Original Contribution
Section Editors: Clare Fraser, MD
The Clinical and Imaging Profile of Skew Deviation: A
Study of 157 Cases
Eyal Walter, MD, Jonathan D. Trobe, MD
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Background: Skew deviation, a vertical misalignment of the
eyes caused by a lesion in the vestibulo-ocular pathway, is
a common manifestation of brainstem dysfunction, yet
comprehensive information about its clinical profile is
lacking. The aim of this study was to document presenting
symptoms, causes, ocular alignment features, accompa-
nying neurologic signs, pertinent brain imaging abnormali-
ties, and measures used to relieve diplopia.
Methods: We searched the electronic medical records text
from 2000 to 2018 for “skew” or “skew deviation” at a ter-
tiary care academic center, including only patients diagnosed
under supervision of faculty neuro-ophthalmologists. After
excluding patients with features suggesting an imitator of
skew deviation, we collected data useful in answering the
selected clinical issues.
Results: In a cohort of 157 patients, vertical misalignment
ranged between 1 and 30 prism diopters (PD) (median 5 PD)
and was comitant in 100 (64%) patients. Diplopia was
reported by 87% and blurred vision by 11% of patients.
Blurred vision was more common when vertical misalign-
ment was less than 3 PD. At least one accompanying
neurologic sign was present in 133 (85%) patients, most
often nystagmus, followed by gaze paresis, ataxia, saccadic
pursuit, and internuclear ophthalmoplegia. Stroke affecting
the thalamus, brainstem, or cerebellum accounted for 82
(52%) of cases. Stroke was usually ischemic, mostly
unprovoked, but also occurring after intracranial or extra-
cranial surgical procedures. Brainstem tumor and operative
injury caused most of the remaining cases. A subgroup of
17 (11%) patients had skew deviation as the only new
clinical sign and had no pertinent brain imaging abnormal-
ities. Resolution of skew deviation, documented in 58 (42%)
of 137 patients who had at least one follow-up visit, usually
occurred within 3 months, but sometimes not until after 12
months. Of 110 patients who still had diplopia on follow-up
examinations, the diplopia was successfully relieved with
prism spectacles in 68 (62%). The cause of the skew
Department of Ophthalmology and Visual Sciences (EW, JDT),
Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan;
and Departments of Neurology (JDT) and Neurosurgery (JDT),
University of Michigan, Ann Arbor, Michigan.
The authors report no conflicts of interest.
Address correspondence to Jonathan D. Trobe, MD, University of
Michigan, Kellogg Eye Center, Department of Ophthalmology and
Visual Sciences, 1000 Wall Street, Ann Arbor, MI 48105; E-mail:
Jdtrobe@umich.edu
Walter and Trobe: J Neuro-Ophthalmol 2021; 41: 69-76
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Susan Mollan, MD
deviation, amount of vertical misalignment, and degree of
incomitance did not predict the success in relieving diplo-
pia. Accompanying neurologic signs, including ataxia,
endured in 44% of patients and were often more debilitating
than the diplopia of skew deviation.
Conclusions: The amplitude of misalignment in skew
deviation varies widely but is generally 5 PD or less. When
misalignment is 3 PD or less, patients report blurred vision
rather than diplopia. Skew deviation is usually accompanied
by other neurologic signs reflecting brainstem dysfunction.
Yet there is a small subgroup in which vertical misalignment
is an isolated sign, and there are no supporting brain
imaging abnormalities. The main cause of skew deviation is
ischemic stroke, which affects not only the brainstem but
also the thalamus. Diplopia from skew deviation frequently
persists, in which case prism spectacles may be successful
in palliating it. Accompanying neurologic signs, especially
ataxia, may outlast skew deviation and be more debilitating.
Journal of Neuro-Ophthalmology 2021;41:69–76
doi: 10.1097/WNO.0000000000000915
© 2020 by North American Neuro-Ophthalmology Society
S kew deviation is a vertical misalignment of the eyes, or
hypertropia, that is part of an abnormal ocular righting
reflex called the “ocular tilt reaction,” which includes ocular
torsion and head tilt (1,2). It occurs when a lesion upsets the
balanced input to the interstitial nuclei of Cajal in the mes-
odiencephalic junction. Experimental and clinical lesions of
the labyrinth, vestibular nerve, brainstem, cerebellum, and
thalamus can produce this phenomenon (3). Common
causes are stroke, tumors, and inflammatory demyelination.
Patients generally do not notice the head tilt or
a deviation in the perceived position of the horizon
(“subjective visual vertical”), reporting only diplopia or
blurred vision resulting from the hypertropia (3). Although
many single case reports and a thorough review (3) have
documented skew deviation from a variety of causes, there
are only 3 reported clinical series. Two of these reports
appeared before the era of high-definition brain imaging
(4,5), and the third was dedicated to the study of ocular
torsion (6).
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 Original Contribution
Smith et al (4) described 12 cases of skew deviation, all
but one of which had accompanying neurologic manifesta-
tions. Skew deviation could be comitant or incomitant, and
the authors surmised that pontine lesions probably ac-
counted for most cases. They reported 2 additional cases
with isolated hypertropia and features of a decompensated
superior oblique palsy that they considered imitators of
skew deviation. When there are no accompanying neuro-
