CASES THAT TEST YOUR SKILLS

Ms. B hears voices and is paranoid but has no other symptoms

of a psychotic disorder. The challenge: narrow the differential
diagnosis and determine what’s causing her hallucinations.

Psychosis: Is it a medical ia
edproblem?
lth M
H Rafeyan, ea
CASES THAT TEST
Aileen MD nRoueen
de SKILLS
Higgins,YOUR
o
nly MD
w Assistant e oprofessor
D ®
a
t RushDepartment us
Chief psychiatry resident
l psychiatry
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yr r per Chicagoo n
University
of
Medical Center
Cop
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HISTORY: SHOP TALK describes her mood as “OK,” but her affect is blunted.
s. B, age 46, presents to the ER at her broth- Thought process is logical but circumstantial at times,
M er’s insistence. For about 6 months, she says, and her thoughts consist of auditory hallucinations,
she has been “hearing voices”—including that of paranoid thinking, persecutory delusions, and ideas of
her boss—talking to each other about work. reference. She has poor insight into her symptoms
Ms. B has no personal or family psychiatric his- and does not want to be admitted.
tory but notes that her sister died 6 months ago, and Physical examination and laboratory tests are
her father died the following month. At work, she is unremarkable. Negative ethanol and urine drug
having trouble getting along with her boss. She adds screens rule out substance abuse, and preliminary
that she has been skipping church lately because noncontrast head CT shows no acute changes.
she believes her church is under investigation and
the inquiry might be targeting her. Ms. B’s symptoms suggest:
Ms. B has been a company manager for 20 a) major depressive disorder, single episode,
years. She is divorced, has no children, and lives with psychotic features
alone. She says she does not smoke or use illicit
b) bipolar disorder, depressed or mixed
drugs and seldom drinks alcohol. She denies suicidal
phase, with psychotic features
or homicidal thoughts, depressed mood, or visual
c) schizophrenia, paranoid type
hallucinations. She says she is sleeping only 3 to 4
hours nightly and feels fatigued in the afternoon. She
d) psychosis due to a medical condition
denies loss of concentration or functioning.
Mental status. Ms. B is well groomed, maintains The author’s observations
good eye contact, and is superficially cooperative but In women, schizophrenia typically emerges
increasingly guarded with further questioning. She between ages 17 and 37;1 onset after age 45 is

VOL. 6, NO. 1 / JANUARY 2007 73

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CASES THAT TEST YOUR SKILLS
Psychosis: Is it a medical problem?

Figure 1

Clinical steps to rule out medical causes of late-onset psychosis

Patient and
collateral history
t

t
Blood alcohol and Physical and
urine drug screen neurologic examination

Studies specific
to examination t
t
Significant
t
findings: basic
Yes findings?
metabolic profile,
CBC, MP, thyroid
panel, chest x-ray,
ECG, head CT
No
t

Treat as

t
medically
t

necessary Acute onset Gradual onset

t
t

Yes History of trauma? No Yes Family history?

t

t
t
t

Trauma? Delirium? Cerebrovascular Huntington’s

CBC, chest x-ray, No
Head CT problem? disease
rapid plasma reagin, MRI
test for herpes simplex
virus and HIV
t

t
t

Malignancy? Dementia? Seizure? MS?

Systemic lupus
Head CT, MRI Neuropsychiatric EEG MRI, lumbar
erythematosus?
testing, MRI puncture
Anaerobic swab,
anti-dsDNA

unusual.2 Ms. B’s age, family history, and lack of and father and difficulties at work—could precip-
a formal thought disorder or negative symptoms itate a mood disorder. Of the possible diagnoses,
make late-onset schizophrenia unlikely, though it major depressive disorder is most likely at this
cannot be ruled out. time.1,3 Because Ms. B’s symptoms do not clearly
Ms. B denies mood symptoms, but significant match any diagnosis, we speak with her brother
stressors—such as the recent deaths of her sister and sister-in-law to seek collateral information.

