Hindawi Publishing Corporation
Behavioural Neurology
Volume 2014, Article ID 780742, 5 pages
http://dx.doi.org/10.1155/2014/780742

Case Report
Late Onset Bipolar Disorder due to a Lacunar State
Elena Antelmi, Margherita Fabbri, Lucia Cretella, Maria Guarino, and Andrea Stracciari
Neurology Unit, S. Orsola-Malpighi University Hospital, Via Albertoni 15, 40138 Bologna, Italy
Correspondence should be addressed to Andrea Stracciari; andrea.stracciari@aosp.bo.it
Received 15 March 2013; Accepted 21 June 2013; Published 27 March 2014
Academic Editor: Argye E. Hillis
Copyright © 2014 Elena Antelmi et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective. To describe a patient with a new onset bipolar disorder (BD) type II, secondary to a lacunar state.Background. Poststroke
BD is rare and mainly associated with lesion in the prefrontal-striatal-thalamic circuit. Materials and Methods. A 51-year-old
woman came to our attention for a mood disorder of recent onset. At 49, she had suffered acute left-sided limb weakness that
improved spontaneously four days later. Arterial hypertension was subsequently diagnosed. After 6 months, she began to suffer
from alternating brief periods of expansive and elevated mood with longer periods of depressed mood, with a suicide attempt. We
performed extensive laboratory and instrumental investigations, as well as, psychiatric consultation, and a cognitive assessment,
which was repeated 9 months later. Results. Brain magnetic resonance disclosed leukoaraiosis and a lacunar state of the basal
ganglia. Transcranial Doppler showed a patent foramen ovale. A psychiatric consultation led to the diagnosis of BP type II.
Neuropsychological evaluation detected deficits in attention/executive functions, verbal fluency, and memory. Nine months later,
after specific psychiatric therapy, the psychiatric symptoms were remarkably improved. Conclusion. Our case sheds light on the role
of the basal ganglia in mood disorders and the importance of ruling out brain injury in late onset BP.

1. Introduction
Bipolar disorder (BD) is a mood disorder typically characterized by oscillating manic and depressive states [1]. It is a
major source of psychiatric morbidity and mortality affecting
approximately 1.5–3% of the population [2]. The etiology of
BD remains unknown, though some data support a genetic
basis [3]. Secondary forms have seldom been reported in the
literature. BD has been reported as a consequence of different
medical conditions and after injury to the right dorsolateral
prefrontal circuit and anterior cingulate circuit [4].
We describe a 51-year-old woman with a new onset BD
type II secondary to a lacunar state of the basal ganglia,
analyzing the clinical and neuropsychological features and
formulating an anatomopathophysiological hypothesis. The
role of neuroimaging in cases of an adult new onset psychiatric disorder is also stressed.

2. Case Report
A 51-year-old woman was referred to our hospital for a
behaviour and mood disorder that had arisen almost one year

before our evaluation together with the complaint of mild
memory deficit.
History taking disclosed a sudden onset of left-sided
limb weakness at the age of 49 that lasted 4 days, for which
patient did not consult a specialist. Subsequent routine medical investigation revealed severe hypertension (of unknown
onset) for which she was started on antihypertensives. Six
months after the acute episode, she began to present a mood
disorder with a change in behaviour. She had at least two
episodes of insomnia, distractibility, increased energy, and
expansive and elevated mood, circumstantially accompanied
by eccentric behaviour (such as bathing while dressed),
lasting nearly one week each. These episodes of elevated
mood alternated with periods of apathy, loss of interest or
decreasing physical energy, and depressive mood. During one
of these depressive periods, she even attempted suicide. She
denied any personal or family history of psychiatric disorders and her medical history was otherwise unremarkable.
History taking from relatives confirmed that the patient had
never had previously any psychiatric symptoms or complains.
We performed a neurologic evaluation (NE), laboratory work-up, carotid duplex ultrasound (CDU), transcranial Doppler (TCD), brain magnetic resonance (MR) with

2

Behavioural Neurology
Table 1: Neuropsychological assessment.