logic abnormalities, they cautioned, the distinction from
other causes of hypertropia is difficult.
Keane (5) described the clinical features of 100 patients
with skew deviation who were examined over a 4-year
period as inpatients at Los Angeles County Hospital. Diag-
nosis was based on clinical features and, in a minority, on
autopsy. No brain imaging was reported. In that cohort, 60
were judged to have suffered stroke, 14 had posterior fossa
tumors, 11 had clinically presumed multiple sclerosis, and
the remainder had other diagnoses. Accompanying neuro-
logic manifestations were common, especially internuclear
ophthalmoplegia, horizontal gaze paresis, sixth nerve and
seventh nerve palsies, and homonymous hemianopia. The
author did not specify how many patients had skew devia-
tion as an isolated neurologic manifestation. Based on the
pattern of accompanying neurologic abnormalities, skew
deviation was localized to all levels of the brainstem and
perhaps the cerebellum. Most patients exhibited some
improvement in ocular alignment over time, but no further
details about recovery were provided.
In 1993, Brandt and Dieterich (6) reported that 56
(36%) of their 155-patient cohort with imaging-
confirmed unilateral brainstem infarction had skew devia-
tion. In that study, the authors’ aim was to document the
prevalence of ocular torsion and the location of the lesion in
relation to the direction of the torsion and the side of the
higher eye. All patients had ocular torsion in at least one
eye, as determined by foveal displacement on fundus photo-
graphs, and all demonstrated a tilt of the subjective visual
vertical, as measured in an earlier study by having the pa-
tients position a line according to their perception of verti-
cality in relation to the horizon (7). The authors did not
state whether the patients had a head tilt or whether they
had reported a tilt of the subjective visual vertical outside
the experimental setting. Infarcts were distributed through-
out the brainstem and thalamus, with skew occurring in
thalamic infarction when the lesion extended caudally into
the rostral midbrain. The hypertropic eye was always ipsi-
lateral to lesions rostral to the midpons and contralateral to
lesions caudal to the midpons. Hypertropia ranged from 2
prism diopters (PD) to 40 PD, averaging 8 PD.
Given these reports, there remain several issues worthy of
more detailed study: 1) in what setting is the diagnosis of
skew deviation most often made? 2) what symptoms do
patients typically report? 3) what are the features of the
hypertropia? 4) how often is skew deviation accompanied by
other neurologic manifestations and which ones are most
70
Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
common? 5) what are the causes of skew deviation and how
often can these causes be verified on brain imaging? 6) how
long does skew deviation persist? 7) how long do accom-
panying neurologic manifestations persist? and 8) how
often, and under what circumstances, is a spectacle prism
successful in relieving the diplopia of skew deviation?
In an attempt to answer these questions, we undertook
a retrospective review of patients diagnosed with skew
deviation by neuro-ophthalmologists at a single tertiary-care
academic institution in which adequate documentation was
available.
METHODS
We obtained Institutional Review Board approval for
a retrospective analysis of the electronic medical records at
the University of Michigan for patients with skew deviation.
We defined skew deviation as an acute onset of vertical
misalignment without other plausible cause, using the
following exclusion criteria: 1) inadequate ocular alignment
data, 2) the Parks 3-step test suggesting fourth nerve palsy,
3) lack of brain imaging, 4) imaging or clinical evidence of
an orbital abnormality, 5) ptosis present at any encounter,
6) positive acetylcholine receptor antibody test or electro-
myography suggestive of myasthenia gravis, 7) nonabrupt
onset of diplopia, 8) examinations performed without
supervision of a University of Michigan faculty neuro-
ophthalmologist, and 9) no follow-up visits to document an
alternative diagnosis when original brain imaging was
negative.
We used the Electronic Medical Record Search Engine
(EMERSE) of the University of Michigan (8) to search the
records of the Neuro-Ophthalmology Clinics from 2000 to
2018 for the terms “skew” and “skew deviation.” We ob-
tained 468 hits and excluded 329 patients, leaving a cohort
of 157 patients, on whom we recorded the following data:
1) age at diagnosis and sex; 2) setting in which the diagnosis
was made, including emergency department (ED), inpatient
ward, follow-up outpatient visit in the Neuro-
Ophthalmology Clinics after hospital discharge, or direct
outpatient referral to the Neuro-Ophthalmology Clinics;
3) presenting chief complaint, including “diplopia,”
“blurred vision,” or “other;” 4) amplitude of the vertical
misalignment in PD recorded in primary gaze position,
right gaze, left gaze, up gaze, down gaze, right head tilt,
and left head tilt, considering the tropia to be comitant if
the same eye was hypertropic in all positions of gaze, and
the amplitude did not vary by more than 30% in the dif-
ferent positions of gaze (alignment measurements in the
lying position had not been recorded on any patient); 5)
degrees of torsional misalignment measured with the double
Maddox rod test (deviation of the subjective visual vertical
had not been recorded on any patient); 6) accompanying
neurologic signs, including saccadic pursuit, nystagmus,
ataxia, extremity weakness, sensory loss, and abnormalities
Walter and Trobe: J Neuro-Ophthalmol 2021; 41: 69-76

