Chiasmal disorders are important in the differential diagnosis of anterior visual pathway dysfunction, particularly when the visual loss is gradually progressive. Involvement of the chiasm is suggested by (1) any amount of temporal field loss in one or both eyes or (2) visual loss of any type associated with endocrine dysfunction. The most common causes are compressive sellar masses, and therefore the diagnosis and management depend heavily on neuroimaging. These lesions produce visual acuity and field deficits by interfering with the optic nerves, chiasm, or optic tracts or, less often, by obstructing the third ventricle and causing chronic atrophic papilledema. Endocrinopathy is the result of pituitary, stalk, or hypothalamic dysfunction, while ocular motility abnormalities can result from lateral extension and involvement of the cavernous sinuses. Because sellar masses are so commonly associated with visual disturbances, neuro-ophthalmic evaluation often leads to their detection and is important for pretreatment assessment and subsequent follow-up.
Anatomical aspects of the chiasm and sellar and parasellar structures are reviewed first, followed by a discussion of the neuro-ophthalmic signs and symptoms of chiasmal disease. Because of its clinical importance, pituitary and hypothalamic physiology are also covered. The differential diagnosis of the various entities affecting the chiasm then are discussed in the context of the patient’s age, clinical history, general physical findings, neuroimaging, and endocrine testing. Finally, the clinical features and treatment of these disorders are detailed, with the greatest emphasis placed on the most common disorders: pituitary adenomas, craniopharyngiomas, meningiomas, aneurysms, and chiasmal–hypothalamic gliomas.
Intracranially, the optic nerves ascend and converge medially to join at the optic chiasm, which has the shape of the letter X when viewed from above or below. The chiasm tilts upward at an angle of 45 degrees and lies in the subarachnoid (cerebrospinal fluid (CSF)–filled) space of the suprasellar cistern ( Fig. 7.1 ). It is approximately 12 mm wide, 8 mm in anteroposterior diameter, and 4 mm thick. Its posterior portion forms the anterior and inferior wall of the third ventricle. The chiasm lies inferior to the hypothalamus and third ventricle and anterior to the pituitary stalk (or infundibulum, which connects the hypothalamus and the pituitary) ( Fig. 7.2 ). The pituitary gland sits 10 mm below the chiasm in a recess in the sphenoid bone called the sella turcica. The bony boundaries of the sella include the tuberculum sellae anteriorly, the dorsum sellae posteriorly, and the anterior and posterior clinoid processes superiorly ( Fig. 7.3 ). The cavernous sinuses, containing cranial nerves III, IV, V1, V2, and VI, the internal carotid arteries, and sympathetic fibers, form the lateral walls of the sella. The diaphragma sellae, penetrated only by the pituitary stalk, is a horizontal fold of dura mater that separates the pituitary gland from the suprasellar cistern (see Fig. 7.3 ). In 80% of individuals, the chiasm is located directly above the pituitary gland, while in 15% it lies over the tuberculum sellae (prefixed chiasm), and in 5% it is over the dorsum sellae (postfixed chiasm) ( Fig. 7.4 ).
Magnetic resonance imaging (MRI) provides exquisite detail of the sellar area ( Fig. 7.5 ). Normally on T1-weighted magnetic resonance (MR) coronal images the body of the chiasm has a dumbbell shape and is located in the middle of the suprasellar cistern. More anteriorly the two optic nerves are visible, but more posteriorly the chiasm lies sandwiched between the vertically oriented third ventricle above it and the pituitary stalk below it. On coronal images within the sella the pituitary gland appears flat, and the cavernous sinuses are lateral to it. The pituitary stalk and cavernous sinuses normally enhance with gadolinium. On sagittal sections, the tilted chiasm is easily identified above the pituitary. On T1-weighted images, the anterior pituitary is isointense with the pons, but the posterior portion of pituitary is bright. Details of the chiasm and sellar region are less evident with computed tomography (CT).
At the chiasm, axons from the nasal retinal ganglion cells (temporal visual field) from both eyes cross, and the most ventral axons originating in the inferonasal retina bend temporarily up to 3 mm into axons of the contralateral optic nerve (Wilbrand’s knee ) ( Fig. 7.6 ). The knee’s existence has been questioned, and one author attributed it to a histopathologic artifact of long-term monocular enucleation. Fibers from the temporal retina (containing information from the nasal field) remain ipsilateral. The ratio of crossed to uncrossed fibers is 53 : 47. The fibers transmitting visual information from the superior retina remain superior in the chiasm; those from the inferior retina remain inferiorly situated. Approximately 90% of chiasmal fibers originate from the macula, and, of these, those that cross lie superiorly and posteriorly within the chiasm.
Most of the ganglion cell axons traveling through the optic chiasm exit posteriorly and diverge to form the left and right optic tracts. Each tract is made up of ipsilateral temporal fibers and contralateral nasal fibers. In addition, retinal ganglion cell axons within the retinohypothalamic tract mediate the visual input responsible for diurnal variations of various neuroendocrine systems (circadian rhythms). These cells, which express melanopsin and respond to short-wavelength (blue) light, travel through the posterior chiasm then project to the hypothalamus, specifically the suprachiasmic nucleus or the supraoptic nucleus. Neurons within the suprachiasmatic nucleus express vasoactive intestinal peptide, a major regulator of circadian rhythms.
The supraclinoid portions of the carotid arteries ascend lateral to the optic chiasm. The precommunicating segments of the anterior cerebral arteries and the anterior communicating arteries are located anterior and superior (dorsal) to the chiasm. Because of the chiasm’s upward tilt, the posterior portion of the circle of Willis lies behind and below it (ventral) (see Fig. 7.2 ). The chiasm derives its blood supply from an inferior and superior anastomotic group of vessels. The inferior group is made up of the superior hypophyseal arteries, which derive their blood supply from the internal carotid, posterior communicating, and posterior cerebral arteries. The superior group of vessels consists of precommunicating branches of the anterior cerebral arteries. There is evidence to suggest that the body of the chiasm receives its blood supply only from the inferior group, while the lateral parts of the chiasm are fed by branches from both inferior and superior groups.
Neuro-ophthalmic Symptoms and Signs in Chiasmal Disorders
Because most chiasmal disturbances are caused by compressive lesions, the visual loss is usually insidious and often not suspected or detected until formal perimetry is performed. Acute visual loss would imply a rapidly expanding mass; hemorrhage within a mass; or an infectious, vascular, or inflammatory etiology, and these situations may mimic retrobulbar optic neuritis. Visual complaints are usually vague, often reflecting blurry or hazy vision or difficulty reading or focusing. Patients with slowly progressive chiasmal field loss may be without visual complaints unless acuity is abnormal, and a temporal field defect may not be apparent until the patient reads only the nasal half of the acuity chart. Others might describe double vision because of ocular motility dysfunction or difficulty aligning noncorresponding nasal fields (see Hemifield Slide Phenomena, discussed later). Photophobia is a rare but reported visual symptom due to compressive lesions of the chiasm.
Visual Acuity, Color Vision, and Afferent Pupillary Defects
When acuity is diminished, asymmetry is the rule. Color vision may be altered only in defective fields, and asymmetric lesions may produce an afferent pupillary defect.
Patterns of Visual Field Loss
Temporal field defects respecting the vertical meridian, in one eye or both eyes, are the hallmarks of chiasmal dysfunction. The actual pattern of field loss depends on the chiasm’s position and the exact location of the culprit lesion (see Fig. 7.6 ). For instance, if the process affects the crossing nasal fibers in the body of the chiasm, in the case of a sellar mass growing upward and impinging upon a normally situated chiasm, a classic bitemporal hemianopia is the result ( Fig. 7.7 ). Incomplete and asymmetric bitemporal defects occur in the majority of cases ( Fig. 7.8 ). Compression of the superior portion of the chiasm will result in visual field defects that are denser inferiorly ( Fig. 7.9 ). More diffuse processes in this location can, of course, eventually cause nasal defects and acuity loss. However, it is a common observation that large sellar masses, despite compression, elevation, and flattening of the chiasm, as well as optic nerves and tracts in many instances, sometimes produce only a bitemporal hemianopia. It is unclear why the crossing fibers are so vulnerable. Mechanical distortion of nerve fiber bundles and impairment of the extrinsic vascular supply are two possible explanations, but a combination of both is likely. The crossing fibers may be more prone to deformation from a mass compressing the chiasm inferiorly. In a cadaveric model of an upward-expanding pituitary mass, the chiasm experienced a nonuniform distribution of pressure, greatest centrally, putting the crossing fibers at higher risk for damage. The smaller surface area exposed to external pressure as well as fiber orientation are also believed to contribute to this vulnerability. Alternatively, an enlarging suprasellar mass might preferentially interrupt the inferior blood supply of the chiasm, affecting the body of the chiasm and crossing fibers, and leave the more lateral and superior vascular supply of the lateral parts of the chiasm relatively spared. The relatively immediate improvement in visual fields following surgical decompression in some patients with chronic mass lesions is also enigmatic. In these instances, vascular compromise seems less likely than reversible axonal compression.
Patients with complete bitemporal hemianopias and post-fixation blindness may have trouble performing near tasks and complain of abnormal depth perception . When the eyes converge on a near target, the blind temporal fields overlap behind it ( Fig. 7.10 ). Objects behind the fixation point are therefore not seen. Affected patients will have difficulty threading a needle, for instance. This can be investigated by having the patient fixate on a near target, then testing whether they see any objects directly behind it ( ).
If the chiasm is postfixed (see Fig. 7.4 ) in relationship to a sellar mass or the lesion affects the anterior portion of the chiasm, several patterns of field loss can be seen. Patients may present with a monocular arcuate or central scotoma if the process primarily affects one optic nerve, and these instances may be difficult to separate from glaucoma or optic neuritis. More characteristic of a chiasmal lesion is involvement of the ipsilateral optic nerve and Wilbrand’s knee, resulting in a junctional scotoma. This field deficit is characterized by a central scotoma or other optic nerve–related defect in the ipsilateral eye and a supratemporal defect in the other eye ( Fig. 7.11 ). This pattern of visual field loss localizes to the proximal optic nerve whether Wilbrand’s knee truly exists or not (see previous discussion). A monocular temporal field defect also localizes to the ipsilateral anterior chiasm and proximal optic nerve. Here a unilateral lesion is posterior enough to disrupt the ipsilateral crossing nasal fibers after they have segregated but is too anterior to involve the contralateral ones. Because this pattern of field loss is also often functional, patients with organic monocular temporal field defects should be distinguished by an associated ipsilateral afferent pupillary defect, sometimes with optic atrophy. Less commonly, a disturbance of the crossing nerve fiber bundle anteriorly may result in an arcuate scotoma emanating from the blind spot and ending abruptly at the vertical meridian ( Fig. 7.12 ). Central bitemporal hemianopic scotomas ( Fig. 7.13 ) or optic tract syndromes may be the product of prefixed chiasms or more posteriorly situated lesions.
The examiner should be aware of processes that produce bitemporal defects which do not respect the vertical meridian. These include tilted or hypoplastic optic discs (see Chapter 5 ), sectoral (nasal) retinitis pigmentosa, and enlarged blind spots (see Chapter 6 ). In these cases, neuroimaging of the chiasm will be unremarkable.
