CLINICAL REPORT

Adult Onset Chronic Unihemispheric Vasculitis Resembling
Rasmussen Encephalitis
Alfredo Damasceno, MD,* Marcondes França, Jr., MD,* Luciano Souza Queiroz, MD, PhD,†
Fernando Cendes, MD, PhD,* Anamarli Nucci, MD, PhD,*
and Benito Pereira Damasceno, MD, PhD*

Introduction: Rasmussen encephalitis (RE), a chronic inflammatory unilateral brain disease, is usually associated with intractable seizures and progressive neurologic deterioration. Despite being initially observed in children, an adult form has been more recently recognized. MRI discloses
progressive atrophy and signal changes through the affected hemisphere, but
rarely gadolinium enhancement, which when observed requires a brain
biopsy to distinguish Rasmussen encephalitis from an alternative diagnosis
as unihemispheric vasculitis.
Case Report: An adult patient had at the age of 35 his first generalized
seizure followed by transient right hemiparesis and aphasia. Two years later,
seizures relapsed with a gradually increasing frequency associated with
progressive neurologic deterioration. Repeated brain imaging, revealed progressive atrophy and signal changes within the left hemisphere with gadolinium enhancement. Histopathology disclosed focal gliosis mainly in white
matter and some small intraparenchymal arteries, and arterioles with perivascular and intramural chronic inflammatory cell infiltrate.
Conclusion: Unihemispheric chronic vasculitis may resemble adult-onset Rasmussen encephalitis, and persistent gadolinium enhancement seen on MRI
lesions is helpful for the differential diagnosis between the 2 conditions.
Key Words: chronic encephalitis, focal epilepsy, cerebral vasculitis,
Rasmussen encephalitis
(The Neurologist 2009;15: 285–288)

F

ew neurologic conditions can be classified as unihemispheric epileptic syndromes such as Rasmussen encephalitis (RE). RE is a
rare chronic inflammatory unilateral brain disease leading to
intractable focal seizures, epilepsia partialis continua, and progressive neurologic and neuropsychological deterioration with
typical onset in childhood.1 The etiology is still unknown and recent
studies point to heterogeneous mechanisms. The diagnosis is based
on clinical and neuroradiologic findings, electrophysiological studies, and biopsy. Histopathologically, RE is characterized by chronic
inflammatory infiltrates with perivascular cuffing, microglial nodules, astrogliosis and neuronal loss, mainly in the cortex. Characteristic MRI features are cortical hyperintense T2/fluid-attenuated
inversion recovery (FLAIR) signal lesions with hemispheric atrophy, usually starting in the temporoinsular region. Gadolinium
enhancement is very rare, and when present, it is observed in the
earliest scans.2 Cases of adult onset have also been described, with
a variable prognosis and more frequent occipital lobe seizure onset.3
Treatment is aimed at controlling seizure disorder with antiepileptic

From the Departments of *Neurology, and †Pathology, School of Medicine, State
University of Campinas, Campinas, Brazil.
Reprints: Alfredo Damasceno, MD, Departmento de Neurologia, Faculdade de
Ciencias Medicas, Universidade Estadual de Campinas (UNICAMP), CEP
13083-970, Campinas, SP, Brazil. E-mail: alfredodamasceno@hotmail.com.
Copyright © 2009 by Lippincott Williams & Wilkins
ISSN: 1074-7931/09/1505-0285
DOI: 10.1097/NRL.0b013e31818fc74e

The Neurologist • Volume 15, Number 5, September 2009

drugs, and at halting the neurologic deterioration with immunotherapy or functional hemispherectomy.1

Rasmussen encephalitis is a rare chronic
inflammatory unilateral brain disease leading to
intractable focal seizures, epilepsia partialis
continua, and progressive neurologic and
neuropsychological deterioration with typical onset
in childhood.

Unihemispheric cerebral vasculitis has been described to share
many similarities with RE, from which it is differentiated by the
findings on biopsy, with inflammatory processes mainly in vessels,
and with brain imaging, with calcifications on CT, or gadolinium
enhancement on MRI.4
We describe an adult patient with epilepsy and unihemispheric
encephalitis showing gadolinium enhancement throughout 10 years of
disease and brain biopsy disclosing signs of cerebral vasculitis.