Test
Attention/executive functions
Attentional matrices (visual search)
Stroop test
Time (s)
Errors
Trail making test A: time (s)
Trail making test B: time (s)
Trail making test B-A: time (s)
Picture interpretation test
Eyes’s test
Reasoning
Raven’s coloured progressive matrices
Elithorn’s maze
Memory
Verbal
Rey’s 15 words: immediate recall
Rey’s 15 words: delayed recall
Brief story
Digit span
Nonverbal
Immediate visual memory
Corsi blocks
Verbal abilities
Phonological word fluency (F, A, and S)
Semantic fluency
Spatial cognition
Freehand copying of drawings
Rating scales
MMSE
BIS-11
Y-BOCS

December 15, 2011 score∗ ES

September 17, 2012 score∗ ES

Range

Cutoff

0–60

31

32.75

1

23.75

0

∞–0
∞–0
∞–0
∞–0
∞–0
0–180
0–36

36.9
4.2
93
282
186
180
15

39.25
1.25
101
299
188
NA
NA

0
3
0
0
0
—
—

27.25
0
139
352
213
47
14.62

2
4
0
0
0
3
—

0–36
0–36

18.9
7.75

16.8
11.75

0
2

15.8
16

0
4

0–75
0–15
0–16
0–9

28.5
4.7
4.75
3.75

27.5
3
9.65
5.5

0
0
2
4

12.5
1
8.75
4.75

0
0
2
3

0–22
0–9

13.8
3.75

16
3.75

1
1

16
4.75

1
4

0–∞
0–∞

17.35
25

21.3
29

1
1

18.3
26

1
1

0–12

7.1

9.4

3

8.4

2

0–30
30–120
0–40

25
—
—

28
NA
NA

—
—
—

29
64
10

—
—
—

∗
Adjusted for age, education, and sex when needed.
ES: equivalent score; NA: not administered.
Defective and borderline scores (ES = 0 and 1, resp.) are in bold type.

gadolinium, psychiatric observation, and a neuropsychological battery of tests comprising an evaluation of attention/executive functions, verbal fluency, and verbal/visual
memory (for details of tests adopted, see [5]). Neuropsychological investigations were performed at two different
occasions: the first evaluation was done almost one year after
the onset of mood disorders, while the second took place nine
months after the first evaluation and after specific psychiatric
treatment.
NE disclosed primitive reflexes and a slight bilateral
postural hand tremor. Laboratory investigations and CDU
were normal. TDC disclosed a patent foramen ovale. Cerebral
MR revealed multiple bilateral subcortical lacunar lesions
both within the periventricular region and at the nucleuscapsular level resulting in a lacunar state (Figure 1). The

psychiatric interview led to diagnosis of type II bipolar
disorder, according to the DSM IV TR criteria [1]. The first
neuropsychological evaluation disclosed a deficit of attention/execution functions, verbal fluency, and long-/shortterm memory (Table 1). By the first assessment, patient was
started on valproic acid, quetiapine, and venlafaxine. The
dose was progressively augmented to valproic acid 250 mg at
8 a.m. and 500 mg at 8 p.m., quetiapine 300 mg once daily,
and venlafaxine 150 mg once daily. The medications offered
partial benefit. Therefore, after nine months, venlafaxine
and quetiapine were stopped and the patient continued
taking only valproic acid 500 mg bd. After nine months, we
performed a new clinical and neuropsychological evaluation.
Clinically, the patient appeared less depressed and she did
not have any further episodes of mania or hypomania.

Behavioural Neurology

3

(a)

(b)

(c)

(d)

Figure 1: Cerebral MRI: lacunar state, with prominent lesions on the left caudate ((a and c) arrow), bilateral putamen ((b and c) arrow), and
left pons (d).

The neuropsychological battery failed to disclose remarkable
differences (Table 1). A mild frailty in emotion recognition
was detected by Eyes’s test [5]. At this time, we also administered Barratt impulsiveness scale 11 (BIS 11) [6] to test for
impulsiveness and Yale-Brown obsessive compulsive scale (YBOCS) [7] to test for obsessive-compulsive disorder. BIS-11
disclosed a moderate degree of impulsiveness, while Y-BOCS
revealed mild obsessive-compulsive traits (Table 1).

