Ocular and Neurologic Evaluation

Correct Answer: Buccal Space

This patient likely has orbital cellulitis, based on the region and visible inflammation. In terms of a source of infection, the buccal space is particularly. As shown in the image on the right, the buccal space contains the infraorbital foramen, providing direct access to the orbit. A molar infection can easily spread from the buccal space up to the orbit.

The submandibular space can become infected, resulting in cellulitis that can become deadly if the airway is obstructed.

Nasal concha infections can become infected, known as concha bullosa, resulting in sinusitis.

The supraorbital foramen contains the trigeminal nerve and would more likely result in sinusitis or neuralgia.

Correct Answer: Pinhole examination

• If you place a single or multiple pinhole occluder in front of each eye and discover that visual acuity markedly improves, you have assigned the problem to the optical segment. It may be an uncorrected refractive error or a defect in the cornea or lens that interferes with the formation of a point focus on the fovea. If visual acuity does not substantially improve with the pinhole test, then the problem lies in the retinocortical segment or the patient is unable or unwilling to cooperate with the pinhole test, providing a “false negative” result. If you do not have a pinhole occluder, make one by puncturing one or more millimeter holes in a piece of paper (more holes is better). Proper pupil, visual field, and ophthalmoscopic examinations provide a lot of information, but are not as well suited as the simple pinhole examination in solving this issue.

Correct Answer: Visual cortex

• These constricted visual fields contain powerful localizing features–the “step-offs” in the visual field defects along the vertical meridian that are identical in the corresponding hemifields. In other words, these are BILATERAL CONGRUOUS HOMONYMOUS HEMIANOPIAS. Although the responsible lesions could lie anywhere in the retrochiasmal portion of the visual pathway on both sides, the most common location would be in visual cortex, where a single event—occlusion of the basilar artery or its two branches, the posterior cerebral arteries, could infarct both sides.
• Do not be surprised if the profound visual field loss is the patient’s only new deficit—that happens if the proximal posterior arterial circulation opens up quickly. Echocardiography showed an aortic valve vegetation, which could have been the source of emboli. Were the optic chiasm the site of damage, visual fields would have been variants of bitemporal hemianopia, not homonymous hemianopia. Bilateral optic nerve damage would cause visual field defect “step-offs” along the horizontal meridian, not seen here. Bilateral simultaneous retinal events—detachments or infarctions—are exceedingly rare and would not cause such symmetrical visual field defects with borders aligned to the vertical meridian. By the way, the patient need not have infarcted both sides of visual cortex at the same time. He could have had an old unilateral homonymous hemianopia about which he was unaware and now experienced a second event affecting only one cerebral hemisphere.

Correct Answer: Retina

• Look carefully at the shape of these defects, noting that they cross the vertical and horizontal meridians without a change in their width. In other words, there are no “step-offs.” These are incomplete “ring defects,” which are characteristic of outer retinal (pigment epithelium/photoreceptor) dysfunction in genetic disorders called “retinal dystrophies.” Very rarely, these defects could be caused by paraneoplastic or idiopathic autoimmune retinopathies.
• Electroretinography will confirm loss of rod function. For most forms of these conditions, there is regrettably no effective treatment yet. The defects become gradually more extensive over ensuing years. Patients also have impaired dark adaptation, but it develops so slowly that they make accommodations and do not suspect a disease. Ophthalmoscopy typically discloses an atrophic retinal pigment epithelium, black spicules, and attenuated arterioles. But do not be surprised if ophthalmoscopy shows a normal-appearing retina! This diagnosis is often long in coming, especially if ophthalmoscopic abnormalities are subtle or absent. In that case, the deficit is often blamed on psychogenic causes. Optic neuropathies would cause defects that have “step-offs” along the nasal horizontal meridian, a feature of nerve fiber bundle defects. Optic chiasm lesions and visual cortex lesions would show “step-offs” along the vertical meridian.

Correct Answer: Optic radiations

• This an incomplete left homonymous hemianopia in which the visual field defects have essentially the same extent in both eyes, earning the term “congruous.” Congruity, a term applied only to INCOMPLETE HOMONYMOUS HEMIANOPIAS, reflects the fact that axons derived from corresponding visual field points in the retinas of both eyes have come to lie next to one another and will therefore be harmed together by single lesions. That “neighborliness” of corresponding axons takes place gradually as the optic radiations proceed backwards toward the visual cortex. Thus, the lesion in this patient is likely to lie in the POSTERIOR part of the optic radiations.
• Of course, it could also lie within the visual cortex (but that was not one of your choices here!).

Correct Answer: Right anterior temporal lobe

These visual field defects have the following distinctive features: they are wedge-shaped in both eyes with one border aligned to the vertical meridian, the other extending out radially. You can see why they are called “homonymous hemianopic pie-in-the-sky” defects. They represent damage to the post-geniculate axons that curve around the anterior portion of the temporal horn of the lateral ventricle (“Meyer’s loop”) before joining up with the remaining axons of the optic radiations. If these defects had had borders aligned to the horizontal meridian, you would have called them “homonymous quadrantanopias,” and properly blamed the damage on a visual cortex lesion. In this case, the patient had undergone laser ablation of the anterior temporal lobe for intractable seizures. By the way, ablation extending beyond 4cm posterior to the anterior temporal tip is bound to cause such “pie-in-the-sky” visual field defects. The good news is that patients will not be impaired by them (or even notice them) unless the ablation extends back more than 6cm from the anterior temporal tip, in which case the root of the optic radiations may be damaged and the radial border of the homonymous defects will stretch closer to the horizontal meridian. Procedures in this region can also damage the anterior choroidal artery and its supply of the optic tract.

Correct Answer: Visual cortex

• No one would fault you for guessing “retina,” thinking that there was an overlooked abnormality–a retinal inflammation, separation, or scar. But that was not the case here. The defect derives from the other end of the visual system. Limited to the peripheral temporal field of the left eye, it is easy to miss unless you remember that the temporal field is normally more extensive than the nasal field. Standard static perimetry, which samples at most the central 30 degrees of the visual field, will always miss this defect. It is called a “temporal crescent defect,” and it occurs when a lesion—nearly always an infarct–damages the far anterior visual cortex in the opposite cerebral hemisphere
• Factoid: this is the only retrochiasmal visual field defect that is not a homonymous hemianopia! By the way, if a lesion can selectively damage the far anterior visual cortex, it can also selectively spare it. If you play the next video, you will see a “temporal crescent-sparing homonymous hemianopia” caused by a lesion that damaged only the mid-portion and posterior portion of visual cortex.
• Patients who have this defect will be able to see in the periphery of the damaged hemifield and believe that they are safe to drive. Not really!

