Ординатура / Офтальмология / Английские материалы / Neuro-Ophthalmology_Kidd, Newman, Biousse_2008

122.Klonoff D, Kahn D, Rosenzweig W, Wilson C: Hyperprolactinemia in a patient with a pituitary and ovarian dermoid tumor: case report. Neurosurgery 1990;26:335–339.

123.Cohen JE, Abdallah JA, Garrote M: Massive rupture of suprasellar dermoid cyst into ventricles. Case illustration. J Neurosurg 1997;87:963.

124.Albright L, Lee PA: Neurosurgical treatment of hypothalamic hamartomas causing precocious puberty. J Neurosurg 1993;78:77–82.

125.Asa S, Kovacs K, Tindall G, et al: Cushing’s disease associated with an intrasellar gangliocytoma producing corticotropin-releasing factor. Ann Intern Med 1984;101:789–793.

126.Towfighi J, Salam M, McLendon R, et al: Ganglion cell-containing tumors of the pituitary gland. Arch Pathol Lab Med 1996;120:369–377.

127.Asa S, Bilbao J, Kovacs K, Linfoot J: Hypothalamic neuronal hamartoma associated with pituitary growth hormone cell adenoma and acromegaly. Acta Neuropathol (Berlin) 1980;52:231–234.

128.Saeger W, Puchner M, Lu¨decke D: Combined sellar gangliocytoma and pituitary adenoma in acromegaly or Cushing’s disease. Virchows Arch Pathol Anat 1994;425:93–99.

129.Horvath E, Kovacs K, Scheithauer BW, et al: Pituitary adenoma with neuronal choristoma (PANCH): Composite lesion or lineage infidelity? Ultrastruct Pathol 1994;18:565–574.

130.Scheithauer BW, Kovacs K, Randall RV, et al: Hypothalamic neuronal hamartoma and adenohypophyseal neuronal: Their association with growth hormone adenoma of the pituitary gland. J Neuropathol Exp Neurol 1983;42:633–648.

131.Asa SL, Scheithauer BW, Bilbao J, et al: A case for hypothalamic acromegaly: A clinicopathologic study of six patients with hypothalamic gangliocytomas producing growth hormone releasing factor. J Clin Endocrinol Metab 1984;59:796–803.

132.Weisberg LA, Housepian EM, Saur DP: Empty sella syndrome as complication of benign intracranial hypertension. J Neurosurg 1975;43:177–180.

133.Neelon FA, Goree JA, Lebovitz HE: The primary empty sella: clinical and radiographic characteristics and endocrine function. Medicine (Baltimore) 1973;52:73–92.

134.Gharib H, Frey HM, Laws ER Jr, et al: Coexistent primary empty sella syndrome and hyperprolactinemia. Report of 11 cases. Arch Intern Med 1983;143:1383–1386.

135.Weisberg LA, Zimmerman EA, Frantz AG: Diagnosis and evaluation of patients with an enlarged sella turcica. Am J Med 1976;61:590–596.

136.Applebaum EL, Desai NM: Primary empty sella syndrome with CSF rhinorrhea. JAMA 1980;244:1606–1608.

137.Garcia-Uria J, Ley L, Parajon A, Bravo G: Spontaneous cerebrospinal fluid fistulae associated with empty sellae: Surgical treatment and long-term results. Neurosurgery 1999;45:766–773; discussion 773–774.

138.Welch K, Stears JC: Chiasmapexy for the correction of traction on the optic nerves and chiasm associated with their descent into an empty sella turcica. Case report. J Neurosurg 1971;35:760–764.

139.Scholtz C, Siu K: Melanoma of the pituitary. J Neurosurg 1976;45:101–103.

140.Copeland D, Sink J, Seigler H: Primary intracranial melanoma presenting as a suprasellar tumor. Neurosurgery 1980;6:542–545.

141.Nagatoni M, Mori M, Takomoto N, et al: Primary myxoma in the pituitary fossa: Case report. Neurosurgery 1987;20:329–331.

