Ординатура / Офтальмология / Английские материалы / Handbook of Pediatric Neuro-Ophthalmology_Wright, Spiegel, Thompson_2006

LN/MLN can appear to be converted to “pure” latent nystagmus if the strabismus is repaired.

With electronystagmography, mild LN/MLN can usually be detected in those patients who appear to have only latent nystagmus clinically. The nystagmus simply becomes more prominent when one eye is occluded. True latent nystagmus is uncommon. LN/MLN tends to dampen on adduction, so patients with this condition may present with a head turn toward the side of the fixating eye. These patients have an adduction null with the fixing eye and not a true “gaze” null position. In addition to causing the anomalous head position, LN/MLN can cause the patient to have much worse monocular than binocular visual acuity.

Infantile Nystagmus Syndrome and Vision Loss (INS and Afferent System Defects)

Vision loss before 2 years of age is usually associated with a less well developed form of INS (previously Cogan’s “sensory” nys- tagmus).13,26,28–30,48,49 Visual loss should be highly suspected in any infant or toddler with onset of nystagmus after early infancy because mild to moderate visual loss may not be readily apparent in the preverbal years. It is never caused by pure cortical visual loss; consequently, careful evaluation of the eye is of utmost importance. The examiner should look for media opacities, high refractive errors, foveal hypoplasia, optic nerve hypoplasia, optic atrophy, and pigmentary retinopathy. Examination of the fundus with adequate magnification to assess the size and color of the optic disc is important. Foveal hypoplasia may be an isolated anomaly, or it may suggest albinism, aniridia, or rod monochromatism. A careful slit lamp examination for iris anomalies or transillumination defects and an electroretinogram (ERG) are necessary in such cases. Optic atrophy may be caused by tumors, hydrocephalus, and neurodegenerative disease. These possibilities need to be evaluated with good radiographic images of the brain and orbit, serum lactate and pyruvate levels, and leukocyte galactocerebrosidase levels.

A complete endocrinological evaluation is necessary in all cases of optic nerve hypoplasia because hypothalamic dysfunction is a commonly associated finding. Growth hormone deficiency in particular may be missed in the first few years of life. Lack of vigilance for this condition may result in unacceptable delays in treatment. We obtain brain MRI scans on young

TABLE 9-4. Extended Nystagmus Workup Is Not Necessary.

History

Onset of nystagmus in the first few 4–6 months of life Family history of INS

No developmental or genetic diseases

Normal pregnancy, labor, delivery, growth, and developmental milestones No exposure to toxins or drugs

Ophthalmic examination

Normal visual behavior in both eyes (e.g., F & F, C, US, M, normal Teller acuity card vision for age)

Normal structural examination of the eyes Nystagmus pattern characteristic of INS or FDN

General pediatric examination Normal growth and/or development.

INS, infantile nystagmus syndrome; LN/MLN, latent nystagmus/manifest latent nystagmus.

torsional movements. SN is usually asymmetrical to the point that it may appear unilateral. Pure unilateral forms are not uncommon. It may appear to switch eyes with changes in direction of gaze and frequently appears worse in the abducting eye. Large degrees of asymmetry are associated with amblyopia of the more involved eye.5,31–33,36,71

Spasmus nutans may be a completely benign condition with onset in infancy and resolution within 2 years. However, tumors of the anterior visual pathway and diencephalon can cause a condition indistinguishable from spasmus nutans. Consequently, neuroimaging or careful monitoring for visual, neurological, or endocrinological decline is essential. An intracranial tumor should be strongly suspected in any child who develops spasmus nutans after 3 years of age. Characteristics of infantile nystagmus syndrome, fusion maldevelopment nystagmus syndrome, and spasmus nutans are listed in Table 9-3.

