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C O M J A N U A R Y 2 0 0 9 C A S E 2
31-YEAR-OLD MAN WITH BALINTS SYNDROME AND VISUAL
PROBLEMSbpa_300 527..531Ewa Izycka-Swieszewska1, Malgorzata
Swierkocka- Miastkowska2, Edyta Szurowska3,
Eliza Lewandowska4, Teresa Wierzba-Bobrowicz4, Krzysztof
Jodzio5
1Department of Pathomorphology; 2Department of Neurology;
3Department of Radiology, Medical University of Gdansk, Poland;
4Department of Neuropathology, Institute of Psychiatry and
Neurology, Warsaw, Poland;
5Institute of Psychology, University of Gdansk, Poland
CLINICAL HISTORY ANDNEUROIMAGING
A 31-year-old man was hospitalized due to retinitis and
progressive
personality changes that had started several weeks earlier. He
was
disorientated andhad changes of affect with mood swings as well
as
signs and symptoms of dementia. Neuropsychologically the
patient
showed Balints syndrome (paralysis of visualfixation, optic
ataxia,
and impairment of visual fixation) with anosognosia, visual
and
spatial agnosia, ideomotor and ideational apraxia, attention
deficits
and visual hallucinations. Electroencephalogram (EEG)
showednon-specific abnormalities. The ophthalmological exam
revealed
retinitis with bilateral macular changes and partial atrophy of
the
optic nerves. Laboratory tests and cerebrospinalfluid (CSF)
exami-
nations were unremarkable. Magnetic Resonance Imaging (MRI)
showed diffuse areas with high signal intensity in
T2-weighted
imagesinvolving periventricularand subcortical white matterof
the
occipital and parietal lobes. (Figure 1A). Furthermore, a focal
1 cm
mass lesion was detected in the sellar region. There was
some
clinical improvement with steroid treatment,but the patient
refused
further diagnostic procedures and wasreleased to home.
He was stable for the next 2.5 years, but then developed
behav-
ioral changes with aggressiveness and hallucinations.At
admission
he was almost blind and had bilateral pyramidal tract signs
and
symptoms. EEG was desynchronized with diffuse slowing
ofbackground activity. T2-weighted MRI scans showed
hyperintense
areas mainly involving the temporal and parietal lobes, while
the
occipital lobes were atrophic (Figure 1B). CSF showed
elevated
gamma-globulins and further testing of the CSF yielded a
diagno-
sis. Treatment with interferon and higher doses of steroids
pro-
duced a good response for the next 10 months. He then
developed
seizures, painful myoclonic jerks, dystonias, spasticity and
hyper-
algesia. MRI scans showed increased size of the cystic
suprasellar
mass (2.53 cm, Figure 1C), generalized cortical and
subcortical
atrophy with focal T2-hyperintense areas in the frontal lobe.
The
patients condition deteriorated rapidly over the next few
weeks,
resulting in tetraparesis and a decerebrate state. He expired
due to
pneumonia 48 months after his initial symptoms.
PATHOLOGICAL AUTOPSY FINDINGS
The brain weighed 1010 g. The cortex was thinned with
segmental
blurring of the gray-white boundary. The white matter was
yellow-
ish, indurated and firm, but in the occipital lobes rarefactions
were present. The cystic sellar tumor contained milky- grayish
fluid.
Histologically it was composed of connective tissue strands
and
septa lined with multilayered squamous epithelium with
peripheral
palisading of the nuclei (Figure 1D).