142.Branch CL, Laws ERJ: Metastatic tumors of the sellar turcica masquerading as primary pituitary tumors. J Clin Endocrinol Metab 1987;65:469–474.

143.Morita A, Meyer FB, Laws ER Jr: Symptomatic pituitary metastases. J Neurosurg 1998;89:69–73.

144.Dhanani A-N, Bilbao J, Kovacs K: Multiple myeloma presenting as a sellar plasmacytoma and mimicking a pituitary tumor: Report of a case and review of the literature. Endocr Pathol 1990;1:245–248.

145.Berger SA, Edberg SC, David G: Infectious disease of the sella turcica. Rev Infect Dis 1986;8:747–755.

146.Domingue JN, Wilson CB: Pituitary abscesses. Report of seven cases and review of the literature. J Neurosurg 1977;46:601–608.

147.Jain KC, Varma A, Mahapatra AK: Pituitary abscess: A series of six cases. Br J Neurosurg 1997;11(2):139–143.

148.Kroppenstedt SN, Liebig T, Mueller W, et al: Secondary abscess formation in pituitary adenoma after tooth extraction. Case report. J Neurosurg 2001;94:335–338.

177.Paramo C, de L, Nodar A, Miramontes S, et al: Intrasellar tuberculoma—A difficult diagnosis. Infection 2002;30(1):35–37.

178.Patankar T, Patkar D, Bunting T, et al: Imaging in pituitary tuberculosis. Clin Imaging 2000; 24(2):89–92.

179.Sharma MC, Arora R, Mahapatra AK, et al: Intrasellar tuberculoma—An enigmatic pituitary infection: A series of 18 cases. Clin Neurol Neurosurg 2000;102(2):72–77.

180.Ramos-Gabatin A, Jordan RM: Primary pituitary aspergillosis responding to transsphenoidal surgery and combined therapy with amphotericin-B and 5-fluorocytosine: case report. J Neurosurg 1981;54:839–841.

181.Endo T, Numagami Y, Jokura H, et al: Aspergillus parasellar abscess mimicking radiationinduced neuropathy. Case report. Surg Neurol 2001;56:195–200.

182.Heary RF, Maniker AH, Wolansky LJ: Candidal pituitary abscess: Case report. Neurosurgery 1995;36:1009–1012; discussion 1012–1013.

183.Del Brutto O, Guevara J, Sotelo J: Intrasellar cysticercosis. J Neurosurg 1988;69:58–60.

184.Osgen T, Bertan V, Kansu T, Akalin S: Intrasellar hydatid cyst. Case report. J Neurosurg 1984;60:647–648.

185.Sano T, Kovacs K, Scheithauer BW, et al: Pituitary pathology in acquired immunodeficiency syndrome. Arch Pathol Lab Med 1989;113:1066–1070.

186.Kidd D, Revesz TR, Miller NR: Neurological complications of Rosai-Dorfman disease. Neurology 2006;67:1551–1555.

187.Lachenal F, Cotton F, Desmurs-Clavel H, et al: Neurological manifestations and neuroradiological presentation of Erdheim-Chester disease: Report of six cases and systematic review of the literature. J Neurol 2006;253:1267–1277.

11 Pupillary Disorders

FION D. BREMNER

Key Points

Careful examination of the pupil is an invaluable exercise, potentially providing information about function in both sympathetic and parasympathetic branches of the autonomic nervous system, the anterior visual pathways, and the upper midbrain.

Autonomic disturbances generally affect both the size and the responsiveness of the pupil and may be confirmed using simple pharmacologic tests.

Damage to the retina or pregeniculate anterior visual pathways has little or no effect on resting pupil diameter but attenuates the pupillary response to light. Unilateral or asymmetric damage gives rise to a relative afferent pupillary defect (RAPD).

When the pupil signs are not easily explained by the neurologic workup, it is advisable to seek the opinion of an ophthalmologist to look for a local cause within the eye.