Acquired Nystagmus

Toxins, drugs, and intracranial disease commonly cause acquired nystagmus. Consequently, further evaluation of acquired nystagmus is typically required (Tables 9-4, 9-5,

9-6).18,25,40,51,52,62,63,70

In general, the workup of nystagmus is directed toward identifying features that are not consistent with typical INS or LN/MLN. If these features are found and the etiology is not readily apparent by history or physical examination, neuroimaging studies are usually warranted. Atypical features

TABLE 9-5. Extended Nystagmus Workup Is Necessary.

History

Onset of nystagmus after 6–9 months of age

History of severe prematurity or developmental or genetic diseases Abnormal pregnancy, labor, or delivery

Abnormal and/or delayed growth Exposure to toxins or drugs

Ophthalmic examination

Abnormal vision of the eye(s) (e.g., photophobia, delayed visual behavior) Abnormal structural examination of the eye(s) (e.g., foveal or optic nerve

dysplasia)

Nystagmus pattern vertical, asymmetrical, dysconjugate, or associated with other ocular motor disorders, e.g., decreased

pursuit, abnormal saccades, and paretic gaze General pediatric examination

Pediatrician is concerned with growth and development, or patient has manifest “hard” or “soft” focal or diffuse neurological signs

include vertical, circular, or elliptical components, dissociation of the nystagmus between the two eyes, the presence of oscillopsia, hearing loss, loss or reversal of developmental milestones, ataxia, and weakness. The rationale for specific neuroimaging studies can be derived from the following sections on various forms of acquired nystagmus.

TABLE 9-6. Components of Extended Nystagmus Workup.

Ophthalmologic Electroretinogram Visual evoked response

Ocular motility recordings Neurological

Pediatric neurological examination Neuroimaging (e.g., CAT Scan or MRI)Brainstem auditory evoked potentialElectroencephalography

Developmental/genetic

Genetic specialist evaluation (e.g., pedigree, specialized physical exam, chromosome analysis)

Pediatric developmental specialist evaluation (e.g., psychometric, fine and gross motor and cognitive evaluations)

Serum and/or urine for metabolic diseases

Storage diseases (Neimann–Pick C, Gaucher, sialidosis types I and II, Pelizaeus–Merzbacher disease, GM2 type III

Amino acidurias

Leukodystrophies and other degenerative neurological conditions Lipid metabolism disorders

Amyloidosis

Periodic Alternating Nystagmus

Periodic alternating nystagmus (PAN) resembles INS except that the null point shifts position in a cyclic pattern, resulting in changes in the amplitude and direction of the nystagmus every few minutes. Adequate observation of the patient for several minutes should exclude this diagnosis. However, PAN should be considered any time a patient’s head turn is different from one examination to the next. PAN is fairly common in patients with oculocutaneous albinism.

Periodic alternating nystagmus is usually congenital and benign. Acquired forms may be associated with vestibulocerebellar lesions, neurodegenerative conditions such as Friedreich’s ataxia, visual loss, and hindbrain abnormalities such as Chiari type I malformation. Neuroimaging is warranted in all cases unless the nystagmus has been stable for a prolonged period of time. Acquired PAN responds to treatment with low-dose baclofen.

Gaze-Evoked Nystagmus

Gaze-evoked nystagmus is a jerk nystagmus that occurs in the direction of eccentric gaze. In contradistinction to INS, most forms of gaze-evoked nystagmus can be stabilized by, or improved with, visual fixation and are accentuated by darkness or image blur. Gaze-evoked nystagmus is called gaze-paretic nystagmus if it occurs in the direction of limited eye movement, as may be associated with a cranial nerve palsy or myasthenia gravis. Gaze-paretic nystagmus may appear dissociated if the limitation of eye movement is asymmetric between the two eyes.

One form of gaze-evoked nystagmus that is completely benign is endpoint nystagmus; this occurs in extreme positions of lateral or upward gaze. It can be distinguished from pathological forms of gaze-evoked nystagmus by its low amplitude, symmetry on right and left gaze, poor sustainability, and absence of associated neurological abnormalities.

