Latent nystagmus and acquired pendular nystagmus masquerading as spasmus nutans.

SUMMARY: We used ocular motility recordings to identify the characteristics of a rare combination of conjugate, horizontal jerk, and pendular nystagmus in a 9-year-old boy. The clinical diagnoses were amblyopia, left esotropia, congenital nystagmus, and an apparently uniocular pendular nystagmus that mimicked spasmus nutans. Ocular motility recordings revealed an unusual latent/manifest latent nystagmus, pendular nystagmus with characteristics of an acquired nystagmus, and uniocular saccades. The ocular motor data identified clinically unrecognized types of nystagmus and suggested that the pendular nystagmus was acquired in infancy rather than as a result of failure to develop good vision or binocularity. The presence of uniocular saccades adds to the mounting evidence that individual control for each eye exists in humans.     

Down syndrome and associated congenital malformations

Congenital malformations are many times more common in individuals with Down syndrome (DS) than in the general population. The scope of these defects is as broad in DS as it is in the general population. A positive correlation exists between the prevalence of these defects in both groups, but the incidence of each is many times greater in DS. Two examples, Brushfield spots and anorectal abnormalities are noted in which racial/ethnic prevalence differences exist. The incidence of each condition in the subpopulation with DS is proportional to but many times greater than the incidence of that condition in the general population from which the subpopulation with DS was derived. Findings presented in this review support the notion that the autosomal trisomic state amplifies expression of exposure to teratogens.     

Suppression of congenital nystagmus.

Suppression of congenital nystagmus by eyelid closure was studied by electrooculography in four cases under various conditions in order to elucidate whether the suppression is caused by blocking of fixation or not. The nystagmus persisted in the light as well as in the dark provided that the eyes were kept open. Frenzel's glasses did not suppress the nystagmus except for one case in whom jerky nystagmus was attenuated. In the other cases, only voluntary lid closure suppressed the nystagmus. Passive lid closure while the patient attempted to keep eyes open did not suppress the nystagmus except in one case. Reflex eyelid closure by glabellar tap did not suppress the nystagmus in spite of the occurrence of Bell's phenomenon. Passive eyelid opening while the patient attempted to keep eyes closed, on the other hand, did not reproduce the nystagmus. The suppression of congenital nystagmus by lid closure, at least in some cases, seems to be related to the voluntary effort to keep eyes closed but not specifically to blocking of fixation.     

The differential diagnosis of congenital nystagmus.

The decision whether a nystagmus is congenital or acquired may be difficult and is of importance in patients presenting with neurological complaints. In this article, established diagnostic criteria are critically reviewed with particular emphasis on types of nystagmus waveform and their relationship to pursuit and optokinetic responses. Attention is drawn to certain acquired nystagmus which may have similar features which have hitherto been accepted as pathognomonic of congenital nystagmus. Symptoms due to congenital nystagmus are discussed and related to the oculomotor abnormalities. The importance of the characteristics of congenital nystagmus are evaluated for use in differential diagnosis.     

Unilateral pursuit-induced congenital nystagmus

We describe two patients with a lifelong history of oscillopsia only when following objects moving toward their left side. Neurologic examination was normal except for eye movements. The patients showed nystagmus during any tasks that required visual following toward the left (ie, smooth pursuit, optokinetic nystagmus, and vestibulo-ocular-reflex-suppression), but had no nystagmus during fixation of stationary targets or visual following tasks to the right. Eye-movement recordings showed waveforms during pursuit to the left that were typical of congenital nystagmus.     

Visual electrophysiological screening in diagnosing infants with congenital nystagmus.

OBJECTIVE: To determine the value of visual electrophysiological screening in evaluating retinal and postretinal visual pathway function in infants with congenital nystagmus. METHODS: In 28 infants with congenital nystagmus electroretinogram (ERG) was recorded with skin electrodes and, since the infants were alert, visual evoked potentials (VEP) were simultaneously recorded. The first recording was performed before the age of 1 year (age 2-11 months, mean age 6.8 months). Follow-up was performed between the ages of 7 months and 6 years (mean age 2.7 years). ERG was detected to flash stimulus and VEP to flash and/or pattern-reversal stimulus. RESULTS: In infants less than 1 year of age, retinal dysfunction was recognised in 36% of infants who had been diagnosed as Leber's congenital amaurosis, achromatopsia and retinal dystrophy; postretinal dysfunction was recognised in 32% of infants who had been diagnosed with ocular albinism, optic nerve hypoplasia and neurological nystagmus; retinal or postretinal function was normal in 7% of infants that had been diagnosed as congenital idiopathic nystagmus, while retinal function was normal and postretinal function was undefined in 25% of infants that had been diagnosed as optic nerve hypoplasia, neurological nystagmus and congenital idiopathic nystagmus. At follow-up the findings were: retinal dysfunction in 36%, postretinal dysfunction in 50% and normal retinal and postretinal function in 14% of children. All those children with normal retinal and postretinal function had been diagnosed as congenital idiopathic nystagmus. CONCLUSIONS: Visual electrophysiological screening of infants with congenital nystagmus can establish or exclude retinal and postretinal pathway dysfunction. Therefore simultaneous skin ERG and VEP which is a non-invasive approach for infants enables an objective means for identifying the basis of congenital nystagmus, thereby assisting in its classification.     

