Ohara et al. BMC Neurology
(2019) 19:351
https://doi.org/10.1186/s12883-019-1580-3

CASE REPORT

Open Access

Neuromyelitis optica spectrum disorder
with massive basal ganglia involvement: a
case report
Shinji Ohara1,2*, Taka-aki Miyahira1, Kenya Oguchi1, Yo-ichi Takei1, Fumihiro Yanagimura3, Izumi Kawachi3,
Kiyomitsu Oyanagi4,5 and Akiyoshi Kakita6

Abstract
Background: Occurrence of basal ganglia involvement in neuromyelitis optica spectrum disorders (NMOSD) has
rarely been reported and none documented pathologically.
Case presentation: A 73-year-old female was clinically diagnosed with a NMOSD based on the clinical and
radiological features and positive serum autoantibodies to AQP4. One month before her death, she became acutely
ill with disturbed consciousness and right hemiparesis, and was diagnosed and treated as having basal ganglia
infarction based on the brain CT. She made a partial recovery but later died from heart failure. At autopsy, the
corresponding basal ganglia process revealed a large fresh area of necrosis. Histologically, several pathological
signatures of NMOSD could be recognized in the lesion, including inflammatory cell infiltrations by B and T
lymphocytes, perivascular complement and fibrinogen deposition, and the appearance of numerous phagocytosed
corpora amylacea within the infiltrating macrophages.
Conclusions: The present case illustrates that basal ganglia may be directly involved in the pathological processes
of NMOSD, although the possibility of modification of the lesions by superimposed regional ischemia could not be
excluded.
Keywords: Neuromyelitis optica spectrum disorder (NMOSD), Astrocytopathy, Basal ganglia, Blood brain barrier

Background
Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory autoimmune disease of the central nervous system (CNS) associated with episodes of transverse
myelitis, optic neuritis and other neurologic manifestations. Antoantibodies to the water channel aquaporin-4
(AQP4), which is predominantly expressed in astrocyte
foot processes, is a serum biomarker and is expressed in a
majority of the cases with this syndrome [1].
Neuropathologically, NMOSD has been regarded as an
autoimmune astrocytopathy, in which vasculocentric inflammatory cell inflammation and complement deposition
are cardinal features [2]. This astrocytopathy results in the
formation of necrotic lesions typically in the spinal cord

and in the optic tracts, often associated with macroscopic
cavity formation [3]. Other CNS areas than spinal cord
and optic tracts could also be involved in NMOSD, such
as the cerebral hemisphere, internal capsule, and periventricular AQP4 enriched regions including the area postrema and hypothalamus [1, 3, 4]. However, direct
involvement of the deep cerebral central gray matter especially of basal ganglia has rarely been documented.
We here report a patient with NMOSD who developed
a large basal ganglia lesion 1 month prior to her death,
which was initially diagnosed as an ischemic infarction.
However, autopsy revealed unequivocal immunohistological features of NMO in the basal ganglia lesion.

* Correspondence: shinji.ohara@iida.or.jp
1
Department of Neurology, Matsumoto Medical Center, Minami 2-20-30,
Matsumoto 399-8701, Japan
2
Department of Neurology, Iida Hospital, 1-15 Ohdori, Iida 395-8505, Japan
Full list of author information is available at the end of the article

Case presentation

A previously healthy 63 year-old Japanese female presented with gait disturbance and was diagnosed as having transverse myelopathy with a sensory level of T5 and

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
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Ohara et al. BMC Neurology

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bilateral Babinski signs. She was given intravenous methyl prednisolone, resulting in a complete clinical recovery. At age 67, she started to complain of numbness on
the left side of her face and developed an ataxic gait.
MRI of the brain and the spinal cord revealed a focal lesion in the pontine tegmentum on the right, a cystic lesion in the subcortical white matter lateral to the basal
ganglia on the right (Fig. 1a, b), and a longitudinally extending cavitary lesion affecting the C2-C6 cervical cord
(Fig. 1c). Cerebrospinal fluid (CSF) examination revealed
normal protein content (43 mg/dl) with increased myelin
basic protein (MBP) (253 pg/ml, normal < 120). Oligoclonal bands were negative. Steroid therapy resulted in a
good recovery. At age 69, she developed optic neuritis
bilaterally. Serum antibodies to AQP4 was positive, and
she was diagnosed as having NMOSD. After intravenous
steroid therapy, she was started on a low maintenance
dose of oral prednisone of 15 mg. At age 70, she was unable to walk and was admitted to our hospital. The
neurologic examination revealed the patient had normal
mental status, bilaterally decreased vision, mild dysarthria,
weakness and sensory loss in the right upper extremity,
and spastic paraplegia. Steroid administration was not effective in reversing her condition and she became wheelchair bound. At age 72, she developed acute myocardial
infarction which was successfully treated with a stent
placement. She was incidentally found to have aplastic