of deep tendon reflexes, where noted; 7) cause, including
imaging-confirmed stroke, imaging-unconfirmed but clini-
cally presumed stroke, posterior fossa tumor, skew immedi-
ately after an intracranial or extracranial procedure,
imaging-based demyelinating brain lesions, nontumorous
cerebellar disorder, traumatic brain injury, other miscella-
neous, and undetermined; 8) other pertinent imaging
abnormalities; 9) time to resolution of skew deviation and
accompanying neurologic signs; and 10) measures used to
relieve diplopia, including occluders, prisms, and eye muscle
surgery.
RESULTS
Demographics
The cohort consisted of 157 patients, among them 81
(52%) men and 76 women with an average age of 58 years.
Diagnostic Setting
Initial diagnosis was made on 102 (65%) outpatients and
55 (35%) inpatients or ED patients. Among the 102
outpatients, 88 had been referred to the clinics by an
ophthalmologist (37), unspecified provider type (21),
neurologist (18), physiatrist (5), primary care physician
(5), or neurosurgeon (2). An additional 14 (9%) outpatients
were diagnosed after an earlier hospital admission or ED
visit at our institution.
Symptoms
There were 136 (87%) patients who reported diplopia, 18
(11%) who reported blurred vision, and only 3 (2%) who
reported no visual symptoms. Among the 136 patients who
reported diplopia, the vertical misalignment averaged 8 PD
(median 5 PD), whereas among the 18 patients who
reported blurred vision, the vertical misalignment averaged
only 3 PD (median 2 PD), being larger than 2 PD in the
primary position in only 3 patients. The 3 patients who
reported no visual symptoms had vertical misalignment
averaging 5 PD, but one patient had pseudophakic
monovision and the other 2 patients had reduced visual
acuity in one eye. No patient reported a tilt of the visual
environment, but documentation of whether that symptom
was explored was not available.
In 91 (58%) patients, diplopia or blurred vision were
accompanied by nonvisual symptoms, including dizziness
(22), imbalance (22), headache (21), weakness (11), slurred
speech (9), nausea (7), numbness (5), extremity weakness
(4), oscillopsia (3), drowsiness (2), hearing loss (2), tinnitus
(2), facial weakness (2), facial numbness (2), facial pain (1),
and visual field loss (1).
In the 63 (40%) patients who had diplopia or blurred
vision as the only recorded new symptoms, 41 (65%) had
an abnormal neurologic examination, including nystagmus
(27), vertical or horizontal gaze deficits (8), internuclear
Walter and Trobe: J Neuro-Ophthalmol 2021; 41: 69-76
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Original Contribution
ophthalmoplegia (7), ataxia (3), facial weakness (3), slow
saccades (2), visual field defect (2), dorsal midbrain
syndrome (2), Horner syndrome (1), or increased deep
tendon reflexes (1).
Features of Vertical Ocular Misalignment
The vertical ocular misalignment was comitant in 100
(64%) patients and incomitant in 57 (36%) patients.
Among the 57 patients with incomitant misalignment, 16
patients had hypertropia that reversed from a right hyper-
tropia in right gaze to a left hypertropia in left gaze
(“alternating skew deviation”). There were no patients with
intermittent (“paroxysmal”) skew deviation. Head tilt was
not recorded in any patient.
The amplitude of vertical misalignment in primary gaze
position ranged from 1 to 30 PD with an average of 7 PD
and a median of 5 PD. The amount of vertical mis-
alignment did not differ substantially according to the cause
of skew deviation. Torsional alignment was measured in
only 33 patients. Among them, there were 6 patients with
excyclodeviation (average 4°) and 4 patients with incyclode-
viation (average 3°). None of these 10 patients reported
perceiving torsional misalignment or a shift in the subjective
visual vertical, but there was inadequate documentation that
these symptoms were queried. Binocular torsion was not
documented.
There was no correlation between the amount of
hypertropia and the frequency of a pertinent imaging
abnormality or accompanying neurologic signs. Thus,
among the 51 patients with a hypertropia of more than 7
PD, 42 (82%) had a pertinent imaging abnormality and 44
(86%) had accompanying neurologic signs. Among the 41
patients with hypertropia of 3 PD or less, a pertinent
imaging abnormality was seen in 31 (76%) and 38 (93%)
had accompanying neurologic signs.
Causes
Stroke
Stroke was imaging-confirmed in 67 patients and clinically
presumed in 15 patients, for a total of 82 (52%) patients. In
13 of these patients, the stroke followed within 24 hours of
a procedure. In 10 of them, the stroke occurred after an
extracranial procedure (3 cardiac catheterizations, 3 trans-
aortic valve replacements, 1 each of coronary artery bypass
graft, mitral valve surgery, popliteal artery bypass surgery,
and cesarean section). In 3 patients, the stroke occurred
after an intracranial procedure (1 trans-sphenoidal surgery,
1 meningioma resection, and 1 basilar artery stenting).
In the 67 patients with imaging-confirmed stroke, there
was a pertinent lesion in the thalamus (17), pons (16),
cerebellum (14), midbrain (12), medulla (9), unspecified
location within the brainstem (7), or “cerebellopontine
angle” (2). Ten of these patients had lesions in 2 locations
that could have accounted for skew deviation. The imaged
71
 Original Contribution
