Neurology_Adams

Neurology_Adams. were similar. Less-common causes of paralysis of the oculomotor nerves, but nonetheless seen by most practitioners, include variants of Guillain-Barré syndrome, herpes zoster, giant cell arteritis, ophthalmoplegic migraine, carcinomatous or lymphomatous meningitis, and the granulomatous disease sarcoidosis and Tolosa-Hunt syndrome, as well as fungal, tuberculous, syphilitic, and other forms of mainly chronic meningitis. Myasthenia gravis, discussed in Chap. 46, must always be considered in cases of ocular muscle palsy, particularly if several muscles are involved and if fluctuating ptosis is a prominent feature. Thyroid ophthalmopathy, discussed further on, presents in a similar fashion but usually with proptosis and eyelid retraction and without ptosis. Actually, in the above-mentioned series, no cause could be assigned in 20 to 30 percent, although more cases are now being resolved with MRI.


Neurology_Adams

Neurology_Adams. The third nerve is commonly compressed by aneurysm, tumor, or temporal lobe herniation. In a series of 206 cases of third-nerve palsy collected by Wray and Taylor, neoplastic diseases accounted for 25 percent and aneurysms for 18 percent. Of the neoplasms, 25 percent were parasellar meningiomas and 4 percent were pituitary adenomas. The palsy is usually chronic, progressive, and painless. As emphasized earlier, enlargement of the pupil is a sign of extramedullary third nerve compression because of the peripheral location in the nerve of the pupilloconstrictor fibers. By contrast, infarction of the nerve in diabetics usually spares the pupil, as the damage is situated in the central portion of the nerve. The oculomotor palsy that complicates diabetes (the cause in 11 percent in the Wray and Taylor series) develops over a few hours and is accompanied by pain, which may be severe, in the forehead and around the eye. The prognosis for recovery (as in other nonprogressive lesions of the


Neurology_Adams

Neurology_Adams. and Taylor series) develops over a few hours and is accompanied by pain, which may be severe, in the forehead and around the eye. The prognosis for recovery (as in other nonprogressive lesions of the oculomotor nerves) is usually good.


Neurology_Adams

Neurology_Adams. In chronic compressive lesions of the third nerve (distal carotid, basilar, or, most commonly, posterior communicating artery aneurysm; pituitary tumor, meningioma, cholesteatoma) the pupil is almost always affected by way of dilatation or reduced light response. However, the chronicity of the lesion may permit aberrant nerve regeneration. This is manifest by pupillary constriction on adduction of the eye or by retraction of the upper lid on downward gaze or adduction.


Neurology_Adams

Neurology_Adams. Rarely, children or young adults have recurrent attacks of ocular palsy in conjunction with an otherwise typical migraine (ophthalmoplegic migraine). The muscles (both extrinsic and intrinsic) innervated by the oculomotor, or less commonly, by the abducens nerve, are affected. Possibly, spasm of the vessels supplying these nerves or compression by edematous arteries causes a transitory ischemic paralysis but these are speculations. Arteriograms done after the onset of the palsy usually disclose no abnormality. Although the oculomotor palsy of migraine tends to recover, after repeated attacks there may be permanent partial paresis.


Neurology_Adams

Neurology_Adams. A fair number of cases of fourth nerve palsies remain idiopathic even after careful investigation. The fourth nerve is particularly vulnerable to head trauma (this was the cause in 43 percent of 323 cases of trochlear nerve lesions collected by Wray from the literature). The reason for this vulnerability has been speculated to be the long, crossed course of the nerves. The fourth and sixth nerves are practically never involved by aneurysm. Herpes zoster ophthalmicus may affect any of the ocular motor nerves but particularly the trochlear, which shares a common sheath with the ophthalmic division of the trigeminal nerve. Diabetic infarction of the fourth nerve occurs, but far less frequently than infarction of the third or sixth nerves. Trochlear-nerve palsy may also be a false localizing sign in cases of increased intracranial pressure, but again, not nearly as often as abducens palsy. Trochlear-nerve palsies have been described in patients with lupus erythematosus and with Sjögren


Neurology_Adams

Neurology_Adams. sign in cases of increased intracranial pressure, but again, not nearly as often as abducens palsy. Trochlear-nerve palsies have been described in patients with lupus erythematosus and with Sjögren syndrome, but their basic pathology is not known. Some cases of fourth-nerve palsy are idiopathic and most of these resolve.


Neurology_Adams

Neurology_Adams. Superior oblique myokymia is an unusual but easily identifiable movement disorder, characterized by recurrent episodes of vertical diplopia, monocular blurring of vision, and a tremulous sensation in the affected eye; in this way it simulates a palsy. If the episodes occur during the examination, the globe is observed to make small arrhythmic torsional movements. The problem is usually benign and responds to carbamazepine. Compression of the fourth nerve by a small looped branch of the basilar artery has been suggested as the cause, analogous to several other better documented vascular compression syndromes affecting cranial nerves. This notion is supported by findings on MRI reported by Yousry and colleagues. Rare instances presage pontine glioma or demyelinating disease.


Neurology_Adams

Neurology_Adams. Microvascular disease is a common cause of sixth nerve palsy in diabetics, in which case there is usually pain near the lateral canthus of the eye at the onset. An idiopathic form that occurs in the absence of diabetes is also well known. Isolated unilateral or bilateral sixth nerve palsy with global headache can be the initial manifestation of raised intracranial pressure from any source—including brain tumor, meningitis, and pseudotumor cerebri; rarely, it may appear after lumbar puncture, epidural injections, or insertion of a ventricular shunt. In children, the most common tumor involving the sixth nerve is a pontine glioma; in adults, it is tumor arising from the nasopharynx.


Neurology_Adams

Neurology_Adams. As the abducens nerve passes near the apex of the petrous bone it is in close relation to the trigeminal nerve. Both may be implicated by inflammatory or infectious lesions of the petrous (apex petrositis), manifest by facial pain and diplopia (Gradenigo syndrome). Among the causes of this syndrome is osteomyelitis of the petrous bone. Fractures at the base of the skull and petroclival tumors may have a similar effect, and sometimes head injury alone is the only assignable cause. Occasionally, the sixth nerve is compressed by a congenitally persistent trigeminal artery. A congenital form of bilateral abducens palsy is associated with bilateral facial paralysis (Mobius syndrome) as discussed in Chap. 38. Patients with the Duane retraction syndrome type 1 (absent sixth nerve) have limited abduction and on adduction show characteristic retraction of the globe because of co-contraction of the medial rectus and lateral rectus muscles.


Neurology_Adams

Neurology_Adams. Cavernous Sinus Syndrome, Tolosa-Hunt syndrome, and Orbital Pseudotumor


Neurology_Adams

Neurology_Adams. Some of the diseases discussed previously are associated with a degree of pain, often over the site of an affected nerve or muscle or in the immediately surrounding area. But the development over days or longer of a painful unilateral ophthalmoplegia should raise suspicion for other conditions such as aneurysm, tumor, or inflammatory and granulomatous process in the anterior portion of the cavernous sinus or the adjacent superior orbital fissure (Table 13-4). In the cavernous sinus syndrome, involvement of the ocular motor nerves on one or both sides is accompanied by periorbital pain and chemosis (Fig. 13-5B). In a series of 151 such cases reported by Keane, the third nerve (typically with pupillary abnormalities) and sixth nerve were affected in almost all and the fourth nerve in one-third; complete ophthalmoplegia, usually unilateral, was present in 28 percent. Sensory loss in the distribution of the ophthalmic division of the trigeminal nerve was often added, a finding that is


Neurology_Adams

Neurology_Adams. complete ophthalmoplegia, usually unilateral, was present in 28 percent. Sensory loss in the distribution of the ophthalmic division of the trigeminal nerve was often added, a finding that is helpful in the differentiation of cavernous sinus disease from other causes of orbital edema and ocular muscle weakness.


Neurology_Adams

Neurology_Adams. Trauma and neoplastic invasion are the most frequent causes of the cavernous sinus syndrome. Thrombophlebitis, intracavernous carotid aneurysm or fistula, fungal infection, meningioma, and pituitary tumor or hemorrhage account for a smaller proportion (see “Septic Cavernous Sinus Thrombophlebitis” and “Cavernous Sinus Thrombosis” in Chaps. 12 and 33). A dural arteriovenous fistula is another rare cause.


Neurology_Adams

Neurology_Adams. The idiopathic granulomatous painful condition of the cavernous sinus has been termed Tolosa-Hunt syndrome; a similar process affecting structures of the orbit is known as orbital pseudotumor. Orbital pseudotumor causes an inflammatory enlargement of the extraocular muscles, which often also encompasses the globe and other orbital contents (Fig. 13-8). It is often accompanied by injection of the conjunctiva and lid and slight proptosis. One or more muscles may be involved and there is a tendency to relapse and later to involve the opposite globe. Visual loss from compression of the optic nerve is a rare complication. Associations with connective tissue disease have been reported and IgG4-related sclerosis has increasingly been identified as a cause. Ultrasonography examination or CT scans of the orbit show enlargement of the orbital muscles including the tendons, as opposed to thyroid ophthalmopathy in which the muscles are enlarged but the muscle tendons are typically spared.


Neurology_Adams

Neurology_Adams. The inflammatory changes of Tolosa-Hunt syndrome are limited to the superior orbital fissure and can sometimes be detected by MRI; coronal views taken after gadolinium infusion show the lesion to best advantage. However, sarcoidosis, lymphomatous infiltration, and a small meningioma may produce similar radiographic findings and granulomatous (temporal) arteritis rarely causes ophthalmoplegia. The sedimentation rate in our patients with orbital pseudotumor or Tolosa-Hunt syndrome has varied but can be elevated, sometimes accompanied by a leukocytosis at the onset of symptoms. Sarcoidosis also can infiltrate the posterior orbit or cavernous sinus and cause a single or multiple unilateral nerve ophthalmoparesis as discussed in Chaps. 12 and 44.


Neurology_Adams

Neurology_Adams. Both orbital pseudotumor and Tolosa-Hunt syndrome are treated with corticosteroids. A marked response with reduction in pain and improved ophthalmoplegia in 1 or 2 days is typical; however, as pointed out in the review by Kline and Hoyt, tumors of the parasellar region that cause ophthalmoplegia may also respond, albeit not to the same extent. In both diseases, we have generally given prednisone 60 mg and tapered the medication slowly; although there are no data to guide the proper treatment, corticosteroids should be continued for several weeks or longer. The absence of a response to steroids should cause reconsideration of the diagnosis of Tolosa-Hunt syndrome.


Neurology_Adams

Neurology_Adams. When a total or nearly complete loss of eye movements of both eyes evolves within a day or days, it raises a limited number of diagnostic possibilities. Keane, who analyzed 60 such cases, found the responsible lesion to lie within the brainstem in 18 (usually infarction and less often Wernicke disease), in the cranial nerves in 26 (Guillain-Barré syndrome or tuberculous meningitis), within the cavernous sinus in 8 (tumors or infection), and at the myoneural junction in 8 (myasthenia gravis and botulism). Our experience has tended toward the Miller Fisher variant of Guillain-Barré syndrome, as did Keane’s later series (2007), and myasthenia. The ophthalmoplegic form of Guillain-Barré syndrome is very frequently associated with circulating antibodies to GQ1b ganglioside (see Chap. 44). There may be an accompanying paralysis of the dilator and constrictor of the pupil (“internal ophthalmoplegia”) that is not seen in myasthenia.


