The n e w e ng l a n d j o u r na l
Case Records of the Massachusetts General Hospital
From the Departments of Psychiatry (J.B.T.,
L.M.P., N.V.Q.) and Radiology (P.W.S.),
Massachusetts General Hospital, and
the Departments of Psychiatry (J.B.T.,
L.M.P., N.V.Q.) and Radiology (P.W.S.),
Harvard Medical School — both in Boston.
N Engl J Med 2018;379:182-9.
DOI: 10.1056/NEJMcpc1712229
Copyright © 2018 Massachusetts Medical Society.
182
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of m e dic i n e
Founded by Richard C. Cabot
Eric S. Rosenberg, M.D., Editor
Virginia M. Pierce, M.D., David M. Dudzinski, M.D., Meridale V. Baggett, M.D.,
Dennis C. Sgroi, M.D., Jo‑Anne O. Shepard, M.D., Associate Editors
Alyssa Y. Castillo, M.D., Case Records Editorial Fellow
Emily K. McDonald, Sally H. Ebeling, Production Editors
Case 21-2018: A 61-Year-Old Man with
Grandiosity, Impulsivity, and Decreased Sleep
John B. Taylor, M.D., Laura M. Prager, M.D., Nadia V. Quijije, M.D.,
and Pamela W. Schaefer, M.D.​​
Pr e sen tat ion of C a se
Dr. Samuel J. Boas (Psychiatry): A 61-year-old man was brought to the emergency
department of this hospital by his family because of concerns about grandiosity,
impulsivity, decreased sleep, and increased alcohol use.
The patient had a history of alcohol-use disorder; he had started drinking heavily
in his 20s. Sixteen years before this presentation, he was involved in a high-speed
motor vehicle accident. He was admitted to this hospital because of multiple trau-
matic rib fractures with pneumothoraxes. An evaluation was notable for a serum
ethanol level of 2659 mg per liter (reference range, <1000), a creatine kinase level
of 670 U per liter (reference range, 60 to 400), and an aspartate aminotransferase
level of 95 U per liter (reference range, 10 to 40); a comprehensive urine and serum
toxicology screen was otherwise negative. Bilateral chest tubes were placed for the
pneumothoraxes. The patient was evaluated by psychiatry and addiction consul-
tants, but longitudinal follow-up was not maintained.
Eight years before this presentation, the patient was evaluated for an episode of
severe depression; an unspecified antidepressant medication was prescribed, but
he declined to follow up with psychiatry. Four years before this presentation, dur-
ing a period in which he reportedly felt impulsive, he was arrested three times
within 2 weeks for driving under the influence of alcohol; he was sentenced to jail
and was forced to surrender his driver’s license. Thereafter, he abstained from
drinking alcohol and participated in an intensive outpatient program and Alcohol-
ics Anonymous. He was referred to a psychiatrist for persistent severe depression,
but he declined to attend the appointments. His primary care physician initiated
several trials of antidepressants, including selective serotonin-reuptake inhibitors
and serotonin–norepinephrine reuptake inhibitors, but the treatments had no clear
benefit.
One year before this presentation, the patient was admitted to a second hospi-
tal after he had a fall in the context of acute weakness and numbness of an arm
and leg. Magnetic resonance imaging (MRI) of the head reportedly revealed evidence
of remote infarcts of the right frontal and left parietal lobes, as well as diffuse
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 Case Records of the Massachuset ts Gener al Hospital
white-matter disease. Aspirin, atorvastatin, and
duloxetine were prescribed. On discharge, there
were no residual neurologic deficits.
Three months before this presentation, after
3.5 years of sobriety, the patient began to drink
1 pint of vodka per day. A few days after resuming
alcohol intake, the patient noted dyspnea and
presented to the second hospital, where atrial
flutter was detected. Transesophageal echocar-
diography revealed moderate left ventricular sys-
tolic dysfunction, mild-to-moderate mitral re-
gurgitation, a patent foramen ovale, and no
evidence of thrombus in the left atrial append-
age. Direct-current cardioversion was performed,
resulting in sinus rhythm. Aspirin and duloxetine
were discontinued, and therapy with apixaban,
torsemide, lisinopril, and metoprolol tartrate
