Unexpected outcome ( positive or negative) including adverse drug reactions

Neuropsychiatric manifestation after a stroke: newly
developed symptoms or side-effect of drug?
Eng Chai Tan, Noor Azah Aziz, Saharuddin Ahmad
Department of Family Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Cheras, Malaysia
Correspondence to Dr Chai Eng Tan, tce@ppukm.ukm.edu.my

Summary
A 55-year-old woman presented with sudden onset of left-sided body weakness and numbness, which was diagnosed as multifocal cerebral
infarct with right thalamic bleed. She had concurrent hypertension, diabetes mellitus and chronic kidney disease. She suffered from central
poststroke pain and reactive depression as poststroke complications, for which amitriptyline was prescribed. Unfortunately, she developed
symptoms suggestive of mania and psychosis upon initiation of medications, which resolved upon withdrawal of amitriptyline. Amitriptyline is
effective for treatment of poststroke pain and particularly useful in concomitant depression. Unexpectedly, this patient developed new
psychopathologies after initiation of this medication. This case highlights the development of new psychopathologies that could be due to the
antidepressant, underlying bipolar disorder or a complication of the stroke itself. Primary care providers need to actively enquire regarding
neuropsychiatric symptoms because they can adversely affect the patient’s quality of life as well as impede rehabilitation efforts.

BACKGROUND
Stroke is a condition that affects a person in many
aspects; from early mortality to various physical disabilities. However, not many are aware that neuropsychiatric
problems are one of the major complications of stroke,
which remains undiagnosed in many stroke patients.1 The
following case illustrates how treatment for common
stroke complications was complicated by the presence of
new neuropsychiatric symptoms as well as renal insufficiency. It is important for primary care providers to identify psychiatric symptoms in stroke patients because they
will adversely affect the quality of life as well as rehabilitation efforts.2 3

CASE PRESENTATION
A 55-year-old woman with no known chronic medical or
psychiatric illnesses developed sudden onset of left-sided
body weakness and numbness upon waking up from
sleep. She did not have any amaurosis, palpitations, headache, slurred speech or seizures. She was brought to an
urban teaching hospital in Kuala Lumpur for medical
treatment.
An urgent CT scan of the brain taken at the emergency
department showed the presence of a hyperdense lesion
measuring 1.6×1.3 cm, which was consistent with intraparenchymal bleed at the right thalamus. Perilesional
oedema was also present. There were also multiple hypodense areas at both right and left external capsule, corona
radiata and frontal regions. Periventricular lucencies were
present, indicating small vessel ischaemia. There was no
midline shift. The CT scan findings were consistent with
a multifocal infarct with thalamic bleed.
She was also found to have hypertension, diabetes mellitus and renal impairment, which was previously undiagnosed. In her 5 days of admission, she was started on oral
captopril 25 mg three times a day, felodipine 10 mg once

BMJ Case Reports 2012; doi:10.1136/bcr-2012-006518

daily, atenolol 50 mg once daily, metformin 1 g twice
daily, gliclazide 80 mg twice daily and lovastatin 40 mg
once daily. Neuropsychiatric assessment was not done as
the primary team found no overt abnormalities of her
cognitive function. Due to limited resources, neuropsychiatric assessment was only performed for specific cases
where the patient’s cognitive function was in doubt.4
Physiotherapy intervention was also initiated in the ward.
She was discharged with residual left-sided hemiparesis,
paraesthesia and instability on walking, with outpatient
physiotherapy intervention and oral medications.
She was later followed up at the primary care clinic
2 weeks following discharge. She revealed that the weakness
and numbness still troubled her. As a result, she could not
perform certain housework such as sweeping or cooking,
although she was still able to perform her basic activities of
daily living. She also admitted to feeling sad most of the day
for 2 weeks prior to the first visit at the primary care clinic.
She had difficulty falling asleep and her appetite was poor.
She claimed that her neighbours had been gossiping about
her, saying that she would not get well. Therefore, she
refused to venture out of her own home. She denied any loss
of concentration, guilt or suicidal ideation. There were no
obvious manic or psychotic symptoms.
Her instability also made it inconvenient for her to go
out. She was afraid she would fall and no one would be
there to help her. Instead, she spent her days watching
television alone in her home while her son worked. She
also defaulted her rehabilitation sessions because there
was no one to take her.
She was a divorcee, who stayed with her bachelor son.
Prior to the stroke, she supported her family by selling
pastries, which contributed significantly to her household
income, after her divorce. Her instability and mood lability made it difficult for her to prepare pastries and this
affected the family’s quality of life.

