vasculitis syndrome in neurology

1. PRIMARY VASCULITIS
SYNDROMES IN
NEUROLOGY
Prashant shringi
Senior resident
Neurology

2. Vasculitis
• Vasculitis constitute a heterogeneous group of diseases
characterized by inflammation and necrosis of the blood
vessel wall.
• Result in variety of clinical neurological manifestations
related to ischemic injury of central nervous system (CNS)
and peripheral nervous system (PNS).

4. International Chapel Hill Consensus
Conference(2012) in the Nomenclature of Vasculitis

7. Epidemiology
• Overall incidence of primary vasculitis is about 40/
1,000,000 persons
• Excluding giant cell (temporal) arteritis
• Incidence of GCA is much higher (around 200/1,000,000
persons in the age group(>50 years).

8. When to suspect vasculitis ?
• Age and sex of the patient- female ,middle age
• often unfold slowly over weeks or months, and frequently
mimic other more common disorders
• History of risk factors for viral hepatitis
• Other infectious exposures
• History of another diagnosis that may predispose to
vasculitis (eg; malignancy or connective tissue disease)

9. Constitutional symptoms
• Fevers
• sweats
• Decreased appetite
• weight loss
• Fatigue, weakness, malaise
• Arthralgias, myalgias
• Abdominal pain

10. Red-flag examination findings
• Mononeuritis multiplex
• Unexplained ischemic events out of proportion to risk
factors
• Glomerulonephritis,
• Chronic inflammatory sinusitis
• Palpable purpura.

11. Neurological Manisfestations
• Headache
• Cranial nerve affections
• Encephalopathy
• Seizures
• Psychosis
• Myelitis
• Stroke
• Intracranial haemorrhage
• Aseptic meningoencephalitis

12. General diagnostic approach
Is this a condition that could mimic the presentation of
vasculitis?
Is there a secondary underlying cause?
What is the extent of vasculitis?
How do I confirm the diagnosis of vasculitis?
What specific type of vasculitis is this?

14. Cont.mimickers

15. Diagnosis
• Comprehensive clinical history and clinical examination
• Laboratory test
• Imaging
• Histopathological examination-gold standard

16. Laboratory tests in suspected vasculitis

17. IMAGING
• CTA
• MR WITH MRA
• PET SCAN
• DSA
• Colour duplex sonography

19. • In large-vessel angiitis digital subtraction angiography
(DSA) is the gold standard for the demonstration of vessel
stenosis or aneurysms
• MRI performed with and without contrast medium is the
investigation of choice to detect and monitor cerebral
involvement
• 18-fluorodeoxyglucose positron emission tomography
(PET) is very sensitive in revealing inflamed vessels

20. Primary angiitis of the central nervous system
(PACNS)
• PACNS is a rare disease with approximately 700 cases
published worldwide
• Most patients are between 40 and 60 years old at the time
of diagnosis
• Most cases underlying pathophysiology is not known
• Granulomatous angiitis affecting the nervous system non-
granulomatous histologies have been reported recently
• Clinical symptoms include headache, non-focal and less
frequently focal neurological signs

21. Diagnostic criteria for PANCS

24. Angio Negative Biopsy positive PCNSV:
• Prominent Cognitive dysfunction
• Raised concentrations of CSF protein
• Meningeal or parenchymal enhancing lesions on MRI
• Favourable response to treatment
• Good outcome
Biopsy-positive PCNSV with evidence of cerebral amyloid
angiopathy:
• Granulomatous histopathological pattern plus vascular deposits of
amyloid β
• PCNSV pts with Amyloid are older than those without
• High frequency of cognitive dysfunction
• Enhancing meningeal lesions on MRI
• Monophasic disease course
• Good response to immunosuppressive treatment

25. Lab, EEG, Imaging
• Usually all tests are normal – ESR, ANA, ENA profile, S CRP
• CSF- Abnormal in 80-90%, increased protein concentration
and mild pleocytosis
• CSF pleocytosis is modest, rarely exceeding 250
cells/μL.
• EEG- diffuse slowing

26. Biopsy
• Cerebral and meningeal biopsy : gold standard for diagnosis :
Transmural vascular inflammation of leptomeningeal or
parenchymal vessels
• Optimum biopsy: samples of dura, leptomeninges, cortex, and
white matter
• Negatve biopsy doesn’t rule out- skip lesions.
• Sensitivity: Calabrese et al – 53%, Salvarani etal - 63%, French
cohort – 62%( 50-75%)
Duna GF, Calabrese LH. Limitations of invasive modalities in the diagnosis of primary angiitis of the
central nervous system. J Rheumatol 1995; 22: 662–67
Miller DV, Salvarani C, Hunder GG, et al. Biopsy fi ndings in primary angiitis of the central nervous
system. Am J Surg Pathol 2009; 33: 35–43

27. PCNSV

33. Reversible Cerebral Vasoconstriction
Syndrome
• Acute onset – monophasic usually; severe headache (thunder
clap)
seizures and FND
• Mainly women
• Mean age - 45 years.
• 60% in post-partum period / exposure to vasoactive drugs
• Csf: Normal
• Complications : localised SAH (22%)
• Angiography : String of bead appearance constriction of cerebral
arteries – (Irregular arterial stenosis/multiple occlusion – s/o
PCNSV)
• RESOLUTION- 12 weeks