The Normal Pupil

The pupil is the diaphragm in the eye through which light enters: It regulates retinal exposure and affects depth of field and optical artefact in much the same way as the aperture stop in a camera. The size of the pupil is determined by the tone in two opposing smooth muscles. The iris sphincter muscle has circular fibers, which lie close to the pupil margin: Activation of its muscarinic (mainly M3) cholinoceptors causes constriction or miosis of the pupil. The iris dilator muscle has radial fibers, which lie within the midperiphery of the iris stroma: Activation of its noradrenergic (mainly a-1) adrenoceptors causes dilation or mydriasis of the pupil. The fibers of both muscles express a number of other receptors on their surfaces including adrenoceptors on sphincter fibers and cholinoceptors on dilator fibers: These probably contribute to reciprocal inhibition but are not of any apparent clinical importance.

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Figure 11–2 Diagram to illustrate the neural pathways underlying the pupil light reflex. Direct response (continuous arrows), consensual response (dashed arrows). CG, ciliary ganglion; EWN, Edinger-Westphal nucleus; N, nasal retina; OC, optic chiasm; PC, posterior commissure; PTN, pretectal nucleus; T, temporal retina.

arc have large receptive fields but small cell bodies and are distributed throughout the retina, with slightly greater density in the macula; it is not known if these cells form a separate population to those serving visual perception (i.e., the retino- geniculo-cortical projection). Their myelinated axons pass along the optic nerves, traverse the optic chiasm with decussation of the nasal fibers, and then continue along the optic tracts leaving just before the lateral geniculate nucleus to terminate in both ipsilateral and contralateral pretectal nuclei. Pretectal neurons emerging from these nuclei project to both the ipsilateral and, via a decussation in the posterior commissure, contralateral Edinger-Westphal nuclei and stimulate bilateral pupillary constriction. A bright light shone in one eye will therefore cause constriction of the ipsilateral pupil (direct response) and the contralateral pupil (consensual response) (Fig. 11–3); both direct and consensual responses occur relatively quickly (reflex latency lies in the range 200 to 500 milliseconds,

varying inversely with light intensity), briskly (constriction should be rapid), and symmetrically (direct responses are often slightly greater in amplitude but this “contraction anisocoria”3 is rarely detectable on clinical examination of healthy subjects). The briskness and extent of the pupil response to a bright light varies considerably between healthy subjects and depends on a number of factors including the starting diameter (larger pupils show bigger responses) and alertness. It has been suggested that iris color and age4 are important, but this has not been established conclusively.

If the light stimulus is rapidly alternated between the eyes (the “swinging flashlight test”5), both pupils remain maximally miosed with little or no “escape” as the light is moved from side to side. The observation of miosis on presenting the light stimulus to one eye but mydriasis when moving the stimulus to the other eye indicates less pupillomotor drive from the latter eye, that is, a relative afferent pupillary defect (RAPD). A false-positive RAPD may be seen in the absence of an anterior visual pathway lesion if the light stimulus is projected away from the macula in one but not both eyes (e.g., in cases of manifest strabismus) or if there is significant anisocoria (less light enters the eye with the smaller pupil). The execution of a swinging flashlight test and its interpretation therefore require considerable experience and are discussed later.

In addition to ambient light levels, pupil size is determined by the accommodative state of the subject. When attempting to view a near object, the healthy subject uses a synergistic triad of convergence, miosis, and accommodation. The degree of pupillary miosis is related to the proximity of the object and the

degree of accommodative effort exerted by the subject. The near response can be elicited even in blind patients by asking them to look at the tip of their own finger held before their eyes. Healthy subjects with a myopic refraction, presbyopic individuals, or individuals with poor motivation may show little or no near response, and so failure to elicit a convincing pupillary constriction when the subject is made to look at a near target does not always indicate pathology. When present this near response is normally brisk but of smaller amplitude than the light response (Fig. 11–4), that is, light-near dissociation (greater miosis during a near effort than that achieved with the brightest light stimulus) is rarely seen in healthy subjects.

