Seminars in Cerebrovascular Diseases and Stroke Vol. 1 No.

3 2001

Noninfectious Cerebral Vasculitis in Children

ALFREDO M. LOPEZ-YUNEZ and BHUWAN R GARG
Indianapolis, Indiana

ABSTRACT
The vasculitides are a heterogeneous group of disorders. Vasculitides secondary to infectious
diseases are more common than those attributable to noninfectious causes, especially in
developing countries. Cerebral vasculitides might be a primary disorder or complicate a
systemic disease. We review the clinical presentation, pathology, and treatment of noninfec-
tious vasculitides in children. Henoch-Sch6nlein purpura and Kawasaki disease are two of the
most common vasculitic disorders in children. Noninfectious cerebral vasculifis is a rare
cause of stroke in childhood. Mimics of vasculitis (look-alikes) should be considered
whenever cerebral vasculitis is suspected.
Key words: cerebral vasculitis, angiitis, cerebrovascular disease, childhood stroke.

The cerebral vasculitides are a group of heterogeneous
disorders that share a central pathologic feature of
inflammation of the blood vessel wall. Tissue injury
follows vascular lumen compromise, resulting in impair-
ment of blood flow and subsequent tissue ischemia;
alternatively, tissue damage might be secondary to hem-
orrhage caused by disruption of the vessel wall. Vascu-
litis associated with infections is discussed elsewhere in
this issue of Seminars in Cerebrovascular Diseases and
Stroke. Noninfectious cerebral vasculitis can be idio-
pathic or secondary to a variety of systemic illnesses.
(Table 1). We review the noninfectious vasculitides that
can be symptomatic in childhood.
Most of the vasculitides have been reported in child-
hood; some, such as Henoch-Schtnlein purpura (HSP) and
Kawasaki disease (KD), are predominantly restricted to
this age group. 1 Vasculitides are infrequent in childhood.
Incidence figures vary widely perhaps because of lack of
definite diagnostic criteria. In the 1990s, better understand-
ing of pathogenic mechanisms led to the development of
new classification criteria. The Chapel Hill Consensus
From the Department of Neurology, Indiana University School of
Medicine, Indianapolis, IN.
Address reprint requests to Alfredo M. Lopez-Yunez, MD, Depart-
ment of Neurology, Indiana University School of Medicine, 1050 Wal-
nut St. 6th Floc~r, Indianapolis, IN 46202. E-mail: alopezl @iupui.edu
Copyright 9 2001 by W.B. Saunders Company
1528-9931/01/0103-0007535.00/0
doi:10.1053/scds.2001.27097
Conference on the Nomenclature of Systemic Vasculitis 2
based its definitions on clinical and histologic features and
the size of the vessel involved. Table 2 shows a classifica-
tion of the main vasculitides according to vessel size.
The cerebral vasculitides are an uncommon cause of
stroke in children. Schoenberg et al 3 did not find any case
of vasculitis in children with cerebrovascular disease
younger than 14 years old. Similarly, no case of cerebral
vasculitis was encountered in the French prospective
study of cerebrovascular disease in children under 16
years old. 4 In our institutional review of stroke in the
young, we found that 4% of strokes among children
younger than 16 years old were caused by vasculitis. 5
Clinical manifestations of cerebral vasculitis are pro-
tean. Childhood cerebral vasculitis should be considered
in the differential diagnosis of recurrent ischemic strokes
in cases with multiple strokes; when strokes are associ-
ated with encephalopathic changes; when strokes are
associated with constitutional symptoms (fever, anemia,
weight loss, fatigue) or elevated erythrocyte sedimenta-
tion rate, skin or mucosal lesions, renal disease, or
multifocal neurologic signs. Neurologic manifestations
are related at least to some degree to the size of vessels
involved by various types of vasculitis. Stroke and other
neurologic symptoms might be the initial manifestation
of vasculitis or complicate the course of a previously
diagnosed systemic illness.
A comprehensive history and thorough general physi-
cal and neurologic examinations are essential. Appropri-

249
250 Seminars in Cerebrovascular Diseases and Stroke Vol. 1 No. 3 September 2001

Table 1. Noninfectious Conditions Associated With Cerebral organ biopsy, can be diagnostic. In some cases, espe-
Vasculitis in Children cially when the central nervous system (CNS) is the only
Necrotizing vasculitides target organ involved, biopsy o f the meninges and gray
Polyarteritis nodosa and white matter might be necessary. Diagnosis is
Wegener's granulomatosis especially challenging when there is isolated nervous
Churg-Strauss syndrome
Microscopic polyangiitis system involvement. Confirmation of a specific diagnosis
Hypersensitivity vasculitides requires a high index of suspicion based on clinical
Henoch-Sch6nlein purpura presentation, complemented with the judicious and se-
Drug-induced vasculitides
Chemical vasculitides quential use of ancillary testing. Tables 3 and 4 list some
Giant cell arteritides useful investigations and special laboratory tests.
Takayasu's arteritis
Juvenile temporal arteritis
Vasculitides associated with collagen vascular disease
Systemic lupus erythematosus
Necrotizing Vascu|itides
Rheumatoid arthritis
SjOgren's syndrome Polyarteritis Nodosa (PAN)
Mixed connective tissue disease
Scleroderma PAN is an uncommon systemic necrotizing vasculitis
Polymyositis/dermatomyositis of medium or small arteries. Older children develop
Vasculitides associated with other systemic diseases fever, hypertension, abdominal pain, and arthritis. Infants
Beh~et's disease might present clinical findings similar to KD. 6 Peripheral
Sarcoidosis
Ulcerative colitis neuropathy classically manifested as mononeuritis mul-
X-linked lymphoproliferative syndrome tiplex might occur in up to 75% of patients. Cerebral
Kohlmeier-Degos disease complications occur in 20% to 40% of PAN patients and
Miscellaneous vasculitides
Kawasaki syndrome usually appear later in the course of disease. Pathoge-
Goodpasture's syndrome netic mechanisms include hypertensive vascular disease,
Post-streptococcal chronic vaso-occlusive changes, and, less frequently,
Graft-versus-host disease segmental inflammation of the vessel wall.