was initiated.
The next month, during a period in which the
patient reportedly felt reckless and out of con-
trol, he borrowed his wife’s car and drove for the
first time since surrendering his license. He lost
control of the car and crashed into a barn, sus-
taining spinal fractures that necessitated the use
of a cane. During the same period, the patient
was also noted to spend impulsively, to need less
sleep, and to be increasingly physically and ver-
bally abusive toward family members. He was
seen by his primary care physician, who thought
that his affect was manic, representing a marked
change from his baseline of depression.
One month before this presentation, the pa-
tient reportedly had increased energy, irritability,
a euphoric mood, and a decreased need to sleep.
He was spending impulsively, including $25,000
on home renovations that were viewed to be un-
necessary by his family. The patient increased
his consumption to more than 1 pint of vodka
daily. He was evaluated by a psychiatrist at an-
other institution, and a diagnosis of bipolar dis-
order was considered. Lurasidone was prescribed,
but the patient took it for only 10 days.
Three days before this presentation, the pa-
tient traveled to Boston by bus and taxi from his
home state. He checked into several hotels,
gambled, shopped extravagantly, and invited
strangers for a steak dinner. He ran out of
money and contacted friends and family in Bos-
ton, including his son, for money. Although the
patient threatened to assault his son, his son
brought him to the emergency department at
this hospital.
On presentation, history was obtained from
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the patient, as well as his wife and son. The
patient reported having a high energy level and
racing thoughts and needing to sleep only 3 hours
per night. He had no weakness, numbness, vi-
sion changes, headache, dysarthria, dysphagia,
or hallucinations. He reported no fever, abdomi-
nal pain, chest pain, palpitations, or dyspnea.
He had not had a previous psychiatric hospital-
ization. The medical history was notable for
stroke, atrial dysrhythmia, hypertension, dyslipid-
emia, and remote migraines. Medications on
presentation were apixaban, atorvastatin, torse-
mide, lisinopril, and metoprolol tartrate. There
was no history of adverse reactions to medica-
tions.
The patient’s father had had one psychiatric
hospitalization for an unclear diagnosis and had
died of stomach cancer; the patient’s brother had
schizophrenia, and his mother had died of heart
failure. There was no family history of substance-
use disorder, stroke, or suicide. The patient re-
ported no illicit-drug use and had smoked 1 to
2 packs of cigarettes daily for 40 years. He had
been born and raised in the Boston area and had
completed community college before working as
a sales manager. He lived with his wife in New
England and had two adult children living near
Boston.
On examination, the temperature was 36.4°C,
the heart rate 78 beats per minute, the blood
pressure 175/90 mm Hg, the respiratory rate 18
breaths per minute, and the oxygen saturation
98% while the patient was breathing ambient
air. He was described as agitated and belligerent,
with some pressured and rapid but interruptible
speech. He had a ruddy complexion and mild,
symmetric pitting edema of the legs. The results
of a comprehensive neurologic examination were
normal, except for the presence of mild dysmet-
ria on bilateral finger–nose–finger tests and a
low-amplitude action tremor. A mental status
examination was notable for impaired short-
term recall and tangential answers to questions.
The patient was described as having an expansive
mood, with some emotional lability, including
intermittent tearfulness.
Results of urinalysis, chest radiography, and
liver-function tests were normal, as were blood
levels of calcium, magnesium, phosphorus, total
protein, and lipase. Other laboratory test results
are shown in Table 1. Transthoracic echocardiog-
raphy revealed left ventricular dilatation and
dysfunction (ejection fraction, 38%), right ven-
183
 The n e w e ng l a n d j o u r na l of m e dic i n e