Binasal defects respecting the vertical meridian that are due to chiasmal dysfunction are extremely unusual. Theoretically this pattern can result from bilateral ectatic carotid artery compression of the lateral portions of the chiasm, compression from a variety of chiasmal region tumors, or third ventricular enlargement (see later discussion). Usually binasal visual field defects have ocular causes such as glaucoma, optic disc drusen, retinitis pigmentosa, and ischemic optic neuropathy. Uncommonly, altitudinal defects can occur when crossed and uncrossed fibers are affected equally by a process involving the inferior or superior portions of the chiasm.
Visual field testing . Patients with suspected chiasmal disorders should undergo careful documentation of visual fields in addition to the neuro-ophthalmic examination. Subtle superior temporal defects respecting the vertical meridian may be the first sign of a compressive sellar mass, so examiners should look carefully in these areas. Goldmann kinetic perimetry may be necessary in poorly cooperative patients and those with severe visual loss. However, we prefer computerized threshold perimetry in most patients with chiasmal disturbances, as they likely will require serial field examinations to monitor disease activity. We do not advocate the use of visual-evoked potentials (VEPs) in the evaluation or follow-up of patients with chiasmal disorders.
Optic Disc Findings
Long-standing processes can lead to optic disc pallor, but this finding is variable and does not correlate with the degree of visual loss. Nevertheless, disc pallor and retinal nerve fiber layer (RNFL) loss generally are associated with a poorer prognosis for visual improvement following treatment. Optic disc swelling in the setting of chiasmal dysfunction indicates either papilledema due to third ventricular compression by a sellar mass or an infiltrative or inflammatory process involving the anterior visual pathway. A pattern of pseudobitemporal hemianopia can also develop in patients with papilledema from lesions unrelated to the chiasm when they develop markedly enlarged blind spots. Cupping of the optic disc may occur due to chronic optic nerve compression.
In patients with bitemporal hemianopias, a characteristic transverse “band” optic atrophy or cupping can result from chiasmal compression of crossing nasal fibers. In each eye, ganglion cells and their axons degenerate in the blind nasal hemiretina, leading to a nasal wedge of optic atrophy. Fibers from the blind nasal half of the macula are similarly affected, resulting in a temporal wedge of optic atrophy. The nerve fibers coming from the “seeing” temporal macula and retina, entering the disc superiorly and inferiorly, are preserved.
Hemifield Slide Phenomena
Rarely, patients with complete bitemporal hemianopias may have odd complaints caused by an inability to align the noncorresponding nasal visual fields of each eye (hemifield slide phenomena ) ( Fig. 7.14 ). With a hypertropia, a patient may describe vertical misalignment or slippage of nasal fields. In contrast, esodeviated eyes can result in horizontal separation of nasal fields. Exodeviated eyes may cause overlap of nasal fields and so-called nonparetic double vision. The examiner can test for these phenomena in patients with horizontal deviations by drawing a line of small dots or circles, then asking the patient to look quickly at the center of them and tell the examiner how many he or she sees ( Fig. 7.15 ).
Eye Movement Abnormalities
Ocular motor palsies and nystagmoid eye movements can be associated with chiasmal disorders but are uncommon. Chiasmal field loss accompanied by an ocular motor palsy implies cavernous sinus involvement, sometimes also suggested by facial pain or numbness resulting from trigeminal nerve dysfunction. The sellar process which most commonly affects both the chiasm and cavernous sinuses, with overt and rapid onset of clinical manifestations, is pituitary apoplexy (see later discussion).
See-saw nystagmus can be a sign of a chiasmal process, and sellar masses and trauma are the usual culprits. In this unique motility disturbance one eye elevates and intorts while the other depresses and extorts, then vice versa, in a pendular fashion (see Fig. 17.13 , ). The exact mechanism is unclear, but almost all patients with acquired see-saw nystagmus have either a bitemporal hemianopia or bilateral involvement of the interstitial nuclei of Cajal (inC) in the mesencephalon. Most sellar masses which exhibit see-saw nystagmus are large, causing both the field defect and midbrain compression. However, each factor by itself is sufficient for the development of this motility disorder. Patients with see-saw nystagmus and chiasmal trauma, for instance, usually have a bitemporal hemianopia, while those with midbrain infarction or hemorrhage involving the inC have no visual loss. Proposed explanations relating the bitemporal hemianopia and see-saw nystagmus include (1) a torsional adaptive process which attempts to increase the overlap of noncorresponding nasal fields and (2) disruption of the visuovestibular connections between the retina and inferior olive. Rare achiasmatic and hemichiasmatic individuals, who may have normal fields, can also have see-saw nystagmus (see Developmental Anomalies of the Chiasm). See-saw nystagmus is also discussed in Chapter 17 .
Asymmetric or Monocular Nystagmus
Young children with sellar masses such as gliomas or craniopharyngiomas may rarely present with monocular or asymmetric nystagmus when the chiasm is involved. Sometimes the full triad of nystagmus, head nodding, and head tilt is present, mimicking the benign symptom complex of spasmus nutans. Usually those with intracranial lesions will have reduced vision, optic atrophy, strabismus, or diencephalic syndrome, and these findings will convince the examiner that neuroimaging should be performed ( ). The mechanism by which sellar masses produce the nystagmus is not clear. For a more detailed discussion of spasmus nutans and its imitators, the reader is referred to the chapter on nystagmus and nystagmoid eye movements ( Chapter 17 ).
Endocrine Disturbances Associated With Chiasmal Disorders
Pituitary Gland, Hormone Physiology, and Endocrinopathy
Traditionally, the pituitary gland is separated into the anterior (adenohypophysis) and posterior (neurohypophysis) lobes (see Fig. 7.3 ). Laterally, the adenohypophysis contains cells which secrete prolactin and growth hormone (GH), while cells which produce thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and adrenocorticotropic hormone (ACTH) are located medially. The hormones vasopressin (or antidiuretic hormone (ADH)) and oxytocin are synthesized in the supraoptic and periventricular nuclei in the hypothalamus, then transported to the posterior lobe via long axons within the pituitary stalk.
Prolactin stimulates production of breast milk in women. GH stimulates liver production of insulin-like growth factor 1 (IGF-1, also called somatomedin C ). Corticotropin (ACTH) causes adrenal secretion of both cortisol and androgens. TSH stimulates thyroid production of triiodothyronine (T3) and thyroxine (T4). In women, FSH and LH lead to estradiol and progesterone secretion, folliculogenesis, and ovulation, while in men, these two hormones stimulate testosterone secretion and spermatogenesis. Hormone secretion in the adenohypophysis is regulated in part by proteins produced in the hypothalamus and brought to the pituitary via the hypophyseal portal venous system ( Fig. 7.16 ). Dopamine tonically inhibits prolactin secretion, for example. End-organ hormone levels confer additional regulation by modulating the production of pituitary- and hypothalamic-releasing hormones. ADH, released in the neurohypophysis, stimulates free-water reabsorption in the collecting ducts of the kidney. Oxytocin stimulates uterine contraction and milk ejection.
Because of the chiasm’s proximity to the pituitary, stalk, and hypothalamus, chiasmal disorders, especially those due to mass lesions, often present concomitantly with endocrine dysfunction. In this setting, the endocrinopathies usually fall into two major categories: pituitary hormone deficiency (hypopituitarism) and hypersecretion. Hypopituitarism can be the result of compression of normal pituitary tissue, impaired blood flow of normal tissue, or interference with hypothalamic production or delivery of releasing hormones. Symptoms consistent with hypopituitarism, which can vary according to sex, are outlined in Table 7.1 . Of these, the most common are those associated with GH deficiency, but the most salient clinical features of hypopituitarism actually vary with age. In children, failure of normal linear growth is the dominant symptom; in adolescence, it is delayed sexual maturation; and in adults, it is secondary hypogonadism. Recent data suggests both pediatric- and adult-onset hypopituitarism negatively affect cardiovascular health, bone mass, and overall life expectancy, despite replacement treatment.
|Hormones Affected||In Women||In Men||In Women and Men|
|Hypogonadism||↓ or normal LH |
↓ or normal FSH
↓ estradiol in women
↓ testosterone in men
|Oligomenorrhea or amenorrhea |
|↓ facial and body hair |
|Hypoprolactinemia||↓ prolactin||Failure to start and maintain lactation|
|Hypothyroidism||↓ or normal TSH |
↓ T3, T4
|Fatigue, weakness, inability to lose weight, puffiness, constipation, cold intolerance, memory impairment, altered mentation, bradycardia, delayed relaxation of deep tendon reflexes|
|Growth hormone deficiency||↓ GH, IGF-1||Short stature in children |
↓ vigor, ↓ exercise tolerance
↓ body muscle:fat ratio
|Hypoadrenalism||↓ or normal ACTH |
|Loss of axillary and pubic hair||Fatigue and malaise, postural hypotension, pallor, anorexia, and nausea|
|Diabetes insipidus||↓ ADH||Polyuria |
|Oxytocin deficiency||↓ milk ejection during lactation|
On the other hand, pituitary hormone excess generally is caused either by hypersecreting pituitary adenomas or by target organ failure with secondary hypersecretion. In the one exception, mild degrees of hyperprolactinemia can be associated with hypothalamic dysfunction or stalk compression, both of which result in decreased delivery of dopamine, which normally inhibits prolactin secretion, to the pituitary gland. Clinical features of pituitary hormone hypersecretion due to adenomas are highlighted in Table 7.2 . When chiasmal dysfunction due to a sellar mass is present, hypopituitarism is more common than hypersecretion, but patients can have elements of one or both (for instance, when a hypersecreting adenoma compresses and compromises adjacent normal pituitary tissue).
|Hormones Affected||In Women||In Men||In Women and Men|
|Hyperprolactinemia||↑ prolactin||Amenorrhea |
|↑ libido |
Galactorrhea (rare in men)
|Growth hormone excess||↑ GH, IGF-1||Acromegaly |
|ACTH excess (Cushing disease)||↑ or normal ACTH |
|↑ libido||Sudden weight gain |
Muscle wasting and weakness
|Hyperthyroidism||↑ or normal TSH |
↑ T3, T4
|Excess LH/FSH||↑ or nl LH |
↑ or normal FSH
↑ or normal estradiol in women
↑ testosterone in men (variable)
|Precocious puberty in childhood |
↑ libido in adults
Hypopituitarism can also be an unavoidable side-effect of surgery or irradiation of sellar lesions. Thus, before and following treatment in many instances, hormone replacement will be required, because cortisol and thyroxine are necessary for life, uncontrolled diabetes insipidus can be life-threatening, and gonadotropin deficiency is associated with osteoporosis and impaired reproductive and sexual functions. It is not uncommon for patients with sellar processes to require replacement regimens consisting of various combinations of corticosteroid, thyroxine, GH (in children), estrogen (for women), testosterone (for men), and DDAVP (desmopressin; 1-deamino-8-d-arginine vasopressin).