Relapsing polychondritis
Cogan's syndrome Diffuse CNS involvement can occur as a result of
Primary vasculitides metabolic derangements or hypertension. Focal neuro-
Primary central nervous system angiitis logic deficits result from cerebral infarction, intracerebral
hemorrhage, or subarachnoid hemorrhage after rupture
of microaneurysms. Cranial neuropathies result from
retinal or optic nerve vasculitis, involvement of choroidal
ate laboratory tests and ancillary procedures should be vessels, or inflammation of the arteries supplying cranial
performed in a systematic manner to arrive at a correct nerves III, IV, or VI. Optic neuritis with temporal artery
diagnosis (Table 3). Magnetic resonance imaging (MRI) enlargement, associated with multiple ischemic changes
scan might show multiple lesions, some of them clini- on MRI and microaneurysms detected by renal and
cally unsuspected. Magnetic resonance angiogram mesenteric angiography have been reported in a 9-year-
(MRA) of the aortic arch and large vessels may show old Haitian girl and in a 16-year-old German girl. 7
stenosis or occlusion; however, M R A is not helpful in Patients received prednisone and cyclophosphamide with
vascutitis involving small vessels (ie, HSP, microscopic partial response and had significant neurologic sequelae
polyangiitis, Behqet's disease). Catheter angiography is characterized by quadriplegia and impaired vision.
preferred in these cases. Cerebrospinal fluid (CSF) might Cerebral infarctions are more frequent than brain
be normal or show elevated protein content and mild hemorrhages; however, when intracranial hemorrhage
pleocytosis. Tissue biopsy, including skin and other (ICH) and subarachnoid hemorrhage (SAH) occur, the

Table 2. Vasculitides Types According to Involved Vessel Size

Vessel size HSP WG CSS PACNS PAN RV GCA TA MPA KD
Small ++ ++ ++ ++ _ ++ _ _ ++
Medium + ++ ++ ++ ++ ~+ + _ ++ ++
Large - + + + ++ ++ _ +

Abbreviations: HSP, Henoch-Sch6nleinpurpura: WG, Wegener's granulomatosis: CSS. Churg-Strauss syndrome; PACNS, primary angiitis of CNS;
PAN, polyarteritis nodosa; RV. rheumatoid vasculitis: GCA, giant cell arteritis: TA. Takayasu's arteritis: MPA, microscopic polyangiitis; KD,
Kawasaki disease.
++, common; +, uncommon; -, no involvement.
 Noninfectious Cerebral Vasculitis in Children 9 Lopez-Yunez and Garg 251

Table 3. Ancillary Testing in Suspected Cerebral Vasculitis (1951) 9 and Henson (1956) 1~ reported necrotizing vas-
culitis from PAN in cases of SAH with involvement of
Fluorescent treponemal antibody absorption (FI'A-Abs)
Human immunodeficiency vires serology cerebral and spinal radicular arteries respectively.
Hepatitis B surface antigen (HbsAg) Although both clinical and laboratory criteria are evolv-
Hepatitis C antibody ing, the diagnosis of PAN remains largely dependent on
Erythrosedimentation rate (ESR)
C-reactive protein angiography and biopsy. Cerebral angiography shows ar-
Antinuclear antibody (ANA), extractable nuclear antigens (Sm, terial beading, vessel occlusion, or aneurysm formation,
nRNP, anti ds DNA, only if ANA+) which correlates pathologically with inflammation of
Rheumatoid factor
small- and medium-sized arteries at the point of bifurca-
C3, C4, CHso
Coombs' test fion. 11 Corticosteroids are the mainstay of treatment, and
Serum immunoglobulin levels most children respond to it. 12 Refractory cases benefit
Anti SS-A, anti SS-B antibodies from cyclophosphamide. Clinical and angiographic
Shirmer's test
Scl 70 antibody (anti-isomerase antibody) follow-up are important to guide long-term management.
Anticentromere antibody
Neutrophilic cytoplasmic antibody (ANCA) Wegener's Granulomatosis
c-ANCA directed against proteinase 3-specific and sensitive for
WG Wegener's granulomatosis is a necrotizing, granulo-
p-ANCA directed to myeloperoxidase-less specific, found in CSS, matous vasculitis of small- and medium-sized vessels
MPA that typically involves the upper airways, lungs, and
Antiphospholipid antibodies
Cryoglobulins
kidneys. Children are rarely affected. Patients, usually
Drug screen adults, seek medical attention most commonly for rhi-
Serum angiotensin-converting enzyme (ACE) norrhea, epistaxis, chronic sinusitis, dyspnea, hoarseness,
Chest radiograph cough, wheezing, and other symptoms of tracheal or
Gallium-67 scanning
Paranasal sinus radiographs/computed tomography parenchymal lung disease. Fever and malaise are com-
Skin test for allergy mon. Evidence of glomerulonephritis is often found on
Pulmonary function tests (spirometry, lung volumes, diffusing investigation. Other manifestations include visual com-
capacity)
CSF examination plaints related to conjunctivitis, scleritis, corneal disease,
Routine cell count, differential, protein, glucose always uveitis, optic neuritis, retinal vasculitis, and retinal artery
AFB stain, culture, viral culture, ACE, cytology/flow cytometry occlusion. Children can present with skin manifestations,
optional
Brain MRI and MRA
including palpable purpura. 13 Other neurologic manifes-
Catheter angiography tations include seizures, multiple cranial neuropathies,
Visceral: renal, hepatic, mesenteric peripheral neuropathy, mononeuritis multiplex, and
Aortic arch stroke. 14-17Laboratory investigations reveal the presence
Four-vessel cerebral angiography
Tissue biopsy of cytoplasmic pattern antineutrophil cytoplasm antibod-
Systemic ies (c-ANCA) in 90% of cases (Table 4). Lung biopsy
Leptomeningeal/cortical brain biopsy has the highest positive yield to provide a histologic
Adapted from Cohen and Biller. 45 diagnosis. Diagnostically useful biopsy specimens also
can be obtained from paranasal sinuses.
