Brain (1976) 99, 207-234
OCULAR MOTOR ABNORMALITIES IN HEREDITARY CEREBELLAR ATAXIA by DAVID S. ZEE, ROBERT D. YEE, DAVID G. COGAN, DAVID A. ROBINSON and W. KING ENGEL {From the Medical Neurology Branch, National Institute of Neurological and Communicative Disorders and Stroke and Clinical Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland, and the Departments of Neurology and Ophthalmology, The Johns Hopkins Hospital, Baltimore, Maryland)
METHODS Saccadic and Smooth Pursuit Eye Movements Eye movements were recorded monocularly from the left eye using an infra-red pupil tracking device (Zee, Friendlich and Robinson, 1974). This system has a linear range and accuracy of 40±0-5°
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A NUMBER of ocular motor abnormalities have been attributed to cerebellar dysfunction (Cogan, 1956; Daroff and Hoyt, 1971; Kornhuber, 1974), but the exact role of the cerebellum in the control of eye movements in human beings remains unclear. Recent studies in monkeys have suggested that the cerebellum specifically functions in (1) maintenance of eccentric positions of gaze; (2) production of smooth pursuit eye movements; (3) modulation of saccadic eye movement amplitude; and (4) visual suppression of caloric-induced nystagmus (Westheimer and Blair, 1974; Aschoff and Cohen, 1971; Takemori and Cohen, 1974). We have had the- opportunity to record and 'analyse the eye movement abnormalities in patients from a kindred with late onset, dominantly inherited, cerebellar ataxia. This has served to define the ocular motor signs of cerebellar dysfunction in human beings, as well as to correlate findings in patients with those in experimental animals. Our patients showed defects comparable to those in monkeys with cerebellar lesions including inability to hold eccentric gaze (with consequent gaze-paretic nystagmus), defective smooth pursuit, saccadic dysmetria and defective visual suppression of vestibular nystagmus. Other findings included downward beating nystagmus, enhanced gain (eye velocity/head velocity) of the vestibulo-ocular reflex during rotation in darkness and rebound nystagmus. Many characteristics of the altered vestibulo-ocular responses and gaze-paretic and rebound nystagmus could be best interpreted by considering the different mechanisms used by the central nervous system to hold positions of gaze.
208
D. S. ZEE AND OTHERS
horizontally and 2O±O-75° vertically with a frequency response of 0-167 Hz. Targets were rear-projected on a screen, 54 cm from the patient's left eye and moved by a mirror galvanometer in the projector's light path. The patient's head was restrained by an acrylic dental bite bar and head rest. Saccadic eye movements were measured either during refixations between stationary visual targets or in response to step changes in target position. From the primary position the target could be moved peripherally in any direction. From an eccentric position, however, the target's next jump was always back to the primary position. Latencies for saccadic eye movements were determined by measuring reaction times to aperiodic, 20°, step changes in target position. Peak eye velocities were measured for 20° horizontal refixations between two stationary targets. Pursuit movements were measured while patients attempted to track a small illuminated dot moving on a dark background. The target moved in a triangular wave fashion with an excursion of 20° (±10° about zero) at various velocities from 2-5 to 55°/s. In several patients, optokinetic nystagmus was induced by full-field stimulation. Patients were placed in an aluminium drum, 4 ft in diameter, painted with alternating black and white stripes, each 1\° in width. The head was steadied by a support. The drum was rotated horizontally at constant velocities ranging from 5 to 90°/s. The patient's instructions were: 'follow the stripes as they pass in front of you.' Eye movements were recorded by DC electrooculography (EOG) with a band width of 100 Hz.
Eccentric Gaze The ability to hold eccentric gaze was measured by EOG. The range of positions tested was ±15-45°. Eye movements from both the infra-red tracking device and electro-oculography were recorded on magnetic tape and transferred to recorder paper by a UV mirror galvanometer with a band width of 2 kHz. The patients in this study took no medication in the week before testing. They were continually urged to stay alert and perform maximally.
CLINICAL FEATURES Family Background and Inheritance Fig. 1 illustrates the family pedigree. All affected members are descendants of a couple who emigrated from Ireland to central Pennsylvania in 1828. The vertical transmission of the disorder from generation to generation and the ratios of unaffected and affected males and females are compatible with autosomal dominant inheritance. Neurological Features Table 1 summarizes the neurological findings in the 12 family members who were examined and found to be affected. Onset of symptoms was between ages 41 and 59, with a mean of about 50. Unsteadiness of gait was invariably the first symptom. In a few individuals, dysarthria was noted soon thereafter.
