Neuro-ophthalmology in Medicine




Keywords

optic neuropathy, diplopia, ocular motor abnormalities, abducens nerve, trochlear nerve, oculomotor nerve, nystagmus, visual field deficits, anisocoria

 


Although rarely a comforting topic for the general neurologist, neuro-ophthalmologic disorders are best diagnosed using a systematic approach that emphasizes the patient’s history followed by confirmation of the localization with specific examination maneuvers. The neurologist needs be familiar with a few specialized techniques concerning ocular misalignment, fundus examination, and pupillary assessment in order to examine patients properly and guide their evaluation.




Afferent Visual Disturbances


Afferent neuro-ophthalmologic disorders may be limited to the eye (e.g., optic neuropathy), may be secondary to a primary neurologic disorder (e.g., papilledema from an intracranial tumor), or may be related to a systemic medical disorder (e.g., giant cell arteritis). The neuro-ophthalmologic examination provides a window to the diagnosis and natural history of the variety of medical conditions that present with afferent disturbances ( Table 24-1 ).



Table 24-1

Selected Manifestations of Neuro-Ophthalmologic Disease Across the Spectrum of Organ Systems












































Organ System Disease State Example of Neuro-Ophthalmologic Manifestation
Psychiatry Conversion disorder Functional blindness
Hematology Sickle cell disease Retrobulbar ischemic optic neuropathy
Cardiovascular Endocarditis Embolic retinal artery occlusion
Pulmonary Pulmonary hypertension Papilledema
Renal Chronic renal failure Intracranial hypertension
Gastrointestinal Pancreatitis Purtscher syndrome
Genitourinary Ovarian cancer Paraneoplastic syndromes with cerebellar degeneration (e.g., with anti-Yo antibodies)
Endocrine Graves disease Compressive optic neuropathy due to increased orbital fat content and enlarged extraocular muscles
Obstetric Eclampsia Cerebral blindness from posterior reversible encephalopathy syndrome (PRES)


Optic Neuropathy


The optic nerve is approximately 50 mm in length and is anatomically separated into intraocular, intraorbital, intracanalicular, and intracranial regions. Damage to the optic nerve can occur anywhere along its course, and optic neuropathy may result from ischemic, demyelinating, compressive, genetic, infiltrative, nutritional, traumatic, or toxic causes ( Table 24-2 ).



Table 24-2

Classification of Optic Neuropathy
















































Category Prototypic Examples Comment
Inflammatory/demyelinating Optic neuritis Usually associated with multiple sclerosis or neuromyelitis optica
Paraneoplastic CRMP5, an autoantibody directed against collapsin response-mediator family Reported with small cell lung cancer, lymphoma, nasopharyngeal carcinoma, and neuroblastoma
Infectious Tuberculosis, cryptococcosis, human herpesvirus 6 infection, Bartonella infection These infections causing optic neuropathy should prompt evaluation for infection with human immunodeficiency virus
Ischemic Ischemic optic neuropathy (arteritic and nonarteritic), retinal artery occlusion (central or branch) Funduscopy may show occlusive material (Hollenhorst plaque) in retinal artery occlusions
Compressive Optic nerve sheath meningioma, Graves ophthalmopathy Proptosis often present.
Exophthalmos is synonymous with proptosis but is specifically used in reference to Graves disease
Infiltrative Sarcoidosis, metastasis, lymphoma Orbit MRI often shows persistent enhancement of the optic nerve
Traumatic Direct (penetrating) trauma, indirect trauma (often frontal or midfacial), or chiasmal Injury due to compression, avulsion, or shear injury.
No evidence-based guidelines regarding optimal treatment
Nutritional Deficiency of vitamin B 1 , B 2 , B 12 , or folate Slowly progressive, symmetric optic neuropathy. Does not present acutely
Toxic Ethambutol, carbon monoxide, methanol, tobacco-alcohol amblyopia, amiodarone Typically bilateral and symmetric.
May improve with removal of offending agent
Hereditary Leber, Kjer (dominant optic atrophy) optic neuropathies Leber optic neuropathy is transmitted via maternally inherited mitochondrial mutation


Although the term “optic neuritis” is often used to describe any type of optic neuropathy, it is most appropriately used only to denote the inflammatory, demyelinating optic neuropathy that is either idiopathic or related to demyelinating disease such as multiple sclerosis (MS) or neuromyelitis optica (NMO). Inflammatory or infectious optic neuropathies from other known etiologies are best described in specific terms (e.g., sarcoid or syphilitic optic neuropathy).