High-dose corticosteroids in addition to low-dose
cyclophosphamide for at least one year are used in
prognosis tends to be considerably worse. Ford 8 de- treating Wegener's granulomatosis. A staged regimen
scribed four patients with ICH and one with SAH; no appears to be effective, while minimizing toxicity. With
evidence of cerebral vasculitis was presented. Griffith this approach, patients are treated in the active phase

Table 4. Some Helpful Laboratory Investigations in Selected Vasculitides

Disease Laboratory Investigation

Isolated CNS vasculitis
Churg-Strauss syndrome
Wegener's granulomatosis
Polyarteritis nodosa
Microscopic polyangiitis
Temporal arteritis
Takayasu's arteritis
Sj6grens syndrome
Elevated ESR, CSF - - modest pleocytosis and protein elevation; multiple, bilateral infarcts on MRI; segmental
narrowing or occlusion in multiple vascular distribution on cerebral angiography (aneurysms may be present)
Eosinophilia; p-ANCA; antibody to myeloperoxidase; extravascular eosinophils on biopsy
c-ANCA; antibody to proteinase 3
Leukocytosis; anemia; elevated ESR and factor VIII-related antigen; positive hepatitis B surface antigen
p-ANCA; antibody to myeloperoxidase
Elevated ESR; giant cell pervascular inflammatory infiltrate on superior temporal artery biopsy
Elevated ESR and factor VIII-related antigen
Anti SSA (Ro) and SSB (La) antibodies; + ANA and rheumatoid factor
252 Seminars in Cerebrovascular Diseases and Stroke Vol. 1 No. 3 September 2001
with steroids and cyclophosphamide until disease remis-
sion is reached. At this time, methotrexate is substituted
for cyclophosphamide for long-term treatment. Metho-
trexate might be contraindicated in some patients with
liver disease, renal insufificiency, or chronic severe pul-
monary impairment. Some patients also might require
prophylaxis against Pneumocystis carinii with trimetho-
prim/sulfamethoxazole. 14
Churg-Strauss Syndrome
Churg-Strauss Syndrome is characterized by small- to
medium-sized vessel vasculitis and extravascular necro-
tizing granulomas with eosinophilic infiltrates in the set-
ring of asthma or allergic rhinitis. 18 The systemic vascu-
lifts itself might be granulomatous or nongranulomatous
and involves arteries, arterioles, capillaries, and venules.
Pulmonary and systemic vessels are involved. It is a rare
type of vasculitis, although in one report 21% of patients
were children. ~9 Lung, heart, kidney, and peripheral
nerves are commonly affected. The American College of
Rheumatology criteria for the diagnosis of Churg-Strauss
syndrome include: asthma, eosinophilia, history of al-
lergy, mononeuropathy or polyneuropathy, migratory pul-
monary infiltrates, paranasal sinus abnormality, and ex-
travascular eosinophils on biopsy. Four of these criteria
are required for diagnosis. Diagnosis is suggested in a
patient with asthma who becomes febrile and has weight
loss, eosinophilia, and pulmonary infiltrates; the presence
of neuropathy is virtually diagnostic, and the presence of
perinuclear ANCA (p-ANCA) and antibodies to myelo-
peroxidase confirms the diagnosis. 2~
CNS involvement in children is extremely rare. A
13-year-old girl who presented with chorea has been
reported. 23 Likewise, a 14-year-old boy with Churg-
Strauss syndrome presented with prolonged fever, weight
loss, sinusitis, myalgias and arthralgias, testicular pain,
pulmonary infiltrates, pericardial effusion, peripheral
neuropathy, and eosinophilia. His clinical course was
further complicated by seizures attributable to cerebral
vasculitis. 24 In adults, peripheral neuropathy has been
reported in 64% to 75% of cases and most often occurs
as mononeuritis multiplex. Intracranial and subarachnoid
hemorrhage, convulsions, optic neuritis, and other cra-
nial neuropathies have been reported. 21 Most patients
respond to glucocorticoids. Cyclophosphamide is recom-
mended among nonresponders. 22'25
Microscopic Polyangiitis
Microscopic polyangiitis (MPA) is a necrotizing vas-
culitis, usually involving small vessels. Pathologically,
MPA is indistinguishable from PAN except that in PAN
there is absence of vasculitis in vessels other than arter-
ies, whereas arterioles, capillaries, and venules are in-
volved in MPA. There is little or no immune complex
deposition; hence it also is called the pauci-immune vas-
culitis. Absence of granulomatous inflammation differen-
tiates it from Wegener's granulomatosis. Patients with
MPA commonly have fever, weight loss, and arthralgias
early in the course of the disease. 26S
Clinical manifestations almost always include a rap-
idly progressive glomerulonephritis that might result in
renal insufficiency. Pulmonary involvement (especially
pulmonary hemorrhage) with renal involvement is char-
acteristic of this condition. Patients also might have
conjunctivitis, scleritis, uveitis, purpura, abdominal pain,
diarrhea and bleeding, myalgias, arthralgias, and arterial
hypertension. Peripheral and cranial nerve involvement
has been reported in 57% of adult patients; CNS involve-
ment has been reported in nearly 12% of adult patients.
Laboratory diagnosis is facilitated by the presence of
p-ANCA and antibodies to myeloperoxidase in 40% to
80% of cases, in addition to the characteristic histology.
Treatment is with corticosteroids and cytotoxic agents
such as cyclophosphamide.2s
Hypersensitivity Vasculitides
Henoch-Sch6nlein Purpura
HSP is a postcapillary venullitis producing the classic
manifestations of palpable purpura, arthralgias, glomem-
lonephritis, abdominal pain, and bleeding. 29 The median
age of onset is 5.5 years, with 93% of patients being less
than 10 years old. Incidence of HSP is 10:100,000
children/year. 3~ Symptoms usually occur over a period of
hours after the onset of an upper respiratory infection or
some other acute infection. HSP is frequently self-limited
and does not require therapy; however, a small percent-
age of cases are complicated by renal, intestinal, or CNS
involvement. HSP is an immune complex-mediated vas-
culitis following infection with bacteria (tuberculosis,
Streptococci, and Helicobacter pylori, among others) or
viruses (Coxsackie B1, Parvovirus B19, Hepatitis B and
C). It has also been associated with cocaine abuse 31 and
has been described as a paraneoplastic syndrome. 32'33
Immunoglobulin A (IgA) deposition has been found in
involved vessels.
HSP typically starts with a palpable purpura over the
buttocks and legs. Abdominal pain usually follows
within hours or days. Severe gastrointestinal and renal
involvement might occur, especially in patients with
severe skin manifestations, increasing age, and decreased
factor XIII activity. CNS involvement can manifest as
diffuse encephalopathy or seizures. Many cases follow a
pattern consistent with posterior reversible leukoen-
cephalopathy rather than a vasculitic pattern. Patients
might present with transient cortical blindness and sei-
zures with typical reversible parieto-occipital hyperin-
tensities on T2-weighted MRI of the brain. 34-36
Cerebral infarction associated with HSP has been
described. 37 We have cared for a patient in whom HSP
 Noninfectious Cerebral Vasculitis in Children
was associated with antiphospholipid antibodies. 38 Our
patient was a 15-year-old girl with a basal ganglia
infarction associated with a transient IgA antiphosphati-
dylethanolamine antibody in serum and CSF, showing
the need to perform a thorough search for the presence of
concomitant prothrombotic factors in HSP patients with
cerebral ischemic complications. Few cases of intracere-
bral hemorrhage also have been reported in association
with HSP. 39-41 These patients may present with seizures,
hemiparesis, and decreased level of consciousness. Brain
hemorrhages are usually lobar and located in the parietal
and occipital lobes. They are most often associated with
underlying severe systemic involvement and hemor-
rhagic lesions in other organs including testicles, gas-
trointestinal tract, and kidneys.