Neurology_Adams

Neurology_Adams. Unilateral complete ophthalmoplegia has an even more limited list of causes, largely related to local disease in the orbit and cavernous sinus, mainly infectious, neoplastic, or thrombotic.


Neurology_Adams

Neurology_Adams. This is most often caused by an ocular myopathy (the mitochondrial disorder known as progressive external ophthalmoplegia). The mitochondrial defect may show a mendelian inheritance pattern, as occurs with POLG1 and twinkle gene mutations, or may be the result or a mutation in mitochondrial DNA and show maternal inheritance only (see Chap. 45), Other causes include myasthenia gravis or Lambert-Eaton syndrome. We have encountered instances of the Lambert-Eaton myasthenic syndrome that caused an almost complete ophthalmoplegia (but not as an initial sign, as it may be in myasthenia) and a patient with paraneoplastic brainstem encephalitis similar to the case reported by Crino and colleagues, but both of these are certainly rare as causes of complete loss of eye movements. The congenital myopathies are typically named for the morphologic characteristic of the affected limb musculature, and may include the central core, myotubular, and nemaline types. Another cause is the slow channel


Neurology_Adams

Neurology_Adams. myopathies are typically named for the morphologic characteristic of the affected limb musculature, and may include the central core, myotubular, and nemaline types. Another cause is the slow channel congenital myasthenic syndrome (see Chap. 46). Among the chronic conditions, progressive supranuclear palsy may ultimately produce complete ophthalmoplegia, after first affecting vertical gaze. Thyroid ophthalmopathy as a cause of chronic ophthalmoparesis is discussed below.


Neurology_Adams

Neurology_Adams. The Duane retraction syndrome takes one of several forms, depending upon the pattern of ocular muscles affected. In the most common presentation, there is impaired abduction with retraction of the globe and narrowing of the palpebral fissure that is elicited by attempted adduction. These features occur because the lateral rectus is aberrantly innervated by branches of the third nerve. Cocontraction of the medial and lateral recti results in retraction of the globe.


Neurology_Adams

Neurology_Adams. Several causes of a pseudoparalysis of ocular muscles that are due to mechanical restriction of the ocular muscles are distinguished from the neuromuscular and brainstem diseases discussed previously. Processes that infiltrate the orbit, such as lymphoma, carcinoma and granulomatosis may limit the range of motion of individual or all the ocular muscles. In thyroid disease, a swollen and tight inferior or superior rectus muscle may limit upward and downward gaze; involvement of the medial rectus limits abduction. The frequency of involvement of the ocular muscles is given by Wiersinga and colleagues as inferior rectus 60 percent; medical rectus 50 percent; and superior rectus 40 percent. In most instances of thyroid ophthalmopathy, diagnosis is clear as there is an associated proptosis, but in the absence of the latter sign, and particularly if the ocular muscles are affected on one side predominantly, there may be difficulty. The extraocular muscle enlargement can be demonstrated by


Neurology_Adams

Neurology_Adams. in the absence of the latter sign, and particularly if the ocular muscles are affected on one side predominantly, there may be difficulty. The extraocular muscle enlargement can be demonstrated by CT scans and ultrasonography. This disorder is discussed further in Chap. 45. In a significant number of cases, 10 percent according to Bahn and Heufelder, there are no signs of hyperthyroidism.


Neurology_Adams

Neurology_Adams. The mechanical restriction of motion is confirmed by forced duction tests in which the eye is physically pulled or pushed over by the examiner. In the past, the insertions of the extraocular muscles were anesthetized and grasped by toothed forceps and attempts to move the globe are palpably restricted; more often, a cotton swab applied to the sclera is used to manipulate the globe. We have already considered two types of neural paralysis of the extraocular muscles: paralysis of conjugate movements (gaze) and paralysis of individual ocular muscles. Here we discuss a third, more complex one—namely, mixed gaze and ocular muscle paralysis. The mixed type is always a sign of an intrapontine or mesencephalic lesion that may have a variety of causes.


Neurology_Adams

Neurology_Adams. With a complete lesion of the left MLF, the left ipsilateral eye fails to adduct when the patient looks to the right; this condition is referred to as internuclear ophthalmoplegia (INO; Fig. 13-1). Reciprocally, with a lesion of the right MLF, the right eye fails to adduct when the patient looks to the left and the patient has a right internuclear ophthalmoplegia. Quite often, rather than a complete paralysis of adduction, there are only slowed adducting saccades in the affected eye while the other eye quickly arrives at its fully abducted position. This slowing can be observed by having the patient make large side-to-side refixation movements between two targets or by observing the slowed corrective saccades induced by optokinetic stimulation. Typically, the affected eye at rest does not lie in an abducted position, but there are exceptions and in most cases the absence of exotropia most dependably differentiates INO from a partial third-nerve palsy with weakness of the medial rectus


Neurology_Adams

Neurology_Adams. lie in an abducted position, but there are exceptions and in most cases the absence of exotropia most dependably differentiates INO from a partial third-nerve palsy with weakness of the medial rectus muscle. The exception is the WEBINO syndrome noted below.


Neurology_Adams

Neurology_Adams. A second component of INO is nystagmus that is limited to, or most prominent in, the opposite (abducting) eye. The intensity of nystagmus varies greatly from case to case. Several explanations have been offered to account for this dissociated nystagmus, all of them speculative. The favored one invokes the Hering law in which activated pairs of yoked muscles receive equal and simultaneous innervation; because of an adaptive increase in innervation of the weak adductor, there is a commensurate increase in innervation to the strong abductor. A mismatch in the generated pulse and step signals results in dissociated nystagmus manifesting in that eye. Zee and colleagues evaluated this concept by assessing whether short-term patching of one eye altered the central adaptive response and therefore modulated the extent of abducting nystagmus in patients with INO. In several cases, they found that patching the affected eye for several days caused the abducting nystagmus in the fellow eye to


Neurology_Adams

Neurology_Adams. modulated the extent of abducting nystagmus in patients with INO. In several cases, they found that patching the affected eye for several days caused the abducting nystagmus in the fellow eye to diminish. Conversely, patching the unaffected eye lead to increased abducting nystagmus in the fellow eye.


Neurology_Adams

Neurology_Adams. The MLF also contains axons that originate in the vestibular nuclei and govern vertical eye position, for which reason an INO may also cause a skew (vertical deviation of one eye). Vertical nystagmus and impaired vertical pursuit are other common features, especially with bilateral INO. The two medial longitudinal fasciculi lie close together, each being situated adjacent to the midline, so that they are frequently affected together, yielding a bilateral internuclear ophthalmoplegia. When the MLF is affected by a lesion in the pons, convergence is spared and the alignment of the eyes in primary gaze is normal. In some cases, both eyes take an abducted position, giving rise to the “wall-eyed bilateral INO,” or WEBINO syndrome. Lesions involving the MLF in the high midbrain impair convergence and also cause an exotropia because of proximity to the medial rectus subnucleus. Abducting nystagmus tends to be slight in this mesencephalic type.


Neurology_Adams

Neurology_Adams. The terms “anterior” and “posterior” INO have also been applied but their meaning has been taken differently by various authors thus making them less useful. Cogan categorized INO as anterior with convergence was impaired, and posterior convergence was spared but abduction or horizontal gaze were partly affected. In contrast, the term “posterior INO of Lutz” refers to abduction paresis that can be overcome by vestibular stimulation. The responsible lesion is proposed to be between the PPRF and the sixth nerve nucleus.


Neurology_Adams

Neurology_Adams. Etiology of INO The main cause of unilateral INO is a small paramedian pontine infarction. Other common lesions are lateral medullary infarction (where skew deviation is often a component), a demyelinating plaque of multiple sclerosis (more common as a cause of bilateral INO, as noted below), and infiltrative tumors of the brainstem and fourth ventricular region. Occasionally, an INO is an unexplained finding after mild head injury or with subdural hematoma or hydrocephalus. Some of the more unusual causes are given in the experience of Keane (2005). In addition, adductor weakness from myasthenia gravis can simulate an INO, even to the point of showing nystagmus in the abducting eye.


Neurology_Adams

Neurology_Adams. Bilateral INO is most often the result of a demyelinating lesion (multiple sclerosis) in the posterior part of the midpontine tegmentum. Pontine myelinolysis, pontine infarction from basilar artery occlusion, Wernicke disease, or infiltrating tumors are other causes. Brainstem damage following compression by a large cerebral mass has on occasion produced the syndrome.


Neurology_Adams

Neurology_Adams. An ipsilateral gaze palsy is the simplest oculomotor disturbance that results from a lesion in the paramedian tegmentum. More complex is the one-and-a-half syndrome that involves the pontine center for gaze plus the adjacent ipsilateral MLF on one side that combines a horizontal gaze palsy and INO on the same side. It is usually of vascular or, less often, demyelinative cause. The gaze palsy is, of course, on the side of the lesion and the eyes are deviated contrawise. As a result, one eye lies fixed in the midline for all horizontal movements; the other eye makes only abducting movements and may demonstrate horizontal abducting nystagmus (see Fisher; also Wall and Wray). Unlike the situation of an INO alone, the mobile eye rests abducted because of the gaze palsy, a sign that has been termed “paralytic pontine exotropia.” In some cases, the patient is able to adduct the eye (“nonparalytic exotropia,” a condition which has other causes). An incomplete version of the one-and-a-half


Neurology_Adams

Neurology_Adams. termed “paralytic pontine exotropia.” In some cases, the patient is able to adduct the eye (“nonparalytic exotropia,” a condition which has other causes). An incomplete version of the one-and-a-half syndrome displays only bilateral nystagmus on gaze in one direction (due to paresis of gaze) and nystagmus only in the abducting eye with gaze directed to the other side (due to the lesion in the MLF on the same side). Thrombotic occlusion of the upper part of the basilar artery (“top of the basilar” syndromes) causes a variety of important eye movement abnormalities. These include upgaze or complete vertical gaze palsy, skew deviation, and so-called pseudoabducens palsy, mentioned earlier. Caplan has summarized these features in detail.


Neurology_Adams

Neurology_Adams. Skew deviation Skew deviation is a disorder in which there is vertical deviation of one eye above the other that is caused by an imbalance of the supranuclear vestibular inputs to the ocular motor system. Unlike fourth nerve palsy, where the separation of images is most pronounced when the affected eye is adducted and turned down, skew deviation is typically comitant, meaning that the amount of ocular misalignment is relatively similar in all directions of gaze. Skew deviation does not have precise localizing value but is associated with a variety of lesions of the cerebellum and the brainstem, particularly those involving the MLF. With skew deviation due to cerebellar disease, the eye on the side of the lesion usually rests lower (in a ratio of 2:1 in Keane’s series), but sometimes it is higher than the other eye.