Two childhood endocrinopathies, Russell’s diencephalic syndrome and precocious puberty, are the most important clinical syndromes associated with hypothalamic lesions in the pediatric age group. The diencephalic syndrome has a typical age of onset between the newborn period and 4 years of age and is characterized by emaciation, hyperkinesis, and euphoria ( Fig. 7.17 ). The weight loss is the most salient trait, and it occurs after initially normal weight gain. Children are often evaluated for failure to thrive. Linear growth and head circumference are unaltered. An alert appearance (due to lid retraction), vomiting, pallor, and nystagmus are other common features. Optic atrophy occurs in approximately one-quarter. Hypothalamic chiasmal gliomas are the usual cause, although craniopharyngiomas should also be considered. Anterior hypothalamic dysfunction is one proposed mechanism for the syndrome.
Precocious puberty is seen in boys more commonly than in girls, and affected children are tall for their age and exhibit early gonadal maturation. Responsible lesions typically lie in the floor of the third ventricle, posterior hypothalamus, tuber cinereum, or median eminence. Common etiologies in these areas include hamartomas of the tuber cinereum, hypothalamic gliomas, and suprasellar germ cell tumors. There may be several mechanisms, each resulting in a premature onset of puberty. Germ cell tumors, for instance (see later discussion), produce β-human chorionic gonadotropin, which stimulates Leydig cells. Alternatively, hypothalamic infiltration might cause increased secretion of gonadotropin-releasing hormone.
Surgery in the hypothalamic region, usually for craniopharyngiomas, commonly causes weight gain and obesity in both children and adults—likely due to injury of the satiety centers in the hypothalamus. Children undergoing surgeries in the hypothalamic region may also experience restricted growth rates.
It is often difficult on the basis of the neuro-ophthalmic signs and symptoms alone to arrive at the specific pathologic diagnosis. The visual complaints and field patterns facilitate chiasmal localization but are usually nondiagnostic with regards to etiology. Only in rare instances, such as progressive superior bitemporal field deficits due to an expanding pituitary adenoma, does the pattern of visual loss suggest a specific entity. Rather, once a chiasmal disorder is suspected on neuro-ophthalmic grounds, the diagnosis is best established by considering the patient’s age, clinical history, general physical findings, neuroimaging results, and endocrine testing.
Most chiasmal disorders are due to compressive lesions, many of which have a tendency to occur more frequently either in (1) children and young adults or (2) middle-aged and elderly individuals. Table 7.3 outlines the differential diagnosis of most sellar and suprasellar processes, based upon age predilection and frequency. In general, congenital tumors and masses are more common in childhood, and rarer vascular processes and metastases in late adulthood. The inflammatory, infectious, and infiltrative disorders occur at all ages.
|Age Group||More Common||Less Common|
|Pediatric–young adult||Chiasmal–hypothalamic glioma |
|Germ cell tumors |
Suprasellar arachnoid cyst
|Middle-aged–elderly||Pituitary adenoma |
Aneurysm (internal carotid)
|Malignant optic glioma |
Metastases to chiasm, sella, or suprasellar region
Rathke’s cleft cyst
Sphenoid sinus mucocele
|No particular age predilection||Histiocytosis |
Both the rate of onset of symptoms and presence and quality of endocrine features are important. Because the most common etiology is a compressive sellar mass, most visual and endocrine symptoms are insidious. Acute chiasmal syndromes can occur when tumors enlarge suddenly, due to cyst expansion or intratumor hemorrhage, as in pituitary apoplexy. However, sudden chiasmal field loss might also suggest chiasmal neuritis, ischemia, or an intrinsic vascular malformation. Patients should also be questioned about double vision or difficulty with depth perception.
Historical features suggestive of endocrine dysfunction should be investigated. In particular, the patient should be asked about symptoms consistent either with hypopituitarism or pituitary hormone hypersecretion. While the former could be due to any sellar mass, the latter suggests a pituitary adenoma. Other types of endocrine dysfunction, such as diabetes insipidus, are characteristic of sellar sarcoidosis and germinoma, for instance. However, diabetes insipidus may be seen in many other suprasellar processes.
General Physical Findings
The examiner should look for evidence of endocrine dysfunction, and in some cases the diagnosis can be made on physical findings alone. Patients with gynecomastia, Cushingoid features, or acromegaly, for example, might harbor hypersecreting pituitary adenomas. Precocious puberty suggests hypothalamic dysfunction, while growth retardation might be due to GH deficiency. Features of neurofibromatosis (NF), such as café-au-lait spots and neurofibromas, should also be excluded because of its association with optic pathway gliomas.
All patients suspected of having a chiasmal disorder should undergo enhanced and unenhanced MRI with special attention to the sellar area, including axial and 3 mm coronal and sagittal sections. If the clinical history and findings on examination suggest chronicity (long duration of symptoms and optic disc pallor, for example), neuroimaging can be performed over the next day or two. However, either sudden visual loss, indicating an acute process, or optic disc swelling, a sign of possible hydrocephalus, are indications for emergent scanning. MRI is far superior to CT in the evaluation of this region, because it provides excellent anatomic detail, sagittal views, and better soft tissue imaging. The only disadvantage of MRI in this regard is its inability to demonstrate small amounts of calcification and changes in the sellar walls, which are made of cortical bone and separate the pituitary gland and cavernous sinuses. When MRI is contraindicated or intolerable, CT can still be useful, especially if contrast images and coronal views (thin 1.5 mm sections) can be obtained. In some instances CT scanning is adjunctive to MRI by outlining bony landmarks and possibly their erosion by a sellar mass. CT can also identify calcification within suspected sellar lesions. When aneurysms are suspected because of MRI or CT findings, an MRI or CT angiogram or a conventional angiogram is necessary.
Intrinsic disorders of the chiasm will be suggested by radiographically demonstrated chiasmal enlargement, signal abnormality, or gadolinium enhancement. Extrinsic compression will be evident if there is a mass lesion and distortion or displacement of the chiasm.
Diagnostic Studies/Endocrine Testing
The outpatient endocrinologic panel should include serum prolactin, serum early morning cortisol, TSH, T4, LH, FSH, estradiol (in women), and testosterone (in men) levels. Other tests which should be ordered include GH (after a 75 g oral glucose load), IGF-1, ACTH, and 24-hour urine-free cortisol. Low values, and even normal ones in some instances, are consistent with hypopituitarism (see Table 7.1 ). High values imply hypersecretion (see Table 7.2 ). Some relevant details should be understood:
As a rule, prolactin-secreting macroadenomas are associated with a serum prolactin level of greater than 150–200 ng/ml (normal 2–15 ng/ml), and elevated levels correlate with tumor size. Microadenomas, hypothalamic dysfunction, pituitary stalk compression, or drugs such as neuroleptics and antidepressants lead to more modest elevations. Physiologic hyperprolactinemia, also modest, occurs during pregnancy and postpartum lactation.
After a 75 g oral glucose load, the normal GH level is <2 ng/ml. Lack of suppression to this extent is the rule in acromegaly , and secretory spikes are frequent in this disorder. IGF-1 levels are also elevated but are more stable and correlate better with the severity of the acromegaly.
If neuroimaging suggests a pituitary adenoma and clinical features are consistent with ACTH hypersecretion despite normal or equivocal ACTH and cortisol levels, an overnight dexamethasone suppression test with measurement of morning plasma cortisol may be required. Finally, petrosal venous or cavernous sinus ACTH sampling may be performed, but this is rarely necessary if an adenoma has already been demonstrated radiographically.
A summary of the evaluation of patients with suspected chiasmal disorders is outlined in Box 7.1 . The discovery of a mass lesion requires neurosurgical consultation, while the presence of endocrine dysfunction, on either clinical or laboratory grounds, should prompt a formal endocrinologic evaluation as well. The remainder of this chapter discusses the various entities leading to chiasmal dysfunction. The clinical features and the management of each are emphasized.
Consideration of patient’s age
Childhood and young adulthood
Middle-aged and elderly
Including careful visual field testing
General physical examination
Evidence of endocrine dysfunction
Evidence of underlying systemic disease
MRI, preferably including sagittal and coronal thin cuts through the sellar region
CT with coronal views
Endocrine testing and evaluation
Serum prolactin, morning cortisol, TSH, T4, LH, FSH, estradiol (in women), and testosterone (in men)
GH (after a 75-g oral glucose load) and IGF-1 if acromegaly suspected; ACTH and dexamethasone suppression tests if inappropriate ACTH secretion suspected.
Other adjunctive tests
Lumbar puncture if neuroimaging suggests an infectious, inflammatory, or infiltrative disorder
Optical coherence tomography imaging of the circumpapillary retinal nerve fiber layer and whole volume imaging of the macula
ACTH, Adrenocorticotropic hormone; CT, computed tomography; FSH, follicle-stimulating hormone; GH, growth hormone; LH, luteinizing hormone; IGF-1, insulin-like growth factor 1; MRI, magnetic resonance imaging; TSH, thyroid-stimulating hormone.
These tumors are the most common cause of chiasmal dysfunction in adults, and they are very common, representing about 10–15% of all intracranial tumors. Pituitary adenomas may be found in 3.1–22.5% of routine autopsies, but frequently these incidental lesions are smaller than 2 mm in size. About 70% of pituitary adenomas occur in individuals aged 30 to 50 years, and only 3–7% occur in patients younger than 20 years. Pituitary adenomas are uncommon but can occur in children.
There is disagreement whether adenomas arise from somatic mutation of a single cell or from hyperstimulation due to hypothalamic or hormonal dysregulation, or both. Recent data has implicated enhanced STAT3 expression, which is not found in nonsecreting pituitary tumors, as the primary cause for hyperstimulation. In general, they are benign epithelial neoplasms which rarely metastasize; primary pituitary carcinomas are rare. Microadenomas are adenomas smaller than 10 mm, and these are rarely large enough to cause chiasmal compression, while macroadenomas are larger than 10 mm. Pituitary adenomas are usually isolated, but they can be associated with tumors of the parathyroid gland and pancreas, and less commonly with those of the thymus, in multiple endocrine neoplasia (MEN) type I syndrome.
Pituitary adenomas can be classified functionally by their endocrine abnormality into two major groups: those with nonfunctional enlargement and those exhibiting hormone hypersecretion. Approximately one-quarter to one-third clinically apparent pituitary adenomas are nonfunctioning or nonsecreting. On the other hand, the two most common hypersecreting adenomas are prolactinomas and GH-secreting tumors, but ACTH, TSH, and LH/FSH-secreting tumors are also clinically important. Modern morphologic techniques have rendered the classification of pituitary adenomas based upon staining characteristics, such as acidophilic, basophilic, and chromophobic, less helpful.
The presentation of pituitary adenomas varies according to tumor subtype. Nonfunctioning adenomas are often asymptomatic until after they have extended beyond the sella, causing signs related to tumor enlargement and compression of surrounding structures: visual loss, headache, and hypopituitarism. Most (70%) of the large adenomas causing visual loss are nonfunctioning. In contrast, hypersecreting tumors present more commonly with characteristic endocrine symptoms, described in detail later in the chapter. In all pituitary adenomas, diabetes insipidus at presentation is unusual.