Optic neuropathy may be classified anatomically as retrobulbar (i.e., posterior to the globe without disc swelling), or bulbar/anterior (usually associated with acute disc edema) ( Fig. 24-1 ). Optic neuropathy from any cause that results in retinal nerve fiber loss will eventually produce optic atrophy, appearing on funduscopic examination as visible nerve fiber layer loss and disc pallor, although disc coloration may be influenced by genetic, media, and retinal factors ( Fig. 24-2 ). Decreased visual function, as measured by visual acuity, perimetry, and color vision, may result from several causes, including etiologies that are not neuro-ophthalmic; however, the presence of a relative afferent pupillary defect strongly suggests the presence of optic nerve dysfunction, although occasionally a mild relative afferent pupillary defect may be present with widespread retinal dysfunction. Bilateral symmetric optic nerve dysfunction does not produce a relative afferent pupillary defect as there is no interside difference in light transmission in the optic nerve, although both pupils will react sluggishly.




Figure 24-1


A , Normal optic nerve. Note clearly visible vessels coursing over the disc edge, small central disc depression of the physiologic cup, and visible nerve fiber layer, especially in the superior and inferior arcades. B , Disc edema. Note obscurations of vessels coursing over the disc and swollen peripapillary nerve fiber layer causing disc elevation.



Figure 24-2


Optic atrophy. Note disc pallor and lack of visible nerve fiber layer striations.


Inflammatory Demyelinating Optic Neuritis


Optic neuritis may be idiopathic or associated with demyelinating disease, most commonly MS. The clinical course is characterized by a relatively sudden onset of typically unilateral visual loss. The condition worsens to a nadir over several days, and then recovery begins, typically within several weeks, independent of corticosteroid treatment (although intravenous corticosteroids given in a 3-day course followed by a 2-week oral prednisone course and taper is a frequently used therapy for optic neuritis).


Visual acuity at nadir ranges from 20/20 to no light perception. Pain occurs in more than 90 percent of cases, and often worsens with eye movement. Although centrocecal scotomas are classically associated with demyelinating optic neuritis, other types of field defects (e.g., central, altitudinal, diffuse, paracentral, and arcuate) frequently occur.


Demyelinating optic neuritis is retrobulbar in two-thirds of instances; the remainder of cases display disc edema acutely (“papillitis”). When disc swelling does occur, it is usually mild and diffuse. Magnetic resonance imaging (MRI) demonstrates contrast enhancement of the optic nerve in approximately 90 percent of cases of demyelinating optic neuritis within the first several weeks ( Fig. 24-3 ). Between 3 and 6 months after optic neuritis, optic atrophy becomes visible if there is nerve fiber loss, and visual evoked potentials may document delayed latencies. Not all cases of optic neuritis result in such optic atrophy.




Figure 24-3


Axial T1-weighted magnetic resonance imaging (MRI) demonstrating gadolinium enhancement of the left retrobulbar portion of the optic nerve ( arrow ).


The Optic Neuritis Treatment Trial followed patients with optic neuritis longitudinally and found that 72 percent of subjects had recovered visual acuity to at least 20/20, and 85 percent had acuity of at least 20/25 at 15 years after onset. If the initial visual acuity was limited to counting fingers or worse, there was a decreased chance of 20/20 (49%) or 20/25 (63%) visual recovery at 15 years. There was only a weak correlation between the severity of visual loss at baseline and recovery of vision in patients with an initial visual acuity between 20/20 and 20/200.


The baseline brain MRI predicts the risk of developing MS in the decades following optic neuritis, and accordingly is an important test following a first attack of optic neuritis. The number of T2-weighted hyperintensities at least 3 mm in size on baseline MRI reflects the likelihood that a patient with optic neuritis will develop MS. A normal baseline MRI is associated with a 25 percent chance of developing MS in 15 years. The presence of just one lesion increases the 15-year cumulative probability of MS to 60 percent, while three or more lesions on the baseline brain MRI increase the likelihood to approximately 80 percent. Optic nerve enhancement itself is not counted as a lesion. The majority of patients developing MS do so within the first 5 years. The overall risk of developing MS within 15 years after optic neuritis is 50 percent, independent of MRI findings, a figure that can be used to counsel those patients who cannot obtain an MRI.