strokes were ischemic in 43 patients and hemorrhagic in 14
patients. Among these patients, 62 (93%) had at least one
other neurologic sign, and 47 (70%) had 2 or more other
neurologic signs. The distribution of strokes did not differ
in the patients with comitant, incomitant, and alternating
skew deviation.
In the 15 patients without pertinent imaging abnormal-
ities, stroke was clinically presumed in 13 patients on the
basis of age, risk factors, and accompanying neurologic
manifestations. In the remaining 2 patients, stroke was
clinically presumed because it immediately followed surgery
and could not be explained by direct surgical injury.
Tumor
There were 15 patients (10%) who developed skew
deviation in the setting of a posterior fossa tumor (3
metastatic breast cancer, 2 glioblastoma multiforme involv-
ing the brainstem, 2 primary central nervous system (CNS)
lymphoma, 1 pilocytic astrocytoma, 1 medulloblastoma, 1
cavernoma, 1 fourth ventricular cyst, 1 meningioma, 1
metastatic non-small-cell lung cancer, 1 metastatic lym-
phoma, and 1 metastatic urothelial carcinoma). All but 1
patient (primary CNS lymphoma) had neurologic signs in
addition to skew deviation.
Operative Injury
There were 15 patients (10%) who developed skew deviation
immediately after intracranial surgery for brainstem or
thalamic tumors in which imaging-confirmed surgical trauma
rather than stroke was judged to be the cause of the skew
deviation (3 cavernomas, 2 subependymomas, 2 meningio-
mas, and 1 ependymoma, 1 schwannoma, 1 glioblastoma, 1
anaplastic astrocytoma, 1 pilocytic astrocytoma, and 1
medulloblastoma). Skew deviation immediately followed 2
intracranial procedures for nontumorous conditions (removal
of an intraventricular shunt and posterior fossa decompres-
sion for trigeminal neuralgia). All but 1 patient (pilocytic
astrocytoma) had accompanying neurologic signs.
Nontumorous Cerebellar Disorders
Skew deviation occurred in 10 (6%) patients with non-
tumorous cerebellar disorders, including 5 patients with
spinocerebellar atrophy, 3 with a paraneoplastic disorder (1
anti-GAD 65, 1 anti-Yo, and 1 with metastatic uterine
cancer but negative paraneoplastic panel and no lesions on
MRI), and 2 with inherited cerebellar degeneration. All 10
patients had other neurologic signs, including nystagmus,
saccadic pursuit, or ataxia. Eight patients had MRI
abnormalities consistent with marked cerebellar volume
loss, and 2 had normal MRI scans.
Demyelination
Skew deviation developed in 7 (4%) patients with MRI
abnormalities compatible with brainstem demyelination (5
pons, 2 cerebellum, 1 midbrain, and 1 thalamus). Among
72
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them, 4 had had no previous diagnosis of multiple sclerosis
at the time of diagnosis of skew deviation. All 7 patients had
accompanying neurologic signs, including internuclear
ophthalmoplegia, nystagmus, ataxia, saccadic pursuit, gaze
paresis, or increased deep tendon reflexes.
Traumatic Brain Injury
Skew deviation occurred in 4 (3%) patients after head
trauma. All had other neurologic signs, including nystag-
mus, quadriplegia, or square wave jerks. Among these 4
patients, 3 had diffuse axonal injury signs on computed
tomography (CT) or MRI, and 1 had a normal CT as the
only brain imaging study.
Posterior Circulation Aneurysm
Skew deviation occurred in 2 (1%) patients with angio-
graphically proven brainstem saccular aneurysms with mass
effect (1 midbasilar and 1 vertebrobasilar junction). Both
had other neurologic signs, including sixth nerve palsy,
facial hypesthesia, ataxia, or nystagmus.
Miscellaneous Causes
Miscellaneous causes accounted for 5 cases of skew
deviation (1 Chiari malformation, 1 brainstem encephalitis,
1 neurosarcoidosis, 1 Parkinson disease, and 1 autoimmune
encephalomyelitis). All 5 patients had other neurologic
signs, and 2 (Chiari malformation and neurosarcoidosis)
had a pertinent imaging abnormality.
Undetermined Cause
Skew deviation without accompanying neurologic signs or
supportive imaging abnormalities was diagnosed in 17
(11%) patients on 2 separate clinic visits at least 3 months
apart. In this group, hypertropia averaged 6 PD (range 2–16
PD, median 5 PD).
Accompanying Neurologic Signs
Among the 157 patients, 133 (85%) had at least one other
neurologic sign besides skew deviation, with 81 (52%)
having 2 or more neurologic signs (Table 1). These signs
included nystagmus in 63 patients (gaze-evoked horizontal
jerk in 16, torsional in 10, upbeat in 6, downbeat in 5,
convergence retraction in 2, Bruns type in 1, mixed in 9,
and unspecified in 14), gaze or ductional deficits in 34
(vertical gaze paresis or palsy in 18, horizontal gaze paresis
or palsy in 6, complete gaze palsy in 2, and abduction deficit
in 8), ataxia in 24 (affecting gait in 4, speech in 2, appen-
dicular movement in 3, trunk in 1, mixed in 1, and unspec-
ified in 14), saccadic pursuit in 23, and internuclear
ophthalmoplegia in 18 (bilateral in 3). Skew was part of
a dorsal midbrain syndrome (documented as a constellation
of light-near dissociation, vertical gaze palsy, and conver-
gence retraction nystagmus) in 6 and was accompanied by
saccadic deficits in 5 (slowed saccades in 3 and saccadic
dysmetria in 2), Horner syndrome in 4, visual field deficits
Walter and Trobe: J Neuro-Ophthalmol 2021; 41: 69-76
 Original Contribution