Table 1. Laboratory Data.*

Variable Reference Range, Adults† On Presentation

Blood
Hematocrit (%) 41–53 44.4
Hemoglobin (g/dl) 13.5–17.5 15.2
Mean corpuscular volume (fl) 80–100 95.3
White-cell count (per mm3) 4500–11,000 7840
Platelet count (per mm3) 150,000–400,000 192,000
Sodium (mmol/liter) 135–145 142
Potassium (mmol/liter) 3.4–5.0 4.3
Chloride (mmol/liter) 98–108 94
Carbon dioxide (mmol/liter) 23–32 33
Urea nitrogen (mg/dl) 8–25 17
Creatinine (mg/dl) 0.6–1.5 0.73
Glucose (mg/dl) 70–110 116
N-terminal pro–B-type natriuretic peptide (pg/ml) 0–900 878
Troponin T (ng/ml) <0.03 <0.01
Thyrotropin (μIU/ml) 0.40–5.00 1.60
Albumin (g/dl) 3.3–5.0 3.2
Cholesterol (mg/dl)
Total <200 139
Low-density lipoprotein 50–129 64
High-density lipoprotein 35–100 57
Triglycerides (mg/dl) 40–150 91
Erythrocyte sedimentation rate (mm/hr) 0–13 29
C-reactive protein (mg/liter) <8.0 11.1
Vitamin B12 (pg/ml) >250 446
Antitreponemal antibody Nonreactive Nonreactive
Acetaminophen (μg/ml) 10.0–25.0 <5.0
Salicylates (mg/dl) 10.0–20.0 <3.0
Ethanol (mg/dl) Negative Negative
Tricyclic antidepressants Negative Negative
Urine
Urine toxicology screen Negative for amphetamines, Negative
barbiturates, benzodiaz‑
epines, cannabinoids,
cocaine, opiates, phen‑
cyclidine

* To convert the values for urea nitrogen to millimoles per liter, multiply by 0.357. To convert the values for creatinine to
micromoles per liter, multiply by 88.4. To convert the values for glucose to millimoles per liter, multiply by 0.05551.
To convert the values for cholesterol to millimoles per liter, multiply by 0.02586. To convert the values for triglycerides
to millimoles per liter, multiply by 0.01129. To convert the values for vitamin B12 to picomoles per liter, multiply by
0.7378. To convert the values for salicylates to millimoles per liter, multiply by 0.07240. To convert the values for ethanol
to millimoles per liter, multiply by 0.2171.
† Reference values are affected by many variables, including the patient population and the laboratory methods used. The
ranges used at Massachusetts General Hospital are for adults who are not pregnant and do not have medical condi‑
tions that could affect the results. They may therefore not be appropriate for all patients.

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 Case Records of the Massachuset ts Gener al Hospital