Most cases of HSP respond to small doses of cortico-
steroids, although close clinical surveillance is mandatory
because they might mask peritonitis in children with ab-
dominal pain. Patients with progressive renal disease or
CNS involvement require more aggressive therapy. The
combination of high-dose corticosteroids and azathioprine;
pulse methylprednisolone followed by oral prednisone; or
triple therapy with oral prednisone, oral cyclophospha-
mide, and dipyridamole are all r e a s o n a b l e options. 42"43
Chen described a 7-year-old girl with HSP who developed
cerebral vasculitis after treatment with pulse intravenous
methylprednisolone and oral prednisone and who re-
sponded to plasma exchange. She presented with seizures,
retinal artery occlusion, and parieto-occipital ischemic
changes associated with progressive loss of consciousness,
all of which improved after plasma exchange. This thera-
peutic modality can be used as rescue therapy when stan-
dard immunosuppressive therapy fails. 44
Drug-Induced Vasculitides
Cerebral vasculitis associated with illicit drugs can
cause cerehrovascular complications by inducing severe
hypertension, vasospasm, and (less frequently) cerebral
vasculitis. Most of these drugs are sympathomimetics.
Amphetamines and cocaine are the most commonly
involved drugs. Other implicated drugs include pentazo-
cine, pyribenzamine, ephedrine, and phenylpropanola-
mine. 45 This last compound has been banned recently in
the United States because of its association with ICH in
young patients.
Hypersensitivity vasculitides have been described in
cases of amphetamine and cocaine abuse. In addition,
systemic necrotizing angiitis indistinguishable from PAN
has been described in 14 patients who had used meth-
amphetamine. 46 Intracerehral hemorrhage can occur af-
ter intravenous, oral, or intranasal amphetamine use.
Cerebral infarction and ICH have been associated with
cocaine abuse at any age, including neonates born of
mothers who used drugs during pregnancy. Other poten-
tial causes of cerebrovascular complications must be
9 Lopez-Yunez and Garg 253
excluded, especially infective endocarditis or foreign
body embolism in intravenous crack cocaine users.
Treatment consists of abstaining from the offending
drugs. Corticosteroids are probably not indicated.
Giant Cell Arteritides
Takayasu's Arteritis
Takayasu's arteritis (TA) is a chronic large-vessel
arteritis of unknown etiology that affects mostly the
aorta, its main branches, and the pulmonary artery. TA is
a relatively rare disease of young women, with an
estimate in North America of 2.6 cases per million. 47 TA
occurs more frequently in women (9:1 female to male
ratio), with at least one third of cases occurring in
patients under 20 years old. 48"49 Lupi-Herrera et al4s
have found a high frequency of positive purified protein
derivative lymphadenopathy and a histologic appearance
similar to caseating granulomas, raising a possible link to
atypical mycobacterial infections.
TA is usually discovered during the evaluation of a
young girl with severe hypertension, although many
patients present with fever and malaise. Children with
TA tend to develop arthritis and congestive heart failure
more often than adults.
TA can be divided into an acute inflammatory phase
and a chronic, pulseless, or sclerotic phase. Children might
recover spontaneously from the acute inflammatory phase
and go on to slowly develop vascular involvement with
multiple stenotic lesions and saccular aneurysms. Symp-
toms reflect the site of involvement. Pulmonary artery in-
volvement can be fatal. Aortitis compromising the aortic
root might lead to myocardial infarction. Subclavian ar-
tery involvement can result in the classic "pulseless dis-
ease," arm claudication, or finger clubbing. Audible bruits
are present in the abdominal aorta or the carotid arteries,
and at least one arterial pulse is absent in a neck or limb
vessel in up to 90% of patients.
Cerebral complications associated with TA can occur
from hypertensive encephalopathy secondary to renovas-
cular hypertension, or direct intracranial vessel involve-
ment. 5~ Headaches are the most common neurologic
symptom, followed by dizziness or syncope. Less than
10% of patients have cerebrovascular complications but
they are the most important cause of serious morbidity
and mortality. 52 Kohrman described a 6-month-old girl
with partial seizures, hemiparesis, and a pulseless arm.
Computed tomography (CT) confirmed a left cerebral
infarction and cerebral angiography showed dilatation of
the aortic root, stenosis of the origin of both common
carotid arteries, beading of the descending aorta, and
aneurysm of the fight sinus of Valsalva. Treatment with
prednisone and azathioprine resulted in resolution of
neurologic deficits and angiographic improvement. 51
254 Seminars in Cerebrovascular Diseases and Stroke Vol. 1 No. 3 September 2001
Subclavian steal syndrome, a well-known complication
of TA in adults, has not been described in children.
Diagnosis of TA requires a high degree of clinical sus-
picion. Patients usually have an elevated erythrocyte sedi-
mentation rate, mild anemia, and widening of the medi-
astinum with or without aortic irregularities on plain chest
radiographs. Catheter angiography is essential to confirm
the diagnosis and should include evaluation of the aortic
arch and the brachiocephalic branches and mesenteric and
renal arteries. High-dose prednisone remains the first line
of treatment; however, for long-term management, the
current tendency is to use adjunctive therapy with azathio-
prine 1 mg/kg/d, cyclophosphamide 0.5 to 2 mg/kg/d, or
methotrexate up to 10 mg/m2/wk as steroid-sparing
agents. 53 These approaches have decreased mortality rates
from 35% to 70% to less than 5%.
Juvenile Temporal Arteritis
Temporal arteritis is extremely rare in childhood and
uncommon among patients younger than 50 years old.
Lie 54 described 4 children with temporal nodules and
giant cells on temporal biopsy consistent with juvenile
temporal arteritis. An 8-year-old boy presented with
superficial temporal artery aneurysm that showed giant
cell arteritis on pathologyY
Vasculitides Associated With
Collagen Vascular Diseases
Systemic Lupus Erythematosus
CNS involvement in patients with systemic lupus
erythematosus (SLE) ranges from 18% to 7 5 % . 56,57 Vas-
culitis in patients with SLE is most commonly caused by
local deposition of DNA:anti-DNA immune complexes
in blood vessel walls generally involving the microvascu-
lature of the skin and kidneys and, less frequently, vessels
of the peripheral nerves, heart, lungs and brain. True vas-
culitis is found in only about 10% of brain specimens of
SLE patients with cerebral involvement. 58 It appears that
the highly vascular choroid plexus can act as a nonspe-
cific trap for circulating immune complexes.