35. Treatment –PCNSV
• Steroids –oral predinslone /iv MPS
• Cyclophosaphamide
• Azathiopirone
• Mycofenolate mofetil
• Rituximab

36. MMF treated – had less severe disability at last follow-up compared
to those receiving other therapies (p = 0.023), and receiving CYC
+ prednisone(p = 0.017)
(Median followup:26months ; range 0-7.4 yrs MMF vs 11.3 months CYC+Pred)
Salvarani C, Brown RD Jr, Christianson TJ, et al. Mycophenolate mofetil in primary central nervous system
vasculitis. Semin Arthritis Rheum 2015; 45:55–59

38. Polyarteritis Nodosa
• Polyarteritis Nodosa (PAN) is the most common systemic
vasculitis that affects the CNS
• Highest prevalence occurs in the fifth and sixth decades
of life
• young people are usually not affected
• Most common neurological manisfesation- peripheral
neuropathy (60%)

39. Fibrinoid necrosis of the internal and external elastic
lamina leads to the destruction of the vessel wall and
consequent formation of microaneurysm and luminal
obliteration

40. • PAN may be associated with hepatitis virus (HV) infection.
• PAN with and without HV association differ in aspects of
clinical course, outcome and response to treatment
• Peripheral nerve involvement in particular is more
prevalent in HV-associated PAN
•

41. • Signs of a systemic illness with fever, malaise and weight
loss,accompanied by arthritis and skin signs.
• Mononeuritis multiplex – M/C P.N.
• DSPN,cutaneous neuropathy

42. • Brain involvement has been reported in up to 20% of patients
• 1) diffuse encephalopathy characterized by cognitive
impairment, disorientation or psychosis (8% to 20%)
• 2) seizures (focal or generalized)
• 3) focal neurologic deficits
• Rosenberg MR, Parshley M, Gibson S, Wernick R. Central nervous system polyarteritis
nodosa. West. J. Med. 1990;153:553–556

43. PAN

44. PAN
• Treatment
Classical PAN HV PAN
Steroids
antiviarals plus steroids
CYC

46. Giant cell arteritis (GCA)
• Cranial or temporal arteritis (TA) is a chronic,
granulomatous vasculitis of large- and medium sized
arteries
• Women are affected more frequently than men (3 : 1 to 5 :
1)
• Mean age at the beginning of the disorder is 65 years

47. • Giant cell arteritis results from granulomatous vessel wall
infiltration of large arteries
• Temporal arteritis may be diagnosed by Doppler
ultrasonography
• Vessel wall edema may be visualized by ultrasound as a
characteristic and highly sensitive concentric
hypoechogenic mural thickening - ‘‘halo sign’’
• Duplex ultrasound, sensitivity is 87% and specificity is
96%

49. Clinical symptoms of GCA
signs of a systemic illness with fever, malaise and weight
loss
polymyalgia rheumatica
New onset of a persisting headache
 jaw claudication
visual symptoms,such as diplopia, scotoma and
amaurosis fugax
blindness as a dreaded complication
 rarely stroke

50. C.F.

51. • High sensitivity of MRI in giant cell arteritis In particular,
vessel wall changes
• On clinical examination, a tenderness or decreased
pulsatility of the temporal arteries
• Laboratory findings reveal a raised ESR and increased
values of CRP.
• BIOPSY – gold standard
• High-dose corticosteroids are the only effective therapy in
TA.

55. Takayasu’s arteritis
• Second variant of giant cell arteritis (GCA) affects people
younger than 50 years
• Rare granulomatous panarteritis of the aorta and its major
branches
• Resulting in localized stenoses, vascular occlusion and
aneurysm formation
• Female predominant
• Pulseless disease

56. • Arthralgia, fever, fatigue, headaches, rashes and weight
loss
• Usually diagnosis is delayed until the occlusive stage
leads to ischemic symptoms of the extremities or to
stroke.
• Visual disturbances or visual loss, syncope, transient
ischemic attacks and stroke(<10%)

58. • DSA still is the gold-standard investigation for the
diagnosis of Takayasu’s arteritis
• Glucocorticoids and immunossupressive agents are
mandatory to induce and maintain remission

59. • An interventional approach in Takayasu’s arteritis should
only be considered if stenotic or occlusive lesions lead to
significant hemodynamic effects, or if aneurysmal
enlargement results in the risk of rupture or dissection

62. Wegener granulomatosis
• Small vessel arteritis is frequently associated with
cANCA/PR3 and sometimes with MPO-ANCA.
• Men are affected twice as often as women.
• Systemic necrotizing vasculitis involving small arteries
and veins leads to affections of the lung and kidney

63. • Neurologic involvement in WG has been described in 3-9
% of patients
• Cranial nerve palsy, polyneuropathies, myelopathies
ischemic stroke, hemorrhages and encephalopathy with
or without seizures
• cANCA/PR3 are present in 70% of patients with limited
WG and in >90% of systemic WG cases.

