Clinical Neurology and Neurosurgery 206 (2021) 106690

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Clinical Neurology and Neurosurgery
journal homepage: www.elsevier.com/locate/clineuro

Case Report

Cognitive impairment and affective disorder: A rare presentation of
cerebellar stroke
Ece Gok-Dursun, Ozge Berna Gultekin-Zaim, Ersin Tan, Isin Unal-Cevik *
Hacettepe University, Faculty of Medicine, Department of Neurology, Ankara, Turkey

A R T I C L E I N F O

A B S T R A C T

Keywords:
Schmahmann syndrome
CCAS scale
Depression
Infarct
Cerebellum

The awareness of the “Cerebellar Cognitive Affective Syndrome” (CCAS) as a clinical entity is emerging. The
CCAS is characterized by impaired executive functions, linguistic skills, visuospatial cognition and personality
change. Here we report a 56-year-old, male teacher who developed acute psychomotor retardation, low energy
level, infrequent speech, and mild cognitive decline. Two months before admission, he was initially diagnosed as
depression, and later misdiagnosed as encephalitis, which misled him to receive high-dose intravenous steroids
and antimicrobial drugs. The Brain MRI revealed multiple posterior cerebellar infarcts predominantly at the
lobules VII and VIII. The standard neuropsychological tests were unremarkable; however, the CCAS Scale
confirmed the diagnosis. The treatment of depression and secondary prevention of stroke was conducted. In cases
that present with features of cognitive and affective disorders but with mild voluntary motor or without typical
cerebellar features, the role of posterior cerebellar and vermian pathologies should be considered. The CCAS
Scale is an appropriate screening tool to detect these patients and provides a framework for evidence-based
treatment.

1. Introduction
Traditionally, the cerebellum has been viewed as an important reg­
ulatory center for the voluntary sensorimotor coordination; the main­
tenance of balance, gait, posture, rapid successive alternating
movements, muscle tone, strength, fine motor movements, control of
eye movements and the articulation of the speech. However, in the last
two decades, accumulating evidence from patients with cerebellar le­
sions, neuroimaging and neuropsychological studies revealed the role of
cerebellum in the cognitive, affective, autonomic and behavioral func­
tions [1]. The “cerebellar cognitive affective syndrome (CCAS)
/Schmahmann’s syndrome” is characterized by impairments of execu­
tive function (planning, set-shifting, abstract reasoning, verbal fluency,
working memory), perseveration, distractibility or inattention; visual­
–spatial disorganization and memory; personality change with blunting
of affect or disinhibited/ inappropriate behavior; and difficulties with
language production including dysprosodia, agrammatism and mild
anomia [2]. The CCAS may be associated with inherited neuro­
developmental diseases or acquired diseases/lesions involving the cer­
ebellum and its various projections [3]. In a study of patients with
cerebellar stroke examined 8.0 ± 6.0 days after the onset of stroke,

33.3% were reported to have normal motor functions, but their stroke in
the posterior lobe of the cerebellum reported to produce the CCAS [4]. In
a meta-analysis study including adult patients with isolated cerebellar
lesions compared to the healthy controls, the cerebellar patients had
significant cognitive deficits in the visuospatial, language and executive
function domains [5].
2. Case report
A 56-year-old male teacher with history of coronary artery disease,
hypertension, hyperlipidemia, and Type 2 diabetes mellitus was
admitted to our clinic with history of acute onset of psychomotor
retardation, emotional blunting, low energy level, disorder in decision
making, inability to plan, prioritize or organize tasks, set and achieve
goals successfully.
Our patient and his family had no previous medical history of psy­
chiatric illness, dementia or inherited disease. Two months earlier,
although the acute onset of these symptoms was reported, he was first
examined by a psychiatrist and diagnosed with depression. Few weeks
later, he was investigated by a neurologist with an initial diagnosis of
encephalitis. The EEG was normal. The CSF examinations, serum

* Correspondence to: Hacettepe University, Faculty of Medicine, Department of Neurology, Sihhiye, 06100, Ankara, Turkey.
E-mail address: isin.unalcevik@gmail.com (I. Unal-Cevik).
https://doi.org/10.1016/j.clineuro.2021.106690
Received 27 February 2021; Received in revised form 11 May 2021; Accepted 12 May 2021
Available online 17 May 2021
0303-8467/© 2021 Elsevier B.V. All rights reserved.