MRI characteristics also predict future disability in patients with optic neuritis. Spinal cord and infratentorial lesions as well as enhancing lesions are associated with a higher future disability. In patients with optic neuritis who go on to develop MS, lesions in the spinal cord have the highest correlation with disability.


Neuromyelitis Optica


Optic neuritis from neuromyelitis optica (NMO) is more likely to be bilateral, involve the chiasm, and result in more severe vision loss ( Fig. 24-4 ). Optical coherence tomography is a noninvasive means of quantifying retinal nerve fiber layer atrophy or elevation. These axons comprise the optic nerve, and axonal thickness correlates with visual function. NMO-related optic neuritis is associated with greater retinal nerve fiber layer loss than MS, corresponding to the more severe vision loss in these patients ( Fig. 24-5 ).




Figure 24-4


Axial T1-weighted gadolinium-enhanced brain MRI at the level of the optic chiasm. A , Normal optic chiasm ( arrow ) does not enhance. B , An acute attack of neuromyelitis optica (NMO) resulting in abnormal enhancement of the optic chiasm ( arrow ).



Figure 24-5


Optical coherence tomography demonstrating severe optic atrophy. Note sector (green arrow) and quadrant (black arrow) maps depicting dramatic nerve fiber layer (RNFL) loss in all quadrants. The average RNFL values of 34.1 (OD) and 27.02 (OS) microns indicate extreme optic atrophy (normal average RNFL ~104).


Early treatment of NMO-associated optic neuritis with high-dose corticosteroids is associated with preservation of retinal nerve fiber layer. In contrast to typical MS-related optic neuritis in which the final visual acuity is not influenced by corticosteroid treatment, visual outcomes in NMO patients may be improved with early corticosteroid therapy. Consequently, it is imperative to attempt to distinguish MS from NMO in the acute stage; bilaterality, severe visual acuity loss at onset, and recurrent visual decline following corticosteroid treatment are factors suggestive of NMO. In cases where corticosteroids are ineffective or only transiently helpful, plasma exchange can be utilized; the effectiveness may depend on how early treatment is initiated.


Ischemic Optic Neuropathy


Several different ischemic conditions may cause visual loss ( Table 24-3 ). Ischemic optic neuropathy is the most common cause of acute visual loss in older patients, and may be divided into arteritic (e.g., giant cell arteritis) and nonateritic varieties. Nonarteritic anterior ischemic optic neuropathy (NAION) is always associated with disc edema acutely; the pathophysiologic mechanism of cell death is presumed to be mainly ischemic, but cellular infiltration with polymorphonuclear cells and macrophages also occurs as a response to the initial insult.



Table 24-3

Neuro-Ophthalmologic Disorders Due to Ischemic Disease
































Category Funduscopic Features Systemic Associations
Nonarteritic anterior ischemic optic neuropathy (NAION) Generalized or sectoral disc edema, flame-shaped peripapillary hemorrhages, disc-at-risk in opposite eye Diabetes, nocturnal hypotension, antihypertensive medications, sleep apnea
Nonarteritic posterior ischemic optic neuropathy Normal in acute stage. May result in disc atrophy chronically Severe systemic hypotension or anemia, sepsis
Arteritic ischemic optic neuropathy Pallidedema, evidence of choroidal ischemia, infarction in distribution of cilio-retinal artery, if present Giant-cell arteritis, polymyalgia rheumatica, thrombocytosis, inflammatory aortitis
Diabetic papillopathy Similar in appearance to NAION, but severity of fundus appearance may be out of proportion to relative sparing of visual function Diabetes mellitus, diabetic retinopathy
Central retinal artery occlusion Normal optic disc, but with generalized retinal edema with cherry-red macular spot Carotid atherosclerosis, hypertension, tobacco use, hyperhomocysteinemia
Branch retinal artery occlusion Normal optic disc with focal area of retinal edema, at times associated with a visible occlusive plaque Carotid atherosclerosis, hypertension, tobacco use


NAION typically presents with sudden, painless, unilateral vision loss, often with an altitudinal visual field defect ( Fig. 24-6 ). Acutely disc edema may be focal or diffuse. The optic disc has a characteristic “disc-at-risk” appearance, defined by a small cup-to-disc ratio that is best observed in the opposite eye in the acute phase. Treatment for NAION is limited—systemic high-dose corticosteroids, intravitreal bevacizumab, and optic nerve decompression surgery are not effective. The risk to the opposite eye is approximately 15 percent over the next several years, and efforts should be made to address vascular risk factors such as hypertension, hyperlipidemia, and tobacco abuse.