Neurodevelopmental criteria in the classification of congenital motor nystagmus.

Congenital motor nystagmus (CMN) can be familial or non-familial. The expressivity of CMN is so variable that in one affected member of the family the oscillations are obvious, while in the others the nystagmus could be overlooked even by the patients themselves. In spontaneous cases the proof of heredity might be discovered by an ophthalmological examination or eye movement recordings of other family members. Our multidisciplinary studies of 27 children with CMN suggests that a neurodevelopmental assessment can also be valuable in establishing a diagnosis of heredity. Our studies suggest that the hereditary form of CMN is free from neurodevelopmental problems, while the non-familial form is not. Therefore, children with spontaneous CMN could be referred for neurodevelopmental evaluation in order to establish a more accurate diagnosis.     

Thyroid function in Down syndrome.

The thyroid function of 181 patients with Down syndrome was investigated. When compared with a control group of 163 children we found T4 and FT4 levels to be significantly lower and T3 and TSH levels to be significantly higher in the Down syndrome population. Of the 181 patients with Down syndrome, 29 (16%) showed evidence of either uncompensated or compensated hypothyroidism: 11 (6%) had both low T4 and high TSH levels, 14 (8%) had only high TSH values, and 4 (2%) had only low T4 values. One of the patients with Down syndrome had a significantly elevated T4 level. Studying different age groups, we observed a decline of the mean T4, FT4, T3, FT3, and TBG values with advancing age. T4, T3, and TSH blood levels obtained in 1988 were slightly but not significantly lower when compared with values from 1985. Because thyroid dysfunctions in patients with Down syndrome are more common than in the general population, periodic thyroid hormone function tests should be performed in persons with Down syndrome in particular as they advance in age. Thus, individuals with significantly abnormal results can be identified early before clinical symptoms become manifest. If patients with Down syndrome are found to have a thyroid hormone disorder, appropriate treatment should be forthcoming, which in turn will enhance their quality of life.     

Assessment of vestibulo-ocular reflexes in congenital nystagmus

The vestibulo-ocular reflex and its suppression by fixation of a target rotating with the subject were tested in 18 subjects with congenital nystagmus using steps of constant velocity rotation and sinusoidal stimuli swept in frequency between 0.01 and 1.0 Hz. Responses to stopping stimuli were abnormal in waveform and of short duration in most subjects tested. This pattern was attributed to masking of the response by spontaneous eye movements and to adaptation. In contrast, during both oscillation in the dark and attempted suppression of the vestibulo-ocular reflex, all subjects had nystagmus that was modulated with the stimulus during all frequencies of stimulation. The phase relationship of the nystagmus to the motion stimulus was the same as in normal subjects. Estimates of the gain of the vestibulo-ocular reflex response were not meaningful because of contamination of the vestibular response by the congenital nystagmus waveforms. Modulation of amplitude and reversal of nystagmus in phase with the vestibular stimulus at all frequencies of oscillation were shown most clearly during attempted suppression of the vestibulo-ocular reflex. This finding is clinically useful because it establishes suppression as a test of the presence of vestibular function in congenital nystagmus.     

The torsional component of "horizontal" congenital nystagmus.

OBJECTIVES: To study the relationship between the major horizontal and minor torsional components of congenital nystagmus to elucidate the diagnostic importance, effects on vision, and pathogenetic implications of the torsional components. METHODS: We recorded the eye movements of 13 subjects with congenital nystagmus using a three-dimensional magnetic search coil technique over a 15-year period. The subjects fixated on stationary targets straight ahead and along the horizontal and vertical meridians. Six of the 10 subjects with horizontal congenital nystagmus were asymptomatic; the remaining 4 (plus two with a vertical component to their congenital nystagmus) had adult-onset symptoms. An additional subject without symptoms had a vertical congenital nystagmus component plus seesaw nystagmus; one of the symptomatic subjects also had seesaw nystagmus. RESULTS: In all 13 subjects, the horizontal and torsional cycles were phase-locked, and positive horizontal (rightward), vertical (upward, if any), and torsional (clockwise) motion coincided in 10 subjects. That is, rightward horizontal eye rotation coincided with clockwise curvilinear motion (rightward and downward) of the upper pole of each eye. During the horizontal foveation periods, torsional motion was also of low velocity. In 2 of 13 subjects, the torsional waveforms differed from those in the horizontal plane; in others, the direction or the variation with gaze angle differed from that predicted by Listing. In each of the 13 subjects, the torsional components ranged from 8.16% to 94.42% (median, 32.94%) of the peak-to-peak magnitudes of the congenital nystagmus. In most cases, the measured torsion was far greater than that predicted by Listing's law for a worst-case analysis (range, 0.69-11.83%; median, 4.91%). The torsional components of the two subjects with seesaw nystagmus were 60.48% and 264.02%. CONCLUSIONS: The manner in which the horizontal and torsional components of "horizontal" congenital nystagmus were phase-locked made clinical detection of the torsional component difficult. Most "horizontal" congenital nystagmus is actually horizontal-torsional congenital nystagmus. Visual acuity during horizontal foveation periods is not significantly diminished by torsional motion. In only one subject did the torsional component of the congenital nystagmus have an amplitude equivalent to Listing torsion; in the other 12 subjects, torsion exceeded our estimate of what Listing's law would predict. The torsional components of the seesaw nystagmus in two subjects also greatly exceeded the torsion predicted by Listing torsion. The most parsimonious explanation for our data is that the cyclic torsion in congenital nystagmus was generated centrally and not a result of Listing torsion, mechanical crosstalk, or normal or abnormal extraocular-muscle (plant) dynamics. Further measurements are needed to confirm this hypothesis.     