Correct Answer: Ischemic optic neuropathy

• The defect in the right eye has a substantial border aligned to the horizontal meridian in the nasal field. That feature marks it as a “nerve fiber bundle defect” that involves the upper arcuate bundles made up of retinal ganglion cell axons that converge upon the upper pole of the optic disc. This arcuate bundle can be damaged in many conditions, including optic nerve compression, inflammation, ischemia, trauma, congenital dysplasia, and retinal artery or vein occlusion. It is typically spared by hereditary (Leber, OPA 1), metabolic (nutritional and vitamin deficiency, alcoholism), and toxic (ethambutol and others) conditions, which usually damage the maculopapillar bundles to create central or centrocecal scotomas in both eyes. The swelling of the right optic nerve and the arcuate nerve fiber bundle visual field defects suggest suggest five choices: 1) inflammation (“papillitis,” “optic neuritis”); 2) an orbital tumor; 3) an intracranial tumor entering the optic canal; 4) cancerous infiltration of the optic nerve; 5) optic nerve ischemia. Inflammation is a distinct possibility. So are tumors compressing the optic nerve in the orbit if they involve the nerve near the eye or the optic canal. So are intracranial tumors if they have entered the optic canal, a phenomenon especially common with sphenoid meningiomas.
• However, the sudden onset of vision loss and her medication list suggesting an arteriosclerotic risk profile favor a diagnosis of ischemic optic neuropathy. If she had a symptom complex to suggest polymyalgia rheumatica or cranial arteritis, you would have to consider the diagnosis of “arteritic ischemic optic neuropathy” and order a blood sedimentation rate and C-reactive protein (“acute phase reactants”), place the patient on prophylactic corticosteroid, and consider performing a temporal artery ultrasound looking for the characteristic “halo sign” of arteritis. However, even if the ultrasound is negative, you would likely move ahead with performing a temporal artery biopsy if the acute phase reactants are elevated or the patient has systemic symptoms of an arteritis. Otherwise—and most likely—she has non-arteritic ischemic optic neuropathy (NAION), a bland infarct in the optic disc caused by hypoperfusion. You would be more certain of that diagnosis in follow-up. If visual function improves, you would favor a diagnosis of papillitis.
• If visual function improves, you would favor a diagnosis of papillitis. If visual function worsens, worry about inflammation, a compressive tumor, or cancer infiltrating the optic nerve. If visual function remains unchanged, your presumptive diagnosis of NAION was probably correct. There are two reasons to make a diagnosis of NAION. First, it suggests that the patient has “small vessel” arterial disease, which may require prophylactic treatment. Second, there is a concern for overtreated systemic hypertension that results in low blood pressure and optic disc hypoperfusion especially during the early morning hours, which could also precipitate NAION in the unaffected eye. Monitoring of blood pressure to rule out nocturnal hypotension might reduce the chance that the second eye would be affected, a visually devastating occurrence. By the way, you should be asking whether orbit and brain imaging is indicated here. Strictly speaking, no, but the truth is that it will often be done in order to rule out those other choices without having to wait for the clinical course to establish visual stability.

Correct Answer: Visual cortex

• This is a right superior homonymous quadrantanopia—a defect pattern that is exquisitely localizing—to the left inferior visual cortex or its adjacent incoming axons. Notice three features of these defects: 1) they are on the same side of visual space (“homonymous”); 2) the defect borders are aligned to the vertical meridian (“hemianopic”); and 3) the defect borders are aligned to the horizontal meridian. Defects with borders aligned to BOTH MERIDIANS can arise only from lesions limited to the upper or lower banks of the calcarine fissure, a brain groove that separates the superior from the inferior primary visual cortex. In this patient, the lesion lies in the lower bank
• Although it is true that a lesion of the inferior portion of the optic radiations would cause a homonymous hemianopia that preferentially affects the superior field, it would not produce visual field defects aligned to the horizontal meridian because the superior and inferior optic radiation axons do not become distinct until they reach the calcarine fissure in the occipital lobe. By the way, you should not apply the term “quadrantanopia” unless the defects are homonymous hemianopias with borders aligned to both the vertical and the horizontal meridian. True quadrantanopias are almost always caused by infarctions in the domain of the posterior cerebral artery, which serves the upper and lower calcarine banks with separate branches. In this patient, MRI revealed restricted diffusion in the lower bank, indicating fresh infarction; the lower branch of the posterior cerebral artery must have been occluded. Embolism is always a consideration, with the heart as a source.

Correct Answer: Optic chiasm

• This is the most easily recognized visual field abnormality—a bitemporal hemianopia. It is the signature of an extrinsic or intrinsic lesion compressing, inflaming, infarcting, or expanding the optic chiasm.
• Actually, the most common cause of chiasmal damage is a mass lesion: pituitary adenoma, meningioma, and aneurysm in adults; craniopharyngioma and pilocytic astrocytoma in children. Why do such lesions produce this defect pattern? Because the crossing axons in the optic chiasm are especially vulnerable to any kind of insult! Patients are slow to notice the defects because the nasal field of each eye almost completely covers the temporal field of the other eye. Although they may eventually sense that peripheral vision is compromised, more often patients present with decreased vision in one eye because the lesion also compromises the function of an optic nerve. Visual fields may show a combination of nerve fiber bundle defects and temporal hemianopic defects (“junction pattern”).
• This patient had a pituitary tumor.
• The serum prolactin level was normal, eliminating prolactinoma as the type of adenoma. Tip: prolactinomas are treated initially with cabergoline, a dopamine agonist that can dramatically shrink the tumor and restore normal pituitary function, but the medication must be taken indefinitely or the tumor will recur. In this patient, transsphenoidal surgery yielded complete recovery of vision. Early diagnosis of this condition unquestionably improves visual outcome!

