Background
Methods
Step one
Step two
Step three
Statistical analysis
Results
First (“testing”) cohort
Second (“validation”) cohort
Niemann-Pick disease Type C (NP-C) | Inflammatory Encephalitis | Tumor | Infarction/ hemorrhage | Multiple sclerosis | Parkinsonian syndromes | Progressive supranuclear palsy (PSP) | |
Sensitivity: | 10/10 | 5/5 | 3/4 | 11/11 | 8/10 | 8/10 | 8/10 |
100% | 100% | 75.0% | 100% | 80.0% | 80.0% | 80.0% | |
95% CI | 1.000–1.000 | 1.000–1.000 | 0.326–1.000 | 1.000–1.000 | 0.552–1.000 | 0.552–1.000 | 0.552–1.000 |
Specificity: | 71/94 | 65/99 | 82/100 | 82/93 | 63/94 | 89/94 | 83/94 |
75.5% | 65.7% | 82.0% | 88.2% | 67.0% | 94.7% | 88.3% | |
95% CI | 0.668–0.842 | 0.563–0.750 | 0.745–0.895 | 0.816–0.947 | 0.575–0.765 | 0.901–0.992 | 0.818–0.948 |
Wernicke’s encephalo-pathy | Ataxia teleangiectasia | Ataxia with oculomotor apraxia 1/2 | Gaucher’s disease Type 3 (GD3) | Huntington’s chorea (HTT) | Cerebellar syndromes | Tay-Sachs disease | |
Sensitivity: | 5/5 | 3/5 | 4/4 | 8/10 | 4/5 | 10/10 | 5/5 |
100% | 60.0% | 100% | 80.0% | 80.0% | 100% | 100% | |
95% CI | 1.000–1.000 | 0.171–1.000 | 1.000–1.000 | 0.552–1.000 | 0.449–1.000 | 1.000–1.000 | 1.000–1.000 |
Specificity: | 89/99 | 86/99 | 78/100 | 86/94 | 94/99 | 79/94 | 78/99 |
89.9% | 86.9% | 78.0% | 91.5% | 94.5% | 84.0% | 78.8% | |
95% CI | 0.840–0.958 | 0.802–0.935 | 0.699–0.861 | 0.858–0.971 | 0.906–0.993 | 0.766–0.914 | 0.707–0.868 |
Midbrain | Pons | Medulla oblongata | Flocculus/ Paraflocculus | Vermis/ Fastigial Nucleus | Nodulus/ Uvula | Basal Ganglia | Fronto- parietal Cortex | |
---|---|---|---|---|---|---|---|---|
Sensitivity: | 30/39 | 28/34 | 4/4 | 34/54 | 14/54 | 0/54 | 22/28 | 5/11 |
76.9% | 82.4% | 100% | 63.0% | 25.9% | 0.0% | 78.6% | 45.5% | |
95% CI | 0.637–0.901 | 0.695–0.952 | 1.000–1.000 | 0.501–0.758 | 0.142–0.376 | 0.000–0.000 | 0.634–0.938 | 0.160–0.749 |
Specificity: | 30/58 | 34/63 | 78/93 | 25/43 | 34/43 | 42/43 | 57/69 | 85/86 |
51.7% | 54.0% | 83.9% | 58.1% | 79.1% | 97.7% | 82.6% | 98.8% | |
95% CI | 0.389–0.646 | 0.417–0.663 | 0.764–0.913 | 0.434–0.729 | 0.669–0.912 | 0.932–1.000 | 0.737–0.916 | 0.966–1.000 |
Type of examination | Question |
---|---|
Inspection | |
Head/body posture | Tilt or turn of head/body |
Position of eyelids | Ptosis |
Eye position/motility | |
Position of eyes during straight-ahead gaze | Misalignment in primary position, spontaneous or fixation nystagmus |
Horizontal or vertical misalignment | |
Cover/Uncover test | |
Examination of eyes in eight positions (binocular and monocular) | Determination of range of motility, gaze-evoked nystagmus (GEN), end-point nystagmus, sustained, unsustained |
Gaze-holding function | |
10–40° in the horizontal | GEN: horizontal, also important for the diagnosis of downbeat nystagmus |
10–20° in the vertical | vertical |
Back to 0° after 30 s | rebound nystagmus |
Slow smooth pursuit movements | |
Horizontal and vertical | Smooth or saccadic |
Saccades | |
Horizontal and vertical when looking around or at targets; important to note: upper eye must be lifted when examining vertical saccades | Latency, velocity, accuracy, conjugacy |
Optokinetic nystagmus (OKN) | |
Horizontal and vertical with OKN drum or tape | Inducible, direction, phase (reversal or monocularly diagonal) |
Peripheral vestibular function | |
Head-impulse test (HIT) for the examination of the VOR (Halmagyi–Curthoys test): rapid turning of the head and fixation of a stationary target; nowadays better to be done by the video-HIT | Unilateral or bilateral peripheral vestibular deficit |
Fixation suppression of the VOR | |
Turning the head and fixation of a target moving at same speed | Impairment of fixation suppression of the VOR |
Examination with Frenzel’s or the M-glasses [27] | |
Straight-ahead gaze, to the right, to the left, downward and upward | Peripheral vestibular spontaneous nystagmus versus central fixation nystagmus |
Head-shaking test | Head-shaking nystagmus |
Discussion
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First, this algorithm can be a helpful tool for diagnosing, in particular, rare diseases associated with central ocular motor disorders. For example, in the validation cohort we reached a sensitivity of 100% for NPC (10/10) and Wernicke’s encephalopathy (5/5). It is assumed that both of them are vastly underdiagnosed [11, 19]. Since these diseases are treatable or, in the case of Wernicke’s encephalopathy, even curable, an early diagnosis has a huge impact on the outcome of these patients.
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Second, the results for the brain zones were generally worse but can still give an indication of where to look for pathologies in imaging. In the validation cohort, the sensitivity for involvement of the medulla oblongata was 100% (4/4) and for the pons 82.4% (28/34).
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Third, the algorithm can be applied in less than 5 min.