Figure 24-6


Bilateral visual field defects in sequential nonarteritic anterior ischemic optic neuropathy. The right eye demonstrates an inferior arcuate defect with “nasal step” while the left eye reveals denser inferior field defect.


Giant-cell arteritis (arteritic anterior ischemic optic neuropathy) is a neuro-ophthalmic emergency, which may cause ischemia to the optic or oculomotor nerve, retina, orbit, or extraocular muscles, leading to permanent visual loss, diplopia, or both. Arteritic anterior ischemic optic neuropathy occurs in elderly patients with systemic symptoms such as tongue or jaw claudication, headache, scalp tenderness, fever, anorexia, weight loss, or polymyalgia rheumatica. Laboratory abnormalities include elevation of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and thrombocytosis; a normal ESR may be present in up to one-third of patients, so CRP and ESR should be ordered together and have a combined sensitivity of 99 percent. The diagnosis is made clinically; temporal artery biopsy often demonstrates characteristic giant cells, noninfectious granulomas, inflammatory infiltrates, and interruption of the internal elastic lamina. Immediate treatment with corticosteroids is indicated when giant cell arteritis is suspected and should be initiated even before biopsy, as histopathologic findings will persist for some time following corticosteroid exposure.


Posterior ischemic optic neuropathy is extremely rare, and usually follows profound hypotension as a complication of surgery (especially prolonged spinal surgeries in the prone position), with severe anemia, or as a result of giant cell arteritis. Because the responsible lesion occurs distal to the lamina cribosa of the optic nerve, the disc is not swollen (thus “posterior”).


Compressive Optic Neuropathy


Compression of the optic nerve can occur anywhere along its pathway, with distinct pathophysiologies corresponding to various locations ( Table 24-4 ). Clinical characteristics of compressive optic neuropathies are dependent on the nature of the particular lesion. In general, these lesions are usually painless (unless other cranial nerves are affected) and subacutely progressive. Associated features of an orbital process may include proptosis and diplopia, the latter related to restricted extraocular muscles or ocular motor nerve involvement. MRI including fat-saturated post-gadolinium images is often the diagnostic tool of choice.



Table 24-4

Compressive Optic Neuropathy Locations and Etiology

























Orbit Sellar Region
Optic nerve sheath meningioma Pituitary adenoma
Orbital metastases Craniopharyngioma
Graves ophthalmopathy Meningioma
Idiopathic orbital inflammatory pseudotumor Internal carotid aneurysm
Primary bone lesions (fibrous dysplasia, Paget disease) Histiocytosis
Orbital fracture or hemorrhage


Genetic Optic Neuropathy


Several inherited optic neuropathies have been characterized, including Leber hereditary optic neuropathy (LHON), a maternally inherited mitochondrial optic neuropathy most common in younger males. Leber hereditary optic neuropathy typically produces bilateral, sequential, painless optic neuropathy with central scotomas. Acutely, the disc may appear erythematous with telangectactic vessels, but no true disc edema is present. Genetic testing for the major mutations is commercially available. There is currently no proven therapy, although idebenone has shown some promise.


Papilledema


Papilledema is defined as optic disc edema caused by elevated intracranial pressure (ICP) and should be distinguished from papillitis. Papilledema is nearly always bilateral, is accompanied by loss of venous pulsations, and varies in appearance from mild to severe ( Fig. 24-7 ). This range of appearances can be described by using the Frisén scale ( Table 24-5 ). The clinical features of papilledema often reflect those of elevated ICP and may include headache, diplopia related to abducens neuropathy, and transient visual obscurations; advanced papilledema produces visual field loss, often starting with an enlarging blind spot and progressing to arcuate nerve fiber layer defects, which may advance toward central visual loss if unchecked. Treatment is directed at the underlying pathology; optic nerve sheath fenestration is sometimes performed to help preserve vision by relieving direct optic nerve pressure. The most common causes of papilledema are listed in Table 24-6 .




