Table e-1. Inter-rater agreement of the ocular motor assessment classification scheme.

Analysis A c
N=117 / Analysis B d
N=306
3-Category Scheme a
Agreement / 53.0% / 59.8%
Kappa (95% CI) / 0.29 (0.16-0.43) / 0.40 (0.33-0.48)
Nystagmus Only Scheme b
Agreement / 71.8% / 77.9%
Kappa (95%) / 0.24 (0.05-0.43) / 0.38 (0.26-0.49)

aThe three category classification scheme was as follows: 0 = no nystagmus; 1 = direction-fixed horizontal nystagmus plus head impulse test (HIT) abnormal to the side opposite the fast phase of horizontal nystagmus; 2 = central pattern of nystagmus, or HIT normal to the side opposite the fast phase of direction-fixed horizontal nystagmus.

b The Nystagmus only scheme was as follows: 0 = no central nystagmus; 1 = central nystagmus.

c Analysis A was performing using two in-person examinations with median time between exams of 56.5 minutes (IQR 34.5-112).

d Analysis B used a second exam that was scored by review of the video-taped first exam. Note that 14 of the 320 subjects not included because subjects declined video-taped exam or video-tape was not interpretable.

Table e-2. Inter-rater agreement 3 x 3 matrix for three-category classification scheme. Presented are results from Analysis A (two in-person examinations, N=117)

Second Exam
0 (No Nystagmus) / 1 (HINTS Peripheral) / 2 (HINTS Central) / Total
First Exam / 0 (No Nystagmus) / 16 / 5 / 9 / 30
1 (HINTS Peripheral) / 8 / 21 / 16 / 45
2 (HINTS Central) / 9 / 8 / 25 / 42
Total / 33 / 34 / 50 / 117

Table e-3. Inter-rater agreement 3 x 3 matrix for three-category classification scheme. Presented are results from Analysis B (second exam that was scored by review of the video-taped first exam, N = 306). Note that 14 of the 320 subjects were not included because subjects declined video-taped exam or video-tape was not interpretable.

Second Exam
0 (No Nystagmus) / 1 (HINTS Peripheral) / 2 (HINTS Central) / Total
First Exam / 0 (No Nystagmus) / 75 / 1 / 6 / 82
1 (HINTS Peripheral) / 15 / 46 / 29 / 90
2 (HINTS Central) / 62 / 10 / 63 / 135
Total / 152 / 57 / 98 / 306

Table e-4.MRI details for the 29 patients with acute infarction or intracerebral hemorrhage on MRI.

Pt / Lesion location(s) / Stroke volume (cm3) b / T / Stroke Type / Time from Onset to MRI (hours) / T / Stroke Type / Time from Onset to MRI (hours)
1 / Cerebellum (L PICA), temporal lobe / 22.3 / 1.5 / Infarction / 10.7
2 / Medulla (R PICA) / 0.04 / 3.0 / None / 7.7 / 3.0 / Infarction / 266.9
3 / Cerebellum (B PICA, R SCA) / 0.42 / 3.0 / Infarction / 255.9
4 / Thalamus / 0.26 / 1.5 / Infarction / 21.8
5 / Cerebellum (L PICA, R SCA), plus other / 0.08 / 3.0 / Infarction / 76.3
6 / Pons (L AICA) / 0.03 / 1.5 / Infarction / 18.2
7 / Caudate c / 0.01 / 1.5 / Infarction / 6.3
8 / Occipital lobe c / 0.05 / 3.0 / Infarction / 336
9 / Cerebellum (R PICA), plus other a / 1.31 / 1.5 / ICH / 47.4
10 / Cerebellum (R PICA), plus other a / 47.8 / 1.5 / ICH / 92.3
11 / Pons (BA) / 0.12 / 3.0 / Infarction / 31.7
12 / Medulla (L PICA) / 0.04 / 1.5 / Infarction / 29.4
13 / Pons (BA) / 0.26 / 3.0 / Infarction / 16.6
14 / Cerebellum (L SCA), plus other / 0.09 / 1.5 / Infarction / 22.4 / 1.5 / Infarction / 172.5
15 / Cerebellum (L PICA) / 4.77 / 1.5 / Infarction / 5.0
16 / Medulla (L PICA) / 0.05 / 1.5 / Infarction / 33.7
17 / Frontal lobe c / 0.03 / 3.0 / Infarction / 111.0
18 / Cerebellum (R PICA) / 33.20 / 1.5 / Infarction / 34.2
19 / Cerebellum (L PICA) / 2.18 / 1.5 / Infarction / 55.1
20 / Cerebellum (R PICA) / 0.08 / 3.0 / Infarction / 28.9
21 / Thalamus / 0.17 / 1.5 / Infarction / 49.1
22 / Cerebellum (L PICA) / 32.26 / 1.5 / Infarction / 35.8
23 / Cerebellum (L AICA) / 0.07 / 1.5 / Infarction / 110.9
24 / Cerebellum (L PICA), plus other / 13.99 / 1.5 / Infarction / 25.9
25 / Cerebellum (B PICA, SCA) / 17.14 / 1.5 / Infarction / 5.0
26 / Cerebellum (R PICA, R SCA)a / 8.39 / 1.5 / ICH / 181.0
27 / Cerebellum (R PICA, R SCA) / 0.32 / 1.5 / Infarction / 5.3
28 / Medulla (R PICA) / 0.09 / 1.5 / Infarction / 25.7
29 / Medulla (L PICA) / 0.04 / 1.5 / Infarction / 11.1