Neurology_Adams

Neurology_Adams. In some cases, the hypertropic eye has been known to alternate with the direction of gaze (“alternating skew”), with the right eye higher in right gaze and the left eye higher in left gaze. A cerebellar or other posterior fossa lesion is the usual cause. A mechanism for this sign has been proposed based on otolithic influences on cerebellar centers. Ford and coworkers have described a rare form of skew deviation caused by a monocular palsy of elevation stemming from a lesion immediately rostral to the ipsilateral oculomotor nucleus; a lesion of upgaze efferents from the ipsilateral riMLF was postulated but an abnormality of the vertical gaze holding mechanism related to the function of the INC is an alternative explanation.


Neurology_Adams

Neurology_Adams. Among the most unusual of the complex ocular disturbances is a subjective tilting of the entire visual field that may produce any angle of divergence but most often creates an illusion of environmental tilting of 45 to 90 degrees (tortopia) or of 180-degree vision (upside-down vision). Objects normally on the floor, such as chairs and tables, are perceived to be on the wall or ceiling. Although this symptom may arise as a result of a lesion of the parietal lobe or in the otolithic (utricular) apparatus, it has most often been associated in our experience with an internuclear ophthalmoplegia and slight skew deviation. Presumably the vestibular-otolithic nucleus or its connections in the MLF that maintain the vertical position of the ipsilateral eye are impaired. Lateral medullary infarction has been a common cause; other cases may be migrainous (Ropper, 1983). Ocular lateropulsion, in which the eyes are driven to one side and the patient feels pushed or pulled in the same direction, is


Neurology_Adams

Neurology_Adams. has been a common cause; other cases may be migrainous (Ropper, 1983). Ocular lateropulsion, in which the eyes are driven to one side and the patient feels pushed or pulled in the same direction, is another component in some cases of lateral medullary infarction as discussed in Chap. 33.


Neurology_Adams

Neurology_Adams. Nystagmus refers to involuntary rhythmic movements of the eyes and is of two general types. In the more common jerk nystagmus, the movements alternate between a slow component and a fast corrective component, or jerk, in the opposite direction. In pendular nystagmus, the oscillations are roughly equal in rate in both directions, although on lateral gaze the pendular type may be converted to the jerk type with the fast component to the side of gaze. Nystagmus reflects an imbalance in one or more of the systems that maintain stability of gaze. The causes may therefore be viewed as originating in (1) structures that maintain steadiness of gaze in the primary position; (2) the system for holding eccentric gaze—the so-called neural integrator; or (3) the VOR system, which maintains foveal fixation of images as the head moves. For the purposes of clinical work, however, certain types of nystagmus are identified as corresponding to lesions in specific structures within each of these systems,


Neurology_Adams

Neurology_Adams. of images as the head moves. For the purposes of clinical work, however, certain types of nystagmus are identified as corresponding to lesions in specific structures within each of these systems, and it is this approach that we take in the following pages. One classification considers nystagmus as the result of a disturbance in the vestibular apparatus or its brainstem nuclei, the cerebellum, or a number of specific regions of the brainstem such as the MLF.


Neurology_Adams

Neurology_Adams. In testing for nystagmus, the eyes should be examined first in the central position and then during upward, downward, and lateral movements. Jerk nystagmus is the more common type. It may be horizontal or vertical and is elicited particularly on ocular movement in these planes, or it may be rotatory and, rarely, retractory or vergent. By custom the direction of the nystagmus is designated according to the direction of the fast component (referred to as “beating” to that side). There are several varieties of jerk nystagmus. Some occur spontaneously; others are readily induced in normal persons by drugs or by labyrinthine or visual stimulation.


Neurology_Adams

Neurology_Adams. Drug intoxication is certainly the most frequent cause of nystagmus. Alcohol, barbiturates, other sedative-hypnotic drugs, phenytoin, and other antiepileptic drugs are the common ones. This form of nystagmus is most prominent on deviation of the eyes in the horizontal plane, but occasionally it also may appear in the vertical plane. For no known reason, it may occasionally be asymmetrical in the two eyes. In many normal individuals, a few irregular jerks are observed when the eyes are moved far to one side (“nystagmoid” jerks), but the movements cease once lateral fixation is attained. A fine rhythmic nystagmus may also occur normally in extreme lateral gaze, beyond the range of binocular vision; but it is bilateral and disappears as the eyes move a few degrees toward the midline. These latter movements are probably analogous to the tremulousness of skeletal muscles when maximally contracted.


Neurology_Adams

Neurology_Adams. Oscillopsia is the symptom of illusory movement of the environment in which stationary objects seem to move back and forth, up and down, or from side to side. It may be caused by ocular flutter (a cerebellar sign as discussed later) or coarse nystagmus of any type. With lesions of the labyrinths (as in aminoglycoside toxicity), the symptom of oscillopsia is only provoked by motion—for example, walking or riding in an automobile—and indicates an impaired ability of the vestibular system to stabilize ocular fixation during body movement (i.e., impaired VOR function). In these circumstances, cursory examination of the eyes may disclose no abnormalities; however, if the patient’s head is rotated slowly from side to side or moved rapidly in one direction while attempting to fixate a target, impairment of smooth eye movements and their replacement by saccadic or nystagmoid movements is evoked (see Chap. 14 for further discussion of these tests). If episodic and involving only one eye,


Neurology_Adams

Neurology_Adams. impairment of smooth eye movements and their replacement by saccadic or nystagmoid movements is evoked (see Chap. 14 for further discussion of these tests). If episodic and involving only one eye, oscillopsia is usually caused by myokymia of an ocular muscle (usually the superior oblique).


Neurology_Adams

Neurology_Adams. Nystagmus of Labyrinthine Origin (See Also Chap. 14) This is predominantly a horizontal or vertical unidirectional jerk nystagmus, often with a slight torsional component, that is evident when the eyes are close to the central position and changes minimally with the direction of gaze. It is more prominent when visual fixation is eliminated (conversely, it is suppressed by fixation). The observation of suppression with visual fixation is facilitated by the use of Frenzel lenses, but most instances are evident without elaborate apparatus. Vestibular nystagmus of peripheral (labyrinthine) origin beats in most cases away from the side of the lesion and increases as the eyes are turned in the direction of the quick phase (the Alexander law). In contrast, as noted below, nystagmus of brainstem and cerebellar origin is most apparent when the patient tries to maintain eccentric fixation and the direction of nystagmus changes with the direction of gaze.


Neurology_Adams

Neurology_Adams. Tinnitus and hearing loss are often associated with disease of the peripheral labyrinthine mechanism; also, vertigo, nausea, vomiting, and staggering may accompany disease of any part of the labyrinthine-vestibular apparatus or its central connections. As a characteristic example, the intense nystagmus of benign positional vertigo (see Chap. 14) is evoked by moving from the sitting to the supine position, with the head turned to one side. In this condition, nystagmus of vertical-torsional type and vertigo develop a few seconds after changing head position and persist for another 10 to 15 s. When the patient sits up, the nystagmus changes to beat in the opposite direction.


Neurology_Adams

Neurology_Adams. When one is watching a moving object (e.g., the passing landscape from a train window, a rotating drum with vertical stripes, or a strip of cloth with similar stripes), a rhythmic jerk nystagmus called optokinetic nystagmus (OKN) normally appears. This phenomenon is explained by a slow involuntary pursuit movement iteratively followed by a quick saccadic movement in the opposite direction in order to fixate the next new target that is entering the visual field. With unilateral lesions of the parietal region, the slow pursuit phase of the OKN may be lost or diminished when the stimulus—for example, the striped OKN drum—is moving toward the side of the lesion, whereas rotation of the drum to the opposite side elicits a normal response. (A prominent neurologist of our acquaintance in past days correctly made the diagnosis of parietal lobe abscess on the basis of fever and absent pursuit to the side of the lesion.) In contrast, patients with hemianopia caused by an occipital lobe lesion


Neurology_Adams

Neurology_Adams. correctly made the diagnosis of parietal lobe abscess on the basis of fever and absent pursuit to the side of the lesion.) In contrast, patients with hemianopia caused by an occipital lobe lesion show a normal optokinetic response bilaterally. The loss of the pursuit phase with a parietal lesion presumably results from interruption of efferent pathways from the parietal cortex to the brainstem centers for conjugate gaze. On the other hand, individuals with a frontal lobe lesion will track a moving target in either horizontal direction but show little or no fast-phase correction in the direction opposite the lesion.


Neurology_Adams

Neurology_Adams. An important additional fact about OKN is that the ability to evoke it proves that the patient is not blind. Each eye can be tested separately to exclude monocular blindness. Thus the test is of particular value in the examination of hysterical patients and malingerers who claim that they cannot see, and of neonates and infants (a nascent OKN is established within hours after birth and becomes more easily elicitable over the first few months of life). Demonstration of an intact OKN, however, merely demonstrates that some vision is preserved, and does not prove that the visual function is actually normal.


Neurology_Adams

Neurology_Adams. Labyrinthine stimulation—for example, irrigation of the external auditory canal with warm or cold water, or “caloric testing”—produces a marked nystagmus. Cold water induces a slow tonic deviation of the eyes toward the irrigated ear and a compensatory nystagmus in the opposite direction in a conscious, awake patient; warm water does the reverse. Thus the acronym taught to generations of medical students: COWS, or “cold opposite, warm same,” to refer to the direction of the fast phase of the induced nystagmus. The slow tonic component reflects impulses originating in the semicircular canals, and the fast component is a corrective movement. Comatose patients with an intact VOR will demonstrate the slow phase gaze deviation without the fast phase nystagmus to which this mnemonic refers. Chapter 14 discusses the production of nystagmus by labyrinthine stimulation and other features of vestibular nystagmus.


Neurology_Adams

Neurology_Adams. Brainstem lesions often cause a coarse, unidirectional, gaze-evoked nystagmus, which may be horizontal or vertical, meaning that the nystagmus is exaggerated when the eyes sustain an eccentric position of gaze. Vertical nystagmus, for example, is brought out usually on upward gaze, less often downward. Unlike the vestibular nystagmus discussed above, the central type usually also changes direction depending on the direction of gaze. Vertigo is less common or less intense than with labyrinthine nystagmus, but signs of disease of other nuclear structures and tracts in the brainstem are frequent.


Neurology_Adams

Neurology_Adams. Downbeat nystagmus, which is always of central origin, is characteristic of lesions in the medullary–cervical region such as syringobulbia, Chiari malformation, basilar invagination, and demyelinating plaques. It has also been seen with Wernicke disease and may be an initial sign of either paraneoplastic brainstem encephalitis or cerebellar degeneration with opsoclonus. Downbeat nystagmus has also been observed in patients with lithium intoxication or with profound magnesium depletion (Saul and Selhorst). Halmagyi and coworkers, who studied 62 patients with downbeat nystagmus, found that half were associated with Chiari malformation and various forms of cerebellar degeneration; in most of the remainder, the cause could not be determined. Cases associated with antibodies against glutamic acid decarboxylase (GAD), a substance that has a documented relationship to the stiff man syndrome, have been reported by Antonini and colleagues and by other groups. Whether this antibody explains the


Neurology_Adams

Neurology_Adams. decarboxylase (GAD), a substance that has a documented relationship to the stiff man syndrome, have been reported by Antonini and colleagues and by other groups. Whether this antibody explains the idiopathic cases of downbeat nystagmus is not known.


