Optic pathway glioma infiltrating into somatostatinergic pathways in a young boy with gigantism

Case report

Full access

✓ The authors report gigantism in a 16-month-old boy with an extensive optic pathway glioma infiltrating into somatostatinergic pathways, as revealed by magnetic resonance imaging and immunocytochemical studies. Stereotactic biopsies of areas showing hyperintense signal abnormalities on T2-weighted images in and adjacent to the involved visual pathways provided rarely obtained histological correlation of such areas. The patient received chemotherapy, which resulted in reduction of size and signal intensity of the tumor and stabilization of vision and growth velocity.

Gigantism with growth hormone (GH) excess is extremely rare in infancy and early childhood.6–16,17,21,30,34,61 The majority of these cases are due to GH-secreting pituitary adenomas;6,16,26,28–30,34,41,43,61 although a few occurrences have been associated with hypothalamic mass lesions. In these few cases, it was postulated that GH excess was secondary to either tumor production of GH-releasing hormone (GRH) or disordered hypothalamic regulation of GH secretion.17,21

This report describes a case of gigantism in a young child with an extensive optic pathway glioma. To our knowledge, this is the first case report to document tumor infiltration of somatostatinergic pathways using immunocytochemical methods. Additional immunocytochemical studies support the argument that gigantism in this patient resulted from disordered regulation of GH secretion, rather than a functionally active GRH-secreting tumor. Moreover, it was demonstrated that areas showing hyperintense signal abnormalities on T2-weighted magnetic resonance (MR) imaging do not necessarily indicate the presence of tumor invasion in diffuse optic pathway glioma.

Case Report

This 16-month-old boy presented with a 3-month history of visual deterioration and a 2-day history of increasing gait difficulties. The child was the product of a full-term pregnancy, and his postnatal life was remarkable for nystagmus2 and a rapid increase in height and weight that began at 5 months of age. At birth his weight was 3.7 kg (80th percentile), length was 53.3 cm (88th percentile), and head circumference was 33.0 cm (10th percentile). Family history was negative for phacomatosis, central nervous system tumors, and gigantism.

Examination

On admission, the patient's weight was 18.0 kg (50th percentile for age 4 years, 8 months), height was 89.3 cm (50th percentile for age 2 years, 2 months), and head circumference was 50 cm (95th percentile). Physical examination revealed an alert, but irritable, tall, obese child who was babbling (Fig. 1). He had coarse facial features, mild macroglossia, and thickening of the fingers and toes. There were no cutaneous abnormalities. He showed no visual interest and would not fixate on the examiner or on objects presented to him. His eyes were deviated slightly downward on primary gaze, and funduscopic examination revealed hypoplastic optic nerves. Neurological examination showed slowly but symmetrically reactive pupils, hyperreflexia in the lower extremities, bilateral ankle clonus, equivocal Babinski's signs, and a broad-based unsteady gait. The child's routine laboratory studies and basal endocrine testing were unremarkable except for a significantly elevated somatomedin C level14,15,19,42,51,52 of 3.1 U/ml (10 standard deviations above the mean). Provocative endocrine testing was not performed. Bone age, evaluated according to the standards of Greulich and Pyle,29 was consistent with chronological age. The MR images of the brain and orbits revealed an extensive optic pathway tumor involving both optic nerves, the optic chiasm, and the posterior optic pathways, as well as an abnormal signal from adjacent structures. Significant hydrocephalus and transependymal edema was present, with stenosis of the aqueduct of Sylvius.

Fig. 1.
Fig. 1.

Photograph of the patient with gigantism at 36 months of age, after surgical treatment and completion of chemotherapy regimen for optic pathway glioma.

Operations and Postoperative Course

The patient underwent placement of a right ventriculoperitoneal shunt and showed improvement in his gait within a few days. Opening pressure was 17 cm H2O, routine cerebrospinal fluid (CSF) studies were normal, and CSF cytology was negative for malignant cells. Serial MR imaging showed resolution of the hydrocephalus and associated transependymal edema, but persistence of hyperintense signal abnormalities on T2-weighted images in and adjacent to the involved visual pathways (Fig. 2). The presence on MR imaging of a diffuse optic pathway tumor that included involvement of the chiasm and hypothalamus indicated the need to obtain a histological diagnosis to correlate with pediatric oncology protocols.27,49

Fig. 2.
Fig. 2.

Magnetic resonance T2-weighted images (axial views) obtained 1 month after placement of a ventriculoperitoneal shunt. There has been interval resolution of the hydrocephalus and transependymal edema, but persistence of hyperintense signal abnormalities in and adjacent to the involved optic pathways (A, B, and C). The intracranial optic nerves and chiasm are thickened by tumor (A, large arrow). Biopsies were taken from the medial left temporal lobe (A, small arrow) and the head of the left caudate nucleus (C, small arrow).