TABLE 1. Types of accompanying neurologic signs in skew deviation, 1 had diffuse axonal injury evident on MRI,
133 patients with skew deviation 2 had a diffuse axonal injury evident on CT, and 1 had
a normal CT.
No. of Patients
Accompanying Neurologic Signs With This Sign
Resolution of Skew Deviation
Nystagmus 63 At least one follow-up visit was recorded in 137 patients,
Gaze paresis 26 with an interval to last follow-up visit ranging between
Ataxia 24 0.25 and 132 months (average 14 months, median 4.5
Saccadic pursuit 23 months) (Tables 2 and 3). Resolution of skew was docu-
Internuclear ophthalmoplegia 18
Abduction deficit 8 mented in 58 (42%) patients, one of whom needed eye
Dorsal midbrain syndrome 6 muscle surgery to produce it. The likelihood of spontane-
Hemiparesis 4 ous resolution of skew deviation varied greatly according
Horner syndrome 4 to its cause (Table 2). It was most likely to resolve in
Visual field defect 4 demyelination (86%), less often in undetermined causes
Saccadic slowing 3 (59%), traumatic brain injury (50%), post-operative
Dysarthria 3 injury (40%), and stroke (39%), rarely in brainstem tumor
Impaired cognition 3
Wallenberg syndrome 3 (13%), and not at all in posterior circulation aneurysms
Saccadic dysmetria 2 and nontumorous cerebellar disorders.
Afferent pupil defect 1 Resolution of skew deviation occurred within 3 months
Quadriplegia 1 in 33 patients, between 3 and 6 months in 7, between 6 and
12 months in 6, and after 12 months in 12 (Table 3).