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Vestibular Eye Movements Vestibulo-ocular responses were assessed during sinusoidal chair rotations typically at a frequency of 0-3 Hz and peak velocity of 20-25°/s. Eye movements were measured by DC electro-oculography (EOG) with a system with a frequency response of 0-300 Hz. Chair position and hence head position was monitored by a potentiometer. Patients were tested for periods of no longer than two minutes at a time and the EOG was calibrated immediately before and after each test. This gave an estimated linear range and accuracy of 40± 10°. To stimulate the vertical canals, the patient's head was positioned with the interorbital axis vertical. Three different testing paradigms were used: rotation in complete darkness with eyes open while performing mental arithmetic; rotation while fixating a stationary target on the wall; and rotation while fixating a target moving with the patient on the chair. Small, red, light emitting diodes were used as fixation targets.
EYE MOVEMENTS IN CEREBELLAR ATAXIA
v
DO
D 00
O
«
•
B
«
»
O
»
11 II ' »
209
»
D
33
II
JO
«
XS
I
1
DO
Thought to bt normal
0
Thought to b« • H i l m J
0 ?
7)
Patient L o g o 81
Neurologic itatui cunllmod by examination Naurotoglc Itmui not knowl
NOTE: ChBdnwi In Generation VI are not shown unfaee parent le affected
FIG. 1. Family pedigree. The rate of progression was slow and patients usually did not become wheelchair-bound until at least age 65. Significant inco-ordination of the upper limbs usually occurred late in the course of the illness. Mental changes, objective muscle weakness or atrophy, sphincter abnormalities and sensory disturbances were absent. In several patients reflexes were somewhat brisk but neither Babinski responses nor increased muscle tone could be detected. Visual symptoms were inconstant and varied. Several patients noted transient episodes of diplopia or vertigo at the onset of their illness. Others reported that while riding in a moving car they had difficulty recognizing faces of individuals walking on the sidewalk. Several individuals also noted occasional vertical oscillopsia when reading. Some patients, including several that were severely affected, had no visual symptoms. Ocular Motor Findings Except for mild limitation of upward gaze in older patients, the range of ocular movements was full. Saccades appeared to be of normal velocity but dysmetria, especially overshoot of downward refixations, • was uniformly present. All patients showed defects in smooth pursuit. They had to substitute catch-up saccades in order to keep the image of the moving target near the fovea. Abnormalities of optokinetic responses, elicited by a hand drum, appeared to parallel the smooth pursuit defects. In the primary position of gaze, most patients showed repetitive, horizontal, to and fro, small amplitude saccades or square wave-jerks. In addition many patients showed a mild degree of downward beating nystagmus which became substantially accentuated on far lateral gaze. Rebound nystagmus and gazeparetic nystagmus were evident to a variable degree in all patients. During doll's head rotation in the
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KEY TO PEDIGREE O
of ent* 1 2 3 4 5 6 7 8 9 10 11 12
Sex
F M M
F M M F M F
F F
F
Age 61 54 64 61 74 52 66 71 70 63 71 57
symptoms (years) 5 5 6 12 20
Gait Dysmetria ataxia Dysarthria UE LE 0 2+ 1 + 2+
1+ 3+ 3+
2+ 3+ 1+
5
1+
1+
7
4+ 4+
4+
4+
19 23 20 30
4+ 4+
7
1+
3+
4+
1+
2+
1+ 3+ 3+
2+ 3 + 4+ 1+ 1+ 3 + 4+ 2+ 3+ 2+ 3+
4+ 3+ 3+
4+
4+
2+
2+
0
0
3+ 1+
Pursuit^ OKN\ (horizontal) Present 1+ Present 2+ Absent 3+ 3-f, Absent Absent 4+
2+ 3+
4+ 4+ 4+ 4+ 2+
Present Absent Absent Absent Absent Absent Present
Saccadic dysmetria Vert. Horiz. 0 1+
1+
0
1+
2+
1+ 1+
4_i_**
i+ 0
1+
0
2+ 2+ 1+ 3+ 1+ 2+ 4+'* 2+ 2+ 2+ 1+
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TABLE 1. SUMMARY OF CLINICAL FEATURES
Nystagmus Square wavejerks 0
Gazeparetic
1+ 1+ l+ll 3+
1+
3+ 2+ 4+ 1+ 2+
2+
2+ 4+H 2+ 1+
0
2+ 0
2+
•
3+ 2-f
0
2+
Rebound
1+ 2+ 4+
3+ 1+ 2+ 3+ 3+ 3+ 3+ 2+ 2+
Downbeat (primary position)
o§ 1+ 3+ 1+ 0
O
0
m m
2+
20)* Right saccades
Patient 1 2 3 4 5
Overshoot Degree^ AmplitudcX 12 8 12 30 12 6 11 13 33 30
Undt•rshoot Degree Amplitude 31 59 25 10 74 17 46 20 47 50
Left saccades Overshoot Degree Amplitude 20 23 14 40 71 9 22 10 37 60
Undershoot Degree Amplitude 52 14 35 22 16 7 54 18 24 35
* Frequency of refutation was about 0-25 Hz. t DegTee = percentage of total number of rightward saccades showing overshoot. j Amplitude = mean overshoot expressed as a percentage of 20°.
