CLINICAL
AND
LABORATORY OBSERVATIONS
Hemiparesis in an Adolescent With Acute Lymphoblastic Leukemia: Everything Is Not Always What it Seems David Andina, MD, Alvaro Lassaletta, MD, Julian Sevilla, PhD, Silvia Gutierrez, MD, and Luis Madero, PhD
Summary: Acute lymphoblastic leukemia is a common malignancy in childhood. Managing adverse events during treatment can result in very complex situations. A previously healthy adolescent diagnosed with T-cell acute lymphoblastic leukemia developed on day + 55 of induction chemotherapy hemiparesis, dysesthesia, and facial palsy. Blood tests and brain imaging techniques were unremarkable. The patient was diagnosed with a conversion disorder, which completely resolved. Although rare in clinical practice, children and adolescents with cancer do not always have organic pathology explaining their symptoms. Psychiatric disorders such as those of the somatoform spectrum must be considered, particularly in patients with anxiety or depression. Key Words: acute lymphoblastic leukemia, conversion disorder, hemiparesis, adolescent
(J Pediatr Hematol Oncol 2016;38:63–64)
A
cute lymphoblastic leukemia (ALL) is the most common malignancy in childhood, constituting 80% of all childhood acute leukemias. Current treatment guidelines include various chemotherapeutic drugs with numerous adverse effects. Secondary effects are also associated with radiation therapy or other treatments used in these patients (antibiotics, antiemetics, and antihistamines). In addition to treatment effects, the course of the illness itself and the existence of intercurrent diseases must be considered. The possibility of other diseases should be considered when symptoms are time-inconsistent or do not follow a classical clinical pattern. Conversion disorder (CD) is rare in the pediatric age group but should be part of the differential diagnosis in patients with neurological symptoms, particularly in those with significant emotional disturbances, such as patients with cancer.
CASE PRESENTATION In this case report, we describe a previously healthy 13-yearold boy with no significant family history who was diagnosed with T-cell ALL and prescribed the German BFM-95 treatment protocol for ALL. After initial induction with prednisone, daunorubicin, vincristine, and asparaginase, he achieved complete remission on day + 33 of treatment. The patient was started on a second induction consisting of cyclophosphamide, daily oral mercaptopurine, and cytarabine. On day + 55 after receiving oral mercaptopurine and intravenous cytarabine, and coinciding with central line manipulation Received for publication May 5, 2014; accepted June 21, 2014. From the Hospital Universitario Nin˜o Jesu´s, Madrid, Spain. The authors declare no conflict of interest. Reprints: Alvaro Lassaletta, MD, Pediatric Hematology-oncology Department, Hospital Universitario Nin˜o Jesu´s, Avda. Menendez Pelayo 65, Madrid 28009, Spain (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Hematol Oncol
for a blood test, the patient developed progressive weakness of the upper and lower right limbs as well as standing instability. No other remarkable findings were observed on physical examination. He also developed right facial palsy, dysesthesia in the right half of the body, and complete absence of tendon reflexes during subsequent hours. Blood tests showed neutropenia (0.4109/L) and thrombocytopenia (34 109/L). Biochemistry and blood clotting values were normal. Suspecting an acute stroke, a cranial computed tomography scan was performed with no findings, and a cerebrospinal fluid examination was normal. The symptoms disappeared completely after the first 24 hours, and magnetic resonance angiography revealed no pathologic findings the next day. After 36 hours of being asymptomatic, the patient lost strength in the right hemibody again, which was more apparent in the upper limb. A repeat cranial computed tomography scan and electroencephalogram were normal. The symptoms disappeared with administration of clorazepate dipotassium. The possibility that the diagnosis was not organic was considered for the first time. When the patient was assessed by a psychiatrist, he verbalized anxiety and concerns regarding the diagnosis and treatment of his disease. The patient improved, and no further neurological or psychiatric symptoms were observed during the course of treatment. He has been in complete remission and completely asymptomatic for >5 years since the chemotherapy ended.