Correct Answer: Optic nerve

• The visual field defects are “cecocentral scotomas” (also called “centrocecal scotomas”) because they affect the visual field that lies between fixation and the physiologic blind spot. Whenever you encounter this pattern of visual field loss in both eyes, think mitochondria of retinal ganglion cells. The unmyelinated axons of those ganglion cells lie in the temporal portion of the optic disc, which is why that portion of the optic disc eventually appears pale.
• The pathology thins out the retinal nerve fiber layer around the fovea and between the fovea and the optic disc, which will be evident on optical coherence tomography (OCT). Toxic, metabolic (including nutritional deficiency), and hereditary conditions are behind this damage. Consider these common causes: ethambutol toxicity, thiamine (B1) and hydroxycobalamin (B12) deficiencies, alcoholism, starvation diets, non-adherence to vitamin supplementation after bariatric surgery, hereditary dominant (OPA 1) and Leber optic neuropathies.

This patient admitted to severe alcoholism. Treatment consisted of heavy thiamine dosing and abstinence. Vision is more likely to recover if the patient is adherent to the treatment regimen, if the optic discs have not developed pallor, and if OCT does not show thinning. Hence the importance of early diagnosis, especially in patients taking ethambutol, where scrupulous monitoring of visual acuity and color vision is advisable, so that the medication can be discontinued at the first sign of optic nerve toxicity.

Correct Answer: Somewhere in the retrochiasmal visual pathway

• Although this seems a relatively evasive answer, it is correct. You are looking at a complete homonymous hemianopia identified on confrontation and formal visual field testing. When a homonymous hemianopia is COMPLETE, you can localize it to the retrochiasmal visual pathway, but not to a specific region within that pathway! As the MRI is certifiably normal, you will wonder if the defect is of psychogenic origin. That presumption is difficult to disprove clinically. Some clinicians have developed maneuvers, such as having patients rapidly switch fixation back and forth between single targets displayed in opposite hemifields, but I have had a hard time convincing myself that I can exclude psychogenic “homonymous hemianopia.” Be careful here, as there are several retrochiasmal lesions that are either invisible on MRI or so subtle that they may be overlooked.
• Among those lesions are: 1) Recent hypoxic-ischemic injury owing to sudden systemic hypotension (MRI visual cortex volume loss may develop months later); 2) Creutzfeldt-Jakob disease, a prion protein disorder that may show subtle relevant MRI abnormalities only months later (positron emission tomography would earlier show a metabolically low visual cortex region); 3) focal encephalitis, also called “cerebritis” (small areas of high T2/FLAIR or cortical enhancement may be overlooked or dismissed); 4) Alzheimer disease with predominant volume loss in posterior cerebral hemisphere (relatively more MRI volume loss on the side opposite to the hemianopia may be overlooked); 5) focal metabolic encephalopathy in nonketotic hyperglycemia or mitochondrial cytopathy (which can be evanescent); and 6) optic tract lesion (because it is a narrow structure wedged between midbrain and temporal lobe, lesions here are often overlooked). This patient had signal abnormalities in the right optic tract and in the cervical spinal cord consistent with multiple sclerosis.

Correct Answer: Visual Cortex

• These small defects in the left hemifields are confined to the central degrees of the visual field. They are called “homonymous hemianopic paracentral scotomas.” Because they lie so close to the fixation point, they cause troublesome visual symptoms. They slow reading speed, as the patient consistently misses the first part of each word. You will be surprised to discover that the lesion occupied the entire back half of the visual cortex on the right side! Why would such a large lesion cause such small defects? Because the human brain devotes the entire posterior half of visual cortex to the central 10 degrees of the visual field, a phenomenon called the “magnification factor.” It testifies to the importance of “foveal vision” in primates.
• Such paracentral defects are routinely overlooked on standard static perimetry protocols, in which the test points are spaced far enough apart (“6 degrees of separation”) to miss the defects. Protocols that sample the central 10 degrees with test points at closer intervals are more likely to find these defects. In this patient, the defects were caused by posterior cerebral artery infarction, possibly related to embolism during the heart surgery.

Correct Answer: Optic Tract

• These visual field defects are confined to the left hemifields in both eyes and they have borders aligned to the vertical meridian, defining them as an incomplete “homonymous hemianopia.” But notice also that the defects in the two eyes are not of the same extent. If you overlaid them, they would not superimpose. This difference in the size of the two defects is called “incongruity.” If that incongruity is a true representation—and not simply an inconsistency in patient performance on the test—then the lesion must lie in the optic tract, where axons from corresponding points in the retinas of the two eyes have not yet come to lie close to one another.
• After all, the optic tract is early in the retrochiasmal portion of the visual pathway, which carries out the transformation of visual representation in the brain from monocular to hemifield. As the axons proceed farther posteriorly, through the lateral geniculate bodies and optic radiations to visual cortex, axons from corresponding retinal points become neighbors and incomplete homonymous hemianopias become more congruous. By the way, why did the patient say that she had lost vision “in my left eye?” Because patients will almost always blame a homonymous hemianopia on the eye on the side of the hemianopia! In this patient, brain MRI disclosed enhancement in the right optic tract and other signal abnormalities consistent with multiple sclerosis.

Correct Answer: Visual Cortex

• Notice three features of these visual field defects: 1) confined to the left hemifields in both eyes; 2) have discrete borders along the vertical meridian; 3) spare the central 10 degrees of the visual fields. These features define a “macular-sparing homonymous hemianopia,” one of the most localizing of all visual field defects! This pattern always derives from a lesion in the visual cortex that spares the posterior portion of that cortex, the termination point of axons carrying visual information from the central 10 degrees of the visual field.
• The patient was slow to notice these defects because of macular sparing, which allowed him to read at nearly normal speed and to ignore the more peripheral scotomas. He thought he could drive safely. However, in most jurisdictions, the finding of macular-sparing homonymous hemianopia would preclude a patient from being issued a driving license! The cause of these defects was an ischemic stroke in the distribution of the right posterior cerebral artery.
• The defects are permanent. He had atrial fibrillation and required long term rate control and anticoagulation to prevent future stroke.

