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Progress in Neuro-Psychopharmacology & Biological Psychiatry 32 (2008) 587 – 588
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Letter to the Editor (Case report)

Despite a steady decline in its incidence over the last 50 years
due to improvement in the treatment of diseases such as hypertension, diabetes mellitus and hypercholesterolemia, stroke
continues to represent a major health problem. Stroke is the
second leading cause of death worldwide (Lavados et al., 2007).
While depression is the most frequently occurring psychiatric disorder after stroke, secondary mania is considered an
uncommon consequence and it is only reported anecdotally.
Since the results published in the literature comprise only case
reports and open label trials, there is no clear evidence regarding
the most effective treatment for post-stroke mania at present
(Wijeratne and Malhi, 2007).
In the present report, we describe a woman with post-stroke
mania with successful outcome with valproic acid.

As she fulfilled clinical criteria for a manic episode according
to DSM-IV-TR, and based on her clinical history and symptoms,
the diagnosis of mania secondary to the stroke was hypothesized. She scored 39 out of 60 in the Young Mania Rating Scale
(YMRS).
She was started on carbamazepine and the dose gradually
increased up to 1200 mg/day (serum level of carbamazepine was
8.7 mg/ml). Haloperidol 2.0 mg/day was also introduced due to
the presence of grandiose delusions and extreme hyperactivity.
As after one month of treatment no significant clinical
improvement was noticed, carbamazepine and haloperidol
were withdrawn and valproic acid initiated. After two weeks
of treatment with valproic acid 1500 mg/daily (serum level of
valproic acid was 92.0 μg/ml), she improved notably, and the
YMRS score dropped from 36 to 9.
During the follow-up period of twelve months, the patient
maintained asymptomatic on a daily dose of 1500 mg of
valproic acid with YMRS scoring five. Subsequent liver panels
and ammonia were normal.

1. Case report

2. Discussion

A 47-year-old Caucasian woman presented to our emergency
department with a history of abnormal behavior during the last
two weeks. She developed elated mood, irritability, motor
excitement, increased rate of speech with racing thoughts and
grandiose delusions. She also displayed insomnia, distractibility
and had no insight into her illness.
She was evaluated with a structured clinical interview and no
previous history of any psychiatric disorder, including mood or
substance use disorders, could be evidenced. Her family
psychiatric history was also unremarkable. Of relevance, the
patient had a stroke three weeks before the onset of psychiatric
symptoms. At the time of the stroke, she presented paresis of left
limbs, but no behavioral symptom. She had a seven year history
of chronic hypertension treated with enalapril (10 mg/day) and
smoked 20 cigarettes per day. No other predisposing factor for
stroke was noticed.
At admission, neurological examination revealed a mild leftsided limb weakness. She scored 27 out of 30 in the Folstein
Mini-Mental State Examination. Laboratory work-up, including
complete blood count, creatine kinase level, electrolytes, renal,
liver and thyroid function tests, serology for syphilis and HIV,
echocardiography, hemoculture and X-ray of thorax were
unrevealing. Magnetic resonance scan showed an area at the
right medial frontal lobe (1.2–1.8 cm) compatible with the recent
stroke and few chronic ischemic lesions widespread throughout
the white matter.

The present case refers to an interesting condition that has
been rarely reported after stroke events. Four reviews have
analyzed the prevalence of post-stroke mania. Starkstein et al.
(1988) and Dunne et al. (1986) identified only three cases
among, respectively, series of 700 and 661 consecutive stroke
patients. In a large community studies that investigated the
prevalence of neuropsychiatric disorders after stroke, secondary
mania was not observed. (House et al., 1991).
As a consequence of the paucity of post-stroke mania, it is
difficult to determine precisely the clinical, demographic and
prognostic features. Nevertheless, family history of mood
disorders seems to be correlated with post-stroke mania
(Wijeratne and Malhi, 2007). Furthermore it has been demonstrated significant correlation between post-stroke mania and
right hemispheric lesions, especially involving right orbitofrontal and basotemporal cortices, the dorsomedial thalamic
nucleus, and the head of the caudate nucleus, leading to
dysfunction of the ventral limbic circuit (Chemerinski and
Levine, 2006; Goyal et al., 2006; Wijeratne and Malhi, 2007).
A hypothesis that may explain the low prevalence of poststroke mania is that dysfunction in more than one area of the
right hemisphere is required for its development, in contrast
with post-stroke depression. Imaging studies evidenced that the
majority of patients with secondary mania demonstrated complicated mixed artery infarctions with lesions in the basal
ganglia, frontal lobe, and temporal lobes (Goyal et al., 2006;

