Rare disease

Case report

Confusion, dissociation and bizarre behaviour as the
onset of an early Susac syndrome
Marta Pérez-Lombardo, 1 Íñigo Alberdi-Páramo,1 Belén Ramos-Barragán,2
Diana Gimeno-Álvarez1
1

Instituto de Psiquiatría y Salud
Mental, Hospital Universitario
Clínico San Carlos, Madrid,
Spain
2
Hospital Universitario Virgen
del Rocío, Sevilla, Spain
Correspondence to
Marta Pérez-Lombardo,
​martaperezlombardo@​gmail.​
com
Accepted 13 August 2019

Summary
A 47-year-old woman presented an episode of confusion
and disorientation. According to remarkable psychiatric
records, she had been treated for major depression
and obsessive-compulsive disorder; however, no other
relevant background was known. After preliminary
examinations, blood analysis and neurological tests
were unspecific and inconclusive. Therefore, the case
was treated as a possible psychiatric episode related to
her previous psychiatric disorders. However, due to the
atypical presentation of the case, a cerebral MRI was
performed, which demonstrated multiple central lesions
of the corpus callosum (’snowball lesions’), as well as
several supratentorial white matter lesions. As a result of
the follow-up of the case, sensorineural hearing loss and
branch retinal artery were detected, which concluded in
the classic triad and the confirmation of the diagnosis of
a Susac syndrome.

Background

Susac syndrome is an autoimmune-mediated microangiopathy which affects the vessels of the brain,
retina and inner ear.1 The classic triad consists of
encephalopathy, branch retinal artery occlusion and
sensorineural hearing loss, although it might not be
present at the beginning of the illness.2
Encephalopathy has a myriad of presentations:
confusion, cerebellar dysfunction, cognitive impairment and neuropsychiatric symptoms.3 In fact, in
recent cases, the diagnosis is made when vision and
hearing loss is documented.4 The purpose of this case
is to outline that Susac syndrome may have various
early-onset symptoms; therefore, the disease can
be diagnosed earlier and treated more aggressively
before it causes severe damage to the patient.

Case presentation

© BMJ Publishing Group
Limited 2019. No commercial
re-use. See rights and
permissions. Published by BMJ.
To cite: Pérez-Lombardo M,
Alberdi-Páramo Í,
Ramos-Barragán B, et al. BMJ
Case Rep 2019;12:e229422.
doi:10.1136/bcr-2019229422

A 47-year-old woman presented an episode of
confusion associated with spatial and temporary
disorientation in the morning. The patient said
that she had difficulties focusing on simple tasks
such as housework over the last 2 months. She
also described episodes of dizziness, normally
associated with high levels of anxiety related to
daily life situations, which concluded to insomnia.
As a result of her anxiety, her family doctor
prescribed betahistine and lorazepam 1 mg/day
for 1 week before the episode, both taken at night,
improving her insomnia. She also verbalised spontaneous hemicrania oppressive headaches, but no

photophobia, phonophobia or symptoms associated with the parasympathetic nervous system
(profuse sweating, dizziness, slow pulse, nausea or
vomiting). The patient also described additional
symptoms such as dizziness and instability similar
to vertigo symptoms. Furthermore, her partner
said that she was having temporary disorientation
episodes and that she was not able to remember
important events of her life, such as the death of
her father 5 years ago.
According to the patient’s psychiatric personal
history, she was diagnosed with obsessive-compulsive disorder 20 years ago and after a 3-year treatment has been in remission. The patient also suffered
from major depression, which was first related to
an abortion and followed by several relapses all
related to stressful life events in the following years.
Apart from her depression, the patient had no other
significant medical or family history.
Observations from the first neurological examination concluded that the patient presented partial
space disorientation (correct city but not the right
hospital) and total temporary disorientation (incorrect date, including the year). Although attention
was preserved (she named all the 12 months backwards correctly), calculation was only possible
subtracting 4 from 100, not 7 from 100. In addition,
her memory was altered, obtaining a digit span task
within six and two recalls (forward and backward),
a score of 0 out of 8 on the Memory Impairment
Screen and a normal clock-drawing test without
visuospatial dysfunction reported. Language was
fluent and spontaneous without aphasic elements,
and nomination of objects and name registration
were preserved. The patient correctly obeyed axial
and appendicular orders. However, phonemic and
semantic fluencies were altered, with a frequency of
only four words per minute. During examination
she tended to manipulate objects with no purpose.
Cranial nerves were not altered. A limb examination
showed normal tone and power. Hyper-reflexia was
noted on stretch reflex tests. Sensory tests showed
altered proprioception with failures in more than
50% of the distal interphalangeal determination
movement of the four limbs. No further abnormalities on sensory tests were found and coordination
was not altered. Cerebellar signs were not observed.
Gait was described as little walk steps, not being
able to explore the tandem gait due to the instability perceived by the patient. Video head impulse
test was negative.

