JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume 12, Number 3, 2002 © Mary Ann Liebert, Inc. Pp. 259–263
Case Report Obsessive-Compulsive Disorder Secondary to Brain Dysgerminoma in an Adolescent Boy: A Positron Emission Tomography Case Report Pilar Gamazo-Garrán, M.D., Cesar A. Soutullo, M.D., and Felipe Ortun˜o, M.D., Ph.D.
ABSTRACT The neuroanatomical model involved in the pathophysiology of obsessive-compulsive disorder (OCD) postulates a hyperactivation of orbitofrontal, limbic, and basal ganglia circuits. We report a case of OCD secondary to brain dysgerminoma affecting this circuit in an adolescent who responded to citalopram. The patient is a 16-year-old-boy with a midline germinal tumor (dysgerminoma) affecting the caudate nuclei; left lenticular, right internal capsule’s genu; and bilateral involvement of the interventricular septum close to the interventricular foramina. He had OCD symptoms and elevated tumor markers when he had a tumor relapse, and fluorodeoxyglucose positron emission tomography showed caudate nuclei involvement. He responded to citalopram that had to be titriated gradually to 80 mg/day. INTRODUCTION
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(OCD) is a chronic, frequently recurrent disorder, characterized by the presence of obsessions and/or compulsions, that often starts in childhood or adolescence (American Psychiatric Association 1994). The prevalence of OCD in youth ranges from 0.3% to 4%, with a mean age of onset of 12 years. It affects more boys than girls (2:1) until adolescence, when the ratio becomes 1:1 (Swedo et al. 1989b). The etiology of OCD is various, involving psychosocial, personality, genetic, neuroanatomic, and neurochemical factors. Studies show that the main neurotransmitter involved in the pathophysiolBSESSIVE COMPULSIVE DISORDER
ogy of OCD is serotonin, and the neuroanatomical model postulates a hyperactivation of orbitofrontal, limbic, and basal ganglia (mainly the caudate nuclei) circuits (Hugo et al. 1999). There are reported cases of patients with neurological disorders involving frontal basal ganglia regions that developed secondary OCD symptoms (Ames et al. 1994; Cummings and Cunningham 1992; Kant et al. 1996), including patients with Tourette’s syndrome (Hollander et al. 1989), Sydenham’s chorea (Swedo et al. 1989a), and other poststreptococcal neuropsychiatric disorders (Swedo et al. 1998). Structural neuroimaging studies using computerized tomography show contradictory results. Luxenberg et al. (1988) found smaller
Department of Psychiatry and Medical Psychology, Clínica Universitaria, University of Navarra College of Medicine, Pamplona, Spain.
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caudate nuclei volume in patients with OCD versus controls. However, magnetic resonance imaging (MRI) studies either did not replicate this difference (Insel et al. 1983; Kellner et al. 1991) or found larger caudate head volume in patients with OCD (Scarone et al. 1992). Functional neuroimaging studies using positron emission tomography (PET) found metabolism dysfunction in patients with primary OCD in areas including the orbitofrontal gyrus, caudate nuclei, and anterior gyrus cinguli. Four of the five available studies found elevated activity in orbitofrontal cortical areas, with orbital gyrus and caudate nuclei hypermetabolism (Baxter et al. 1988), orbitofrontal hypermetabolism and parietal hypometabolism (Nordahl et al. 1989), and prefrontal orbitofrontal and anterior cinguli hypermetabolism (Sawle et al. 1991; Swedo et al. 1989c). However, another study found lateral prefrontal hypometabolism (Martinot et al. 1990). Caudate nuclei findings are not always replicated, suggesting that activity may change over time from initial hypermetabolism to normal metabolism as a possible adaptation mechanism and that different symptom dimensions have different neuroanatomical correlates (Rauch et al. 1998). There are also studies in patients with OCD after therapeutic interventions showing normalization of function after successful treatment (Baxter et al. 1992; Schwartz et al. 1996). We describe a case report of OCD secondary to brain dysgerminoma in an adolescent boy.
