doi:10.1111/j.1750-3639.2009.00300.
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COM JANUARY 2009 CASE 2
31-YEAR-OLD MAN WITH BALINT’S SYNDROME AND VISUAL
PROBLEMS bpa_300 527..531
Ewa Izycka-Swieszewska1, Malgorzata Swierkocka- Miastkowska2, Edyta Szurowska3,
Eliza Lewandowska4, Teresa Wierzba-Bobrowicz4, Krzysztof Jodzio5
1—Department of Pathomorphology; 2—Department of Neurology; 3—Department of Radiology, Medical University of Gdansk, Poland;
4—Department of Neuropathology, Institute of Psychiatry and Neurology, Warsaw, Poland;
5—Institute of Psychology, University of Gdansk, Poland
CLINICAL HISTORY AND
NEUROIMAGING
A 31-year-old man was hospitalized due to retinitis and progressive
personality changes that had started several weeks earlier. He was
disorientated and had changes of affect with mood swings as well as
signs and symptoms of dementia. Neuropsychologically the patient
showed Balint’s syndrome (paralysis of visual fixation, optic ataxia,
and impairment of visual fixation) with anosognosia, visual and
spatial agnosia, ideomotor and ideational apraxia, attention deficits
and visual hallucinations. Electroencephalogram (EEG) showed
non-specific abnormalities. The ophthalmological exam revealed
retinitis with bilateral macular changes and partial atrophy of the
optic nerves. Laboratory tests and cerebrospinal fluid (CSF) exami-
nations were unremarkable. Magnetic Resonance Imaging (MRI)
showed diffuse areas with high signal intensity in T2-weighted
images involving periventricular and subcortical white matter of 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 was released 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 of
background 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
A B
Figure 1.
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mass (2.5–3 cm, Figure 1C), generalized cortical and subcortical
atrophy with focal T2-hyperintense areas in the frontal lobe. The
patient’s 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 throughout
the nervous tissue. The most intense lymphocytic and rod cells
infiltrates and nodular concentrations 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).
C D
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B
Figure 2.

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A B
Figure 3.

Figure 4.

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Correspondence
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 prominent
demyelination 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 process spreads 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 Balint’s 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 actively changed 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
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© 2009 The Authors; Journal Compilation © 2009 International Society of Neuropathology
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
78:63–70.
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
Neuropathol 39:193–202.
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 Microbiol 20:16–8.
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 Neuropathol 22:110–8.
5. Osetowska E (1980) Subacute Sclerosing Panencephalitis (SSPE) in:
Tissue neuropathology of viral and allergic encephalitides. Warsaw,
Washington, TT 75–54021, pp. 138–157.
6. Prashanth LK, Taly AB, Ravi V, Sinha S, Arunodaya GR (2006)
Adult onset subacute sclerosing panencephalitis: clinical profile of 39
patients from a tertiary centre. J Neurol Neurosurg Psychiatry
77:630–3.
7. Praveen- Kumar S, Sinha S, Taly AB (2007) Electroencephalographic
and imaging profile in a SSPE cohort: a correlative study. Clin
Neurophysiol 118:1947–54.
8. Singer C, Lang A, Suchowersky O (1997) Adult- onset subacute
sclerosing panencephalitis: case reports and review of the literature.
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9. Yakub BA (1996) Subacute sclerosing panencephalitis (SSPE): early
diagnosis, prognostic factors and natural history. J Neurol Sci
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10. Yapici Z (2006) SSPE presenting with Balint’s syndrome. Brain Dev
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ABSTRACT
A 31-year-old man presented with Balint’s 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).
Brain Pathology 19 (2009) 527–530