Figure 24-7


Fundus photos showing papilledema. Both eyes are affected, as is typical. Features demonstrated include elevation of the retinal nerve layers, resulting in the appearance of a “doughnut”-shaped opacity around the optic disc. Peripapillary flame-shaped hemorrhages are visible, as well as engorgement of the retinal veins. Obscuration of the peripapillary blood vessels as they pass across the disc can be appreciated. The physiologic cups have disappeared.


Table 24-5

Frisén Scale for Rating Papilledema

























Frisen Grade Funduscopic Features
0 Normal except for mild blurring of the nasal and temporal disc
1 C-shaped peripapillary gray halo sparing temporal quadrant
2 360-degree gray peripapillary halo, nasal elevation
3 Obscuration of≥1 major vessel segment at disc border, 360-degree elevation
4 Total obscuration of a major vessel on the disc
5 Partial obscuration of all vessels on the disc


Table 24-6

Causes of Increased Intracranial Pressure Resulting in Papilledema








































Etiology Concomitant Features
Space-occupying brain lesion Subacutely worsening headache. Various neurologic defects depending on location
Meningoencephalitis Meningismus, abnormal cerebrospinal fluid chemistries
Subarachnoid hemorrhage Terson syndrome (intravitreal hemorrhage)
Cerebral edema Vasogenic (due to loss of intracranial capillary integrity), cytotoxic (due to cell death, often as a result of ischemic stroke), or interstitial edema
Venous sinus thrombosis Triad of seizure, encephalopathy, and headache is classic acute presentation
Cerebral aqueductal stenosis May be asymptomatic until critical stenosis causes drowsiness and stupor
Superior vena cava syndrome Dyspnea, face and arm swelling, Pemberton sign
Right heart failure Peripheral edema, ascites, hepatomegaly
Sleep apnea Hypertension, frequent napping, crowded oropharynx
Pulmonary hypertension Parasternal heave, jugular venous distention, clubbing
Idiopathic intracranial hypertension Obesity, female gender, childbearing age


Idiopathic Intracranial Hypertension


Idiopathic intracranial hypertension (IIH), or pseudotumor cerebri, is most characteristically a syndrome of obese females of childbearing age. Pediatric IIH is distinct in that the predisposition for obesity and female gender does not apply. The clinical characteristics of IIH include headache, pulsatile tinnitus, transient visual obscurations, and diplopia related to abducens nerve palsy. Patients with IIH may have variable Frisén grades of optic disc edema. Spontaneous venous pulsations are absent on funduscopic examination in patients with increased ICP, and lack of these may precede papilledema. The pathophysiology of IIH is not fully understood, but vitamin A metabolism, endocrine-secreting adipose tissue, and cerebral venous dysregulation are all proposed possibilities.


The diagnostic workup of IIH requires brain imaging to exclude other etiologies of papilledema including venous sinus thrombosis and mass lesions; this is best accomplished with MRI. Radiologic features of IIH that are supportive of the diagnosis include an enlarged optic nerve sheath, optic nerve tortuosity, protrusion of the optic nerve head, an empty sella, and concavity or flattening of the posterior globes ( Fig. 24-8 ). Conversely, the commonly described “slit-like ventricles” are not helpful in diagnosing IIH, and may reflect a normal imaging feature in young patients without brain atrophy.




Figure 24-8


Axial T2-weighted orbital MRI from a patient with idiopathic intracranial hypertension showing bulging of the papilla ( red arrows ), flattening of the posterior globe ( curved arrow ), and intraorbital nerve tortuosity ( white arrow ).


Initial treatment for IIH may include weight loss, low-salt diet, and pharmacotherapy with acetazolamide. In some cases, the cause is not idiopathic, and predisposing factors may include obstructive sleep apnea, vitamin A supplementation, tetracycline, or chronic anemia. When visual loss is severe and progressive despite medical management, or when headaches are intractable, surgical options include optic nerve sheath fenestration or lumboperitoneal or ventriculoperitoneal shunting.


Retrochiasmal Vision Loss


Lesions affecting postchiasmal afferent nerve pathways generally produce homonymous visual field loss, which may be a hemianopia or quadrantanopia depending on the location of the lesion. Unless there is concomitant involvement of the optic nerve or the field loss is bilateral, visual acuity is typically spared. The most common causes of homonymous visual field loss are stroke (69%), trauma (13%), tumor (11%), brain surgery (2%), and demyelinating lesions.