Pérez-Lombardo M, et al. BMJ Case Rep 2019;12:e229422. doi:10.1136/bcr-2019-229422

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Rare disease
Psychopathological examination showed remarkable inhibition during the interview. For example, no proper eye contact
was made with the interviewer. Language was spontaneous and
fluent, and the patient had coherent and grammatically correct
structured speech, with no semantic or syntactic errors. The
thinking process was unaltered, although ruminative thoughts
classified as obsessive kind were present, with no behavioural
consequences in daily life described by her or her partner. No
psychotic symptoms (delusion or altered perceptions) were
reported at first examination, and the patient said her mood was
low. A diminution of expressions of emotions was observed, not
categorised as alexithymia as concerns about her problems were
verbalised by the patient. Anxiety was verbalised but not shown
at this time. Insomnia and low appetite were also reported.
Insight was conserved, as she recognised all limitations caused
by her mental status.
The cognitive impairment was not congruent with the possibility of describing anxiety symptoms as the principal cause of
the disease. Therefore, the patient was hospitalised to make
further examinations.

Investigations

Brain CT was normal. An MRI of the brain showed T2 hyperintense multifocal supratentorial white matter lesions located in
the periventricular, subcortical and juxtacortical areas. The cerebellum, basal ganglia, median cerebellar peduncles and corpus
callosum were also affected (figure 1A–C). Routine laboratory analysis, thyroid stimulating hormone, ACE, antinuclear
antibody, antiendothelial cell antibodies, lupus anticoagulant,
protein electrophoresis, anti-NMO antibodies titre, and testing
for HIV, hepatitis B and C, Epstein-Barr, toxoplasmosis, herpes
zoster, herpes simplex, cytomegalovirus, Borrelia burgdorferi and
measles virus were all negative. Oligoclonal bands in the cerebrospinal fluid (CSF) were absent. CSF showed an isolated elevation
of protein (147), with normal levels of glucose, and no white or
red blood cells present. Electroencephalography was unspecific.
Tests for autoimmune encephalitis were not carried out due to
limitations in hospital resources.
Retinal fluorescein angiography was normal at this time,
showing a vasculitis focus on the right eye 1 month later. Tone
audiometry revealed right light sensorineural hearing loss,
getting worse one month later as it became mild to moderate.

time of the first interview. On the third day of hospitalisation,
the patient presented disorientated behaviour: she looked for
her personal things at the same place several times, could not
give concrete answers to the questions asked, and presented
loss of anal sphincter during one of the neurological examinations. Nevertheless, the MRI showed white matter lesions, and
according to the inconclusive and unspecific psychiatric symptoms primary psychiatric disorders were excluded.
Afterwards, the differential diagnosis was focused on inflammatory, degenerative, tumorous, infectious, vascular, toxic-metabolic and autoimmune causes. Given the negative results
obtained from the investigations carried out and the answer to
corticosteroids registered, an autoimmune cause was the first
diagnosis proposed.

Treatment

The patient was first treated with intravenous methylprednisolone and intravenous immunoglobulin (IVIG), with good initial
response. Azathioprine (50 mg/day) was added for maintenance.
Oral prednisone (40 mg/day) was prescribed with gradual dose
reduction for the outpatient follow-up.

Outcome and follow-up

The initial differential diagnosis took place in a wider field than
usual: neurological versus psychiatric disorder. As mentioned
above, cognitive impairment was not congruent with a mood
disorder, and psychotic symptoms were not present at the

One month later, after her first treatment, the patient suffered
a relapse which was caused by insufficient doses of oral prednisone after leaving the hospital. The patient presented language
alterations and cognitive impairment, similar to the first episode.
Therefore, she was treated with methylprednisolone once more
and covered with higher doses of prednisone (60 mg/day)
until azathioprine reached therapeutic doses 3 months later. A
new MRI was done, which showed radiological improvement
of the corpus callosum lesions and the left cerebellar lesion
(figure 2A,B), without new lesions and no contrast enhancement.
Two days after leaving the hospital for the second treatment, the patient was hospitalised once again for emesis and
behavioural alterations (psychomotor inhibition and oppositionist attitude). However, this time, the brain MRI showed new
subcortical and pons (mostly in the pons and medulla oblongata
junction) T2 hyperintense lesions (figure 2C). In addition, millimetric leptomeningeal lesions showed up with contrast enhancement, along with deterioration of hearing capacity in the right
ear (figure 3) and retinal branch ischaemia on the left eye. The
patient was again treated with IVIG, and two treatment cycles
with cyclophosphamide (15 mg/kg) were added to the initial
treatment, resulting in good initial response and tolerance.
In conclusion, the patient experienced recovery from the
neurological symptoms, as well as an improvement in neuropsychiatric symptoms; no further psychotic or dissociative episodes