Correct Answer: Assessment of right pupil constriction to a near target

• Whenever a pupil does not constrict properly to direct light, you should assess whether it constricts to a target placed within reading distance. Why? Because if the pupil constricts poorly to direct light, but much better to a target placed within reading distance, you will diagnose “light-near dissociation,” a phenomenon of great clinical value. In the presence of anisocoria, it signifies a lesion in either the midbrain/pretectum or the ciliary ganglion/ciliary nerves. A dorsal midbrain/pretectum region lesion causes anisocoria and light-near dissociation by asymmetric interruption of afferent input to the Edinger-Westphal (parasympathetic) nuclei. An irregular (oval) pupil and slow (tonic) constriction to a near target should not be present. And other signs of dorsal midbrain syndrome—especially upgaze deficiency—will always be present! You could not be ashamed if you chose, as an answer here, to perform biomicroscopic examination in search of iris defects. However, light-near dissociation and tonicity will not be present in iris sphincter dysfunction. If you presumptively diagnose a tonic pupil, you could instill a few drops of dilute (0.1%) pilocarpine in both eyes to search for postganglionic parasympathetic iris sphincter denervation supersensitivity. But as pilocarpine 0.1% is not commercially available, you would have to dilute 1% pilocarpine, a maneuver full of errors and a risk of contamination. And some patients with preganglionic third nerve lesions will display denervation supersensitivity, misleading you from the correct localization. In summary, then, your clinical diagnosis of Adie tonic pupil should be based on finding pupil ovality, tonicity, and light-near dissociation. To be even more certain of the diagnosis, make sure that there are no signs of a preganglionic third nerve palsy. A small pupil with light-near dissociation would prompt consideration of syphilis– the Argyll Robertson (AR) pupil. Some people (including this observer) believe that the AR pupil is actually a chronic Adie pupil caused by syphilitic involvement of the ciliary ganglion. But you should initiate an evaluation for syphilis ONLY if there are other neurologic signs typical of this disease! Apraclonidine and cocaine are topical agents used when the patient has anisocoria and both pupils constrict normally to light.

Correct Answer: Photoreceptor disorder

• You cannot be faulted for judging the sensitivity to light, impaired visual acuity and color vision, and unreliable formal visual field results as manifestations of a psychogenic disorder. But organic causes could be at work! A bilateral optic neuropathy is not it because Ishihara color vision is too poor. Congenital dyschromatopsia would not cause degraded visual acuity. You must consider a diagnosis of cone dystrophy–even if the optic fundus examination appears normal, as it often does in that condition. You would settle the issue with an electroretinogram (ERG), which should show abnormalities in cone function. Optical coherence tomography might also show a disordered outer retina. Were you thrown off by the normal confrontation visual fields? Don’t be. That technique is insensitive to central scotomas. Why is he bothered by sunshine? Patients with cone dystrophy often complain of being aversive to normal daylight (“hemeraopia”) because the disordered cone function cannot transduce light into neural signals. The lack of a family history should not dissuade you from the diagnosis. For now, there are no proven treatments for cone dystrophy, which can become apparent at any age. Visual acuity will gradually decline over time. Two extremely rare conditions—autoimmune retinopathy and cancer-associated (paraneoplastic) retinopathy—should be excluded in the proper setting. Diagnosis depends on demonstrating anti-retinal antibodies in addition to the typical ERG abnormalities.

Correct Answer: Infantile esotropia

• If your observation is correct that ocular ductions are full and the esotropia is comitant (the misalignment is of the same amount in right and left gaze), the abnormality is not likely to be a sixth nerve palsy. Why not? Because sixth nerve palsy should show an abduction deficit (although it could be mild) and produce an incomitant esotropia with greatest amount in ipsilateral gaze. Yes, sixth nerve palsy can eventually develop full ductions and become a comitant esotropia, but that would be highly unusual in a 6 month old child. Accommodative esotropia is ruled out by the plano refraction. Sensory esotropia, a diagnosis applied when the misalignment represents a breakdown of fusion owing to an underlying vision deficit, is an unlikely choice because the examination shows apparently good vision in each eye, a normal fundus examination, and no afferent pupil defect. Of course, these conclusions depend on a skillful, thorough examination and reliable findings—not easy in such a young child. Be careful!

Correct Answer: The second examiner is correct; the first examiner failed to instruct the patient to make the viewed target “come into focus.”

• This is the most common technical error in using the cover test. If patients do not understand to bring the viewed target into focus, they will fail to execute a refixational movement to place the viewed target onto the fovea. In that circumstance, ocular misalignment in any plane will be overlooked. The single Maddox rod test, which does not depend on refixational eye movements, would reveal the ocular misalignment.

Correct Answer: Posterior reversible encephalopathy syndrome

• The abnormalities in the optic fundus—cotton wool spots, retinal hemorrhages, optic disc swelling—are the result of retinal vasospasm, microinfarction, and vascular incompetence. But they do not account for the profound loss of vision. In acute systemic hypertension, the optic disc surface vessels often leak and cause an engorged appearance of the discs, but the optic disc tissue is rarely infarcted. Instead, the vision loss comes from vascular leakage in the occipital lobe white matter, where binocular profound vision loss can occur in a condition known as “posterior reversible encephalopathy syndrome” (PRES).
• If blood pressure is lowered, these abnormalities disappear rapidly and normal function is restored. If there is a delay, infarction may occur, leaving the patient with persistent retrogeniculate vision impairment. The optic fundus abnormalities—often dramatic—are a distraction. The real action is elsewhere and must be detected with brain imaging, preferably MRI. PRES occurs in two main settings: use of calcineurin inhibitors to prevent graft rejection or to treat intractable autoimmune phenomena, and in sudden systemic hypertension, often during or after pregnancy. By the way, intracranial pressure is generally not much elevated in PRES; lumbar puncture is not indicated. This patient had acute glomerulonephritis as the cause of elevated blood pressure.

Correct Answer: Parietal lobes

• This patient is simply unable to point accurately to objects in an array. Also, she forgets which ones she has already identified, so she miscounts. Her problem derives from a combination of visuospatial and attentional dysfunction. The term “simultanagnosia” has been applied to this deficit. The lesions lie in the inferior parietal lobules on both sides, interrupting the integration of visual and somatosensory information and the application of attention appropriate to the task. Called Balint syndrome, or Balint-Holmes syndrome, it most often arises acutely from biparietal stroke, usually in the setting of systemic hypotension (“watershed” or “border zone” infarction).
• When these deficits appear chronically, the most common cause is the “visual variant” of Alzheimer disease, sometimes known as “posterior cortical atrophy.”

