatory cells indicate the presence of vasculitis

38.  Scleroderma.
 Diffuse fibrosis affecting firstskin and later
systemic organs and nervous system.
 Vascular lesions-
 increased collagen deposition sclerosis, and hyalinization
 proliferation of endothelium, fibrosis of adventitia and
intima, and duplication and fraying of internal elastic
membrane
 progressive luminal obliteration
 Associated with HLA-DQb1 & mediated by three
autoantibodies (anticentromere, anti-SCL-70 or
topoisomerase, anti-RNA polymerase III)
 CREST syndrome

39. Digital artery-severe intimal hyperplasia and greater than 90% luminal
narrowing. Severe adventitial fibrosis and marked telangiectasia of vasa
vasorum is seen, media and internal elastic lamina are relatively spared

40.  Rheumatoid arthritis.
 Three forms of vasculitis occur
1. Proliferative endarteritis of few organs, notably heart,
skeletal muscle, and nerves characterized by
inflammatory infiltration of all layers of small arteries
and arterioles, with intimal proliferation, necrosis, and
thrombosis.
2. Fulminant vasculitis indistinguishable from PAN
3. LCV with palpable purpura, arthritis, cryoglobulinemia,
and low complement levels.
 Nonvasculitis spinal and epidural involvement-
vertebral collapse, subluxation, and direct
narrowing of spinal canal due to rheumatoid
pannus.

41.  Sjogren syndrome
 Keratoconjunctivitis sicca and xerostomia.
 Two types of vasculitis
1. LCV of skin with palpable purpura, urticaria,
erythematous macules, and papules
2. Resembles PAN with muscle, nerve, CNS, visceral
vascular involvement without aneurysm formation.
 Associated with extractable RNA proteins Ro
or SS-A and intranuclear RNA-associated
antigen La or SS-B.

42.  Mixed connective tissue disease.
 Clinical and histopathological features of SLE,
scleroderma, and polymyositis
 Proliferative vascular changes, capillary
involvement, and mild tissue fibrosis.
 Behcet’s disease.
 Triad of oral and genital ulcers, uveitis, and
vasculitis
 Cutaneous, retinal, and CNS vasculitis.
 Direct inflammation of neuraxis-focal brain stem
meningoencephalitis.

43.  Purulent bacterial meningitis
 Mycobacterial
 Treponema pallidum
 Borrelia burgdorferi
 Varicella zoster
 Fungal-Aspergillus, Candida, Coccidioides,
mucormycosis
 HIV-associated granulomatous angiitis of
brain, eosinophilic temporal arteritis,
vasculitic meningoencephalitis, MNM
resembling PAN

44.  Parenteral drug use
 Necrotizing arteritis of polyarteritis type
 Amphetamine, cocaine, phenypropanolamine
and opioids, alone or in combination.

45.  Paraneoplastic encephalomyelitis, sensory
neuronopathy, high anti-Hu antibody titers
 Transmural inflammation of epimysial and
epineurial vessels on muscle and nerve
biopsy
 Mostly seen with cancer of lung, kidney,
prostate, lymphoma.

46.  Blood Studies
 Complete blood count
 Erythrocyte sedimentation rate
 Chemistry panel-creatine phosphokinase
 Antinuclear antibody
 Complement levels
 Rheumatoid factor

47.  Cryoglobulins
 Immunofixation electrophoresis
 Quantitative immunoglobulins
 Antibodies (selectively) to: Ro (Sjogren
syndrome [SS]-A), La (SS-B), Smith (Sm), SCL-
70, hepatitis B and C virus, human
immunodeficiency virus type 1, Borrelia
burgdorferi (ELISA, Western blot), c-ANCA, p-
ANCA

48.  Electroencephalography
 Electromyography and nerve conduction
studies
 Cerebrospinal fluid analysis: protein, glucose,
cell count, immunoglobulin G level, cytology,
VDRL, gram stain, culture, India ink; viral
antigens, Lyme Ab, PCR (as indicated)

49.  MRI
 Multiple bilateral cortical and deep white matter
signal abnormalities and enhancement of
meninges after gadolinium.
 MR angiography-useful in evaluation of medium
and large-vessel disease but misses fine-vessel
contours
 DSA-Beading of vessels-found only in 1/3rd with
histologically proven CNS vasculitis, as well as in
CNS infection, atherosclerosis, cerebral
embolism, and vasospasm of diverse causes.
 Multiple microaneurysms-rare in CNS vessels.

50. Ectasia and beading in M1 segment and lack of flow in the A1
segment of the right anterior cerebral artery (arrow).

51. (a) MRangiography showing basilar
artery narrowing with irregularity
(long arrow) and abrupt cut off of
the right vertebral artery (short
arrow)..
(b) Angiogram showing narrowed
left internal carotid artery.

53.  Muscle and nerve biopsy
 Temporal artery biopsy
 Meningeal and cortex
 Skin
 Systemic organs
 Lymph nodes

54.  Immunomodulating agents
◦ IvIg
 Immunosuppresants
◦ Corticisteroids
◦ Cyclophosphamide
◦ Azathioprine

55.  Physical therapy and orthosis-to maintain range
of motion and strength, to improve function
status, and to maintain ambulation.
 Effective pain management- tricyclic
antidepressants, gabapentin, mexiletine, opioids,
clonazepam, and topical anesthetic creams
 Limit ischemic enhancing effects of other
conditions,
 such as diabetes mellitus, hypertension and
hyperlipidemia
 Cessation of cigarette smoking.

56. THANK YOU

57.  NEUROVASCULITIS; Younger, David
S;CONTINUUM: Lifelong Learning in Neurology:;
Feb 2005:Vol11 - Issue 1:11-42
 Central nervous system vasculitis; Rula A. Hajj-
Alia, Leonard H. Calabrese: Current Opinion in
Rheumatology 2009, 21:10–18
 Central nervous system vasculitis:Neil J. Scolding:
Semin Immunopathol (2009) 31:527–536
 Vasculitis of the nervous system: David S.
Younger: Current Opinion in Neurology 2004,
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