(Investigative Ophthalmology and Visual Science. 1999;40:2546-2553.)
© 1999
by The Association for Research in Vision and Ophthalmology, Inc.
The Incidence and Waveform Characteristics of Periodic Alternating Nystagmus in Congenital Nystagmus
Josephine Shallo–Hoffmann1,
Mary Faldon1 and
Ronald J. Tusa2
1 From the MRC Human Movement and Balance Unit, National Hospital, London, United Kingdom; and the
2 Bascom Palmer Eye Institute, University of Miami, Florida.
 |
Abstract
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PURPOSE. To investigate the incidence and waveform characteristics of periodic
alternating nystagmus (PAN) in congenital nystagmus (CN).
METHODS. In a prospective study, 18 patients with CN without associated sensory
defects agreed to undergo eye movement documentation using binocular
infrared oculography. Two of the 18 had a diagnosis of suspected PAN
before entering the study. The patients sat in a dimly lit room and
viewed an LED (4 mm in diameter) located in the primary position, at a
distance of 100 cm. During an 8-minute recording, patients were read a
story of neutral interest to hold attention at a constant level. PAN
was defined as a left-beating nystagmus, a transition phase, a
right-beating nystagmus, and a final transition phase; the sequence was
then repeated.
RESULTS. Seven of the 18 patients had PAN (median cycle: 223 seconds, range
180–307 seconds). The periodicity of the cycles for each adult patient
was regular, although the phases within a cycle were often asymmetric.
Six of the seven patients had an anomalous head posture (AHP), and in
five the AHP was in only one direction. Except for one patient, the PAN
waveforms had an increasing slow-phase velocity in at least one phase
of the cycle; in the other phase they were linear.
CONCLUSIONS. The occurrence of PAN in CN is not as rare as previously thought and
can be missed because of the long cycles and the use of only one AHP.
The AHP was dependent on, and could be predicted from, the waveforms
containing the longest foveation times. Although the waveforms and
foveation times may differ among the phases of the PAN cycle, the
periodicity of the cycle was usually regular and therefore predictable.
Identification of PAN is essential in cases in which surgical treatment
is considered for correction of AHPs.
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Introduction
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Congenital periodic alternating nystagmus (CN + PAN) is a
specific form of infantile nystagmus that is involuntary and conjugate
and involves regular epochs of "active" and "quiet"
phases.1
A cycle of PAN includes a left-beating nystagmus,
a quiet or transitional phase, a right-beating nystagmus, and a second
transitional phase. Patients with congenital PAN, as with CN, rarely
report oscillopsia.2
3
4
Congenital PAN had been thought to be a rare
occurrence.5
6
7
However, two recent reports, using eye
movement recordings as the basis for diagnosis, have shown that PAN is
prevalent in CN associated with albinism1
and in CN
patients with and without sensory defects.8
Abadi and
Pascal1
reviewed the eye movements of 32 CN patients with
oculocutaneous or ocular albinism and found that 12 patients (37.5%)
had PAN. In general, the nystagmus intensity varied over the PAN cycle.
None of the 12 patients had an anomalous head posture (AHP) or were
able to null the nystagmus with convergence. Gradstein et
al.8
performed a retrospective analysis of clinical
findings from approximately 200 CN patients with and without sensory
defects and found 18 patients (9%) with a diagnosis ofPAN.
Five of these 18 had albinism; all but two used AHPs. Both studies
concluded that congenital PAN is underdiagnosed.
AHPs are used by patients with CN to maximize visual acuity by placing
the eyes in the orbital location where nystagmus is least. When an AHP
causes physical or social discomfort, surgery should be considered to
move the null point to the center of gaze. In the case of PAN, the AHP
is more difficult to detect, because the null point changes orbital
location and could result in intermittent or more than one AHP.
The focus of this study was to investigate the incidence of PAN,
including a description of cycle time and waveform characteristics in
patients with PAN who do not have sensory defects. It is this group of
patients in which misidentification of the null point may lead to
inappropriate surgery.