CASE
The patient is a 45-year-old, right-handed, white man who had
had a past history of pulmonary tuberculosis treated twice in early
adulthood (at 26 and 28 years age). There was no family history of
neurologic disease or consanguinity. At the age of 35, he had his first
generalized seizure, followed by right pyramidal weakness and expressive aphasia that recovered completely within 2 months. MRI showed
atrophy and increased cortical/subcortical T2/FLAIR signal mainly in
the left frontoparietal region, with areas of gadolinium enhancement
(Fig. 1A). He was commenced on phenytoin but 2 years later a second
generalized seizure brought back those neurologic deficits, recovering
partially after 3 months. A 1-year intramuscular beta-interferon-1a
course was tried, with the initial hypothesis of a demyelinating disease,
without success. Three years after disease onset, simple partial motor
and complex partial seizures started, with a gradual increasing frequency up to a peak of 2 per month, leading to multiple changes in
antiepileptic drug therapy and later plasmapheresis, both without success. The postictal period was marked by acute worsening of neurologic
deficits and, despite a partial recovery, the previous baseline was not
reached during the interictal interval. Repeated laboratory assessments
were negative for autoantibodies, or infectious, or metabolic diseases.
Cerebrospinal fluid always showed mildly elevated protein (0.46 –
0.68 g/L) and cell count (6 lymphocytes per mm3) with high IgG
immunoglobulin on electrophoresis (6.6 mg/dL, normal range ⬍3.4
mg/dL), but without oligoclonal bands. Serological cerebrospinal
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The Neurologist • Volume 15, Number 5, September 2009

FIGURE 1. MRI scans at 1 month (A), 5 years (B), and 10 years (C) after disease onset. Numbers refer to sagittal T1-weighted
with gadolinium (1), Axial T2/FLAIR (2), and Axial T1-weighted with gadolinium (3). Arrows indicate gadolinium-enhanced
lesions.

fluid tests, PCR, and culture were negative for neurotropic virus
(including CMV, EBV, VZV, and HSV I/II), bacteria, fungi,
mycobacteria, and other parasites. Five years after disease onset,
serial EEG showed left frontocentral polymorphic delta activity
and rare epileptiform discharges in the left frontal region. Ninetysix-hour continuous video-EEG telemetry recorded no seizure.
MRI disclosed spreading of signal changes and atrophy within
the left hemisphere, again with gadolinium enhancement (Fig.
1B). A cerebral angiography was normal. One year later, neuropsychological assessment revealed deficits in verbal fluency and
verbal memory (Table 1). A left frontal brain biopsy was performed, showing only subcortical focal gliosis with sparse macrophages. Azathioprine was administered for a year, also without success.
A second left frontoparietal brain biopsy was undertaken 8 years after
disease onset. At this time, histology disclosed focal gliosis mainly in
white matter, and some small intraparenchymal arteries and arterioles
with thickened walls and narrowed lumen, resembling cerebral vasculitis. There was perivascular cuffing by lymphocytes and leptomeningeal lymphomononuclear infiltration, with few parenchymal inflammatory cells. No granulomas or microglial nodules were seen (Fig. 2).
286 | www.theneurologist.org

Despite that fast progression, seizure frequency begun to gradually
decrease, even without immunotherapy. Currently, 10 years after disease onset, he has had only 2 partial seizures in the last 8 months, and
he has never had epilepsia partialis continua. There is permanent right
hemiparesis and transcortical motor aphasia, but without hemianopia.
The expanded disability status scale (EDSS) is 3.5 and a comprehensive
neuropsychological reassessment revealed progression of aphasia,
worsening of verbal fluency and memory, and deficits of intellectual
reasoning (Table 1). As yet, there have not been any signs or symptoms
of a systemic disease. CT has never shown calcifications. MRI disclosed progression of atrophy and signal changes in the temporoinsular
cortex, still with gadolinium enhancement (Fig. 1C). Magnetic resonance spectroscopy showed decreased N-acetyl-aspartate levels in the
lesions. Magnetic resonance angiography revealed a scarcity of left
middle cerebral artery frontoparietal branches. For the last 6 months he
is on monthly intravenous immunoglobulin.

