INTRODUCTION
Conversion disorder is a disturbance of bodily function that
does not conform to current concepts of anatomy and physiology of
the central or the peripheral nervous system. Typically, it
occurs in a setting of stress and produces considerable dysfunction
(Kaplan & Sadock, 1995). According to the
Diagnostic and Statistical Manual of Mental Disorders, 4th edition
(DSM-IV; American Psychiatric Association,
1994), diagnostic criteria for conversion disorder are as
follows: (1) One or more symptoms or deficits affecting voluntary motor
or sensory function that suggest a neurological or other general
medical condition; (2) psychological factors are judged to be
associated with the symptom or deficit because the initiation or
exacerbation of the symptom or deficit is preceded by conflicts or
other stressors; (3) the symptom or deficit is not intentionally
produced or feigned; (4) the symptom or deficit cannot, after
appropriate investigation, be fully explained by a general medical
condition or by the direct effects of a substance or as a culturally
sanctioned behavior or experience; (5) the symptom or deficit causes
clinically significant distress or impairment in social, occupational,
or other important areas of functioning or warrants medical evaluation;
(6) the symptom or deficit is not limited to pain or sexual
dysfunction, does not occur exclusively during the course of
somatization disorder, and is not better accounted for by another
mental disorder.
Conversion disorder challenges the diagnostic competence of a
physician, as it may include various types of motor, sensory, and
autonomic nervous system symptoms. If it is overlooked, inappropriate
examinations and treatments might be performed (Thomassen et al., 2003). However, little is known
about conversion disorder in leukemia patients during treatment of the
disease.
In this communication, we report an acute leukemia patient who
developed conversion disorder mimicking the adverse effects of
high-dose cytosine arabinoside (Ara-C) treatment after the patient
received high-dose Ara-C treatment.
CASE REPORT
A 21-year-old woman was referred by her hematologist for psychiatric
consultation because of convulsion. The patient had been diagnosed as
having minimally differentiated acute myeloid leukemia (FAB
M0) in August 1998 and received chemotherapy, total body
irradiation, and bone marrow transplantation from HLA-matched unrelated
donor in May 1999.
The patient was discharged in April 2000 and followed by the
out-patient clinic thereafter. In August 2001, 2 years and 3 months
after bone marrow transplantation, she developed dyspnea. Physical and
laboratory examination showed myeloid cells in the peripheral blood,
heart failure, pericardial effusion, cardiac tamponade, and superior
vena cava syndrome due to tumor formation by leukemia cells. Bone
marrow examination demonstrated a relapse of acute myeloid leukemia.
She was diagnosed as having recurrence of acute myeloid leukemia and
hospitalized for treatment with high-dose cytocine arabinoside (Ara-C;
HDAC) therapy (Ara-C 2g/m2 × 2/day × 6
days; Cole & Gibson, 1997).
On day 2 after HDAC, she developed insomnia, anxiety, and
irritability. On day 9 after HDAC, the patient presented with facial
convulsion of short duration. On day 10 after HDAC, the patient
presented again with facial convulsion of short duration and the
hematologist was called to check her condition. As the hematologist
walked into the patient's room, the patient developed convulsion
involving all limbs beginning from the right hand and progressing to
the left hand then to both lower extremities. After the convulsion
terminated, there was no sluggishness, sleepiness, or confusion
recognized and the patient could respond to instructions from the
hematologist.
At the time of referral to a psychiatrist, the patient was bedridden
and seemed calm. She answered questions asked by the psychiatrist
slowly but correctly and consciousness was clear. There was no neck
stiffness observed. Cranial nerve examinations were unremarkable.
Although all limbs looked hypotonic, tendon reflexes of all limbs were
normal and there was no pathological reflex recognized. When her hand
was dropped onto her own face, it fell next to her face but not on her
face.
Laboratory data were unremarkable except for decreased white blood
cell count (below 100/μl) due to high dose Ara-C therapy. We
could not perform head CT, MRI, or electroencephalogram because the
white blood cell count was below 100/μl and she could not be
moved from the clean room. On the following day, she showed a similar
convulsion of the limbs; however, symptoms disappeared soon.
Thereafter, she did not develop further convulsions or paresis of the
limbs.
The patient later told the following stories of experiences she had
suffered. During her first hospital admission, she made friends with a
patient who also had leukemia that was treated by a bone marrow
transplantation. The two patients became good friends and talked about
the disease experiences. On the second admission for the recurrence,
she learned of the death of her friend, and was severely shocked and
saddened by the news. The death of a close friend and the recurrence of
leukemia made her intensely aware of her own mortality.
