Ординатура / Офтальмология / Английские материалы / Clinical Neuro-ophthalmology A Practical Guide_Schiefer, Wilhelm , Hart_2007

Poster 5.1

procedure is the same as with the cocaine test, except that the pupils are measured 45 min after the administration of the drops. The mydriatic effect matches that effect found with cocaine testing. If the unaffected pupil dilates well and the affected pupil dilates by 0.5 mm or less, the loss of adrenergic function of the affected pupil can be attributed with confidence to damage to the third (terminal) neuron of the sympathetic pathway, i.e., at or above the ganglion cervicale superius of the sympathetic chain.

• Pearl

If the affected pupil dilates as well or better than its contralateral partner, the site of damage lies somewhere below the level of the ganglion cervicale superius, i.e., in the firstor second-order neurons of the sympathetic pathway.

Lower concentrations of phenylephrine (about 2%) are well suited to the pharmacologic detection of weakened pupillary dilators. Among infants, one often finds an anisocoria with normal pupillary light reactions and no ptosis that persists after instillation of topical cocaine. If the anisocoria persists after instillation of 2.5% solution of phenylephrine, it can be concluded that the dilator of the smaller pupil is probably hypoplastic. This is a benign disorder not associated with any other abnormalities of anterior segment development, and it commonly normalizes with the passage of time.

Unilateral or Bilateral Disturbances of Pupillary Light Reactions

Testing the Near Reaction

The near reaction must be tested when there is a unilateral or bilateral abnormality of the pupillary light reaction.

pupillary near reaction. An exception may be the pupillary disturbances found associated with botulism or diphtheria, in which accommodation and the pupillary near response are significantly more affected than is the light reaction. Nonetheless, the pupillary light response is not normal in this setting.

When testing the pupillary near reaction, the level of illumination should be bright enough that the pupils can be easily seen, and an object with fine surface detail (to encourage accommodation) is slowly brought toward the eye.

:Definition

Pupillary testing results most often show that the light and near reactions of the pupil are equally impaired or preserved. In some cases, the near response will be found better preserved than the reaction to light. The latter state is called light-near dissociation.

Oculomotor Testing

A monocular defect in the light response of the pupil raises the question of a third nerve paresis (see Chap. 10), while bilateral deficits can be associated with vertical gaze palsies, such as in Parinaud’s syndrome (see Chap. 11).

Slit-Lamp Examination

The slit lamp allows close examination of the anatomy of the pupil and iris, particularly with respect to evidence of sphincter atrophy or traumatic disruption. The examiner should note whether the sphincter shows spontaneous movements, whether a strong light stimulus produces a correspondingly large response of contraction, whether some segments of the sphincter move more strongly than

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Video 5.5 Video 5.4

When preganglionic pharmacologic testing is positive:

λEvaluation by an internist and a neurologist,

and neuroradiologic evaluation for cases in which there are additional signs and symptoms

When postganglionic pharmacologic testing is positive:

λIf the problem is isolated and not acute, seek a history of cluster headaches or migraine

λWhen additional cranial nerves are involved, or the problem is acute, refer for MRI or CT

When the problem is congenital or infantile: λ Rule out neuroblastoma

have failed to detect a cause (■ Table 5.2). Monitoring of the patient’s findings for changes in signs or the onset of additional symptoms is recommended. Any significant change should be cause for a renewed attempt at localizing the site of damage, since there are disorders that can respond to interventional treatment.

!Note

It is important, however, to keep in mind that acute and painful onset of Horner’s syndrome is the classic presentation of a carotid artery dissection of the carotid artery, which can occur spontaneously or after minor trauma. It has been associated at times with chiropractic manipulation of the neck. The risk of stroke in these patients is very high, and correct management involves immediate anticoagulation. Patients with this syndrome are commonly tall and slender people, and there is an association with connective tissue disorders like Ehlers-Danlos syndrome.

A singular form of Horner’s syndrome is the congenital or infantile onset. Hydroxyamphetamine testing is not usually helpful, since trans-synaptic degeneration can affect the third-order neuron, even though the lesion may lie upstream in the first or second-order neurons. In such cases, the drug may not cause pupillary dilation. In addition, there is usually a visible heterochromia iridis, since development of the iris pigmentation requires an intact sympathetic innervation. The affected eye appears bluer. In addition, in adults with Horner’s syndrome, depigmentation of the iris can occur over a period of years.

• Pearl

Horner’s syndrome in children is most trauma. Another less common but cause is neuroblastoma, which should

out.