Figure 1 Fluid-attenuated inversion recovery (FLAIR) MRI
at presentation. (A) FLAIR sagittal MRI showing white matter lesions in
the corpus callosum (snowball lesions) and cerebellum lesion. (B) FLAIR
sagittal MRI which shows the extension of the cerebellum lesion and
the affection of the basal ganglia. (C) FLAIR axial MRI with a new view
of the cerebellum lesion.

Figure 2 Fluid-attenuated inversion recovery sagittal MRI 1 month
later at second (A,B) and third (C) hospitalisations. (A) The remaining
lesions still including the characteristic lesions of the corpus callosum,
although to a lesser extent than those shown on the first MRI. (B)
Diffuse subcortical white and grey matter lesions. (C) New subcortical
and pons and medulla oblongata junction T2 hyperintense lesions.

Differential diagnosis

2

Pérez-Lombardo M, et al. BMJ Case Rep 2019;12:e229422. doi:10.1136/bcr-2019-229422

Rare disease

Figure 3 Tone audiometry. The horizontal axis shows the frequency
in kilohertz, while the vertical axis shows the decibel level at which the
frequency is perceived. (A) Tone audiometry at presentation. No damage
was found. (B) Tone audiometry at relapse 1 month later. It shows
sensorineural hearing loss in the right ear, with 40% drop in the middle
and low frequencies. FF1, Free Field 1 and FF2, Free Field 2 (right and
left ear); PTA, Pure Tone Average.
were reported and her memory was recovered. The patient is
currently on treatment with azathioprine.

Discussion

Susac syndrome is a rare disease which has probably been misdiagnosed numerous times, although the reported cases over the
past 10 years have helped create awareness of the disease and
the neuropsychiatric symptoms that may be observed. Gender
is a relevant characteristic in this syndrome, as it affects women
between 20 and 40 years old, with a male to female ratio of
1:3.5.1 The development of the illness depends on gender, with
a better prognosis among men.2
In 2013, Dörr et al2 published a review of all Susac cases
reported until December 2012. Only 13% of the patients had the
typical clinical triad at disease onset. Normally, after 21 weeks,
the triad was complete. Some primary symptoms are headaches,
cognitive impairment (usually with loss of memory, concentration and executive functions), confusion (normally with disorientation), emotional disturbance and behavioural changes.2 In
our case, the triad only took 4 weeks to be reported, and the
symptoms at onset consisted of headache, confusion and also
dissociation. The patient had almost no memory of her three
stays in the hospital. In fact, she could not remember any confusion state, bizarre behaviour or even how she arrived at the
hospital.
It is essential to understand the neuropsychiatric outcome of
the disease because, in the case presented, symptoms and side
effects became extremely aggressive for the patient. Even though
there was slow tapering of corticosteroids after the acute episode,
a relapse was reported. Therefore, an absence of a complete triad