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Accuracy of saccades was assessed by measuring eye movements both in response to sudden target jumps away from and back to the primary position and during refixations between two stationary targets. Fig. 2 illustrates the pattern of vertical saccadic dysmetria in one of our patients (No. 5). For downward refixations, the initial saccade overshot the position of the target by as much as 100 per cent and one or more corrective saccades were required to bring the eyes back to the target. The interval between corrective saccades ranged between 50 and 200 ms. We did not observe the form of dysmetria in which the eyes overshoot and then smoothly oscillate about the position of the target for 500-1 000 ms as reported by Higgins and Daroff (1966). Table 3 summarizes the degree, magnitude and type of dysmetria for horizontal refixations between stationary targets 20° apart (±10° about zero). A variety of patterns of dysmetria were observed. One patient (No. 3) made hypometric
EYE M O V E M E N T S IN C E R E B E L L A R A T A X I A
213
saccades to the right and hypermetric saccades to the left. Two patients (Nos. 2 and 5) made a nearly even mixture of hyper- and hypometric saccades in both horizontal directions. Two others (Nos. 1 and 4) made predominantly hypometric saccades. In contrast, a different pattern of dysmetria emerged for saccades in response to 20° step changes in target position (Table 4). Under these conditions, patients usually showed less hypermetria and improved accuracy overall. TABLE 4. SACCADIC DYSMETRIA: 20° HORIZONTAL REFIXATIONS TO STEP CHANGES IN TARGET POSITION (N>16) Right saccades Patient 1 2 3 4 5
Overshoot Degree* Amplitude^ 12 5 10 0 —
o0
— —
Undershoot Degree Amplitude 50 5 37 10 i \ot available 20 18 80 27
Left saccades Overshoot Degree Amplitude 0 — 18 5 9 0
20 —
Undershoot Degree Amplitude 11 80 54 11 27 91
17 26
* Degree = percentage of total number of rightward saccades showing overshoot. t Amplitude = mean overshoot expressed as a percentage of 20°.
TABLE 5. SACCADIC DYSMETRIA: 10° VERTICAL REFIXATIONS TO STEP CHANGES IN TARGET POSITION (N>16) Upward saccades Patient 1 2 3 4 5
Overshoot Degree* Amplitude^ 0 — 0 — 0 — 0 — 0 —
Undershoot Degree Amplitude — 0 13 33 — 0 30 27 58 100
Downward saccades Overshoot Degree Amplitude 9-2 38 100 32 22-5 80 27 17 84 100
Undershoot Degree Amplitude 0 — 0 — 0 — 18 12 0 —
* Degree = percentage of total number of upward saccades showing overshoot, t Amplitude = mean overshoot expressed as a percentage of 10°.