After general anesthesia was administered to the patient, the Cosman-Roberts-Wells stereotactic system was used to obtain computerized tomography (CT)-guided stereotactic biopsies of two hypodense areas of brain that corresponded to two areas demonstrating hyperintense signal abnormalities on long TR sequences on MR imaging (Fig. 2). Through a direct approach via frontal and temporal burr holes, biopsies were obtained from the head of the caudate nucleus on the left and from the medial left temporal lobe (in the region of the optic radiation). The patient tolerated the procedure well. Microscopic pathological examination was consistent with atypical gliosis in the left caudate nucleus and a well-differentiated astrocytoma in the medial left temporal lobe. At 18 months of age, the boy began a chemotherapy treatment protocol with actinomycin D and vincristine.49,56 Toxicity levels were acceptable and manageable. The patient's visual function fluctuated throughout his course of chemotherapy, varying from no reaction at all to bright lights and large brightly colored objects, to accurate grasping for nearby small objects (level of visual function at completion of chemotherapy). Serial MR images of his brain and orbits were obtained after completion of each of the six cycles of chemotherapy. Changes included a mild-to-moderate reduction in the size and signal intensity of the extensive optic pathway tumor. Following treatment, at 3 years of age, his height velocity had stabilized, but the rapid weight gain and hyperphagia continued.47,60 At this time, the patient's height was 112.5 cm (50th percentile for age 5 years and 5 months), weight was 29.7 kg (50th percentile for age 9 years and 6 months), and head circumference was 51.5 cm (75th percentile). Follow-up endocrine testing at the end of the course of chemotherapy revealed that basal endocrine values were within normal ranges. Developmental assessment of this child during and after treatment showed a delay in intellectual and speech abilities; motor development assessment revealed a broad-based gait and an ability to grasp and handle objects well.

Pathological Examination

Microscopically, sections from the left caudate nucleus were consistent with atypical gliosis characterized by a mild increase in astrocytic cell density with slight nuclear pleomorphism (Fig. 3 left). Mitotic figures and capillary endothelial hyperplasia were not identified. Immunocytochemical studies were negative for GH, GRH, and somatostatin. Sections obtained from the medial left temporal lobe showed a greater increase in atypical astrocytic cell density (Fig. 3 right); immunocytochemical studies confirmed the presence of neoplastic fibrillary astrocytes (consistent with a well-differentiated astrocytoma) and demonstrated immunopositivity for somatostatin (Fig. 4), but not for GH and GRH.

Fig. 3.
Fig. 3.

Photomicrographs. H & E, original magnification × 300. Left: Section from the head of the left caudate nucleus showing atypical gliosis characterized by a mild increase in astrocytic cell density with slight nuclear polymorphism. Right: Section obtained from the medial left temporal lobe showing a well-differentiated astrocytoma.

Fig. 4.
Fig. 4.

Immunohistochemical findings showing immunopositivity for somatostatinergic neurons (arrows) in a section from the medial left temporal lobe. H & E, original magnification × 300.

Discussion
Evaluation of Neuroendocrinology

Patients with tumors in the region of the hypothalamus, optic nerves, and optic chiasm often have associated endocrine and metabolic abnormalities that are most frequently manifested clinically as the diencephalic syndrome or precocious puberty.10,16,20,57,62 It is rare for such tumors to be associated with gigantism and GH excess.17,21,28,58 Our patient's gigantism is best explained by a disorder in hypothalamic regulation of GH release as a result of tumor infiltration into somatostatinergic pathways. The positive immunostaining for somatostatin in the medial left temporal lobe lesion was thought to correspond to somatostatinergic neurons in the corticomedial amygdala, which sends efferent pathways to the septal and preoptic areas via the stria terminalis.37,42 These efferent pathways and the somatostatinergic areas of the hypothalamus to which they project normally exert an inhibitory influence on GH release. Pathological examination and immunocytochemical studies confirmed the presence of neoplastic fibrillary astrocytes infiltrating into this somatostatin-rich area of the brain. Furthermore, T2-weightcd MR imaging revealed an abnormal signal involving the somatostatin-rich areas in the medial temporal lobes (corticomedial amygdalae) and anterior hypothalamus (preoptic areas) (Fig. 2).

We believe that the patient's tumor disrupted the normal GH-inhibitory effects of the somatostatinergic system in these areas, resulting in accelerated growth and gigantism. It also seems likely that the child's hyperphagia and obesity may be explained by bilateral tumor involvement of the ventromedial hypothalamic nuclei, with disruption of the satiety center.42,54