DISCUSSION
This patient developed a chronic unihemispheric neurologic
condition that resembles, in some aspects, RE. This disorder, first
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The Neurologist • Volume 15, Number 5, September 2009

Adult Onset Chronic Unihemispheric Vasculitis

TABLE 1. Neuropsychological Data
Tests
Vigilance: Strub and Black test (no.
errors)
Attention: WAIS-R* digit span: forward
Attention: WAIS-R* digit span:
backward
Visual-spatial perception (LNI** subtest)
Verbal fluency (category: animal)
Constructional praxis (Kohs cubes)
Spatial memory (5 hidden objects)
Visual memory (recall of 10 abstract
figures): immediate
Visual memory (recall of 10 abstract
figures): delayed 30 min
Verbal memory (10 words): immediate
recall (mean)
Verbal memory (10 words): delayed
recall (30 min)
Verbal memory (10 words): recognition
Poblem solving (LNI** subtest)

Scores at
6 Years

Scores at
10 Years

1

2

Not done
Not done

3
2

20/20
15
Normal
3/5
10/10

19/20
8
Normal
3/5
10/10

10/10

8/10

8.2/10

6.4/10

8/10

4/10

10/10
Normal

9/10
Impaired

*Wechsler Adult Intelligence Scale – Revised.
†
Luria’s Neuropsychological Investigation.

described in 1958,5 was initially observed in children, but later became
recognized in an adult form,3,6 which is estimated to account for 10%
of all RE cases.3 The clinical course is marked by development of a
slowly progressive neurologic deterioration, sometimes with Todd
paralysis, what differs from our patient, who presented initially in a
stroke-like fashion, with acute postictal neurologic deficits lasting for
months, initially recovering but later on remaining fixed. Nevertheless,
he further developed a chronic slowly progressive disease.
The MRI evolution in RE has been divided in 4 stages,
from an initial swelling and hyperintense signal (stage 1) to
atrophy and normal signal (stage 4).2 Gadolinium enhancement is
an exception,1,7 but it has been reported in the earliest scans of a few
patients.2,6 In our case, the initial MRI, performed about 4 months
after disease onset, already disclosed hyperintense signal and atrophy in the left frontoparietal region, compatible with stage 3, but
presented additionally with gadolinium enhancement. This feature
has also been described in a unihemispheric vasculitis mimicking
RE.4 Throughout 10 years of follow-up, serial MRI has disclosed
progression of signal changes and atrophy within the left hemisphere, always with gadolinium enhancement, a unique observation
for an unihemispheric encephalitis.
Another stratified analysis has been done in histology of RE
through comprehensive pathologic evaluation.2,8 Four stages have been
divided from a normal cortex (stage 0) or mild cortical focal inflammation and gliosis (stage 1) to panlaminar cortical cavitation and severe
neuronal loss, with rare T-cell infiltration (stage 4). The highest inflammatory changes (T-cell infiltration and microglial nodules) in the early
“active” stages were followed by a subsequent decrease. Despite performing the first biopsy from an increased MRI signal area in our
patient,2 the result was inconclusive, probably because normal and
abnormal tissue may be in very close apposition.8 The second biopsy,
however, was much more contributory. It was also performed from an
area of increased signal in MRI and gadolinium enhancement, which
are features of active disease. The patient himself was also in a period
where the seizures were in its highest frequency. Interestingly, histology
disclosed inflammatory changes most prominent around vessels and in
© 2009 Lippincott Williams & Wilkins