Neurology_Adams

Neurology_Adams. Spontaneous upbeat nystagmus can be observed in patients with demyelinating or vascular disease, tumors, or Wernicke disease. There is still uncertainty about the anatomic basis of coarse upbeat nystagmus, but it has been associated with lesions of the midbrain and cerebellum (particularly the anterior cerebellar vermis). Kato and associates also cite cases with a lesion at the pontomedullary junction involving the nucleus prepositus hypoglossi, which receives vestibular connections and projects to all brainstem and cerebellar regions concerned with ocular motor functions.


Neurology_Adams

Neurology_Adams. Nystagmus of several types—including gaze-evoked nystagmus, downbeat nystagmus, and “rebound nystagmus” (gaze-evoked nystagmus that changes direction with refixation to the primary position)—occurs with cerebellar disease, particularly with lesions of the vestibulocerebellum or with brainstem lesions that involve the nucleus prepositus hypoglossi and the medial vestibular nucleus. Also characteristic of cerebellar disease are several closely related disorders of saccadic movement that appear as nystagmus (opsoclonus, flutter, dysmetria) described in the following text. Tumors situated in the cerebellopontine angle may cause a coarse bilateral horizontal nystagmus that is higher amplitude to the side of the lesion (Brun’s nystagmus). Nystagmus that occurs only in the abducting eye is referred to as dissociated nystagmus and is a common sign of internuclear ophthalmoplegia, as discussed earlier. Infantile (Congenital, Pendular) Nystagmus


Neurology_Adams

Neurology_Adams. Infantile (Congenital, Pendular) Nystagmus This nystagmus can occur in association with profound visual loss or as an isolated abnormality with relatively preserved visual function. When accompanied by visual loss, it may be associated with albinism, Leber’s congenital amaurosis, and various other diseases of the retina and refractive media. Occasionally it is observed as a congenital abnormality, even without poor vision. The defect in infantile nystagmus is postulated to be instability of smooth pursuit or gaze-holding mechanisms. A cardinal feature of this type of nystagmus is that it is in one plane; that is, it remains horizontal even during vertical movement. It is mainly pendular (sinusoidal) except in extremes of gaze, when it comes to resemble jerk nystagmus. Eye movement recordings demonstrate an exponentially increasing velocity of the slow phase that is unique among nystagmus.


Neurology_Adams

Neurology_Adams. Infantile nystagmus is often suppressed during convergence. Many individuals have a “null position,” where the nystagmus is dampened in a particular direction of gaze. These patients, therefore, adopt a compensatory head turn in order to utilize the null position, where the retinal image is most stable, to its maximum effect. Also characteristic is a paradoxical response to optokinetic testing (see later), in which the quick phase is in the same direction as the drum rotation.


Neurology_Adams

Neurology_Adams. The related condition of latent nystagmus refers to nystagmus that occurs when one eye is covered. The fast phase of the nystagmus is in the direction of the covered eye. The finding may occur when either is covered, or it may be asymmetric and occur only with covering one of the eyes but not the other. Latent nystagmus is considered to be a result of impaired development of binocular stereoscopic vision. In some individuals with this condition who then lose vision in one eye later in life, the latent nystagmus becomes unmasked constantly and is termed manifest latent nystagmus.


Neurology_Adams

Neurology_Adams. Even in adulthood, severe acquired blindness can produce nystagmus of pendular or jerk variety. Both horizontal and vertical components are evident and the characteristic feature is a fluctuation over several seconds of observation in the dominant direction of beating. The oscillations of the eyes are usually very rapid, increase on upward gaze, and may be associated with compensatory oscillations of the head. The formerly common syndrome of “miner’s nystagmus” is an associated condition that occurs in patients who have worked for many years in comparative darkness.


Neurology_Adams

Neurology_Adams. Spasmus nutans, a specific type of pendular nystagmus of infancy, is accompanied by head nodding, and occasionally by wry positions of the neck. Most cases begin between the 4th and 12th months of life, never after the 3rd year. The nystagmus may be horizontal, vertical, or rotatory; it is usually more pronounced in one eye than the other (or limited to one eye) and can be intensified by immobilizing or straightening the head. Most infants recover within a few months or years. Most cases are idiopathic, but symptoms like those of spasmus nutans may betray the presence of a perichiasmal or third ventricular tumor (see also seesaw nystagmus below in “Other Types of Nystagmus”); rare cases accompany childhood retinal diseases. Although there is no direct connection to the rare childhood condition of bobble-head syndrome, which is caused by lesions in or adjacent to the third ventricle, they are similar in the rhythmic head movements as described in Chap. 29.


Neurology_Adams

Neurology_Adams. Acquired forms of pendular nystagmus may occur with leukodystrophies, including Pelizaeus-Merzbacher syndrome (see Chap. 36), multiple sclerosis (see Chap. 35), and toluene intoxication. In the oculomasticatory myorhythmia of Whipple disease, the nystagmus is conjoined to rhythmic jaw movements (see Chap. 31). Other Types of Nystagmus


Neurology_Adams

Neurology_Adams. Other Types of Nystagmus Convergence nystagmus refers to a rhythmic oscillation in which a slow abduction of both eyes is followed by a quick movement of adduction, usually accompanied by quick rhythmic retraction movements of the eyes (retraction nystagmus) and by one or more features of the Parinaud–dorsal midbrain syndrome discussed earlier in the chapter. There may also be rhythmic movements of the eyelids or a maintained spasm of convergence, best brought out on attempted elevation of the eyes on command or downward rotation of an OKN drum (see below for discussion of optokinetic nystagmus). These unusual phenomena all point to a lesion of the upper midbrain tegmentum and are usually manifestations of vascular disease, traumatic damage, or tumor, notably pinealoma that compresses this region.


Neurology_Adams

Neurology_Adams. Seesaw nystagmus is a torsional-vertical oscillation in which the intorting eye moves up and the opposite (extorting) eye moves down, then both move in the reverse direction. It is occasionally observed in conjunction with chiasmatic bitemporal hemianopia caused by sellar or parasellar masses and after pituitary surgery.


Neurology_Adams

Neurology_Adams. Periodic alternating nystagmus (PAN) is a remarkable horizontal jerking that periodically (every 90 s, or so) changes direction, interposed with a brief neutral period during which the eyes show no nystagmus, or jerk downward. PAN is seen with lesions in the lower brainstem but has also been reported with Creutzfeldt-Jakob disease, hepatic encephalopathy, lesions of the cerebellar nodulus, carcinomatous meningitis, anti-GAD antibodies, and varied other processes. A congenital form is associated with albinism. It differs from ping-pong gaze, which is a saccadic variant with a more rapid alternating of gaze from side to side and usually the result of severe bilateral hemispheric disease. So-called oculopalatal tremor is caused by a lesion of the central tegmental tract and may be accompanied by a pendular nystagmus that has the same beat as the palatal and pharyngeal muscles, as discussed in Chap. 4.


Neurology_Adams

Neurology_Adams. Roving conjugate eye movements are characteristic of light coma. Horizontal ocular deviations that shift every few seconds from side to side (ping-pong gaze) is a form of roving eye movement that occurs with bihemispheric infarctions or sometimes with posterior fossa lesions. Fisher has noted a similar slower, side-to-side pendular oscillation of the eyes (“windshield-wiper eyes”). This phenomenon has been associated with bilateral hemispheric lesions that have presumably released a brainstem oscillatory pacemaker. Ocular bobbing is a term coined by Fisher to describe a distinctive spontaneous fast downward jerk of the eyes followed by a slow upward drift to the midposition. It is observed in comatose patients in whom horizontal eye movements have been obliterated by large destructive lesions of the pons, less often of the cerebellum. The movements may be disconjugate in the vertical plane, especially if there is an associated third-nerve palsy on one side.


Neurology_Adams

Neurology_Adams. Other spontaneous vertical eye movements have been given a variety of confusing names: atypical bobbing, inverse bobbing, reverse bobbing, and ocular dipping. For the most part, they are observed in coma of metabolic or anoxic origin in which reflexive horizontal eye movements may be preserved (in distinction to ocular bobbing). Ocular dipping describes an arrhythmic slow conjugate downward movement followed in several seconds by a more rapid upward movement; it occurs spontaneously but may at times be elicited by moving the limbs or neck. Anoxic encephalopathy has been the most common cause, but a few cases have followed drug overdose (Ropper, 1981). Oculogyric crisis, formerly associated with postencephalitic parkinsonism, is now most often caused by phenothiazine drugs, as discussed earlier. Saccadic Intrusions (Opsoclonus, Ocular Flutter, and Square Wave Jerks)


Neurology_Adams

Neurology_Adams. This group of phasic or repetitive eye movements is distinguished from nystagmus in that each is composed of abnormal saccades without intervening slow phase eye movements. Opsoclonus is the term applied to rapid, conjugate oscillations of the eyes in horizontal, rotatory, and vertical directions, often made worse by voluntary movement or the need to fixate the eyes. These movements are continuous and chaotic, without an intersaccadic pause (hence the colorful term saccadomania). They can be observed even when the eyes are closed, and often persist in sleep. As indicated in Chap. 4, they are usually part of a widespread myoclonus associated with paraneoplastic or parainfectious disease. In adults, lung, breast, and testicular cancer are important considerations, while in children an evaluation for neuroblastoma is essential (see “Paraneoplastic Cerebellar Degeneration” discussed in Chap. 30). Other less frequent causes include HIV, poststreptococcal infection, West Nile virus


Neurology_Adams

Neurology_Adams. an evaluation for neuroblastoma is essential (see “Paraneoplastic Cerebellar Degeneration” discussed in Chap. 30). Other less frequent causes include HIV, poststreptococcal infection, West Nile virus encephalitis, and rickettsial infections. Opsoclonus may also be observed in patients who are intoxicated with antidepressants, anticonvulsants, organophosphates, cocaine, lithium, thallium, and haloperidol; in the nonketotic hyperosmolar state; and in cerebral Whipple disease, where the eye movements are coupled with rhythmic jaw movements (oculomasticatory myorhythmia). A benign childhood form can persist for years without explanation and is responsive to adrenocorticotropic hormone (ACTH), as in the “dancing eyes” syndrome of Kinsbourne. In addition, a self-limited benign form exists in neonates.


Neurology_Adams

Neurology_Adams. Ocular flutter refers to intermittent bursts of very rapid horizontal oscillations around the point of fixation; this abnormality is also associated with cerebellar disease. Flutter at the end of a saccade, called flutter dysmetria (“fish-tail nystagmus”) has the appearance of dysmetria, but careful analysis indicates that it is probably a different phenomenon. Whereas the inaccurate saccades of ocular saccadic dysmetria (an ataxic phenomenon) are separated by a brief pause (intersaccadic interval), flutter consists of consecutive saccades without an intersaccadic interval; that is, back-to-back saccades (Zee and Robinson). All those movements have the same implication of cerebellar cortical disease. One hypothesis relates opsoclonus and ocular flutter to a disorder of the saccadic “pause neurons,” but their exact anatomic basis has not been elucidated. Similar movements have been produced in monkeys by creating bilateral lesions in the pretectum. Some normal individuals can


Neurology_Adams

Neurology_Adams. “pause neurons,” but their exact anatomic basis has not been elucidated. Similar movements have been produced in monkeys by creating bilateral lesions in the pretectum. Some normal individuals can voluntarily induce flutter for brief periods, but the movement cannot be sustained (voluntary “nystagmus”).