The level of alertness of a subject has a profound influence on the pupil. When asleep, our pupils are miosed and show diminished responses to light; the more awake we are, the bigger and more responsive our pupils become. The relationship between pupil size and arousal has been known for centuries: Women in 16th century Venice used the extract of Atropa belladonna (atropine) to dilate the pupils and make them look youthful and more “interested” in their suitors, and in China jade dealers used to watch for pupillary dilation as a sign to raise the price when bartering a price for their goods. Reflex dilation of the pupil can be observed in normal subjects around 1 second after a sudden “wake-up” noise such as a loud bang: This “startle” response is generated mainly by central inhibition of the Edinger-Westphal nucleus and activation of the peripheral sympathetic supply, although circulating adrenaline may also contribute with more continuous stimulation. If instead, a subject is allowed to become

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drowsy, for example, by placing him or her in a darkened, warm room, the pupils gradually miose over the course of 10 to 20 minutes, and superimposed on this progressive miosis the pupils are seen to oscillate in size. These so-called fatigue waves are very slow (frequency < 0.5 Hz) but of increasing amplitude (reaching several millimeters excursion from peak to trough in some individuals) and have been used as an objective and quantifiable index of fatigue in some experimental studies.6

An understanding of the pharmacology of the pupil is important in its clinical evaluation. Normal pupils respond symmetrically to topically applied receptor agonists such as phenylephrine 2.5% to 10% (producing mydriasis) or pilocarpine 1% to 4% (producing miosis) with maximum effect after 30 to 45 minutes. Supersensitivity, defined as an enhanced response to a receptor agonist at a concentration that has little or no effect on the size of a normal pupil (e.g., 1% phenylephrine, 0.5% to 1% apraclonidine, or 0.1% pilocarpine), indicates muscle denervation (e.g., Horner’s syndrome), muscle disuse atrophy (e.g., long-standing bilateral blindness), or increased drug penetration into the eye (e.g., dry eyes). In contrast, failure of the pupil to respond to a normal concentration of a receptor agonist indicates receptor blockade (e.g., inadvertent atropinization by jimson weed), although the clinician must be confident that the test drug got into the eye and was not “squeezed out” by an unwilling subject. A number of indirect sympathomimetic agents are also useful in evaluating Horner’s syndrome. Cocaine (4% to 10%) blocks the active reuptake process for noradrenaline at sympathetic neuroeffector junctions in the dilator muscle and so increases the concentration of endogenous agonist at the receptors causing dilation of the normal pupil; failure of the pupil to dilate following cocaine administration indicates oculosympathetic palsy (Horner’s syndrome), but the test has no localizing value. One percent hydroxyamphetamine, 0.5% pholedrine, or 2.5% tyramine all displace noradrenaline from its storage vesicles in the sympathetic nerve endings and so may be used to test the integrity of the postganglionic sympathetic neuron, dilating the normal pupil and the pupils of patients with preganglionic Horner’s syndrome but not those with postganglionic lesions.

A number of caveats apply to correct interpretation of pharmacologic tests of the pupil. First, the effect and duration of action of many drugs depend on iris color because of melanin binding.7 For this reason it is advisable that the clinician allows at least 48 hours “wash-out” time between sequential drug tests to be certain the effects have worn off. Second, the sensitivity of pharmacologic tests in the detection of pupil abnormality is much greater when the lesion is unilateral; in conditions giving rise to bilateral symmetrical sympathetic or parasympathetic blockade (e.g., patients with generalized autonomic failure) it is sometimes not possible to use drug testing to make a diagnosis. Finally, drug responses depend critically on drug penetration; patients with dry eyes may give false-positive results following instillation of weak receptor agonists because of greater penetration of the drug into the eye.8

The Abnormal Pupil

There is a wide range of pupil abnormalities seen in clinical practice, reflecting the many parts of the central and peripheral nervous systems that influence the