Neuro-Ophthalmic Symptoms and Signs
Chiasmal visual field loss is the most important neuro-ophthalmic manifestation of pituitary adenomas. Usually it is insidious and slowly progressive, and often there is a delay of months or years between the onset of visual loss and diagnosis of the pituitary tumor. Since the chiasm is located directly above the pituitary in most instances, the crossing inferonasal fibers are usually the first to be disturbed by upward-growing adenomas, causing superotemporal defects respecting the vertical meridian. Further tumor enlargement results in more complete interruption of crossing fibers in the body of the chiasm, leading to a complete bitemporal hemianopia. Because of the distance between the diaphragm and the chiasm, only macroadenomas with significant suprasellar extension are associated with field loss. These principles are reflected in the excellent data from a review of 1000 cases by Hollenhorst and Younge who reported that 30% of patients had no visual field abnormalities. Of those with vision loss, superotemporal field defects and bitemporal hemianopias were the most common field defects. Junctional scotomas, central scotomas, and homonymous hemianopias were less frequent, consistent with the lower incidence of post-fixed and prefixed chiasms. More recent prospective studies show that approximately 50% of patients have visual field loss, perhaps reflecting earlier tumor detection by more modern endocrinologic testing and neuroimaging.
Acuity is affected less commonly (estimated between 16–25%) than visual fields; it is typically altered in those with central scotomas or generalized depression. Disc pallor occurs in about 30% of patients and correlates with the presence of decreased visual acuity better than with field loss or the severity of visual loss. Papilledema is unusual unless the adenoma is large enough to cause hydrocephalus and instead suggests other sellar processes which have a greater tendency for causing third ventricular obstruction. Formed visual hallucinations, presumably release phenomena (see Chapter 12 ), have been reported in association with field loss due to pituitary adenomas.
Cavernous sinus invasion, following lateral erosion of the thin sellar wall, may lead to ocular motor palsies (in 1–5% of patients ) or trigeminal dysfunction. However, motility disturbances are much more common with pituitary apoplexy (see later discussion) than with pituitary adenomas. When ocular motor palsies occur, the III nerve is the most commonly affected. Rarely, a III, IV, or VI nerve palsy is the sole presenting feature of the pituitary adenoma. Orbital invasion and extrasellar pituitary adenomas have been reported but are uncommon growth patterns.
Traditionally headaches have been thought not to be caused by pituitary tumors. One prospective series identified headache as the primary reason for presentation in 14% of patients with newly diagnosed pituitary adenomas. However, Levy et al. analyzed a large number of patients with pituitary adenomas and headaches, many of whom improved following medical or surgical treatment of the tumor. Headache types included migraine, trigeminal autonomic cephalgias such as cluster headache, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), and trigeminal neuralgia. SUNCT syndrome occurred usually in association with prolactinomas and GH-secreting adenomas. Large tumor size and cavernous sinus invasion may be but are not always associated with headache, suggesting dural stretching and trigeminal involvement, respectively, were not necessarily the cause.
In 80–95% of microadenomas, a hypointense lesion is evident within the normal pituitary on T1-weighted MRI. A hyperintense region on T1-weighted images usually indicates a hemorrhagic component. Most of the time (75%) the hemorrhage is not associated with clinical apoplexy (see later discussion). In about one-third to one-half of cases, the adenoma is hyperintense on T2-weighted images. Contrast may be helpful if the unenhanced images are equivocal. The various types of adenomas usually cannot be distinguished by MRI, although prolactinomas and GH-secreting adenomas tend to be more lateral, while ACTH, TSH, and LH/FSH-secreting adenomas are usually more midline. This pattern reflects the normal location of the secreting cells.
Macroadenomas share similar MRI signal characteristics but differ morphologically ( Fig. 7.18 ). They are characterized frequently by suprasellar extension, enlargement of the sella turcica, and a dumbbell or figure-eight shape on sagittal and coronal images (caused by the limitations of the bony sella). In some instances there is demonstrable lateral extension into the cavernous sinus. Approximately 20% of macroadenomas may exhibit radiographic evidence of cystic changes, necrosis, or hemorrhage, but only 1% are associated with a history of sudden clinical deterioration (see Pituitary Apoplexy). MRI should be sufficient to outline vascular structures and rule out coexisting aneurysms, so routine angiography is unnecessary in most preoperative assessments. On CT the pituitary adenomas are hypodense compared with the normal gland on both enhanced and unenhanced images. Sellar erosion can be evident on CT with larger adenomas.
Optical coherence tomography (OCT) has demonstrated a strong relationship between vision loss and a decline in RNFL thickness in subjects with pituitary adenomas. RNFL thinning before treatment of these tumors is associated with a poorer prognosis for visual recovery.
Diagnostic Studies/Laboratory Tests
In addition to the MRI, endocrinologic studies are necessary to classify the tumor type and direct treatment (see Box 7.1 ). Abnormal results and their interpretation are outlined in Tables 7.1 and 7.2 .
Treatment . Some generalizations regarding treatment, outcome, and management of pituitary adenomas can be made:
Except for prolactinomas, the first-line treatment of symptomatic adenomas is transsphenoidal neurosurgery. Advantages of this method versus a craniotomy include direct visualization of the pituitary gland and tumor, no external scars, and better tolerance of the surgery even by elderly and medically complicated individuals. Access to the sphenoid is usually via a sublabial or transnasal approach or combinations of both, and tumors are removed with the aid of the operating microscope. When necessary, the sella floor is reconstructed with a plate of nasal bone or cartilage, and the sphenoid sinus is packed with muscle, fat, or Gelfoam. Postoperative diabetes insipidus (usually transient), CSF leak, visual loss, ocular motor nerve palsy, hemorrhage, traumatic aneurysm, and cerebral ischemia are potential complications, but the morbidity and mortality rates are usually very low. At some institutions, the sella is exposed transnasally or transseptally using an endoscope, and the tumor removal is accomplished also endoscopically or with an operating microscope. A pterional or transfrontal approach via craniotomy should be considered when there is extensive extrasellar tumor.
The prognosis for visual improvement is excellent following surgical or medical decompression. Recovery to some degree may occur within days or weeks of treatment ( Fig. 7.19 ). In Trautmann and Laws’ large series of patients who underwent transsphenoidal surgery, approximately half of those with reduced acuity experienced improvement in this parameter, while about three-quarters of those with field loss had restoration or improvement in visual fields. Slightly better results were reported in smaller studies. Prognostic signs which are associated with lack of improvement included optic disc pallor, lengthy delay before diagnosis, and poor visual acuity. Interestingly the degree of visual field loss has no predictive value, as patients with profound field defects still have a reasonable chance for improvement.
External beam radiotherapy is useful in instances of residual or recurrent tumor, but, in general, the clinical effects (e.g., reduced hormone levels) and reduction in tumor size are not seen for months or years. Patients should be informed of the possible late side-effects of radiation, such as chiasmal or optic neuropathy in up to 3%, hypopituitarism, brain parenchymal necrosis, and secondary neoplasms (meningiomas and sarcomatous transformation of the pituitary adenoma). Fortunately, radiation optic neuropathy is becoming less common in this setting. Stereotactic radiosurgery and proton beam radiation allow more precise delivery of radiation to this area with less risk to surrounding tissues.
We recommend a neuro-ophthalmic examination, including visual field testing, within the first few weeks postoperatively, and Klibanski recommends a follow-up MRI at this time to check for residual tumor. Serial neuroimaging and neuro-ophthalmic examinations then can be performed at 1, 6, and 18 months postoperatively, and, if stable, the patient can be discharged after that. Postradiation follow-up can be similar. Follow-up of prolactinomas is slightly different because the primary treatment is medical (see later discussion). However, if surgery or radiation becomes part of the management of a prolactinoma, the mentioned schedule may be applied. Endocrine follow-up is also necessary.
Rarely, a delayed visual loss months or years following transsphenoidal resection without radiation can occur. The visual deficits are slowly progressive, and possible mechanisms include chiasmal prolapse into an empty sella or tethering scar tissue. Some authors have advocated surgical removal of adhesions and repair of the sellar floor. Postoperative pneumatoceles causing visual loss have also been reported.
The Clinical Features and Treatment of Nonfunctioning and Hypersecreting Pituitary Adenomas
Nonfunctioning (nonsecreting) pituitary tumors . These are usually macroadenomas without clinical evidence of pituitary hormone hypersecretion. In one report, visual loss occurred in 72%, hypopituitarism in 61%, headache in 36%, and cranial neuropathies in 10%. Tumor compression of the normal residual pituitary gland or the stalk often leads to loss of normal LH/FSH, ACTH, and TSH secretion along with mild degrees of hyperprolactinemia.
Although classically “nonfunctioning,” immunocytochemical techniques have demonstrated that cells in the majority of these tumors are capable of producing a small amount of hormone, but not enough to elevate serum levels. In one surgical series, 82% percent were null-cell adenomas, while the rest were silent prolactinomas, gonadotropic adenomas, and corticotropic adenomas.
Transsphenoidal tumor removal is the treatment modality of choice. All patients with headache in the series of Ebersold et al. were relieved of this symptom. However, the prognosis for recovery of pituitary function following transsphenoidal surgery of nonfunctioning tumors is fair to good. Because these tumors are nonfunctioning, hormone levels are unhelpful in detecting residual tumor or recurrences. In younger patients with moderate residual tumor postoperatively, local irradiation should be considered. Surgery is the preferred modality when tumors recur following radiotherapy.
Medical options such as bromocriptine (see Prolactinomas) or octreotide (see Growth Hormone–Secreting Pituitary Tumors) are available to patients with nonfunctioning adenomas in whom surgery is contraindicated, or in whom postoperative or postradiation recurrence is documented. The mechanism of action of these medications in this setting is unclear.
Prolactinomas . Prolactin-secreting tumors are the most common hormone-secreting pituitary adenomas. In women, endocrine symptoms caused by prolactinomas include galactorrhea and evidence of gonadal dysfunction such as decreased libido, amenorrhea, oligomenorrhea, or infertility (see Table 7.2 ). In men, diminished libido, gynecomastia, or impotence are the most common manifestations, and galactorrhea is less frequent. Prolactinomas have been reported in childhood and adolescents.
Medical therapy with dopamine agonists, such as bromocriptine and cabergoline, which inhibit the synthesis and secretion of prolactin, are the first-line treatment of prolactinomas. These medications can afford tumor shrinkage and reduction in serum prolactin level in the majority of patients with prolactinomas. Common side-effects include nausea, vomiting, dizziness, and orthostatic hypotension, but sometimes these can be avoided by starting with lower dosages. Cabergoline, now a first-line treatment, needs to be taken only twice a week and is better tolerated than bromocriptine. Moster et al. followed 10 patients with prolactinomas treated with bromocriptine. Improvement in visual acuity and fields and reduction in tumor size occurred in 9 of 10 patients, and in general the salutary effect was sustained. Patients often noticed the visual improvement within days of starting the drug, and subsequent studies have confirmed the potential for rapid visual recovery.
In patients who experience normalization of prolactin levels and whose MRIs show no evidence of residual tumor, cabergoline may be tapered with careful monitoring. However, in many others the medication must be taken indefinitely.