Neurology_Adams

Neurology_Adams. Square wave jerks refer to involuntary saccades that disrupt fixation. The eyes are seen to horizontally move off target, pause for approximately 200 ms, and then move back. The term square wave jerks comes from a description of the recording of these eye movements. Square wave jerks can be a normal finding in the elderly, but their frequency becomes increased many conditions, particularly neurodegenerative disorders such as progressive supranuclear palsy. An eye movement difficult to classify is ocular neuromyotonia that is found after radiation that includes the field of the ocular motor nerves (and less characteristically from vascular or tumor compression). There is intermittent diplopia owing to paroxysmal contraction of one or more ocular muscles, usually after their activation. Like superior oblique myokymia (discussed earlier), ocular neuromyotonia may respond to anticonvulsant medications such as carbamazepine. Disorders of the Eyelids and Blinking


Neurology_Adams

Neurology_Adams. Disorders of the Eyelids and Blinking A consideration of oculomotor disorders would be incomplete without reference to the eyelids and blinking. In the normal individual, the eyelids on both sides are at the same level with respect to the limbus of the cornea and there is a variable prominence of the eyes, depending on the width of the palpebral fissure. The function of the lids is to protect the delicate corneal surfaces against injury and the retinae against glare; this is done by blinking and lacrimation. Eyelid movement is normally coordinated with ocular movement—the upper lids elevate when looking up and descend when looking down. Turning the eyes quickly to the side is sometimes attended by a single blink, which is necessarily brief so as not to interfere with vision. When the blink duration is prolonged, it is indicative of an abnormally intense effort required to initiate the saccade; usually this is because of frontal lobe or basal ganglionic disease.


Neurology_Adams

Neurology_Adams. Closure and opening of the eyelids is accomplished through the reciprocal actions of the levator palpebrae and orbicularis oculi muscles. Relaxation of the levator and contraction of the orbicularis effect closure; the reverse action of these muscles effects opening of the closed eyelids. Opening of the lids is aided by the superior tarsal (Müller) muscle, which is tonically innervated by sympathetic fibers. The levator is innervated by the oculomotor nerve, and the orbicularis by the facial nerve. The trigeminal nerves provide sensation to the eyelids and are also the afferent limbs of corneal and palpebral reflexes. Central mechanisms for the control of blinking, in addition to the reflexive brainstem connections between the third, fifth, and seventh nerve nuclei, include polysynaptic circuits of the cerebrum, basal ganglia, and hypothalamus. Voluntary lid closure is initiated through frontobasal ganglionic connections.


Neurology_Adams

Neurology_Adams. The eyelids are kept open by the tonic contraction of the levator muscles, which overcomes the elastic properties of the periorbital muscles. The eyelids close during sleep and certain altered states of consciousness as a result of relaxation of the levator muscles. Facial paralysis causes the closure to be incomplete. Normal blinking is always bilateral and occurs irregularly at a rate of 12 to 20 times a minute, the frequency varying with the state of concentration and with emotion. The natural stimuli for the blink reflex are corneal contact, a tap on the brow or around the eye, visual threat, an unexpected loud sound, and, as indicated above, turning of the eyes to one side. There is normally a rapid adaptation of blinking in response to visual and auditory stimuli but not to corneal stimulation.


Neurology_Adams

Neurology_Adams. Electromyography of the orbicularis oculi reveals two components of the blink response, an early and late one; these features are difficult to appreciate by clinical observation alone. The early monosynaptic response consists of only a slight movement of the upper lids; the immediately following polysynaptic response is more forceful and approximates the upper and lower lids. Whereas the early part of the blink reflex is beyond volitional control, the second part may be inhibited voluntarily.


Neurology_Adams

Neurology_Adams. Blepharospasm, an excessive and forceful closure of the lids with increased frequency, is a common disorder that is seen in isolation or as part of a number of dyskinesias and drug-induced movement disorders. Extremes of this condition may result in functional blindness. Treatment for dry eye syndrome is often attempted by ineffective; periodic injections with botulinum toxin can alleviate symptoms. The combination of blepharospasm with dystonic grimacing movements of the lower face is termed Meige syndrome. The opposite sign, reduced frequency of blinking (< 10/min), is characteristic of Parkinson disease and progressive supranuclear palsy. In these cases, there is reduced adaptation to repeated supraorbital tapping at a rate of about 1/s; therefore, the patient continues to blink with each tap on the forehead or glabella, referred to as the glabellar, or Myerson sign.


Neurology_Adams

Neurology_Adams. A lesion of the oculomotor nerve, by paralyzing the levator muscle, causes ptosis, that is, drooping of the upper eyelid. In contrast, a lesion of the facial nerve, as in Bell palsy, impairs the ability to close the eyelids because of weakness of orbicularis oculi (lagophthalmos). In some instances of Bell palsy, even after nearly full recovery of facial movements, blink frequency and amplitude may be reduced on the previously paralyzed side. A trigeminal nerve lesion on one side, by reducing corneal sensation, interferes with the blink reflex on both sides, whereas Bell palsy reduces the ipsilateral blink but does not affect the contralateral blink. Aberrant regeneration of the third nerve after an injury may result in a condition wherein the upper lid retracts on lateral or downward gaze (pseudo-von Graefe sign). Aberrant regeneration of the facial nerve after Bell palsy has an opposite effect—closure of the lid with jaw movements or speaking (one of the Marcus Gunn phenomena, the


Neurology_Adams

Neurology_Adams. (pseudo-von Graefe sign). Aberrant regeneration of the facial nerve after Bell palsy has an opposite effect—closure of the lid with jaw movements or speaking (one of the Marcus Gunn phenomena, the other being an afferent pupillary defect to light). There is also a congenital and sometimes hereditary anomaly in which a ptotic eyelid retracts momentarily when the mouth is opened or the jaw is moved to one side. In other cases, inhibition of the levator muscle and ptosis occurs with opening of the mouth (“inverse Marcus Gunn phenomenon,” or Marin Amat syndrome).


Neurology_Adams

Neurology_Adams. Unilateral ptosis is a notable feature of third nerve lesions (see above) and of sympathetic paralysis, namely, the Horner syndrome. With the former, weakness of the levator palpebrae can produce marked, or even complete ptosis, whereas with the latter, weakness of the Müller muscle produces only 1 to 2 m of ptosis. In some cases of Horner syndrome, there is also “inverse ptosis” with a slight elevation of the lower eyelid contributing to the illusion that the eye is slightly retracted (pseudo-enophthalmos). A common cause of unilateral static ptosis is a dehiscence of the tarsal muscle attachment; it can be identified by the loss of the upper lid fold just below the brow.


Neurology_Adams

Neurology_Adams. Ptosis may be accompanied by an overaction (compensation) of the frontalis and the contralateral levator palpebrae muscles. In patients with myasthenia, Cogan has described a “lid twitch” phenomenon, in which there is a transient retraction of the upper lid when the patient moves visual fixation from the down position to straight ahead. Brief fluttering of the lid margins upon moving the eyes vertically is also characteristic of myasthenia. Another useful clinical rule is that a combined paralysis of the levator, and orbicularis oculi muscles (i.e., the muscles that open and close the lids) indicates myasthenia gravis or a myopathic disease such as myotonic dystrophy. This is because the third and seventh cranial nerves are rarely affected together in peripheral nerve or brainstem disease.


Neurology_Adams

Neurology_Adams. Bilateral ptosis is a characteristic feature of myasthenia gravis and certain muscular dystrophies; congenital ptosis and progressive sagging of the upper lids in the elderly are other common forms. Botulism also produces ptosis, whether naturally acquired of occurring iatrogenically after botulinum toxin treatments. An effective way of demonstrating that mild, ostensibly unilateral ptosis is in fact bilateral is to lift the ptotic side and observe that the opposite lid promptly droops. This reflects the enhanced effort required to maintain patency of the lids.


Neurology_Adams

Neurology_Adams. The opposite of ptosis, that is, retraction of the upper lids, with a staring expression (Collier sign) is observed in thyroid disease, progressive supranuclear palsy, and hydrocephalus and other causes of the dorsal midbrain syndrome. In thyroid eye disease is the “lid-lag” refers to delayed relaxation of the eyelid on attempted downgaze (Von Graefe sign). Proptosis and ocular muscle restriction are present in the full form of the condition. PSP has prominent volitional vertical gaze abnormalities. In hydrocephalus, the downturning of the eyes is often referred to as the “sunset sign.” The elements of the dorsal midbrain syndrome have been described earlier in this chapter. The von Graefe sign on downward gaze is usually not present, in distinction to what is observed in thyroid ophthalmopathy. Slight lid retraction has been observed in a few patients with hepatic cirrhosis, Cushing disease, chronic steroid myopathy, and hyperkalemic periodic paralysis. Lid retraction can also be a


Neurology_Adams

Neurology_Adams. Slight lid retraction has been observed in a few patients with hepatic cirrhosis, Cushing disease, chronic steroid myopathy, and hyperkalemic periodic paralysis. Lid retraction can also be a reaction to ptosis on the other side; this is clarified by lifting the ptotic lid manually, and observing the disappearance of contralateral retraction as mentioned previously.


Neurology_Adams

Neurology_Adams. Myotonic dystrophy features ptosis as a component of the myopathic facies. In myotonia congenita, forceful closure of the eyelids may induce a strong aftercontraction. In certain extrapyramidal diseases, particularly progressive supranuclear palsy and Parkinson disease, even gentle lid closure may elicit blepharoclonus and blepharospasm on attempted opening of the lids; or there may be a delay in the opening of the tightly closed eyelids. Acute right parietal or bifrontal lesions often produce a peculiar disinclination to open the eyelids, even to the point of offering active resistance to forced opening. The closed lids give the false impression of diminished alertness and has incorrectly been called an apraxia of lid opening.


Neurology_Adams

Neurology_Adams. The testing of pupillary size and reactivity, which can be accomplished by the use of a flashlight and simple printed gauge, yields important, often vital clinical information. Essential, of course, is the proper interpretation of pupillary reactions, and this requires some knowledge of their underlying neural mechanisms.


Neurology_Adams

Neurology_Adams. The diameter of the pupil is determined by the balance of innervation between the constricting sphincter and radially arranged dilator muscles of the iris. The pupilloconstrictor (parasympathetic) fibers arise in the Edinger-Westphal nucleus in the high midbrain, join the third cranial (oculomotor) nerve, and synapse in the ciliary ganglion, which lies in the posterior part of the orbit. The postganglionic fibers then enter the globe via the short ciliary nerves. Only 3 percent of these fibers mediate pupillary constriction to light, while the remaining 97 percent are responsible constriction occurring as part of the near response during accommodation. The sphincter of the pupil comprises 50 motor units, according to Corbett and Thompson.