Drugs, particularly anticonvulsants and sedatives, as well as posterior fossa disease are the most common causes of pathologic gaze-evoked nystagmus. Such etiologies can usually be elicited by a careful medical history and review of systems. Disease of the cerebellum or vestibular system usually results in asymmetry of gaze-evoked nystagmus. For example, tumors

of the cerebellopontine angle may result in a special type of nystagmus called Bruns’ nystagmus. In gaze toward the side of the lesion, there is a low-frequency, large-amplitude oscillation due to defective gaze-holding (gaze-evoked nystagmus). In gaze away from the side of the lesion, a high-frequency, small-amplitude oscillation caused by vestibular imbalance is seen. In patients with pathological gaze-evoked nystagmus, associated neurologic abnormalities such as ataxia, hearing loss, tremor, or hemiparesis should always be sought. Certain characteristics of vestibular nystagmus can localize the etiology to the peripheral or central neuronal pathways of the vestibular systems. Central vestibular nystagmus is frequently uniplanar in contrast to peripheral vestibular nystagmus, which is usually torsional or multiplanar. Visual fixation easily inhibits peripheral vestibular nystagmus but not central vestibular nystagmus. Vertigo and tinnitus are common in peripheral vestibular nystagmus and uncommon in central vestibular nystagmus.

Acquired Pendular Nystagmus

Acquired pendular nystagmus may be caused by tumors, infarction, inflammation, or degeneration of the brainstem or cerebellum. The nystagmus may be horizontal, vertical, or both. A single lesion in the brain results in horizontal and vertical components that oscillate at the same frequency of 2 to 7 cycles per second. If the horizontal and vertical components are in phase, the nystagmus will appear oblique; if they are out of phase, it will appear circular or elliptical. Circular or elliptical nystagmus that is constantly changing character is caused by horizontal and vertical components that are oscillating on different frequencies and implies more than one lesion in the brain.

Localizing Forms of Acquired Nystagmus

Certain forms of acquired nystagmus have features so distinct that neuroanatomic localization of the lesion can be determined by clinical examination alone (Fig. 9-6). See-saw nystagmus consists of an upward and incyclotorsional movement of one eye with a simultaneous downward and excyclotorsional movement of the other eye. Lesions of the diencephalon are the usual cause. Congenital see-saw nystagmus is a rare form of neonatal nystagmus with upelevation and excyclotorsion of one eye and concomitant depression and incyclotorsion of the other eye.6

FIGURE 9-6. Sites within the brain responsible for the “localizing” forms of acquired nystagmus.

Isolated downbeat nystagmus is usually caused by drugs (particularly lithium or sedatives) or lesions at the cervicomedullary junction. In children, it is usually due to Arnold–Chiari malformation or syringo-myelia. Without a drug history, downbeat nystagmus should be evaluated in all patients with a sagittal MRI scan of the brainstem and cervical spinal cord.12

Convergence-retraction nystagmus is usually caused by lesions of the dorsal midbrain, especially those affecting the posterior commissure. It is not true nystagmus because there is no slow phase. A pinealoma is the most common etiology. Involvement of the pupillary light reflex pathway in the posterior commissure results in light–near dissociation of the pupils. The patients have a deficiency of upgaze, because supranuclear upgaze pathways also travel through the posterior commissure. The convergence-retraction nystagmus generally occurs when upgaze is attempted, and it is associated with lid retraction (Collier’s sign). Unlike most forms of nystagmus, the pathological movement is the converging fast phase, which is associated with retraction of the globes into their orbits.10,50 Convergence-

retraction nystagmus is most easily elicited with a downward rotating OKN drum. Convergence-retraction nystagmus may be elicited with OKN stimulation long after other signs of dorsal midbrain involvement have resolved.