Correct Answer: Left occipital-temporal lobe

• She is demonstrating the manifestations of “alexia without agraphia,” also known as “pure alexia.” It is a recognition disturbance for written language (and often other familiar symbols). It is not an aphasia (language disturbance). Written information cannot reach the posterior portion of the angular gyrus in the left temporal lobe. This disconnection happens most often when a lesion—almost always an ischemic stroke in the domain of the posterior cerebral artery—damages the left medial occipital lobe, causing a right homonymous hemianopia, and extends anteriorly enough to damage the splenium of the corpus callosum to interrupt transmission of visual information from the intact right visual cortex to the left angular gyrus. Patients can spell, understand spoken language, and express themselves normally, because those functions are generated in the angular gyrus without needing transmission from the visual cortex. Which critical neuro-ophthalmic abnormality was bound to be present (although not always!) and not mentioned in the vignette? A complete right homonymous hemianopia. This patient did have a left posterior cerebral artery stroke with forward extension into the splenial region.
• Over time, her reading deficit gradually improved, but she still hesitated. The homonymous hemianopia was permanent.

Correct Answer: Right pons

• This patient has a palsy of right horizontal conjugate gaze (“gaze palsy”) that involves saccades, pursuit, and the vestibulo-ocular reflex. Although you could postulate lesions affecting the extraocular muscles or the neuromuscular junction activated in right gaze, such a symmetrical deficit of conjugate gaze to one side will virtually always originate within the brain. If volitional and reflex gaze are both completely impaired, expect to find the lesion in the pons. You should be surprised that there are no other neurologic deficits–seventh nerve palsy, internuclear ophthalmoplegia, nystagmus, ataxia, skew deviation, or limb weakness. However, a lesion confined to a small area in the tegmental pons—in the location of the sixth nerve nucleus– might not produce any obvious accompanying signs (although you should look for them as “fellow travelers”). This patient had a hemorrhage from a right pontine tegmental cavernous malformation (“cavernoma”).
• The only effective treatment is surgical excision, which is hazardous. No treatment was undertaken in this case. The patient’s deficits gradually resolved enough to give him partial restoration of right gaze. He was advised to avoid any activity that would generate increased intracranial pressure (like weight-lifting, evacuative straining, and standing on his head!)

Correct Answer: Right cerebral hemisphere

In order to answer this question correctly, you had to know three things: 1) horizontal saccades are generated in the cerebral hemispheres and that they move the eyes toward the opposite side; 2) This patient is displaying a dissociation between loss of volitional leftward horizontal saccades and preservation of the leftward vestibulo-ocular reflex (“supranuclear ophthalmoplegia”); and 3) the vestibulo-ocular reflex pathway is confined motorically to the brainstem. Acute right hemisphere lesions (usually infarcts or hemorrhages), especially if they involve the parietal lobe or its efferent pathway, often produce ipsilateral gaze deviation and a supranuclear gaze disturbance, as described here. These phenomena may be manifestations of “motor neglect.” In fact, sensory aspects of hemispatial neglect are usually present, including extinction to double simultaneous stimulation in the visual, auditory, and tactile domains. Extinction of the visual field in one hemifield could, by itself, reflect a subtle homonymous hemianopia. But the presence of multimodal–visual, auditory, and tactile–extinction favors neglect over a topographic disorder of vision such as a homonymous hemianopia. Patients with homonymous hemianopias rapidly develop the ability to explore into their deficient hemifield and will bisect a line segment in the midline, especially if cued. Patients with hemispatial neglect consistently ignore stimuli in one hemifield and bisect a line segment more toward the side of the lesion. When the lesion is severe, neglect will extend to lack of awareness of contralateral limbs (“anosognosia”). Fortunately, the manifestations of neglect gradually lessen with time, but may never completely disappear. This patient had a right parietal infarct.

Correct Answer: Posterior commissure

• This is an important neuro-ophthalmic landmark! Lying at the junction of the thalamus and midbrain, it mediates upward gaze by connecting the rostral interstitial nuclei of the medial longitudinal fasciculus (RIMLF) and interstitial nucleus of Cajal (INC) on both sides.
• A lesion here SELECTIVELY interferes with upward gaze, sparing downward gaze, which is mediated more ventrally. When this commissure is damaged by an intrinsic lesion of the caudal thalamus or pretectal or tectal midbrain regions, or by an extrinsic lesion like a pinealoma, expect elements of a “dorsal midbrain syndrome” (also called “pretectal syndrome,” “Sylvian aqueduct syndrome,” or “Parinaud syndrome” if you are French, “Koerber-Salus-Elschnig syndrome” if you are German). The clinical features of this syndrome include lid retraction (“Collier’s sign”), dilated pupils with light-near dissociation, and sometimes esotropia, exotropia, or skew deviation. Why does a lesion here cause such a diverse set of clinical phenomena? Disruption of upgaze produces a “spill-over” activation of all extraocular muscles, pulling the eyes backwards into the orbit. Because the medial recti are the most powerful muscles, the eyes tend to converge. Dilated pupils with light-near dissociation (“tectal pupils”) are attributed to interruption of the pupillary light reflex pathway in the dorsal midbrain. Esotropia and exotropia result from disruption of the vergence pathway in that region, and skew deviation results from interruption of the vestibulo-ocular pathway as it reaches the midbrain. This patient had a pinealoma.
• Early diagnosis favors a better outcome of treatment. By the way, even with early diagnosis of pineal tumor, some features of a dorsal midbrain syndrome—especially upgaze deficiency and convergence-retraction–often linger. Why is this fact important? Because if upgaze deficiency and convergence-retraction are detected long after treatment, they should not be taken as signs of tumor recurrence or of a complication of radiotherapy, even if not previously documented!

