CHAPTER 19 THE OPTIC CHIASM IN ENDOCRINOLOGIC DISORDERS
Principles and Practice of Endocrinology and Metabolism
CHAPTER 19 THE OPTIC CHIASM IN ENDOCRINOLOGIC DISORDERS
R. MICHAEL SIATKOWSKI AND JOEL S. GLASER
Anatomy and Embryology of the Optic Chiasm
Clinical Manifestations of Chiasmal Syndromes
Eye Movement Disorders
Pallor of the Optic Discs
Evaluation of Field Defects
Developmental Chiasmal Dysplasias
De Morsier Syndrome
Forebrain Basal Encephaloceles
Radiologic Investigation of Gliomas
Rathke Cleft Cysts
Effect of Pregnancy
Vision Aspects of Therapy
Follow-Up of Treated Pituitary Adenomas
Empty Sella Syndrome
Miscellaneous Lesions of the Optic Chiasm
Traumatic Chiasmal Syndrome
Situated in the floor of the third ventricle, in close proximity to the hypothalamus, hypophysial stalk, and pituitary gland, the optic chiasm is commonly involved by intracranial disease processes, many of which have endocrinologic manifestations. Such disorders include, but are not limited to, pituitary adenomas, optic gliomas, and congenital forebrain anomalies.
ANATOMY AND EMBRYOLOGY OF THE OPTIC CHIASM
The optic chiasm may be considered the “Grand Central Station” of the vision sensory system, containing some 2.4 million afferent axons. Many of the disease processes that involve the intracranial optic nerves likewise involve the chiasm. Because of the relationship of the nerves and chiasm to the basal structures of the anterior and middle cranial fossae, pituitary adenomas and parasellar meningiomas frequently encroach on the anterior vision pathways. Failure of early diagnosis of chiasmal disorders may endanger the life of the patient and lessen the likelihood of reversal of visual deficits.
The chiasm is situated in the anteroinferior recess of the third ventricle. The inferior aspect of the chiasm usually is 8 to 13 mm above the nasotuberculum line (i.e., the plane of the diaphragma sellae or clinoid processes). The intracranial portion of the optic nerves is inclined as much as 45 degrees from the horizontal and measures 17 ± 2.5 mm in length (Fig. 19-1). The chiasm measures ~8 mm from anterior to posterior notch, 12 mm across, and 4 mm in height. The inferior surface of the chiasm projects more or less directly above the bony dorsum sellae (79%). When the chiasm lies more anteriorly over the diaphragm sellae, it is said to be prefixed (17%), and behind the dorsum, postfixed (4%).1, 2 and 3 The lateral aspect of the chiasm is embraced by the supraclinoid portion of the internal carotid artery. The anterior cerebral arteries of the circle of Willis (Fig. 19-2) pass over the dorsal surface of the optic nerves as they converge. The optic nerves are fixed at the intracranial entrance of the optic canals, the dorsal aspect of which is formed by an unyielding falciform fold of dura.
FIGURE 19-1. A, The relationships of the optic nerves (ON) and chiasm (X) to sellar structures and the third ventricle (3). (C, anterior clinoid; D, dorsum sellae; P, pituitary gland in sella.) B, Base of the brain, showing some of the pertinent anatomic structures. The cranial nerves are numbered. (A, From Glaser JS. Topical diagnosis: the optic chiasm. In: Glaser JS. Neuro-ophthalmology, 3rd ed. Philadelphia: Lippincott, 1999:81; B, From Akesson EJ, Loeb JA, Wilson-Pauwels L. Thompson’s core textbook of anatomy, 2nd ed. Philadelphia: JB Lippincott, 1990:81.)
FIGURE 19-2. The circle of Willis and its environs. A, Relationship to intracranial contents, view from below. B, Anatomy of major intracranial arteries (caudal, top and dorsal, bottom). (From Akesson EJ, Loeb JA, Wilson-Pauwels L. Thompson’s core textbook of anatomy, 2nd ed. Philadelphia: JB Lippincott, 1990:81.)
The pituitary gland lies within the sella turcica and is covered by the diaphragma sellae, through which the hypophysial stalk passes. The chiasmatic (suprasellar) cistern is the subarachnoid space between the chiasm and the pituitary gland into which pituitary macroadenomas grow, often becoming large before affecting the optic nerves or chiasm (see Chap. 11 and Chap. 20).
Basal mass lesions, even of moderate size, do not necessarily encroach on the chiasm. For example, pituitary adenomas must extend well above the confines of the sella turcica to contact the chiasm. Conversely, in the presence of chiasmal visual field defects, advanced suprasellar extension of an adenoma may be predicted. Smaller tumors may be detected clinically only when signs of unilateral optic nerve compression evolve or when secretory manifestations accrue.
Although the anatomic variations in the position of the chiasm, as well as its arterial supply, have been studied,3, 4 it is difficult to draw conclusions regarding the preferential vulnerability of a particular portion of the chiasm based on blood supply. Moreover, it is unclear whether field defects are due to direct compression of vision axons or to interference with vasculature (or to both). At craniotomy, major stretching, distortion, and thinning of the nerves and chiasm are commonly encountered, shedding little light on the mechanisms of impairment of function.
The intrinsic nerve fiber anatomy of the optic nerves and chiasm provides the functional substrate for the clinical evolution of field defects. The retinal topographic pattern is preserved, even at the junction of the optic nerves with the chiasm (Fig. 19-3). Superior retinal quadrants are represented in the superior portion of the nerve, inferior retina below, with nasal and temporal retinal fibers maintaining their relative positions in the optic nerve. Most axially located fibers within the optic nerves and chiasm are macular in origin. Some 2.4 million nerve fibers, ~1.2 million per nerve, enter the optic chiasm, with a crossed/uncrossed fibers ratio of 53:47.5
FIGURE 19-3. Retinotopic organization of visual fibers in the anterior visual pathways (after Hoyt). Diagram of homonymous retinal quadrants and their fiber projections, anterior aspect. (SN, superior nasal; ST, superior temporal; it, inferior temporal; in, inferior nasal.) Note: The superior fibers retain a superior course; the inferior fibers retain an inferior position; the anterior notch (1) is occupied by inferonasal (superior temporal field) fibers; inferior homonymous fibers, contralateral eye (2), and ipsilateral eye (3) converge in the chiasm, but superior homonymous fibers converge in the chiasm in the optic tract (4); the posterior notch (5) is occupied by the superior nasal (inferior temporal field) fibers as well as by macular fibers. (From Glaser JS. Topical diagnosis: the optic chiasm. In: Glaser JS. Neuro-ophthalmology, 3rd ed. Philadelphia: Lippincott, 1999:90.)