Childhood SLE has been associated with arterial
thrombosis, intracerebral hemorrhage, and cerebral
venous thrombosis. 59'6~ Seizures and behavioral changes
are the most common manifestations of SLE in children,
followed by cerebral infarction. Montes de Oca 59 found
only two children (1.7%) with cerebral infarction in his
series of 120 patients with SLE, a rate lower than the one
reported in adults (3.7%).
Autopsy studies have shown that cerebral vasculitis is
not a common cause of cerebral infarction in SLE. 61
Other stroke mechanisms must be excluded in patients
with SLE before assuming that a cerebral infarction is
secondary to vasculitis. Libman-Sacks endocarditis, an-
tiphospholipid antibodies, and thrombotic thrombocy-
topenic purpura have been found to cause infarction in
patients with SLE. 62 Kaell et al 6~ also emphasized that
adverse effects of treatments and CNS infections may
mimic stroke symptoms.
Cerebral angiography and determination of anti-P-
ribosomal antibody in CSF are helpful ancillary tests in
the diagnosis of SLE-related cerebral vasculitis. Once the
diagnosis is supported by ancillary studies and other
mechanisms for strokes have been excluded, the dose of
corticosteroids may be increased and the addition of
other immunosuppressive modalities should be consid-
ered. Autologous stem cell transplantation can be used in
patients not responding to heavy immunosuppression.
Trysberg 63 reported on a 16-year-old patient with bilat-
eral optic neuritis, probable hemispheric involvement,
and transverse myelitis refractory to high doses of
immunosuppressive agents. Hematopoietic stem cells
were mobilized with cyclophosphamide and granulocyte
colony stimulating factor, followed by enrichment of
CD34 cells and depletion of T and B cells resulting in
prompt neurologic improvement. Further studies are
needed to establish the role of this new technology in
refractory SLE-related CNS vasculitis.
Rheumatoid Arthritis
Rheumatoid vasculitis is frequently found postmortem
in rheumatoid arthritis (RA), but clinical manifestations
are seen in only 1% to 3% of patients. 64 However,
rheumatoid vasculitis might be one of the more common
systemic vasculitides, given the high prevalence of the
disease. Patients who develop clinical vasculitis usually
have had symptoms for several years associated with
high rheumatoid factor titers. Those with Felty's syn-
drome have a higher risk of vasculitis. CNS involvement
by RA includes the presence of rheumatoid nodules,
pachymeningitis or leptomeningitis, and cerebral vascu-
litis, usually presenting with seizures or cerebral infarc-
tion as described in Bathon's review of 18 cases. 65
Seizures and changes in mental status might occur in
8% of children with juvenile RA; however, no cases have
been described with pathologically proven vasculitis. 66
Some cases have shown remarkable improvement of focal
neurologic deficits after corticosteroid treatment without
further evidence for the diagnosis of vasculitis. A 17-year-
old boy with RA had aphasia and right hemiparesis asso-
ciated with angiographic changes suggestive of vasculitis,
but without pathologic confirmation. 67 A similar clinical
presentation occurred in a 16-year-old girl with right hemi-
paresis, dense cataracts, and polyarthritis who was found
to have multiple segmental arterial narrowing of the left
anterior and middle cerebral arteries on MRA. Pulse
methylprednisolone resulted in clinical improvement and
resolution of MRA changes. 6s Immunosuppression with
corticosteroids, azathioprine, cyclophosphamide, or
chlorambucil has been used in the past. The impact of
 Noninfectious Cerebral Vasculitis in Children
methotrexate and the new agent etanercept in the incidence
of rheumatoid vasculitis has not been established.
Sjiigren's Syndrome
Sj6gren's Syndrome (SS) is a chronic autoimmune dis-
order that can be primary or secondary. Primary SS is rare
in children. 69 Secondary forms might precede or follow
other autoimmune disorders such as SLE, RA, mixed con-
nective tissue disease, scleroderma, or dermatomyositis.
Dry eyes (xerophthalmia) and dry mouth (xerostomia) are
characteristic features of SS. Other symptoms include
Raynand's phenomenon, epistaxis, hoarseness, recurrent
otitis media, keratoconjunctivitis, and parotid gland en-
largement. Laboratory investigations show positive rheu-
matoid factor, and the presence of anti-SS-A and anti-
SS-B antibodies. Biopsy of minor salivary glands reveals
periductal lymphocytic infiltration. 7~
CNS involvement is more common in adults and has
been reported in 25% to 66% of cases. Neurologic
manifestations include acute encephalopathy, cognitive
and behavioral disorders, seizures, aseptic meningitis,
hemiparesis, movement disorders, and myelopathy.
Aseptic meningitis, optic neuritis, and cerebral infarction
have been reported in children. 7~ Multifocal neuro-
logic deficits associated with optic neuropathy occurred
in a 10-year-old girl with SS and anti-Ro (SS-A) anti-
bodies. MRI showed bilateral hyperintensities on T2-
weighted imaging, involving both gray and white matter.
Cerebral angiography revealed multiple areas of narrow-
ing in the anterior and posterior inferior cerebellar
arteries and in the small cerebral vessels. 76 Spinal cord
involvement has been reported in one child. 69 Cortico-
steroids and cyclophosphamide are used in the treatment
of SS with CNS involvement.77
Mixed Connective Tissue Disease
Patients with mixed connective tissue disease initially
present with Raynaud's phenomenon, sausage-shaped
fingers, polyarthralgias or arthritis, myalgias, and high
titers of antibodies directed to U1 ribonucleoprotein
(RNP). Common CNS manifestations are headache,
aseptic meningitis, psychosis, and seizures. Cerebrovas-
cular complications occur infrequently.
Graf7s described two young patients with mixed con-
nective tissue disease who suffered acute cerebrovascular
events. A 13-year-old girl had a fatal parieto-occipital
hemorrhage after seizures and aseptic meningitis. A
9-year-old girl presented with a large left hemispheric
cerebral infarction secondary to occlusion of the supra-
clinoid portion of the internal carotid artery. Cerebral
vasculitis was suggested as possible etiology.