3. Discussion
Our patient fulfills the DSM-IV criteria for BD type II
(having presented at least two hypomanic phases lasting at
least one week and an episode of major depression) due
to a medical condition with mixed features (293.83) [1].
Indeed, the patient’s negative family and personal history for
psychiatric disorders, the presence of vascular risk factors,

the age of onset and the neuroimaging finding together with
the temporal relationship (within two years after the stroke)
made a secondary mood disorder more likely, rather than
primary mood disorder [1, 4, 8]. In this case, damage to
the basal ganglia, together with periventricular white matter
changes, which have been described as a predisposing factor,
is thought to have led to the mood disorder.
Literature reports have linked different medical conditions to secondary BD, for example, lupus erythematosus,
normal pressure hydrocephalus, anoxic encephalopathy or
tumour, and stroke lesions. Even though the neural circuits
involved in mood regulation are complex, the dorsolateral
prefrontal circuit and the anterior cingulate circuit (originating in the prefrontal cortex, projecting to the striatum and
thalamus, and then returning to the cortex) seem to be the
“core” of mood regulation [8–13]. To support this hypothesis, several studies have shown structural and functional

4
abnormalities within the anterior limbic network, including
the basal ganglia, namely, the caudate nucleus. In particular,
basal ganglia structures seem to be particularly closely networked with both cortical and subcortical regions involved
in mood expression and regulation, including the amygdala
and ventral prefrontal cortex, and appear to be critical in
affective regulation [9–12]. Several literature reports seem to
confirm this role and postlesional mania and BD have been
reported after damage to limbic regions of the frontal and
temporal lobes and to the basal ganglia, mainly the caudate or
pallidum and thalamus, particularly in the right hemisphere
[4, 13, 14]. Data confirming the central role of this network
in the genesis of BD also emerged from neuroimaging and
neurofunctional studies in idiopathic cases. Indeed, increased
caudate volume has been widely observed in BD patients
compared with matched groups of healthy subjects [15–17].
In addition, functional abnormalities in the basal ganglia,
and particularly the caudate, have been widely observed in
BD patients using both positron emission tomography and
functional magnetic resonance imaging [18]. Similarly, to
further support this hypothesis, depression in Parkinson’s
disease, Huntington’s disease, and epilepsy is correlated with
reduced metabolic activity in the orbitofrontal cortex and
caudate nucleus [19, 20].
Moreover, as already reported [21], the microstructural
white matter changes in our patient may have triggered
further mood impairment because of a disconnection of
cortical and subcortical regions [12].
Another important issue in our case is the cognitive
impairment. Cognitive deficits are also recognized as an
integral part of the clinical expression of BD. Even if some
tasks may improve with euthymia (such as visual and working
memory), others tend to persist [22]. Whether the cognitive
dysfunctions are related to the mood disturbances and
fluctuations or to structural and functional impairment of the
same circuits implicated in the mood disorder is still a matter
of debate [22]. However, our patient presented cognitive
dysfunction related to executive, visual, and verbal memory
which persisted in the follow-up evaluation despite mood
improvement, confirming the crucial role of the frontostriatal
system for adaptive behaviour [12]. Moreover, the cognitive
changes in our patient were those typical of subcortical
alterations due to a lacunar state, even if other lesions, namely,
leukoaraiosis, can also exacerbate cognitive deficits in bipolar
disorder.
Finally, several studies have also shown structural and
functional involvement of the frontal-subcortical circuit
in the pathogenesis of obsessive compulsive disorder [12].
Hence, it is not surprising that the neuropsychological evaluation in our patient disclosed mild impulsiveness and mild
obsessive compulsive traits.
In conclusion, damage to the interactive and reciprocal
connections between limbic structures and the prefrontal
cortex and striatum in our patient may explain the deregulation of emotional control and concomitant dysfunction of
executive functions together with mild obsessive-compulsive
and impulsiveness traits. Our case therefore supports the role
of the basal ganglia in mood disorders and the importance of
ruling out brain injury in late onset BD.

Behavioural Neurology

Conflict of Interests
The authors declare no conflict of interests.

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Behavioural Neurology
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