74 VOL. 6, NO. 1 / JANUARY 2007

COLLATERAL HISTORY BEWARE OF SPIES The author’s observations
Collateral information about Ms. B points to
M s.strangely
B’s brother says his sister began behaving
about 8 months ago and has wors- psychosis rather than a mood disorder with psy-
ened lately. He says she suspects that her boss chotic features, but she lacks the formal thought
hired spies to watch her house, car, and her parent’s disorder and negative symptoms common in pri-
house. After work, she often parks in paid garages mary psychotic disorders.
rather than at home to avoid being “followed.” When Because Ms. B’s presentation is atypical, we
visiting, he says, she leaves her keys outside order brain MRI to check for a general medical
because she fears they contain a tracking device. condition (Figure 1). If brain MRI suggests a
Family members say Ms. B sometimes drops by at medical problem, we will follow with EEG, lum-
night—as late as 5 AM—complaining that she cannot bar puncture, or other tests.
sleep because she is being “watched.”
Ms. B’s family hired a private investigator 3 or 4 TREATMENT, TESTING WHAT MRI SUGGESTS
months ago to examine her house and car.
Although no tracking devices were found, her broth-
W eatricadmit Ms. B to the locked inpatient psychi-
unit—where she remains paranoid and
er says, Ms. B remains convinced she is being fol- guarded—and prescribe risperidone, 1 mg/d, to
lowed. He says she often speaks in “code” and address her paranoia. She refuses medication at
whispers to herself. first because she feels she does not need psychi-
According to her brother, Ms. B often hears atric care, but we give her lorazepam, 0.5 mg/d for
voices while trying to sleep, saying such things as her anxiety, along with psychoeducation and family
“Why won’t she turn over?” She reportedly wears a support. After 3 days, we stop lorazepam and Ms. B
towel while showering because the “spies” are agrees to take risperidone.
watching. During a conference she attended last Within 4 days of starting risperidone, Ms. B’s
week, she told her brother that a group of govern- auditory hallucinations and paranoia have lessened
ment investigators followed her there and arrested and her insight is improved. We recommend increas-
her boss. ing the dosage to 2 mg/d because we feel that 1
Ms. B’s sister-in-law says the patient’s function- mg/d will not sufficiently control her symptoms. She
ing has declined sharply, and that she has been help- remains paranoid but is reluctant to increase the
ing Ms. B complete routine work. Neither she nor dosage for fear of adverse effects, though she has
Ms. B’s brother have noticed a change in the reported none so far.
patient’s energy, productivity, or speech production Brain MRI taken the night Ms. B was admitted
or speed, thus ruling out bipolar disorder. Ms. B’s shows:
brother confirms that there is no family history of • multiple focal, well-defined hyperintense
mental illness. periventricular lesions on fluid-attenuated inversion
recovery (FLAIR)- and T2-weighted images (Figure 2,
page 76). Some lesions are flame-shaped.
Based on clinical findings and collateral
• a 1.5-cm lesion adjacent to the right frontal horn
information, you would order:
showing a hyperintense signal on T2-weighted
a) EEG images and a hypointense signal on T1-weighted
b) brain MRI images without contrast enhancement. White-matter
c) lumbar puncture edema surrounds this lesion.
d) none of the above • no gadolinium-enhancing lesions.
continued

VOL. 6, NO. 1 / JANUARY 2007 75

CASES THAT TEST YOUR SKILLS
Psychosis: Is it a medical problem?

Ms. B has MS
Figure 2
a) yes
FLAIR-weighted image
b) no
after Ms. B’s brain MRI
c) cannot be determined at this point

The authors’ observations

Determining disease dissemination in time and
space is key to diagnosing MS. Clinical presenta-
u
tion or MRI can determine both criteria (Table,
u page 86). Ms. B’s lesions and CSF results suggest
u

that MS has disseminated throughout her body,

but neurologic examination shows no objective
u clinical evidence of lesions.
Neuropsychological testing might help eval-
uate Ms. B’s cognition and executive functioning,
but these deficits do not specifically suggest MS.
The cortex, particularly the prefrontal cortex, is
believed to coordinate organization, planning,
and socially appropriate behavior. MS typically
Right 1.5-cm lesion adjacent to right frontal horn and
multiple left hyperintense lesions on fluid-attenuated
involves white matter rather than the cortex, but
inversion recovery (FLAIR)-weighted image. researchers have suggested that MS-related
demyelination might disrupt the axonal circuits
that connect the cortex to other brain areas.18
Two radiologists confirm possible demyelina- Increased lesion load has been correlated with
tion, suggesting multiple sclerosis (MS). Final decreased cognitive function. Neuropsychological
report of initial brain CT shows low-density, periven- testing could indirectly point to a lesion load
tricular white matter changes consistent with the increase by recording decreased cognitive func-
MRI findings. tion, but this decline cannot be attributed to MS
Results of subsequent laboratory tests are nor- without an MRI.
mal. Erythrocyte sedimentation rate is slightly ele- Ms. B’s psychotic symptoms could be clinical
vated at 35 mm/hr, suggesting a possible autoim- evidence of MS, but we cannot solidify the diag-
mune disorder. ECG shows sinus bradycardia, and nosis until we establish dissemination in time. To
chest x-ray and MR angiogram are unremarkable, as do that, we need a second MRI 3 months after the
are EEG and visual evoked potential results. first one. Concurrent late-onset paraphrenia and
Lumbar puncture and CSF studies show MS is possible but rare.
increased immunoglobulin G-to-albumin ratio. CSF
fluid is clear, blood counts and protein are normal, FOLLOW-UP WHERE IS SHE?
Gram’s stain and culture are negative, and cytolog-
ic findings show a marked increase in mature lym-
B is discharged after 10 days. She denies
M s.hallucinations, and staff notices decreased
phocytes. These results suggest inflammation, but paranoia, brighter affect, and improved insight. We
follow-up neurologic exam is unremarkable. tell her to continue taking risperidone, 1 mg/d.
continued on page 86