Transsphenoidal surgery of prolactinomas is less effective, as hyperprolactinemia often recurs postoperatively. Radiotherapy alone may reduce tumor mass effect and prevent further growth, but it is generally an ineffective treatment of hyperprolactinemia. Surgery and radiotherapy should be reserved for patients who do not tolerate or who fail medical therapy.
Besser recommends biweekly neuro-ophthalmic follow-up and prolactin levels initially at the start of medical therapy in individuals with compromised vision. Neuroimaging can be repeated in 6 weeks if vision and prolactin levels have improved. Alternatively, repeat neuroimaging should be performed in 2–3 weeks in patients who do not improve, and surgery should be recommended in such cases.
A prolactinoma in the setting of pregnancy is a special situation. During pregnancy, the normal pituitary gland increases in size by 50–70% due to lactotroph hyperplasia, but chiasmal compression is rarely an issue. On the other hand, pregnant women with microprolactinomas have a 1% chance of developing symptomatic pituitary enlargement, but those with macroprolactinomas have a 10–25% chance. Although bromocriptine and cabergoline are probably safe during pregnancy, most experts suggest stopping the medication in women with prolactinomas who become pregnant, and then monitoring visual function carefully. If visual acuity or field abnormalities develop, either continued observation or restarting medication would be reasonable approaches. Finally, transsphenoidal surgery can also be carried out successfully during pregnancy if absolutely necessary.
Growth hormone–secreting pituitary tumors. The mean age of affected patients at diagnosis is 42 years, and approximately half are women. Up to one-third of patients with McCune–Albright syndrome can develop GH-secreting tumors, most of whom have clinical symptoms within the first or second decade of life. Endocrine manifestations are the most common symptom, while visual field defects occur in approximately 20% of patients with this type of tumor. Headaches occur in 55%, but their etiology is unclear because they correlate poorly with tumor size.
Gigantism and acromegaly are the two major medical conditions which result from GH hypersecretion. Characteristic bony and soft-tissue changes occur, primarily owing to GH-induced increases in IGF-1. GH oversecretion in childhood is associated with pituitary gigantism, as in this disorder longitudinal bone growth is still possible. In acromegaly, typified by overgrowth of acral segments (hands, feet, nose, chin, and forehead), epiphyseal closure has already occurred, prohibiting bone elongation. The disfiguring frontal bossing and enlargement of the mandible and hands are characteristic ( Fig. 7.20 ). Because the changes are insidious, patients may notice only a gradual increase in glove or hat size. Furthermore, because acromegaly primarily occurs in middle-aged individuals, the changes are often attributed to “normal aging.” In fact, the delay between onset of symptoms and diagnosis averages 8.7 years.
In addition, bony and soft tissue overgrowth commonly results in carpal tunnel syndrome and other entrapment neuropathies. Myopathy, arthropathy, and depression are also seen in association with acromegaly. Patients with acromegaly have a higher mortality rate than the normal population, due in part to greater frequencies of hypertension, diabetes, cardiovascular disease, hypertrophic cardiomyopathy, upper and lower airway restrictive pulmonary disease, and gastrointestinal malignancies (in the colon, especially) occurring in individuals with this endocrinopathy. GH hypersecretion can also cause ocular hypertension and exophthalmos. Hypogonadism occurs in 30–40%, likely a result of stalk compression and hyperprolactinemia (by inhibiting gonadotropin-releasing hormone secretion). Some GH-secreting adenomas cosecrete prolactin.
Definitive treatment of GH-secreting adenomas is imperative because of their associated disfigurement and increased mortality. Transsphenoidal surgery is the primary treatment, and successful surgery results in a rapid fall in the GH level, although usually not to normal levels. Unfortunately, advanced acromegalic features are rarely reversible, but mild soft tissue enlargement can be reduced.
Surgical, medical, and radiotherapeutic treatment options can be combined in an overall approach to patients with acromegaly. Octreotide, a somatostatin analog, can normalize growth hormone levels and decrease tumor size. Octreotide alone can lead to marked improvement in chiasmal visual field defects. The major side effects are transient diarrhea and nausea, and less frequent ones are gallbladder sludge and asymptomatic gallstones. Melmed’s treatment algorithm is a reasonable one and suggests octreotide before surgery to facilitate removal in patients with tumors >5 mm. A cure is considered a reduction in GH levels to <2 µg/l after an oral glucose challenge. Bromocriptine and cabergoline may be used but are not as effective as octreotide. Cabergoline may be more efficacious than bromocriptine. Pegvisomant, a GH-receptor antagonist, can also be used. Patients with persistently high GH levels despite these measures can be retreated with octreotide or receive radiotherapy. Despite doses of 4000–5000 cGy, radiation can take years to lower GH levels.
Adrenocorticotropin-secreting pituitary tumors (Cushing disease) . These adenomas occur primarily in women of childbearing age, and approximately three-quarters of cases of Cushing syndrome (excess circulating cortisol) are caused by ACTH-secreting pituitary tumors (Cushing disease). Elevated ACTH levels result in adrenocortical hyperplasia and increased secretion of cortisol. Common clinical features include obesity with moon facies and a buffalo hump, hypertension, hirsutism, striae, psychiatric symptoms, gonadal dysfunction, osteopenia, and glucose intolerance. Usually these tumors are microadenomas without extrasellar involvement.
Transsphenoidal removal is the procedure of choice. Radiotherapy can be used in patients with persistent or recurrent disease, but cortisol levels may not be controlled until 1–2 years later. Medical therapy has not proved helpful historically, although recently the use of pasireotide has been proposed as monotherapy for adults with mild to moderate disease. As a last resort, those individuals failing both surgery and radiation are candidates for bilateral adrenalectomy to suppress the hypercortisolism, but this procedure carries significant risk and is associated with a high mortality. Nelson syndrome, characterized by hyperpigmentation, elevated ACTH levels, and an enlarging pituitary gland, is the clinical progression of an ACTH-secreting pituitary adenoma following bilateral adrenalectomy for Cushing disease.
Thyrotropin-secreting pituitary tumors . These are uncommon but occur in two varieties. In the first type, which is really not a tumor per se, primary hypothyroidism leads to compensatory hyperplasia of pituitary thyrotroph cells. In one review, one-third of affected patients developed visual defects (types unspecified) due to pituitary enlargement and chiasmal compression. Reduction in pituitary size and improvement in visual field deficits are often achieved after thyroid replacement.
In contrast, the second type, a thyrotropin-secreting adenoma (thyrotropinoma), is usually associated with thyrotoxicosis due to inappropriate TSH secretion. The diagnosis is established by demonstrating high circulating levels of T3 and T4, normal or elevated TSH, and a pituitary lesion. In Smallridge’s literature review, 54% of affected individuals had abnormal visual fields (again, types unspecified). In general, patients do not develop thyroid-associated ophthalmopathy. Transsphenoidal surgery, followed by radiation if necessary, is the treatment of choice. Thyroidectomy or radioactive iodine controls the hyperthyroidism but not the pituitary enlargement. Octreotide, which can improve chiasmal field defects in this setting, may also be considered.
Gonadotropin-secreting pituitary tumors . Patients with gonadotropin (LH or FSH)-secreting adenomas are typically female and premenopausal and have normal gonadal function. Both genders frequently have headache and vision problems at diagnosis, while women will have menstrual irregularities and men experience testicular enlargement or hypogonadism. In Snyder’s series, 17% of 139 men with pituitary macroadenomas had this type of tumor. In a series of 100 patients from the Mayo Clinic, 43% presented with visual loss, 22% with symptoms of hypopituitarism, and 8% with headache. Hypersecretion of FSH is the most common endocrinologic abnormality. Precocious puberty results when this tumor occurs in childhood. Transsphenoidal surgery usually results in some visual improvement, and octreotide may have a beneficial effect with this type of adenoma as well.
Three other situations related to pituitary adenomas—pituitary apoplexy, metastases to the pituitary, and incidental pituitary adenomas—deserve special mention.
Pituitary apoplexy . This clinical syndrome is characterized by sudden visual loss, headache, and ophthalmoplegia due to rapid expansion of a pituitary adenoma into the suprasellar space and cavernous sinuses ( Fig. 7.21 ). Defined in this way, pituitary apoplexy presents with headache in 95% of cases, vomiting in 69%, ocular motor paresis in 78%, visual field deficits in 64%, and reduction in acuity in 52%. Third nerve palsies are more common than IVth and VIth nerve deficits. When visual loss and headache are the primary symptoms, the condition can be confused with retrobulbar optic neuritis. Alteration in consciousness occurs in 30% of patients due to diencephalic compression, and hypopituitarism, facial pain or numbness, and signs of meningeal irritation (blood or necrotic tumor tissue–induced) are common associated features. Other rare but reported clinical manifestations include retraction nystagmus, presumably due to dorsal midbrain compression, and Horner syndrome caused by interference of the oculosympathetic fibers surrounding the cavernous internal carotid artery. Diabetes insipidus is surprisingly uncommon in this setting. Most affected patients were previously unaware that they harbored a pituitary adenoma. The syndrome is uncommon, and only about 2% of pituitary adenomas will present apoplectically.
Often pituitary apoplexy is the result of extensive tumor infarction or hemorrhage. Although most cases are associated solely with a pituitary adenoma, predisposing factors may include sudden trauma, hypertension, anticoagulation, alteration of pressure gradients (angiography, for example), cardiac surgery, diabetic ketoacidosis, estrogen use, bromocriptine, radiotherapy, and postpartum hemorrhage (Sheehan syndrome).
The clinical suspicion of pituitary apoplexy mandates MRI, as routine CT may miss the lesion. MRI usually demonstrates a macroadenoma with heterogeneous signal characteristics due to the presence of blood, while CT can reveal an unenhancing, hyperdense sellar mass. Hemorrhage, when present, can extend in the subarachnoid space and ventricles. Lumbar puncture may demonstrate an aseptic meningitis, sometimes accompanied by red blood cells. Since the sudden headache and ocular motor palsies associated with pituitary apoplexy may mimic aneurysmal subarachnoid hemorrhage, a CSF hemorrhagic component may warrant angiographic exclusion of an aneurysm if CT or MRI are inconclusive. Transsphenoidal surgery and emergent steroid and other hormonal replacement have facilitated the management of pituitary apoplexy. Some cases improve spontaneously. The prognosis for visual improvement depends more upon early surgical decompression than upon the severity of the visual deficit. One study found that patients with tumor infarction had a slightly better visual prognosis than those with hemorrhage. Almost all patients undergoing surgery within 1 week will experience some improvement in acuity, fields, and ocular motility. A conservative approach may be appropriate for stable or improving patients without visual loss or mental status changes who have a medical contraindication for surgery.
Metastatic tumors to the pituitary . These can have clinical and radiographic presentations similar to nonsecreting pituitary adenomas, except that patients with metastases to the pituitary are more likely to have diabetes insipidus and ocular motor palsies, and a more rapidly evolving clinical course is seen. The most common primary sources are the breast and lung. The pituitary lesion may be the first indication of malignancy, and in these instances patients may undergo transsphenoidal surgery with an incorrect preoperative diagnosis of pituitary adenoma.