in 4, lateral medullary (Wallenberg) syndrome in 3, dysar- Resolution of Accompanying Neurologic Signs

thria in 3, hemiparesis or hemiplegia in 4, impaired cogni-
tion in 3, and by quadriplegia and afferent pupillary defect
in 1 case each.
Among the 24 (15%) patients with skew deviation as an
isolated neurologic sign, a pertinent imaging abnormality
was present in 7 (38%) patients. That left 17 patients, or
11% of the entire cohort, with skew deviation as an isolated
neurologic sign and no pertinent imaging abnormality. By
the last follow-up visit, no new diagnostic information had
appeared in those 17 patients and hypertropia persisted in 7
(41%) of them.
Brain Imaging
Brain imaging included MRI alone in 118 patients, CT
alone in 22, and MRI and CT in 17 (Table 2). Across the
entire cohort, correlative lesions were present in 119 pa-
tients (76%). There was no association between correlative
imaging lesions and amount of hypertropia. In other words,
imaging-positive patients had an average hypertropia of 8
PD (median 5 PD), whereas imaging-negative patients had
an average hypertropia of 6 PD (median 4 PD).
In the 15 patients with clinically presumed stroke and no
correlative lesions on imaging, 9 had undergone MRI and 6
had undergone only CT. Among the 15 patients with
operative injury as the cause of skew deviation, all had
nonstroke lesions on MRI. In the 7 patients with
demyelination as the cause of skew deviation, all had
pertinent brainstem or diencephalic demyelinating lesions
on MRI. Of the 10 patients with a cerebellar disorder as the
cause of skew deviation, all but 2 had an abnormal MRI. Of
the 4 patients with traumatic brain injury as the cause of
Among 137 patients with at least one follow-up visit, 120
patients had accompanying neurologic signs at the initial
visit (Tables 2 and 3). Accompanying signs had partially
resolved in 37 (31%) patients and completely resolved in
31 (26%) of these patients by the last follow-up examina-
tion, leaving 52 (43%) of the cohort with persistent
accompanying neurologic signs. When resolution of
accompanying neurologic occurred, it did so within 3
months of diagnosis in 27 patients, between 3 and 6
months in 10 patients, between 6 and 12 months in 8
patients, and after more than 12 months in 23 patients.
Thus, accompanying neurologic signs generally lingered
longer than did skew deviation. Among these signs was
ataxia, which was often more debilitating than the diplopia
(Table 3).
As with skew deviation, the likelihood of recovery of
accompanying neurologic signs varied according to their
cause. Partial or complete resolution occurred most often in
demyelination (86%), less often in tumor (53%), stroke
(52%), aneurysm (50%), and operative injury (33%), rarely
in nontumorous cerebellar disorders (10%), and not at all in
traumatic brain injury. Among the 17 patients with skew
deviation of undetermined origin, 7 (41%) had failed to
resolve at the last follow-up visit (Table 2).
Measures to Relieve Diplopia
Of the 110 patients who still had diplopia on follow-up
examinations, prism spectacles successfully relieved diplopia
in 68 (62%). The cause of the skew deviation, the size of
the primary position vertical misalignment, and the pres-
ence or absence of incomitance did not predict success in