In the brain tissue chronic changes of variable duration and
distribution were found. The white matter findings included:
perivascular and intraparenchymal lymphocytic and macrophage
infiltrates, glial reaction, myelin loss and nuclear
abnormalities
within the glial cells. In the cortex neuronal cell loss,
gliosis and
sparse intranuclear inclusions were present (Figure 2A) The
inclusions were also apparent on plastic-embedded thick
sections
stained with toluidine blue (Figure 2B). The perivascular
lympho-
cytic cuffs were CD3 and CD20- positive. Moreover the rod
and
ramified LCA, and CD68- positive cells were scattered
throughoutthe nervous tissue. The most intense lymphocytic and rod
cells
infiltrates and nodularconcentrations were encountered in the
fron-
totemporal regions, where multiple foamy macrophages were
also
noted (Figures 3A and 3B). In the occipital and parietal lobes
the
loss of myelinated axons was most severe and was accompanied
by fibrillary gliosis as seen by GFAP. Ultrastructural
examination
revealed abnormal filamentous accumulations in both neuronal
and
oligodendroglial nuclei (Figure 4).
DCBA
Figure 1.
doi:10.1111/j.1750-3639.2009.00300.x
527Brain Pathology 19 (2009) 527530
2009 The Authors; Journal Compilation 2009 International Society
of Neuropathology
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DIAGNOSIS
Subacute sclerosing encephalitis (SSPE) and
craniopharyngioma.
At the second hospitalization, elevated anti- measles antibody
titers
were detected (1:16 in CSF and 1:256 in the blood).
DISCUSSION
Subacute sclerosing panencephalitis (SSPE) is a chronic
neuroin-
fection caused by a mutant measles virus (1, 3) that usually
occurs
in children. The clinical differential diagnosis of SSPE
includes
Schilder sclerosis, leukodystrophies, progressive paralysis,
atypi-
cal forms of multiple sclerosis and variant CJD (1, 3, 6).
Diagnosis
is usually based upon a specific presentation with four stages,
EEG
with periodic stereotyped high voltage discharges, and
elevated
titers of anti-measles antibodies in the CSF and blood (3, 4, 7,
9).
Stage I of disease is characterized by behavioral changes and
cog-
nitive decline. The visual problems and myoclonic jerks are
typical
for stage II, and stage III symptoms include dystonias,
choreoathe-
tosis and spasticity. In stage IV the symptoms progress to
auto-
nomic disturbances, coma and vegetative state (6, 9).
Histopathologically, SSPE is an encephalitis with
prominentdemyelination with variable topography and duration of
lesions
(1, 5). The occipital lobes are usually the initial location of
the
changes, and along with the chorioretinitis (which usually
accom-
panies the presentation) are the main causes of visual symptoms
(5,
6, 9). During the course of disease the processspreads into
contigu-
ous areas, including the basal ganglia and sometimes the
spinal
cord (5, 7). The perivascular and parenchymal inflammatory
infil-
trates are composed of lymphocytes, macrophages and
activated
microglia. Further characteristic and diagnostic findings are
intra-
nuclear Cowdry type A inclusions, which can be absent in
long-
standing cases(2, 4, 5, 8). Depending on duration of the process
the
active inflammation and/ or chronic destructive- reparative
changes
can be seen as diffuse demyelination, intense fibrillary
gliosis,neuronal loss and brain atrophy. In some chronic cases
Alzheimer-
type changes are encountered (1, 4, 8).
Our patient had an unusual clinical picture with a prolonged
period of stages I/ II and a fulminant course in the last few
weeks of
disease. The neuroimaging showed the evolution of the
process
which corresponded to some clinical symptoms and timing and
topography of neuropathological changes. Lesions from the
initial
MRI correlated with Balints syndrome, which is associated
with
bilateral posterior parietal and occipital damage(10).
Histologically
these areas showed inactive demyelinization, astrogliosis and
severe
cortical atrophy. In the temporal regions that activelychanged
in the
second MRI there was inflammation along with chronic
reparative
gliosis and neuronal loss. The T2-hyperintense frontal areas in
the
last neuroimaging showed active demyelinating
inflammation.Neuropathological differential diagnosis of SSPE
includes other
types of viral encephalitides, as well as demyelinating diseases
and
neurometabolic disorders (4, 5, 8). The clue for the diagnosis
is
confirmation of the presence of the measles virus
nucleocapsids
within the inclusions with immunohistochemical, molecular or
ultrastructural methods (2, 8, 10). In our case electron
microscopy
disclosed Paramyxovirus nucleocapsids, both in neuronal and
oli-
godendroglial nuclei. Although SSPE is usually seen in
children
and young adults, this case demonstrates that SSPE should still
be
considered in the neurological and neuropathological
differential
diagnoses even in adult patients. Furthermore this is a first
reported
case of SSPE coexisting with a brain tumor
(craniopharyngioma).