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Figure 1 Right thalamic bleed with multifocal infarcts at right
frontal region.

Figure 3 Infarcts of both corona radiata.

On examination, her gait was unstable and she required
the aid of a walking stick. There was no abnormal
movement noted. Her blood pressure was high, measuring
170/100 mm Hg, whereas her pulse rate was 92 beats per
minute. Her body mass index was 20.3 kg/m2. There were
no obvious neurological deficits, except for slight reduction of power (4/5) for left elbow flexion and hyperreflexia
over the left upper and lower limbs. Tone and power for
both lower limbs were normal. There were no objective
sensory deficits to fine touch or pin prick over her limbs.
Cardiorespiratory examination and funduscopy were unremarkable. There was no pedal oedema. Apart from low
mood, mental state examination was normal.

Blood investigations done at the clinic showed impaired
renal function; her estimated glomerular filtration rate
(eGFR) was 45 ml/min/1.73m2. She had poor glycaemic
control with an HbA1c of 11.6%.
In view of the new depressive symptoms and concurrent paraesthesia, she was started on oral amitriptyline
25 mg once daily. She was given an appointment within
the same week to review her blood pressure after titration
of her antihypertensives.
During the subsequent visit, she reported that her paraesthesia and sleep had improved. Her low mood persisted
because she held to the thought that her neighbours had
said that she would not recover. Her random capillary
glucose was within the target range. However, blood
investigations revealed that renal function had deteriorated to an eGFR of 25 ml/min. Doppler ultrasound of the
renal arteries ruled out renal artery stenosis. However, she
was found to have bilateral renal parenchymal disease. At
that point, amitriptyline was retained at the current dose.
During the fourth visit, she appeared happy and attributed it to feeling good after a visit by her relatives. She
was able to sleep well on amitriptyline.
However, by the next visit, she was apparently elated.
She was dressed in bright red attire. At times, she smiled
for no particular reason. There were no other symptoms
of mania such as pressure of speech, grandiosity or
pleasure-seeking behaviour. The paraesthesia of her lower
limb had improved. She claimed that she had a better relationship with her neighbours. As a result, she had been
overindulging in sweet and fatty food. However, she also
complained of drowsiness and still chose to isolate herself
at home. Amitriptyline was discontinued due to her
hypomanic symptoms, excessive drowsiness, as well as
resolved paraesthesia.
Two weeks later, the drowsiness and hypomanic symptoms persisted. She revealed her plans to restart her business and subletting her home for extra income. She
giggled for no apparent reasons. Upon further probing,
she claimed that other people could read her mind and

Figure 2 Right thalamic bleed with multifocal infarcts at the
right frontal region and both external capsules.
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BMJ Case Reports 2012; doi:10.1136/bcr-2012-006518

also believed that something had entered her body,
causing her paraesthesia. There were no overt auditory or
visual hallucinations or bizarre delusions.
She was referred for psychiatric assessment. She was
diagnosed with adjustment disorder and subsequently
defaulted follow-up at the psychiatry clinic after the
second visit.