Neuroradiology Studies

Various series have reported that 6% to 58% of patients with optic pathway gliomas have neurofibromatosis type 1 (NF1), but the true incidence is not known because clinical stigmata of NF1 may not be present at the time the lesion is diagnosed, especially in young children.3,64 In our patient, short TR/TE MR images showed some confluent nodular foci of increased signal involving the basal ganglia, internal capsule, and thalami: findings thought by some investigators to represent ectopic Schwann cells or melanocytes within heterotopic or hamartomatous lesions in patients with NF1.45 The MR images also revealed “double-intensity tubular thickening, elongation, and downward kinking” of both optic nerves (Fig. 5), findings thought to be indicative of NF1, even in the absence of other clinical stigmata of NF1.36 Hydrocephalus associated with aqueductal stenosis, another recognized central nervous system manifestation of NF1, was also evident on MR imaging.11 Long TR sequences showed extensive hyperintense signal abnormalities in the optic chiasm, optic tracts, lateral geniculate bodies, and optic radiations, as well as in adjacent areas of the brain including the basal ganglia, brain stem, thalamus, hypothalamus, internal capsule, medial temporal lobes, and periventricular white matter (Fig. 2). On long TR images, more than 50% of NF1 patients have hyperintense signal abnormalities involving various areas of the brain (basal ganglia, brain stem, thalamus, hypothalamus, internal capsule, cerebellum, centrum semiovale, corpus callosum, and optic radiations), many of which are the same as seen in our patient.8,9,11,31,33,40,44,64

Fig. 5.
Fig. 5.

Magnetic resonance images, sagittal T1-weighted (left) and axial proton-density-weighted (right) views, showing double-intensity tubular thickening, elongation, and downward kinking of the optic nerves.

It was difficult to discern on radiographic examination whether the hyperintense signal abnormalities in our patient represented infiltration of an extensive optic pathway glioma into adjacent areas of brain, or whether they represented the characteristic hyperintense signal abnormalities often seen in NF1 patients.40 The precise histological correlates of the hyperintense signal abnormalities in NF1 patients are rarely known, but the differential diagnosis includes hamartoma, atypical gliosis, dysplasia, foci of dysmyelination, vascular alteration, edema, forme fruste of glioma, and extension of an infiltrating glioma.11,40–44

Radiographically, our patient had signs consistent with NF1, but the clinical stigmata were absent. Regardless of whether this child had NF1, the histological correlates obtained of the abnormal hyperintense areas on T2-weighted MR images are interesting. Even in patients who have extensive optic pathway gliomas without NF1, the precise histological correlate of the hyperintense signal abnormalities in the posterior optic pathways is not known. This is largely because it is rare that a biopsy is taken of this area and a pathological specimen obtained from patients whose tumors may be stable for many years.3

Therapeutic Considerations

Our patient received chemotherapy because of the apparent progressive nature of the tumor and his youth. Encouraging results have been reported for the administration of actinomycin D and vincristine on the same schedule used by Packer, et al.49 Responses to nitrosourea, cisplatin, and the second-generation cisplatin analogue carboplatin have also been reported.13,27,39,46,50 Radiation therapy is an effective treatment for optic glioma,5,12,23,25,32,38,53,55 but in the developing central nervous system, it may result in significant long-term intellectual and endocrinological morbidity.4,18,22,24,48,59 The natural history of optic glioma and the roles of chemotherapy and radiation therapy are not yet fully defined.1,7,23,32,35,38,39,49–50,55,63 Clinical trials are under way to address these issues.

Disclaimer

The opinions and assertions contained herein are the views of the authors and are not to be construed as official or as reflecting the views of the Department of the Navy, Department of the Army, or the Department of Defense.

Acknowledgments

The authors thank Kalman T. Kovacs, M.D., Ph.D., and E. Horvath, Ph.D., for performing the immunocytochemical studies and for their helpful discussions.

References

  • 1.

    AJvord EC JrLofton S: Gliomas of the optic nerve or chiasm. Outcome by patients' age, tumor site, and treatment. J Neurosurg 68:85981988J Neurosurg 68:

  • 2.

    Appleton REJan JE: Delayed diagnosis of optic nerve glioma: a preventable cause of visual loss. Pediatr Neurol 5:2262281989Pediatr Neurol 5:

  • 3.

    Atlas SWGaletta SL: The orbit and visual systemAtlas SW (ed): Magnetic Resonance Imaging of the Brain and Spine. New York: Raven Press1991709794Magnetic Resonance Imaging of the Brain and Spine.

  • 4.

    Bamford FNMorris Jones PPearson Det al: Residual disabilities in children treated for intracranial space-occupying lesions. Cancer 37:114911511976Cancer 37:

  • 5.

    Bataini JPDelanian SPonvert D: Chiasmal gliomas: results of irradiation management in 57 patients and review of literature. Int J Radiat Oncol Biol Phys 21:6156231991Int J Radiat Oncol Biol Phys 21:

  • 6.

    Behrens LHBarr DP: Hyperpituitarism beginning in infancy. The Alton giant. Endocrinology 16:1201281932Endocrinology 16:

  • 7.

    Borit ARichardson EP Jr: The biological and clinical behaviour of pilocytic astrocytomas of the optic pathways. Brain 105:1611871982Brain 105:

  • 8.

    Braffman BHBilaniuk LTZimmerman RA: MR of central nervous system neoplasia of the phakomatoses. Semin Roentgenol 25:1982171990Semin Roentgenol 25:

  • 9.

    Brown EWRiccardi VMMawad Met al: MR imaging of optic pathways in patients with neurofibromatosis. AJNR 8:103110361987AJNR 8:

  • 10.