Neurology_Adams

Neurology_Adams. The pupillodilator (sympathetic) fibers arise in the posterolateral part of the hypothalamus and descend, uncrossed, in the lateral tegmentum of the midbrain, pons, medulla, and cervical spinal cord to the eighth cervical, and first and second thoracic segments, where they synapse with lateral horn neurons. The latter give rise to preganglionic fibers, most of which leave the cord by the second ventral thoracic root and proceed through the stellate ganglion to synapse in the superior cervical ganglion. The postganglionic fibers ascend along the internal carotid artery and traverse the cavernous sinus, where they join the first division of the trigeminal nerve, finally reaching the eye as the long ciliary nerves that innervate the dilator muscle of the iris. Some of the postganglionic sympathetic fibers also innervate the sweat glands and arterioles of the face, and Müller’s muscle in the eyelid. The Pupillary Light Reflex


Neurology_Adams

Neurology_Adams. The Pupillary Light Reflex The most common stimulus for pupillary constriction is exposure of the retina to light. Reflex pupillary constriction is also part of the act of convergence and accommodation for near objects (near synkinesis).


Neurology_Adams

Neurology_Adams. The pathway for the pupillary light reflex consists of three parts (Fig. 13-9). There is an afferent limb, fibers of which originate in the retinal receptor cells, pass through the bipolar cells, and synapse with the retinal ganglion cells. In addition to stimulating rod and cone photoreceptors, light also drives pupillary constriction by stimulating special intrinsically photosensitive retinal ganglion cells (ipRGC) that contain melanopsin and directly signal the presence of light (Hattar). The light reflex fibers course through the optic nerve and chiasm and then leave the optic tract just rostral to the lateral geniculate body and enter the rostral midbrain, where they synapse in the pretectal nucleus. From here, the special intercalated neurons pass ventrally to the ipsilateral Edinger-Westphal nucleus and, via fibers that cross in the posterior commissure, to the contralateral Edinger-Westphal nucleus as well (Fig. 13-9). The effector arm of the reflex consists of an efferent


Neurology_Adams

Neurology_Adams. nucleus and, via fibers that cross in the posterior commissure, to the contralateral Edinger-Westphal nucleus as well (Fig. 13-9). The effector arm of the reflex consists of an efferent two-neuron pathway from the Edinger-Westphal nucleus that synapses in the ciliary ganglion, from which the short ciliary nerves innervate the sphincter to cause pupillary constriction. Following initial constriction, the pupil may normally dilate slightly in spite of a light shining steadily in one or both eyes.


Neurology_Adams

Alterations of the Pupils

Neurology_Adams. Alterations of the Pupils


Neurology_Adams

Neurology_Adams. The pupils tend to be large in children and small in the aged, sometimes markedly miotic but still reactive (senile miosis). An asymmetry of the pupils of 0.3 to 0.5 mm is found in 20 percent or more of normal individuals (Lam). Normally the pupil constricts under a bright light (direct reflex), and the other unexposed pupil also constricts (consensual reflex). With complete or nearly complete interruption of the optic nerve, the pupil will fail to react to direct light stimulation; however, the pupil of the blind eye will still show a consensual reflex, that is, it will constrict with illumination of the healthy eye. Contrariwise, lack of direct and consensual light reflex with retention of the consensual reflex in the opposite eye places the lesion in the efferent limb of the reflex arc, that is, in the homolateral oculomotor nerve or its nucleus. A lesion of the afferent limb of the light reflex pathway will not affect the near responses of the pupil, and lesions of the visual


Neurology_Adams

Neurology_Adams. arc, that is, in the homolateral oculomotor nerve or its nucleus. A lesion of the afferent limb of the light reflex pathway will not affect the near responses of the pupil, and lesions of the visual pathway caudal to the point where the light reflex fibers leave the optic tract will not alter the pupillary light reflex (Fig. 13-9).


Neurology_Adams

Neurology_Adams. The “relative afferent pupillary defect,” or Marcus Gunn pupillary sign, exposes a retrobulbar optic neuropathy. It is best identified by the “swinging-flashlight test,” in which each pupil is alternately exposed to light at 1-s intervals; the pupils both show a poor constriction or even paradoxical dilatation when light is shined on the side of an optic neuropathy. It is best to assess in a dimly lighted room with the patient fixating on a distant target. Hippus, a rapid fluctuation in pupillary size, is common in metabolic encephalopathy but otherwise has no particular significance and is occasionally seen in normal persons. To distinguish hippus from the Marcus Gunn afferent pupillary defect one carefully observes the first movement of the pupil as the light is repeatedly moved to the affected eye; in hippus, half of the initial responses will be dilation and half, constriction, whereas in a deafferented pupil all the initial movements are dilation.


Neurology_Adams

Neurology_Adams. Interruption of the sympathetic fibers results in miosis and ptosis (because of paralysis of the pupillary dilator muscle and of Müller muscle, respectively). The lesion may be central, between the hypothalamus and the points of exit of sympathetic fibers from the spinal cord (C8 to T3, mainly T2), or peripheral, in the cervical sympathetic chain, superior cervical ganglion, or along the carotid artery. A congenital form caused by perinatal injury, usually of the sympathetic chain in the neck is seen regularly (Fig. 13-10). A hereditary form of the Horner syndrome (autosomal dominant) is also known, usually but not always associated with a congenital absence of pigment in the affected iris (heterochromia iridis) (Hageman et al).


Neurology_Adams

Neurology_Adams. To the ophthalmic findings may be added loss of sweating on the same side of the face and redness of the conjunctiva. The entire complex is called the Horner syndrome, Bernard-Horner syndrome, or oculosympathetic palsy. The pupillary change may be subtle and may require covering the eyes or dimming the room lights to observe the lack of expected mydriasis on one side.


Neurology_Adams

Neurology_Adams. Most cases are caused by peripheral interruption of the sympathetic chain but the same effect may be produced by ipsilateral lesions of the sympathetic tract in the medulla or cervical cord. The pattern of sweating may be helpful in localizing the lesion in the following manner: With lesions at the level of the common carotid artery, loss of sweating involves the entire side of the face. With lesions distal to the carotid bifurcation, loss of sweating is not found or is confined to the medial aspect of the forehead and side of the nose (Morris et al). Retraction of the eyeball (enophthalmos), considered a component of the syndrome, is probably an illusion created by narrowing of the palpebral fissure.


Neurology_Adams

Neurology_Adams. Bilateral Horner syndrome is a rare occurrence; usually it is found in autonomic neuropathies and in high cervical cord transection. Although difficult to appreciate, bilateral miosis may be detected (using pupillometry or direct observation) by noting a lag in the redilation of the initially small pupils when light is withdrawn (Smith and Smith, 1999). Stimulation or irritation of the sympathetic fibers, a rare phenomenon, has the opposite effect, that is, lid retraction, dilatation of the pupil, and apparent proptosis. Use is made of this phenomenon in the testing of the ciliospinal pupillary reflex, which is evoked by pinching the neck (afferent, C2, C3) and effecting pupillary enlargement through cervical efferent sympathetic fibers.


Neurology_Adams

Neurology_Adams. Extreme bilateral constriction of the pupils (miosis) is commonly observed with pontine lesions, presumably because of interruption of the pupillodilator fibers but the mechanism is not entirely clear. Narcotic ingestion is the most common cause of bilateral miosis in clinical practice except in the elderly, who often acquire small pupils, particularly if medication drops for glaucoma are being used. Interruption of the parasympathetic fibers causes an abnormal dilatation of the pupils (mydriasis), often with loss of pupillary light reflex; in cases of coma, the “blown” pupil (Hutchinson pupil) is the result of a midbrain lesion or direct compression of the oculomotor nerve (see Chap. 16). Other signs of oculomotor palsy are usually conjoined.


Neurology_Adams

Neurology_Adams. As an ancillary test to determine the cause of changes in the size of the pupils, the functional integrity of the sympathetic and parasympathetic nerve endings in the iris may be determined by the use of certain drugs detailed in the next section. Atropinics dilate the pupils by paralyzing the parasympathetic nerve endings; physostigmine and pilocarpine constrict the pupils, the former by inhibiting cholinesterase activity at the neuromuscular junction and the latter by direct stimulation of the sphincter muscle of the iris. Epinephrine and phenylephrine dilate the pupils by direct stimulation of the dilator muscle. Morphine and other narcotics act centrally to constrict the pupils.


Neurology_Adams

Neurology_Adams. In an eye with intact sympathetic innervation, cocaine dilates the pupils by preventing the reabsorption of norepinephrine into the nerve endings. With Horner syndrome, the normal pupil will dilate but the miotic pupil will remain small, and a difference in size of 0.8mm or greater is considered diagnostic (Kardon). More recently, apraclonidine, a weak direct alpha-agonist drug has been shown to reliably reverse the anisocoria of Horner syndrome and has become the preferred drug for testing. Normally apraclonidine does not exert significant dilatory effect, but with denervation hypersensitivity that accompanies Horner syndrome, the miotic pupil dilates in response to the drug. One drop (0.5 percent solution) is placed in each eye, the eyes are kept closed for 1 min and the drops are repeated 5 min later. Enlargement of the miosis with the affected pupil becoming larger than the unaffected one 30 to 45 min after instillation is definite evidence of a Horner syndrome. Ptosis is also


Neurology_Adams

Neurology_Adams. 5 min later. Enlargement of the miosis with the affected pupil becoming larger than the unaffected one 30 to 45 min after instillation is definite evidence of a Horner syndrome. Ptosis is also reduced, sometimes to a remarkable extent. It was originally developed as a treatment for glaucoma (Koc et al).


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Neurology_Adams. In diabetes mellitus, where autonomic spinal and cranial nerves are often involved, the pupils are affected in the majority of cases. They are smaller than would be expected for age because of involvement of pupillodilator sympathetic fibers, and mydriasis may be excessive upon instillation of sympathomimetic drugs. The light reflex, mediated by parasympathetic fibers is also reduced, usually to a greater degree than constriction on accommodation (Smith and Smith, 1987). Some of these abnormalities require special methods for their demonstration.


Neurology_Adams

Neurology_Adams. In almost all the forms of late syphilis, particularly tabes dorsalis, the pupils are bilaterally small, irregular, and unequal; they fail to react to light, although they do constrict on accommodation (light-near dissociation) and do not dilate properly in response to mydriatic drugs. Atrophy of the iris is associated in some cases. This is known as the Argyll Robertson pupil. The exact locality of the lesion is not certain but it is generally believed to be in the tectum of the midbrain proximal to the oculomotor nuclei where the descending pupillodilator fibers are in close proximity to the light reflex fibers (Fig. 13-9). A similar pupillary abnormality has been observed in the meningoradiculitis of Lyme disease and in diabetes. A dissociation of the light reflex from the accommodation-convergence reaction is also part of the dorsal midbrain syndrome but miosis, irregularity of pupils, and failure to respond to a mydriatic are usually not present.


Neurology_Adams

Neurology_Adams. Another interesting pupillary abnormality is the tonic reaction, also referred to as the Adie pupil. This syndrome is caused by a degeneration of the ciliary ganglia and the postganglionic parasympathetic fibers that normally constrict the pupil and effect accommodation. The patient may complain of unilateral blurring of vision or photophobia or may have noticed that one pupil is larger than the other. At the outset of the syndrome, the affected pupil is slightly enlarged in ambient light and the reaction to light is absent or greatly reduced if tested in the customary manner, although the pupil will slowly constrict with prolonged bright light stimulation. Characteristically, there is a light-near dissociation, that is, like the Argyll Robertson pupil, the Adie pupil responds better to near (accommodation) than it does to light. The most characteristic feature is that once the pupil has constricted, it tends to remain tonically constricted and redilates very slowly (the “tonic”


Neurology_Adams

Neurology_Adams. to near (accommodation) than it does to light. The most characteristic feature is that once the pupil has constricted, it tends to remain tonically constricted and redilates very slowly (the “tonic” aspect of the syndrome). Once dilated, the pupil remains in this state for many seconds, up to a minute or longer. Paralysis of a segment or segments of the pupillary sphincter is also characteristic of the syndrome; this segmental irregularity can be seen with the high plus lenses of an ophthalmoscope. The affected pupil constricts promptly in response to the common miotic drugs and, due to denervation supersensitivity, is unusually sensitive to a 0.1 percent solution of pilocarpine, a concentration that has only minimal effect on a normal pupil.