Correct Answer: Wernicke encephalopathy

• You are looking at gaze-evoked horizontal jerk nystagmus on side gaze and upbeat nystagmus on upgaze. This form of nystagmus is a common feature of Wernicke encephalopathy, a deficiency of thiamine (vitamin B1), which is a co-factor in many metabolic pathways critical to central nervous system function. The classic clinical triad consists of a confusional state, ataxia, and ophthalmoplegia, but only a minority of patients have all three components. Nystagmus is actually more common than ophthalmoplegia (which, in Wernicke encephalopathy, usually means reduced conjugate gaze or abduction deficits). So look for nystagmus, even when no other neurologic manifestations are present. In the past, the common setting for Wernicke encephalopathy was alcohol binge drinking, but with the growth of bariatric surgery, it is seen in those patients, especially if they are not adherent to vitamin supplementation regimens. (This patient had not been taking the supplements because she could not afford them. Other patients fail to absorb them because they are vomiting.) The manifestations of Wernicke encephalopathy usually develop from 4 to 8 weeks after surgery. Treatment is prompt administration of thiamine 500 mg intravenously three times a day for 3 days, followed by thiamine 250 mg intravenously or intramuscularly once daily for 5 days to prevent permanent amnestic dementia (Korsakoff syndrome). The ophthalmic manifestations often resolve within days of treatment, but ataxia and cognitive impairment often endure. The neuropathology consists of capillary proliferation, microhemorrhages, and neuronal and glial loss. It is prominent in the thalamus, mammillary bodies, and periventricular regions of the brainstem, including the sixth nerve nuclei. In this patient, T2 and FLAIR MRI sequences showed high signal in the dorsomedial thalamus and mammillary bodies.
• These MRI abnormalities are specific for Wernicke encephalopathy, but a negative MRI occurs in at least 50% of cases. Blood tests (whole blood thiamine, erythrocyte transketolase, and thiamine pyrophosphate levels), which should be drawn before administering thiamine, can help confirm the diagnosis, but may also be normal. So, whenever you see this kind of nystagmus after bariatric surgery or with a history of binge drinking, the presumptive diagnosis is Wernicke encephalopathy! The other answer choices here are reasonable, but less apt. Infectious meningoencephalitis is always an important consideration, eliciting further prompt evaluation with imaging, lumbar puncture, and other studies. Hypertensive encephalopathy, which typically manifests with homonymous visual field loss, cognitive impairment, and seizures, discloses high T2/FLAIR MRI signal in the posterior cerebral hemispheres (“posterior reversible encephalopathy syndrome, or PRES”), and does not typically cause nystagmus. Osmotic demyelination syndrome (formerly called “central pontine myelinolysis”) occurs after rapid correction of hyponatremia usually following heavy alcohol intake. The increase in extracellular sodium results in rapid escape of intracellular water and cellular dysfunction, most often affecting the pons. Patients present with impaired consciousness and quadriparesis. MRI should show symmetrical high T2/FLAIR sign in the central pons and sometimes in the lateral geniculate bodies.

Correct Answer: Right parietal lobe

In order to get the correct answer here, you must be aware that pursuit is mediated by a pathway that starts in the parietal lobe and generates pursuit eye movements ipsilaterally. When you move the optokinetic drum, you generate an obligatory pursuit movement in the direction of the moving stripes (the patient must be paying attention!). Each pursuit movement is met by an oppositely-directed conjugate saccadic movement that restores the eye position to straight ahead. You can use this device to generate repetitive jerk nystagmus. If you consistently see a discrepancy in nystagmus amplitude between rightwardly and leftwardly directed stripes, you must conclude that there is a unidirectional pursuit deficit caused by a lesion in the ipsilateral parietal lobe. By the way, the patient will not notice this pursuit deficit.

Correct Answer: Diencephalon

This patient has suffered severe damage to all parts of his brain, but the comitant esotropia with full ocular ductions suggests diencephalic dysfunction. There has been a breakdown of fusion, such that the balance between convergence and divergence has been upset. A lesion in the cerebral hemispheres could also upset that balance, but you were not offered that answer option here. Bilateral sixth nerve palsy is a common mistaken explanation for esotropia, but that should reduce abduction and cause more esotropia on side gaze than in primary gaze position (“incomitant esotropia”). Bilateral third nerve palsy would cause an exotropia. Bilateral fourth nerve palsy would cause a right hypertropia in left gaze and a left hypertropia in right gaze, features not present here.

Correct Answer: Midbrain

• You should find this combination of neuro-ophthalmic abnormalities challenging. Why? First, the complaint of blurred vision suggests that something is wrong with the visual pathway. But patients will often interpret mild misalignment of the eyes as blurred vision. The clue that the blurred vision is actually diplopia comes from the fact that covering either eye improves vision! Second, when eye movements are full, many examiners will assume that there is no disorder of ocular alignment. Not true. This patient has a vertical misalignment (“hypertropia”) discovered with the cover test. The challenge here is that the misalignment is small, so difficult to see. You could use the Maddox rod, which might show a consistent vertical displacement of the two images. Third, the oscillations of the eyes, present only in extremes of gaze, will often go unnoticed. This pattern of oscillations–called “nystagmus”– is important evidence of brainstem (rather than semicircular canal or otolith) dysfunction. The lesion is affecting one side of the pathway carrying the vertical vestibulo-ocular reflex. That pathway travels from the medulla to the rostral midbrain and diencephalon. A unilateral or asymmetric lesion here creates an abnormal “ocular tilt reaction,” which includes torsional displacement of the eyes and vertical misalignment.
• The patient may notice torsional displacement of the environment, and will report the vertical misalignment of the eyes (called “skew deviation”) as diplopia or blurred vision
• In this case, the cause proved to be multiple sclerosis. The brainstem did not show any MRI signal abnormalities, but there were characteristic T2/FLAIR signal abnormalities in the cerebral white matter.

Correct Answer: Cerebral peduncle

This is a classic “Weber syndrome” of third nerve palsy and contralateral hemiparesis. It arises from a lesion in the left third nerve fascicles as they pass through the cerebral peduncle, which carries corticopontine fibers that cross in the rostral pons and corticospinal fibers that cross in the medullary pyramids to innervate musculature on the opposite side of the body. Although most third nerve palsies have no accompanying neurologic abnormalities, occurring in the subarachnoid segment of the third nerve, you should recognize this particular “third nerve palsy plus” syndrome because it implies a lesion of the ventral midbrain, usually an infarction in the domain of an occluded paramedian arterial perforator, but inflammations and cancers can also do this. Aneurysm is not a consideration, but rarely Weber syndrome may be an early sign of rostral basilar thrombosis, so prompt vascular imaging and surveillance is necessary. MRI may show restricted diffusion in the ventral midbrain, yet very often the stroke is too small to show up. Even so, assume there is a stroke and direct your attention to future stroke prevention caused by disorders affecting small arterial vessels.