Macular axons constitute the largest portion of these fibers, which cross primarily in the central and posterior portions of the chiasm. The concept of Wilbrand knee (i.e., that contralateral, inferior nasal fibers cross in the anterior notch of the chiasm and loop forward into the terminal portion of the opposite optic nerve) is no longer universally accepted (see next paragraph). Superior nasal fibers cross more posteriorly in the chiasm. The lateral portions of the chiasm are composed of uncrossed superior and inferior temporal retinal fibers.
Elegant anatomic autoradiography studies have been made of the chiasm in normal monkeys and in both monkey and human cadavers that had undergone monocular enucleation.6 In normal monkeys, the optic nerve fibers cross the chiasm without entering the contralateral optic nerve, but after short-term monocular enucleation, fibers from the normal optic nerve begin to approach the entry zone of the degenerating optic nerve. Only after long-term enucleation (in both humans and monkeys) was “Wilbrand knee” identified. Thus, because Wilbrand knee does not occur in normal humans, the phenomenon of a superior temporal hemianopia in the so-called “junctional scotoma” must be due to “herniation” of optic nerve fibers subserving the superotemporal visual field into the chiasm after prolonged compression and subsequent neural atrophy.
The development of the embryonic optic chiasm begins between the fourth and sixth weeks of gestation (8- to 10-mm stage), when the optic nerves start to converge,7 and a true chiasm is clearly evident by the end of the second month of gestation. The structures of the diencephalon, including the posterior lobe of the hypophysis, the tuber cinereum, and mammillary bodies, are well defined by the third month of gestation, but the infundibular pouch contacts the stomodeal hypophysial pouch even during the fourth week of development.
Congenital absence of the chiasm is a rare, but well-documented, phenomenon. It may occur in association with marked microphthalmia and aplasia of the optic nerves and tracts,8 or, conversely, in children with normal eyeballs and only minimal optic nerve anomalies.9 The latter cases are associated with strabismus and nystagmus and are likely to be secondary to developmental visuotopic misrouting.
CLINICAL MANIFESTATIONS OF CHIASMAL SYNDROMES
Most chiasmal syndromes are caused by extrinsic tumors: classically, pituitary adenomas or suprasellar meningiomas and craniopharyngiomas. With few exceptions, these slow-growing tumors produce insidiously progressive visual deficits in the form of variations on a bitemporal theme (Fig. 19-4). Sophisticated neuroradiologic and psychophysical testing has attempted to correlate the degree of vision loss with the degree of anatomic displacement of the chiasm10; these studies have demonstrated that vision loss occurs well before it is detectable by conventional outpatient methods of assessing visual field and visual acuity.11 Asymmetry of field loss is the rule, such that one eye may show advanced deficits, including reduced acuity, whereas only relative temporal field defects are present in the other eye. Unless acuity is diminished, patients report rather vague vision symptoms—for example, trouble seeing to the side, a history of fender accidents to their automobiles, or that, when passed by another automobile, the overtaking vehicle suddenly appears in their lane. The first clue to the presence of an hemianopic defect may be the manner in which acuity charts are read (i.e., with the right eye, only the left letters are seen, and with the left eye, only the right letters are seen). Progressive painless loss of peripheral field or central acuity (symmetric or asymmetric) may go unnoticed by many children as well as by some adults. Unilateral visual defects, especially in children, frequently are found during routine school vision tests. Rarely, vision may decrease precipitously when parachiasmal masses enlarge abruptly, as with infarction of an adenoma (“pituitary apoplexy”). Chiasmal visual field loss may differ depending on the anatomic area affected. Anterior lesions may cause an ipsilateral optic neuropathy with a contralateral superotemporal field deficit. Lesions in the body of the chiasm usually produce more symmetric bitemporal field loss, with normal visual acuity. Posterior lesions (with prefixed chiasm) may cause incongruous homonymous field loss secondary to involvement of the optic tract. Usually, many vision symptoms are vague and nonspecific until central acuity fails in one or both eyes. Unfortunately, it is all too common that visual field loss is already marked before initial perimetry is accomplished.
FIGURE 19-4. Chiasmal field defects. A, “Junctional scotoma” combines typical optic nerve defect (central scotoma) in left eye with temporal hemianopia in right (see also C). B, Classic bitemporal hemianopia. Riddoch phenomenon (movement perception) demonstrable in shaded area of the left field. C, Automated perimetry (Humphrey) of a junction-type field defect demonstrates diffuse field loss in the left eye (left) and temporal hemianopia in the right (right). D, Automated perimetry from patient with pituitary tumor compressing chiasm from below demonstrates asymmetric bitemporal superior quadrantic defects. (LE, left eye; RE, right eye.)
Vision loss of a chiasmal pattern during pregnancy should suggest the possibility of an enlargement of a preexisting pituitary adenoma or of an estrogen-dependent meningioma. There is little evidence to support the notion of a physiologic enlargement of a normal pituitary gland during pregnancy that is sufficient to encroach on the anterior visual pathways, nor is “lactation optic neuritis” a valid concept.
Even now, vision loss is the first palpable clinical manifestation of pituitary macroadenomas, but this symptom cannot be construed as an early sign. From the Mayo Clinic experience,12>40% of adenomas present as vision symptoms, and 70% show field defects.
Chronic headaches, mild or severe, are noted by most patients with pituitary adenomas.13 Headache symptoms are variable but may be most marked where advancing pituitary adenomas are restrained by a taut diaphragma sellae. In acromegaly, chronic headaches may indicate paranasal sinus enlargement, with or without active sinusitis. In children, headaches usually are not thoroughly evaluated until nausea, vomiting, and behavioral changes occur, at which point an intracranial lesion should be suspected. Additionally, obesity, precocious or delayed sexual development, somnolence, and diabetes insipidus should alert the clinician to hypothalamic dysfunction (see Chap. 9, Chap. 18 and Chap. 26).
Peculiar sensory phenomena may be noted by patients with bitemporal field defects, resulting in a nonparetic form of strabismus or diplopia and in difficulty with visual tasks requiring depth perception (e.g., use of a screwdriver, threading a needle, and the like). Loss of portions of normally superimposed binocular fields results in the absence of corresponding points in visual space (and on the retina) and subsequently diminished fusional capacity. In essence, the patient has two free-floating nasal hemi-fields with no interhemispheral linkage to keep them aligned. Vertical and horizontal slippage produces doubling of images, gaps in otherwise continuous visual panorama, and steps in horizontal lines. A series of 260 patients with pituitary adenoma included some degree of double vision preoperatively in 98 patients, but a demonstrable ocular palsy was present in only 14.13 Additionally, without temporal fields, objects beyond the point of binocular fixation fall on nonseeing nasal hemiretina, so that a blind area exists with extinction of objects beyond the fixation point.
EYE MOVEMENT DISORDERS
The association of extraocular muscle palsies with chiasmal field defects implies involvement of the structures in the cavernous sinus, usually a sign of rapid expansion of a pituitary adenoma. Only rarely is tumor diagnosis delayed sufficiently for obstruction of the ventricular system to occur, with elevation of intracranial pressure and unilateral or bilateral sixth nerve palsies (Fig. 19-5 and Fig. 19-6).