    Burr IMSlonim AEDanish RKet al: Diencephalic syndrome revisited. J Pediatr 88:4394441976J Pediatr 88:

  • 11.

    Byrd SE: Central nervous system manifestations of inherited syndromesAtlas SW (ed): Magnetic Resonance Imaging of the Brain and Spine. New York: Raven Press1991539566Magnetic Resonance Imaging of the Brain and Spine.

  • 12.

    Capo HKupersmith MJ: Efficacy and complications of radiotherapy of anterior visual pathway tumors. Neurol Clin 9:1792031991Neurol Clin 9:

  • 13.

    Chamberlain MCLevin VA: Chemotherapeutic treatment of the diencephalic syndrome. A case report. Cancer 63:168116841989Cancer 63:

  • 14.

    Clemmons DRUnderwood LE: Somatomedin-c/insulin-like growth factor I in acromegaly. Clin Endocrinol Metab 15:6296531986Clin Endocrinol Metab 15:

  • 15.

    Clemmons DRVan Wyk JJRidgway ECet al: Evaluation of acromegaly by radioimmunoassay of somatomedin-C. N Engl J Med 301:113811421979N Engl J Med 301:

  • 16.

    Costin G: Endocrine disorders associated with tumors of the pituitary and hypothalamus. Pediatr Clin North Am 26:15311979Costin G: Endocrine disorders associated with tumors of the pituitary and hypothalamus. Pediatr Clin North Am 26:

  • 17.

    Costin GFefferman RAKogut MD: Hypothalamic gigantism. J Pediatr 83:4194251973J Pediatr 83:

  • 18.

    Danoff BFCowchock FSMarquette Cet al: Assessment of the long-term effects of primary radiation therapy for brain tumors in children. Cancer 49:158015861982Cancer 49:

  • 19.

    Daughaday WHHerington ACPhillips LS: The regulation of growth by endocrines. Annu Rev Physiol 37:2112441975Annu Rev Physiol 37:

  • 20.

    DeSousa ALKalsbeck JEMealey J Jret al: Diencephalic syndrome and its relation to opticochiasmatic glioma: review of twelve cases. Neurosurgery 4:2072091979Neurosurgery 4:

  • 21.

    Duchowny MSKatz RBejar RL: Hypothalamic mass and gigantism in neurofibromatosis: treatment with bromocriptine. Ann Neurol 15:3023041984Ann Neurol 15:

  • 22.

    Duffner PKCohen METhomas PRMet al: The long-term effects of cranial irradiation on the central nervous system. Cancer 56:184118461985Cancer 56:

  • 23.

    Easley JDScharf LChou JLet al: Controversy in the management of optic pathway gliomas. 29 patients treated with radiation therapy at Baylor College of Medicine from 1967 through 1987. Neurofibromatosis 1:2482511988Neurofibromatosis 1:

  • 24.

    Ellenberg LMcComb JGSiegel SEet al: Factors affecting intellectual outcome in pediatric brain tumor patients. Neurosurgery 21:6386441987Neurosurgery 21:

  • 25.

    Flickinger JCTorres CDeutsch M: Management of low-grade gliomas of the optic nerve and chiasm. Cancer 61:6356421988Cancer 61:

  • 26.

    Frasier SD: Abnormalities of growthCollu RDucharme JRGuyda HJ (eds): Pediatric Endocrinologyed 2. New York: Raven Press1989171215

  • 27.

    Friedman HSKrischer JPBurger Pet al: Treatment of children with progressive or recurrent brain tumors with carboplatin or iproplatin: a Pediatric Oncology Group randomized phase II study. J Clin Oncol 10:2492561992J Clin Oncol 10:

  • 28.

    Frohman LAThominet JLSzabor M: Ectopic growth hormone-releasing factor syndromesRaid STolman RA (eds): Human Growth Hormone. New York: Plenum1986347360Human Growth Hormone.

  • 29.

    Greulich WWPyle SI: Radiographic Atlas of Skeletal Development of the Hand and Wristed 2. Stanford: Stanford University Press1959

  • 30.

    Haigler ED JrHershman JMMeador CK: Pituitary gigantism. A case report and review. Arch Intern Med 132:5885941973Arch Intern Med 132:

  • 31.

    Hashimoto TTayama MMiyazaki Met al: Cranial MR imaging in patients with von Recklinghausen's disease (neurofibromatosis type I). Neuropediatrics 21:1931981990Neuropediatrics 21:

  • 32.

    Horwich ABloom HJG: Optic gliomas: radiation therapy and prognosis. Int J Radiat Oncol Biol Phys 11:106710791985Int J Radiat Oncol Biol Phys 11:

  • 33.

    Hurst RWNewman SACail WS: Multifocal intracranial MR abnormalities in neurofibromatosis. AJNR 9:2932961988AJNR 9:

  • 34.

    Hurxthal LM: Pituitary gigantism in a child 5 years of age: effect of x-radiation, estrogen therapy and self-imposed starvation diet during an 11-year period. J Clin Endocrinol Metab 21:3433531961J Clin Endocrinol Metab 21:

  • 35.