Correct Answer: Junction of internal carotid and posterior communicating arteries

• The combination of neuro-ophthalmic deficits described here suggests a left third nerve palsy. Intracranial aneurysm is an uncommon–but the most feared–cause of third nerve palsy. When an aneurysm causes a third nerve palsy, it is of the extradural “berry” type, in which focal congenital defects in the intima and media at arterial branch points cause bubble-like expansion that worsens with aging, systemic hypertension, and other conditions that weaken arterial walls. Berry aneurysms are prone to rupture with a mortality rate of 50%. But mere expansion without rupture is sufficient to cause third nerve palsy if the expanded aneurysm measures at least 3 millimeters in diameter. The third nerve is most likely to be compressed by an expanding (or ruptured) aneurysm at the junction of the internal carotid and posterior communicating aneurysm
• Less common sites of aneurysms are the junction of basilar and superior cerebellar arteries and the junction of the basilar and posterior cerebral arteries
• Modern computed tomographic (CT) angiography and magnetic resonance (MR) angiography are about 96% likely to detect aneurysms that cause third nerve palsies, provided the interpreting radiologist is experienced enough to detect the often subtle abnormalities. If you suspect a recent-onset third nerve palsy, you must order such a non-invasive vascular imaging study immediately, particularly in a patient in whom the most common ischemic palsy is less favored, because rupture of an expanding aneurysm could be imminent—and fatal!

Correct Answer: Superior oblique muscle/tendon

• The pattern of ocular misalignment fulfills the features of the Bielshowsky “three-step test,” a strong indication of a “fourth nerve palsy.” In addition, the fact that the hypertropia in left gaze is greater when the patient is looking up than when he is looking down is critical to localizing the lesion: it lies in the superior oblique muscle or its tendon.
• Why does this part of the body give out? Consider that the anatomy of the superior oblique muscle and its tendon is awkward: the muscle passes forward along the medial orbital wall, passes through a sleeve of dura called the trochlea, and must turn more than 90 degrees to insert onto the top of the eye.
• It should not be surprising that the efficiency of its pulling power might decline as the years go by! Sometimes the diplopia in this condition can be palliated with a spectacle prism. But because of the incomitance, the prism is usually an imperfect or temporary solution, and eye muscle surgery the answer. Fortunately, a minor procedure (weakening of the inferior oblique muscle) is likely to provide relief of diplopia. Acquired causes of “fourth nerve palsy,” including trauma, tumor, and inflammation, would cause a hypertropia that is greater in downgaze than in upgaze. If you selected “neuromuscular junction” as your choice, you could hardly be faulted here, because myasthenia gravis can produce any pattern of ocular misalignment. In fact, the intermittency of the diplopia is likely to send you toward that diagnosis, but when the misalignment obeys the features of the three-step test, myasthenia is a less likely diagnosis. By the way, myasthenia gravis is not the only cause of intermittent diplopia. Here are other reasons for this phenomenon: 1) diplopia is present only in certain fields of gaze, and 2) fusion is breaking down because of fatigue or CNS depressants, which convert a phoria to a tropia.

Correct Answer: Dorello’s canal

• The likely cause of the diplopia is a right sixth nerve palsy. His ear abnormalities are likely caused by an infected middle ear (“otitis media”) with spread of the infection to the mastoid region. How can you connect that infection with the sixth nerve palsy? By assuming that the infection has spread through the petrous bone to its apex, where the bone forms the lateral wall of Dorello’s canal, the narrow space through which the sixth nerve travels to get from the subarachnoid space into the cavernous sinus.
• The association between middle ear infection and sixth nerve palsy was described long ago by Gradenigo and is now known as “Gradenigo’s syndrome.” The sixth nerve in the tight space of Dorello’s canal is vulnerable to a “compartment syndrome” as infections and cancers come from a lateral source in the petrous bone, from a medial source in the clivus (a favorite site for cancer metastasis), and from an inferior source in the sphenoid sinus (infections and cancer). You cannot be faulted here if you chose “transverse-sigmoid (dural) sinus junction” as your answer. Mastoid inflammation from middle ear infections can cause venous sinus thrombosis at the transverse-sigmoid junction, raising intracranial pressure and causing a secondary sixth nerve palsy. Why does high intracranial pressure cause a sixth nerve palsy? Because the high pressure drives the brain downward, tugging on the sixth nerve where it is tethered in Dorello’s canal. But in such cases, papilledema is usually present (and it was not in this boy). By the way, low intracranial pressure also drives the brain downward, which is why sixth nerve palsy also occurs in intracranial hypotension. A final tip: when intracranial pressure goes up, you might instead encounter a comitant esotropia with full ocular ductions, representing a breakdown in “ocular fusion.”

Correct Answer: Cavernous sinus

An incomitant esotropia with image separation greatest in right gaze suggests a right abduction deficit, even if you cannot see it. Many processes can cause an abduction deficit, but when you add an ipsilateral Horner syndrome, you are closing in on the place where the oculosympathetic pathway and the sixth nerve pathway come together—the cavernous sinus. In the cavernous sinus, the sixth nerve is the only cranial nerve lying within the venous lake (the other cranial nerves travel in the outer dural wall). The sixth nerve passes inferolateral to the carotid artery. On the outer wall of the carotid artery, you will find the oculosympathetic nerve. The combination of sixth nerve palsy and Horner syndrome is common with lesions arising within the cavernous sinus, including aneurysms and metastases.