In addition to primary visual loss, compromise of visuospatial function, recognition of objects and faces (prosopagnosia), and motion perception can occur with damage to visual association areas. Current theory hypothesizes a ventral visual stream involving the temporal lobe (the “what” pathway) that is concerned with object recognition, and a dorsal stream connected to the parietal lobe (the “how” pathway) involved with object spatial location and motion. Ventral pathway dysfunction may produce difficulty with object recognition, whereas dorsal pathway lesions are associated with difficulty orienting to a location, which requires spatial attention. Spatial attention is also important for searching through a cluttered visual scene; as distracters are added to the environment, patients may demonstrate more difficulty in quickly identifying a target.


Early involvement with predominant visual deficits in neurodegenerative disorders occurs in Lewy body dementia and some forms of Alzheimer disease that involve the occipital and parietal lobes early in the course. Posterior cortical atrophy has been regarded by some as a variant of Alzheimer disease because of histologic similarities. The Heidenhain variant of Creutzfeldt–Jakob disease affects the occipital regions first.




Efferent Visual Disturbances


Clinical Assessment


The history in patients with diplopia should concentrate on whether the disorder is binocular or monocular, the orientation of the images, and symptom modifiers. Diplopia is always sudden in onset. Monocular diplopia—diplopia that remains when one eye is closed—is generally related to ocular causes (e.g., corneal or lens opacity, refractive error), and is not neurologic in origin. It typically resolves with the pinhole test and should prompt ophthalmology referral. Binocular diplopia—related to misalignment of the eyes—resolves with closure of either eye, and is typically neurogenic in origin. The direction of misalignment and presence or change with position of gaze provide clues to the diagnosis. Other factors such as age, associated features (e.g., ptosis, pain), modifiers, and diurnal variation (e.g., fluctuations) guide the localization and differential diagnosis as discussed below.


Ocular misalignment refers to any deviation of the visual axis of one eye compared to the other. Ocular alignment can be measured on examination in several ways. The least precise method involves estimation of misalignment by displacement of the corneal light reflex (Hirschberg method). Light reflects from the same position on both corneas if the eyes are orthophoric, whereas the light is displaced from the center in one eye when misalignment exists; each millimeter of light reflex displacement equals approximately 7 to 10 deg or 15 to 20 prism diopters.


The red Maddox rod is a simple method to quantify even very small amounts of ocular misalignment. The Maddox rod is composed of a series of parallel cylindrical grooves in a piece of red glass, mounted in a circular rim. (The original consisted of a single cylindrical rod, hence the name.) The device converts a light source into a red line perpendicular to the axis of the rod. The patient views a white light source with the left eye, while the Maddox rod is placed over the right eye. The position of the red line relative to the light source (seen by the left eye) indicates the presence and amount of misalignment. The red line can be made to appear vertically (to measure horizontal deviation from the light) or horizontally (to measure vertical deviation from the light), and prisms can be placed over the Maddox rod until the line dissects the light. If the red line appears to the left of the light, then an exotropia exists. If the line appears to the right of the light, an esotropia is present. If the line appears below the light, then a right hypertropia is present, and red line above the light indicates a left hypertropia. Vertical misalignment is by convention always quantified by the hypertropic eye.


The alternate cover test is more difficult to perform, but is reliable and the most widely used method. The patient fixates on a specific letter of the Snellen chart at distance or near, while the examiner alternately covers one eye and then the other, thus forcing the patient to fixate with the uncovered eye. If the eyes are orthophoric, then no corrective eye movement will be required to fixate on the target when the occluded eye is switched. If the right eye moves down to fix the target immediately after it is uncovered and the left eye is occluded, then a hypertropia exists, while an eye that has to move in toward the nose to fixate the target represents an exotropia, and eye movement out to fixate a target indicates an esotropia. A prism can be placed over one eye to neutralize this shift and quantify the misalignment. These alignment tests are repeated in the nine cardinal positions of gaze to discern the pattern of involvement.