T = Teslas; R = right; L = left; PICA = posterior inferior cerebellar artery; AICA = anterior inferior cerebellar artery; SCA = superior cerebellar artery; BA = basilar artery.

a Intracerebral hemorrhage cases. Etiology of intracerebral hemorrhage was melanoma metastasis in 2 subjects and cavernoma in 1 subject.

b If there was more than one lesion, the volume of the largest lesion is reported. The median volume of infarction or ICH was 0.17 cm3 (IQR: 0.05, 4.78; range: 0.01 to 47.8).

c Suspect infarction was incidental finding.

Table e-5.Results of separate multivariable logistic regression sensitivity analyses with dependent variable of acute infarction or intra-cerebral hemorrhage on MRI.

Sensitivity Analysis 1. Increased threshold for abnormal HIT. d
(OR, 95% CI)
(n=272) / Sensitivity Analysis 2.
Three patients with possible incidental MRI infarction reclassified to non-stroke cases. e
(OR, 95% CI)
(n=272) / Sensitivity Analysis 3. HINTS Positive category expanded to include nystagmus patients with bilaterally abnormal HIT.
(OR, 95% CI)
(n=272) / Sensitivity Analysis 4. Imputation of stroke status in cases not receiving MRI. f
(OR, 95% CI)
(n=320) / Sensitivity Analysis 5. Analysis limited to cases with ocular motor exam performed by neuro-otologist.
(OR, 95% CI)
(n=259)
Primary Variables
ABCD2 (continuous) a / 1.78 (1.23-2.56)** / 1.49 (1.02-2.17)* / 1.73 (1.20-2.50)** / 1.72 (1.19-2.50)** / 1.69 (1.17-2.45)**
Prior Stroke / 0.39 (0.04-3.99) / 0.84 (0.09-8.31) / 0.48 (0.05-4.84) / 0.48 (0.05-4.79) / 0.48 (0.05-4.81)
Other CNS Features b / 2.57 (1.07-6.13)* / 3.30 (1.34-8.12)** / 2.52 (1.05-6.03)* / 2.54 (1.06-6.05)* / 2.53 (1.05-6.06)*
Ocular motor assessment
3-category scheme c
No Nystagmus or Skew / Reference / Reference / Reference / Reference / Reference
HINTS Negative / 1.14 (0.25-5.30) / 0.55 (0.09-3.25) / 1.07 (0.26-4.40) / 0.98 (0.24-4.00) / 0.93 (0.23-3.85)
HINTS Positive / 2.48 (0.85-7.27) / 3.45 (1.08-10.98)* / 2.69 (0.92-7.90) / 2.88 (0.99-8.41) / 2.73 (0.92-8.07)
c-statistic (95% CI) / 0.76 (0.68-0.84) / 0.75 (0.67-0.83) / 0.77 (0.69-0.84) / -- / 0.76 (068-0.84)

OR = odds ratio; CNS = central nervous system; HIT = head impulse test.

a ABCD2 (modeled continuously) assigns points based on the following: age 60 years or older = 1; systolic blood pressure ≥ 140 or diastolic blood pressure ≥ 90 = 1; clinical features (symptoms or exam findings of unilateral weakness =2, speech disturbance without weakness =1); duration of symptoms (<10 minutes = 0, 10-59 minutes = 1, ≥ 60 minutes =2) (Note, duration of symptoms was > 60 minutes for all subjects); and diabetes =1.