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Methods
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Subjects
Eighteen CN patients who did not report oscillopsia, ranging in
age from 11 to 57 years (13 males and 5 females), participated in this
study (Table 1
. As far as possible, an effort was made during patient
recruitment to select only CN patients without sensory defects referred
by colleagues from surrounding medical centers.
All participants underwent ophthalmologic examination before testing.
Patients with visual acuity less than 0.5 and no obvious sensory
deficit underwent further electrophysiological testing. Visual evoked
potential examinations were performed to rule out albinism and optic
nerve lesions, and flash electroretinograms (ERGs) or pattern ERGs were
performed to test for the presence of possible inherited retinal
degeneration or dystrophies. Neuroimaging (computed tomography or
magnetic resonance imaging) of the posterior fossa was performed on the
children in the study to rule out optic nerve compression.
Investigations were performed according to the guidelines of the
Declaration of Helsinki. Subjects were fully informed about the nature
of the procedures and gave their written consent before the beginning
of the testing. The parents of the two children in the study signed the
consent form.
Eye Movement Recordings
The patients sat in a dimly lit room and were instructed to fixate
a stationary LED (4 mm in diameter) located in the primary position, at
a distance of 100 cm. Head movements were minimized using chin and head
rests. Each subject’s eye movements were recorded for an average
duration of 8 minutes, except in the case of the two children, who
underwent eye movement recordings for 4 to 5 minutes. During the
session, patients were read stories of neutral interest to hold
attention at a constant level. Binocular, horizontal eye movements were
recorded using an infrared limbal reflection technique (resolution,
0.1°; range, ± 20°). Eye movements were calibrated monocularly and
binocularly before and after the 8-minute recording session. The eye
position signals were digitized at 250 Hz and stored on computer for
off-line analysis.
Data Analysis
The following features of the nystagmus were examined:
amplitude (peak-to-peak slow-phase displacement), frequency (number of
oscillations per second), expanded foveation time (the period when the
slow-phase velocity was between 0° and 10°/sec), beat direction of
the fast phase, and, when found, cycles of PAN.
Cycles of PAN
Fast-phase components of the PAN recordings were detected
automatically using velocity and acceleration criteria. The remaining
slow-phase regions were checked manually, to eliminate artifacts and
undetected fast phases; then, the mean slow-phase velocity over each
second of the eye movement recording was found. Plots of these mean
slow-phase velocities versus time provided a concise illustration of
the PAN cycles.
For foveation time to have a meaningful relationship to acuity, the
target image must lie within the foveal area, and retinal slip velocity
must be low. When we measured the amount of time (beat-to-beat
throughout the PAN cycle) that velocity was within a ±4°/sec window,
few waveforms had periods of 60 msec or longer. Thus the usefulness of
the method was less obvious. For clarity, plots were based on a
velocity criterion of ±10°/sec to assist identification of best
foveation times. This method describes the portion of the cycle that
afforded best visual acuity and indicates a cause for a preferred AHP.
In two cases, (patients 15 and 17), in which linear or decreasing
slow-phase velocities occurred, the analysis was referred to as
"low-velocity" time.
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Results
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Seven of the 18 CN patients (39%) had PAN. The PAN cycle duration
ranged from 180 seconds to 307 seconds, with a median cycle duration of
223 seconds. PAN and CN waveform characteristics are summarized in
Tables 2
and 3
, respectively. With the exception of one child (patient 17) and one
adult (patient 4) who were referred with a clinical diagnosis of
suspected congenital PAN, the patients entered this investigation with
a diagnosis of CN only.
Patient 1
A 30-year-old man with infantile esotropia underwent three
surgeries (at ages 2, 10, and 11 years) to correct strabismus before
entering this study. Funduscopy and visual evoked potential testing for
chiasmal misrouting were normal. At 25 years of age, he was
unsuccessfully treated with botulinum toxin to correct residual
right-alternating esotropia (near 30 D and far distance 20 D).
Eye movement recordings showed PAN, with one complete cycle lasting 185
seconds (Fig. 1)
. At the time of the eye movement recordings, the patient had a
constant 10° left AHP. This placed the eyes in a right orbital
position, which was optimal for nulling the left-beating nystagmus, the
phase of the PAN that had the shortest foveation times.