tricular hypokinesis, biatrial dilatation, a patent
foramen ovale with an interatrial septal aneurysm,
aortic-valve sclerosis, and mild mitral regurgi-
tation.
The patient was admitted to the hospital, and
a diagnosis was made.
Differ en t i a l Di agnosis
Dr. John B. Taylor: This 61-year-old man with chron-
ic alcohol-use disorder presented with mood
symptoms and cognitive and neurologic deficits.
His mood symptoms — including a high energy
level, a decreased need to sleep, racing thoughts,
a tangential thought process, rapid speech, and
impulsive behavior — reflect a manic episode.
We do not know the nature of his cognitive
function before this presentation or whether his
alcohol use correlated with his previous depres-
sive episodes. Developing the differential diag-
nosis of a manic episode begins with determin-
ing whether it is a primary psychiatric disorder
or a secondary disorder related to substance
use or to a general medical condition.1
Bipolar Disorder
Bipolar disorder is characterized by the occur-
rence of a manic episode that does not have
another medical cause. Patients with bipolar
disorder vacillate between manic episodes and
euthymia, and they often (but not always) have
major depressive episodes, as well. Although
mania associated with bipolar disorder may first
occur at any age during adulthood, it usually oc-
curs within one of two age ranges: the most
common age at the onset of mania is between
16 and 25 years, but there is a second peak be-
tween 46 and 55 years.2 An initial episode of
mania at 61 years of age would be unusual.
Although the patient had had episodes of de-
pression in the context of ongoing alcohol use,
he had no known instances of mania until
2 months before presentation. In addition, al-
though cognitive deficits such as verbal learning
impairment, memory impairment, and executive
dysfunction can be seen with bipolar disorder,
the onset of a manic episode itself would not
produce neurologic deficits.3 Therefore, bipolar
disorder is an unlikely diagnosis in this case.
Schizoaffective Disorder
Schizoaffective disorder is characterized by a base- clude antidepressants, glucocorticoids, levodopa,
line of chronic psychotic illness punctuated with antibiotic agents (especially macrolides, fluoro-
mood episodes (depression, mania, or both). In
patients with schizoaffective disorder, the psy-
chotic symptoms persist despite resolution of the
mood episodes. Although this patient had a fam-
ily history of schizophrenia, he did not have a
history of psychotic symptoms or have evidence
of psychosis during this manic episode.
Delirium
Delirium — which is marked by acute fluctua-
tions in attention, awareness, and cognition —
may resemble a manic episode, with shared
features including decreased sleep, disorganized
thinking and speech, impulsivity, distractibility,
and hallucinations. Delirium is always caused by
an underlying medical condition. This patient
had cognitive deficits, but they were not fluctuat-
ing, and he did not have impaired awareness.
Dementia
Patients with dementia may present with impul-
sivity, executive dysfunction, mood and sleep dis-
turbance, and personality changes, findings that
mimic mania. This patient’s age is consistent
with the usual age at the onset of frontotempo-
ral dementia or early-onset Alzheimer’s disease,
but these disorders typically develop in a gradual
fashion. The patient had multiple risk factors for
vascular disease and vascular dementia, includ-
ing hypertension, dyslipidemia, and tobacco use.
In addition to a history of multiple strokes and
loss of brain volume, he had evidence of sub-
stantial white-matter disease on MRI of the head,
which is a marker of diffuse cerebrovascular dis-
ease. Patients with vascular dementia may pres-
ent with personality changes and mood symp-
toms and may have evidence of white-matter
disease on imaging. It is possible that his earlier
episodes of depression, rather than representing
discrete mood episodes, were a dementia pro-
drome. No known cognitive testing had been
performed before symptoms developed in this
patient. The deficits elicited on cognitive testing
during this presentation were confounded by the
acute manic episode.3 Imaging studies of the
head and formal cognitive testing would need to
be conducted once the mania resolved, to deter-
mine whether the patient has vascular dementia.
Medication-Induced Mania
Medications that are known to induce mania in-

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 The n e w e ng l a n d j o u r na l of m e dic i n e