Walter and Trobe: J Neuro-Ophthalmol 2021; 41: 69-76 73

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 Original Contribution

TABLE 2. Clinical and imaging features in our cohort of 157 patients with skew deviation
Improvement or Resolution
Presence of Presence of Resolution of Skew of Accompanying
Cause of Skew Pertinent Imaging Accompanying Deviation by Last Neurologic Signs by
Deviation (No. of Cases) Abnormality Neurologic Signs Follow-up Visit‡ Last Follow-up Visit§

Stroke (82) 82% 94% 39% 52%

Hemorrhagic (14) 100% 100% 29% 43%
Ischemic (68) 78% 93% 41% 54%
Procedure-related (13) 85% 77% 46% 62%
Tumor (15) 100% 93% 13% 53%
Operative injury (15) 100% 93% 40% 33%
Nontumorous cerebellar 80% 100% 0% 10%
disorders (10)
Demyelination (7) 100% 100% 86%† 86%†
Traumatic brain injury (4) 75%* 100% 50% 0%
Posterior circulation 100% 100% 0% 50%
aneurysm (2)
Miscellaneous (5) 40% 100% 0% 80%
Undetermined (17) 0% 0% 59% NA

*One patient with negative imaging had CT only.

†
One patient had last follow-up visit at 0.5 months.
‡
One hundred thirty-seven patients had at least follow-up visit.
§
One hundred twenty patients with accompanying neurologic signs at initial visit had at least one follow-up visit.