A successful outcome with valproic acid in a case of mania
secondary to stroke of the right frontal lobe
Dear editor,

0278-5846/$ - see front matter © 2007 Elsevier Inc. All rights reserved.
doi:10.1016/j.pnpbp.2007.10.013

588

Letter to the Editor (Case report)

Wijeratne and Malhi, 2007). In line with these findings, our
patient presented white-matter lesions besides the right frontal
lobe lesion.
Furthermore, biochemical response of the two hemispheres
to stroke may be different, as has been demonstrated by PET
scan findings. Right hemisphere stroke produces an increase in
serotonin receptor binding, which is not found following
comparable left hemisphere strokes. If mania could be related to
increased levels of serotonin in brain synapses, what it seems to
occur in antidepressant-induced mania, this biochemical
dysfunction secondary to right hemisphere stroke probably
contributes to the development of manic episodes (Robinson,
1997; Goyal et al., 2006). Thus the pharmacological action on
the serotonin system could explain why mood stabilizing drugs
can be effective in this clinical context.
For the treatment of this condition, some drugs including
olanzapine, lithium, carbamazepine and acid valproic have been
tried with variable or no response (Robinson, 1997; Goyal et al.,
2006; Wijeratne and Malhi, 2007). In our case, a successful
outcome was achieved with valproic acid.
Concluding, anticonvulsant mood stabilizers may be superior to lithium or atypical antipsychotics in the treatment of
secondary mania, and given the propensity for seizures in the
post-stroke period, mood stabilizing anticonvulsants may be the
agents of choice.
References
Chemerinski E, Levine SR. Neuropsychiatric disorders following vascular brain
injury. Mt Sinai J Med 2006;73:1006–14.

Dunne JW, Leedman PJ, Edis RH. Inobvious stroke: a cause of delirium and
dementia. Aust N Z J Med 1986;16:771–8.
Goyal R, Sameer M, Chandrasekaran R. Mania secondary to right-sided strokeresponsive to olanzapine. Gen Hosp Psychiatry 2006;28:262–3.
House A, Dennis M, Mogridge L, Warlow C, Hawton K, Jones L. Mood
disorders in the year after stroke. Br J Psychiatry 1991;158:83–92.
Lavados PM, Hennis AJ, Fernandes JG, Medina MT, Legetic B, Hoppe A, et al.
Stroke epidemiology, prevention, and management strategies at a regional
level: Latin America and the Caribbean. Lancet Neurol 2007;6:362–72.
Robinson RG. Mood disorders secondary to stroke. Semin Clin Neuropsychiatry
1997;2:244–51.
Starkstein SE, Boston J, Robinson RG. Mechanisms of mania after brain injury: 12
case reports and review of the literature. J Nerv Ment Dis 1988;176:87–100.
Wijeratne C, Malhi GS. Vascular mania: an old concept in danger of sclerosing?
A clinical overview. Acta Psychiatr Scand 2007;116(Suppl. 434):35–40.

Felipe Filardi da Rocha*
Humberto Correa
Department of Psychiatry, Faculty of Medicine,
Federal University of Minas Gerais, Belo Horizonte, Brazil
⁎ Corresponding author. Rua Sapucaia 83, Condomínio Retiro
das Pedras. 30140970, Belo Horizonte, MG, Brazil.
E-mail address: fil_bh@yahoo.com.br (F.F. da Rocha).
Antônio Lúcio Teixeira
Department of Internal Medicine, Neurology Branch,
Faculty of Medicine, Federal University of Minas Gerais, Belo
Horizonte, Brazil
1 September 2007