    Imes RKHoyt WF: Childhood chiasmal gliomas: update on the fate of patients in the 1969 San Francisco study. Br J Ophthalmol 70:1791821986Br J Ophthalmol 70:

  • 36.

    Imes RKHoyt WF: Magnetic resonance imaging signs of optic nerve gliomas in neurofibromatosis 1. Am J Ophthalmol 111:7297341991Am J Ophthalmol 111:

  • 37.

    Kaplan SA: Growth and growth hormone: disorders of the anterior pituitaryKaplan SA (ed): Clinical Pediatric Endocrinologyed 2. Philadelphia: WB Saunders1990162

  • 38.

    Kovalic JJGrigsby PWShepard MJet al: Radiation therapy for gliomas of the optic nerve and chiasm. Int J Radiat Oncol Biol Phys 18:9279321990Int J Radiat Oncol Biol Phys 18:

  • 39.

    Kretschmar CSLinggood RM: Chemotherapeutic treatment of extensive optic pathway tumors in infants. J Neurooncol 10:2632701991J Neurooncol 10:

  • 40.

    Kucharczyk WMontanera WJ: The sella and parasellar regionAtlas SW (ed): Magnetic Resonance Imaging of the Brain and Spine. New York: Raven Press1991625667Magnetic Resonance Imaging of the Brain and Spine.

  • 41.

    Martin JB: Pathophysiology of growth hormone regulationTolis GLabrie FMartin JBet al (eds): Clinical Neuroendocrinology: A Pathophysiological Approach. New York: Raven Press1979269277Clinical Neuroendocrinology: A Pathophysiological Approach.

  • 42.

    Martin JBReichlin S: Clinical Neuroendocrinologved 2. Philadelphia: FA Davis1987233294379–421

  • 43.

    Melmed SBraunstein GDHorvath Eet al: Pathophysiology of acromegaly. Endocr Rev 4:2712901983Endocr Rev 4:

  • 44.

    Menor FMarti-Bonmati LMulas Fet al: Imaging considerations of central nervous system manifestations in pediatric patients with neurofibromatosis type 1. Pediatr Radiol 21:3893941991Pediatr Radiol 21:

  • 45.

    Mirowitz SASartor KGado M: High-intensity basal ganglia lesions on T1-weighted MR images in neurofibromatosis. AJR 154:3693731990AJR 154:

  • 46.

    Moghrabi AFriedman HSBurger PCet al: Carboplatin treatment of progressive optic pathway gliomas to delay radiotherapy. J Neurosurg 79:2232271993J Neurosurg 79:

  • 47.

    Nelson WE: Growth and developmentBehrman REKliegman RMNelson WEet al (eds): Nelson Textbook of Pediatricsed 14. Philadelphia: WB Saunders199213104

  • 48.

    Packer RJSutton LNAtkins TEet al: A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results. J Neurosurg 70:7077131989J Neurosurg 70:

  • 49.

    Packer RJSutton LNBilaniuk LTet al: Treatment of chiasmatic/hypothalamic gliomas of childhood with chemotherapy: an update. Ann Neurol 23:79851988Ann Neurol 23:

  • 50.

    Petronio JEdwards MSBPrados Met al: Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy. J Neurosurg 74:7017081991J Neurosurg 74:

  • 51.

    Phillips LSVassilopoulou-Sellin R: Somatomedins. First of two parts. N Engl J Med 302:3713801980N Engl J Med 302:

  • 52.

    Phillips LSVassilopoulou-Sellin R: Somatomedins. Second of two parts. N Engl J Med 302:4384461980N Engl J Med 302:

  • 53.

    Pierce SMBarnes PDLoeffler JSet al: Definitive radiation therapy in the management of symptomatic patients with optic glioma. Survival and long-term effects. Cancer 65:45521990Cancer 65:

  • 54.

    Reeves AGPlum F: Hyperphagia, rage, and dementia accompanying a ventromedial hypothalamic neoplasm. Arch Neurol 20:6166241969Arch Neurol 20:

  • 55.

    Rodriguez LAEdwards MSBLevin VA: Management of hypothalamic gliomas in children: an analysis of 33 cases. Neurosurgery 26:2422471990Neurosurgery 26:

  • 56.

    Rosenstock JGPacker RJBilaniuk Let al: Chiasmatic optic glioma treated with chemotherapy. A preliminary report. J Neurosurg 63:8628661985J Neurosurg 63:

  • 57.

    Russell A: Diencephalic syndrome of emaciation in infancy and childhood. Arch Dis Child 26:2742841951Russell A: Diencephalic syndrome of emaciation in infancy and childhood. Arch Dis Child 26:

  • 58.

    Scheithauer BWKovacs KRandall RVet al: Pathology of excessive production of growth hormone. Clin Endocrinol Metab 15:6556811986Clin Endocrinol Metab 15:

  • 59.

    Shalet SMMorris-Jones PHBeardwell CGet al: Pituitary function after treatment of intracranial tumours in children. Lancet 2:1041071975Lancet 2:

  • 60.