Syndrome

syndrome is a usually monocular loss of innervation of the eye. The site of ciliary ganglion or in the short poste-

rior ciliary nerves.

The tonic pupil presents a frequent diagnostic problem, since it is common and does not have a single, typical appearance. It commonly leads to extensive diagnostic testing that fails to identify the source and causes the patient considerable anxiety. Once the diagnosis has been correctly established, further testing is only occasionally necessary.

Most commonly, the affected patients are women between 30 and 40 years of age. However, it can occur at any age. In a few cases, the cause can be established, or at least confidently suspected, e.g., after orbital trauma, extensive panretinal photocoagulation, outbreaks of varicella zoster, orbital ischemia with active giant cell arteritis, and only rarely associated with a malignancy and a suspected paraneoplastic syndrome.

Typically, though, the tonic pupil is harmless. In most instances it is idiopathic (has no identifiable cause). It is frequently associated with a loss of deep tendon reflexes (Adie-Holmes’ syndrome), or less commonly with sudomotor disturbances (Ross syndrome) or with vascular disease. None of these idiopathic types of tonic pupil is so severe as to cause the patient significant loss of visual function.

• Pearl

Presentation of an acutely tonic pupil in patients over 50 years of age should lead to testing of the erythrocyte sedimentation rate or of C-reactive protein levels, since giant cell arteritis can present in this way.

In rare cases, there have been (possibly coincidental) associations with malignant disorders. Being so very uncommon, this possibility does not require diagnostic testing in most cases. It does help to be aware of the risk, however, and to plan accordingly. Patients with a history of breast carcinoma, for instance, should have an imaging procedure to rule out an orbital metastasis.

see also Video 5.4

see also Video 5.5

Chapter 5 H. Wilhelm, B. Wilhelm

Fig. 5.6. Oculomotor nerve paralysis with pupillary involvement (a) is closely associated with aneurysms (b) and tumors. The parasympathetic fibers lie on the exterior surface of the nerve (c, arrow) exposing them to damage when the oculomotor nerve is compromised by an external mass effect

company with a progressive loss of third nerve function, it is referred to as primary aberrancy. This is most often a sign

of a slowly growing mass lesion in the cavernous sinus. An 10.7 uncommon variant of this presentation includes a com-also bined sixth and third nerve paralysis with signs of aberrant Video movement and simultaneous constriction of the pupil onsee attempted abduction.

Lesions of the Dorsal Midbrain:

Parinaud’s Syndrome

:Definition

Damage to the pretectal region of the dorsal midbrain producing a deficit in the light reactions of the pupil, retained accommodative miosis, and loss of connection to the Edinger-Westphal nucleus and the final common pathway of third nerve function. The clinical presentation of this syndrome includes loss of upward saccadic movements, and convergence retraction nystagmus. The entire constellation of signs is referred to as Parinaud’s syndrome (see Chap. 11).

The cause is most commonly a pinealoma with compression of the quadrigeminal plate from above, also causing obstruction of cerebral spinal fluid flow and signs of papilledema. Lesions arising within the midbrain (usually among older patients) are usually ischemic in nature and can cause more widespread damage, with complex neurological deficits.

• Pearl

Detection of the clinical signs of this syndrome mandates imaging of the midbrain and the surrounding structures.

Fig. 5.7. Datura suaveolens, D. aurea and D. candida may cause dilated pupils because they contain scopolamine

Uncommon Pupillary Disturbances

Argyll-Robertson Pupils

Argyll-Robertson pupils are characterized by bilateral miosis, no responses to light stimuli, a preserved near response, and little or no response to mydriatics. They have been reported in cases in the late stages of tertiary neurosyphilis. We have seen many cases that mimic this appearance, but in which segmental pupil sphincter activity clearly labeled them as long-standing cases of tonic pupillary syndrome. Serological tests for luetic disease were negative in all instances. In those cases that suggest the diagnosis of ArgyllRobertson pupils, a fluorescent treponemal antibody absorption test (FTA-abs) test should be done, although the probability of a positive finding is low.

Intermittent Mydriasis

:Definition

Intermittent mydriasis appears as an abrupt enlargement of the pupil, lasting 5 to 60 min, and it is unassociated with signs of visual loss.