E. Gok-Dursun et al.

Clinical Neurology and Neurosurgery 206 (2021) 106690

Fig. 1. Brain MRI images. Eight sequential axial T2-weighted images, from superior to inferior cerebellar slices (thickness 5 mm) demonstrating multiple chronic
infarcts in the bilateral cerebellar hemispheres (thin arrows) and a predominant wedge shaped chronic infarct on the left cerebellar VII and VIII lobules (thick arrow).

3. Discussion

autoimmune antibody panel and tumor markers were reported to be
negative. On Brain MRI non-specific, white matter lesions in the cerebral
hemisphere and bilateral subacute cerebellar infarcts were detected.
Although the diagnosis of encephalitis was not confirmed, he was
treated with intravenous methylprednisolone 1 g daily for 10 days
accompanied by empirical monotherapy with intravenous ceftriaxone 2
g bid for 10 days. Two months after the acute onset of his symptoms, the
patient was admitted to our university hospital. On neurologic exami­
nation, he had psychomotor retardation, but no signs of meningeal
irritation, cranial nerve deficits, pyramidal/extrapyramidal signs or
definite voluntary sensorimotor coordination deficit. The Mini-Mental
State Examination (MMSE) score was 24 out of 30 (orientation: 10/
10, registration: 3/3, attention and calculation: 1/5, recall: 1/3, lan­
guage: 9/9). On standard neuropsychological assessment, mild impair­
ment was reported in attention and executive functions. The Beck
Depression Inventory revealed an intermediate degree of intensity of
depression. The Brain MRI revealed multiple, non-specific, cerebral
white matter hyperintensities and bilateral posterior cerebellar infarcts
predominantly involving the left cerebellar lobules VII and VIII (Fig. 1).
To confirm the diagnosis we performed CCAS/ Schmahmann Scale test
[6]. On CCAS-Scale, among the 10 items; he passed in semantic fluency
(18/26), phonemic fluency (10/19), category switching (10/15), digital
span backward (4/6), cube draw (15/15), similarities (8/8) and go
no-go (1/2) items. However he failed in digital span forward (5/8),
verbal recall (7/15) and affect (3/6) items. His total raw score was
91/120. On CCAS scale, our patient failed in three items and the diag­
nosis of “definite CCAS” was made. The antidepressant treatment and
secondary prevention of stroke was conducted for his long-term
follow-up.

Here we report an active male teacher with acute onset of affective
disorder and mild cognitive impairment, initially misdiagnosed as
depression and encephalitis, and received high dose intravenous steroids
and antimicrobial drugs. The CCAS may be due to acquired or inherited
conditions such as post-infectious cerebellitis, cerebellar infarction,
trauma, toxic insults, neoplasia or cerebellar cortical atrophy [3]. In
most cases with cerebellar infarcts, the main complaint of the patient
may be a sudden onset of vertigo, ataxia, dysarthria, dizziness, nausea
and vomiting [7,8]. However in CCAS the major symptom is impaired
cognition and altered affective modulation [4].
The proposed mechanism of the CCAS relates to the disruption of the
neural circuits that link prefrontal, posterior parietal, superior temporal
and limbic cortices with the cerebellum [2]. Considering the clinical
consequences of cerebellar topographic injury, the anterior lobe (lobules
I-V) damage was reported to be characterized by motor syndromes, the
posterior lobe (Lobules VI, VII and IX) with cognitive and affective
syndrome, whereas the vermis and fastigial nuclei constitute the limbic
cerebellum associated with pronounced affective presentations [4,9]. In
a fMRI study, functional connections of the posterior cerebellum with
the right frontal lobe, left hippocampus and right cingulate gyrus were
found to be decreased in cases of cerebellar infarction with respect to
healthy population [10]. The cognitive impairment occurs as a result of
impaired corticocerebellar connections. Apart from cerebellar infarc­
tion; CCAS can be due to posterior fossa tumors [11], ataxia - telangi­
ectasia (especially AT-3) [12], congenital cerebellar malformations
[13], spinocerebellar ataxias [14], post-infectious cerebellitis [2,15] and
paraneoplastic cerebellar degeneration [16]. Nevertheless, in these
complex diseases, cognitive and psychiatric problems accompany motor
symptoms and other neurological symptoms. The isolated and acute/­
subacute onset CCAS cases are frequently associated with cerebellar
2