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Figure 1. (Top) The mean slow-phase velocity (spv) of PAN in
patient 1 as a function of time. Positive spv indicates movement to the
subject’s right. Each data point represents the mean spv over a period
of 1 second. The PAN cycle had a regular periodicity, with greater
slow-phase velocities occurring during phases of left-beating nystagmus
(up to 60°/sec) than right-beating nystagmus (up to 20°/sec).
(Middle) The expanded foveation time of each nystagmus
beat during the recording. The expanded foveation time was defined as
the duration for which the spv of each beat was less than ±
10°/sec. For this subject, the shortest foveation times (<60 msec)
occurred during periods of left-beating nystagmus, which could be the
basis of the patient’s poor visual acuity. The longest foveation times
occurred during the transition phases (indicated by the vertical
bars between the top and middle
plots) and shortest during left-beating nystagmus.
(Bottom) Representative infrared right eye movement
recordings for each phase of the PAN cycle (right-beating nystagmus
phase, pseudopendular, bidirectional jerk transition phase,
left-beating nystagmus phase) had increasing slow-phase velocities. The
upper trace shows eye position (R, right;
L, left); the lower trace shows the eye velocity.
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Patient 3
This 40-year-old journalist had a normal fundoscopy and visual
evoked potential. Eye movement recordings showed a PAN cycle of
approximately 180 seconds (Fig. 2)
. The constant left AHP, which placed his eyes in a right orbital
position, was optimal for nulling the left-beating nystagmus.
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Figure 2. Notation as in Figure 1
. (Top) The PAN cycle of
patient 3 has a left-beating bias with a minimal right-beating
nystagmus. (Middle) During periods of left-beating
nystagmus, occasional, long-duration slow phases produced intermittent
long foveation times. For this subject, consistently long foveation
times occurred during the transition and right-beating nystagmus (e.g.,
at approximately 200 seconds into the recording) and could explain good
visual acuity. Foveation times of 600 msec and more are represented on
the y-axis at the 600-msec mark. (Bottom)
Representative right eye movement recordings of a left-beating
nystagmus phase, a transition phase with one of the intermittent
long-duration slow-phase velocity waveforms, and a right-beating
phase.
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Patient 4
A 27-year-old man with normal visual acuity underwent two
Kestenbaum9
–Anderson10
procedures at 12 and
14 years of age to correct an AHP. He continued to have a
slight to moderate right AHP. He never used a left AHP and reported
double vision in lateral gaze that was caused by a postsurgical
limitation in abduction of the right eye. Eye movement recordings
showed PAN with a mean cycle time of 236 seconds (Fig. 3)
.
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Figure 3. Notation as in Figure 1
. (Top) The peak spv of the
right-beating nystagmus reached 55°/sec, whereas peak spv of the
left-beating nystagmus remained below 25°/sec.
(Middle) Longest foveation times occurred during
transition and left-beating nystagmus phases. (Bottom)
Representative right eye movement recordings for each phase of the PAN
cycle, with increasing spv waveforms in both left- and right-beating
phases and a nulled transition phase.
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Patient 10
A 38-year-old pharmacist with inherited CN and exophoria used an
intermittent right AHP but never used a left AHP. Eye movement
recordings showed PAN with a mean cycle of 293 seconds. The AHP placed
the eyes either in the primary position or in left orbital gaze, which
was optimal for nulling the right-beating nystagmus (Fig. 4) .
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Figure 4. Notation as in Figure 1
. (Top) PAN of patient 10 with a
regular 5-minute cycle. (Middle) Foveation times were
relatively short for both right- and left-beating nystagmus phases and
could account for this patient’s poor visual acuity.
(Bottom) Representative right eye movement recordings
for each phase of the PAN cycle, with increasing spv waveforms in both
left- and right-beating phases and a damped transition phase.