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anemia and received blood transfusions. One month prior
to death, she developed right hemiparesis and disturbed
consciousness over several days, and the brain CT revealed a large low-density lesion involving the left basal
ganglia (Fig. 2d, e). A diagnosis of acute infarction was
made and she was treated conservatively. She gradually recovered consciousness but never returned to her baseline.
She died from heart failure at age 73.
The general autopsy was granted and was performed 1
hour after the death, which revealed old and recent myocardial infarcts and aspergillosis of the lung.
There was no evidence of systemic vasculitis. The
brain was small and weighed 1080 g. There were mild
atheromatous changes in the basal arteries of Willis. The
bilateral optic nerves and chiasma were atrophic.
On the coronal sections, there was a large soft necrotic
focus involving the putamen, globus pallidus, internal
capsule and caudate nucleus on the left side (Fig. 2a). A
soft necrotic lesion was also seen in the corpus callosum
(arrowhead in Fig. 2a). On the opposite side of the cerebral hemisphere, there were cystic lesions in the subcortical and deep white matter (Fig. 2a. Thin and thick
arrows). In the brainstem, there was a focal plaque-like
lesions in the medial lemniscus. The spinal cord revealed
central cavitary lesions extending from C3 to C5.
Formalin-fixed, paraffin embedded sections of the
brain and the spinal cord were stained with Hematoxylin

Fig. 1 Radiologic findings. a-c) Brain MRI images taken 3 years after the onset revealed a cystic lesion in the right basal ganglia (arrow), which
was subsequently histologically examined at autopsy (Fig. 2a, j). a) T2 MRI, b) Flair MRI. c) T2-MRI of the spinal cord taken 4 years after the onset,
revealing longitudinal lesions involving C3–6 spinal segments. d) Brain CT taken 1 month prior to the death, a few days after the patient
developed right hemiparesis and disturbed consciousness. The left basal ganglia show extensive low densities accompanied by narrowing of the
lateral vetricles (arrow)

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Fig. 2 (See legend on next page.)

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(See figure on previous page.)
Fig. 2 Neuropathology of the basal ganglia. a Coronal section of the brain after fixation with formalin. There is a large soft necrotic lesion
involving the basal ganglia and a part of the internal capsule. A separate small necrotic focus is seen in the corpus callosum (arrowhead). In the
right cerebral hemisphere, a large cystic lesion in the white matter lateral to the putamen (large arrow) and lesions in the subcortical white
matter (small arrows) are seen. The optic chiasm appeared atrophic and there was a mild to moderate atherosclerotic changes in the basal
arteries. b Klüver-Barrera myelin stain of the section approximately 1 cm posterior to. The necrotic area is well demarcated involving the globus
pallidus extending to the internal capsule to the head of the caudate. c-f Serial sections stained immunohistochemically using the antibody for
GFAP (c), AQP4 (d), CD138 for plasma cells (e) and CD8 for the marker of cytotoxic T cells (f). The necrotic lesions lacked immunostaining of both
GFAP and AQP4 with a tendency to more preservation of the former (arrows in C). There are extensive CD138 and CD8 positive lymphocytic cell
infiltrations in vasocentric patterns around small and medium sized vessels surrounding the area of necrosis. Bar = 200 μm. g-i
Immunohistochemistry of the necrotic lesion stained for C9neo (g), fibrinogen (h), H.E. (i) and CD68 for macrophage (Inset of I). There were
scattered foci of vasocentric complement deposition (g) and exudation of fibrinogen around the vessel wall (h). There are numerous
macrophages containing corpora amylacea in the cytoplasm(I), as identified as such by the lack of immunostaining for CD68 (Inset of I). Bar =
100 μm (g, h), 20 μm (I, Inset). j-l Right basal ganglia lesions stained with Klüver-Barrera (j). There are well demarcated cystic lesions in the
basolateral of the basal ganglia (*). k Enlarged area of (*) in (j). Microscopically, the lesion consisted of loosely associated fibrillary astrocytosis with
few inflammatory cells. Klüver-Barrera myelin stain. l Enlarged area indicated by the arrow in (k). The neurons appeared relatively well preserved
in the loosely arranged myelinated fibers. Arrows indicate axonal spheroid bodies. H&E. Bar = 20 μm