quinolones, and isoniazid4), and sympathomimetic
agents. This patient had received a prescription
for duloxetine, a serotonin–norepinephrine reup-
take inhibitor. Any class of antidepressant can
precipitate a manic episode. Although the patient
had been taking duloxetine before the initial
development of his manic symptoms, the medi-
cation had been discontinued 3 months before
the onset of this episode. In addition, 1 month
before this presentation, he had received a pre-
scription for lurasidone, an atypical antipsychotic
agent, which was meant to treat the manic symp-
toms. His other medications — apixaban, atorva­
statin, torsemide, lisinopril, and metoprolol tar-
trate — are not known to precipitate mania.
Substance-Induced Mania
Among illicit substances, cocaine and amphet-
amines are most likely to precipitate mania. The
patient’s urine and serum toxicology screens
were negative at the time of presentation, ruling
out common drugs of abuse. He was not known
to be using any substances other than alcohol
that would not show up on toxicology studies
(e.g., synthetic cannabinoids or synthetic cathi-
none). There is a clinically significant correla-
tion between bipolar disorder and alcohol use,
but the relationship is not explicitly causative
— that is, alcohol consumption does not defini-
tively precipitate mania in patients who do not
have preexisting bipolar disorder. Alcohol con-
sumption may, however, amplify the symptoms
of mania, making a patient with mania more
likely to present with mood lability, impulsivity,
and violent behavior, symptoms that were seen
in this patient.5
Mania Due to a General Medical Condition
Mania can be caused by a medical illness. Endo-
crine disorders — including hyperthyroidism,
hypothyroidism, and Cushing’s disease — must
be considered. Some of these disorders were
ruled out with laboratory testing. Infections that
affect the brain — including neurosyphilis,
meningitis, viral encephalitis, and human im-
munodeficiency virus (HIV) infection — would
probably cause additional symptoms, such as
fever or impaired arousal. HIV infection could
easily be ruled out with laboratory testing, and
syphilis is unlikely in this case, given the non-
reactive antitreponemal antibody test. A wide Secondary mania, most likely related to a new
range of neurologic conditions, including vascu- stroke.
lar illness, can cause mania. Stroke most fre-
quently causes depression, but emotional labil-
ity, personality changes, psychosis, and mania
are all possible psychiatric manifestations of
stroke.6
This patient had previously had strokes in-
volving the left parietal and right frontal lobes.
Mania is more likely to develop in patients with
stroke lesions on the right side of the brain, but
it can also result from a lesion on the left side
of the brain. A stroke associated with mania is
usually located in the right ventral prefrontal
cortex, right medial frontal lobe, or right basal
ganglia.1 Mania most frequently develops within
a few days after a stroke occurs, but it can de-
velop up to 2 years after a stroke.6 It is possible
that this patient had had a new stroke on the
right side within the past year, which could ac-
count for the onset of mania 2 months before
this presentation. If such an infarct had occurred
in the thalamus or thalamocapsular junction, it
could also explain the development of tremor
and dysmetria. On the basis of this patient’s
history and clinical presentation, I suspect that
he had manic symptoms due to a stroke. To
establish this diagnosis, I would perform MRI
of the head.
Dr. David M. Dudzinski (Medicine): Dr. Prager,
what was your impression when you initially
evaluated this patient?
Dr. Laura M. Prager: When we evaluated this
patient in the emergency department, we thought
that his presentation was consistent with sec-
ondary mania,7 or mania due to a general medi-
cal condition, rather than bipolar disorder with
primary mania. Factors that led us to this con-
clusion included his older age, numerous vascu-
lar risk factors, previous stroke, previous treat-
ment with antidepressants that had not triggered
a manic episode, unclear family history of affec-
tive disorder, and short-term memory problems
on a mental status examination. Given his
2-month history of mood symptoms with wors-
ening over the 3-day period before presentation,
we were primarily concerned that he might have
had another stroke, and we performed MRI of
the head.
Cl inic a l Di agnosis

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 Case Records of the Massachuset ts Gener al Hospital

A B C

D E F

Figure 1. MRI of the Head.

A diffusion‑weighted image shows a punctate, hyperintense lesion consistent with acute infarction in the left thala‑
mocapsular junction (Panel A, arrow). On a corresponding apparent‑diffusion‑coefficient image, the lesion is hy‑
pointense (Panel B, arrow). Fluid‑attenuated inversion recovery (FLAIR) images show evidence of remote infarctions
in the left inferior parietal lobe (Panel C, arrow), at the right thalamocapsular junction (Panel D, arrow), in the right
thalamus (Panel D, arrowhead), in the right frontal centrum semiovale (Panel E, arrow), and in the right sensory
strip (postcentral gyrus) (Panel F, arrow). FLAIR images also show extensive periventricular hyperintensity that is
most consistent with small‑vessel ischemic changes (Panels C and D).