FIGURE 19-5. Diagram illustrating nerves and structures in and near the cavernous sinus. (a, artery; ant., anterior; n., nerve; post., posterior; sup., superior.) (From Glaser JS. Topical diagnosis: the optic chiasm. In: Glaser JS. Neuro-ophthalmology, 3rd ed. Philadelphia: Lippincott, 1999:408.)
FIGURE 19-6. A, Acromegalic patient with involvement of left oculomotor nerve. B, Patient had reported a gradual onset of left-sided ptosis and diplopia with a mild headache.
Patients with large parasellar masses may display “seesaw” nystagmus, with alternate depression and extorsion of one eye and elevation and intorsion of the other. This results from expansion of tumors within the third ventricle, with secondary midbrain compression, rather than from chiasmal involvement per se.14
PALLOR OF THE OPTIC DISCS
Pallor of the optic discs, although an anticipated physical sign of chiasmal interference, is not a prerequisite for diagnosis. In a series of 156 cases of pituitary tumors, optic atrophy was found in only 155 of 312 eyes (50%)15, disc pallor was present in 34% of the adenomas studied at the Mayo Clinic.12 Optic atrophy may not be present even when vision symptoms have lasted as long as 2 years.16 Furthermore, extensive field loss in chiasmal syndromes may be associated with normal or minimally pale discs. Therefore, it is unwise to rely on the presence of optic atrophy as an indication of chiasmal interference; such findings are corroborative evidence at best, after the visual fields have been carefully evaluated.
It is somewhat risky to predict on the basis of disc appearance the ultimate level of vision anticipated after chiasmal decompression. As a rule, the more atrophic the disc, the less likely is the return of function in defective areas of field. However, vision recovery to surprisingly good levels may occur despite relatively advanced disc pallor.
Papilledema is a less common finding and results from large tumors compressing the third ventricle, with resultant hydrocephalus.
EVALUATION OF FIELD DEFECTS
The importance of establishing that the vertical meridian forms the central border of the defect (see Fig. 19-4) is paramount in distinguishing chiasmal interference from deficits that mimic temporal hemianopia. Such mimicking conditions include tilted discs (congenital inferior scleral crescents); nasal sector retinitis pigmentosa; bilateral cecocentral scotomas; papilledema with greatly enlarged blind spots; nutritional optic neuropathy; retinal inflammatory disease; and redundant overhanging upper lid tissue.17
The endocrinologist should be aware of the general pattern of evolution of chiasmal field defects and of the useful screening procedures that are appropriate in the context of the general physical examination.
Visual field defects caused by chiasmal interference may be characterized by the following17: depressions initially occur in the central 20-degree field (therefore, exploration of the periphery is time-consuming and insensitive) (see Fig. 19-4); the central edge of the defect is aligned along the vertical meridian that passes through the point of visual fixation, in one or both eyes; the defect is more readily apparent with red targets than, for example, white against black (Fig. 19-7); and the loss of monocular acuity (“reading vision”) that is not explained by uncorrected refractive error or ocular disease (cataract, macular degeneration, etc.) is evidence of prechiasmal optic nerve compression until proved otherwise. Three additional caveats are that normal visual fields do not preclude the presence of a parachiasmal lesion (e.g., a microadenoma does not cause field defects); the screening technique described does not replace other formal perimetric techniques, such as Goldmann or automated perimetry; and the assessment of visual fields in no way obviates the need for anatomic studies, that is, computed tomography (CT) or magnetic resonance imaging (MRI). Only limited information is available on plain films; subtle changes in the bony structures of the sella may be easily overlooked by the inexperienced. Radiologic measurements of the sella, whether linear or volumetric, are not intrinsically important. In marginal cases, such measurements are unreliable; in obvious cases, they are superfluous; and in neither case is the problem of suprasellar extension solved. Thus, plain films have little, if any, use today in the diagnostic evaluation of patients with parasellar disease.
FIGURE 19-7. A, Finger-counting fields in adults. Four quadrants of each eye should be tested. Patient may name or hold up same number of fingers. Simultaneous finger counting may bring out subtle hemian-opic defect. B, Hand comparison in hemianopic depression appears “darker,” “in shadow,” or “blurred.” (From Glaser JS. Topical diagnosis: the optic chiasm. In: Glaser JS. Neuro-ophthalmology, 3rd ed. Philadelphia: Lippincott, 1999:31–33.)
The advent of thin-section CT and of gadolinium-enhanced MRI has greatly simplified the diagnosis of intracranial mass lesions. Pneumoencephalography no longer is indicated, and cerebral angiography is reserved for those patients in whom the precise configuration of neighboring vessels may be relevant to transsphenoidal or transcranial surgical approaches to intrasellar or suprasellar tumors. The question of “full” or “empty” sella is clearly settled by coronal-section MRI (Fig. 19-8).
FIGURE 19-8. Empty sella syndrome. An MRI shows flattened remnant of pituitary (arrowheads) on sellar floor; chiasm above (arrow).
DEVELOPMENTAL CHIASMAL DYSPLASIAS
The chiasm is infrequently the site of developmental anomalies; at times, it is related to malformation of other diencephalic mid-line structures, including the third ventricle. Embryonic dysgenesis may result in the abnormal development of the primitive optic vesicles with resulting unilateral or bilateral anophthalmos (absent globe) or useless microphthalmic cysts. Such gross ocular abnormalities may occur in isolation or may be associated with a spectrum of neural defects, including major malformations that preclude survival.
Perhaps of greater clinical import are the more subtle ocular dysplasias that accompany those anterior forebrain malformations compatible with long life. Certain specific congenital anomalies of the optic disc may indicate the presence of otherwise occult forebrain malformations.
DE MORSIER SYNDROME
The clinical constellation of pituitary dysfunction and optic nerve hypoplasia (Fig. 19-9) is recognized as the de Morsier syndrome.18,19 Variable findings may include neonatal hypotonia; seizures; prolonged bilirubinemia; deficiencies of growth hormone, adrenocorticotropic hormone, or vasopressin; panhypo-pituitarism; mental retardation; or a combination of these.20 The association of this entity with midline cerebral anomalies (i.e., absence of septum pellucidum, agenesis of the corpus callosum) has been well documented.21 Additional neuropathologic findings have included extensive atrophy of the optic nerves and chiasm, aplasia of olfactory bulbs and tracts, and hypoplasia of the hypophysial stalk and infundibulum.22 Although the exact etiology of this condition has not been determined, it is well known to occur in association with maternal gestational diabetes and maternal use of phenytoin, quinine, alcohol, and lysergic acid.19 Genetic defects—including partial deletion of chromosome 1423 and mutations in the PAX324 and HESX125 genes—have been reported. Others have hypothesized that this group of defects represents a vascular disruption sequence.26
FIGURE 19-9. De Morsier syndrome. A, Hypoplastic optic discs. Note depigmented ring around discs. B, MRI, coronal view, demonstrates single ventricle with absence of septum pellucidum.