Scleroderma
Transient ischemic attacks and cerebral infarctions
have been described in up to 3% of adults with sclero-
derma and no vascular risk factors. Scleroderma "en
9 Lopez-Yunez and Garg 255
coup de sabre" has been associated with epilepsy, stroke,
and other neurologic symptoms. 79-sl
Polymyositis/Dermatomyositis
Childhood polymyositis/dermatomyositis (PM/DM) is
characterized by generalized muscle weakness, more
severe in the pelvic and pectoral muscles, erythematous
skin lesions over the extensor surfaces of the joints,
muscle pain, and a malar rash. The association with
underlying malignancy described in 6% to 45% of adult
DM is rare in childhood PM/DM.
Cerebral vasculitis has been reported in a child with
PM/DM and agammaglobulinemia. 82 Jimrnez s3 de-
scribed a 6-year-old girl with PM/DM who had a rapid
deterioration from cardiac and cerebral involvement. Au-
topsy showed endothelial tubuloreticular aggregates and
multiple thromboses in the heart and brain capillaries.
Treatment consists of corticosteroids supplemented
with cytotoxic agents in refractory cases. Intravenous
immunoglobulin or plasma exchange for refractory cases
have been tried with limited data on efficacy.
Vasculitides Associated With
Other Systemic Diseases
Behqet's Disease
In 1937, Hulusi Behqet, a Turkish dermatologist,
described the clinical triad of recurrent buccal aphthosis,
genital ulcers, and uveitis with hypopion that now bears
his name. s4 Since then, skin lesions, arthritis, and neu-
rologic and pulmonary involvement have been reported
in association with Behqet's disease. The International
Study Group for Behqet's disease has proposed diagnos-
tic criteria that require recurrent oral ulceration observed
by a physician at least three times over a period of 12
months plus at least two of the following symptoms:
recurrent genital ulcerations, uveitis or retinal vasculitis,
skin lesions (erythema nodosum or pustules), and a
positive pathergy test result. 85 The pathergy test is
performed usually by needle prick of the skin, and the
appearance of a papule, pustule, or papule with surround-
ing erythema at 48 hours constitutes a positive pathergy
test. This vasculitis of unknown etiology, more common
in Asian and Mediterranean patients, is uncommon in
children. A French nationwide survey estimated the
prevalence of Behqet's disease in children younger than
15 years at 1 in 600,000. 84 Patients are more likely to
have uveitis rather than mucocutaneous ulcers when the
disease begins before 15 years old. s5
Symptomatic CNS involvement is present in 10% to
20% of patients. 86 Neurologic manifestations include
headache, papilledema, aseptic meningitis and menin-
goencephalitis, loss of memory and personality change,
seizures, hemiparesis, paraparesis and quadriparesis, cra-
256 Seminars in CerebrovascularDiseasesand Stroke Vol. 1 No. 3 September 2001
nial nerve palsy, and peripheral neuropathy.87 Dural sinus
venous thrombosis has been reported, ss In one review of
childhood Behqet's disease, headache was the most com-
mon complaint (21.5%), followed by meningitis (9%), in-
tracranial hypertension (4%), motor deficits (4%), sei-
zures (3%), and peripheral neuropathy (3%). 84 Arterial
occlusions might occur in 0.5% to 2.5% of patients with
Behget's disease. Subclavian and carotid occlusions lead
to hemispheric and brainstem stroke syndromes or to sub-
clavian steal. Subarachnoid hemorrhage from multiple in-
tracranial aneurysms also has been described in childhood
Behqet's. s9 Treatment is controversial. Corticosteroids
and immunosuppressive agents might be beneficial.
Sarcoidosis
Neurosarcoidosis can manifest with optic neuritis,
aseptic basilar meningitis, and granulomata involving the
hypothalamus, brain parenchyma, or spinal cord. Vascu-
lifts in neurosarcoidosis is rare. 9~ Granulomatous angiitis
associated with cerebellar hemorrhage has been re-
ported9a; however, even when perivascular granulomas
are found, cerebrovascular complications seldom occur.
Prednisone at doses of 0.5 to 1 mg/kg/d remains the
treatment of choice.
Ulcerative Colitis
Stroke might be a complication in approximately 3%
of children with inflammatory bowel disease. 92 Probable
stroke mechanisms include hypercoagulable states and
cerebral vasculitis. Patients with cerebral infarction have
shown angiographic changes consistent with vasculitis. 93
A patient with ulcerative colitis developed cerebral
infarctions secondary to biopsy-proven necrotizing cere-
bral vasculitis. Treatment with prednisone and cyclo-
phosphamide led to a good outcome. 94 Another patient
with ulcerative colitis developed intracerebral hemor-
rhage associated with angiographic changes suggestive
of vasculitis that resolved after evacuation of the he-
matoma. No pathologic confirmation was obtained. 95
X-Linked Lymphoproliferative Syndrome
Necrotizing cerebral vasculitis was found at autopsy in
a child with X-linked lymphoproliferative syndrome and
recurrent intracerebral hemorrhages. 96
Kohlmeier-Degos Disease
Kohlmeier-Degos disease, or malignant atrophic papu-
losis, is a rare vasculopathy characterized by cutaneous
lesions with frequent gastrointestinal and neurologic
involvement, and almost invariably with a fatal outcome.
Papular lesions may occur in the trunk or the limbs, and
show multiple microinfarcts in the dermal collagen on
biopsy. These are usually accompanied by ischemic
ulcers, which may lead to apical necrotic amputations of
the fingers. Occasionally, cyclical nodular cutaneous
eruptions occur associated with fever, hepatospleno-
megaly, and episodic abdominal pain.
Cerebral involvement might manifest before the typi-
cal cutaneous lesions are evident. 97 Patients often present
with recurrent ischemic infarctions in multiple vascular
territories. Pathology shows intimal thickening without
inflammation, leading to narrowing or occlusion of me-
dium and small vessels. Widespread leptomeningeal fi-
brosis and multiple infarcts at different stages are the rule.
Symptoms associated with Kohlmeier-Degos disease
may begin as early as the first year of age or as late as the
fifth decade of life. 9s Sotrel et a199 described a 16-year-
old boy with a history of maculopapular skin lesions and
episodic fever since childhood; he had multiple brain-
stem infarctions, leading to ophthalmoplegia, hemipare-
sis, and, eventually, his death. Autopsy showed the
characteristic pattern of the disease in the CNS, gas-
trointestinal tract, and skin. Another patient presented
with a subcortical cerebral infarction at age 17 months,
associated with multiple spontaneous finger amputations.