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The degree and amplitude of dysmetria were compared for saccades in response to 5, 10 and 20° step changes in the horizontal target position. No consistent change in the pattern of dysmetria was observed for saccades of different amplitudes. However, the total number of saccades of each size and direction was relatively small (average about 10). For very large refixations (40°) the degree of hypermetria diminished and hypometria became more apparent. The pattern of vertical dysmetria is shown in Table 5. All patients made hypermetric downward saccades and 3 made hypometric upward saccades. For one patient (No. 1) the degree of vertical dysmetria depended upon the position in the orbit from which the saccade began. Ten degree downward saccades beginning from 10° above the horizontal meridian were normometric. Ten degree downward saccades beginning from the horizontal meridian, however, were consistently
214
D. S. ZEE AND OTHERS
Smooth Pursuit Eye Movements During horizontal tracking, all patients showed inadequate smooth pursuit. In all cases, pursuit movements were too slow and the patient needed to make catchup saccades to keep the image of the moving target near the fovea. The degree of pursuit deficit was quantitated by measuring the pursuit system gain (the output/ input ratio or the ratio of pursuit eye velocity/target velocity). If tracking is perfect, eye velocity matches target velocity and the gain is 1 0. Fig. 3 shows the pursuit gain for our patients over the range of velocities tested. In the minimally affected patients (Nos. 1 and 2), the pursuit defect became apparent only when the target was moving at higher velocities. In contrast, the more severely affected patients tracked abnormally at every target velocity tested. Fig. 4 shows the pursuit gain during vertical tracking. In all patients except No. 1, downward tracking was more severely affected. For 3 patients (Nos. 2, 3 and 5) the ability to produce slow phases of nystagmus in response to full-field optokinetic stimulation by being enclosed in a rotating drum was compared with the ability to generate pursuit eye movements while tracking small moving targets. All 3 patients showed a relative preservation of the ability to produce slow phases of optokinetic nystagmus (OKN). Infig.5, maximum optokinetic slow phase velocity is compared to maximum pursuit eye velocity for Patient 3. Both maximum and mean (not plotted) slow phase velocities of OKN were higher than pursuit velocities at every stimulus velocity tested. Patient 3 also had been tested about one year before the results shown in fig. 5 were obtained. At that time a large drum for full-field stimulation was not available and nystagmus
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hypermetric with an average overshoot of 9 per cent. In contrast, the pattern of vertical dysmetria in the other patients did not depend upon initial eye position. During repetitive refixations between two stationary targets at a constant frequency of about 0-25 Hz, both the degree and amplitude of dysmetria remained relatively constant, but when the patient was stressed by asking him to increase the rate of refixations, the amplitude of dysmetria increased (fig. 2). When patients were placed in total darkness and instructed to continue to refixate between the imagined locations of the two previously visible targets, their saccadic dysmetria persisted. All patients except No. 1 showed varying degrees of square wave-jerks. Upon attempted steady fixation, they made to and fro, horizontal saccades with frequencies between 1-5 and 2-8 Hz and amplitudes between 1-2° and 2-5°. Square wave-jerks persisted in complete darkness and both frequency and amplitude were independent of whether the patient was instructed to look straight ahead at an imagined target or to disregard the position of his eyes and perform mental arithmetic. During eye closure the frequency of square wave-jerks diminished. Square wave-jerks also persisted during attempted smooth tracking and during vestibular rotation either in darkness or with fixation targets (fig. 6).
EYE MOVEMENTS IN CEREBELLAR ATAXIA
215
Normal Patient 1 Patient 2 Patient 3 Patient 4 Patient 5
.25--
30
20
Left
10
10
20
30
Target Velocity (Degrees/Second)
Right
1.00-r • Normal o Patient 1 A Patient 2 D Patient 3 • Patient 4 & Patient 5
.75--
.50--
.25--
30 Up
20
10
10
20
Target Velocity (Degrees/Second) FIG. 4. Vertical tracking behaviour (see legend tofig.3).
30 Down
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FIG. 3. Horizontal tracking behaviour. Patients attempted to track a small illuminated dot moving on a dark background. The target moved in a triangular-wave fashion with an excursion of 20° (± 10° about zero). Pursuit velocity was measured as the eye passed through the primary position. Mean gain (eye velocity/target velocity) is plotted against target velocity (N> 5). Normal values based upon observations in our laboratory as well as Baloh e! al. (1976).
216
D. S. ZEE AND OTHERS
CD
CO CD (U O)
O OKN-Right OKN-Left
50
A Pursuit-Right A Pursuit-Left
Q •5
40 —
"53
30 -
#
O
O
CD CO
20 #
Q.
A
CO
x CO
10
A
" 8
A
A A I
10
20
l
i
I
30
40
50
60
Stimulus Velocity (Degrees/Sec) FIG. 5. Comparison of maximum slow phase velocity during full-field optokinetic stimulation to maximum pursuit velocity during attempted tracking of a small moving dot. Optokinetic slow phases are relatively preserved. (Patient 3.)
was induced by projecting the image of moving stripes on a screen in front of the patient. Using vertical stripes moving at 30°/s, slow phase velocity attained a value of about 10°/s within the first second after stimulus onset. Then, slow phase velocity gradually increased over a period of 5-10 s to 30°/s, matching stripe velocity. When the stripes stopped moving, OKN did not cease immediately but decayed in 5-10 s (optokinetic after-nystagmus), even with the lights on. On the other hand, during attempted smooth tracking of a small dot moving at 30°/s, maximum pursuit velocity was only 12°/s. Therefore, at this stage in the evolution of Patient 3's neurological disorder, an even more striking dissociation between optokinetic nystagmus and smooth pursuit tracking was apparent. Patients 2 and 5 showed a similar but less pronounced disparity between optokinetic and smooth pursuit tracking. All 3 patients tested with full-field optokinetic stimulation experienced the normal illusion of self-rotation (circularvection) (Brandt, Dichgans and Biichele, 1974).
