Benign focal cerebral vasculitis:
Case report
Joseph R. Berger, MD; Jose Romano, MD; Martin Menkin, MD; and Michael Norenberg, MD

Article abstract-We report a 47-year-old man who presented with partial seizures complicating focal cerebral vasculitis of the right temporal lobe. Excisional biopsy of the mass lesion revealed fibrinoid necrosis of small vessels.
These vessels were infiltrated by neutrophils, eosinophils, lymphocytes, and plasma cells. Despite extensive evaluation, no etiology was apparent for the vasculitis. No immunosuppressive agents were administered, and 4% years after
the diagnosis, he remains healthy except for an incongruous left homonymous hemianopia. Follow-up cranial magnetic
resonance images revealed only postoperative changes. This case demonstrates that focal lesions and a benign course
may represent one end of the spectrum of primary angiitis of the central nervous system.
NEUROLOGY 1995;45:1731-1734

A classification of the CNS vasculitides includes
those illnesses in which the CNS is affected in the
course of a systemic vasculitis and those in which
the vasculitis occurs solely in the CNS. Granulomatous angiitis of the CNS is the prototypical illness
of the latter category. It affects men more than
women, has an average age of onset of 46 years,
and typically results in death in untreated cases
within 1 year.l A benign course with recovery in
the absence of treatment and with prolonged survival is uncharacteristic.2 In rare instances, it may
present as a focal 1 e ~ i o n . l -In
l ~ 12% of patients,
seizures are the presenting manifestation of the
d i ~ 0 r d e r .We
l ~ describe an individual presenting
with seizures caused by focal cerebral vasculitis
who has remained healthy more for than 4Xyears
after diagnosis.
Case report. On November 18, 1990, while playing tennis, this 47-year-old man developed recurrent waves of a
peculiar odor described as “like tar” and associated with
intense nausea and a n incapacitating malaise. During
the initial episode, he may have had a brief loss of consciousness. The spells recurred a t 5- to 10-minute intervals and were accompanied by pallor and diaphoresis. He
was quickly taken to a local emergency room where a diagnosis of partial seizures was suspected. Following the
intravenous administration of Valium 10 mg and phenytoin 1,000 mg, the episodes stopped.
Two days earlier, he had had an uncharacteristically
intense headache that prevented him from engaging in
his scheduled social activities. Although he had no history of a seizure disorder, he recalled that, 3 weeks earlier, he found himself i n the middle of a wide thoroughfare without any recollection of having driven through a
stop sign. He had driven this route many times and was

quite perplexed by the experience. Additionally, his wife
related that his memory had been a “bit o f f in the preceding weeks. He denied any systemic illnesses.
He was afebrile and his general physical examination
was unremarkable. Neurologic examination revealed him
to be alert and oriented. Funduscopy was normal. There
was a suggestion of a left superior-quadrant visual field
defect to confrontation. Muscle strength and tone were
normal, and his muscle stretch reflexes were brisk and
symmetric. Sensory perception to all modalities was normal. Chest x-ray, ECG, and results of routine laboratory
studies, including complete blood count with differential,
chemistries, rapid plasma reagin, fluorescent treponemal
antibody test, and urinalysis, were normal or negative. A
head CT without contrast (figure 1)showed a focal hypodense lesion within the medial right temporal lobe associated with minimal mass effect. The lesion had associated areas of calcification. Cranial MRI (figure 2) on admission showed this same mass lesion with associated
areas of signal void, consistent with calcification. The lesion enhanced irregularly with gadolinium. A glioma was
suspected, and on November 19, 1990, he underwent a
right temporal craniotomy with temporal lobectomy and
removal of a n intratemporal mass, and was started on
acyclovir 10 mg intravenously every 8 hours for possible
herpes simplex virus (HSV) encephalitis.
Sections from the convexity cortex and underlying
white matter showed no significant changes. However, in
the hippocampus, several small blood vessels showed
marked fibrinoid necrosis of their walls, which were infiltrated by acute and chronic inflammatory cells including
neutrophils, eosinophils, lymphocytes, and plasma cells
(figure 3). The adjacent neuropil was edematous, and a
few necrotic neurons were present. Rare psammomatous
bodies were noted. There were no microglial nodules,
perivascular lymphocytic infiltrates, or intranuclear inclusions. The meninges were free of pathologic changes.
There was no evidence of a neoplastic process. Im-