E. Gok-Dursun et al.

Clinical Neurology and Neurosurgery 206 (2021) 106690

infarcts.The strategic infarcts of the hippocampus, fronto-cingulate
cortex, insular cortex, angulate gyrus, thalamus, caudate nucleus,
diffuse subcortical white matter lesions, cortical laminar necrosis and
typically any disorder affecting the cholinergic pathways, the region­
s/networks essential for cognition, memory and behavior may be asso­
ciated with vascular cognitive impairment and vascular dementia [17].
The brain MRI findings and acute onset of cognitive and affective
symptoms in our patient were also consistent with CCAS. The diagnosis
of CCAS relies on neuropsychological testing. The Mini-Mental State
Examination (MMSE) test [18] or the Montreal Cognitive Assessment
(MoCA) test [19], are reported to be insensitive to detect the CCAS pa­
tients [6]. Recently, the CCAS/ Schmahmann scale has been developed,
which can be applied at bedside and provides a detailed evaluation of
executive, visual-spatial, linguistic regions and affect domains of the
CCAS cases [6]. The CCAS-Scale is a 10-item scale with a sensitivity of
94% and a specificity of 78%. Based on pass/fail criteria it determines
“possible CCAS” (one item failed), “probable CCAS” (two items failed)
and “definite CCAS” (three or more items failed) [6]. The current status
for CCAS scale usage is in an expedited manner. In Friedreich ataxia
patients, significant positive correlation between severity of ataxia
progression and cognitive deficits assessed by CCAS-Scale is reported
[20]. In a cohort study of spinocerebellar ataxia type 3 (SCA3) patients,
the CCAS-S is reported to differentiate the SCA3 patients from healthy
controls, detect neuropsychological deficits early in the disease course,
and correlate with ataxia severity measures [21].
To conclude, the awareness of the CCAS as a clinical entity is
emerging. The role of posterior cerebellar and vermian pathologies
should be considered in the differential diagnosis of patients with
cognitive and affective disorders. The standard neuropsychological test
are reported to be insensitive to detect the CCAS patients. The CCAS
Scale is a good screening tool to determine patients accurately and
provides a framework for the evidence-based treatment. We hope, this
manuscript to foster and encourage communications between all related
physicians and experts by adding to their knowledge and alerting them
to this clinical entity which may affect their practice of medicine.