and Eosin (H&E), Klüver-Barrera (KB) and Grocott methenamine silver staining for fungi. Immunohistochemistry with a streptavidin-Biotin method was performed
with the following antibodies. Rabbit polyclonal antibodies against AQP4 (Chemicon, 1:1000), glial fibrillary
acidic protein (GFAP; DAKO, 1:800), myelin basic protein (MBP 1:150, Novocastra), the cytotoxic T-cell
marker CD8 (1:50, DAKO), the plasma cell marker
CD138 (1:200, DAKO), macrophage/microglial marker
CD68 (1:100, DAKO), fibrinogen (1:3000, DAKO),
C9neo (Dr. Paul Morgan, UK, 1:200). Reaction products
were visualized with DAB.
Histologically, optic nerves revealed moderate gliosis
without active features of neuronal degeneration. The
wall of the small vessels in the optic nerve invariably
showed hyalinized thickening. The necrotic foci in the
left ganglia stained pale with H&E and KB stains, and
was well demarcated and irregular in contour (Fig. 2b).
The lesion was largely GFAP and AQP4 negative, with
some tendency of relatively more GFAP preservation
than AQP4 (Fig. 2c, d). At the margin surrounding the
lesion, there was a prominent perivascular inflammatory
cell infiltration around small and medium sized vessels.
Many of the infiltrating cells were immunoreactive either for B and T lymphocyte or plasma cell markers
(Fig. 2e, f). Immunohistochemistry with antibodies for
C9neo and fibrinogen were positive in vasocentric patterns, which was found exclusively in the necrotic lesion
(Fig. 2g, h). Numerous macrophages were also found to
contain corpora amylacea in their cytoplasm (Fig. 2i).
The Grocott methenamine silver stain was negative in
the necrotic lesions. Occasional eosinophils and neutrophils could be recognized in the macroscopically fresh
appearing lesion of the corpus callosum.
By contrast, the cystic lesions contralateral hemispheres
were lined by fibrillary gliosis and there were few inflammatory cells (Fig. 2j-l). In the periphery of a lesion, many
viable looking neurons were seen within the loosely

arranged myelinated fibers (Fig. 2k, l). No thrombotic occlusions could be found in the lenticulostriate arteries on
both sides despite an intensive search. There were no cortical demyelinating lesions except for several scattered foci
of ischemic infarcts of various stage.
In the brain stem, the pontine tegmentum showed a few
foci of gliosis associated with demyelination and relatively
preserved axons. In the spinal cord, there were cystic lesions predominantly involving the central gray matter of
the thoracic cord. There was relative sparing of axons
compared to myelin in the area surrounding the cystic lesions, where the loss of AQP4 was much broader than
those area with GFAP loss. In and around the cystic lesions, small vessels with thickened hyalinized walls were
seen. There were only a few infiltrating T and B cells.

Discussion and conclusion
The present case could be unequivocally diagnosed as
NMOSD based on typical clinical course and imaging
features, and a presence of positive serum AQP4 antibody [1, 5], except that, one-month pre-mortem, the patient developed consciousness disturbance and
hemiparesis, which was considered to be due to a large
basal ganglia infarct. However, upon autopsy, the affected basal ganglia revealed immunohistological signatures of NMO, such as perivascular deposition of active
complement component and extensive vasocentric inflammatory cell infiltration consisting of T and B lymphocytes and plasma cells [2], a tendency of relative
preservation of GFAP compared with AQP4 in the margin of the necrotic lesions [3]. Furthermore, numerous
phagocytosed corpora amylacea were observed in the
necrotic lesion. Corpora amylacea are age-dependent
spherical, basophilic, PAS positive inclusions that are
predominantly found in the astrocytic foot processes
with certain predilections including around small vessels
[6], and their appearance in phagocytosed state has been
regarded as a histological hallmark of astrocytic injury in