Incidental pituitary adenomas . Incidental identification of a pituitary lesion may occur in as many as 10% of patients undergoing neuroimaging for other reasons. All such individuals require endocrinologic screening, but those with macroadenomas also need neuro-ophthalmic evaluation. If endocrine and visual function are normal, neuroradiologic and neuro-ophthalmic assessments can be repeated on a semiannual or annual basis. Surgery would be indicated if there is evidence of tumor compression or growth. Incidentally detected macroadenomas have approximately a one-third chance of enlarging, while only 15% of microadenomas will increase in size.
Craniopharyngiomas are cystic, calcified sellar-region tumors which constitute 1.2–3% of all intracranial neoplasms. They may present at any age, but in various series, the peak age incidence occurred in either the first or second decade of life. Approximately half of all cases are seen in adults, and some present in patients in their sixth decade. They are epithelial in origin and are thought to derive from remnants of Rathke’s pouch, which ordinarily migrates upward from the primitive buccal cavity. Craniopharyngiomas can be found anywhere along the migratory path. Others have suggested that craniopharyngiomas might originate from squamous metaplasia in cells of the adenohypophysis. Although benign in histology, craniopharyngiomas may act aggressively by invading local structures and by recurring despite apparent complete resection.
There are two major histologic subtypes, adamantinomatous and squamous papillary, each with different age predilections that are driven by distinct genetic mutations. Although seen in all age groups, adamantinomatous craniopharyngiomas most often occur in childhood and frequently contain CTNNB1 (β-catenin) mutations. The microscopic appearance is characterized by angulated columnar cells, and keratin nodules and calcification are common. Cysts are present in 90% and are mixed frequently with solid components. The cyst fluid has the consistency of light machinery (“crank-case”) oil and contains suspended cholesterol crystals. Although usually well-defined, adamantinomatous craniopharyngiomas may adhere to surrounding brain and vascular structures. Reactive gliosis and tumor islets may be seen in adjacent brain tissue. These features may, in part, account for recurrences of adamantinomatous craniopharyngiomas despite “total” resection.
Craniopharyngiomas in adulthood tend to be squamous papillary, and nearly all contain BRAF mutations. Calcification, keratin nodule formation, and adamantinous epithelium are conspicuously absent in these tumors. Cysts occur in approximately 50% of cases. Squamous papillary craniopharyngiomas tend to be well demarcated, and after complete resection they tend not to recur.
Location and Growth Characteristics
Craniopharyngiomas may occur in the sella, suprasellar area, or third ventricle. Typically they traverse more than one of these spaces, and entirely intrasellar or intraventricular craniopharyngiomas are unusual. Prechiasmatic tumors, when large, can protrude between the optic nerves and lift the A1 segments of the anterior cerebral arteries. Retrochiasmal tumors can extend posteriorly into the third ventricle and abut the basilar artery and midbrain. Their size may vary from a few millimeters to several centimeters, but the majority of tumors are 2–4 centimeters in greatest diameter. Tumors may be densely adherent to the hypothalamus with small papillary projections. Hydrocephalus, due to third ventricular compression, occurs in approximately 40% of patients presenting with acute symptoms.
Craniopharyngiomas typically disrupt the anterior visual pathways by external compression. However, unusual instances of intrachiasmatic craniopharyngioma, causing chiasmal thickening, have been described. Tumor extension through the optic foramen and canal into the orbit is also rare but has been reported. Other unusual growth patterns include spread beyond the sellar area into the anterior, middle, and posterior fossas. Midbrain, hemispheric, and cerebellopontine angle involvement have also been reported. On rare occasions, ectopic spread can occur.
Fluid leakage, from surgical or spontaneous cyst rupture, can result in a severe chemical arachnoiditis or meningitis. Spontaneous hemorrhage with subarachnoid component is a reported but unusual complication.
Initial manifestations can be grouped into four major categories: visual, endocrinologic, cognitive abnormalities, and headaches. Visual symptoms are usually the most common manifestation, occurring in 52–77% of patients. These and endocrinologic abnormalities are discussed in more detail later in the chapter. Cognitive deficits include personality changes, memory loss, depression, and confusion. Headaches are nonspecific, but are sometimes accompanied by nausea and vomiting. Some authors have touted a varied presentation according to age group, with visual loss and endocrine symptoms seen at all ages, but with headaches and papilledema occurring more frequently in childhood and mental status changes more often in adult cases.
In the series by Repka et al., visual acuity was less than 20/40 in 41% of eyes at presentation, and approximately 15% were worse than 20/400. However, a recent study from the United Kingdom reported 32% of pediatric patients had visual acuity of 20/400 or worse. Bitemporal hemianopias are commonly observed field abnormalities, and asymmetry and incomplete defects appear to be the rule. Homonymous hemianopias, due to optic tract compression, are less frequent. Usually visual impairment occurs gradually, but sudden unilateral or bilateral visual loss, mimicking retrobulbar optic neuritis, has been reported. The majority of patients with visual loss will have optic atrophy. Sixth nerve palsies are common and usually due to third ventricular compression and elevated intracranial pressure, but they can also result from infiltration of the cavernous sinuses. Children may present with comitant or incomitant esotropia. See-saw nystagmus may also be an associated finding.
Some authors have written that children with craniopharyngiomas may be less apt to report visual loss, so visual deficits at presentation may be more severe than in adults. However, not all comparative data support this notion. In one analysis, the difference was not statistically significant. In another series, more children had subnormal acuities, but more adults had visual field deficits.
Common endocrine abnormalities associated with craniopharyngiomas include diabetes insipidus, weight gain, short stature, hypogonadism, myxedema, and somnolence. It is uncertain whether endocrinopathy is more frequent in adults or children, because different series give conflicting results. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) at presentation can occur but is uncommon.
The MRI appearance of craniopharyngiomas is characteristic. They are discrete intrasellar or suprasellar masses which can be hyperintense on T1-weighted images due to increased amounts of cholesterol or protein or hemorrhage. Cysts appear as round masses which are hypointense on T1-weighted images ( Fig. 7.22 ) and hyperintense on T2-weighted images. Areas of signal void within the tumor represent calcification, and on rare occasions the solid component is completely calcified. After administration of gadolinium, the solid portion may exhibit modest enhancement (see Fig. 7.22 ). High signal within the optic tracts and posterior limbs of the internal capsules has been observed with MRI, producing a “moustache” appearance, but resolution of this finding following tumor resection suggests perifocal edema rather than tumor invasion. In some instances MR angiography may be helpful in excluding an aneurysm and defining the tumor’s relationship to vascular structures within the circle of Willis, which can be either displaced or surrounded by the tumor. Conventional invasive angiography, which may demonstrate absence of neovascularity or tumor staining, is rarely necessary.
CT scanning, especially with coronal views, is complementary and often diagnostic when calcification is evident ( Fig. 7.23 ). Cysts and solid components are easily distinguishable, and the solid portions variably enhance after administration of intravenous contrast. Cysts may ring enhance. Calcification within an intrasellar or suprasellar mass on CT is highly characteristic of craniopharyngiomas and occurs in approximately 80% of cases. Thus, preoperatively many authorities would recommend MRI, with its sagittal views and emphasis on anatomic detail, as well as CT.
The primary treatment of craniopharyngiomas is neurosurgical, utilizing microsurgical techniques. Tumors which are primarily intrasellar or subdiaphragmatic may be amenable to transsphenoidal surgery, which offers a lower surgical morbidity. However, the two most common approaches are unilateral pterional and subfrontal craniotomies, which can be combined with a transcallosal approach if the tumor involves the third ventricle, or a transsphenoidal procedure when there is subdiaphragmatic extension. Multiple procedures may be required for complete decompression of large and recurrent tumors. Shunt placement may be necessary when hydrocephalus is present.
Experts disagree whether the best treatment is complete excision or subtotal resection plus radiation. The controversy exists in part because many authors espouse just one treatment approach. Advocates of complete resection argue that modern neuroimaging, microsurgical techniques, and hormonal replacement therapy allow aggressive surgery, and patients are spared the side-effects of radiation. However, extensive surgery can result in debilitating visual, endocrinologic, emotional, sleep, and cognitive deficits and has an operative mortality of 2.5–10%. Accidental tears in the carotid artery, leading to cerebral infarction, have been reported when complete excision was attempted. Furthermore, this approach does not guarantee a cure, as recurrence rates still range from 6–50% despite apparent complete removal.
Proponents of subtotal resection plus external beam radiation readily emphasize a lower rate of operative morbidity and mortality associated with this method of treatment. Given the significant impact of endocrinologic abnormalities on overall health and quality of life, some investigators believe that fewer gross total resections have resulted in improved endocrine outcomes. Postoperative radiotherapy decreases the rate of recurrence and improves patient survival compared with partial removal alone. Craniopharyngiomas that recur after surgery and radiation are especially hard to treat and manage. Radiation doses usually range from 5000–5500 cGy, given in 180 cGy fractions. Unfortunately, dose-related radiation toxicity, manifesting as endocrinopathy, optic neuropathy, vascular events, and secondary malignancies, can occur in approximately 50% of patients treated in this fashion.
Comparisons of the various approaches suggest the following: (1) hypothalamic–pituitary dysfunction occurred least commonly in patients treated with limited excision plus radiotherapy, (2) tumor recurrence rate was similar in children and adults, (3) subtotal resection alone had the highest rate of recurrence, and (4) subtotal resection combined with radiation is associated with a lower recurrence rate than total resection. Metaanalyses, however, show that the recurrence rates for the latter two approaches were similar.
Therefore, based upon these results, the most reasonable approach seems to be to attempt complete resection if possible, especially in young children, in whom radiation is less desirable. Most tumors can be handled in this way. When involvement of visual and endocrine structures precludes complete excision, and when neuroimaging indicates residual tumor following surgery, external beam irradiation should be performed postoperatively. This is the treatment algorithm currently practiced by the neurosurgery service at the Children’s Hospital of Philadelphia.
Another recognized complication of surgery is fusiform enlargement of the supraclinoid internal carotid artery ipsilateral to the surgical approach. The mechanism is thought to be related to surgical manipulation, but the abnormality has no clinical consequences.
Some craniopharyngiomas can be treated with either single dose (e.g., gamma-knife) or fractionated stereotactic radiosurgery, which deliver more concentrated radiation doses within narrower fields. However, these modalities may not be suited for residual perichiasmal tumor. Ideal craniopharyngiomas for stereotactic radiosurgery are smaller than 2.5 cm and are sufficiently distant from the optic chiasm (>5 mm) to limit the chance of chiasmal radiation necrosis. Recently, proton beam therapy has been used to treat craniopharyngiomas. Bishop et al. found equivalent rates of recurrence and toxicity between proton beam therapy and intensity modulated radiation therapy. When cysts recur after subtotal resection, interferon α has been used, but with mixed success.
Although survival in craniopharyngioma is excellent, the visual and endocrinologic complications can be devastating. These are discussed separately.