DISCUSSION Patients with cancer may have different complications secondary to the disease itself, the treatment received, or the presence of intercurrent disease, primarily those of infectious etiology. The variety of chemotherapeutic regimens used today and the many reported side effects associated with each of them can result in a very complex situation with regard to managing the adverse outcomes. A physician may be faced with medical conditions that are difficult to understand because the symptoms and signs do not follow a characteristic pattern. Therefore, it is important to include the possibility of somatoform spectrum disorder in the differential diagnosis when facing a patient with symptoms that do not fit a clinically known pattern, especially with the addition of an important psychological component. Unresolved conflicts and underlying psychological problems in the form of somatic symptoms and signs are unconsciously experienced by patients with these disorders. CD is a somatoform disorder defined by the presence of pseudoneurological symptoms related to voluntary sensory or motor function. Some of the most typical symptoms include blindness, partial or complete paralysis, inability to speak, deafness, numbness, sores, difficulty swallowing, incontinence, balance problems, seizures, tremors, and difficulty walking.1 Information on the frequency of CD is limited, in part due to the complexity of the diagnosis. Although there are a
Volume 38, Number 1, January 2016
www.jpho-online.com |
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
63
J Pediatr Hematol Oncol
Andina et al
great number of unexplained symptoms in clinical practice, it is difficult to know what proportion is due to conversion. An Australian surveillance study of CD in children and adolescents estimated an annual incidence rate of 2.3 to 4.2/ 100,000 children.2 A diagnosis of a CD may be suspected by physical examination if the psychogenic neurological presentation does not follow the usual patterns characteristic of neurological injury but stems from the patient’s belief of how the disease should be manifested. A worsening of neurological signs is also observed when these patients are evaluated or when circumstances make the patient pay attention to their own deficits. Other typical features of a CD are sudden onset, spontaneous remission or return of the symptoms, and a lack of typical signs of organic disease. Although the prototypical patient is a mid- to late-30s woman of average intelligence suffering a depressive disorder, CD can occur any time in either sex and even in those without a comorbidity. When a case of CD is suspected, a comprehensive patient assessment to rule out an organic disease and a thorough mental status examination in search of a primary psychiatric disorder and triggers are always required.3,4 There is no specific treatment for CD. In addition to treating the underlying psychiatric disorder, it is essential to establish a narrow therapeutic alliance that allows the patient to understand their condition.5 Conversion symptoms, particularly acute ones, may resolve spontaneously in response to an explanation and suggestion, whereas other patients may require long-term monitoring to manage mood disorders or associated psychosocial distress particularly if improvement has failed to occur during the initial period in the hospital.6 Our patient met all of the specific diagnostic criteria for CD according to the Diagnostic and Statistical Manual for Mental Disorders, Revised Fourth Edition (Table 1). The patient had, for instance, hemiparesis on the right side with facial palsy on the same side. However, when considering whether the symptomatology may be part of a CD, it is important to ensure that the signs and symptoms are not part of any other psychiatric illness or unusual presentation of a physical disorder.
CONCLUSIONS We would like to stress the importance of expanding differential diagnosis to include psychiatric disorders such as those of the somatoform spectrum, particularly in patients with anxiety or depression. Although rare in clinical practice with a young population, cancer patients do not always have organic pathology; thus, by not considering a CD, the medical diagnosis
64 | www.jpho-online.com
Volume 38, Number 1, January 2016
TABLE 1. Diagnostic Criteria for Conversion Disorder According to DSM-IV-TR7 (1) One or more symptoms or deficits are present that affect voluntary motor or sensory function suggestive of a neurological or other general medical condition; (2) Psychological factors are judged to be associated with the symptom or deficit because conflicts or other stressors precede the initiation or exacerbation of the symptom or deficit; (3) The symptom or deficit is not intentionally produced or feigned; (4) The symptom or deficit, after appropriate investigation, cannot be explained fully by a general medical condition, 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.
can be prolonged unnecessarily by performing unnecessary procedures and prescribing treatments that can result in harm to the patient or delay proper care. Above all, when neurological symptoms are present that do not correlate with known organic disease patterns and have a sudden onset and spontaneous remission or return, the physician must consider the possibility of this disorder, which is probably underdiagnosed in children and adolescents. REFERENCES 1. Zeharia A, Mukamel M, Carel C, et al. Conversion reaction: management by the paediatrician. Eur J Pediatr. 1999;158: 160–164. 2. Kozlowska K, Nunn KP, Rose D, et al. Conversion disorder in Australian pediatric practice. J Am Acad Child Adolesc Psychiatry. 2007;46:68–75. 3. Stone J, Smyth R, Carson A, et al. Systematic review of misdiagnosis of conversion symptoms and “hysteria”. BMJ. 2005;331:989. 4. Sar V, Akyu¨z G, Kundakc¸i T, et al. Childhood trauma, dissociation, and psychiatric comorbidity in patients with conversion disorder. Am J Psychiatry. 2004;161:2271–2276. 5. Stonnington CM, Barry JJ, Fisher RS. Conversion disorder. Am J Psychiatry. 2006;163:1510–1517. 6. Couprie W, Wijdicks EF, Rooijmans HG, et al. Outcome in conversion disorder: a follow up study. J Neurol Neurosurg Psychiatry. 1995;58:750–752. 7. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000.