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E
217
EYE MOVEMENTS IN CEREBELLAR ATAXIA
Vestibulo-ocular Responses
>Ld
CD
OCULAR MOTOR ABNORMALITIES IN HEREDITARY CEREBELLAR ATAXIA by DAVID S. ZEE, ROBERT D. YEE, DAVID G. COGAN, DAVID A. ROBINSON and W. KING ENGEL {From the Medical Neurology Branch, National Institute of Neurological and Communicative Disorders and Stroke and Clinical Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland, and the Departments of Neurology and Ophthalmology, The Johns Hopkins Hospital, Baltimore, Maryland)
METHODS Saccadic and Smooth Pursuit Eye Movements Eye movements were recorded monocularly from the left eye using an infra-red pupil tracking device (Zee, Friendlich and Robinson, 1974). This system has a linear range and accuracy of 40±0-5°
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A NUMBER of ocular motor abnormalities have been attributed to cerebellar dysfunction (Cogan, 1956; Daroff and Hoyt, 1971; Kornhuber, 1974), but the exact role of the cerebellum in the control of eye movements in human beings remains unclear. Recent studies in monkeys have suggested that the cerebellum specifically functions in (1) maintenance of eccentric positions of gaze; (2) production of smooth pursuit eye movements; (3) modulation of saccadic eye movement amplitude; and (4) visual suppression of caloric-induced nystagmus (Westheimer and Blair, 1974; Aschoff and Cohen, 1971; Takemori and Cohen, 1974). We have had the- opportunity to record and 'analyse the eye movement abnormalities in patients from a kindred with late onset, dominantly inherited, cerebellar ataxia. This has served to define the ocular motor signs of cerebellar dysfunction in human beings, as well as to correlate findings in patients with those in experimental animals. Our patients showed defects comparable to those in monkeys with cerebellar lesions including inability to hold eccentric gaze (with consequent gaze-paretic nystagmus), defective smooth pursuit, saccadic dysmetria and defective visual suppression of vestibular nystagmus. Other findings included downward beating nystagmus, enhanced gain (eye velocity/head velocity) of the vestibulo-ocular reflex during rotation in darkness and rebound nystagmus. Many characteristics of the altered vestibulo-ocular responses and gaze-paretic and rebound nystagmus could be best interpreted by considering the different mechanisms used by the central nervous system to hold positions of gaze.
208
D. S. ZEE AND OTHERS
horizontally and 2O±O-75° vertically with a frequency response of 0-167 Hz. Targets were rear-projected on a screen, 54 cm from the patient's left eye and moved by a mirror galvanometer in the projector's light path. The patient's head was restrained by an acrylic dental bite bar and head rest. Saccadic eye movements were measured either during refixations between stationary visual targets or in response to step changes in target position. From the primary position the target could be moved peripherally in any direction. From an eccentric position, however, the target's next jump was always back to the primary position. Latencies for saccadic eye movements were determined by measuring reaction times to aperiodic, 20°, step changes in target position. Peak eye velocities were measured for 20° horizontal refixations between two stationary targets. Pursuit movements were measured while patients attempted to track a small illuminated dot moving on a dark background. The target moved in a triangular wave fashion with an excursion of 20° (±10° about zero) at various velocities from 2-5 to 55°/s. In several patients, optokinetic nystagmus was induced by full-field stimulation. Patients were placed in an aluminium drum, 4 ft in diameter, painted with alternating black and white stripes, each 1\° in width. The head was steadied by a support. The drum was rotated horizontally at constant velocities ranging from 5 to 90°/s. The patient's instructions were: 'follow the stripes as they pass in front of you.' Eye movements were recorded by DC electrooculography (EOG) with a band width of 100 Hz.
Eccentric Gaze The ability to hold eccentric gaze was measured by EOG. The range of positions tested was ±15-45°. Eye movements from both the infra-red tracking device and electro-oculography were recorded on magnetic tape and transferred to recorder paper by a UV mirror galvanometer with a band width of 2 kHz. The patients in this study took no medication in the week before testing. They were continually urged to stay alert and perform maximally.
CLINICAL FEATURES Family Background and Inheritance Fig. 1 illustrates the family pedigree. All affected members are descendants of a couple who emigrated from Ireland to central Pennsylvania in 1828. The vertical transmission of the disorder from generation to generation and the ratios of unaffected and affected males and females are compatible with autosomal dominant inheritance. Neurological Features Table 1 summarizes the neurological findings in the 12 family members who were examined and found to be affected. Onset of symptoms was between ages 41 and 59, with a mean of about 50. Unsteadiness of gait was invariably the first symptom. In a few individuals, dysarthria was noted soon thereafter.