Visual outcome . Dramatic visual recovery can occur, but in general, the prognosis for visual improvement following therapy for craniopharyngiomas is modest at best and less sanguine than that associated with pituitary adenomas. Optic atrophy was associated with poorer postoperative visual acuities, whereas normal preoperative optic nerve appearance almost always predicted a postoperative visual acuity of 20/30 or better. Adults had a greater chance for improvement in acuity and fields compared with children, and the authors attributed this difference to longer periods of undetected visual loss in younger patients. A poorer visual prognosis in children was confirmed in other series. Based on personal experience, I agree with Repka and Miller that “one should not be optimistic regarding postoperative visual outcome after removal of craniopharyngioma, particularly in children … cautious optimism may be appropriate for some adults, particularly those without ophthalmoscopic evidence of optic atrophy.”
Endocrine outcome . Posttreatment pituitary dysfunction is the rule, usually the result of surgery but occasionally due to radiation. In one series, 74% of patients had diabetes insipidus posttreatment, 100% were growth hormone deficient, 72% had ACTH deficiency, 65% had TSH deficiency, and 93% had gonadotrophin deficiency. Thus, after treatment most patients require some combination of GH, corticosteroid, thyroid, and gonadal steroid replacement and DDAVP. Diabetes insipidus, if not present preoperatively, usually manifests after surgery, sometimes following a transient phase of SIADH. There may be slight improvement, and a minority recover, but most affected patients develop permanent ADH deficiency. Interestingly, even without GH replacement, some patients experience normal or accelerated growth posttreatment, sometimes accompanied by obesity and hyperphagia.
Rathke’s Cleft Cysts
Rathke’s cleft cysts are similar to craniopharyngiomas in derivation, location, and symptoms, but there are some important differences. Although small incidental cysts are found commonly on neuroimaging and in the pars distalis or pars intermedia in 2–26% of routine autopsy cases, symptomatic Rathke’s cleft cysts are unusual. Patients are typically older; the average age at presentation is 41 years. Other dissimilarities, including a better visual prognosis, are highlighted in the following sections.
Rathke’s cleft cysts also originate from Rathke’s pouch, but histopathologically are less complex than craniopharyngiomas. The cysts are lined by a single layer of cuboidal or ciliated columnar epithelium, contain a gold-colored or white serous or mucinous fluid, and do not demonstrate the BRAF mutations known to occur in papillary craniopharyngiomas. Calcification is rare.
Location and Growth Characteristics
Most cysts are intrasellar, and when symptomatic lead to headache and hypopituitarism. A prominent suprasellar component can result in chiasmal compression and hypothalamic dysfunction and, in unusual situations, obstructive hydrocephalus. Rarely, symptomatic Rathke’s cleft cysts are entirely suprasellar.
In one series, the most common presenting symptom was pituitary dysfunction, found in 69% of cases. Hypopituitarism, amenorrhea–galactorrhea, and diabetes insipidus occurred in decreasing order of frequency. Visual disturbances were present in 56% (see later discussion), and headache in 49%. In another large series, Chotai et al. found headache to be the most common presenting symptom, occurring in 76% of patients, while one-third or less had endocrinologic symptoms.
Approximately one-half of patients have visual field deficits, and about one-quarter will have visual acuity loss. Most visual field deficits indicate a chiasmal disturbance (i.e., bitemporal or monocular temporal field abnormalities).
There are two characteristic patterns. Serous lesions are hypodense on CT, and on MRI they are hypointense in T1-weighted images and hyperintense on T2-weighted images, like CSF ( Fig. 7.24 ). On the other hand, mucoid cysts on CT are either isodense or hyperdense compared with brain. On MRI they are hyperintense on T1-weighted images and isointense or hypointense on T2-weighted images. The cyst wall (rim) may enhance, and blood or hemosiderin can also be evident.
Neurosurgical decompression is curative and often affords symptomatic improvement. Because Rathke’s cleft cysts are primarily intrasellar, transsphenoidal drainage and biopsy of the cyst wall is the favored surgical approach. In a large metaanalysis of 1151 patients, Mendelson et al. reported an overall recurrence rate of 12.5%. Associated morbidity and mortality is limited to diabetes insipidus. In one series, headache was cured in all cases in which it was present preoperatively, but endocrine outcomes were variable. Hypopituitarism and diabetes insipidus frequently persist.
In contrast to visual loss associated with craniopharyngiomas, the visual prognosis associated with Rathke’s pouch cysts is excellent following decompression, with over two-thirds experiencing improvement in visual acuity or fields.
Suprasellar Arachnoid Cysts
Suprasellar arachnoid cysts are uncommon lesions, and they are thought to derive from an anomaly in Liliequist’s membrane, either as a diverticulum or as a cleavage within the membrane and CSF secretion into the cavity. On CT and MRI, suprasellar arachnoid cysts contain fluid with neuroimaging characteristics of CSF, and the cyst wall does not enhance. The cysts are usually noncommunicating but in some instances may connect with the basal cisterns. Rare instances of intraluminal hemorrhage may give a cyst a “blue-domed” appearance. Half of cases present before 6 years of age. Improved prenatal imaging has also detected these cysts in-utero. Common clinical features include signs and symptoms of slowly progressive obstructive hydrocephalus, visual impairment, endocrine dysfunction, spasticity, and gait disturbances, but many, particularly in younger children, are asymptomatic. Approximately 10% of patients will have a peculiar to-and-fro head bobbing.
Asymptomatic suprasellar arachnoid cysts can be observed, but in symptomatic cases the treatment is neurosurgical. Endoscopic ventriculocystosomy seems to be the safest and most effective technique. Removal or fenestration via subfrontal craniotomy or fenestration of the cyst into the lateral ventricle and shunt insertion are other options.
Meningiomas of the Skull Base
Meningiomas can affect the chiasm when they arise from the tuberculum sellae, anterior clinoid processes, or diaphragma sellae (see Fig. 7.3 ). Dorsum sellae meningiomas are rare. When they become large enough, juxtasellar and parasellar meningiomas can also cause chiasmal compression, but these are discussed in the chapters dealing with their primary neuro-ophthalmic disturbance: planum sphenoidale, olfactory groove, and optic sheath meningiomas in Chapter 5 and middle and lateral sphenoid wing and cavernous sinus meningiomas in Chapter 15 . This section concentrates on the meningiomas that occur primarily in the suprasellar region, which account for approximately 8% of all intracranial meningiomas.
Meningiomas arise from the arachnoid mater, and in particular suprasellar meningiomas derive from the meninges covering the medial portion of the sphenoid bone, tuberculum, and anterior clinoid processes. They tend to be vascular and firm in consistency. Histologically they are usually of the “classic” variety, characterized by whorls and psammoma bodies. “Classic” subtypes include meningotheliomatous, fibroblastic, transitional, psammomatous, and angiomatous. Other classes of meningiomas, such as angioblastic, are much less common in the sellar region. For the most part meningiomas grow slowly, are benign, and cause dysfunction by compressing adjacent structures. They generally do not invade brain. They can grow exclusively along a dural surface (en plaque meningioma), or a similar flat dural component can be attached to a more clearly defined soft tissue mass (dural tail).
Progesterone and sometimes estrogen receptors can be found in meningiomas. The functional significance of these receptors is not clear, except meningiomas are more common in women than in men, can enlarge during pregnancy and during hormonal replacement, and are associated with breast carcinoma. They are found frequently in patients with NF type II (NF-2) and prior intracranial irradiation. They generally present in middle and older age. Metastases from distant systemic cancers are recognized to spread to meningiomas.
Neuro-Ophthalmic Symptoms and Signs
Painless, progressive visual loss is a feature of almost all symptomatic suprasellar meningiomas, and often it is the only manifestation. The pattern of the visual deficit depends on the exact location of the meningioma in relationship to the optic nerve, chiasm, and tract (see later discussion). Because meningiomas take years to enlarge, visual loss is usually accompanied by optic atrophy. Third ventricular obstruction and papilledema can occur in association with large meningiomas, but big asymmetric tumors involving the optic foramen may instead present with ipsilateral optic disc pallor and contralateral disc swelling (Foster Kennedy syndrome; see Chapter 6 ). Optociliary shunt vessels would be more characteristic of intraorbital optic nerve sheath meningiomas, but in some rare instances they can occur with suprasellar meningiomas, especially those associated with elevated intracranial pressure. Ocular motility deficits, proptosis, and eye pain can result when there is more lateral involvement of the superior orbital fissure or cavernous sinus.
Other Symptoms and Signs
Headache, usually frontal, occurs in about half of patients. Much less frequent symptoms include changes in personality or mentation (due to frontal lobe dysfunction), anosmia, and seizures. Endocrine dysfunction is also uncommon, but when it occurs the symptoms are consistent with hypopituitarism.
On CT meningiomas are round and isodense compared with brain on unenhanced scans, may be partially calcified, and enhance uniformly with contrast ( Fig. 7.25 ). Surrounding cerebral edema may be evident. Hyperostosis, bony erosion, and calcification are best demonstrated by CT. On T1-weighted MRI, meningiomas are usually isointense to gray matter (see Fig. 5.61 ) and less commonly are hypointense. Half the time on T2-weighted images, they remain isointense, while in remaining instances they are hyperintense. Thickening of the dura, a wide dural base, a dural tail, and homogeneous gadolinium enhancement are also characteristic features ( Fig. 7.26 ). MR or conventional angiography may be necessary to outline the tumor’s relationship to vascular structures. Angiography may be necessary in the preoperative evaluation of these meningiomas because large tumors commonly elevate and encase the proximal anterior cerebral arteries. Conventional angiography also may add more information regarding arterial supply and venous drainage, especially if embolization is considered.
Visual loss is the best indication for intervention, which is primarily neurosurgical. In some instances preoperative embolization facilitates removal, given the hypervascularity of these lesions. Pterional or subfrontal craniotomies are the most popular surgical approaches. When the tumor is densely adherent to the internal carotid or anterior cerebral arteries or the anterior visual pathway, a subtotal resection is recommended. Smaller, less-complicated sellar meningiomas may be removed transsphenoidally using endoscopic techniques. External beam radiation (5000–5500 cGy) or gamma-knife stereotactic radiosurgery should be considered when there is residual or recurrent tumor or when surgery is contraindicated.
Alternatively, observation may be the best approach in some cases. Elderly patients or poor operative candidates with mild to minimal visual loss, for instance, may be better off with conservative management. Hormonal therapy may be another option when tumors recur despite surgery or radiation, when they become unresectable because of location, or when these traditional approaches are contraindicated. Experience with suprasellar meningiomas, however, is limited, and some hormonal treatments such as RU-486 are poorly tolerated because of a flulike side-effect.
The chance for visual improvement following neurosurgical decompression is good and only slightly less than that of treated pituitary adenomas. However, this is tempered by the fact that suprasellar meningiomas have a higher risk of recurrence, and their surgical removal is associated with much higher rates of visual loss, morbidity, and mortality. In a large series by Symon and Rosenstein, 64% of patients experienced some improvement in visual acuity or fields, while visual function remained unchanged in 12% and worsened in 24%. Other authors have described similar results. Patients with large tumor size and long-standing or severe visual deficits tend to have the poorest visual prognosis, but those factors do not preclude the chance for some visual recovery following surgery. Radiation alone in some instances can afford visual improvement as well. Symon and Rosenstein found that one-third of partially resected tumors recurred, compared with only 1.4% of completely resected ones. Recurrences typically occurred years (average 3.7 years) after initial therapy and were treated with either radiation or repeat craniotomy.
