fixation. Relatively large movements that break fixation, such as macrosquare-wave jerks, tend to occur in short bursts. Macrosaccadic oscillation develops because of a hypermetria that produces repetitive inaccuracies in attempts to fixate on a target and is a manifestation of cerebellar dysfunction.
Saccadic Intrusions Without Normal Intersaccadic Intervals
Two types of eye movement abnormalities lack the intersaccadic interval that normally occurs between sequential saccades: (1) ocular flutter and (2) opsoclonus. Ocular flutter typically presents as bursts of small-amplitude, very high frequency (10–15 Hz) horizontal movements (Fig 9-3D). Opsoclonus (or saccadomania), however, presents as multidirectional eye movements with a similarly high frequency but often larger amplitude. A patient may have both ocular flutter and opsoclonus, or the movements may shift from one form to the other during the course of disease. Both conditions can be diagnosed with reasonable confidence through clinical examination alone, although a definitive demonstration of the lack of an intersaccadic interval requires eye movement recordings. Their pathology is unknown but may relate to dysfunction of the omnipause neurons of the pons or to connections with these cells (see Chapter 7).
A paraneoplastic etiology must be excluded in evaluating patients with ocular flutter or opsoclonus. In children, neuroblastoma (or other tumor of neural crest origin) is the primary consideration, whereas in adults, small cell carcinoma of the lung or cancer of the breast or ovaries is of prime concern. Abnormal antibodies directed against neuronal RNA are found in some patients with paraneoplastic-induced ocular flutter or opsoclonus. Serologic or cerebrospinal fluid assay for the IgG anti–neuronal nuclear antibody type 2 (ANNA-2, or anti-Ri) can help confirm the diagnosis in cases secondary to cancer of the breast or ovary, whereas anti–neuronal nuclear antibody type 1 (ANNA-1, or anti-Hu) is present in some children with neuroblastoma. Multiple sclerosis is a common cause of ocular flutter in young adults. Ocular flutter and opsoclonus may develop after brainstem encephalitis. Other reported causes include drug intoxication, environmental toxins, and hyperosmolar coma. Despite the generally dire implications, opsoclonus may be a transient finding in otherwise healthy infants and, though rare, may occur in some patients without explanation in the absence of associated neurologic or systemic abnormalities. Opsoclonus may coexist with myoclonus (opsoclonus-myoclonus syndrome).
Voluntary Flutter (“Nystagmus”)
Voluntary “nystagmus” consists of rapidly oscillating eye movements (almost always horizontal) that can be induced volitionally. The movements, which are not a form of nystagmus (because they lack slow phases), appear as high-frequency, conjugate, back-to-back saccades without an intersaccadic interval associated with convergence and often with eyelid flutter and facial grimacing. Episodes rarely last longer than 10–12 seconds. At times, voluntary nystagmus can be difficult to distinguish from ocular flutter; however, ocular flutter is typically associated with other abnormal examination features and does not have the convergence and eyelid accompaniments of voluntary nystagmus.
Additional Eye Movement Disorders
Convergence-Retraction Nystagmus
Convergence-retraction nystagmus does not meet the true definition of nystagmus because it lacks slow phases. The condition results from co-contraction of the extraocular muscles on attempted upgaze. The medial rectus muscles are the most powerful of the extraocular muscles, and their contraction produces convergent movements even when all other extraocular muscles are contracting. The co-contraction of all extraocular muscles produces retraction of the globe into the orbit. Convergence-retraction nystagmus localizes the disease process to the dorsal midbrain, and hence this “nystagmus” is often associated with paresis of upgaze, pupillary light–near dissociation, skew deviation, and bilateral eyelid retraction (Collier sign). Convergence-retraction nystagmus is best demonstrated by having the patient make an upward saccade or follow a downward-rotating optokinetic nystagmus (OKN) drum.
Superior Oblique Myokymia
Superior oblique myokymia is a disorder that produces paroxysmal, monocular, high-frequency bursts of contraction of the superior oblique muscle. These bursts typically last for seconds, occur numerous times per day, and produce vertical or torsional oscillopsia. The movements are of very small amplitude and usually require magnification (obtained, for instance, with a slit lamp or 20 D lens) to observe them. The abnormal movements may occur spontaneously or immediately after a downward eye movement. The contraction of the superior oblique muscle may also produce transient vertical diplopia, because a tonically contracting superior oblique muscle will depress the affected eye. Electromyographic recordings of some patients have demonstrated abnormal discharge from some muscle fibers, either spontaneously or after contraction of the muscle. The etiology of superior oblique myokymia is unknown. The disorder is almost always benign, although there are rare reports of its association with multiple sclerosis or posterior fossa tumor. Some clinical and neuroimaging findings suggest this disorder may be due to neurovascular compression, similar to cases of hemifacial spasm and trigeminal neuralgia.
The clinical course of superior oblique myokymia is highly variable. Some patients enjoy spontaneous recovery or experience only brief spells of symptoms. Most patients, however, experience chronic oscillopsia or intermittent diplopia. Treatment with carbamazepine, phenytoin, baclofen, gabapentin, or topical betaxolol may be helpful for some patients. In more severe cases, a combined superior oblique muscle tenotomy and recession of the ipsilateral inferior oblique muscle may be helpful.
Brazis PW, Miller NR, Henderer JD, Lee AG. The natural history and results of treatment of superior oblique myokymia. Arch Ophthalmol. 1994;112(8):1063–1067.