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Vestibular Eye Movements Vestibulo-ocular responses were assessed during sinusoidal chair rotations typically at a frequency of 0-3 Hz and peak velocity of 20-25°/s. Eye movements were measured by DC electro-oculography (EOG) with a system with a frequency response of 0-300 Hz. Chair position and hence head position was monitored by a potentiometer. Patients were tested for periods of no longer than two minutes at a time and the EOG was calibrated immediately before and after each test. This gave an estimated linear range and accuracy of 40± 10°. To stimulate the vertical canals, the patient's head was positioned with the interorbital axis vertical. Three different testing paradigms were used: rotation in complete darkness with eyes open while performing mental arithmetic; rotation while fixating a stationary target on the wall; and rotation while fixating a target moving with the patient on the chair. Small, red, light emitting diodes were used as fixation targets.
EYE MOVEMENTS IN CEREBELLAR ATAXIA
v
DO
D 00
O
«
•
B
«
»
O
»
11 II ' »
209
»
D
33
II
JO
«
XS
I
1
DO
Thought to bt normal
0
Thought to b« • H i l m J
0 ?
7)
Patient L o g o 81
Neurologic itatui cunllmod by examination Naurotoglc Itmui not knowl
NOTE: ChBdnwi In Generation VI are not shown unfaee parent le affected
FIG. 1. Family pedigree. The rate of progression was slow and patients usually did not become wheelchair-bound until at least age 65. Significant inco-ordination of the upper limbs usually occurred late in the course of the illness. Mental changes, objective muscle weakness or atrophy, sphincter abnormalities and sensory disturbances were absent. In several patients reflexes were somewhat brisk but neither Babinski responses nor increased muscle tone could be detected. Visual symptoms were inconstant and varied. Several patients noted transient episodes of diplopia or vertigo at the onset of their illness. Others reported that while riding in a moving car they had difficulty recognizing faces of individuals walking on the sidewalk. Several individuals also noted occasional vertical oscillopsia when reading. Some patients, including several that were severely affected, had no visual symptoms. Ocular Motor Findings Except for mild limitation of upward gaze in older patients, the range of ocular movements was full. Saccades appeared to be of normal velocity but dysmetria, especially overshoot of downward refixations, • was uniformly present. All patients showed defects in smooth pursuit. They had to substitute catch-up saccades in order to keep the image of the moving target near the fovea. Abnormalities of optokinetic responses, elicited by a hand drum, appeared to parallel the smooth pursuit defects. In the primary position of gaze, most patients showed repetitive, horizontal, to and fro, small amplitude saccades or square wave-jerks. In addition many patients showed a mild degree of downward beating nystagmus which became substantially accentuated on far lateral gaze. Rebound nystagmus and gazeparetic nystagmus were evident to a variable degree in all patients. During doll's head rotation in the
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KEY TO PEDIGREE O
of ent* 1 2 3 4 5 6 7 8 9 10 11 12
Sex
F M M
F M M F M F
F F
F
Age 61 54 64 61 74 52 66 71 70 63 71 57
symptoms (years) 5 5 6 12 20
Gait Dysmetria ataxia Dysarthria UE LE 0 2+ 1 + 2+
1+ 3+ 3+
2+ 3+ 1+
5
1+
1+
7
4+ 4+
4+
4+
19 23 20 30
4+ 4+
7
1+
3+
4+
1+
2+
1+ 3+ 3+
2+ 3 + 4+ 1+ 1+ 3 + 4+ 2+ 3+ 2+ 3+
4+ 3+ 3+
4+
4+
2+
2+
0
0
3+ 1+
Pursuit^ OKN\ (horizontal) Present 1+ Present 2+ Absent 3+ 3-f, Absent Absent 4+
2+ 3+
4+ 4+ 4+ 4+ 2+
Present Absent Absent Absent Absent Absent Present
Saccadic dysmetria Vert. Horiz. 0 1+
1+
0
1+
2+
1+ 1+
4_i_**
i+ 0
1+
0
2+ 2+ 1+ 3+ 1+ 2+ 4+'* 2+ 2+ 2+ 1+
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TABLE 1. SUMMARY OF CLINICAL FEATURES
Nystagmus Square wavejerks 0
Gazeparetic
1+ 1+ l+ll 3+
1+
3+ 2+ 4+ 1+ 2+
2+
2+ 4+H 2+ 1+
0
2+ 0
2+
•
3+ 2-f
0
2+
Rebound
1+ 2+ 4+
3+ 1+ 2+ 3+ 3+ 3+ 3+ 2+ 2+
Downbeat (primary position)
o§ 1+ 3+ 1+ 0
O
0
m m
2+
20)* Right saccades
Patient 1 2 3 4 5
Overshoot Degree^ AmplitudcX 12 8 12 30 12 6 11 13 33 30
Undt•rshoot Degree Amplitude 31 59 25 10 74 17 46 20 47 50
Left saccades Overshoot Degree Amplitude 20 23 14 40 71 9 22 10 37 60
Undershoot Degree Amplitude 52 14 35 22 16 7 54 18 24 35
* Frequency of refutation was about 0-25 Hz. t DegTee = percentage of total number of rightward saccades showing overshoot. j Amplitude = mean overshoot expressed as a percentage of 20°.