Saccadic Oscillations and Other Eye Movements

Saccadic oscillations may be mistaken for nystagmus on cursory examination. However, on closer inspection, or with eye movement recordings, their nonrhythmic nature and lack of slow phases make them distinguishable. As in nystagmus, recognizing those forms of saccadic oscillations that indicate intracranial or systemic disease is important (Fig. 9-7).64,72

Ocular dysmetria is a consistent undershooting or overshooting of a saccade toward a target. Saccades falling short of the target are hypometric; saccades that are too long are hypermetric. This event is usually followed by one or more correctional saccades toward the target. Ocular dysmetria usually is a sign of cerebellar disease, although it can occur with brainstem lesions it tends to have a stereotypical pattern in any given individual. Any patient with new-onset dysmetria requires neurological evaluation.

Ocular flutter consists of random conjugate, to-and-fro horizontal saccades that disrupt fixation. An additional pathological feature is the absence of the normal intersaccadic latency period. Ocular flutter also indicates cerebellar disease and is usually associated with ocular dysmetria.

Opsoclonus is multidirectional ocular flutter. It presents as conjugate, chaotic saccades sometimes described as “saccadomania” or “lightening eye movements.” It is also a sign of cerebellar disease and frequently occurs as a manifestation of postviral encephalitis. When it is associated with ataxia and myoclonus, it is known as the dancing eyes, dancing feet syndrome. It may also occur as a paraneoplastic syndrome associated with neuroblastoma. Consequently, all children with opsoclonus should have a complete medical evaluation, CT scan of the abdomen and thorax, and urinary vanillylmandelic acid levels. Opsoclonus may respond to treatment with steroids or ACTH. It may convert to ocular flutter as it resolves. It can be elicited by forced eyelid closure long after it has otherwise resolved.

Square-wave jerks refer to small, conjugate, horizontal saccades away from fixation followed by a saccadic return to fixa-

FIGURE 9-7. Saccadic oscillations and intrusions. Ocular motility recordings of major types of saccadic disorders. 0, the point of origin of eye.

tion after a 200-ms interval. These jerks may occur in normal individuals, particularly in the elderly. More than nine squarewave jerks per minute is considered abnormal in children. Such children should have a neurological evaluation and neuroimaging for a possible cerebellar disease.

Voluntary nystagmus (present in 7%–15% of the population) refers to a series of volitional, rapid alternating saccades with little to no intersaccadic interval (more like flutter). It is

not a true nystagmus. The movements are usually horizontal but may be vertical or torsional and can only by sustained for a few seconds. Voluntary nystagmus is a popular party trick and is often seen in patients with functional visual complaints. It is frequently associated with convergence of the eyes or facial grimacing. Voluntary nystagmus warrants no laboratory or radiographic investigation.

CLINICAL ASSESSMENT

Examination Techniques: General

The first goal of the history and physical examination is to determine whether the nystagmus has been present from birth (the first few months of life) or acquired later. Information regarding a family history of neonatal eye disease, the pregnancy, labor, delivery, and growth and development since birth should be sought. Neonatal forms are generally benign, whereas acquired forms require further investigation. Patience is essential in the examination of childhood nystagmus. Because anxiety can affect nystagmus, the eye movements should be observed at a comfortable distance, in a nonthreatening manner, while talking to the child or the parent. The most important features of nystagmus can usually be ascertained while playing with the child. Head turns or tilts while the child is viewing distant or near objects should be noted. An adequate fundus examination is a necessary part of the evaluation of involuntary ocular oscillations in infants and children. Many of these patients have prechiasmal visual disorders.

The second goal of the history and physical examination is to assess the level of vision (see Techniques, following). This information may, in fact, be easier to determine than establishing the time of onset of the nystagmus. The types of nystagmus associated with decreased vision differ from nystagmus without visual loss, and this information, combined with the age of onset of the nystagmus, will aid in diagnosis. For example, in a child with acquired nystagmus and good vision, the finding of a conjugate, jerk, downbeat nystagmus points to a hindbrain abnormality and an MRI is indicated. As another example, if there is vision loss along with the nystagmus, the ocular examination is unremarkable and the child is neurologically normal, then an ERG is indicated to evaluate for possible retinal dystrophy. Figure 9-8 gives