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A 7-month-old boy was referred for monocular nystagmus and failure to thrive. He was born at full term weighing 3.63 kg after a normal pregnancy, labor, and delivery. He grew appropriately until 3 months of age, after which his weight dropped from the 50th percentile to the fifth percentile in 2 months despite maintenance of a fairly adequate caloric intake. The patient had multiple episodes of emesis. Results of his gastrointestinal evaluation were normal. At 6 months of age, he developed a constant rapid nystagmus of the right eye.
On presentation, he was a happy, engaged, alert child with an emaciated appearance (Figure, A). His head was of normal size, although it appeared large relative to his small body size. During the examination, the patient was socially interactive and visually attentive. He had normal, optokinetic responses and brisk pupillary responses with no relative afferent pupillary defect. He had a rapid pendular horizontal nystagmus, with no associated strabismus, head nodding, or torticollis (Video). The patient looked readily toward objects held in the peripheral visual field of either eye. The retinal examination showed normal-sized optic discs without swelling or pallor. The patient had no history or findings suggestive of neurofibromatosis type 1.
A, On presentation, the patient appeared emaciated but alert. B, T1 fluid-attenuated inversion recovery sagittal magnetic resonance (MR) image showing large globular suprasellar mass enveloping the optic chiasm (arrows).
Perform visual evoked potential test
Perform magnetic resonance imaging of the brain and spine
Perform blood culture
Read the Discussion.
Russell diencephalic syndrome of infancy
What To Do Next
C. Perform magnetic resonance (MR) imaging of the brain and spine
Magnetic resonance imaging of the brain showed a homogeneous enhancing mass within the suprasellar region measuring approximately 2.8 × 3.2 × 5.4 cm, suggestive of chiasmatic glioma (Figure, B), and a small nodular lesion in the medulla. There was no associated hydrocephalus. Magnetic resonance imaging of the spine showed a homogeneously enhancing 4-mm nodule along the thecal sac. Multifocal cauda equina nerve root tiny nodularities, possibly leptomeningeal enhancement, were noted. Results of genetic testing for NF1 were negative.
The differential diagnosis of acquired monocular nystagmus in infancy includes spasmus nutans, chiasmal or hypothalamic glioma, and congenital unilateral visual loss.1 Spasmus nutans is a benign clinical entity characterized by the triad of nystagmus, head nodding, and an abnormal head position. The nystagmus is characteristically asymmetrical and may be monocular. The association of chiasmal glioma with spasmus nutans is usually signaled by 1 or more of the following clinical findings: a relative afferent pupillary defect, optic atrophy or disc swelling, large head size, café au lait spots, and coexistent neurologic dysfunction or emaciation.2 Our patient had monocular nystagmus with no other features of spasmus nutans. His body habitus provided the critical clue to the diagnosis of Russell diencephalic syndrome of infancy, which was confirmed by the results of MR imaging.
In 1951, Russell3 first described the clinical entity of diencephalic syndrome as consisting of profound emaciation in infancy with an absence of subcutaneous adipose tissue despite a normal or only slightly diminished caloric intake. Affected children have a paradoxically alert appearance with motor overactivity, euphoria, and normal or accelerated linear growth.3,4 Resting energy expenditure studies can demonstrate a hypermetabolic state.4 Drop et al5 hypothesized that a lipolytic peptide, B-lipotropin, which is produced in excess by a tumor, could explain the decrease in subcutaneous tissue and release of excess human growth hormone. Possible roles of the hormones leptin and ghrelin have also been suggested.6
Diencephalic syndrome has since been described almost exclusively in young children with space-occupying lesions of the hypothalamic-optic chiasm region.7 These tumors are larger, occur at a younger age (usually <12 months), and behave more aggressively than similarly located tumors without diencephalic syndrome.4,6 One study found an association between diencephalic syndrome and early dissemination of gliomas.8 In another study, all tumors associated with diencephalic syndrome had either a BRAF fusion mutation or NF1 mutations, both of which are associated with a more favorable survival in low-grade gliomas.4 Since our patient did not have any biopsy or resection, the BRAF status of his tumor is unknown.
Treatment options for Russell diencephalic syndrome are limited by tumor involvement of the optic chiasm and adjacent anterior visual pathways, which precludes surgical resection. Adjuvant radiotherapy has been shown to be beneficial; however, radiotherapy in young children carries significant long-term morbidity.9 Recent studies have demonstrated the efficacy of chemotherapy supplemented with nutritional support as the first line of treatment, with favorable overall survival and metabolic outcomes.4 Long-term sequelae of Russell diencephalic syndrome include visual and pituitary dysfunction, learning difficulties, and paradoxical inappropriate weight gain.
Tumors associated with diencephalic syndrome often have a poor response to treatment, requiring multiple courses of therapy over time. Given the rarity of diencephalic syndrome, studies with a large number of patients and long-term follow-up are limited. One study reported a 5-year progression-free survival of 22%, with all children remaining alive at a median follow-up of 5.3 years.4
The patient was treated with a chemotherapeutic regimen consisting of carboplatin and vincristine.9 Following 10 weeks of induction chemotherapy, successive MR imaging showed progression of the suprasellar mass with mild interval progression of the leptomeningeal disease. He was then treated with vinblastine monotherapy. At the last follow-up after 5 months of vinblastine monotherapy, the patient continues to do well clinically with weight gain and good vision, although MR imaging showed mild enlargement of the suprasellar mass with stable leptomeningeal disease.
Corresponding Author: Michael C. Brodsky, MD, Department of Ophthalmology, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
Published Online: August 27, 2015. doi:10.1001/jamaophthalmol.2015.1940.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and no conflicts were reported.
Funding/Support: This work was supported by the Knights Templar Eye Foundation, Inc (Dr Brodsky) and by an unrestricted grant from Research to Prevent Blindness Inc and the Mayo Foundation.
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Dhannawat SS, Rao AAN, Brodsky MC. Nystagmus in an Emaciated Infant. JAMA Ophthalmol. 2015;133(11):1349–1350. doi:10.1001/jamaophthalmol.2015.1940
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