b Other CNS features includes mild findings of any of the following: visual field deficit, dysmetria, or sensory symptoms or deficits. These are CNS features not included in the ABCD2 score or HINTS assessment.

c 3 category scheme is as follows: No nystagmus or Skew = No nystagmus on exam and no skew deviation; HINTS Negative = direction-fixed horizontal nystagmus, plus abnormal HIT to side opposite fast phase of horizontal nystagmus, plus no skew deviation; HINTS Positive = central pattern of nystagmus, or direction-fixed horizontal nystagmus with normal HIT to side opposite fast phase of horizontal nystagmus, or presence of skew deviation.

dThe threshold for considering the head impulse test as abnormal in the ocular motor assessment was increased from a small to a medium amplitude corrective saccade.

eLesion of the MRI infarction cases re-classified in this sensitivity analysis were as follows (location [volume]): caudate (0.01 cm3), occipital lobe (0.05 cm3), or frontal lobe (0.03 cm3).

f MRI status (i.e., presence or absence of infarction/ICH on MRI) for the 48 subjects with missing MRI data was generated using 100 imputations (Stata command “mi impute”). Models were then fit using imputed data, and output was adjusted for the variability between imputations by applying combination rules to the 100 completed-data estimates. (Stata Multiple Imputation Reference Manual Release 13. StataCorp. 2013. College Station, TX: StataCorp LP)

*p<0.05, **p<0.01, *** p<0.001

Table e-6.Clinical details for the 29 patients with acute infarction or intracerebral hemorrhage on MRI and 4 patients with other acute central nervous system findings. Shaded cells indicate high-risk categories for the model variables.