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Accuracy of saccades was assessed by measuring eye movements both in response to sudden target jumps away from and back to the primary position and during refixations between two stationary targets. Fig. 2 illustrates the pattern of vertical saccadic dysmetria in one of our patients (No. 5). For downward refixations, the initial saccade overshot the position of the target by as much as 100 per cent and one or more corrective saccades were required to bring the eyes back to the target. The interval between corrective saccades ranged between 50 and 200 ms. We did not observe the form of dysmetria in which the eyes overshoot and then smoothly oscillate about the position of the target for 500-1 000 ms as reported by Higgins and Daroff (1966). Table 3 summarizes the degree, magnitude and type of dysmetria for horizontal refixations between stationary targets 20° apart (±10° about zero). A variety of patterns of dysmetria were observed. One patient (No. 3) made hypometric
EYE M O V E M E N T S IN C E R E B E L L A R A T A X I A
213
saccades to the right and hypermetric saccades to the left. Two patients (Nos. 2 and 5) made a nearly even mixture of hyper- and hypometric saccades in both horizontal directions. Two others (Nos. 1 and 4) made predominantly hypometric saccades. In contrast, a different pattern of dysmetria emerged for saccades in response to 20° step changes in target position (Table 4). Under these conditions, patients usually showed less hypermetria and improved accuracy overall. TABLE 4. SACCADIC DYSMETRIA: 20° HORIZONTAL REFIXATIONS TO STEP CHANGES IN TARGET POSITION (N>16) Right saccades Patient 1 2 3 4 5
Overshoot Degree* Amplitude^ 12 5 10 0 —
o0
— —
Undershoot Degree Amplitude 50 5 37 10 i \ot available 20 18 80 27
Left saccades Overshoot Degree Amplitude 0 — 18 5 9 0
20 —
Undershoot Degree Amplitude 11 80 54 11 27 91
17 26
* Degree = percentage of total number of rightward saccades showing overshoot. t Amplitude = mean overshoot expressed as a percentage of 20°.
TABLE 5. SACCADIC DYSMETRIA: 10° VERTICAL REFIXATIONS TO STEP CHANGES IN TARGET POSITION (N>16) Upward saccades Patient 1 2 3 4 5
Overshoot Degree* Amplitude^ 0 — 0 — 0 — 0 — 0 —
Undershoot Degree Amplitude — 0 13 33 — 0 30 27 58 100
Downward saccades Overshoot Degree Amplitude 9-2 38 100 32 22-5 80 27 17 84 100
Undershoot Degree Amplitude 0 — 0 — 0 — 18 12 0 —
* Degree = percentage of total number of upward saccades showing overshoot, t Amplitude = mean overshoot expressed as a percentage of 10°.