Correct Answer: Mydriasis and light-near dissociation

A lesion of the ciliary ganglion in the orbit interrupts the parasympathetic supply to the iris sphincter and ciliary muscle, creating a pupil that does not constrict to light or to a target viewed at close range. Within weeks, pupil constriction to a target viewed at close range (“the near response”) is reestablished, but that constriction occurs slowly, creating the term “tonic pupil.” When gaze is redirected from a near to a distant target, pupil dilation is also slow. You might also note that the affected pupil is slightly oval and that the tonic constriction is segmental. Why do those phenomena occur? Because a lesion of the ciliary ganglion affects its nerve outflow segmentally; that is, one part of the iris sphincter is damaged more than other parts. Query: if you are confronted with a unilaterally dilated pupil, how would you know that it might be caused by a relatively acute ciliary ganglionopathy (before development of light-near dissociation and tonic features) rather than by exposure to a topical parasympatholytic agent? There are two clues: 1) in the short term, ciliary denervation causes asymmetric enlargement of the pupil (it has an oval shape) because the denervation is segmental, whereas parasympatholytic agents cause symmetric enlargement of the pupil (it has a round shape); and 2) a ciliary denervated pupil will constrict following instillation of pilocarpine 1%, whereas a pupil that is dilated because of topical exposure to a parasympatholytic agent will constrict minimally after instillation of pilocarpine 1%. Finally, here is a comment about the other answer choices. The combination of ptosis and supraduction deficit could represent a lesion of the superior division of the somatic portion of the third cranial nerve, which would occur intracranially, not in the orbit. The combination of ptosis and miosis suggests Horner syndrome, which arises from a lesion of the oculosympathetic pathway, which does not include the ciliary ganglion. The combination of mydriasis, adduction deficit, and lack of constriction to light or a near target is suggestive of a lesion of the intracranial third nerve that affects its inferior division.

Correct Answer: Third-order neuronal projection

• The first-order neuronal projection extends from the hypothalamus to the upper thoracic spinal cord. Lesions in the hypothalamus are rare and usually cause other neurologic manifestations. Lesions in the brainstem that cause Horner syndrome usually lie in the medulla and never cause Horner syndrome alone. Spinal cord lesions would also be expected to cause other neurologic manifestations. The second-order neuronal projection extends from the spinal cord to the superior cervical ganglion in the neck. Lesions here could cause Horner syndrome in isolation, but almost never acutely. The third order neuronal projection extends from the superior cervical ganglion to the eye. Acute Horner syndrome with ipsilateral facial or neck pain is most commonly caused by cervical carotid dissection, which damages the oculosympathetic axons lying on the outer edge of the vessel wall. The deformation of the carotid artery wall also causes turbulent flow, which may generate emboli that can cause cerebral stroke. The risk of stroke rapidly declines within the first 10 days after the dissection. Patients are usually placed acutely on prophylactic aspirin. The ciliary ganglion and nerves do not lie within the oculosympathetic pathway.

Correct Answer: Medulla

• The combination of Horner syndrome, hypertropia (from skew deviation), and ataxia is strong evidence of a lesion in the dorsolateral medulla. In that region, infarction is the overwhelmingly likely cause, secondary to occlusion of the ipsilateral vertebral artery and its posterior inferior cerebellar artery branch. A stroke in this territory, known as the “Wallenberg syndrome,” may also damage the inferior cerebellum. If the infarction is large, the cerebellum may swell enough to compress the medulla, creating a neurological emergency. The damaged cerebellum may have to be surgically excised. This is the most common brainstem stroke at any age, but especially in young adults. The underlying lesion may be idiopathic or traumatic dissection of the vertebral artery. By the way, can you guess whether the right eye or the left eye was the higher eye? Answer: the right eye. Use this rule: in skew deviation, the higher eye will always be on the side opposite to a medullary or caudal pontine lesion, whereas the higher eye will be on the same side as a rostral pontine or midbrain lesion.

Correct Answer: Right afferent pupil defect

A lesion in the optic tract is apt to cause a contralateral afferent pupil defect because axons coming from that eye and crossing into the opposite optic tract outnumber non-crossing axons. Such an afferent pupil defect is more likely to occur if the lesion damages the optic tract severely enough to cause a complete or nearly complete homonymous hemianopia. Why is this phenomenon important clinically? Because the combination of a unilateral complete homonymous hemianopia and an ipsilateral afferent pupil defect localizes the lesion to the contralateral optic tract, provided there is no evidence of an optic neuropathy on the side of the afferent pupil defect. Without that afferent pupil defect, you might not be able to localize a complete homonymous hemianopia to a particular region in the retrochiasmal visual pathway. Light-near dissociation occurs with lesions of the dorsal midbrain, not from lesions in the optic tract.

Correct Answer: Midbrain

• When the right eye is higher in left gaze and the left eye is higher on right gaze, you are looking at BILATERAL fourth nerve palsies, especially in the setting of head trauma. In concussive head trauma, the brain moves more than its coverings, including the dura. As a result, the dorsal midbrain slams into the rigid, knife-like inner margin of the tentorium cerebelli at exactly the place where the crossing fourth nerves exit from the brainstem. The fourth nerves are often injured together, although usually asymmetrically.
• Bilateral fourth nerve palsies create this pattern of “alternating hypertropia,” a large (at least 10 degrees) excyclodeviation, and an esotropia in downgaze. Imaging generally does not show a pertinent abnormality, although sometimes there is hemorrhage in the caudal dorsal midbrain.
• Recovery is delayed for months and is of variable degree. Eye muscle surgery may eventually be necessary.

Correct Answer: Right vestibular nerve

• The new imbalance, unidirectional horizontal rotary nystagmus, and the positive head impulse test strongly suggest an acute right peripheral vestibulopathy. It has upset the balance between the right and left vestibular pathway inputs. The right-sided lesion produces a drift of the eyes toward the right, which is met by compensatory leftwardly directed saccades, making up a left jerk nystagmus. The nystagmus remains left-beating in all three positions of horizontal gaze, a feature relatively unique to acute peripheral vestibulopathy.
• The positive head impulse test, which can be difficult to interpret in the presence of nystagmus, supports a peripheral lesion.
• The vestibular imbalance explains why the patient falls to her right. A common cause for this condition is “vestibular neuritis/neuronitis,” attributed to a virus. It can be frightening to patients and examiners and very unpleasant. In that condition, there is good evidence of reactivation of herpes simplex type 1 virus in the vestibular ganglia. A large trial showed no benefit of anti-viral therapy, but symptoms resolved more quickly in patients treated with prednisone 1mg/kg for 10 days. Therefore, steroid is often prescribed once the diagnosis is ascertained. Meclizine is also often prescribed for nausea. In this patient, the manifestations rapidly lessened and disappeared completely within 10 days.