64. • Limited stage of the disease, necrotizing granulomas of
the nose and the paranasal sinuses may lead to
compression of neighborhood structures with cranial
nerve lesions
• Cranial nerves (M/c)- 2, 3,4, and 6 are affected most
frequently
• Nonseptic meningitis with enhancement of the basal
meninges the development of an obstructive or
communicating hydrocephalus

66. From: Central nervous system involvement of granulomatosis with polyangiitis: clinical–radiological
presentation distinguishes different outcomes
Rheumatology (Oxford). 2014;54(3):424-432. doi:10.1093/rheumatology/keu336
Rheumatology (Oxford) | © The Author 2014. Published by Oxford University Press on behalf of the British Society for
Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

68. RAVE Trial
• Rituximab (RAVE- Rituximab in ANCA associated
Vasculitis ) trial showed that Rtx is not inferior to CYC in
remission induction and superior to CYC in pts with
relapsing disease

69. Microscopic polyangiitis
• Differs from PAN in affliction of small arterioles,
capillaries, and venules of lungs and kidney with
necrotizing glomerulonephritis.
• C-ANCA, usually myeloperoxidase or p-ANCA -80%
• Epineurial arteries involvement-polyneuropathy ( M/C)
• Mononeuritis multiplex - 1/4th
•
• Headache, stroke ,seizures ,TIA

71. Behcet’s Disease- Neurobechet
syndrome
• Multisystem, chronic-relapsing vasculitis affecting
predominantly the venous system.
• Recurrent oral ulcerations must be present in combination
with at least two of the following:
• Recurrent genital ulceration, eye lesions (uveitis, retinal
vasculitis),
• skin lesions (erythema nodosum)
• positive pathergy test result.

72. • CNS involvement (Neuro Behcet or NB) occurs in about 30%
of patients after an average of 5 years.
• Of these, 80% present parenchymal NB with motor tract signs,
stroke and headache
• Brainstem is predominantly involved
• Pseudotumour is the most frequent presentation of sinus
thrombosis and present in 20% of NB patients.
• Only 3% of patients develop neurologic symptoms without
mucocutaneous lesions or ocular symptoms

73. • No specific test
• In NB, combinations of high doses of corticosteroids and
immunosuppressive drugs are recommended.
• Prednisone is started with daily parenteral pulses of
1000mg for 3-5 days followed by oral therapy starting at 1
mg/kg daily

75. Churg Strauss syndrome (CSS)
• Necrotizing small-vessel vasculitides
• Clinically patients present with a history of allergic
diathesis and asthma
• Pathologic hallmark of the disease are eosinophil-rich
granulomas.
• pANCA/MPO are present in 40% of patients

76. • In ANCA-positive patients most coomon neurological
symptoms – mononeuritis multiplex
• associated with the histologic detection of small vessel
vasculitis
Symmetrical polyneuropathies possibly caused by
eosinophil infiltrates are seen in the ANCA negative group

77. • CNS involvement observed in 8-14 % of patients
• Cerebral infarctions (M/C)
•
• Intracerebral hemorrhages and subarachnoid
hemorrhages frequent manifestations

80. Cryoglobulinemia
• 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- M/C CNS involement
• Type III-mixed polyclonal and non-immunoglobulin
• Most of the cases associated to hepatitis C virus
infection.

81. SUMMARY
• Vasculitis should be included in the differential diagnosis
for any patient presenting with unexplained constitutional
symptoms and red-flag examination findings
• Differential diagnosis of vasculitis is broad and includes
any systemic disease process, the first step in evaluation
is exclusion of multisystem mimickers.
• Therapy is aimed at inducing and maintaining remission
of disease activity and preventing complications arising
from treatment
• Regular monitoring of both disease activity and adverse
effects from treatments is critical to successful patient
care

82. • 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
Encephalopathy, stroke, transient ischemic attacks,
lacunar infarctions and hemorrhage
Peripheral neuropathy-epineurial vasculitis

83. References
• M alba et al; Central Nervous System Vasculitis: Still More
Questions than Answers, Curr Neupharmaco 2011 Sep;
9(3):437448.doi: 10.2174/157015911796557920
• Martina Wengenroth et al;S. Hähnel (ed.), Inflammatory
Diseases of the Brain, Medical Radiology. Diagnostic
Imaging,DOI: 10.1007/174_2012_661, Springer-Verlag
Berlin
• Diagnosis and treatment of cerebral vasculitis; Peter
Berlit:Ther Adv Neurol Disord(2010) 3(1) 2942,DOI:
10.1177/1756285609347123

84. • An Approach to theEvaluation and Management of
Vasculitis:Nathan Houchenset al:Hosp Med Clin - (2014)
http://dx.doi.org/10.1016/j.ehmc.2014.03.004
• Primary Angiitis of the Central Nervous System; Grégoire
Boulouis et al, Stroke. 2017;48:00-00. DOI:
10.1161/STROKEAHA.116.016194
• Bradleys Neurology , 7 edition