The three major types of suprasellar meningiomas, tuberculum sellae, anterior clinoidal, and diaphragma sellae, are considered separately in the following sections, as they differ slightly in presentation and treatment. They are named after the bony or meningeal structure from which they arise. There is considerable overlap, and when the tumors are large sometimes the distinction is artificial. The classification, however, is most useful regarding outcome. In general, meningiomas restricted to the tuberculum sellae have a more favorable visual prognosis following surgical decompression. On the other hand, those involving the anterior clinoid and diaphragma sellae are more difficult to remove completely and are associated with higher rates of operative visual loss, postoperative visual deterioration, and surgical morbidity.
Tuberculum sellae meningiomas . The tuberculum sellae lies midline in the sphenoid bone and is anterior and inferior to the chiasm (see Fig. 7.26 ). Classically tuberculum sella meningiomas present in middle age and interfere with the anterior portion of the chiasm, causing asymmetric bitemporal or junctional field defects and optic atrophy. Loss of vision is usually insidious and progressive. Grant and Hedges observed a characteristic pattern: the visual loss was “invariably asymmetric in its progression and accompanied initially by central hemianopic temporal visual field defects. Slowly developing blindness in one eye with diminution of acuity is then accompanied by a temporal field defect in the opposite eye.” This temporal sequence of progressive monocular visual loss followed months later by fellow eye involvement was confirmed by Gregorius et al. In some instances the visual loss may mimic that of retrobulbar optic neuritis or fluctuate. Ocular motor palsies and proptosis are very unusual, reflecting the midline origin of the tumor.
Because of their location, sometimes radical resection of tumor, dura, and bone is possible. Smaller lesions may be amenable to transsphenoidal, endoscopic removal. Surgical morbidity consists of further visual impairment and hypopituitarism, including diabetes insipidus. Operative visual loss is usually the result of interruption of the blood supply of the chiasm or optic nerve. The small surgical mortality is in part due to the risk of pulmonary embolism.
Anterior clinoidal meningiomas . The two anterior clinoid processes lie on the medial ridge of the lesser wings of the sphenoid bone. They look like two triangles pointing toward the back of the head. On each side of the midline, the intracranial and canalicular portions of the optic nerve, and the internal carotid artery, exiting from the cavernous sinus just below the nerve, lie just inferomedial to the anterior clinoid process. Meningiomas of the anterior clinoid can cause either an optic neuropathy or chiasmal disturbance. Foster Kennedy syndrome and superior orbital fissure or cavernous sinus involvement are more common with this type, given its more lateral location. Complete neurosurgical removal may be impossible when the tumor encases either the optic nerve or the internal carotid artery, and adjuvant radiotherapy is required in these instances. Surgical mortality, related to injury of the internal carotid or middle cerebral arteries, can be as high as 42%. Visual recovery in general is poor.
Diaghragma sella meningiomas . A less common type of meningioma in this area arises from the diaphragma sellae. Kinjo et al. presented their personal experience with 12 such patients and reviewed 27 other reported cases. Visual field disturbances are still frequent with this variation. When these meningiomas originate from the diaphragm’s upper leaf, they grow upward into the suprasellar cistern, so their presentation and management is similar to that of other suprasellar meningiomas. Those originating from the lower leaf, when they grow large enough, expand the sella, and can mimic a nonsecreting pituitary adenoma clinically and radiographically. Some of the latter type may be amenable to a combined transsphenoidal-transcranial resection. In either type, however, complete resection may be limited when the tumor encases the chiasm or pituitary stalk.
Because of the intimate relationship of the circle of Willis to the chiasm and sella (see Fig. 7.2 ), large saccular aneurysms in this area can cause chiasmal visual loss and endocrinopathy. In some instances, their presentation may be clinically indistinguishable from a pituitary adenoma or craniopharyngioma.
Aneurysms most likely develop from congenital defects in arterial walls, and pathologically they are characterized by disruption of the media and fibrinoid changes. Arterial bifurcations which are either sharp or give rise to a hypoplastic branch may predispose to development of an aneurysm. In addition, hypertension, hemodynamic stress, smoking, heavy alcohol use, cocaine abuse, and atherosclerosis are modifiable risk factors for their development. Affected patients tend to be female and middle-aged.
Location and Growth Characteristics
Any aneurysm arising from the anterior circle of Willis may compress the chiasm, but chiasmal syndromes are most characteristic of those of the supraclinoid internal carotid artery. These tend to be large (several centimeters in diameter) with upward and medial growth, resulting in compression of the anterolateral portion of the chiasm.
Carotid–ophthalmic artery aneurysms are also frequently associated with chiasmal disturbances. This type of aneurysm arises in the first 2 mm of the internal carotid artery above the cavernous sinus. The overwhelming majority of individuals presenting with visual loss are women. There is up to a 20% incidence of bilateral carotid–ophthalmic aneurysms, and many affected individuals have multiple aneurysms elsewhere. When they enlarge superiorly, they can erode the ipsilateral anterior clinoid process, then grow upward toward the chiasm. Anterior chiasmal compression is the likely cause of visual loss in these instances, and these aneurysms are similar to anterior clinoidal meningiomas in location and associated field defects.
When cavernous or anterior communicating artery aneurysms cause visual loss, the mechanism is usually optic nerve compression. However, less commonly these two types can cause chiasmal disturbances, depending on their growth pattern. For instance, cavernous aneurysms can extend medially to invade the pituitary fossa, then superiorly to compress the chiasm. Anterior communicating aneurysms with downward extension (because the anterior communicating artery is above the chiasm) rarely can encroach upon the chiasm.
Pregnancy may be associated with a higher risk of aneurysmal rupture, with subsequent high rates of morbidity and mortality for both the mother and the fetus. Thus, in their review of the management of a pregnant patient with aneurysmal visual loss, Shutter et al. emphasized that pregnancy should not alter the neurosurgical management of symptomatic ruptured or unruptured aneurysms.
Some individuals have headache, although most patients with visually symptomatic aneurysms in this area will not. Retro-orbital pain is also an occasional accompanying feature. Visual loss and endocrinopathy have already been alluded to and are discussed in more detail later. Although many patients will present with neuro-ophthalmic symptoms, others may present following aneurysmal rupture, and the visual loss is detected at that time. The ocular features of aneurysmal rupture and subarachnoid hemorrhage are discussed in Chapter 6 .
The visual presentation is usually similar to that of other sellar masses, with chronic visual acuity and field loss and optic atrophy. However, the examiner should be alert for the possibility of an aneurysm if the visual loss fluctuates. Sudden worsening or improvement can result from aneurysmal thrombosis or dilation, and acute visual loss might be the result of hemorrhage into the chiasm. In addition, aneurysmal chiasmal disturbances tend to produce very asymmetric field loss. A symmetric bitemporal hemianopia caused by an aneurysm would be unusual and more suggestive of a pituitary adenoma.
Because of their varying location and growth patterns as described previously, the different aneurysmal subtypes are purported to have characteristic patterns of chiasmal visual loss:
Supraclinoid carotid artery aneurysms. These arise from the supraclinoid portion of the internal carotid artery. Visual loss is typically highly asymmetric and sequential, beginning in the ipsilateral eye. Because the aneurysm is lateral to the chiasm, the visual loss in the ipsilateral eye is first nasal, then central and temporal. Vision is usually severely reduced in this eye; then, as the aneurysm enlarges, the crossing nasal fibers of the other eye are affected. The end result is a blind ipsilateral eye and a temporal defect in the fellow eye. Uncommonly the aneurysms compress the chiasm from above rather than from the side. In these cases patients can develop an asymmetric bitemporal hemianopia.
Carotid–ophthalmic aneurysms. In Ferguson and Drake’s series of 100 patients with carotid–ophthalmic aneurysms, which arise from the origin of the ophthalmic artery, 32 (25 of 61 with intact aneurysms, 7 of 39 with ruptured aneurysms) had visual abnormalities. Giant aneurysms (larger than 2.5 cm in diameter) were found in 28 of the 32 patients. Evidence of chiasmal compression was found in 16, based upon the pattern of field loss (3 of the 16 had bilateral aneurysms). The chiasmal field defects fell roughly into two groups: asymmetric bitemporal hemianopias and junctional field loss characterized by severe visual loss in the ipsilateral eye and a temporal field defect in the fellow eye. More recently, Ferrell and colleagues reported a much lower incidence of visual complications from these aneurysms both before and after endovascular embolization. Carotid–ophthalmic aneurysms are discussed further in Chapter 5 .
Cavernous carotid aneurysms. The diagnosis is suggested by signs of cavernous sinus involvement: III, IV, or VI nerve palsies, ipsilateral facial pain or dysesthesias, or Horner syndrome. In the late stages of aneurysmal expansion, optic nerve and pituitary dysfunction may occur. These aneurysms receive more attention in Chapter 15 .
Anterior communicating aneurysms. An aneurysm of the anterior communicating artery or of its junction with an anterior cerebral artery more commonly ruptures before becoming large enough to compress the optic apparatus. When visual loss occurs, monocular or binocular inferior altitudinal defects can be observed because of the aneurysm’s location above the anterior visual pathway. Chiasmal compression and bitemporal hemianopias are rare but can result from an aneurysm of this type growing downward between the optic nerves, then enlarging and forcing the chiasm upward and backward.
Posterior communicating aneurysms. The most common neuro-ophthalmic presentation associated with an aneurysm at the junction of the internal carotid and posterior communicating artery is a pupil-involving III nerve palsy. Visual loss is unusual, because the aneurysm usually points away from the optic pathways. However, when a giant posterior communicating aneurysm projects into the suprasellar region, the optic tract can be involved. Rarely, medial chiasmal compression and a bitemporal hemianopia can be observed. These aneurysms also receive more attention in Chapters 13 and 15 .
The frequency of endocrinopathy has not been well studied, but it is clear that hypopituitarism of varying degrees can occur due to pituitary or stalk compression by an adjacent suprasellar aneurysm. Following treatment, it is interesting that few patients require endocrine replacement, in contrast to those with other types of sellar lesions.
On MRI suprasellar aneurysms will appear as round lesions in this area ( Fig. 7.27 ). The signal characteristics depend on the presence of clot. Nonthrombosed aneurysms have a telltale internal signal void (hypointense on T1) produced by rapid blood flow and disappearance of protons before they have a chance to emit a signal. Aneurysmal blood flow can also cause a characteristic phase-encoded artifact which runs through the aneurysm and across the image. Partially thrombosed aneurysms contain clot which can appear laminated and bright on T1- and T2-weighted images, mixed with areas of signal void. Hemosiderin, evident as dark areas on T2-weighted images, may be visible outside of the aneurysm in adjacent tissues. Gradient-echo images may be helpful in demonstrating intraluminal flow in equivocal cases.