at onset should not be a reason to reject the diagnosis. Moreover,
typical snowball lesions in the corpus callosum should be considered a main sign for the diagnosis, as it is normally present with
the first symptoms of the disease. We suggest that the presence of
this kind of lesions (in the absence of acute disseminated encephalomyelitis or multiple sclerosis lesions) could be considered as a
diagnostic sign given the two other symptoms of the triad.
According to the proposed criteria for diagnosis by Kleffner et
al,4 initially our patient could only be defined as a probable Susac
syndrome. Specifically in this case, brain involvement consisted
on typical findings on cranial MRI and cognitive impairment,
headache and behavioural changes.Vestibulocochlear involvement included mild hearing loss supported by audiogram and
peripheral vertigo symptoms. One month later, the triad was
complete, with damage shown on spectral domain optical
coherence tomography, funduscopy and in the tone audiometry,
which eventually defined our case as definite diagnosis of Susac
syndrome.
The definition of the severity of symptoms is related to the
implication on the central nervous system during the initial
peak of the disease and course of illness. This case is considered ‘severe’ according to the definition of Rennebohm et al.5
The patient presented a moderate encephalopathy and a moderate-severe cognitive and language dysfunction, and the follow-up
MRI showed new ischaemic lesions. Moreover, the response to
immunosuppressive treatment was initially positive, but it was
not followed by a sustained trend of adequate improvement.
The mechanisms involved in the development of the disease
are still unclear. However, it is thought to be an autoimmune
process, which would explain the good and long-term response
to immunosuppressive therapy. Recent findings focus future
research on the blood–brain barrier as an important agent in
the immune cell penetration and the reactivation of the immune
system. The study of disease-specific antigens, T cell involvement, as well as the brain endothelial cell and components of
the neurovascular junction in different central nervous system
inflammatory diseases would lead to a better understanding of
the inflammatory process occurring in Susac syndrome.6
According to this evidence, first-line treatments are focused on
the immune system: high doses of corticosteroids, IVIG, cyclophosphamide or azathioprine in the acute period, and a slow
tapering of corticosteroids as maintenance.2 Although target
treatment must be considered according to the main organic
threat, all cases must be first treated with corticosteroids. If
symptoms are not just mild, treatment with IVIG, cyclophosphamide, mycophenolate mofetil or tacrolimus should be
considered gradually, according to the severity of symptoms.5
In the case presented, our patient was first treated with corticosteroids and recovery was complete, showing no more cognitive
impairment. However, relapse occurred after only 3 weeks of
complete recovery.
Although the presented case was treated correctly and early
on, sometimes this uncommon disease makes diagnosis or treatment difficult to identify. Our team presented a defined Susac
syndrome with an unspecific onset but an aggressive outcome.
It was necessary to increase the treatment, as it was not enough
with the first line used. It was noted through the study that it is
important to consider this disease as a possible cause of neuropsychiatric symptoms, as well as the necessity of an aggressive
treatment according to its severity. Therefore, misdiagnosis of
Susac syndrome will be reduced and prognosis will be better. .
Further studies are required to get an earlier diagnosis, to optimise treatment options, and to provide both patients and professionals an improved understanding of this rare disease.

Pérez-Lombardo M, et al. BMJ Case Rep 2019;12:e229422. doi:10.1136/bcr-2019-229422

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Rare disease
Learning points
►► Susac syndrome is a rare disease with a diagnosis that has

increased in the past years.
►► The early outcome of this disease is normally unspecific, with
a wide range of neuropsychiatric symptoms.
►► Suspicion of Susac syndrome when the classic triad is not
complete ensures a faster diagnosis and an earlier treatment.
►► The distinctive snowball lesions in the corpus callosum should
be considered as almost pathognomonic, as their presence
and typical localisation are normally directly related with
Susac syndrome.
►► Immunosuppressive therapy is the least recommended in the
guidelines, although further studies are required to decrease
the high risk of relapse in these patients.
Contributors MP-L: study concept and design, drafting of the manuscript, data
collection and interpretation. IA-P: critical revision of the manuscript, analysis
and interpretation of data. BR-B: critical revision and design of the manuscript,

interpretation of data. DG-A: supervisor of the study, collection and interpretation
of data, critical revision of the manuscript. All authors provided final approval of the
version to be published and are guarantors.
Funding The authors have not declared a specific grant for this research from any
funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.

References

1 Greco A, De Virgilio A, Gallo A, et al. Susac’s syndrome — Pathogenesis, clinical
variants and treatment approaches. Autoimmun Rev 2014;13:814–21.
2 Dörr J, Krautwald S, Wildemann B, et al. Characteristics of Susac syndrome: a review of
all reported cases. Nat Rev Neurol 2013;9:307–16.
3 Ben David C, Sharif K, Watad A, et al. Susac syndrome: a rare cause of a confusional
state. Isr Med Assoc J 2017;19:651–3.
4 Kleffner I, Dörr J, Ringelstein M, et al. Diagnostic criteria for Susac syndrome. J Neurol
Neurosurg Psychiatry 2016;87:1287–95.
5 Rennebohm RM, Asdaghi N, Srivastava S, et al. Guidelines for treatment of Susac
syndrome – An update. Int J Stroke 2018:1–11.
6 Lindner M, Klotz L, Wiendl H. Mechanisms underlying lesion development and lesion
distribution in CNS autoimmunity. J Neurochem 2018;146:122–32.

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Pérez-Lombardo M, et al. BMJ Case Rep 2019;12:e229422. doi:10.1136/bcr-2019-229422