Five years later, he had a malabsorption syndrome
secondary to intestinal ischemia, followed by two large
cerebral infarctions, resulting in death. Interestingly, the
typical skin lesions were absent, although autopsy
showed vascular involvement of the skin as well as the
brain and gut. 97 There is no known effective treatment
for this disease. Antiplatelet therapy and plasma ex-
change have been tried without success, l~176
Miscellaneous Vasculitides
Kawasaki Disease
Kawasaki Disease (KD) is an acute systemic vasculitis
of childhood. Mucocutaneous lymph node syndrome and
infantile PAN are probably the same condition as KD.
Histopathology in KD reveals a panvasculitis with en-
dothelial necrosis and mononuclear cell infiltration into
small- and medium-sized blood vessels. 1~
KD was first described in Japanese children but is now
recognized all over the world. Incidence rates of 120 to
150 cases per 100,000 children younger than 5 years old
have been reported in Japan. In the United States, inci-
dence rates of 6.5 (for the years 1985 through 1986) and
15.2 (for the years 1987 through 1989) per 100,000 chil-
dren younger than 5 years old have been reported. 1~176
KD is a febrile disease of young children; 80% of
cases occur in children less than 5 years old. Table 5 lists
clinical diagnostic criteria. The course of KD can be
divided into three phases: In the first phase, lasting 10 to
14 days, the child is febrile and ill, appearing with
conjunctival injection, dry cracked lips, mucous mem-
brane changes, rash, swelling, and erythema of the palms
and soles. Diarrhea, cervical lymphadenopathy, hepatic
 Noninfectious Cerebral Vasculitis in Children
Table 5. Diagnostic Criteria for Kawasaki Disease
Both A and B should be present:
A. Fever of more than 5 days duration and 4 of the following 5 criteria:
I. Bilateral conjunctival injection
2. Upper respiratory tract mucosal changes including injected oropharynx, dry, injected fissured lips, strawberry tongue
3. Peripheral extremity changes including desquamation or erythema of hands and feet, peripheral edema
4. Polymorphous (not vesicular) skin rash
5. Cervical adenopathy
B. Illness cannot be explained by some other known disease process
Reprinted from Morens DM, O'Brien RJ. Kawasaki disease in the United States. J Infect Dis 137:91-93, 1978, with permission.
dysfunction, and aseptic meningitis are other associated
findings. Conjunctival injection continues in the second
phase, whereas other symptoms resolve. The child is
irritable and anorexic. Desquamation of the skin starts in
the periungual region and can extend to the palm and
soles. Arthralgias and arthritis as well as myocardial
dysfunction might occur. Thrombocytosis is nearly uni-
versal. This phase lasts between 2 and 3 weeks. The
convalescent, or third, phase might be as long as 8 weeks
and is characterized by the gradual resolution of clinical
signs and symptoms and a return of sedimentation rate to
normal levels. KD might result in nonatherosclerotic
aneurysmal abnormalities of the coronary arteries in 20%
to 25% of untreated patients, associated with a risk of
sudden death. Coronary aneurysms can be identified as
early as the second or third week of illness or as late as
the sixth week. Myocardial infarction might occur.
Nearly one half of the coronary artery aneurysms regress
on follow-up. Some patients develop cardiac valvular
insufficiency. Long-term cardiac monitoring of patients
is essential after recovery from acute K D . 104-106
Neurologic involvement can manifest early in illness
or occur as a late complication. Children are strikingly
more irritable than in other febrile illnesses. Aseptic
meningitis is present in almost one fourth of patients.
CSF analysis shows modest lymphocytic pleocytosis
with normal glucose and protein concentration. Cerebral
hypoperfusion has been reported in the acute phase of
KD. It has been suggested that this finding supports the
presence of a cerebral vasculitis. 1~ Embolic cerebral
infarction, often in patients with cardiac dysfunction,
might complicate the course of KD in some patients (Fig
1). Facial palsy, sensory-neural hearing loss, ataxia,
hemiparesis, and encephalopathy are other reported neu-
rologic complications of KD. 1~
A single intravenous infusion of 2,000 mg of intrave-
nous immunoglobulin (IVIg) over 12 hours is recom-
mended in the acute phase of illness. Aspirin in a dose of
80 to 100 mg/kg/d is administered for the first two weeks
of acute illness (to achieve serum levels of around 100 to
125 mg/dL) and is followed by 3 to 5 mg/kg/d for 6 to 8
weeks until the erythrosedimentation rate is normal.
Aspirin can be continued for a longer duration in patients
9 Lopez-Yunezand Garg 257
with cardiac complications. Pulsed corticosteroid therapy
has been proposed for patients who do not respond to
IVIg therapy. Corticosteroids are not recommended for
the initial treatment of patients with K D . 108-110
Goodpasture Syndrome
Goodpasture syndrome is an acute pulmonary-renal
syndrome characterized by pulmonary hemorrhages,
glomerulonephritis, and the presence of antiglomerular
base membrane antibodies. CNS involvement is usually
secondary to arterial hypertension. At least one case has
been reported with biopsy-proven cerebral vasculitis.
This 18-year-old boy presented with refractory partial
seizures despite plasma exchange and cytotoxic therapy.
During tapering of immunosuppressive therapy, he de-
veloped status epilepticus and bilateral lacunar infarc-
tions. Reinstitution of corticosteroids and immunosup-
pression, followed by a renal transplant, resulted in
complete cure. H~
Other Vasculitides
Poststreptococcal Vasculitis
Two cases of possible cerebral vasculitis without
histologic confirmation have been described in children
after streptococcal infection. A 13-year-old girl had a
streptococcal upper respiratory infection, followed by
glomerulonephritis and generalized seizures, associated
with bilateral white and gray matter changes on MRI
suggestive of posterior reversible leukoencephalopa-
thy]12 A 10-year-old girl presented with acute hemicho-
rea associated with ischemic changes in the distribution
of the middle and anterior cerebral arteries. Cerebral
angiography showed segmental narrowing of these ar-
teries; ancillary testing supported the diagnosis of Sy-
denham's chorea without evidence of systemic vasculi-
tis. 113
Graft-Versus-Host Disease
Cerebral angiitis has been reported in patients after al-
logenic bone marrow transplantation (BMT). Neurologic
complications might occur as a direct effect of used drugs
258 Seminars in Cerebrovascular Diseases and Stroke Vol. 1 No. 3 September 2001
Fig. 1. Axial unenhanced CT
scan of a boy with an embolic
right frontal infarct associated
with myocardial infarction
as a late complication of Ka-
wasaki disease.
or as a result of immunosuppression-induced viral, bacte-
rial, or fungal infections. In a few cases, graft-versus-host
disease (GVHD) might be associated with a vasculitic pro-
cess, starting months to years after transplantation. These
patients show the typical skin and renal involvement asso-
ciated with a variety of CNS manifestations such as pro-
gressive leukoencephalopathy, cerebral infarction, or neu-
ropsychiatric symptoms. Iwasaki 114 reported two children
with chronic GVHD beginning within the first year after
BMT who developed progressive white matter disease,
leading to death. Pathologic studies showed diffuse lym-
phocytic perivascular infiltrates (more prominent in the
white matter) that were positive for the CD3 marker. Pa-
dovan 1~5 described 5 cases of BMT patients with GVHD
who developed bilateral lacunar infarctions and leukoen-
cephalopathy on MRI imaging with pathology-proven vas-
culitis in one case. This patient had no evidence of super-
imposed cytomegalovirus or other associated infection.