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The degree and amplitude of dysmetria were compared for saccades in response to 5, 10 and 20° step changes in the horizontal target position. No consistent change in the pattern of dysmetria was observed for saccades of different amplitudes. However, the total number of saccades of each size and direction was relatively small (average about 10). For very large refixations (40°) the degree of hypermetria diminished and hypometria became more apparent. The pattern of vertical dysmetria is shown in Table 5. All patients made hypermetric downward saccades and 3 made hypometric upward saccades. For one patient (No. 1) the degree of vertical dysmetria depended upon the position in the orbit from which the saccade began. Ten degree downward saccades beginning from 10° above the horizontal meridian were normometric. Ten degree downward saccades beginning from the horizontal meridian, however, were consistently
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Smooth Pursuit Eye Movements During horizontal tracking, all patients showed inadequate smooth pursuit. In all cases, pursuit movements were too slow and the patient needed to make catchup saccades to keep the image of the moving target near the fovea. The degree of pursuit deficit was quantitated by measuring the pursuit system gain (the output/ input ratio or the ratio of pursuit eye velocity/target velocity). If tracking is perfect, eye velocity matches target velocity and the gain is 1 0. Fig. 3 shows the pursuit gain for our patients over the range of velocities tested. In the minimally affected patients (Nos. 1 and 2), the pursuit defect became apparent only when the target was moving at higher velocities. In contrast, the more severely affected patients tracked abnormally at every target velocity tested. Fig. 4 shows the pursuit gain during vertical tracking. In all patients except No. 1, downward tracking was more severely affected. For 3 patients (Nos. 2, 3 and 5) the ability to produce slow phases of nystagmus in response to full-field optokinetic stimulation by being enclosed in a rotating drum was compared with the ability to generate pursuit eye movements while tracking small moving targets. All 3 patients showed a relative preservation of the ability to produce slow phases of optokinetic nystagmus (OKN). Infig.5, maximum optokinetic slow phase velocity is compared to maximum pursuit eye velocity for Patient 3. Both maximum and mean (not plotted) slow phase velocities of OKN were higher than pursuit velocities at every stimulus velocity tested. Patient 3 also had been tested about one year before the results shown in fig. 5 were obtained. At that time a large drum for full-field stimulation was not available and nystagmus
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hypermetric with an average overshoot of 9 per cent. In contrast, the pattern of vertical dysmetria in the other patients did not depend upon initial eye position. During repetitive refixations between two stationary targets at a constant frequency of about 0-25 Hz, both the degree and amplitude of dysmetria remained relatively constant, but when the patient was stressed by asking him to increase the rate of refixations, the amplitude of dysmetria increased (fig. 2). When patients were placed in total darkness and instructed to continue to refixate between the imagined locations of the two previously visible targets, their saccadic dysmetria persisted. All patients except No. 1 showed varying degrees of square wave-jerks. Upon attempted steady fixation, they made to and fro, horizontal saccades with frequencies between 1-5 and 2-8 Hz and amplitudes between 1-2° and 2-5°. Square wave-jerks persisted in complete darkness and both frequency and amplitude were independent of whether the patient was instructed to look straight ahead at an imagined target or to disregard the position of his eyes and perform mental arithmetic. During eye closure the frequency of square wave-jerks diminished. Square wave-jerks also persisted during attempted smooth tracking and during vestibular rotation either in darkness or with fixation targets (fig. 6).
EYE MOVEMENTS IN CEREBELLAR ATAXIA
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Normal Patient 1 Patient 2 Patient 3 Patient 4 Patient 5
.25--
30
20
Left
10
10
20
30
Target Velocity (Degrees/Second)
Right
1.00-r • Normal o Patient 1 A Patient 2 D Patient 3 • Patient 4 & Patient 5
.75--
.50--
.25--
30 Up
20
10
10
20
Target Velocity (Degrees/Second) FIG. 4. Vertical tracking behaviour (see legend tofig.3).
30 Down
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FIG. 3. Horizontal tracking behaviour. Patients attempted to track a small illuminated dot moving on a dark background. The target moved in a triangular-wave fashion with an excursion of 20° (± 10° about zero). Pursuit velocity was measured as the eye passed through the primary position. Mean gain (eye velocity/target velocity) is plotted against target velocity (N> 5). Normal values based upon observations in our laboratory as well as Baloh e! al. (1976).
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CD
CO CD (U O)
O OKN-Right OKN-Left
50
A Pursuit-Right A Pursuit-Left
Q •5
40 —
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O
O
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A
CO
x CO
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A
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A
A A I
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i
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30
40
50
60
Stimulus Velocity (Degrees/Sec) FIG. 5. Comparison of maximum slow phase velocity during full-field optokinetic stimulation to maximum pursuit velocity during attempted tracking of a small moving dot. Optokinetic slow phases are relatively preserved. (Patient 3.)
was induced by projecting the image of moving stripes on a screen in front of the patient. Using vertical stripes moving at 30°/s, slow phase velocity attained a value of about 10°/s within the first second after stimulus onset. Then, slow phase velocity gradually increased over a period of 5-10 s to 30°/s, matching stripe velocity. When the stripes stopped moving, OKN did not cease immediately but decayed in 5-10 s (optokinetic after-nystagmus), even with the lights on. On the other hand, during attempted smooth tracking of a small dot moving at 30°/s, maximum pursuit velocity was only 12°/s. Therefore, at this stage in the evolution of Patient 3's neurological disorder, an even more striking dissociation between optokinetic nystagmus and smooth pursuit tracking was apparent. Patients 2 and 5 showed a similar but less pronounced disparity between optokinetic and smooth pursuit tracking. All 3 patients tested with full-field optokinetic stimulation experienced the normal illusion of self-rotation (circularvection) (Brandt, Dichgans and Biichele, 1974).
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E
217
EYE MOVEMENTS IN CEREBELLAR ATAXIA
Vestibulo-ocular Responses
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