The diagnosis of intermittent mydriasis (■ Table 5.3) is complicated by the absence of findings at the time of the examination, including normal pharmacologic tests of pupil function. It is very unlikely that these episodes will be linked to any credible threat to the patient’s vision. When

a sign of a compressive lesion. The patient should be instructed to keep records during subsequent episodes, detailing changes in the light reaction, the interpalpebral lid fissure, and the near response, which can be done with the help of a member of the patient’s family. If the initial findings suggest a parasympathetic paresis, further study should be done, using the same tests as for an oculomotor paralysis. Neuroradiologic diagnosis by MRI, including gadolinium enhancement and MRI angiography, is the preferred test. The probability of an aneurysm being the cause is very low, as long as the mydriasis is not associated with signs of oculomotor paralysis. Cerebral angiography should be considered, if there are signs of paresis of the extraocular muscles. Sometimes the eye with the smaller pupil is the problem, as in Horner’s syndrome.

Tadpole-Shaped Pupil

If hypersympathetic activity affects only a portion of the pupillary dilators, the pupil loses its normal, circular shape. The result is an irregular oval shape or a circle with a narrow segment that extends in the direction of the affected dilators, producing a shape that has been likened to that of a tadpole. This variant is not common, but it is occasionally described by affected patients. The basis for this behavior is unknown, but it is often encountered in patients with a prior history of migraine. If the ophthalmic examination is normal between episodes, it is not necessary to do any additional workup, as this phenomenon is thought to be benign.

Paradoxical Pupils

A paradoxical pupillary response to a light (constriction in the dark) has been associated with heredofamilial retinal dystrophies. In our experience, this condition is rare.

Congenital Miosis and Persistent Mydriasis

Two anomalies of pupillary size are of clinical importance, one is congenital miosis, and the other is a persistent mydriasis that develops during the second or third decade of age. Congenital miosis is associated with tapetoretinal degenerations but can be an isolated finding. An asymmetric mydriasis, acquired in adults, has been reported in a large group of patients in Labrador and is probably hereditary.

Normal Pupil Size?

The variance of normal pupil sizes is very large. It is practically impossible to establish limiting values for normal pupil sizes. In addition, pupil sizes change with age. Starting at puberty, the pupils have a steady rate of decrease in pupil size that averages 0.04 mm/year. This is presumed caused by a steady decrease in the centrally controlled level of sympathetic activity. In general, older people consequently have smaller pupils than do younger people.

Medications and drugs that affect autonomic neural activity can change the pupil’s diameter. The normal range of pupil diameters is so large that they have little diagnostic meaning. The effects of systemic medications are always bilateral. Opiates produce a marked miosis.

Occasionally patients have bilaterally large pupils that respond poorly to light, without there being any other signs of pathology. In these cases, the tonus of sympathetic activity is markedly elevated, most commonly caused by anxiety. Later during the examination, the pupils will often revert to their usual size, as the patient becomes more comfortable with the situation.

Control of the Pupil’s Size

The resting diameter of the pupil is primarily (and in the dark exclusively) controlled by the central level of sympathetic activity. Strong emotional states produce a mydriasis that can be impressive. Sympathetic regulation of the pupil size acts by stimulating the smooth muscle cells of the dilator pupillae muscle. This muscle is, however, a weak opponent of the much stronger parasympathetic sphincter muscle, which is controlled by central inhibition of parasympathetic activity. This arises from neurons in the brainstem that are noradrenergically controlled by a center in the hypothalamus. The second channel of inhibition arises in the locus ceruleus (which also controls the phases of sleep) and reaches the Edinger-Westphal nucleus in the oculomotor complex. Currently the neurotransmitter is thought to be gamma-aminobutyric acid (GABA). The sympathetic effect on the pupil thus involves a direct stimulus of the

pupillary dilator muscle and a dual channel of inhibition to the iris sphincter.

Oscillations of the Pupil

The size of the pupil under all conditions of illumination has continuous oscillatory movements. These are often not visible to the naked eye. When visible, they are often said to show a state of pupillary unrest. This is a physiologic phenomenon. In the past, and still used in current publications, this has been called hippus (from the Greek word for “horse”). This is an unfortunate term, since it refers to a highly variable phenomenon that is not well defined. A better term would be spontaneous pupillary oscillations. There are two principal forms, light-induced and vigilancedependent pupillary oscillations.