The wide clinical spectrum of patients with bilateral optic nerve hypoplasia is now well recognized. In one study, only 30 of 40 such children had coexistent central nervous system anomalies. Concomitant endocrinologic defects were associated with posterior pituitary ectopia rather than agenesis of the corpus callosum or other central nervous system abnormalities.27 Some investigators feel that endocrine function may be predicted on the basis of pituitary appearance on MRI,28 but others have documented normal-appearing glands in patients with central diabetes insipidus.29 In 35 patients with bilateral optic nerve hypoplasia, endocrine dysfunction was seen in only 27% (growth hormone deficiency and hypothyroidism being most common), and abnormal neuroimaging in 46%.30 Eighty percent of these patients were legally blind (34% had no light perception in either eye), but 10% of eyes had vision 20/60 or better. The “full-blown” syndrome (i.e., septo-optic dysplasia with panhypopituitarism) occurred in only 11.5% of these patients.
An important clinical point is that children with such disorders are at risk for sudden death during febrile illnesses secondary to hypocortisolism, thermoregulatory disturbances, and dehydration.31 The occurrence of segmental superior optic nerve hypoplasia has been observed in infants born to mothers with gestational diabetes32; this, perhaps, represents a forme fruste of the de Morsier syndrome.
FOREBRAIN BASAL ENCEPHALOCELES
A variety of optic nerve abnormalities (hypoplasia, colobomata, peripapillary staphylomata, and the “morning glory” disc) may be associated with other developmental defects; principally, they take the form of midline craniofacial anomalies,33,34 including hypertelorism; defects of the lip, palate, and maxilla; anencephaly35 and prosencephaly36; skeletal malformations37; or combinations B thereof. Of special neuro-ophthalmologic interest is the association of optic disc malformation with forebrain basal encephaloceles. Herniated brain tissue may present as pulsating exophthalmos (spheno-orbital encephalocele usually associated with neurofibro-matosis), hypertelorism with a pulsatile nasopharyngeal mass (transsphenoidal encephalocele), or a frontonasal mass, with or without hypertelorism (frontoethmoidal encephalocele). Congenital disc anomalies, such as hypoplasia or the coloboma dysplasia variety38 (Fig. 19-10), associated with hypertelorism or other mid-facial malformation, are evidence of basal encephalocele until proved otherwise. There are also reports of isolated retinal colobomas, sparing the optic nerve, in association with sphenoethmoidal encephaloceles. The physical findings of transsphenoidal or transethmoidal basal encephalocele39 are listed as follows:
FIGURE 19-10. Transsphenoidal encephalocele. A, Large dysplastic optic disc (coloboma of nerve). B, Polytomogram demonstrates transsellar herniation of forebrain (arrows).
Midline facial anomalies: Broad nasal root, hypertelorism, mid-line lip defect, wide bitemporal skull diameter, cleft palate
Nasopharyngeal mass: Midline epipharyngeal space in location pulsatile; often symptoms of nasal obstruction may be confused with a nasal polyp; rare in infancy
Hypopituitarism/dwarfism, ocular: Congenital disc anomalies such as colobomatous dysplasias, chiasmal field defects, poor vision, exotropia
In the evaluation of basal encephalocele, neuroradiologic imaging of the cranial base is indicated. Biopsy or attempted resection of posterior nasopharyngeal masses should be avoided because these masses invariably are encephalomeningoceles, and surgical manipulation may result in meningitis with tragic outcome.
Because both optic disc hypoplasia and colobomatous dysplasia may reflect developmental defects of the chiasm, it is essential to recognize that such ophthalmologic anomalies may be a clue to underlying brain and endocrine defects.
Hypogonadotropic hypogonadism (Kallmann syndrome) is an autosomal dominant disorder characterized by low levels of serum follicle-stimulating hormone and luteinizing hormone and by eunuchoid features40 (see Chap. 115). Other pituitary hormone levels are usually normal, but midline facial anomalies and unilateral renal agenesis may be present. This disorder can be associated with anosmia, hypoplasia of the nose and eyes, hypogeusia (taste deficiency),41 retinitis pigmentosa,42 and Möbius syndrome (congenital facial diplegia and horizontal gaze palsies with esotropia) with peripheral neuropathy.43,44 Hypoplastic development of the olfactory bulbs and the hypothalamus has been documented.
A large series45 of 101 pituitary dwarfs revealed MRI evidence of posterior pituitary ectopia in 59. Pituitary volume did not change with hormonal therapy. There was a 3:1 male predominance, and a higher incidence of breech delivery (32% versus 7%) and congenital brain anomalies (12% versus 7%) in children with posterior pituitary ectopia. Defective induction of mediobasal brain structures in early embryonic life is the presumed cause, and mutation in the PIT-1 gene may be implicated.
Most chiasmal syndromes are caused by extrinsic masses: classically, pituitary adenomas, suprasellar meningiomas, craniopharyngiomas, and internal carotid artery aneurysms. Although certain patterns of vision failure may suggest the location and type of lesion, such clinical impressions often prove fallible in the face of neuroradiologic procedures (and at craniotomy). At any rate, the diagnostic evaluation of all nontraumatic chiasmal syndromes is stereotyped: to rule in or out the presence of a potentially treatable mass lesion. Inflammatory or infectious causes are extremely rare, and chiasmal involvement by head trauma or radionecrosis is uncommon. The distinction is made by age-related incidence; accompanying signs and symptoms; and typical, if not diagnostic, radiologic appearance.
OPTIC AND HYPOTHALAMIC GLIOMAS
Primary astrocytic tumors of the anterior visual pathways assume two major clinical forms: the relatively benign glioma (juvenile pilocytic astrocytoma) of childhood and the rare malignant glioblastoma of adulthood. With the exception of vision loss and anatomic location, these two groups have little in common, and the assumption that the progressive malignant form stems from the static childhood form is untenable.
For the indolent glioma of childhood, clinical presentation is predicated on the location and extent of the tumor. Gliomas may be separated into roughly three topographic groups: unilateral optic nerve (orbital, intracranial, or both, but not involving the chiasm); principally chiasmal mass; or simultaneous infiltration of the hypothalamus. Strictly intraorbital gliomas present as insidious proptosis of variable degree, and although vision is usually diminished, remarkably good vision function is not uncommon. Strabismus, disc pallor, or disc swelling may be observed. Progressive proptosis, even if abrupt, or increased visual deficit does not imply an aggressive activity of the tumor, a hemorrhage, or necrosis. These tumors may rarely extend intracranially and have a low (~10%) mortality rate.46
Chiasmal gliomas are more common than the isolated orbital type. These tumors present with unilateral or bilateral vision loss, strabismus, optic atrophy, and/or infantile nystagmus. The nystagmus may mimic spasmus nutans (usually unilateral or asymmetric nystagmus), complete with head nodding and torticollis, or may show a coarse, conjugate mixed horizontal–rotary pattern, especially when vision is severely defective. “Seesaw” nystagmus may also rarely be seen in these patients.