REFERENCES
1. Garg RK (2002) Subacute sclerosing panencephalitis. J
Postgrad Med
78:6370.
2. Lewandowska E, Szpak GM, Lechowicz W, Pasennik E, Sobczyk
W(2001) Ultrastructural changes in neuronal and glial cells in
subacute
sclerosing panencephalitis: correlation with disease duration.
Folia
Neuropathol39:193202.
3. Manayani DJ, Abraham M, Gnanamuthu C, Solomon T,
Alexander
M, Sridharan G (2002) SSPE- the continuing challenge. A
study
based on serological evidence from a tertiary care center in
India.
Indian J of Med Microbiol20:168.
4. Ortega-Aznar A, Romero-Vidal FJ, Castellvi J, Ferrer JM,
Codian A
(2003) Adult-onset of subacute sclerosing panencephalitis:
clinico-
pathological findings in 2 new cases. Clin
Neuropathol22:1108.
5. Osetowska E (1980) Subacute Sclerosing Panencephalitis (SSPE)
in:
Tissue neuropathology of viral and allergic encephalitides.
Warsaw,
Washington, TT 7554021, pp. 138157.
6. Prashanth LK, Taly AB, Ravi V, Sinha S, Arunodaya GR
(2006)
Adult onset subacute sclerosing panencephalitis: clinical
profile of 39patients from a tertiary centre. J Neurol Neurosurg
Psychiatry
77:6303.
7. Praveen- Kumar S, Sinha S, Taly AB (2007)
Electroencephalographic
and imaging profile in a SSPE cohort: a correlative study.
Clin
Neurophysiol118:194754.
8. Singer C, Lang A, Suchowersky O (1997) Adult- onset
subacute
sclerosing panencephalitis: case reports and review of the
literature.
Mov Disord12:34253.
9. Yakub BA (1996) Subacute sclerosing panencephalitis (SSPE):
early
diagnosis, prognostic factors and natural history. J Neurol
Sci
139:22734.
10. Yapici Z (2006) SSPE presenting with Balints syndrome. Brain
Dev
28:398400.
ABSTRACT
A 31-year-old man presented with Balints syndrome. Radiology
studies suggested an inflammatory demyelinating process
within
the occipital and parietal lobes. A cystic sellar/suprasellar
mass
was also found. Neuroimaging 2.5 years later showed
progression
of the lesions and growth of the tumor. Based on elevated
anti-
measles antibody titers in the cerebrospinal fluid subacute
scle-
rosing panencephalitis (SSPE) was diagnosed. After 4 years
of
disease the patient died in a decerebrate state with
tetraparesis.
Neuropathological examination showed brain atrophy with dis-
coloration and irregular induration of the white matter. The
sellar
tumor was a craniopharyngioma. Microscopically a chronic and
active panencephalitis was revealed with intranuclear
inclusions.Ultrastructural examination confirmed SSPE by
demonstrating
measles virus nucleocapsids within the inclusions. SSPE is a
rare
progressive neurological disorder caused by persistent
defective
measles virus infection and is usually seen in children and
young
adults. This disease has been eradicated in many countries
by
obligatory immunization. This case demonstrates, however,
that
SSPE should still be considered in the neurological and
neuro-
pathological differential diagnoses even in adult patients.
Further-
more this is a first reported case of SSPE coexisting with a
brain
tumor (craniopharyngioma).
Correspondence
530 Brain Pathology 19 (2009) 527530
2009 The Authors; Journal Compilation 2009 International Society
of Neuropathology