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
AND
LABORATORY OBSERVATIONS
Hemiparesis in an Adolescent With Acute Lymphoblastic Leukemia: Everything Is Not Always What it Seems David Andina, MD, Alvaro Lassaletta, MD, Julian Sevilla, PhD, Silvia Gutierrez, MD, and Luis Madero, PhD
Summary: Acute lymphoblastic leukemia is a common malignancy in childhood. Managing adverse events during treatment can result in very complex situations. A previously healthy adolescent diagnosed with T-cell acute lymphoblastic leukemia developed on day + 55 of induction chemotherapy hemiparesis, dysesthesia, and facial palsy. Blood tests and brain imaging techniques were unremarkable. The patient was diagnosed with a conversion disorder, which completely resolved. Although rare in clinical practice, children and adolescents with cancer do not always have organic pathology explaining their symptoms. Psychiatric disorders such as those of the somatoform spectrum must be considered, particularly in patients with anxiety or depression. Key Words: acute lymphoblastic leukemia, conversion disorder, hemiparesis, adolescent
(J Pediatr Hematol Oncol 2016;38:63–64)
A
cute lymphoblastic leukemia (ALL) is the most common malignancy in childhood, constituting 80% of all childhood acute leukemias. Current treatment guidelines include various chemotherapeutic drugs with numerous adverse effects. Secondary effects are also associated with radiation therapy or other treatments used in these patients (antibiotics, antiemetics, and antihistamines). In addition to treatment effects, the course of the illness itself and the existence of intercurrent diseases must be considered. The possibility of other diseases should be considered when symptoms are time-inconsistent or do not follow a classical clinical pattern. Conversion disorder (CD) is rare in the pediatric age group but should be part of the differential diagnosis in patients with neurological symptoms, particularly in those with significant emotional disturbances, such as patients with cancer.
CASE PRESENTATION In this case report, we describe a previously healthy 13-yearold boy with no significant family history who was diagnosed with T-cell ALL and prescribed the German BFM-95 treatment protocol for ALL. After initial induction with prednisone, daunorubicin, vincristine, and asparaginase, he achieved complete remission on day + 33 of treatment. The patient was started on a second induction consisting of cyclophosphamide, daily oral mercaptopurine, and cytarabine. On day + 55 after receiving oral mercaptopurine and intravenous cytarabine, and coinciding with central line manipulation Received for publication May 5, 2014; accepted June 21, 2014. From the Hospital Universitario Nin˜o Jesu´s, Madrid, Spain. The authors declare no conflict of interest. Reprints: Alvaro Lassaletta, MD, Pediatric Hematology-oncology Department, Hospital Universitario Nin˜o Jesu´s, Avda. Menendez Pelayo 65, Madrid 28009, Spain (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Hematol Oncol
for a blood test, the patient developed progressive weakness of the upper and lower right limbs as well as standing instability. No other remarkable findings were observed on physical examination. He also developed right facial palsy, dysesthesia in the right half of the body, and complete absence of tendon reflexes during subsequent hours. Blood tests showed neutropenia (0.4109/L) and thrombocytopenia (34 109/L). Biochemistry and blood clotting values were normal. Suspecting an acute stroke, a cranial computed tomography scan was performed with no findings, and a cerebrospinal fluid examination was normal. The symptoms disappeared completely after the first 24 hours, and magnetic resonance angiography revealed no pathologic findings the next day. After 36 hours of being asymptomatic, the patient lost strength in the right hemibody again, which was more apparent in the upper limb. A repeat cranial computed tomography scan and electroencephalogram were normal. The symptoms disappeared with administration of clorazepate dipotassium. The possibility that the diagnosis was not organic was considered for the first time. When the patient was assessed by a psychiatrist, he verbalized anxiety and concerns regarding the diagnosis and treatment of his disease. The patient improved, and no further neurological or psychiatric symptoms were observed during the course of treatment. He has been in complete remission and completely asymptomatic for >5 years since the chemotherapy ended.