Pt / Age (years) / Prior Similar Dizziness / A / B / C / D1 / D2 / Total / Other CNS features / HI / N / TS / OM category
R / L / R / L / V/T / R / L
Patients With Acute Infarction or intracerebral Hemorrhage on MRI
1 / 89 / 0 / 1 / 1 / 0 / 0 / 2 / 4 / 1 / 0 / 0 / 0 / 1 / 1 / 0 / 0 / 2
2 / 84 / 1 / 1 / 1 / 0 / 0 / 2 / 4 / 0 / 1 / 1 / 0 / 0 / 0 / 0 / 0 / 0
3 / 82 / 1 / 1 / 1 / 0 / 0 / 2 / 4 / 0 / 0 / 1 / 0 / 1 / 0 / 0 / 0 / 2
4 / 80 / 0 / 1 / 1 / 2 / 0 / 2 / 6 / 1 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0
5 / 79 / 0 / 1 / 1 / 0 / 1 / 2 / 5 / 0 / 0 / 0 / 1 / 1 / 0 / 0 / 0 / 2
6 / 75 / 0 / 1 / 1 / 0 / 0 / 2 / 4 / 0 / 1 / 0 / 1 / 1 / 1 / 0 / 1 / 2
7a / 72 / 1 / 1 / 1 / 1 / 1 / 2 / 6 / 0 / 1 / 0 / 0 / 1 / 0 / 0 / 0 / 1
8a / 71 / 1 / 1 / 1 / 0 / 1 / 2 / 5 / 0 / 1 / 1 / 0 / 0 / 0 / 0 / 0 / 0
9 / 67 / 1 / 1 / 1 / 0 / 0 / 2 / 4 / 0 / 1 / 0 / 1 / 1 / 0 / 0 / 0 / 2
10 / 67 / 0 / 1 / 1 / 1 / 1 / 2 / 6 / 1 / 0 / 1 / 1 / 1 / 1 / 0 / 0 / 2
11 / 65 / 0 / 1 / 1 / 0 / 1 / 2 / 5 / 1 / 0 / 1 / 1 / 1 / 0 / 0 / 0 / 2
12 / 62 / 0 / 1 / 0 / 0 / 1 / 2 / 4 / 1 / 0 / 1 / 1 / 0 / 0 / 1 / 0 / 2
13 / 61 / 0 / 1 / 0 / 0 / 1 / 2 / 4 / 0 / 0 / 0 / 1 / 1 / 0 / 0 / 0 / 2
14 / 60 / 0 / 1 / 1 / 1 / 0 / 2 / 5 / 0 / 0 / 0 / 1 / 1 / 0 / 1 / 0 / 2
15 / 60 / 0 / 1 / 1 / 2 / 1 / 2 / 7 / 1 / 0 / 0 / 1 / 1 / 1 / 0 / 0 / 2
16 / 59 / 0 / 0 / 1 / 0 / 1 / 2 / 4 / 0 / 0 / 0 / 1 / 1 / 1 / 0 / 0 / 2
17a / 57 / 1 / 0 / 1 / 0 / 1 / 2 / 4 / 0 / 1 / 0 / 0 / 1 / 0 / 0 / 0 / 1
18 / 56 / 0 / 0 / 1 / 0 / 0 / 2 / 3 / 0 / 0 / 1 / 1 / 1 / 1 / 0 / 0 / 2
19 / 55 / 1 / 0 / 0 / 0 / 0 / 2 / 2 / 1 / 0 / 1 / 0 / 0 / 0 / 0 / 0 / 0
20 / 54 / 1 / 0 / 1 / 0 / 1 / 2 / 4 / 0 / 0 / 0 / 1 / 0 / 0 / 0 / 0 / 2
21 / 53 / 0 / 0 / 0 / 2 / 0 / 2 / 4 / 1 / 0 / 0 / 1 / 1 / 0 / 0 / 0 / 2
22 / 50 / 0 / 0 / 1 / 0 / 1 / 2 / 4 / 0 / 0 / 1 / 1 / 1 / 0 / 0 / 0 / 2
23 / 46 / 0 / 0 / 1 / 1 / 1 / 2 / 5 / 0 / 1 / 0 / 0 / 0 / 0 / 0 / 0 / 0
24 / 45 / 0 / 0 / 1 / 0 / 0 / 2 / 3 / 0 / 0 / 0 / 1 / 1 / 0 / 0 / 0 / 2
25 / 43 / 0 / 0 / 0 / 0 / 0 / 2 / 2 / 1 / 1 / 0 / 1 / 1 / 0 / 0 / 0 / 2
26 / 35 / 1 / 0 / 0 / 0 / 0 / 2 / 2 / 0 / 0 / 0 / 1 / 1 / 0 / 0 / 0 / 2
27 / 35 / 0 / 0 / 1 / 0 / 0 / 2 / 3 / 1 / 0 / 1 / 1 / 0 / 0 / 0 / 0 / 1
28 / 31 / 0 / 0 / 1 / 0 / 0 / 2 / 3 / 1 / 1 / 0 / 0 / 1 / 0 / 0 / 0 / 1
29 / 18 / 0 / 0 / 0 / 0 / 0 / 2 / 2 / 1 / 0 / 0 / 1 / 0 / 1 / 0 / 0 / 2
Other Patients With Non-Stroke Acute Central Nervous System MRI Findingsb
55 / 0 / 0 / 0 / 0 / 0 / 2 / 2 / 0 / 0 / 0 / 0 / 1 / 0 / 0 / 0 / 2
44 / 0 / 0 / 1 / 2 / 0 / 2 / 5 / 1 / 1 / 0 / 1 / 1 / 1 / 0 / 0 / 2
32 / 0 / 0 / 0 / 0 / 0 / 2 / 2 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0
19 / 0 / 0 / 0 / 0 / 0 / 2 / 2 / 1 / 0 / 0 / 1 / 1 / 1 / 0 / 0 / 2

A = Age (≥60 years = 1); B = Blood pressure (systolic ≥ 140 or diastolic ≥ 90 = 1); C = Clinical features (symptoms or exam findings of unilateral weakness = 2, speech disturbance without weakness = 1); D1 = Diabetes (present = 1); D2 = duration of symptoms (<10 minutes = 0, 10-59 minutes = 1, ≥ 60 minutes = 2); HI = Head impulse test (abnormal = 1); N = nystagmus (abnormal = 1); TS = Test of skew (abnormal = 1) ; R = right side; L = left side; V/T = dominant vector vertical or torsional; CNS = central nervous system; OM = ocular motor.

a Suspect infarction was incidental finding.

b Non-stroke acute central nervous system MRI findings were as follows (in order of patient age): presumed inflammatory brainstem lesion (non-enhancing), enhancing demyelinating plaque, cerebellar tumor, and cerebellitis.