Children with extensive basal tumors also show hydrocephalus and signs and symptoms of increased intracranial pressure. Hypothalamic signs include precocious puberty, obesity, dwarfism, hypersomnolence, and diabetes insipidus. Usually, the non-vision complications of extensive gliomas occur in infancy or early childhood, and onset of obstructive signs or hypothalamic involvement much beyond the age of 5 years is uncommon.
Gliomas of the optic nerves and chiasm may be associated with neurofibromatosis in 20% to 40% of cases; the patients either show other characteristic stigmata or have affected relatives.47, 48 and 49 Indeed, there is good evidence that children with neurofibromatosis type 1 and chiasmal gliomas have a better long-term prognosis than those with chiasmal gliomas alone.46 Absence of neurofibromatosis, electrolyte abnormalities, and intracranial hypertension are all indicators of a poor prognosis.50,51
Treatment of benign optic gliomas in childhood is somewhat controversial, with most pediatric and neuro-ophthalmologists favoring a conservative approach. When there is documented progressive vision loss, significant tumor growth, or obstructive signs, intervention is obviously indicated. Debulking surgery, radiation therapy, and chemotherapy have all been advocated. Newer radiation techniques may allow a higher percentage of treated patients to grow normally,52 and, when chemotherapy is indicated, reports suggest success with a combined carboplatin/vincristine regimen,53 as well as oral etoposide (VP-16).54
When the hypothalamus is the site of childhood glioma, a dien-cephalic syndrome evolves.55 Findings consist of emaciation, despite adequate food intake, that develops after a period of normal growth; hyperactivity and euphoria; skin pallor (without anemia); hypotension; and hypoglycemia. Other notable signs include nystagmus and disc pallor, to which may be added sexual precocity and laughing seizures.56 Twelve cases of histologically proven opticochiasmatic glioma with diencephalic syndrome were culled from a 22-year review.57 There were 6 men and 6 women, all with “failure to thrive” but with normal linear growth; none had stigmata of neurofibromatosis. Two patients died in the immediate postoperative period, and 10 patients received radiotherapy with “reversal of their diencephalic syndrome” (weight gain, deposition of subcutaneous fat, normal development). Six of 10 are alive, 3 being considered normal, and 3 are blind, retarded, or both. Clinical evidence of bilateral optic nerve involvement was seen in 10 of these 12 cases, but it was not possible during surgery to determine the origin of these tumors. The diencephalic syndrome appears to be related to the age at which the hypothalamus becomes compressed; none of the 12 patients (and only 4% of all published cases) had onset of symptoms after 2 years of age. Craniotomy with biopsy and radiotherapy is often indicated, as tumors involving the hypothalamus appear to be larger and more aggressive than other astrocytomas arising in this region.58
RADIOLOGIC INVESTIGATION OF GLIOMAS
The radiologic investigation of suspected gliomas is now sophisticated to the extent that “neuroradiologic biopsy” may obviate tissue diagnosis. The typical, but variable, findings include CT and MRI evidence of enlarged orbital or intracranial optic nerves; enlarged chiasm; a homogeneous hypothalamic mass; enlarged optic canals; and J-shaped or gourd-shaped sellae. The demonstration of such typical dysplastic changes of the sella turcica and optic canals, coupled with CT or MRI evidence of intrinsic chiasmal mass, so strongly suggests the diagnosis of glioma that histopathologic affirmation probably is superfluous and hazardous to vision.
Analysis of visual fields in patients with chiasmatic gliomas has shown no consistent relationship between the pattern of field defects and the location, size, or extent of tumor; in 12 of 20 patients, the putative bitemporal pattern of chiasmal involvement was absent.59 Central scotomas or measurable depression of the central field occurred in 70% of the eyes; therefore, the absence of bitemporal hemianopia, or one of its variants, cannot be interpreted as a sign that the glioma does not involve the chiasm.
Craniopharyngiomas (see Chap. 11) are developmental tumors that arise from vestigial epidermoid remnants of Rathke pouch, scattered as cell nests in the infundibulohypophysial region. These tumors are usually admixtures of solid cellular components and variable-sized cysts containing oily mixtures of degenerated blood and desquamated epithelium or of necrotic tissue with cholesterol crystals. Calcification of such debris may be radiologically detectable, a helpful diagnostic sign. In rare instances, these tumors may present in the neonate, attesting to their congenital origin.60 Craniopharyngiomas constitute 3% of all intracranial tumors (~15% in children), with two distinctive modes of presentation—in childhood and in adulthood—with a peak in the 40- to 70-year-old age range (Fig. 19-11).
FIGURE 19-11. Age distribution of craniopharyngioma. (Data from Svolos D. Craniopharyngiomas: a study based on 108 verified cases. Acta Chir Scand Suppl 1969; 403:1; Matson DD, Crigler JF. Management of craniopharyngioma in childhood. J Neurosurg 1969; 30:377; Bartlett JR. Craniopharyngiomas: an analysis of some aspects of symptomatology, radiology and histology. Brain 1971; 94:725. Note: Matson and Crigler series limited to children younger than 16 years of age.)
The symptomatology of childhood craniopharyngioma is variable, depending on the position and mass of the tumor.61,62 Frequently, progressive vision loss goes unnoticed until a level of severe impairment is reached, or unless headache, vomiting, or behavioral changes occur because of hydrocephalus. Obesity, delayed sexual development, somnolence, and diabetes insipidus attest to hypothalamic dysfunction, and other endocrinopathies may be present. Increased intracranial pressure is not uncommon, and papilledema may be observed. Some optic atrophy is usually present, but its absence does not conflict with the presence of chronic compression of the anterior visual pathways, even with severe vision loss. Suprasellar or intrasellar calcification is a rather constant radiologic finding in childhood craniopharyngiomas, occurring in 80% to >90% of affected children. Cystic areas frequently occur in craniopharyngioma but rarely in opticochiasmatic gliomas. CT scanning retains special sensitivity in diagnosis, being superior to MRI in detecting calcifications and cyst formations. However, involvement of adjacent structures is more clearly defined by MRI.
In adults, defects in visual field or acuity are the initial symptoms, although increased intracranial pressure or endocrine dysfunction less frequently occur. Visual field defects often take the form of asymmetric bitemporal hemianopia or homonymous patterns, indicating optic tract involvement. Intracranial calcification is seen much less regularly in adults than in children.