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Patient 15
A 12-year-old boy with suspected X-chromosomal recessively
inherited CN and exophoria had PAN with a mean cycle duration of 221
seconds. The patient had an intermittent left AHP (0–10°) and never
used a right AHP. Results of neurologic and ophthalmologic
examinations, ERG, and magnetic resonance imaging were normal (Fig. 5)
.
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Figure 5. Notation as in Figure 1
. (Top) The plot shows part of a
relatively long PAN cycle from patient 15. (Middle) The
low slow-phase velocity times were short, except during the transition
phase when this patient had better visual acuity.
(Bottom) Representative right eye movement recordings
show that the left-beating nystagmus had mostly linear waveforms with a
decreasing spv component that did not return to zero velocity before a
saccade was executed. The right-beating nystagmus consisted of a
decreasing spv waveform. Both waveforms had no acceptable foveation
times. The longest low-velocity times occurred during and just before
the transition phases. These times were often less than 60 msec, during
the periods of both right- and left-beating nystagmus and could account
for the patient’s poor visual acuity.
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Patient 17
An 11-year-old girl with infantile strabismus and CN, which was
observed in the first few weeks of life, showed PAN with a cycle
duration of 307 seconds (Fig. 6)
. She used an alternating, intermittent AHP, left when fixating right
and right when fixating left. Extensive neurologic and ophthalmologic
examinations, including electroencephalogram and a computed tomographic
scan, did not detect any abnormalities.
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Figure 6. Notation as in Figure 1
. (Top) The plot shows a section
of a relatively long PAN cycle in patient 17. (Middle)
Foveation times were generally below 60 msec during right-beating
nystagmus and were negligible during the main phase of left-beating
nystagmus. (Bottom) Representative right eye movement
recordings of the left-beating phase, the transition phase with
pendular nystagmus, and the right-beating nystagmus phase. The
right-beating nystagmus, with slow phases of increasing velocity, had
short foveation times, and the linear slow phase left-beating nystagmus
and pendular transition phases had no foveation time. These waveforms
yielded foveation times that would not support good visual acuity.
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Patient 18
A 29-year-old man who was an audiovisual engineer had good visual
acuity and stereopsis and stopped using an alternating AHP as a
teenager. Eye movement recordings showed a PAN with a mean cycle of 223
seconds (Fig. 7)
.
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Figure 7. Notation as in Figure 1
. (Top) Two complete cycles of
PAN (patient 18). The cycles were regular, approximately 4 minutes
long. (Middle) This patient had relatively long
foveation times during all phases of PAN, which can account for the
patient’s good visual acuity. (Bottom) Representative
right eye movement recordings show that both right- and left-beating
nystagmus had increasing spv waveforms that yielded relatively long
foveation times. During transitions, the waveforms damped increasing
foveation times.
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Discussion
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Thirty-nine percent of the sample had PAN, which is consistent
with the percentage reported in CN patients with
albinism.1
One important clinical difference between the
two sample groups is that none of the CN patients with albinism had an
AHP, which would exclude them as candidates for surgical correction. It
is not surprising that patients with sensory deficits (in this case,
albinism) may not use AHPs, because increasing foveation time by way of
a head turn would not markedly improve visual acuity.
Gradstein et al.8
and earlier
investigators5
6
7
11
12
reported a lower percentage of PAN
in CN than either this study or the study by Abadi and
Pascal.1
Some factors that may have influenced this
difference beyond the inherent limitations of a retrospective analysis,
are as follows.
- PAN may have been missed because of the long duration of a cycle.
Gradstein et al.8
used 2 to 3 minutes of continuous
straight-ahead recording time. Our study showed that median PAN cycles
were approximately 4 minutes and could be as long as 5 minutes.
- The absence of control for attention during the recording session. This
factor has been pointed out by Gradstein et al.8p927 It
can affect arousal and thereby modify nystagmus intensity. Although
recording sessions were long in our study, it was not difficult to
maintain the attention of the patients with the aid of storytelling.
All participants, including the two children, could easily comply with
the task demand and listen to the stories.Further, the
recordings from the adult patients provided evidence that PAN found in
CN can have regular, predictable cycles, which is critical when surgery
is indicated.