When we evaluated him, he had been admitted to the pediatric oncology unit due to elevation of tumor markers and “behavioral problems.” His behavior included episodic irritability, checking obsessions, and compulsions of pinching people (usually his mother) and asking “Does it hurt?”, and also tapping doors and tables repeatedly. He would become very irritable if his mother would not answer him fast enough, or if someone tried to stop his compulsions, and would kick his mother and ask if it hurt. He also had frequent mood changes: crying episodes and irritability. A new MRI and fluorodeoxyglucose (FDG)PET study showed a tumor relapse with a new tumor at brain stem level and hypermetabolism at the septum pellucidum level close to posterior areas of the caudate nucleus head bilaterally (Fig. 1). He also had bilateral occipital and left temporal-parietal-frontal hypometabolism and asymmetry due to caudate nuclei, thalamic nuclei, and left mesencephalic hypometabolism. We recommended treatment with citalopram that was titrated gradually to 40 mg/day and risperidone 1.5 mg/day; he also received chemotherapy. Five months later he returned for his scheduled follow-up appointment. His tumor markers were negative, and he had a clear improvement in his obsessions, compulsions, and mood problems. He no longer had to ask ques-
CASE REPORT The patient is a 16-year-old Spanish boy who had a midline germinal tumor (dysgerminoma) affecting the caudate nuclei; left lenticular, right internal capsule’s middle area (genu); and interventricular septum bilateral involvement, close to the interventricular foramina. The tumor was diagnosed at age 15 and treated with radiotherapy; the boy then received systemic chemotherapy and after the initial treatment achieved full radiologic remission. He had no personal or family psychiatric history.
FIG. 1. Taken October 2000 by fluorodeoxyglucosepositron emission tomography. (a) Bilateral occipital hypometabolism and left frontal-temporal-parietal hypometabolism.
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FIG. 2. Taken March 2001 by fluorodeoxyglucose-positron emission tomography. (a) Minimal brain stem metabolic activity.
tions in a compulsive way, and his FDG-PET showed minimal pons metabolic activity (Fig. 2). Because of his good response and lack of adverse effects, we continued the treatment with citalopram and risperidone at the same doses. Three months later, however, his psychiatric symptoms worsened; he presented with compulsive tapping of objects and mood lability. A new MRI showed worsening of his tumor process, with a new tumor on the third ventricle ceil-
ing, at the interventricular septum level. A new FDG-PET (Fig. 3) showed low global cerebral activity, lower in posterior regions, and a localized midline hypermetabolic area at the caudate nuclei’s head level bilaterally. C-11 methionine-PET (that shows tumor cells) showed increased uptake at the levels previously described, in the brain stem, and at pons level (Fig. 4). His symptoms improved after we increased the citalopram to 60 mg/day, continuing risperidone at 1.5 mg/day. He remained asymptomatic until a new tumor relapse 2 months later. Again his symptoms responded to an increased citalopram dose of 80 mg/day, the addition of clonazepam 0.5 mg/day, and risperidone continued at a dose of 1.5 mg/day.
DISCUSSION
FIG. 3. Taken May 2001 by fluorodeoxyglucosepositron emission tomography. (a) Low global brain activity, lower in posterior regions. (b) Midline hypermetabolism at the caudate nuclei’s head level.
We found six cases in the literature of OCD secondary to neurologic lesion, involving brain hemorrhage (n = 1), head trauma (n = 2), stroke (n = 1), aneurism (n = 1), and bullet wound (n = 1). (Ames et al. 1994; Cummings and Cunningham 1992; Hugo et al. 1999; Kant et al. 1996). In this case report, the adolescent’s OCD was the first clinical indication of tumor relapse, verified by functional neuroimaging, which responded to a combination of citalopram and risperidone. The tumor affected the
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FIG. 4. Taken May 2001 by C-11 methionine-positron emission tomography. (a) Midline increased uptake (caudate nuclei head). (b) Increased uptake in the pons area.
frontal lobes and basal ganglia, the circuits involved in the pathophysiology of OCD according to the available studies.
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