The surgical therapy for craniopharyngiomas ranges from total (or at least radical) excision63 or postoperative radiotherapy after partial removal of tumor, to radiation therapy administered after simple biopsy or cyst decompression.64 Transsphenoidal decompression may be indicated for large tumors filling the sella. When possible, total removal of the tumor is ideal, but radical manipulations should not be attempted when adhesions to the optic nerves, chiasm, carotid arteries, or hypothalamus are present. The more conservative approach of simple decompression of the anterior visual pathways and relief of third-ventricle obstruction appears judicious, and postoperative radiation therapy has established efficacy. Endocrine replacement therapy is anticipated in the vast majority of cases, often for life.
As with pituitary adenoma and meningioma, craniopharyngiomas may enlarge abruptly during pregnancy.65
RATHKE CLEFT CYSTS
Although previously regarded as a rare lesion in the sellar area, these cysts derive from Rathke cleft, an embryonic vestige of Rathke pouch. In a series of 18 patients with this lesion,66 7 presented with visual disturbance or bitemporal hemianopia, and 7 presented with a variety of endocrine dysfunctions. Unlike craniopharyngiomas, partial removal or decompression of these cysts with one procedure is usually sufficient, and regrowth is less common.
Enlarging loculations of cerebrospinal fluid (CSF) contained in arachnoidal cysts infrequently present as a chiasmal syndrome. These may arise, for example, in the floor of the third ventricle, causing chiasmal compression, a J-shaped sella, and occasional precocious puberty.67 Women with benign intrasellar cysts have been reported,68 showing bitemporal hemianopia, headache, optic atrophy, and panhypopituitarism. Another patient presented with obesity and amenorrhea but without visual defects.69
Primary suprasellar dysgerminomas (atypical teratoma, “ectopic pinealoma”) are rare causes of chiasmal interference, but they constitute a more or less distinguishable clinical syndrome. These tumors likely arise from cell rests in the anterior portion of the third ventricle and are not directly related to the pineal itself, although histologically, they resemble atypical pineal teratomas. A review of 64 cases67 revealed that the classic triad consists of early diabetes insipidus; visual field loss, not necessarily of a clearly chiasmal pattern (owing to infiltration of the anterior visual pathways); and hypopituitarism. Symptoms commence at the end of the first or during the second decade of life. Girls are affected more frequently, with a peak incidence at 10 to 20 years of age. Usually, plain film radiology of the sella is normal, but MRI readily reveals the lesion. Frequently, there is growth retardation. The diagnosis is confirmed by CSF cytology, measurement of human chorionic gonadotropin, or both, but often biopsy is necessary.70
The radical excision of tumor invading the optic nerves and chiasm, infundibulum, and floor of third ventricle is not possible, but radiotherapy offers excellent palliation, if not a cure. Because subarachnoid seeding of the neuraxis is a distinct possibility, more extensive radiation may be indicated. Long-range endocrine replacement is critical.
Asymptomatic pituitary adenomas occur in >20% of pituitary glands, and some degree of adenomatous hyperplasia can be found in almost every pituitary gland.71 A postmortem study72 of pituitaries removed from 120 patients without clinical evidence of pituitary tumors revealed a 27% incidence of microadenomas, of which 41% stained for prolactin, without gender difference. To generalize, >1 in 10 people in the general population dies harboring a prolactinoma. The incessant parade of this clinical syndrome is, therefore, not surprising. Tumor of the pituitary gland is the single most common intracranial neoplasm that produces neuro-ophthalmologic symptomatology, and chiasmal interference is overwhelmingly the most frequent presentation (see Chap. 11). Strictly speaking, a microadenoma refers to a tumor that is 10 mm or less in diameter and confined to the sella.
Symptomatic adenomas occur infrequently before 20 years of age but are common from the fourth through seventh decades of life. When these tumors do occur in childhood, most are asymptomatic. When symptoms are present, headache, visual field loss, and endocrinopathies are the most common. Dissimilar to adults, in children there is a definite male predominance, and many tumors are hemorrhagic.73 Histologic staining characteristics alone do not correlate well with patterns of growth or clinical symptomatology. A functional classification of pituitary adenomas, as elaborated by electron microscopy and immunohistochemistry, has replaced the previous simplistic classification of “eosinophilic, basophilic, and nonfunctioning” (see Chap. 11).
Nonocular symptoms include chronic headaches (severe or mild) in more than two-thirds of patients, fatigue, impotence or amenorrhea, sexual hair change, or other signs of gonadal, thyroid, or adrenal insufficiency (see Chap. 17). Prediagnostic signs and symptoms, affecting vision or otherwise, may exist for months to years before diagnosis is established.
With pituitary tumors, vision failure may take the form of a rather limited number of field patterns. As suprasellar extension evolves, a single optic nerve may be compromised, with resultant progressive monocular vision loss in the form of a central scotoma. More frequently, as the tumor splays apart the anterior chiasmal notch, superotemporal hemianopic defects occur (Wilbrand knee, as discussed previously). However, this well-touted superior bitemporal hemianopia is almost always accompanied by minor or major hemianopic scotomas approaching the fixational area along the vertical meridian (see Fig. 19-4). Asymmetry of field defects is common, the eye with the greater field deficit also being likely to show diminished central vision. Marked asymmetry is not uncommon, such that one eye may be blind and the other may show a temporal hemianopic defect, the so-called junctional scotoma; this combination is as exquisitely localizing to the chiasm as is the classic bitemporal hemianopia. Adenomas extending posteriorly produce incongruous homonymous hemianopias by optic tract involvement; central vision usually is diminished, at least in the ipsilateral eye. In late stages, the only suggestion of the chiasmal character of field defects may be minimal preservation of the nasal field of one eye.
The absence of field defects in patients undergoing evaluation for amenorrhea or a sella enlargement that is incidentally discovered does not imply the absence of an adenoma. For example, many patients with acromegaly do not show field defects, and microadenomas by definition do not escape the confines of the sella.
EFFECT OF PREGNANCY
The effect of pregnancy on pituitary adenomas is of interest diagnostically and therapeutically. Enlargement of preexisting pituitary tumors during the third trimester of pregnancy may occur,74 with reduction in size postpartum. That an otherwise normal pituitary gland may enlarge owing to the changes of pregnancy alone, causing symptoms affecting vision, is controversial.75 Nevertheless, a 30-week pregnant woman with an enlarged pituitary and bitemporal hemianopia that regressed spontaneously postpartum was reported76; a retrospective diagnosis of lymphocytic hypophysitis was made.
Many pituitary tumors deform the sella turcica sufficiently to be detected by plain film techniques, but, normal or otherwise, such procedures must be considered preliminary or superfluous. CT with contrast or gadolinium-enhanced MRI is mandatory when chiasmal lesions are suspected (see Chap. 20).