Psychiatric disorders in persons with Down syndrome.

This study was designed to provide information on the prevalence and nature of psychiatric disorders in 497 individuals with Down syndrome. There were 261 patients under 20 years of age and 164 patients 20 years and older, with both groups followed as outpatients, and 72 residents from a state school. The overall frequency of psychiatric disorders in our study population was 22.1%. Patients under 20 years of age often displayed disruptive behaviors, anxiety disorders, and repetitive behaviors. Individuals with Down syndrome 20 years and older who were followed as outpatients more often exhibited major depressive disorders and state school residents were found to have an increased prevalence of dementia.     

Down syndrome in Israel

The incidence of Down syndrome was studied in Jerusalem for the years 1964-1970 showing an overall incidence rate of 2.43 per 1,000 live births. A National Down Syndrome Register was established in 1978 and data on annual incidence and mortality rates from 1979-1997 is presented. The incidence in 1997 was 1.0 per 1,000 live births, but 2.32 per 1,000, when live births and terminated pregnancies are summed. Infant mortality has generally decreased in the past 20 years in Israel, and a decrease in infant mortality in Down syndrome has also been noted. This is due to better medical treatment and increased parental involvement in the care for infants with Down syndrome.     

Peripheral vision and optokinetic nystagmus in children with unilateral congenital cataract

The vision of cats which were monocularly deprived during early infancy, of kittens, and of young human infants shares two limitations: detection in the nasal visual field is far poorer than detection in the temporal visual field, and optokinetic nystagmus (OKN) is difficult to elicit when a pattern moves nasally to temporally.Here we report similar limitations on the vision of children who had a dense central cataract in one eye during early infancy. Extensive static perimetry with one of these children whose visual acuity was good in both eyes revealed that her threshold for detection all along the horizontal meridian was higher in her aphakic than in her normal eye, with this difference much more pronounced in the nasal visual field than in the temporal visual field. Three children who developed cataracts after 6 months of age showed no such discrepancy between thresholds in the temporal and nasal fields.We tested the symmetry of OKN in 12 children treated for unilateral congenital cataract. In every test of an aphakic (n = 4) or normal eye (n = 12), OKN occurred significantly more often when stripes moved temporally to nasally than when they moved nasally to temporally. In contrast, no asymmetry was observed in any of 13 children treated for traumatic cataracts incurred after 3 years of age.We conclude that children treated for unilateral congenital cataract, like young human infants and monocularly deprived cats, show asymmetric OKN and relatively poor detection in the nasal visual field.     

Torsional nystagmus in the lateral medullary syndrome

Torsional nystagmus was recorded in 3 patients with the lateral medullary syndrome. Magnetic search coil oculography demonstrated slow phases of nystagmus of increasing, decreasing, and constant velocity. Neural integration of torsional eye velocity commands to position commands is impaired by lateral medullary infarction. Torsional pulsion of saccades, consisting of torsional fast eye movements induced during saccades downward or away from the side of infarction, was recorded in 2 patients. All patients had skew deviation with hypotropia on the side of brainstem damage. The torsional nystagmus beat away from the side of infarction in each patient, but in one it alternated direction as the eyes drifted about a neutral position of torsion. We attribute the torsional nystagmus to an imbalance of central projections from the anterior and posterior semicircular canals and the otolith receptors that mediate ocular counterroll.     

Alzheimer degeneration in Down syndrome. Electrophysiologic alterations and histopathologic findings.

Progressive electroencephalographic disorganization and decreased voltage amplitude in the late components of the averaged visual evoked potentials were recorded in the last two years of life of a patient with Down disease and Alzheimer degeneration. Taken together with quantitative histopathologic findings, the electrophysiologic alterations are interpreted in terms of recent evidence from an experimental animal model of dementia. Neurons with neurofibrillary degeneration become electrically inactive and contribute to the loss of voltage generators associated with neuron death in Alzheimer disease. Loss of voltage generators may result in disfacillitation and disinhibition of surviving neurons, thus causing the loss of normal rhythms.