Relapsing Polychondritis (RP)
Relapsing polychondritis is a rare disorder manifested
by recurrent inflammatory episodes involving nonarticu-
lar cartilaginous structures, mainly the external ears, nose,
larynx, trachea, and bronchi. One third of patients develop
vascular involvement that might affect the aorta and its
main branches, the microvasculature, or the veins.~16 Tho-
racic aortic aneurysms are typical in RP and carry a poor
prognosis. Aneurysms, arterial stenosis, or both have been
described in most major vessels, including the carotid ar-
teries 1 1 7 and the intracranial vessels. 118 MRA is generally
the diagnostic method of choice because of the increased
incidence of pseudoaneurysms associated with conven-
tional angiography in patients with RP.
Prognosis is serious in most patients. In young pa-
tients, saddle-nose deformity and systemic vasculitis are
associated with poor prognosis. ~19 They frequently re-
quire high doses of steroids and immunosuppressive
therapy. Patients with aortic dilatation can benefit from
treatment with [3-blockers.
Main differential diagnoses for RP include TA, Behqet's
disease, Wegener's granulomatosis, and Cogan syndrome.
Cogan syndrome can be associated with aortic aneurysms
and optic neuritis, but typically is characterized by fluctu-
ating cochleo-vestibular symptoms and nonluetic intersti-
tial keratitis. ~a~ Finally, the overlap syndrome MAGIC
(mouth and genital ulcers with inflamed cartilage) also
might present with aortic aneurysms and vasculitis.~2~
Primary Vasculitides
Primary Angiitis of the CNS
Primary angiitis of the CNS (PACNS) has been re-
ported rarely in children. A total of 11 cases were reported
until 2001, and only one report was published before
1990. Symptoms and signs are restricted to the CNS and
include headaches, encephalopathy, ischemic strokes, cra-
nial neuropathies, subarachnoid hemorrhage, and mye-
lopathy. 122 The spectrum of pathologic manifestations of
PACNS in children is wide, and histologic appearances
range from nongranulomatous lymphocytic infiltrates to
granulomatous and necrotizing angiitis. 123124
 Noninfectious Cerebral Vasculitis in Children
CSF analysis is abnormal in about half of the patients,
usually showing pleocytosis and elevated protein con-
tent; however, CSF studies are important in excluding
other conditions, such as viral or postviral vasculopathy
and lymphomatous meningitis, which can mimic
PACNS. Four-vessel cerebral angiography is the most
sensitive diagnostic study, but the angiographic features
are not specific. Angiographic findings consistent with,
but not diagnostic of, vasculitis include single or multiple
areas of segmental vessel stenosis, abrupt vessel termi-
nation, hazy vessel margins, and neovascularization.
Cortical and leptomeningeal brain biopsy remains the
cornerstone of diagnosis, although it might be nondiag-
nostic in up to 25% of the casesJ 25 Electron microscopy
also might exclude the presence of viral inclusions.
It is useful to divide childhood PACNS in two groups
according to vessel size as proposed by Lanthier et al,126
who showed that clinical presentation and prognosis
differ between the small-vessel PACNS and the
medium/large-vessel PACNS. Angiography is helpful in
classifying the size of vessels involved as follows: small
vessels are quaternary branches of less than 1 mm and
best seen on magnification; medium vessels are second-
ary and tertiary branches of the large arteries; large
vessels are the carotid arteries and vertebrobasilar arter-
ies and their primary branches, including the first seg-
ments of the anterior cerebral artery (A1), middle cere-
bral artery (M1), and posterior cerebral artery (P1).
Five children have been reported with small-vessel
PACNS. 126-129 Patients presented with gradual onset of
headaches (n = 3), multifocal neurologic deficits (n =
2), cognitive decline (n = 1), and mood disorder (n = 1).
Focal seizures occurred in three of these children. Brain
MRI was always abnormal, showing hyperintensities in
the cerebral cortex and white matter (n = 3) or single,
large, enhancing lesions mimicking a brain tumor (n =
2). Angiography was often normal (n = 4), as was the
CSF in 2 of 3 children. Brain biopsy showed a nongranu-
lomatous lymphocytic pattern involving small vessels
without fihrinoid necrosis in 5 patients. Treatment with
prednisone with or without cyclophosphamide resulted
in good outcome in 4 children; one patient died.
Five children have been reported with medium/large-
vessel P A C N S . 13~ In this group, patients presented
with large artery ischemic infarction (n = 2), transient
ischemic attacks (n = 1), and subarachnoid hemorrhage
(n = 2). CT scan might show small to large hypodensi-
ties. CSF is usually inflammatory (2 of 3), and angiog-
raphy might show multiple stenotic areas or aneurysms.
Four children died within 10 days of presentation and
one died 7 years after presentation. Autopsy showed
granulomatous infiltration of large and medium arteries
(n = 5), vessel wall fibrinoid necrosis (n = 2), and
inflammatory infiltration of the aneurysm wall (n = 1).
None of these patients received immunosuppression.
9 Lopez-Yunezand Garg 259
Once the diagnosis of PACNS is confirmed, patients
should receive prednisone 1 to 2 mg/kg/d alone or com-
bined with cyclophosphamide 2 mg/kg/d, especially in
patients with the large-vessel type of PACNS. Close clini-
cal surveillance is mandatory and angiographic follow-up
is helpful in selected cases. Long-term outcomes with im-
munosuppression in children are unknown.
Conclusion
Childhood cerebral vasculitides comprise a heteroge-
neous group of disorders. Reaching a specific diagnosis
and exclusion of vasculitis mimics are necessary to
institute appropriate therapy. This can only be accom-
plished by a thorough clinical evaluation and the judi-
cious use of ancillary testing.
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