The rational approach to treatment of pituitary adenomas has evolved radically over the past 2 decades with the advent of thin-section CT; MRI; transsphenoidal microsurgery; hormonal assays; and dopamine agonists (e.g., bromocriptine), potent inhibitors of pituitary synthesis and release of prolactin. The choice of treatment is open to discussion, with enthusiastic advocates in each camp, but the prime consideration is the ultimate well-being of the patient. Patients with high surgical risk, especially the elderly, should not be subjected to frontal craniotomy. After uncomplicated transsphenoidal surgery alone, vision recovery approaches 90%.77 Radiation therapy, used either primarily or postoperatively, has great efficacy,78 and stereotactic radiosurgery has been shown to be effective for select patient groups.79
The administration of bromocriptine may rapidly improve vision function when prolactinomas compress the chiasm. In a study80 of 10 men with field defects caused by prolactinomas (initial prolactin level range 1535–14,200 ng/mL) who were treated with 7.5 to 30 mg per day bromocriptine, an increase in vision usually began within days of commencing therapy, and CT evidence of a decrease in tumor volume was documented somewhat later. Pregnancy apparently is not a contraindication for bromocriptine therapy.81 An extraordinary, rare complication of chiasmal herniation from shrinkage of a pituitary tumor treated with bromocriptine has been reported; recovery of vision ensued after a decrease in the dosage.82
With the advent of pergolide, another ergot-derived dopamine agonist, comes another viable treatment alternative, with apparently fewer frequent side effects of hypotension, nausea, and headache. Also, cabergoline has a very long duration of action, as well as fewer adverse effects. Quinagolide, a non-ergot long-acting prolactin inhibitor, a pure D2 agonist, is also useful.83 Finally, the long-acting somatostatin analog octreotide may be effective in the treatment of somatotropic, thyrotropic, gonadotropic, and nonfunctioning adenomas.84 In many cases, hormonal therapy of prolactinomas results in rapid improvement in vision function, often independently of decrease in tumor size.
Acromegaly is the relatively rare clinical condition related to adenomatous secretion of growth hormone, with resultant hypertrophy of bones, soft tissues, and viscera (see Chap. 12). Sellar changes, when present, are indistinguishable from those caused by other adenomas. Of 1000 pituitary adenomas, 144 of 228 acromegalic patients had visual field defects.96 Possibly, this relatively high incidence of visual defects reflects delay in diagnosis in a series commenced 5 decades ago.
Diabetes mellitus in acromegaly may be associated with typical retinopathy.85 Increase in corneal thickness and elevated ocular tension (glaucoma) has been reported,86 and CT scan has revealed thickened extraocular muscles.87
An unusual developmental condition with a dominant inheritance pattern, the so-called ACL (acromegaly, cutis verticis, leukoma) syndrome, has been described.88 This syndrome consists of acromegaloid features combined with severe ridging of the skin of the scalp (cutis verticis gyrata) and corneal whitening (leukoma). Pathologic examination of corneal leukoma has demonstrated a propensity for the nasal limbus, with whorl-like accumulations of disorganized collagen material and mucinous deposits.89 Signs tend to increase with age, with variable family penetrance.
Pituitary apoplexy—an acute change in adenoma volume resulting from hemorrhage, edematous swelling, or necrosis—is not rare, although the appropriate diagnosis may be elusive (see Chap. 17). Perhaps some 10% of pituitary adenomas undergo such acute or subacute changes,90 with clinical signs and symptoms including change in headache pattern (often severe frontal cephalgia), rapid drop in visual function, unilateral or bilateral ophthalmoplegia, epistaxis or CSF rhinorrhea, and other complications of blood or necrotic debris in the CSF. In a review of 320 verified pituitary adenomas,91 evidence of hemorrhage was found in 98 cases (18.1%). There was a high incidence of giant or large recurrent adenomas (41%). The mean age was 50 years (range, 17–71 years). The clinical course included acute apoplexy (7 cases); subacute apoplexy (11 cases); recent silent hemorrhages (13 cases); and old silent hemorrhages (27 cases). Sella enlargement was present in all patients.
These patients need not be stuporous, but rapid deterioration and obtundation are highly suggestive. There appears to be a tendency for such events to take place in intrasellar secretory adenomas confined by a competent diaphragma sellae. Ischemic necrosis causes sudden expansion of the tumor with acute compression of neighboring structures, including the optic nerves and chiasm and the ocular motor nerves in the cavernous sinus.
Although this syndrome should now be well known, delay in diagnosis is frequent. Common misdiagnoses usually include meningitis, ruptured intracerebral aneurysm, or sphenoidal mucocele. Almost all cases show abnormal sellae on plain skull series. The CT and MRI scans are typical, if not diagnostic.92 MRI and CT scans distinguish between many tissue densities, and MRI can detect the presence of blood; the finding of acute or subacute bleeding within a tumor based in an enlarged sella is highly suggestive of pituitary apoplexy.
Although in a few cases (limited suprasellar extension and intact or improving vision) corticosteroid replacement and other expectant medical management may suffice, as a rule, rapid transsphenoidal decompression of the often hemorrhagic tumor should be accomplished without delay to minimize devastating visual consequences; final endocrine status is less likely to be affected.
VISION ASPECTS OF THERAPY
The medical, surgical, and radiation therapies of pituitary adenomas are covered elsewhere (see Chap. 21, Chap. 22, Chap 23 and Chap. 24). The present role of irradiation of pituitary adenomas is problematic, considering the palpable failure rate and question of untoward side effects. Radiation therapy does indeed appear to reduce the rate of recurrence of pituitary adenomas.93 However, optic nerve and chiasm damage have occurred secondary to radiation necrosis anywhere from 2 months to 6 years after treatment.94 Radiation retinopathy, empty sella syndrome, cranial neuropathies, and further pituitary–hypothalamic disturbances may result from radiation therapy of pituitary lesions. There are also anecdotal reports of sarcomas, gliomas, and meningiomas occurring after radiation treatment of pituitary adenomas.95 The addition of bromocriptine before, during, or after radiotherapy may be helpful in controlling tumor secretion and size until the radiation treatment reaches its maximal effect.
After uncomplicated surgical decompression, visual acuity and fields may return rapidly within 24 to 48 hours or improve weekly (Fig. 19-12). Such restoration is dependent on the duration of visual morbidity and the degree of pallor of the optic discs. After surgery, if careful ophthalmoscopy reveals attrition of the retinal nerve fiber layer, corresponding field defects are permanent. For the most part, what vision returns does so by 3 to 4 months, although continued improvement to 1 year postoperatively is possible. Although fortunately the exception rather than the rule, vision loss is a well-known complication of both transsphenoidal surgery and craniotomy. Failure of vision recovery within the 24-48 hour postoperative interval is highly suggestive of occult hemorrhage in the tumor bed or from related vessels. MRI is essential and decompression may be necessary.
FIGURE 19-12. A, Preoperative automated visual fields from a 68-year-old man with a nonfunctioning pituitary adenoma. Note dense bitemporal defect. B, Same patient, 10 weeks after transsphenoidal decompression, enjoys dramatic recovery and near-normalization of visual fields. (Left, left eye; right, right eye.)