Oculomasticatory Myorhythmia
Vertical saccadic palsy may be an early neurologic finding in Whipple disease. In addition, pendular vergence oscillations may develop that occur with contractions of the masticatory muscles. This combination of abnormal movements is known as oculomasticatory myorhythmia. Patients may have only the neurologic manifestations, but more commonly they also have unexplained fever, diarrhea, cognitive dysfunction, weight loss, and lymphadenopathy. Whipple disease can be diagnosed through duodenal biopsy (using periodic acid-Schiff [PAS] staining) to document infection with Tropheryma
whipplei or by serologic polymerase chain reaction (PCR) testing. Although Whipple disease is progressive and potentially life-threatening, it is curable with antibiotic therapy.
Schwartz MA, Selhorst JB, Ochs AL, et al. Oculomasticatory myorhythmia: a unique movement disorder occurring in Whipple’s disease. Ann Neurol. 1986;20(6):677–683.
Treatment of Nystagmus and Other Eye Movement
Disorders
Nystagmus is often difficult to treat, although successful therapy has been reported for some forms. Several treatment options are described here, but clinicians should review the referenced publications to obtain more in-depth information.
The use of baclofen (a GABAB receptor agonist) for the acquired form of PAN and carbamazepine derivatives for superior oblique myokymia is well established and frequently effective. Downbeat nystagmus and other central vestibular forms of nystagmus can occasionally be helped by clonazepam, a GABAA receptor agonist. Memantine or gabapentin (another GABAergic medication) may reduce nystagmus severity and improve vision in patients with both acquired and congenital forms of nystagmus. Dalfampridine has been used in the treatment of downbeat nystagmus and may be more efficacious than the similar drug amifampridine.
Nonpharmacologic treatment options are also available. Nystagmus associated with amblyopia can be improved with traditional amblyopia therapy. The use of base-out prisms to induce convergence may help some patients whose nystagmus diminishes with convergence. Use of contact lenses may improve visual acuity in patients with congenital nystagmus.
Unilateral retrobulbar injection of botulinum toxin type A reduces the amplitude of nystagmus and may produce a visual benefit for patients who are willing to view monocularly. However, total cessation of eye movements has its own consequences; for example, some patients report blurred vision when walking because of the loss of the normal VOR that adjusts eye position as the head moves.
Some patients with congenital nystagmus can be helped by extraocular muscle surgery (eg, the Anderson-Kestenbaum procedure) to mechanically shift the null point to primary position. A similar procedure may be performed on the vertical recti of a patient with upbeat or downbeat nystagmus, although diplopia may result postoperatively because of limited vertical fusional amplitudes. Surgeons have achieved variable reduction of the amplitude of eye movements and improved visual acuity in some adult patients with congenital nystagmus by performing horizontal rectus muscle tenotomy, with reattachment of the muscles to their original insertion site.
Shery T, Proudlock FA, Sarvananthan N, McLean RJ, Gottlob I. The effects of gabapentin and memantine in acquired and congenital nystagmus: a retrospective study. Br J Ophthalmol. 2006;90(7):839–843. Epub 2006 Mar 23.
Straube A, Leigh RJ, Bronstein A, et al. EFNS task force—therapy of nystagmus and oscillopsia. Eur J Neurol. 2004;11(2):83– 89.
Eye Movements in Comatose Patients
Coma is caused by bilateral lesions of the brainstem (typically structural) or cerebral hemispheres (structural or metabolic disturbances). Coma also can result from a large, unilateral hemispheric stroke when the accompanying edema or hemorrhage produces a mass effect that is sufficient to cause midline shift or tentorial herniation and compression of the brainstem.
A variety of eye movement abnormalities may occur in unconscious patients, including conjugate deviation of the eyes. In a gaze preference, the eyes deviate toward the side of a cerebral hemispheric lesion (and away from the side of the hemiparesis, if present) because the intact contralateral frontal eye field imposes a bias that drives the eyes to the opposite side. Intact horizontal eye movements are demonstrable with supranuclear activation such as the VOR (during a doll’s head maneuver). This type of ocular deviation typically persists for only a few days, after which compensatory adjustments are made by the brain to balance the tonic input that controls resting eye position. A pontine brainstem stroke that produces coma may also produce conjugate ocular deviation, although in this situation (gaze palsy) the eyes deviate away from the side of the lesion (remember the mnemonic device, “Brainstem lesions are too terrible to look at”). Here, the intact, contralateral horizontal gaze center drives the eyes to the ipsilateral side. Ocular deviation from brainstem strokes usually persists for long periods of time.
Comatose patients may also manifest spontaneous, slow, roving horizontal eye movements. The conjugate nature of these eye movements indicates intact brainstem ocular motor pathways, as may occur in patients with coma due to metabolic derangement. Spontaneous eye movements of this type may also be somewhat disconjugate. In cases of coma caused by bilateral hemispheric lesions, spontaneous eye movements may be confined to the horizontal plane and rapidly alternate in gaze from one side to the other every few seconds (ie, “ping-pong” gaze). Periodic alternating gaze deviation, a longer period of alternating deviation lasting minutes, may occur in patients with metabolic coma.
Ocular Bobbing
Ocular bobbing is a rare sign characterized by rapid downward movement of both eyes, followed by a slow return of the eyes to the midline position. The causative lesion is usually in the pons, secondary to infarction or hemorrhage. Ocular bobbing portends an extremely poor prognosis for neurologic recovery. Bilateral pontine lesions lead to loss of horizontal eye movements.
Similar vertical eye movements may have an initially slow downward movement followed by a fast return to primary position (eg, inverse bobbing, or ocular dipping), or the deviation from primary position may be upward. An initially fast upward deviation followed by a slow return to primary position is reverse ocular bobbing; a slow initial upward drift followed by a fast return to primary position is converse bobbing, or reverse ocular dipping. Although ocular bobbing provides valuable localization and prognostic information, inverse bobbing, reverse bobbing, and ocular dipping are nonlocalizing phenomena (most often noted with hypoxic-ischemic encephalopathy).