- PAN may have been missed in the past, because patients may have used
only one head turn. Patients with CN and PAN deploy strategies to use
the waveform that affords the longest foveation times and thereby
optimizes visual acuity. For example, as in patient 1 of our study, an
AHP to the left was optimal for left-beating nystagmus. This is because
a left AHP puts the eyes in right gaze position where left-beating
nystagmus is minimal. The left-beating nystagmus could not be nulled
when the eyes wereplaced in left orbital gaze. Therefore, a
patient with PAN may use only one head turn, as was observed in five of
the seven patients in this study, and this may be an important reason
why the disorder had been missed in the past.
Findings from our study not only underscore the importance of
diagnosing PAN but also show the advantage of describing the waveform
characteristics that may be useful in determining the optimal surgical
procedure. Review of the mean and peak slow-phase velocities along with
the foveation time of each slow phase during the recording indicates
which part of the cycle yields the best visual acuity and predicts the
AHP that would most benefit the patient.
Although studies with larger sample sizes are needed to provide the
evidence necessary to suggest how long a patient with suspected PAN
should be observed to determine whether PAN is present, our study
provides two guidelines:
- If the predominant waveform is bidirectional (for example,
pseudopendular), unidirectional with an alternating direction, or a
mixture of bidirectional waveforms, the chance that PAN is present is
negligible.
- In the case of a predominant jerk waveform, the methods presented in
this study should be adequate to detect most PAN cycles.
The role of eye muscle surgery in patients with congenital
PAN is still uncertain. Gradstein et al.8
recently
compared the outcome of the
Kestenbaum9
–Anderson10
procedures with large
recessions of all four horizontal muscles13
and found that
the latter procedure yielded satisfactory results for correction of
AHPs. However, this may not always be the operation of choice for PAN,
as suggested by the authors. A patient may have one consistent AHP as
well as foveation characteristics that suggest a procedure that
attempts to move the null zone from eccentric to primary gaze, as in
patient 3 of our study who had a 20° to 25° left AHP and showed PAN
that almost completely cycled within a left-beating nystagmus (Fig. 2)
.
Using an animal model, Dell’Osso et al.14
suggested that
an extraocular muscle tenotomy may be sufficient to damp nystagmus and
improve visual acuity when AHPs are inconsistent and convergence does
not diminish nystagmus intensity. The advantage of this procedure may
be the elimination of double vision in extreme lateral gaze, which
sometimes occurs after large rectus muscle recession procedures. This
technique has yet to be used in patients in a controlled trial.
In summary, the occurrence of PAN in CN is not as rare as
previously suggested and can be missed because of long cycles and the
patient’s preference for only one AHP. Although phases within a PAN
cycle can be asymmetric (greater duration of beating in one direction
over the other), evidence indicates that the cycles of PAN in CN are
usually regular and that the motion of the null is not susceptible to
modification. This is in contrast to the waveform and foveation
characteristics of the nystagmus. Identification of PAN and its
waveform characteristics are essential in cases in which surgical
treatment is considered for correction of AHPs.
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Footnotes
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Submitted for publication December 21, 1998; revised May 27, 1999; accepted June 15, 1999.
Commercial relationships policy: N.
Corresponding author: Josephine Shallo–Hoffmann, College of Optometry,
Nova Southeastern University Health Professions Division, Fort
Lauderdale, Florida. E-mail: shoffman{at}hpd.nova.edu
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References
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Bedell, HE (1992) Sensitivity to oscillatory target motion in congenital nystagmus Invest Ophthalmol Vis Sci 33,1811-1821[Abstract/Free Full Text]
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Dell’Osso, LF, Leigh, RJ (1992) Ocular motor stability of foveation periods Neuro-ophthalmol 12,303-326
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Anderson, JR (1953) Causes and treatment of congenital eccentric nystagmus Br J Ophthalmol 37,267-281
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Collewijn, H, Apkarian, P, Spekreijse, H. (1985) The oculomotor behavior of human albinos Brain 108,1-28[Abstract/Free Full Text]
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Top
Abstract
Introduction