Light-Induced Pupillary Oscillations

Oscillatory variations in pupil size are thought to be a characteristic of the regulatory mechanism. At low levels of light, the light-induced oscillations are most apparent. The amplitude and frequency of these oscillations varies considerably in the same person and in comparisons between all members of any group. They can be barely visible or very striking. There are no normative values for physiologic, light-induced pupillary unrest. For this reason, it makes no sense to attempt to quantify the oscillations. True, particularly large amplitude oscillations can be seen in life-threat- ening circumstances, such as in Cheyne-Stokes breathing. However, such striking oscillations by themselves are never a sign of serious illness. Anxious patients are sometimes bothered by oscillations of the pupil, mistakenly assuming they are a sign of serious disease. They can be relieved with a simple explanation that the phenomenon is normal.

Vigilance-Dependent Pupillary Oscillations

(“Sleepiness Waves”)

When one is sleepy and in the dark, the pupil acquires a slow (<1 Hz) oscillation, with an amplitude of up to several millimeters. These oscillations can often be seen in a drowsy patient during an ophthalmic examination in a darkened room, and they are striking in their appearance. They are usually obscured by light-induced oscillations, as long as there is some light in the room. In recent years, the phenomenon of sleepiness waves has been used as an objective method for measuring daytime sleepiness. Registration of pupillary oscillations in the pupillographic sleepiness test is

Fig. 5.8. Pupillary behavior, recorded over a 10.5-min period, in a patient with sleep apnea syndrome. In the third minute, slow oscillations of the pupil’s diameter appear and then gradually increase.

This is an objective sign of a strong, soporific effect. The diagram to the right gives the average pupillary diameter for each time unit of recording

done by infrared pupillography (■ Fig. 5.8). The sleepiness waves become more prominent in healthy people when they are sleep deprived (■ Fig. 5.8). The fatigue-related oscillations subside if the daytime sleepiness is reduced.

Sleepiness waves stem from the decreasing sympathetic tonus that accompanies fatigue, and they are a direct expression of the level of central nervous system activity. The abovementioned sympathetic inhibition of the EdingerWestphal nucleus diminishes and becomes unstable. The pupil’s diameter diminishes and wide swings of dilation and constriction appear.

Conclusion

Testing the pupil’s reactions to photic and accommodative stimuli is a key part of any ophthalmic examination. They require little effort and often bring out important facts relative to the patient’s vision and health. Without exception, disorders of pupillomotor function should be evaluated by an ophthalmologist as a part of the patient’s evaluation and treatment. Relevant history taking to determine the source of a Horner’s syndrome should be systematic and complete. It often happens that the pathogenic source of the pupillary findings is identified only after careful history taking. The ophthalmic physician can reassure the patient, and explain that the phenomenon is harmless, e.g., when physiologic anisocoria or a tonic pupil is the cause.

Further Reading

Jacobson DM, Berg R, Grinstead GF et al (2001) Duration of positive urine for cocaine metabolite after ophthalmic administration: implications for testing patients with suspected Horner syndrome using ophthalmic cocaine. Am J Ophthalmol 131: 742–747

Kardon RH, Denison CE, Brown CK, Thompson HS (1990) Critical evaluation of the cocaine test in the diagnosis of Horner's syndrome. Arch. Ophthalmol 108: 384–387

Loewenfeld IE (1999) The pupil. Anatomy, physiology and clinical applications, Vol. I. Butterworth and Heinemann, Boston

Thompson HS, Miller NR (1998) Disorders of pupillary function, accommodation, and lacrimation. In: Miller NR, Newman NJ (eds) Walsh and Hoyt’s clinical neuro-ophthalmology, Vol. I. Williams and Wilkins, Baltimore, pp 961–1040

Thompson HS (1978) Segmental palsy of the iris sphincter in Adie's syndrome. Arch Ophthalmol 96: 1615–1620

Trobe JD (1988) Third nerve palsy and the pupil. Footnotes to the rule [editorial]. Arch Ophthalmol 106: 601–602

Wilhelm B, Wilhelm H, Lüdtke H, Streicher P, Adler M (1988) Pupillographic assessment of sleepiness in sleep-deprived healthy subjects. Sleep 21: 258–265

Wilhelm H, Ochsner H, Kopycziok E, Trauzettel-Klosinski S, Schiefer U, Zrenner E (1992) Horner’s syndrome: a retrospective analysis of 90 cases and recommendations for clinical handling. Ger. J Ophthalmol 1: 96–102

Wilhelm H, Schäffer E (1994) Pholedrin zur Lokalisation des Horner-Syn- droms. Klin Monatsbl Augenheilk 204: 169–175

Color saturation screening test with the panel D-15 or a complete Farnsworth-Munsell 100-hue test