Neurology_Adams

Neurology_Adams. The tonic pupil usually appears during the third or fourth decade of life and is much more common in women than in men; it may be associated with absence of knee or ankle jerks (Holmes-Adie syndrome) and hence be mistaken for tabes dorsalis. From all available data, it represents a special form of mild inherited polyneuropathy. There can be a familial tendency to the syndrome. We have observed it as an accompaniment of a diffuse ganglionopathy associated with Sjögren disease, other autoimmune or paraneoplastic illnesses, and following recovery from the Guillain-Barré syndrome.


Neurology_Adams

Neurology_Adams. This rare pupillary phenomenon is characterized by transient episodes of unilateral mydriasis for which no cause can be found (the springing pupil). Episodes of mydriasis, which are more common in women, last for minutes to days and may recur at random intervals. Oculomotor palsies and ptosis are not present. Sometimes the pupil is distorted into an ovoid or tadpole shape during the attack. Some patients complain of blurred vision and head pain on the side of the mydriasis, suggesting an atypical ophthalmoplegic migraine. In children, following a minor or major seizure, one pupil may remain dilated for a protracted period of time. The main consideration in an awake patient is that the cornea has inadvertently (or purposefully) been exposed to mydriatic solutions, among them bronchodilator drugs, scopolamine, and some organophosphate pesticides. Differential Diagnosis of Anisocoria (Fig. 13-11)


Neurology_Adams

Neurology_Adams. Differential Diagnosis of Anisocoria (Fig. 13-11) In regard to pupillary disorders, there are two main issues with which the neurologist has to contend. One is the problem of unequal pupils (anisocoria), and determining whether this abnormality is derived from sympathetic or parasympathetic denervation. The second problem is the relative afferent pupillary defect, and how to recognize it; this was discussed earlier. In dealing with anisocoria, 20 percent of normal persons show an inequality of 0.3 to 0.5 mm or more in pupillary diameter. This is “simple,” or physiologic, anisocoria, and it may be a source of confusion in patients with small pupils. Its main characteristic is that the same degree of asymmetry in size is maintained in low, ambient, and bright light conditions. It is also variable from day to day and even from hour to hour, and often will have disappeared at the time of a second examination (Loewenfeld; Lam et al).


Neurology_Adams

Neurology_Adams. The first step in the analysis of pupillary asymmetry is to determine which of the pupils is abnormal. An abnormal larger pupil can be identified by a reduced direct and consensual light reaction. If the smaller pupil is causing asymmetry, it will fail to enlarge in response to shading both eyes, or reducing ambient light. More simply stated, light exaggerates the anisocoria caused by a third-nerve lesion, and darkness accentuates the anisocoria in the case of a Horner syndrome.


Neurology_Adams

Neurology_Adams. A persistently small pupil always raises the question of a Horner syndrome, a diagnosis that may be difficult if the ptosis is slight. In darkness, the Horner pupil dilates more slowly and to a lesser degree than the normal one because it lacks the pull of the dilator muscle (dilation lag). The diagnosis in the past had been confirmed by placing 1 or 2 drops of 2 to 10 percent cocaine in each eye; the Horner pupil dilates not at all or much less than the normal one. A more recently introduced approach that is more dependable and obviates the difficulties in obtaining cocaine is to apply the α-agonist apraclonidine to both eyes and observe the reversal of miosis on the affected side of Horner syndrome (the opposite effect to cocaine). Such responses to either drug will occur with a lesion at any point along the sympathetic pathway because lesions of the firstor second-order sympathetic neurons reduce the release of norepinephrine from third-order neurons. The reduction of


Neurology_Adams

Neurology_Adams. a lesion at any point along the sympathetic pathway because lesions of the firstor second-order sympathetic neurons reduce the release of norepinephrine from third-order neurons. The reduction of neurotransmitter at the nerve endings in the ciliary dilator muscle greatly reduces the reuptake blocking effects of cocaine. If the subsequent (24 h after cocaine) application of the adrenergic mydriatic hydroxyamphetamine (1 percent) has no effect, the lesion can be localized to the postganglionic portion of the pathway as this drug releases any norepinephrine that may remain in the third-order neuron. Localization of the lesion to the central or preganglionic parts of the sympathetic pathway depends upon the associated symptoms and signs (see Chap. 26).


Neurology_Adams

Neurology_Adams. A variety of lesions, some of them purely ocular, such as uveitis, may also give rise to a dilated pupil. Drug-induced iridoplegia is another cause of anisocoria. Not infrequently, particularly among nurses and pharmacists, a mydriatic fixed pupil is the result of accidental or deliberate application of an atropinic or sympathomimetic drug. We have observed this in house officers after they had participated in resuscitation from a cardiac arrest and been inadvertently sprayed with a sympathomimetic drug. Failure of 1 percent pilocarpine drops to contract the pupil provides proof that the iris sphincter has been blocked by atropine or some other anticholinergic agent. This is particularly the case when only one eye is affected.


Neurology_Adams

Neurology_Adams. As a rule, bilateral smallness of pupils does not pose a difficult diagnostic problem. The clinical associations, acute and chronic, have already been discussed. Long-standing bilateral Adie pupils tend to be small and show tonic near responses. They can be readily distinguished from Argyll Robertson pupils, which constrict quickly to near (accommodation) and redilate quickly on release from the near stimulus. Figure 13-11 is a useful schematic, devised by Thompson and Pilley, for sorting out the various types of anisocoria. Antonini G, Nemni R, Giubilei F, et al: Autoantibodies to glutamic acid decarboxylase in downbeat nystagmus. J Neurol Neurosurg Psychiatry 74:998, 2003. Aramideh M, Ongerboer de Visser BW, et al: Electromyographic features of levator palpebrae superioris and orbicularis oculi muscles in blepharospasm. Brain 117:27, 1994. Bahn RS, Heufelder AE: Pathogenesis of Graves’ ophthalmopathy. N Engl J Med 329:1468, 1993.


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Neurology_Adams. Bahn RS, Heufelder AE: Pathogenesis of Graves’ ophthalmopathy. N Engl J Med 329:1468, 1993. Baloh RW, Yee RD, Honrubia V: Late cortical cerebellar atrophy: Clinical and oculographic features. Brain 109:159, 1986. Bogousslavsky J, Miklossy J, Deruaz JP, et al: Unilateral left paramedian infarction of thalamus and midbrain: A clinicopathological study. J Neurol Neurosurg Psychiatry 49:686, 1986. Büttner-Ennever JA, Akert K: Medial rectus subgroups of the oculomotor nucleus and their abducens internuclear input in the monkey. J Comp Neurol 197:17, 1981. Caplan LR: “Top of the basilar” syndrome. Neurology 30:72, 1980. Cogan DG: A type of congenital ocular motor apraxia presenting jerky head movements. Am J Ophthalmol 36:433, 1953. Cogan DG: Internuclear ophthalmoplegia, typical and atypical. Arch Ophthal 84:583, 1970. Cogan DG: Neurology of the Ocular Muscles, 2nd ed. Springfield, IL, Charles C Thomas, 1956.


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Neurology_Adams. Cogan DG: Internuclear ophthalmoplegia, typical and atypical. Arch Ophthal 84:583, 1970. Cogan DG: Neurology of the Ocular Muscles, 2nd ed. Springfield, IL, Charles C Thomas, 1956. Cogan DG: Neurology of the Visual System. Springfield, IL, Charles C Thomas, 1966. Corbett JJ, Thompson HS: Pupillary function and dysfunction. In: Asbury AK, McKhann GM, McDonald WI (eds): Diseases of the Nervous System, 2nd ed. Philadelphia, Saunders, 1992, pp 490–500. Crino PR, Galetta SL, Sater RA, et al: Clinicopathologic study of paraneoplastic brainstem encephalitis and ophthalmoparesis. J Neuroophthalmol 16:44, 1996. Donahue SP: Pediatric strabismus. N Engl J Med 356:1040, 2007. Fisher CM: Some neuro-ophthalmological observations. J Neurol Neurosurg Psychiatry 30:383, 1967. Ford CS, Schwartze GM, Weaver RG, Troost BT: Monocular elevation paresis caused by an ipsilateral lesion. Neurology 34:1264, 1984.


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Neurology_Adams. Ford CS, Schwartze GM, Weaver RG, Troost BT: Monocular elevation paresis caused by an ipsilateral lesion. Neurology 34:1264, 1984. Glaser JS (ed): Neuro-Ophthalmology, 3rd ed. Philadelphia, Lippincott Williams & Wilkins, 1999. Hageman G, Ippel PF, Nijenhuis F: Autosomal dominant congenital Horner syndrome in a Dutch family. J Neurol Neurosurg Psychiatry 55:28, 1992. Halmagyi GM, Rudge P, Griesty M, Sanders MD: Downbeating nystagmus. Arch Neurol 40:777, 1983. Hanson MR, Hamid MA, Tomsak RL, et al: Selective saccadic palsy caused by pontine lesions: Clinical, physiological and pathological correlations. Ann Neurol 20:209, 1986. Hattar S, Liao HW, Takao M, Berson DM, Yau KW: Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 295: 1065, 2002. Hommel M, Bogousslavsky J: The spectrum of vertical gaze palsy following unilateral brainstem stroke. Neurology 41:1229, 1991.


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Neurology_Adams. Hommel M, Bogousslavsky J: The spectrum of vertical gaze palsy following unilateral brainstem stroke. Neurology 41:1229, 1991. Kardon RH, Denison CE, Brown CK, Thompson HS: Critical evaluation of the cocaine test in the diagnosis of Horner’s syndrome. Arch Ophthalmol 108:384, 1990. Kato I, Nakamura T, Watanabe J, et al: Primary posterior upbeat nystagmus: Localizing value. Arch Neurol 42:819, 1985. Keane JR: Acute bilateral ophthalmoplegia: 60 cases. Neurology 36:279, 1986. Keane JR: Bilateral ocular paralysis. Analysis of 31 inpatients. Arch Neurol 64:178, 2007. Keane JR: Cavernous sinus syndrome: Analysis of 151 cases. Arch Neurol 53:967, 1996. Keane JR: Internuclear ophthalmoplegia. Unusual causes in 114 of 410 patients. Arch Neurol 62:714, 2005. Keane JR: Ocular skew deviation. Arch Neurol 32:185, 1975. Kline IB, Hoyt WF: The Tolosa-Hunt syndrome. J Neurol Neurosurg Psychiatry 71:577, 2001.