    Tanner JMWhitehouse RHTakaishi M: Standards from birth to maturity for height, weight, height velocity, and weight velocity: British children, 1965, part II. Arch Dis Child 41:6136351966Arch Dis Child 41:

  • 61.

    Todd RM: Acromegaly in a girl of 8 years. Arch Dis Child 33:49541958Todd RM: Acromegaly in a girl of 8 years. Arch Dis Child 33:

  • 62.

    Van der Werff ten Bosch JJ: Isosexual precocityGardner LI (ed): Endocrine and Genetic Diseases of Childhood. Philadelphia: WB Saunders1969544563Endocrine and Genetic Diseases of Childhood.

  • 63.

    Wright JEMcNab AAMcDonald WI: Optic nerve glioma and the management of optic nerve tumours in the young. Br J Ophthalmol 73:9679741989Br J Ophthalmol 73:

  • 64.

    Zimmerman RA: Pediatric brain tumorsLee SHRao KCVGZimmerman RA (eds): Cranial MRI and CTed 3. New York: McGraw-Hill1992381416

Article Information

Address reprint requests to: Thomas J. Manski, M.D., Neurosurgery Department, National Naval Medical Center, Bethesda, Maryland 20889.

© AANS, except where prohibited by US copyright law."

Headings

Figures

  • View in gallery

    Photograph of the patient with gigantism at 36 months of age, after surgical treatment and completion of chemotherapy regimen for optic pathway glioma.

  • View in gallery

    Magnetic resonance T2-weighted images (axial views) obtained 1 month after placement of a ventriculoperitoneal shunt. There has been interval resolution of the hydrocephalus and transependymal edema, but persistence of hyperintense signal abnormalities in and adjacent to the involved optic pathways (A, B, and C). The intracranial optic nerves and chiasm are thickened by tumor (A, large arrow). Biopsies were taken from the medial left temporal lobe (A, small arrow) and the head of the left caudate nucleus (C, small arrow).

  • View in gallery

    Photomicrographs. H & E, original magnification × 300. Left: Section from the head of the left caudate nucleus showing atypical gliosis characterized by a mild increase in astrocytic cell density with slight nuclear polymorphism. Right: Section obtained from the medial left temporal lobe showing a well-differentiated astrocytoma.

  • View in gallery

    Immunohistochemical findings showing immunopositivity for somatostatinergic neurons (arrows) in a section from the medial left temporal lobe. H & E, original magnification × 300.

  • View in gallery

    Magnetic resonance images, sagittal T1-weighted (left) and axial proton-density-weighted (right) views, showing double-intensity tubular thickening, elongation, and downward kinking of the optic nerves.

References

1.

AJvord EC JrLofton S: Gliomas of the optic nerve or chiasm. Outcome by patients' age, tumor site, and treatment. J Neurosurg 68:85981988J Neurosurg 68:

2.

Appleton REJan JE: Delayed diagnosis of optic nerve glioma: a preventable cause of visual loss. Pediatr Neurol 5:2262281989Pediatr Neurol 5:

3.

Atlas SWGaletta SL: The orbit and visual systemAtlas SW (ed): Magnetic Resonance Imaging of the Brain and Spine. New York: Raven Press1991709794Magnetic Resonance Imaging of the Brain and Spine.

4.

Bamford FNMorris Jones PPearson Det al: Residual disabilities in children treated for intracranial space-occupying lesions. Cancer 37:114911511976Cancer 37:

5.

Bataini JPDelanian SPonvert D: Chiasmal gliomas: results of irradiation management in 57 patients and review of literature. Int J Radiat Oncol Biol Phys 21:6156231991Int J Radiat Oncol Biol Phys 21:

6.

Behrens LHBarr DP: Hyperpituitarism beginning in infancy. The Alton giant. Endocrinology 16:1201281932Endocrinology 16:

7.

Borit ARichardson EP Jr: The biological and clinical behaviour of pilocytic astrocytomas of the optic pathways. Brain 105:1611871982Brain 105:

8.

Braffman BHBilaniuk LTZimmerman RA: MR of central nervous system neoplasia of the phakomatoses. Semin Roentgenol 25:1982171990Semin Roentgenol 25:

9.

Brown EWRiccardi VMMawad Met al: MR imaging of optic pathways in patients with neurofibromatosis. AJNR 8:103110361987AJNR 8:

10.

Burr IMSlonim AEDanish RKet al: Diencephalic syndrome revisited. J Pediatr 88:4394441976J Pediatr 88:

11.

Byrd SE: Central nervous system manifestations of inherited syndromesAtlas SW (ed): Magnetic Resonance Imaging of the Brain and Spine. New York: Raven Press1991539566Magnetic Resonance Imaging of the Brain and Spine.

12.

Capo HKupersmith MJ: Efficacy and complications of radiotherapy of anterior visual pathway tumors. Neurol Clin 9:1792031991Neurol Clin 9:

13.

Chamberlain MCLevin VA: Chemotherapeutic treatment of the diencephalic syndrome. A case report. Cancer 63:168116841989Cancer 63:

14.