DISCUSSION Patients with cancer may have different complications secondary to the disease itself, the treatment received, or the presence of intercurrent disease, primarily those of infectious etiology. The variety of chemotherapeutic regimens used today and the many reported side effects associated with each of them can result in a very complex situation with regard to managing the adverse outcomes. A physician may be faced with medical conditions that are difficult to understand because the symptoms and signs do not follow a characteristic pattern. Therefore, it is important to include the possibility of somatoform spectrum disorder in the differential diagnosis when facing a patient with symptoms that do not fit a clinically known pattern, especially with the addition of an important psychological component. Unresolved conflicts and underlying psychological problems in the form of somatic symptoms and signs are unconsciously experienced by patients with these disorders. CD is a somatoform disorder defined by the presence of pseudoneurological symptoms related to voluntary sensory or motor function. Some of the most typical symptoms include blindness, partial or complete paralysis, inability to speak, deafness, numbness, sores, difficulty swallowing, incontinence, balance problems, seizures, tremors, and difficulty walking.1 Information on the frequency of CD is limited, in part due to the complexity of the diagnosis. Although there are a
Volume 38, Number 1, January 2016
www.jpho-online.com |
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
63
J Pediatr Hematol Oncol
Andina et al
great number of unexplained symptoms in clinical practice, it is difficult to know what proportion is due to conversion. An Australian surveillance study of CD in children and adolescents estimated an annual incidence rate of 2.3 to 4.2/ 100,000 children.2 A diagnosis of a CD may be suspected by physical examination if the psychogenic neurological presentation does not follow the usual patterns characteristic of neurological injury but stems from the patient’s belief of how the disease should be manifested. A worsening of neurological signs is also observed when these patients are evaluated or when circumstances make the patient pay attention to their own deficits. Other typical features of a CD are sudden onset, spontaneous remission or return of the symptoms, and a lack of typical signs of organic disease. Although the prototypical patient is a mid- to late-30s woman of average intelligence suffering a depressive disorder, CD can occur any time in either sex and even in those without a comorbidity. When a case of CD is suspected, a comprehensive patient assessment to rule out an organic disease and a thorough mental status examination in search of a primary psychiatric disorder and triggers are always required.3,4 There is no specific treatment for CD. In addition to treating the underlying psychiatric disorder, it is essential to establish a narrow therapeutic alliance that allows the patient to understand their condition.5 Conversion symptoms, particularly acute ones, may resolve spontaneously in response to an explanation and suggestion, whereas other patients may require long-term monitoring to manage mood disorders or associated psychosocial distress particularly if improvement has failed to occur during the initial period in the hospital.6 Our patient met all of the specific diagnostic criteria for CD according to the Diagnostic and Statistical Manual for Mental Disorders, Revised Fourth Edition (Table 1). The patient had, for instance, hemiparesis on the right side with facial palsy on the same side. However, when considering whether the symptomatology may be part of a CD, it is important to ensure that the signs and symptoms are not part of any other psychiatric illness or unusual presentation of a physical disorder.
CONCLUSIONS We would like to stress the importance of expanding differential diagnosis to include psychiatric disorders such as those of the somatoform spectrum, particularly in patients with anxiety or depression. Although rare in clinical practice with a young population, cancer patients do not always have organic pathology; thus, by not considering a CD, the medical diagnosis
64 | www.jpho-online.com
Volume 38, Number 1, January 2016
TABLE 1. Diagnostic Criteria for Conversion Disorder According to DSM-IV-TR7 (1) One or more symptoms or deficits are present that affect voluntary motor or sensory function suggestive of a neurological or other general medical condition; (2) Psychological factors are judged to be associated with the symptom or deficit because conflicts or other stressors precede the initiation or exacerbation of the symptom or deficit; (3) The symptom or deficit is not intentionally produced or feigned; (4) The symptom or deficit, after appropriate investigation, cannot be explained fully by a general medical condition, 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.
can be prolonged unnecessarily by performing unnecessary procedures and prescribing treatments that can result in harm to the patient or delay proper care. Above all, when neurological symptoms are present that do not correlate with known organic disease patterns and have a sudden onset and spontaneous remission or return, the physician must consider the possibility of this disorder, which is probably underdiagnosed in children and adolescents. REFERENCES 1. Zeharia A, Mukamel M, Carel C, et al. Conversion reaction: management by the paediatrician. Eur J Pediatr. 1999;158: 160–164. 2. Kozlowska K, Nunn KP, Rose D, et al. Conversion disorder in Australian pediatric practice. J Am Acad Child Adolesc Psychiatry. 2007;46:68–75. 3. Stone J, Smyth R, Carson A, et al. Systematic review of misdiagnosis of conversion symptoms and “hysteria”. BMJ. 2005;331:989. 4. Sar V, Akyu¨z G, Kundakc¸i T, et al. Childhood trauma, dissociation, and psychiatric comorbidity in patients with conversion disorder. Am J Psychiatry. 2004;161:2271–2276. 5. Stonnington CM, Barry JJ, Fisher RS. Conversion disorder. Am J Psychiatry. 2006;163:1510–1517. 6. Couprie W, Wijdicks EF, Rooijmans HG, et al. Outcome in conversion disorder: a follow up study. J Neurol Neurosurg Psychiatry. 1995;58:750–752. 7. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000.
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
