Transcript Effects of Immunomodulating Agents on Relapses and Disability in

中枢神经系统血管炎
James Jinxing Wang, MD, PhD
Clinical Assistant Professor
University of TN
Memphis, TN
[email protected]
Classification of CNS vasculitis
INFECTIOUS VASCULITIS
--------
Spirochetal (syphilis)
Mycobacterial
Fungal
Rickettsial
Bacterial (purulent) meningitis
Viral
Other organisms
NECROTIZING VASCULITIDES
-- Classic polyarteritis nodosa
-- Wegener’s granulomatosis
-- Allergic Angitis and granulomatosis (ChurgStrauss)
-- Necrotizing systemic vasculitis-overlap syndrome
-- Lymphomatoid granulomatosis
VASCULITIS ASSOCIATED WITH
COLLAGEN VASCULAR DISEASES
-----
Systemic lupus erythematosus
Rheumatoid arthritis
Scleroderma
Sjogren’s syndrome
GIANT CELL ARTERITIDES
-- Takayasu’s arteritis
-- Temporal (cranial) arteritis
VASCULITIS ASSOCIATED WITH OTHER
SYSTEMIC DISEASES
------
Behcet’s disease
Ulcerative colitis
Sarcoidosis
Relapsing polychondritis
Kohlmeier-Degos disease
HYPERSENSITIVITY VASCULITIDES
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Henoch-Schonlein purpura
Drug-induced vasculitides
Chemical vasculitides
Essential mixed cryoglobulinemia
MISCELLANEOUS
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Vasculitis associated with neoplasia
Vasculitis associated with radiation
Cogan’s syndrome
Dermatomyositis-polymyositis
X-linked lymphoproliferative syndrome
Thromboangiitis obliterans
Kawasaki syndrome
PRIMARY CNS VASCULITIS
History
 1922
Harbitz’s first report.
 1959 Gravioto and Feigin’s extensive
autopsy descriptions
 1970s Primary CNS angiitis, Granulomatous
angiitis of the CNS, isolated CNS angiitis.
 1980s High dose steroid and
Cyclophosphamide started.
 Prognosis is very poor without treatment.
Mortality is almost 100% without treatment
Pathology of the isolated CNS
vasculitis
The essential feature is a giant cell,
granulomatous inflammation of the
small arteries and veins, which exhibits
a nearly constant affinity for the vessels
of the leptomeninges and the branches
that arise from them to penetrate the
cortex.
 The size is 2-300 micron.

Animal Models
Intrvanous
injection of Mycoplasma
gallisepticum in turkeys produced similar
damage as human vasculitis.
Clinical Presentation
AUTOPSY
BIOPSY
SYMPTOMS OR
CASES
CASES
SIGNS
(N = 45)
(N = 26)
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Altered mentation
Headache
Hemiparesis
Stupor or coma
Dysphasia
Seizures
“Eye signs”
Paraparesis
Ataxia
Fever
Papilledema
Weight Loss
39
29
20
19
14
13
15
11
8
8
9
8
76%
64
44
42
31
29
33
24
18
18`
20
18
11
13
11
4
11
8
3
4
9
3
1
0
42%
50
42
15
42
31
12
15
35
12
4
0
Diagnostic Testing-1

Labs: CBC




Anti-BM abs, ANCA, ACE, SSA, SSB, FANA, RF,
Cryoglobulin, etc
ESR, C-reactive protein
Normal ESR for man is age/2, for women is (age
+10)/2.
Corrected ESR = ESR – (standard Hct-actual Hct)
x 1.75. Standard Hct is 45 for man, 42 for women.
Initial ESR (n=47)
Less than 20 mm/hr
 21-40
 41-60
 61-80
 >81

22
14
7
3
1
47%
30%
15%
6%
2%
Diagnostic studies for CNS
vasculitis
TEST
SENSITIVITY
ESTIMATED SPECIFICITY
CT
33-50%
(even lbiopsy-proven cases)
Data not available
no pathognomonic findings
MRI
50-100%
(It approaches 100% in histologically confirmed cases,
and is lowest in those diagnosed
only by angiography)
Data not available
no patholognomonic findings
ANGIography
30-100%
(It is less than 40% in
histologically confirmed
cases, and 100% in reports
not supported by histology)
BIOPSY
75%
(The negativity can be due
to the patchy nature of the
disease and small tissue
sample
22%
Assessed in only one study but
may be higher if vasculitis is
secondary to other causes are
excluded)
80%
The same pattern of inflammation
can be due to other causes
“VASCULITIS” Look-Alikes on Cerebral Angiography
____________________________________________
CONDITION
AUTHOR(S)
___________________________________________________________
Neoplastic angioendotheliosis
Witt et al.
Spasm after subarachnoid hemnorrhage
Ferris and Levine
Atherosclerosis
Ferris and Levine
Oral contraceptive use
Irey et al.
Hypertension
with pheochromocytoma
ALrmstrong and Hayes,
Postpartum
Garner et al.
Eclampsia
Trommer, Homer, and
Migraine
Schon and Harrison
Postcoital headache (?)
Kapoor, Kendall,
Trauma
Suwanwela and
Surgical manipulation of intracranial arteries
Khodadad
“Reversible cerebral segmental vasoconstriction” Call et al.
Sumatriptan and isometheptane
Diagnostic Testing-3
 CSF:
Very sensitive, but not specific
 90% abnormal
Differential Diagnosis









1. CVA
2. MS
3. Infection
4. Tumor
5. Specific / systemic vasculitis
6. Toxic
7. Leukodystrophy
8. MERRF, MELAS
9. Hypertensive encephalopathy
7-26-08
8-3-08
7-26-08
7-26-08
7-26-08
82 y/o WF with no
PMH
admitted because of
MS change
MELAS DNA testing
MELAS 3243-tRNA leu 3243G
MELAS 3271-tRNA leu T3271C
MELAS 3252-tRNA leu A3252G
MELAS 3256-tRNA leu C3256T
MELAS 3291-tRNA leu T3291C
MELAS 13,513-ND5 G13513A
Treatment for CNS vasculitis
CYTOXIC AGENT
CORTICOSTEROIDS
_____________________________________________
Induction
therpay
4 – 6 mo
Maintenance
therapy
6 – 24 mo
Escalation
therapy
Cyclophosphamide 2mg/kd daily
by mouth (max 150mg); lower
dose by 25mg if >60 years WBC
must be >4.0 x 10 /1
Azathioprine 2mg/kg daily
Prednisolone 1mg/kg daily
(max 80mg); Reduce weekly to
10mg/day by 6 months
Prednisolone 5 - 10mg/day
MTX
Acute severe disease with creatinine >500 umol/1 or pulmonary
hemorrhage; Consider 7 – 10 plasma exchange treatment over 14
days such that 60 ml/kg of plasma is exchanged for 4.5% or 5% human
albumin solution or consider three pulses of methylprednisolone, 15 mg/kg
daily for 3 days. These patients (if under 60 years) may also require 2.5mg/kg
daily of cyclophosphamide.
Thank you!