The atypical convulsions of the patient were preceded by recurrence
of leukemia and bereavement of a close friend and could not be
explained by the general medical condition or by the direct effect of
any substances. Her psychiatric features fulfilled the DSM-IV criteria
for conversion disorder with mixed presentation (code no.300.11)
Thereafter, she received two more courses of HDAC treatment. However,
she did not show any further neuro-psychiatric symptoms or adverse
effects of HDAC. One year later, she died of pneumonia.
Medical History
The patient was a nursing school student with no medical history of
psychiatric or neurological illness or alcohol or drug abuse. She was
normally cooperative in character and was kind to others.
DISCUSSION
Our patient developed conversion disorder mimicking the adverse
effects of HDAC treatment after she received HDAC. This is the first
description of conversion disorder in an adult leukemia patient during
the course of chemotherapy and this case highlights the importance of
differentiating conversion disorder from other chemotherapy-induced
adverse effects.
Conversion disorder challenges the diagnostic competence of a
physician, as it may include various types of motor, sensory, and
autonomic nervous system symptoms (Thomassen et al.,
2003). In addition, the symptoms are similar to the adverse
effects of chemotherapy and infection in cancer patients. In the
differential diagnosis of conversion disorder, many serious
neurological disorders and psychiatric conditions such as brain tumor,
meningo-encephalitis, subdural hemorrhage, major depressive disorder,
and catatonic schizophrenia should be considered (Kaplan & Sadock, 1995). Neurological and
psychiatric complications may arise in leukemia patients receiving
chemotherapy or bone marrow transplantation. Adverse effects of
chemotherapy, steroid-induced psychosis, encephalopathy induced by
immunosuppressive agents, and viral encephalitis must also be included
in the differential diagnosis (Sullivan et al.,
1991). In this case, the patient had received HDAC treatment 10
days earlier, which means that the adverse effects of HDAC should be
included. Adverse effects of HDAC include cerebellar signs,
encephalopathy, seizures, and encephalopathy, which usually occur 1 to
10 days after treatment starts (Damon et al.,
1989; Hwang et al., 1985, Nand et al., 1986). However, laboratory findings,
inexplicable neurological signs, and coincidence of emotional conflict
may help to distinguish conversion disorder from adverse effects of
HDAC.
Differential diagnosis is very important. Proper clinical diagnosis
made further HDAC treatment possible. If conversion disorder is
overlooked and misdiagnosed as adverse effects of chemotherapy,
effective chemotherapy might be stopped and unnecessary examinations
and treatments may be applied to the patients.
The death of a friend who also had leukemia and had received bone
marrow transplantation as well as the recurrence of her own leukemia
were regarded as marked stressors. It has been reported that the news
of cancer recurrence is more upsetting to patients than the initial
diagnosis (Northouse et al., 1995). The
patient later reported that she was severely shocked and saddened by
the death of her friend. The short interval between the death of her
friend, recurrence of leukemia, and the onset of conversion disorder
also makes it seem unlikely that conversion disorder in this case
occurred without stressors.
In considering why the patient developed a conversion disorder, we
speculated that the patient used denial as a defense mechanism, which
can be an expression of severe psychopathology (in psychosis and
personality disorders), but which can also be normal when facing major
stressors (Hughes, 1986; Stiefel & Razavi, 1994). However, the death of
a close friend and the recurrence of leukemia made her intensely aware
of her own fragile condition and broke down her denial, and the patient
developed conversion symptoms.
In our previous reports (Onishi et al., 2000, 2003), we described
two cancer patients in whom bereavement of a close friend due to cancer
caused a manic episode and a brief psychotic disorder, respectively.
The present case, together with previous reports, indicates that
bereavement felt by cancer patients at the deaths of close friends from
cancer during the course of their own disease would be a stressor
promoting psychiatric disorder. Depending on predisposing factors,
precipitating factors, vulnerability factors, and other factors, the
patient is likely to exhibit various clinical symptoms.
In conclusion, appropriate diagnosis of conversion disorder is very
important to avoid inappropriate examinations and treatments in
leukemia patients receiving chemotherapy and/or bone marrow
transplantation. Clinicians should consider conversion disorder in the
differential diagnosis when patients develop unexplained neurological
symptoms.
ACKNOWLEDGMENT
This work was supported by a grant from the Ministry of Health, Labor
and Welfare to H.O.