The motility examination also includes assessment of pursuit, saccades, ductions, and versions. Pursuit is tested with the patient following a target (a large letter on the near card) moving slowly (less than 20 deg/sec) in the horizontal and vertical gaze. Saccades are rapid eye movements that “jump” fixation from one target to another. Saccadic assessment highlights certain abnormalities, such as a subtle internuclear ophthalmoparesis (see later) with adduction lag; some diseases preferentially affect saccades, producing slowing or inaccuracies. Binocular movements in various directions are known as versions (e.g., leftward version, rightward version), while ductions refer to monocular eye movements (e.g., supraduction in the right eye, indicating elevation of that eye). Ductions can be semiquantified in millimeters of “scleral show” in a position of gaze.


Patients with diplopia may adopt a head posture to avoid the position of diplopia; patients with impaired abduction of one eye may turn the head toward the side of the palsy, thus placing the eyes in contraversion. Patients with trochlear nerve palsy may present with a contralateral head tilt and chin-down position to avoid gaze into the diplopic field. Ptosis should be quantified through measurement of the height of the palpebral fissure in millimeters. Pupil size should be measured in light, in dark, and with reactivity. Proptosis can be measured in millimeters of anterior displacement of each eye from the lateral canthus.


Anatomic location is always the first task for a neurologist, and the site of lesions causing binocular diplopia may be supranuclear (e.g., skew deviation or vergence dysfunction) or involve the ocular motor nerve nuclei (cranial nerves nuclei III, IV, and VI), infranuclear segment (cranial nerves III, IV, and VI), internuclear segment (i.e., medial longitudinal fasciculus [internuclear ophthalmoplegia]), neuromuscular junction (e.g., myasthenia gravis), or muscle (e.g., trauma, thyroid eye disease, neoplasm).


A first step in localization is to consider the most specific patterns of ocular misalignment related to the ocular motor nerves or their nuclei as well as supranuclear and internuclear lesions. Even if the pattern fits that of an ocular motor nerve, nucleus, or internuclear ophthalmoplegia, mimics such as myasthenia gravis, which can masquerade as any pupil-sparing, painless, nonproptotic cause of diplopia, must also be considered. If the misalignment pattern does not conform to these specific patterns, attention should be directed toward neuromuscular junction disease, myopathy, or multiple cranial nerve palsies (e.g., Miller Fisher syndrome, Wernicke encephalopathy). In such cases, it may be helpful to consider each eye separately to arrive at a differential diagnosis.


Supranuclear Causes of Ocular Dysmotility


The supranuclear ocular motor system is principally concerned with bilateral eye movements, and when injured, produces gaze preferences or palsies. Supranuclear causes of dysmotility may also produce binocular diplopia. The supranuclear ocular motor system includes premotor afferent connections from the cerebral hemispheres, cerebellum, and brainstem projecting to the ocular motor nuclei, which govern distinct classes of eye movements including saccades, pursuit, the vestibular ocular reflex, gaze-holding, fixation, optokinetic nystagmus, and vergence.


Burst neurons facilitating vertical saccades reside within the rostral interstitial medial longitudinal fasciculus, which is situated rostral to the oculomotor nucleus ; dysfunction of the rostral portion of this fasciculus produces slow or absent vertical saccades, and may result from infarct, demyelination, neoplasm, or neurodegenerative processes. Given that the deficit is supranuclear, intact vertical eye movements may be possible when bypassing volitional pathways (such as with the oculocephalic reflex—eye movements in response to head movement while foveating).


The cerebellum performs critical coordination and calibration functions for the ocular motor system, particularly the vestibulocerebellum (i.e., flocculus, paraflocculus, nodulus, and uvula), vermis, and fastigial nuclei. The flocculus and paraflocculus are involved in smooth pursuit, gaze holding, and calibration of the vestibular ocular reflex. The vermis and fastigial nuclei are involved in saccadic and pursuit control. The nodulus and uvula participate in modulation of the vestibular system.


Parinaud dorsal midbrain syndrome is one of the most common and distinct supranuclear causes of ocular motor dysfunction. Lesions within the dorsal midbrain, typically affecting the posterior commissure and neighboring structures (often infarcts, neoplasms of pineal origin, hydrocephalus, or demyelinated plaques) produce combinations of vertical gaze palsy, vergence dysfunction, light-near dissociation of the pupils, lid retraction, square-wave jerks, convergence retraction nystagmus, and skew deviation.