DISCUSSION
This patient had symptoms of central poststroke pain,
commonly found in strokes involving the thalamic
region.5 Central poststroke pain is a condition where persisting neuropathic pain develops due to a lesion in the
central nervous system after a stroke.6 This patient had
persisting paraesthesia over the left side of her body,
which began within 6 months of stroke in the contralateral side of the body, corresponding to the lesion in the
right thalamus, which were features of central poststroke
pain.6 This condition can be very distressing for stroke
patients and affects their quality of life.
Low-dose amitriptyline, a tri-cyclic antidepressant, is
the standard first-line therapy for central poststroke pain,
which has been found to be safe and effective.5 6 Onset of
relief can be as early as 2 weeks from initiation of
therapy,6 and could also benefit her depressive symptoms.
Amitriptyline worked well for this patient, and she did
not complain of the anticholinergic side-effects commonly
caused by tri-cyclic antidepressants. However, over time,
she developed excessive drowsiness and mood changes.
The mood changes were not the result of altered drug
metabolism or excretion due to her renal insufficiency. It
has been shown that plasma levels of amitriptyline are
reduced in patients with renal insufficiency.7 In fact,
patients with renal insufficiency would require higher
doses of amitriptyline to achieve the desired effect for
either neuropathic pain or depression.
Stroke itself is often associated with neuropsychiatric
symptoms. The commonest neuropsychiatric complications are poststroke depression (35% prevalence), anxiety
(25%), apathy (20%) and catastrophic reactions (20%).1 8
Mania and psychosis have also been reported to occur
poststroke; however, they are very rare.8 An early neuropsychological assessment while she was still warded may
have been beneficial by detecting any cognitive or psychological complications which were not readily apparent.4
This will facilitate rehabilitation efforts to include management of any psychological complications of stroke.9
This patient initially had depressive symptoms. However,
after 4 months from the initiation of low-dose amitriptyline, she started demonstrating hypomanic symptoms, such
as elated mood and increased appetite. Nevertheless, her
hypomanic symptoms did not fulfil the Diagnostic and
Statistical Manual-IV criteria for hypomania.
Her hypomanic symptoms could be attributed to
several causes. Antidepressants, such as amitriptyline,
have been shown to induce mania and hypomania in
patients with underlying bipolar disorder.8 It could be
possible that she had soft hypomania,10 which became
apparent after the initiation of amitriptyline.
Her symptoms could also be at the milder end of the
spectrum of poststroke mania.11 This rare condition has a
prevalence of 1% among acute stroke patients and is
usually associated with strokes involving the right
BMJ Case Reports 2012; doi:10.1136/bcr-2012-006518

hemisphere of the brain.11 Despite preliminary evidence
that right hemisphere strokes may be associated with
poststroke mania,12 13 the link between stroke location
and mood disorders are still unclear.14
With the discontinuation of amitriptyline, her mood
gradually returned to normal. The presence of psychotic
symptoms, such as somatic passivity and thought broadcasting, prompted the need for in-depth psychiatric
evaluation.
After psychiatric evaluation, her symptoms were diagnosed to be due to adjustment disorder. However, adjustment disorders tend to present with symptoms of
depression and anxiety or conduct disorder rather than
manic or psychotic symptoms.15 Unfortunately, discontinuation of follow-up hindered the confirmation of diagnosis because the full evolution of psychopathology could
not be assessed. The possibility of an underlying bipolar
disorder could not be excluded in this case.

Learning points
▸ Neuropsychiatric complications of stroke are common,
but are often not screened or detected by primary care
doctors.
▸ We need to inquire regarding symptoms suggestive of
neuropsychiatric disorders in all stroke patients.
▸ Central poststroke pain can be treated with
antidepressants, which will also help to improve
symptoms of depression. Despite the small risk of
inducing hypomania, treating central poststroke pain
with antidepressants will improve patients’ quality of
life and facilitate rehabilitation efforts.

Competing interests None.
Patient consent Obtained.

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14. Kouwenhoven SE, Kirkevold M, Engedal K, et al. Depression in acute stroke:
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Tan EC, Aziz NA, Ahmad S. Neuropsychiatric manifestation after a stroke: newly developed symptoms or side-effect of drug?. BMJ Case Reports
2012;10.1136/bcr-2012-006518, Published XXX
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