Clemmons DRUnderwood LE: Somatomedin-c/insulin-like growth factor I in acromegaly. Clin Endocrinol Metab 15:6296531986Clin Endocrinol Metab 15:

15.

Clemmons DRVan Wyk JJRidgway ECet al: Evaluation of acromegaly by radioimmunoassay of somatomedin-C. N Engl J Med 301:113811421979N Engl J Med 301:

16.

Costin G: Endocrine disorders associated with tumors of the pituitary and hypothalamus. Pediatr Clin North Am 26:15311979Costin G: Endocrine disorders associated with tumors of the pituitary and hypothalamus. Pediatr Clin North Am 26:

17.

Costin GFefferman RAKogut MD: Hypothalamic gigantism. J Pediatr 83:4194251973J Pediatr 83:

18.

Danoff BFCowchock FSMarquette Cet al: Assessment of the long-term effects of primary radiation therapy for brain tumors in children. Cancer 49:158015861982Cancer 49:

19.

Daughaday WHHerington ACPhillips LS: The regulation of growth by endocrines. Annu Rev Physiol 37:2112441975Annu Rev Physiol 37:

20.

DeSousa ALKalsbeck JEMealey J Jret al: Diencephalic syndrome and its relation to opticochiasmatic glioma: review of twelve cases. Neurosurgery 4:2072091979Neurosurgery 4:

21.

Duchowny MSKatz RBejar RL: Hypothalamic mass and gigantism in neurofibromatosis: treatment with bromocriptine. Ann Neurol 15:3023041984Ann Neurol 15:

22.

Duffner PKCohen METhomas PRMet al: The long-term effects of cranial irradiation on the central nervous system. Cancer 56:184118461985Cancer 56:

23.

Easley JDScharf LChou JLet al: Controversy in the management of optic pathway gliomas. 29 patients treated with radiation therapy at Baylor College of Medicine from 1967 through 1987. Neurofibromatosis 1:2482511988Neurofibromatosis 1:

24.

Ellenberg LMcComb JGSiegel SEet al: Factors affecting intellectual outcome in pediatric brain tumor patients. Neurosurgery 21:6386441987Neurosurgery 21:

25.

Flickinger JCTorres CDeutsch M: Management of low-grade gliomas of the optic nerve and chiasm. Cancer 61:6356421988Cancer 61:

26.

Frasier SD: Abnormalities of growthCollu RDucharme JRGuyda HJ (eds): Pediatric Endocrinologyed 2. New York: Raven Press1989171215

27.

Friedman HSKrischer JPBurger Pet al: Treatment of children with progressive or recurrent brain tumors with carboplatin or iproplatin: a Pediatric Oncology Group randomized phase II study. J Clin Oncol 10:2492561992J Clin Oncol 10:

28.

Frohman LAThominet JLSzabor M: Ectopic growth hormone-releasing factor syndromesRaid STolman RA (eds): Human Growth Hormone. New York: Plenum1986347360Human Growth Hormone.

29.

Greulich WWPyle SI: Radiographic Atlas of Skeletal Development of the Hand and Wristed 2. Stanford: Stanford University Press1959

30.

Haigler ED JrHershman JMMeador CK: Pituitary gigantism. A case report and review. Arch Intern Med 132:5885941973Arch Intern Med 132:

31.

Hashimoto TTayama MMiyazaki Met al: Cranial MR imaging in patients with von Recklinghausen's disease (neurofibromatosis type I). Neuropediatrics 21:1931981990Neuropediatrics 21:

32.

Horwich ABloom HJG: Optic gliomas: radiation therapy and prognosis. Int J Radiat Oncol Biol Phys 11:106710791985Int J Radiat Oncol Biol Phys 11:

33.

Hurst RWNewman SACail WS: Multifocal intracranial MR abnormalities in neurofibromatosis. AJNR 9:2932961988AJNR 9:

34.

Hurxthal LM: Pituitary gigantism in a child 5 years of age: effect of x-radiation, estrogen therapy and self-imposed starvation diet during an 11-year period. J Clin Endocrinol Metab 21:3433531961J Clin Endocrinol Metab 21:

35.

Imes RKHoyt WF: Childhood chiasmal gliomas: update on the fate of patients in the 1969 San Francisco study. Br J Ophthalmol 70:1791821986Br J Ophthalmol 70:

36.

Imes RKHoyt WF: Magnetic resonance imaging signs of optic nerve gliomas in neurofibromatosis 1. Am J Ophthalmol 111:7297341991Am J Ophthalmol 111:

37.

Kaplan SA: Growth and growth hormone: disorders of the anterior pituitaryKaplan SA (ed): Clinical Pediatric Endocrinologyed 2. Philadelphia: WB Saunders1990162

38.

Kovalic JJGrigsby PWShepard MJet al: Radiation therapy for gliomas of the optic nerve and chiasm. Int J Radiat Oncol Biol Phys 18:9279321990Int J Radiat Oncol Biol Phys 18:

39.