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Neurology_Adams. Keane JR: Ocular skew deviation. Arch Neurol 32:185, 1975. Kline IB, Hoyt WF: The Tolosa-Hunt syndrome. J Neurol Neurosurg Psychiatry 71:577, 2001. Koc F, Kavuncu S, Kansu T, et al: The sensitivity and specificity of 0.5% apraclonidine in the diagnosis of oculosympathetic paralysis. Br J Ophthalmol 89:1442, 2005. Lam BL, Thompson HS, Corbett JJ: The prevalence of simple anisocoria. Am J Ophthalmol 104:69, 1987. Leichnetz GR: The prefrontal cortico-oculomotor trajectories in the monkey. J Neurol Sci 49:387, 1981. Leigh RJ, Zee DS: The Neurology of Eye Movements, 2nd ed. Philadelphia, Davis, 1991. Lewis RF, Zee DS: Ocular motor disorders associated with cerebellar lesions: Pathophysiology and topical localization. Rev Neurol 149:665, 1993. Loewenfeld IE: “Simple, central” anisocoria: A common condition seldom recognized. Trans Am Acad Ophthalmol Otolaryngol 83:832, 1977. Morris JGL, Lee J, Lim CL: Facial sweating in Horner’s syndrome. Brain 107:751, 1984.


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Neurology_Adams. Morris JGL, Lee J, Lim CL: Facial sweating in Horner’s syndrome. Brain 107:751, 1984. Palla A, Straumann D: Neurological evaluation of acute vertical diplopia. Schweiz Arch Neurol Psychiatr 153:180, 2002. Ropper AH: Illusion of tilting of the visual environment. J Clin Neuroophthalmol 3:147, 1983. Ropper AH: Ocular dipping in anoxic coma. Arch Neurol 38:297, 1981. Rucker CW: Paralysis of the third, fourth, and sixth cranial nerves. Am J Ophthalmol 46:787, 1958. Rucker CW: The causes of paralysis of the third, fourth and sixth cranial nerves. Am J Ophthalmol 61:1293, 1966. Rush JA, Younge BR: Paralysis of cranial nerves III, IV, and VI: Cause and prognosis in 1000 cases. Arch Ophthalmol 99:76, 1981. Safran AB, Kline LB, Glaser JS, Daroff RB: Television-induced formed visual hallucinations and cerebral diplopia. Br J Ophthalmol 65:707, 1981. Saul RF, Selhorst JB: Downbeat nystagmus with magnesium depletion. Arch Neurol 38:650, 1981.


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Neurology_Adams. Saul RF, Selhorst JB: Downbeat nystagmus with magnesium depletion. Arch Neurol 38:650, 1981. Smith AS, Smith SC: Assessment of pupillary function in diabetic neuropathy. In: Dyck PJ, Thomas PK, Asbury AK, et al (eds): Diabetic Neuropathy. Philadelphia, Saunders, 1987, pp 134–139. Smith SA, Smith SE: Bilateral Horner’s syndrome: Detection and occurrence. J Neurol Neurosurg Psychiatry 66:48, 1999. Thach WT, Montgomery EB: Motor system. In: Pearlman AL, Collins RC (eds): Neurobiology of Disease. New York, Oxford University Press, 1990, pp 168–196. Thompson HS, Pilley SFJ: Unequal pupils: A flow chart for sorting out the anisocorias. Surv Ophthalmol 21:45, 1976. Tijssen CC: Contralateral conjugate eye deviation in acute supratentorial lesions. Stroke 25:215, 1994. Vidailhet M, Rivaud S, Gouider-Khouja N, et al: Eye movements in parkinsonian syndromes. Ann Neurol 35:420, 1994.


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Neurology_Adams. Vidailhet M, Rivaud S, Gouider-Khouja N, et al: Eye movements in parkinsonian syndromes. Ann Neurol 35:420, 1994. Wall M, Wray SH: The one-and-a-half syndrome—a unilateral disorder of the pontine tegmentum: A study of 20 cases and review of the literature. Neurology 33:971, 1983. Warwick R: Representation of the extraocular muscles in the oculomotor nuclei of the monkey. J Comp Neurol 98:449, 1953. Warwick R: The so-called nucleus of convergence. Brain 78:92, 1955. Wiersinga WM, Smit T, van der Gaag R, et al: Clinical presentation of Grave’s ophthalmopathy. Ophthalmic Res 21:73, 1989. Wray SH: Neuro-ophthalmologic diseases. In: Rosenberg RN (ed): Comprehensive Neurology. New York, Raven Press, 1991, pp 659–697. Wray SH, Taylor J: Third nerve palsy: A review of 206 cases. Unpublished data, quoted in Wray SH (above).


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Neurology_Adams. Wray SH, Taylor J: Third nerve palsy: A review of 206 cases. Unpublished data, quoted in Wray SH (above). Yousry I, Dieterich M, Naidich TP, et al: Superior oblique myokymia: Magnetic resonance imaging support for the neurovascular compression hypothesis. Ann Neurol 51:361, 2002. Zee DS: Ophthalmoscopy in examination of patients with vestibular disorders. Ann Neurol 3:373, 1978. Zee DS, Robinson DA: A hypothetical explanation of saccadic oscillations. Ann Neurol 5:405, 1979. Zee DS, Yee RD, Cogan DG, et al: Ocular motor abnormalities in hereditary cerebellar ataxia. Brain 99:207, 1976. Zee DS, Hain TC, Carl JR: Abduction nystagmus in internuclear ophthalmoplegia. Ann Neurol 21:383, 1987.


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Neurology_Adams. Zee DS, Hain TC, Carl JR: Abduction nystagmus in internuclear ophthalmoplegia. Ann Neurol 21:383, 1987. Figure 13-1. The supranuclear pathways subserving horizontal gaze to the left. The pathway originates in the right frontal cortex, descends in the internal capsule, decussates at the level of the rostral pons, and descends to synapse in the left pontine paramedian reticular formation (PPRF). Further connections with the ipsilateral sixth nerve nucleus and contralateral medial longitudinal fasciculus are also indicated. The right MLF (green line) is labeled between the abducens and oculomotor nuclei and the vestibular nuclei (VN) are shown on the right. LR, lateral rectus; MLF, medial longitudinal fasciculus; MR, medial rectus.


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Neurology_Adams. Figure 13-2. Pathways for the control of vertical eye movements. The main structures are the interstitial nucleus of Cajal (INC), the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), and the subnuclei of the third nerve, all located in the dorsal midbrain. Voluntary vertical movements are initiated by the simultaneous activity of both frontal cortical eye fields. The riMLF serves as the generator of vertical saccades and the INC acts tonically to hold eccentric vertical gaze. The INC and riMLF connect with their contralateral nuclei via the posterior commissure, where fibers are subject to damage. Projections for upgaze cross through the commissure before descending to innervate the third nerve nucleus, while those for downgaze may travel directly to the third nerve, thus accounting for the frequency of selective upgaze palsies (see text). The MLF carries signals from the vestibular nuclei, mainly ipsilaterally, to stabilize the eyes in the vertical plane


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Neurology_Adams. nerve, thus accounting for the frequency of selective upgaze palsies (see text). The MLF carries signals from the vestibular nuclei, mainly ipsilaterally, to stabilize the eyes in the vertical plane (VOR) and maintain tonic vertical position.


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Neurology_Adams. Figure 13-3. Topographic arrangement of oculomotor fascicular fibers in the mesencephalon. CCN, central caudal nucleus; IO, inferior oblique; IR, inferior rectus; LP, levator palpebrae; MR, medial rectus; P, pupil; SR, superior rectus. (From Ksiazek SM, Slamovits TL, Rosen CE, et al: Fascicular arrangement in partial oculomotor paresis. Am J Ophthalmol 118: 97, 1994. With permission.) Cerebral aqueductCorticospinal tractCorticospinal tractSubstantia nigraOculomotor nucleus (III N.)Red nucleusIII N.fibersVI N.fibersVII N.fibersFacial nucleusVII N.4th ventricleAbducens nucleus(VI N.)Inferior cerebellarpeduncleSuperior vestibularnucleusIII NerveNodulusAB


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Neurology_Adams. Figure 13-4. A. Midbrain in horizontal section, indicating the effects of lesions at different points along the intramedullary course of the third-nerve fibers. A lesion at the level of oculomotor nucleus results in homolateral third-nerve paralysis and homolateral anesthesia of the cornea. A lesion at the level of red nucleus results in homolateral third-nerve paralysis and contralateral ataxic tremor (Benedikt and Claude syndromes). A lesion near the point of exit of third-nerve fibers results in homolateral third-nerve paralysis and crossed corticospinal tract signs (Weber syndrome; see Table 44-2). B. Brainstem at the level of the sixth-nerve nuclei, indicating effects of lesions at different loci. A lesion at the level of the nucleus results in homolateral sixthand seventh-nerve paralyses with varying degrees of nystagmus and weakness of conjugate gaze to the homolateral side. A lesion at the level of corticospinal tract results in homolateral sixth-nerve paralysis and crossed


Neurology_Adams

Neurology_Adams. with varying degrees of nystagmus and weakness of conjugate gaze to the homolateral side. A lesion at the level of corticospinal tract results in homolateral sixth-nerve paralysis and crossed hemiplegia (Millard-Gubler syndrome).


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Neurology_Adams. AVein ofGalenTransversesinusCavernoussinusTrigeminalganglionInternal carotid arteryPituitarystalkN. XIIN. XN. IXN. VIIIN. VIIN. VIN. IVN. IIIV3V2V1Oculomotor N.Optic chiasmInternal carotidarteryHypophysisSella turcicaDiaphragmasellaDuramaterSphenoidsinusNasopharynxTrochlear N.Ophthalmic N. (V1)Maxillary N. (V2)Abducens N.B Figure 13-5. The cavernous sinus and its relation to the cranial nerves. A. Base of the skull; the cavernous sinus has been removed on the right. B. The cavernous sinus and its contents viewed in the coronal plane. SUP. RECT.INF. RECT.SUP. RECT.INF. RECT.INF. OBL.SUP. OBL.INF. OBL.SUP. OBL. Figure 13-6. Muscles chiefly responsible for vertical movements of the eyes in different positions of gaze. (Adapted by permission from Cogan DG: Neurology of the Ocular Muscles, 2nd ed. Springfield, IL, Charles C Thomas, 1956.) Upward gazeLeft gazeRight gazeDownward gazeRt. lat. rectusARt. med. rectusBRt. inf. rectusCRt. sup. rectusDRt. sup. obl.ERt. inf. obl.F


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Neurology_Adams. Figure 13-7. Diplopia fields with individual muscle paralysis. The red Maddox rod is in front of the right eye and gives rise to the straight line image, and the fields are projected as the patient sees the images. A. Paralysis of right lateral rectus. Characteristic: right eye does not move to the right. Field: the vertical red line is displaced to the right and the separation of images increases on looking to the right. B. Paralysis of right medial rectus. Characteristic: right eye does not move to the left. Field: horizontal crossed diplopia increasing on looking to the left. C. Paralysis of right inferior rectus. Characteristic: right eye does not move downward when eyes are turned to the right. Field: vertical diplopia (with the red line, seen by the right eye, displaced inferiorly) increasing on looking to the right and down. D. Paralysis of right superior rectus. Characteristic: right eye does not move upward when eyes are turned to the right. Field: vertical diplopia (with red