FOLLOW-UP OF TREATED PITUITARY ADENOMAS
From the standpoint of detecting recurrence, the follow-up of treated adenomas has been problematic. Even as adenomas must be large initially to cause visual defects, so must recurrences be substantial before defects again evolve. Although progressive vision failure may be the incontestable impetus for reoperation, consecutive perimetry may not be counted on to reveal early tumor recurrence. One should obtain an anatomic assessment, as provided by CT scanning or MRI. Recurrence of vision failure may be caused by regrowth of tumor, arachnoidal adhesions associated with progressive empty sella syndrome, or delayed radionecrosis. Tumor recurrence is, by far, the most common mechanism of vision deterioration, but field examination alone may not make this distinction.
EMPTY SELLA SYNDROME
Extension of the subarachnoid space into the sella turcica through a deficient sellar diaphragm may manifest itself clinically and radiologically as a syndrome mimicking pituitary adenoma. The empty sella may be defined as nontumorous remodeling that results from a combination of incomplete diaphragma sellae and CSF fluid pressure.96
Diaphragmal openings are common; in one study, defects >5 mm were found in 39% of normal autopsy cases.97 The sella is characteristically enlarged, but an empty sella may be of normal size. Primary empty sella occurs spontaneously and may be associated with arachnoidal cysts or, possibly, infarction of the diaphragma and pituitary. Secondary empty sella follows pituitary surgery or radiotherapy (see Chap. 11 and Chap. 17) and may also be seen in cases of elevated intracranial pressure (e.g., pseudotumor cerebri or hydrocephalus). Neuroradiographic evidence of a reversible empty sella syndrome after therapy for idiopathic intracranial hypertension has been reported.98 Visual field defects, hypopituitarism, headaches, and spinal fluid rhinorrhea occasionally occur. A thorough review of the clinical and radiographic characteristics of primary empty sella99 has revealed the following features: obese women predominate, ranging in age from 27 to 72 years, with a mean age of 49 years; headache is a common symptom; there is no vision impairment because of chiasmal interference; usually, an enlarged sella turcica is found serendipitously on radiologic studies obtained for evaluation of headaches, syncope, or other symptoms; pseudo-tumor cerebri was present in 13% of patients; approximately two-thirds of the patients had normal pituitary function; and the remaining one-third demonstrated endocrine disturbances, including panhypopituitarism and growth hormone, gonadotropin, and thyrotropin deficiency. In another series of patients with primary empty sella,100 the following features are noteworthy: all 19 were female; 12 patients initially reported headache; in 7, vision disturbances were prominent subjective symptoms (blurred vision, diplopia, micropsia); 3 patients had bilateral papilledema, and pseudotumor cerebri was diagnosed; and 2 patients demonstrated minimal, relative hemianopias without obvious cause. Additionally, visual field defects typical of those seen in glaucoma are well documented in patients with empty sella syndrome; the normal intraocular pressures implicate the empty sella syndrome as a potential cause of so-called low-tension glaucoma.101
Secondary empty sella occurs after pituitary surgery or radiotherapy, wherein adhesions form between the tumor “capsule” (or sellar diaphragm) and the nerves and chiasm. Retraction of these adhesions into the empty sella draws the chiasm and nerves downward, with resulting visual defects. Packing the sellar cavity to elevate the diaphragma (chiasmapexy) has been suggested for prophylactic purposes102 or after the fact.
Primary empty sella may rarely occur in children in association with multiple congenital anomalies, including the de Morsier syndrome.103
MISCELLANEOUS LESIONS OF THE OPTIC CHIASM
TRAUMATIC CHIASMAL SYNDROME
Vision loss that follows closed-head trauma usually is attributed to contusion or laceration of the optic nerves occurring abruptly at the time of impact. Much less frequently, a chiasmal syndrome may be identified by the pattern of field loss and associated deficits, including diabetes insipidus, anosmia, CSF rhinorrhea, and fractures of the sphenoid bone. From a report of several such patients,104 it was clear that neither the degree of vision loss nor the extent of diabetes insipidus was necessarily related to the severity of craniocerebral trauma. Transient diabetes insipidus was present in approximately one-half of these patients. Rarely, panhypopituitarism may occur.105 The traumatic chiasmal syndrome may occur more commonly than recognized because of its frequent association with extensive basilar skull fractures and its concomitant altered level of consciousness and high mortality rate.106
Lesions of the hypophysial stalk and, more frequently, of the hypothalamus may follow blunt head trauma. Hypothalamic lesions have been noted in 42% of patients who died after head trauma.107 Ischemic lesions and microhemorrhages were attributed to shearing of small perforating vessels.
Pituitary metastases are uncommon manifestations of systemic cancer and, initially, may be difficult to distinguish from simple adenomas. To ascertain the incidence of pituitary tumors in cancer patients and to characterize the clinical presentations of metastases, the experience at Memorial Sloan-Kettering Cancer Center was reviewed.108 Also, a series of 500 consecutive autopsies was analyzed, with inclusion of examination of the pituitary gland. In the clinical series, histologic diagnosis was made in 60% of patients. Radiologic evaluation, including polytomography and CT, did not reliably distinguish metastasis from adenoma, but the clinical syndromes were distinctive. In the metastasis group, the review108 revealed an 82% incidence of diabetes insipidus but vision loss in only 11%. In the autopsy series, metastases were found in 36% of cases and adenomas in 1.8%. Two other reported cases109 of sellar metastases showed diplopia resulting from palsies of the third, fourth, and sixth cranial nerves and eventually diabetes insipidus in one patient. In another report, a man with known colon carcinoma developed panhypopituitarism, hyperprolactinemia, chiasmal field loss, and a right third nerve palsy but no diabetes insipidus.110
Several generalizations emerge from these reports of meta-static involvement of the pituitary gland: either the anterior or posterior lobe may be involved; diabetes insipidus is more common than with simple adenoma; cranial nerve palsies are more common than simple adenomas; hyperprolactinemia may be seen, but the serum prolactin level usually is <200 ng/mL.
Chiasmal neuritis has been well documented and may occur in multiple sclerosis, systemic lupus erythematosus, and a variety of other vasculitic and autoimmune disorders. Such a case with positive serology for Lyme disease has been reported.111 Sarcoidosis has a well-known predilection for leptomeninges at the base of the brain. The hypothalamus, pituitary, and optic chiasm all are involved in a variety of cases.112
Chiasmal arachnoiditis, secondary to tuberculosis or syphilis, is now a rare cause of the chiasmal syndrome in the United States but may be seen with increasing frequency in various immunodeficient states.
Such lesions are indeed rare, but cavernous malformations appear to be the most common intrachiasmal vascular anomaly.113 Suprasellar hemangioma with progressive vision loss has also been reported to occur in von Hippel-Lindau disease.114
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