Kretschmar CSLinggood RM: Chemotherapeutic treatment of extensive optic pathway tumors in infants. J Neurooncol 10:2632701991J Neurooncol 10:

40.

Kucharczyk WMontanera WJ: The sella and parasellar regionAtlas SW (ed): Magnetic Resonance Imaging of the Brain and Spine. New York: Raven Press1991625667Magnetic Resonance Imaging of the Brain and Spine.

41.

Martin JB: Pathophysiology of growth hormone regulationTolis GLabrie FMartin JBet al (eds): Clinical Neuroendocrinology: A Pathophysiological Approach. New York: Raven Press1979269277Clinical Neuroendocrinology: A Pathophysiological Approach.

42.

Martin JBReichlin S: Clinical Neuroendocrinologved 2. Philadelphia: FA Davis1987233294379–421

43.

Melmed SBraunstein GDHorvath Eet al: Pathophysiology of acromegaly. Endocr Rev 4:2712901983Endocr Rev 4:

44.

Menor FMarti-Bonmati LMulas Fet al: Imaging considerations of central nervous system manifestations in pediatric patients with neurofibromatosis type 1. Pediatr Radiol 21:3893941991Pediatr Radiol 21:

45.

Mirowitz SASartor KGado M: High-intensity basal ganglia lesions on T1-weighted MR images in neurofibromatosis. AJR 154:3693731990AJR 154:

46.

Moghrabi AFriedman HSBurger PCet al: Carboplatin treatment of progressive optic pathway gliomas to delay radiotherapy. J Neurosurg 79:2232271993J Neurosurg 79:

47.

Nelson WE: Growth and developmentBehrman REKliegman RMNelson WEet al (eds): Nelson Textbook of Pediatricsed 14. Philadelphia: WB Saunders199213104

48.

Packer RJSutton LNAtkins TEet al: A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results. J Neurosurg 70:7077131989J Neurosurg 70:

49.

Packer RJSutton LNBilaniuk LTet al: Treatment of chiasmatic/hypothalamic gliomas of childhood with chemotherapy: an update. Ann Neurol 23:79851988Ann Neurol 23:

50.

Petronio JEdwards MSBPrados Met al: Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy. J Neurosurg 74:7017081991J Neurosurg 74:

51.

Phillips LSVassilopoulou-Sellin R: Somatomedins. First of two parts. N Engl J Med 302:3713801980N Engl J Med 302:

52.

Phillips LSVassilopoulou-Sellin R: Somatomedins. Second of two parts. N Engl J Med 302:4384461980N Engl J Med 302:

53.

Pierce SMBarnes PDLoeffler JSet al: Definitive radiation therapy in the management of symptomatic patients with optic glioma. Survival and long-term effects. Cancer 65:45521990Cancer 65:

54.

Reeves AGPlum F: Hyperphagia, rage, and dementia accompanying a ventromedial hypothalamic neoplasm. Arch Neurol 20:6166241969Arch Neurol 20:

55.

Rodriguez LAEdwards MSBLevin VA: Management of hypothalamic gliomas in children: an analysis of 33 cases. Neurosurgery 26:2422471990Neurosurgery 26:

56.

Rosenstock JGPacker RJBilaniuk Let al: Chiasmatic optic glioma treated with chemotherapy. A preliminary report. J Neurosurg 63:8628661985J Neurosurg 63:

57.

Russell A: Diencephalic syndrome of emaciation in infancy and childhood. Arch Dis Child 26:2742841951Russell A: Diencephalic syndrome of emaciation in infancy and childhood. Arch Dis Child 26:

58.

Scheithauer BWKovacs KRandall RVet al: Pathology of excessive production of growth hormone. Clin Endocrinol Metab 15:6556811986Clin Endocrinol Metab 15:

59.

Shalet SMMorris-Jones PHBeardwell CGet al: Pituitary function after treatment of intracranial tumours in children. Lancet 2:1041071975Lancet 2:

60.

Tanner JMWhitehouse RHTakaishi M: Standards from birth to maturity for height, weight, height velocity, and weight velocity: British children, 1965, part II. Arch Dis Child 41:6136351966Arch Dis Child 41:

61.

Todd RM: Acromegaly in a girl of 8 years. Arch Dis Child 33:49541958Todd RM: Acromegaly in a girl of 8 years. Arch Dis Child 33:

62.

Van der Werff ten Bosch JJ: Isosexual precocityGardner LI (ed): Endocrine and Genetic Diseases of Childhood. Philadelphia: WB Saunders1969544563Endocrine and Genetic Diseases of Childhood.

63.

Wright JEMcNab AAMcDonald WI: Optic nerve glioma and the management of optic nerve tumours in the young. Br J Ophthalmol 73:9679741989Br J Ophthalmol 73:

64.

Zimmerman RA: Pediatric brain tumorsLee SHRao KCVGZimmerman RA (eds): Cranial MRI and CTed 3. New York: McGraw-Hill1992381416

TrendMD

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 36 36 36
PDF Downloads 4 4 4
EPUB Downloads 0 0 0

PubMed

Google Scholar