From the Departments of Neurology (Drs. Berger and Romano), Internal Medicine (Dr. Berger), and Pathology (Dr. Norenberg), the University of Miami
School of Medicine; and the Department of Neurology (Dr. Menkin), Baptist Hospital, Miami, FL.
Received August 30,1994. Accepted in final form February 7,1995.
Address correspondence and reprint requests to Dr. Joseph R. Berger, Department of Neurology, University of Kentucky College of Medicine, Chambers
Building (Annex 41, Room 228, 800 Rose Street, Lexington, KY 40536.
S e p t e m b e r 1995 NEUROLOGY 45 1731

munoperoxidase staining and polymerase chain reaction
for HSV 1and 2 were negative.
Following surgery, he had dysprosodic speech, a denial of the left side, difficulty with visual tracking leftward, and a left homonymous hemianopia. Because of

Figure 1. CT (General Electric, Milwaukee, WI) without
contrast reveals a focal hypodense lesion in the right
medial temporal lobe with a small area of high density
within the lesion (arrowhead), consistent with
calcification and minimal associated mass effect.

the nature of the pathology observed on brain biopsy,
further studies were performed. His ESR was 4 seconds.
Other studies included serum immunoelectrophoresis,
serum complements (C3, C4, and CH,,), ANA, rheumatoid factor, anti-DNA antibodies, anti-neutrophil antibodies, cryoglobulins, Lyme antibody, serum HSV 1 and
2 IgG and IgM antibodies, cryptococcal antigen, a n giotensin-converting enzyme, prolactin, and follicle-stimd a t i n g and luteinizing hormones. All results were either
negative or normal. Examination of the CSF showed 1
white blood cell per mm3, 0 red blood cells per mm3, protein 68 mg/dl (normal, 15 to 45 mg/dl), glucose 66 mg/dl,
IgG 4.7 mg/dl (normal, 2.2 t o 4 mg/dl), and IgG index
0.49 (normal, 0.3 t o 0.7). On CSF electrophoresis, two
oligoclonal bands were present. An abdominal CT revealed a liver cyst.
Within 2 months of surgery, his examination was remarkable for an incongruous left homonymous hemianopia compatible with optic tract disease (N. Schatz,
Bascom Palmer Eye Institute, Miami, FL, personal communication). A cranial MRI obtained in December 1990
revealed postoperative changes that included an abnormal signal in the distal end of the right optic tract and
the right geniculate body. A detailed neuropsychological
battery revealed distinct abnormalities in his Performance I&,but he retained a high Verbal I&. He was able
to return to full-time work as a pediatrician and has had
no seizures on carbamazepine 800 mg daily. As of May
1995, he remains healthy. Repeat cranial MRI revealed
only postoperative changes.

Discussion. The remarkable features of this case
are the exquisite focality and the benign course of
pathologically confirmed cerebral vasculitis. The
illness presented with focal seizures. The radiographic properties suggested the possibility of a
process that was not
firmed by
biopsy. HSV encephalitis was also seriously considered in light of the partial seizures with a medial
temporal lobe lesion. However, the patient remained afebrile; there was no CSF pleocytosis;

Figure 2. (A) Axial T2-weighted (TE
90, T R 2,000) MRI obtained on a
1.5-tesla imager (Signa, Milwaukee,
WI) shows a large, oblong, hyperintense signal abnormality in the
medial aspect of the right temporal
lobe. There is minimal mass effect.
A signal void in the lesion is consistent with calcium. (B) Coronal T I weighted (TE 14, T R 516) MRI with
gadolinium contrast shows irregularly enhancing lesion abutting the
temporal horn.