Dr . John B . Ta y l or’s Di agnosis loss and hyperintensity associated with gliosis

Secondary mania, probably related to stroke in
the context of severe alcohol-use disorder.
Di agnos t ic Im aging
Dr. Pamela W. Schaefer: In this case, the diagnosis
was established by MRI of the head, which re-
vealed a punctate lesion in the left thalamocap-
sular region that was mildly hyperintense on
fluid-attenuated inversion recovery (FLAIR) im-
ages, hyperintense on diffusion-weighted images
(Fig. 1A), and hypointense on apparent-diffusion-
coefficient images (Fig. 1B); these findings are
consistent with an acute infarction. FLAIR im-
ages showed findings that were consistent with
other, bilateral, remote cerebral infarctions: tissue
in the left inferior parietal lobe (Fig. 1C), small
cavitated lesions with surrounding gliosis in the
right thalamocapsular junction (Fig. 1D) and the
right frontal centrum semiovale (Fig. 1E), and
punctate, hyperintense lesions in the right thala-
mus (Fig. 1D) and the right sensory strip (post-
central gyrus) (Fig. 1F). FLAIR images also
showed diffuse, global tissue loss, as well as
extensive periventricular hyperintensity (Fig. 1C
and 1D), a finding that is most consistent with
small-vessel ischemic changes.
Computed tomographic angiography of the
head and neck revealed mild, partially calcified
atherosclerotic plaque at the bifurcations of the
bilateral common carotid arteries, at the siphons
of the bilateral internal carotid arteries, and at
the origin of the left vertebral artery. There was

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Table 2. Criteria for a Manic Episode Due to a General Medical Condition.*

Diagnostic Criterion Features of This Patient’s Presentation

Persistent expansive, abnormally euphoric, or irritable mood Had expansive, euphoric mood and reportedly felt
­irritable for 1 month
Unusually high activity or energy level Needed only 3 hr of sleep
Personal distress, increased risk of self-harm, adverse effects Spent money on unnecessary renovations, gambled,
on areas of function such as work or social interactions, and threatened to assault family
or psychosis
A combination of the patient’s history, examination, laboratory, Had findings on neurologic examination and magnetic
and imaging findings indicates that the disturbance is a result resonance imaging of the head that suggested a
of an underlying medical condition stroke was the underlying cause
Another medical condition, such as delirium, does not better Did not have delirium or evidence of another cause on
­explain the cause of the mood disorder medical evaluation

* The criteria are adapted from the Diagnostic and Statistical Manual of Mental Disorders, fifth edition.