FIGURE 2. Cerebral biopsy performed 8 years after disease
onset (hematoxylin and eosin stain). A Focal gliosis in white
matter with sparing of cerebral cortex (Bar, 250 ␮m). B Leptomeningeal chronic inflammatory cell infiltrate (Bar, 100
␮m). C and D Small intraparenchymal arteries with hyalinized walls and narrowed lumens. E Three vascular lumens in
the place of one. F Intracerebral vessel with perivascular and
intramural chronic inflammatory cell infiltrate. (Bars C–F, 25
␮m).
leptomeninges, with little intraparenchymal infiltration. There were also
features of chronic nonspecific vasculitis and focal gliosis resembling
small infarcts. Similar findings have been described in 2 children with
clinical findings compatible with RE,4,9 pointing to the possibility of an
immunopathogenetic mechanism with vascular injury. Despite an initially normal angiography, a later MRA showed scarcity of left middle
cerebral artery frontoparietal branches.
Central nervous system (CNS) vasculitic syndromes are classified as primary, when the involvement is confined to the CNS, or
secondary, when they occur in the setting of an acknowledged
systemic vasculitis and other disorders known to cause inflammatory
vasculopathy such as connective tissue diseases and systemic infections.10 Our case is in accordance with the former because no
symptoms or signs of a systemic disorder have been found during 10
years of follow-up.
Primary CNS vasculitis (PCNSV) is an uncommon disease
characterized by inflammation of small and sometimes medium-sized
blood vessels. Neither the clinical presentation and behavior of the
disease, nor the histopathology is uniform, and thus, the course may be
either remitting, progressive with fluctuations, or fulminant.10 CNS
involvement is usually bilateral and multifocal, but unilateral changes
have also been reported, yet mostly in children.4,9,11 The most common
presentation is headache with encephalopathy or multifocal signs, but
stroke-like episodes and seizures, as seen in this patient, have also been
described as clinical manifestations.10,12 The diagnosis of PCNSV is
made definitively by brain biopsy, but since this procedure is invasive
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Damasceno et al

and findings may be negative in some patients, some authors have
recommended presumptive treatment on the basis of clinical history and
typical arteriography results.12 However, the real accuracy of conventional angiography in PCNSV is uncertain, and sensitivity was found to
be low in pathologically documented cases.10,12,13 Conversely, the
treatment of PCNS usually follows the standard recommendation,
which involves the combination of glucocorticoids and cyclophosphamide.10 Nevertheless, this approach should be reserved for patients with
symptoms related to severe outcome because the morbidity associated
with glucocorticoids and cytotoxic drugs is noteworthy.10,12 Our patient
began a phase with stable manifestations shortly after the evidence of
vasculitis on brain biopsy, and treatment with cyclophosphamide was
deferred for a period when more aggressive treatment should be needed.
The treatment and pathogenesis of RE, however, has been
a matter of extensive discussion in the literature. The possible
role of a virus infection has been reported,14,15 and albeit it is
controversial,1 improvement after antiviral therapy has been
described.15 The focus of research has moved to humoral autoimmunity after the proposed role of antiGLUR3 antibodies in
RE.16 Mechanisms of how these antibodies may trigger epileptic
seizures and kill neurons were studied, but later challenged
because these antibodies are nonspecific for RE, besides being only
infrequently found in RE.17 In spite of this, the presence of other
antibodies in RE and improvement after plasma exchange support a
humoral pathogenesis.16,18 More recently, T cell mediated cytotoxicity
has been suggested to play a major role in destruction of neurons and
astrocytes,8,19,20 and even in the origin of GLUR3 autoantigenic peptide, by cleavage of glutamate receptor by granzyme B, a serine
protease released by cytotoxic T lymphocytes.21 Furthermore, treatment with tacrolimus, a suppressor of T cell activation, has also been
studied in patients with RE with good results.22
In our patient, azathioprine, plasma exchange and interferon
beta have been of no benefit, and despite an independent decrease in
seizure frequency, we began intravenous immunoglobulin due to the
cognitive decline.1,23
Finally, the possibility of a double pathology has also been
proposed and diagnosed in about 10% of RE cases.24 We conclude
that unihemispheric chronic vasculitis may resemble an adult onset
RE, and persistent gadolinium enhanced lesions on MRI are helpful
for differential diagnosis between the 2 conditions.

Unihemispheric chronic vasculitis may resemble
an adult onset Rasmussen encephalitis, and
persistent gadolinium enhanced lesions on
magnetic resonance imaging are helpful for
differential diagnosis between the 2 conditions.

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The Neurologist • Volume 15, Number 5, September 2009

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