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NMO [7]. It is speculated that corpora amylacea liberated
from the degenerating astrocytic foot processes around
blood vessels could be engulfed by infiltrating macrophages through intact regional blood supply [7].
Occurrence of basal ganglia involvement in NMOSD has
been rarely reported in the literature [8, 9] and none documented pathologically. Therefore, one may wonder if NMO
pathology could solely be responsible for causing such large
area of necrosis in the basal ganglia as seen in the present patient. In this regard, it should be noted that the presence of
AQP4 antibody alone does not exhibit any pathological effects in animals and humans [10, 11]. Nishiyama et al. suggested that certain immunologic events that increase in the
Blood brain barrier (BBB) permeability are needed to allow
entry and binding to AQP4 on astrocytes [11]. Recently, however, Jueneman et al. reported that in a rat stroke model, the
animal infused with AQP4 antibodies suffered more vasogenic edema formation as compared to the controls, and that
the size of the infarct was larger in the AQP4 antibody infused animals [12].
In the present case, exudation of fibrinogen could be
demonstrated immunohistochemically around small vessels in the necrotic lesion, indicating the occurrence of
BBB breakdown prior to the development of the necrotic
lesion. The BBB anatomically consists of both the endothelial cells lining the capillary lumen and the surrounding astrocytic foot processes [13]. Moreover, it seems
worthy of note that Ikuta et al. studied ultrastructural
changes of astrocytes in various acute model of brain injuries including ischemia, and found that the first stage
is characterized by swelling of the astrocytic foot processes surrounding the vessels and neurons, followed by
the detachment of the astrocytic processes from vessel
wall, suggesting the occurrence of BBB breakdown in
the very acute stage of ischemia [14]. Therefore, it is
possible to consider that pre-existing vasculopathy and/
or focal ischemia may have been contributory to the acceleration of AQP4 antibody-mediated astrocytopathy
through leaky BBB, resulting in the formation of a large
necrotic lesions in the basal ganglia.
Because the basal ganglia are a common site of ischemic stroke especially with elderly patients with preexisting vasculopathy, its involvement in NMOSD may have
been under-diagnosed so far. Further clinicopathological
studies are required to elucidate the frequency and the
nature of basal ganglia lesions in NMOSD.
Abbreviations
AQP4: Aquaporin 4; BBB: Blood brain barrier; CSF: Cerebrospinal fluid; GFAP: Glial
fibrillary acidic protein; H.E.: Hematoxylin-eosin stain; MRI: Magnetic resonance
imaging; NMO: Neuromyelitis optica; NMOSD: Neuromyelitis optica spectrum
disorders; PAS: Periodic acid—Schiff stain
Acknowledgements
The authors thank Ms. Mieko Chino, Department of Clinical Laboratory,
Matsumoto Medical Center for her technical assistance. We thank Dr. B. P.

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Morgan for provision of complement antibody. We also thank Dr. Takeo
Misu, Department of Neurology, Tohoku University School of Medicine,
Sendai, Japan, for his helpful discussion, and Prof. Robert E Schmidt, Division
of Neuropathology, Washington University School of Medicine at St.Louis, for
his critical reading of the manuscript.
Author’s contribution
SO wrote manuscript. MT, YT, K Oguchi, SO took care of the patient and
collected clinical data including CSF. TM, YT, SO and K Oyanagi performed
brain cutting. FY and IK performed immunostaining of C9neo. AK performed
immunostaining of AQP4 and various leucocyte antigens. SO, YT, K Oyanagi,
IK and AK reviewed all of the histopathological data. All authors read and
approved the manuscript.
Funding
There is no targeted funding for this publication.
Availability of data and materials
The datasets used in the current study are available form the corresponding
author on reasonable request.
Ethics approval and consent to participate
Not applicable.
Consent for publication
Written informed consent was obtained from the legal guardian of the
patient for publication of this autopsy case report and any accompanying
images. A copy of the written consent is available for review by the Editorin-Chief of this journal.
Competing interests
The authors declare that they have no competing interests.
Author details
Department of Neurology, Matsumoto Medical Center, Minami 2-20-30,
Matsumoto 399-8701, Japan. 2Department of Neurology, Iida Hospital, 1-15
Ohdori, Iida 395-8505, Japan. 3Department of Neurology, Brain Research
Institute, Niigata University, Niigata, Japan. 4Division of Neuropathology, Brain
Research Center, Shinshu University School of Medicine, Matsumoto, Japan.
5
Brain Research Laboratory, Hatsuishi Hospital, Chiba, Japan. 6Department of
Neuropathology, Brain Research Institute, Niigata University, Niigata, Japan.
1

Received: 23 September 2019 Accepted: 19 December 2019

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