no evidence of clinically significant stenosis or apy.8,9 Lithium may also protect against further
of vasculitis. neuronal death after an infarct.9 Second-generation
antipsychotics, benzodiazepines, and gabapentin
can be used as adjunct medications while the
A ddi t iona l Di agnos t ic a nd
M a nagemen t C onsider at ions dose of the mood stabilizer is adjusted to the
therapeutic level.
Dr. Prager: The MRI results confirmed our suspi- Dr. Dudzinski: Dr. Quijije, are there other psychi-
cion that this patient had had a new infarct. We atric diagnoses to consider in this patient?
reviewed the diagnostic criteria for a manic epi- Dr. Nadia V. Quijije: In addition to poststroke
sode due to a general medical condition from mania, this patient appears to have had an ad-
the Diagnostic and Statistical Manual of Mental Disor- ditional diagnosis of the frontal lobe syndrome,
ders, fifth edition (Table 2), arriving at a diagnosis also known as the dysexecutive syndrome. The
of poststroke mania. The patient was not deliri- frontal lobe syndrome is characterized by dys-
ous, but he had an expansive mood and an in- regulation of executive functions, such as plan-
creased energy level and reportedly felt irritable. ning, abstract thinking, and behavioral control.
His symptoms had interfered with his ability to Patients with this syndrome have a constellation
behave appropriately with family members and of cognitive, emotional, and behavioral symptoms.
in a social setting. We thought that the patient’s The cognitive symptoms include an impairment
new cerebral infarct was temporally and causally of short-term memory, attention, speech, planning,
related to his current manic episode and that it and reasoning. The emotional manifestations
had precipitated the acute behavioral changes. include difficulty inhibiting anger, excitement,
The dysmetria and tremor could be explained by sadness, frustration, and aggression. Abnormal
the acute left thalamocapsular stroke. In addition, behavioral actions result from impairments in the
we thought that his multiple previous bilateral emotional and cognitive domains. The frontal
infarcts were temporally related to the episode lobe syndrome can be caused by strokes, head
of mania that had occurred 1 month before this trauma, tumors, neurodegenerative disorders, and
presentation, which had been thought to repre- certain psychiatric disorders. This patient had
sent bipolar disorder and had been treated with clinically significant cerebral white-matter dis-
the antipsychotic lurasidone. ease, acute and remote cerebrovascular infarcts,
The initial management of poststroke mania and possible neurodegenerative effects from his
revolves around minimizing risk factors for the chronic alcohol-use disorder. These features, along
development of additional stroke. Pharmacologic with the history of symptoms that occurred dur-
treatment of poststroke affective disorders is sim­ ing the 8 years before the current presentation,
ilar to treatment for primary affective disorders. are suggestive of the frontal lobe syndrome.
Lithium or valproate can be used as monother- A diagnosis of the frontal lobe syndrome is

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 Case Records of the Massachuset ts Gener al Hospital

made on the basis of history obtained from the
patient, family, friends, and other collateral
sources, such as primary care physicians.10 Ad-
ditional factors — such as demographic charac-
teristics, clinical course, neuropsychological test
results, and neuroimaging results — can aid in
establishing this diagnosis. There is no cure for
the frontal lobe syndrome, but management in-
cludes neuropsychological interventions (cogni-
tive analytic therapy, general planning approach-
es,11 and cognitive stimulation therapies), greater
support at the place of residence (increased super-
vision, visiting services, and physiotherapy12), and
administration of pharmacologic agents (off-
label antidepressants, a mood stabilizer,13 and
dopaminergic agents).
Dr. Dudzinski: Dr. Boas, would you tell us what
happened with this patient?
Dr. Boas: The patient was admitted to the neu-
rology stroke service. After imaging and labora-
tory studies were performed, he was treated with
aspirin, a high-dose statin, and apixaban. Repeat
detailed mental status examinations revealed
subtle disorientation, difficulty calculating, the
inability to draw a clock face, and the inability
to explain an idiom.
Treatment with quetiapine was initiated, with
the dose adjusted to 100 mg nightly, but the
patient continued to have a euphoric mood, im-
pulsivity, and poor insight. After 6 days, he was
transferred to the inpatient psychiatry unit,
where he was treated with valproate but had a
minimal decrease in symptoms. During this
time, he was cooperative, future-oriented, and
motivated for abstinence. After another week,
the patient was discharged home, and close
follow-up care was scheduled.
One week after discharge, the patient followed
up with his primary care physician. The physician
had concerns about ongoing mania, but the pa-
tient declined psychiatric intervention. One month
after discharge, he presented to the emergency
department of another hospital because of atrial
flutter. Cardioversion was performed, and he was
discharged. In the following months, he had
support from home health services, but he did
not adhere to the medication regimens and con-
tinued to use alcohol. Unfortunately, the patient
died within 6 months after this hospitalization.
We have no additional information about the
circumstances of his death.
Fina l Di agnosis
Poststroke mania and the frontal lobe syndrome.
This case was presented at Psychiatry Grand Rounds as the
Inaugural Avery D. Weisman, M.D., Grand Rounds Lecture in
Consultation Psychiatry.
No potential conflict of interest relevant to this article was
reported.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
We thank Dr. Scott Beach for assistance with case preparation
and conference organization.

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