Skew deviation is among the most common supranuclear causes of diplopia and produces a vertical misalignment of the eyes (hypertropia). As a supranuclear problem, all ductions in the eyes are full in contrast to a cranial nerve palsy, for example, which as an infranuclear process produces limitations of ductions in one eye. The vertical misalignment with skew may be comitant (the same in all positions of gaze) or incomitant; uncrossed hypertropia is a relatively common pattern (right hypertropia in right gaze with left hypertropia in left gaze). The vertical misalignment tends to be similar in up- or downgaze for any given horizontal eye position.


Skew deviation may be difficult to localize precisely within the posterior fossa, but connections from the vestibular nuclei, the medial longitudinal fasciculus, or connecting pathways involving the cerebellum are often implicated. With lesions above the level of the pontine vestibular decussation, the ipsilesional eye is often hypertropic, while lesions below this decussation more often produce a contralesional hypertropia. The ocular tilt reaction is a special circumstance of skew deviation with the additional features of head tilt and torsion of both eyes.


Supranuclear networks control vergence eye movements, and with dysfunction of this circuitry, binocular horizontal diplopia results. Both divergence and convergence dysfunction produce differing horizontal misalignment at distance compared to near viewing. In addition, supranuclear circuitry is responsible for fusion of any phorias; most normal patients have small horizontal phorias that are asymptomatic due to proper functioning of the vergence networks, which serve to fuse small amounts of misalignment. Occasionally dysfunction of these pathways (from medications, structural disease, fatigue, or idiopathic causes) produces intermittent binocular horizontal diplopia. Convergence insufficiency is perhaps the most common of these vergence dysfunction patterns, producing a larger exophoria (with diplopia) at near than far distance.


Supranuclear lesions may also produce limitations of horizontal gaze. Within the pons, the paramedian pontine reticular formation (PPRF) just rostral to the abducens (VI) nucleus houses horizontal burst neurons. Lesions in this region produce slow or absent ipsilesional saccades. The frontal eye fields of the cerebral hemispheres generate volitional contralateral saccades, and cerebral hemispheric lesions affecting these regions produce a supranuclear gaze preference. In this situation, horizontal eye movements can typically be bypassed by employing the vestibular ocular reflex, which serves to maintain foveation during angular head acceleration.


Ocular Motor Nuclei and Nerves


Dysfunction of the oculomotor (III), trochlear (IV), or abducens (VI) nerves is the most common cause of diplopia. Etiologies are varied and include compression, infection, inflammation, and ischemia.


Oculomotor Nerve (III) Palsy


The third cranial nerve innervates the superior, inferior, and medial recti, inferior oblique, levator palpebrae, iris sphincter, and ciliary muscles, thus controlling adduction, extorsion, supraduction, most of infraduction, lid opening, and pupil miosis. The collection of nuclei lie in the midline of the dorsal midbrain and are composed of a complex arrangement of subnuclei. The oculomotor nerve fascicles travel ventrally, traversing the red nucleus, substantia nigra, and cerebral peduncle before entering the subarachnoid space within the interpeduncular fossa. Within the subarachnoid space, the nerve projects between the superior cerebellar and posterior cerebral arteries, adjacent to the posterior communicating artery. It has an important anatomic relationship to the uncus, rendering the nerve vulnerable to compression with uncal herniation. Within the cavernous sinus, the nerve resides within the superior wall and divides into a superior division (innervating the levator palpebrae and superior rectus) and inferior division (innervating all its other muscles) prior to passing through the superior orbital fissure.


The oculomotor nerve has unique features of clinical importance including the potential for aberrant regeneration. Lesions of the oculomotor nucleus are uncommon, and have patterns dictated by the anatomy including bilateral involvement or sparing of the pupils and levator palpebrae. Complete unilateral oculomotor nerve palsy produces complete ptosis, a mid-position light-fixed pupil, and an inability to adduct, supraduct, or infraduct the eye. The eye may appear depressed and abducted (e.g., “down and out”), and patients report binocular oblique diplopia when the lid is elevated. Partial oculomotor palsies may spare some aspects of this function. Any abnormality of extraocular movement must be distinguished from other possible causes ( Tables 24-7 and 24-8 ).


Aug 12, 2019 | Posted by in NEUROLOGY | Comments Off on Neuro-ophthalmology in Medicine

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