D. Timmann, D.K. van, Consensus paper: revisiting the symptoms and signs of
cerebellar syndrome, Cerebellum 15 (2016) 369–391.
[2] J.D. Schmahmann, J.C. Sherman, The cerebellar cognitive affective syndrome,
Brain 121 (Pt 4) (1998) 561–579.
[3] G.P.D. Argyropoulos, D.K. van, M. Adamaszek, M. Leggio, M. Manto, M. Masciullo,
M. Molinari, C.J. Stoodley, O.F. Van, R.B. Ivry, J.D. Schmahmann, The cerebellar
cognitive affective/Schmahmann syndrome: a task force paper, Cerebellum 19
(2020) 102–125.
[4] J.D. Schmahmann, J. MacMore, M. Vangel, Cerebellar stroke without motor deficit:
clinical evidence for motor and non-motor domains within the human cerebellum,
Neuroscience 162 (2009) 852–861.
[5] N. Ahmadian, B.K. van, Z.M. van, P.A. Robe, The cerebellar cognitive affective
syndrome-a meta-analysis, Cerebellum 18 (2019) 941–950.
[6] F. Hoche, X. Guell, M.G. Vangel, J.C. Sherman, J.D. Schmahmann, The cerebellar
cognitive affective/Schmahmann syndrome scale, Brain 141 (2018) 248–270.
[7] L.R. Caplan, Cerebellar infarcts: key features, Rev. Neurol. Dis. 2 (2005) 51–60.
[8] M. Venti, Cerebellar infarcts and hemorrhages, Front. Neurol. Neurosci. 30 (2012)
171–175.
[9] C.J. Stoodley, J.P. MacMore, N. Makris, J.C. Sherman, J.D. Schmahmann, Location
of lesion determines motor vs. cognitive consequences in patients with cerebellar
stroke, Neuroimage Clin. 12 (2016) 765–775.
[10] L. Fan, J. Hu, W. Ma, D. Wang, Q. Yao, J. Shi, Altered baseline activity and
connectivity associated with cognitive impairment following acute cerebellar
infarction: a resting-state fMRI study, Neurosci. Lett. 692 (2019) 199–203.
[11] D. Omar, T. Ryan, A. Carson, T.H. Bak, L. Torrens, I. Whittle, Clinical and
methodological confounders in assessing the cerebellar cognitive affective
syndrome in adult patients with posterior fossa tumours, Br. J. Neurosurg. 28
(2014) 755–764.
[12] F. Hoche, M.P. Daly, Y.K. Chutake, E. Valera, J.C. Sherman, J.D. Schmahmann, The
cerebellar cognitive affective syndrome in Ataxia-Telangiectasia, Cerebellum 18
(2019) 225–244.
[13] A. Tavano, R. Grasso, C. Gagliardi, F. Triulzi, N. Bresolin, F. Fabbro, R. Borgatti,
Disorders of cognitive and affective development in cerebellar malformations,
Brain 130 (2007) 2646–2660.
[14] L. Orsi, F. D’Agata, P. Caroppo, A. Franco, M.M. Caglio, F. Avidano, C. Manzone,
P. Mortara, Neuropsychological picture of 33 spinocerebellar ataxia cases, J. Clin.
Exp. Neuropsychol. 33 (2011) 315–325.
[15] A. Rosinski, M. Goldman, O. Cameron, A case of cerebellar psychopathology,
Psychosomatics 51 (2010) 171–175.
[16] M.M. Le, S. Dent, Anti-Yo antibody-mediated paraneoplastic cerebellar
degeneration associated with cognitive affective syndrome in a patient with breast
cancer: a case report and literature review, Curr. Oncol. 25 (2018) e585–e591.
[17] M.B. Paradise, P.S. Sachdev, Vascular cognitive disorder, Semin Neurol. 39 (2019)
241–250.
[18] M.F. Folstein, S.E. Folstein, P.R. McHugh, “Mini-mental state”. A practical method
for grading the cognitive state of patients for the clinician, J. Psychiatr. Res. 12
(1975) 189–198.
[19] Z.S. Nasreddine, N.A. Phillips, V. Bedirian, S. Charbonneau, V. Whitehead,
I. Collin, J.L. Cummings, H. Chertkow, The montreal cognitive assessment, MoCA:
a brief screening tool for mild cognitive impairment, J. Am. Geriatr. Soc. 53 (2005)
695–699.
[20] G. Naeije, M. Rai, N. Allaerts, M. Sjogard, T. De, M. X, Pandolfo, Cerebellar
cognitive disorder parallels cerebellar motor symptoms in Friedreich ataxia, Ann.
Clin. Transl. Neurol. 7 (2020) 1050–1054.
[21] R.P.P.W. Maas, S. Killaars, B.P.C. van de Warrenburg, D.J.L.G. Schutter, The
cerebellar cognitive affective syndrome scale reveals early neuropsychological
deficits in SCA3 patients, J. Neurol. (2021).

Funding
N/A.
Conflicts of interest
The authors declare no conflicts of interest.
References
[1] F. Bodranghien, A. Bastian, C. Casali, M. Hallett, E.D. Louis, M. Manto, P. Marien,
D.A. Nowak, J.D. Schmahmann, M. Serrao, K.M. Steiner, M. Strupp, C. Tilikete,

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