1732 NEUROLOGY 45 September 1995

Among the primary vasculitides, polyarteritis nodosa, hypersensitivity vasculitis, Wegener’s granulomatosis, and lymphomatoid granulomatosis frequently affect the CNS. To the best of our knowledge, none of these primary vasculitides affects the
CNS in an isolated and focal manner. Furthermore,
a benign course in the absence of immunosuppressive therapy is unexpected.
The primary CNS vasculitis, primary angiitis of
the CNS (PACNS) or granulomatous angiitis of the
nervous system, affects small vessels, chiefly small
arteries and arterioles (200 to 500 microns in diameter) of the leptomeninges and brain parenchyma,
in a segmental f a s h i ~ n . ~
The
, ~ ,infiltrate
~
is composed of mononuclear cells, giant multinucleated
cells, and plasma cells with a granulomatous react i ~ n .There
~ . ~ are no polymorphonuclear cells or
Figure 3. Histopathology. Fibrinoid necrosis of vessel
with infiltration of vessel wall with neutrophils,
eosinophils. Most patients present with a diffuse
eosinophils, plasma cells, and lymphocytes.
encephalopathy.1,2JsFocal lesions tend to develop
(Hematoxylin and eosin; X240 before 48% reduction)
gradually when they occur.18The pathophysiologic
mechanism is believed to be chiefly cerebral ischemia, b u t hemorrhage may be 0 b ~ e r v e d . l ~
Seizures have been reported in 23%of patients, but
serum HSV antibody titers were negative; and the
headache, confusion, and cognitive changes are
pathology, including immunoperoxidase staining
more common.2 Neuroimaging often reveals hypoand polymerase chain reaction for HSV 1 and 2,
densities with enhancement and occasional mass
was negative. There were no clinical or laboratory
e f f e ~ t . Angiography
~J~
lacks diagnostic specificity.20
features to suggest the diagnosis of a systemic vasIn their original description, Cravioto and Feigin4
culitis. Certain infections, such as syphilis, tuberinitially suspected brain tumor in two of their paculosis, and herpes zoster, may also result in a
tients. Even with the application of more sophistiCNS vasculitis, but none was demonstrated. Addicated brain imaging techniques, misdiagnosis as
tionally, there was no history of toxin exposure or
brain tumor
Cerebral biopsy remains
drug use. The significance of calcification in the le.~
generally occurs
the standard for d i a g n o ~ i sDeath
sion detected both radiographically and histopathowithin 1 year in untreated case^,^,^ but corticologically remains obscure. The sizable lesion evisteroids and cyclophosphamide treatment have had
dent on radiographic imaging was likely the consefavorable results.22
quence of multiple confluent infarcts due t o the
In summary, we describe a unique illness charangiitic process5 and associated edema.
acterized by a focal vasculitis that was heralded by
“Vasculitis” refers to a broad group of conditions
partial seizures. Other than a brief course of corticharacterized by inflammation of the vessel wall.
costeroids, no immunosuppressive treatment was
Vasculitis may result from different pathophysioadministered, and the patient remains well 4%
logic mechani~rns.~
In immune complex-mediated
years after presentation except for a visual field
vasculitis, soluble immune complexes are formed in
deficit. Benign isolated arteritis of the CNS has
the presence of slight antigen excess, which results
been previously observed.l-13Calabrese et
argue
in increased vascular permeability with infiltration
that there is a spectrum of PACNS. In a subset of
of the arterial elastic walls and basement mempatients in whom the diagnosis was established anbranes of v e n ~ 1 e s . lActivation
~
of complement atgiographically without histopathologic confirmatracts polymorphonuclear cells that release proteotion, the disease was often heralded by focal neurolytic enzymes, with further injury t o vascular
logic deficit and typically occurred in young women
structures. This mechanism is the presumed mechwho had relatively unremarkable CSF findings. A
anism for polyarteritis nodosa and hypersensitivity
benign course was often observed. However, in the
vasculitis. In cell-mediated injury, macrophages
absence of pathologic confirmation, the true nature
may be activated by phagocytosing immune comof this disorder remains suspect. Another explanaplexes, by F c receptor interaction, or by lymphokines released by antigen-sensitized T cells.16 tion for the angiographically observed changes is
vasospasm caused by migraine, drugs, head
Activated macrophages releasing lysosomal en~ ~ , ~cases
~ of focal
trauma, or other e t i o l ~ g i e s . Few
zymes cause, by granulomatous reaction, vascular
cerebral v a s ~ u l i t i s ~
have
~~~
been
~ J ~confirmed histodamage. Vasculitis may also result from neoplastic
cell inuasion, as in lymphomatoid g r a n u l o m a t ~ s i s . ~ ~logically. Among the pathologically proven cases of
benign focal cerebral vasculitis, the patient deOther, as yet unproven, possibilities of vessel wall
scribed by Beresford et a17 was very similar to our
injury include damage arising from cellular T-cell
patient. Features that either preclude comparison
activity, natural killer cell activity, and antibodies
directed against components of the vessel walL3 or distinguish other cases from our own include inSeptember 1995 NEUROLOGY 45 1733

sufficient follow-up to determine the benign or nonrecurrent nature of the disorder5;the presence of a
positive ANA and mild leukopenia, suggesting a
systemic vasculitis8; and the admixture of amyloid
in the cerebral biopsy.12
In our patient, a middle-aged man with no history of migraine, head trauma, drug use, or preceding or concomitant infectious illness, the diagnosis
was confirmed by biopsy. As in other cases of focal
cerebral vasculitis, a brain tumor was initially susp e ~ t e d . ~ ,Whether
~ , ~ ~ , ~this
' entity is truly one end of
the spectrum of PACNS remains uncertain, as vascular inflammation may be a physiologic or pathologic process. Despite that, this case confirms the
existence of an entity of focal cerebral vasculitis
with a benign course that does not require corticosteroid or other immunosuppressive therapy.

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Benign focal cerebral vasculitis: Case report
Joseph R. Berger, Jose Romano, Martin Menkin, et al.
Neurology 1995;45;1731-1734
DOI 10.1212/WNL.45.9.1731
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