76 VOL. 6, NO. 1 / JANUARY 2007

CASES THAT TEST YOUR SKILLS
Psychosis: Is it a medical problem?

continued from page 76

Table
The authors’ observations
Findings needed to determine MS diagnosis Ms. B’s case highlights the impor-
based on clinical presentation tance of:
• recognizing an atypical presentation
Clinical presentation Findings needed
for MS diagnosis
of a primary psychotic disorder
• checking for a medical cause
>2 clinical attacks* None of psychosis (see list of possible
Objective clinical evidence
medical causes of psychosis
of >2 lesions
accompanying this article at
>2 clinical attacks Dissemination in space www.currentpsychiatry.com)
Objective clinical evidence by MRI • knowing which psychiatric symp-
of 1 lesion or
>2 MRI-detected lesions toms are common in MS.
consistent with MS plus Despite absence of neurologic
positive CSF symptoms, Ms. B’s psychosis could
or have been the initial presentation of
Await further attack
implicating a different site MS, which is more prevalent among
psychiatric inpatients than in the
1 clinical attack Dissemination in time by MRI general population.6,7 In a prospective
>2 objective clinical lesions or
Second clinical attack
study,8 95% of patients with MS had
neuropsychiatric symptoms, and
1 clinical attack Dissemination in space by MRI 79% had depressive symptoms.
1 objective clinical lesion or
>2 MRI-detected lesions
Hallucinations and delusions were
consistent with MS reported in 10% and 7% of MS
plus positive CSF patients, respectively. These findings
and suggest that mood disturbances are
Dissemination in time by MRI
or
considerably more common than psy-
Second clinical attack chosis among patients with MS.
Diagnosis of MS-related psy-
* Clinical attack: neurologic disturbance defined by subjective report or objective
observation lasting at least 24 hours. chosis has been addressed only in case
Source: Reference 5 reports or small studies, most of
which have not clearly defined psy-
chosis or adequately described the
Three weeks later, Ms. B sees an outpatient symptoms or confounding factors such as med-
psychiatrist. She is paranoid, guarded, and has not ications. Findings on prevalence of psychosis as
been taking risperidone. the initial presentation in MS are more limited
Because Ms. B’s previous MRI results are sus- and confounded by instances in which neurolog-
pect, we ask the hospital’s neurology service to ic symptoms might have been overlooked.9-11
examine her. Findings are unremarkable, but the Few studies have investigated whether lesion
neurologist recommends a follow-up brain MRI in 3 location correlates with specific neuropsychiatric
months or sooner if symptoms emerge. More than symptoms. In one study,8 brain MRI taken with-
2 years later, she has not completed a second MRI in 9 months of presenting symptoms showed that
or contacted her psychiatrist or neurologist. MS was not significantly more severe among

86 VOL. 6, NO. 1 / JANUARY 2007

patients with psychosis compared with nonpsy-
Related resources
chotic MS patients. These data support psychosis
u Feinstein A. The clinical neuropsychiatry of multiple sclerosis.
as a possible early finding in MS. New York: Cambridge University Press; 1999.
At least two studies12,13 suggest a correlation u National Multiple Sclerosis Society. www.nationalmssociety.org.
between temporal lobe lesions and psychosis, but
DRUG BRAND NAME
both study samples were small (8 and 10 patients)
Clozapine • Clozaril Risperidone • Risperdal
and used a combination of diagnoses. One case Haloperidol • Haldol Ziprasidone • Geodon
Lorazepam • Ativan
report also supports this correlation.14
DISCLOSURES
Dr. Higgins reports no financial relationship with any company whose products
TREATING MS-RELATED PSYCHOSIS are mentioned in this article or with manufacturers of competing products.
MS-related psychosis should abate with MS treat- Dr. Rafeyan is a speaker for AstraZeneca, Bristol-Myers Squibb Co.,
ment, but no systematized studies have verified Eli Lilly and Co., GlaxoSmithKline, Pfizer, and Wyeth. He is also an advisor to
Abbott Laboratories and Forest Pharmaceuticals.
this or determined which antipsychotics would be
suitable. Single case reports suggest successful 11. Kohler J, Heilmeyer H, Volk B. Multiple sclerosis presenting as
treatment with risperidone,13 haloperidol,15 clozap- chronic atypical psychosis. J Neurol Neurosurg Psychiatry 1988;
51:281-4.
ine,16 or ziprasidone.17 Ms. B showed initial improve- 12. Honer G, Hurwitz T, Li D, et al. Temporal lobe involvement in
ment with risperidone, but because she was lost to multiple sclerosis patients with psychiatric disorders. Arch Neurol
1987;44:187-90.
follow-up we cannot say if this medication would
13. Feinstein A, du Boulay G, Ron M. Psychotic illness in multiple
work long-term. sclerosis: a clinical and magnetic resonance imaging study.
Br J Psychiatry 1992;161:680-5.
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