relieving diplopia. Thus, among the 68 patients in whom DISCUSSION

prism spectacles relieved diplopia, the primary gaze position
hypertropia averaged 5 PD (range 1 PD–30 PD, median 3
PD). In that group, 47 (69%) had a comitant hypertropia
and 21 (31%) had an incomitant hypertropia, including 5
patients who had a right hypertropia on right gaze and a left
hypertropia on left gaze. Among the 42 patients in whom
prism spectacles did not relieve diplopia, the average pri-
mary gaze position hypertropia averaged 6 PD (range 1–30
PD, median 4 PD). In that group, 24 (57%) had a comitant
deviation and 18 (43%) had an incomitant deviation,
including 8 patients who had a right hypertropia on right
gaze and a left hypertropia on left gaze.
In the 42 patients in whom prism glasses did not relieve
diplopia, 2 had diplopia relieved with an opaque contact lens
in 1 eye, and 6 had diplopia relieved by eye muscle surgery (1
surgery for 5 patients and 3 surgeries for 1 patient).
This reported series on patients with skew deviation, the
largest to date, confirms and further quantitates clinical
impressions derived from smaller reported series (4,5) and
adds some valuable new information.
Based on this and earlier studies, skew deviation is
usually embedded in a complex of neurologic manifesta-
tions reflecting dysfunction at any level of the brainstem, as
well as the thalamus. At least one other neurologic sign
accompanied skew deviation in 85% of our cohort.
Nystagmus was most common, appearing in nearly half of
the cohort. Gaze paresis, saccadic pursuit, and internuclear
ophthalmoplegia were other common neuro-ophthalmic
abnormalities, as noted in an earlier series (5). Ataxia was
the most common nonophthalmic manifestation. Impor-
tantly, in the 63 patients reporting diplopia or blurred

TABLE 3. Time to resolution of skew deviation and accompanying neurologic signs

Resolution of Accompanying Neurologic Signs†
Time Interval Complete Resolution of
From Initial Diagnostic Visit Skew Deviation* Partial Resolution Complete Resolution

#3 months 33 10 17
.3 #6 months 7 7 3
.6 #12 months 6 5 3
.12 months 12 15 8
Total 58 (42%) 37 (30%) 31 (26%)
*In 137 patients with at least one follow-up visit.
†
In 120 patients with at least one follow-up visit who displayed accompanying neurologic signs at the initial visit.

74 Walter and Trobe: J Neuro-Ophthalmol 2021; 41: 69-76

Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.

vision as the only symptom, neurologic signs were found in
65%, making the search for these accompanying features
particularly important from a diagnostic point of view.
Because these accompanying neuro-ophthalmic signs were
often subtle, and the neurologic examination sometimes
incomplete, we suspect that they may have been even more
prevalent and often overlooked.
Stroke accounted for half of causes, with lesions
distributed throughout the brainstem, cerebellum, and
thalamus. The thalamus emerged as the most common site
of stroke, a finding that has not been emphasized. Although
brain imaging could not verify the full extent of the
thalamic lesion, it probably reached into the rostral
termination of the pathway mediating vertical ocular
alignment. As suggested by Keane (5) in the preimaging
era, strokes proved to be more often ischemic than hemor-
rhagic. Although most were unprovoked, an important
number immediately followed intracranial and extracranial
procedures, including heart catheterization, heart valve sur-
gery, and bypass grafting, as well as popliteal artery bypass
surgery, and even cesarean section. Brainstem stroke in
these settings is a known phenomenon, perhaps because
of autonomic dysregulation or emboli (9). Notably, there
were 9 patients in our study with a strong clinical presump-
tion of a provoked brainstem stroke in whom MRI was
negative. Even high-definition brain MRI does not always
detect stroke in the brainstem (10).
Aside from stroke, brainstem tumor and operative injury
were common causes. Demyelination, traumatic brain
injury, posterior circulation aneurysms, and miscellaneous
causes accounted a much smaller proportion of cases.
An important subgroup of our cohort consisted of 24
patients with skew deviation who had no accompanying
neurologic manifestations. In that group, sometimes called
“ambulatory skew deviation,” only 7 patients had pertinent
brain imaging abnormalities, leaving 17 with neither imag-
ing nor clinically supportive information toward a diagnosis.
CT was the only study in 6 of them; MRI might have
detected the lesion. In the 11 patient studies with MRI,
we surmise that skew deviation might have been caused
by a brainstem stroke too small to be detected even on
MRI (10).
In this study, the pattern of ocular misalignment was
incomitant in 1/3 of cases. Within that group, 1/3 showed
reversal of the hypertropia with lateral gaze (“alternating
skew deviation”). Although these phenomena have been
well described, this report provides the first quantitation
of their relative prevalence in a large group of patients.
Previous reports have mentioned that the hypertropia of
skew deviation may show improvement over time, but no
specific details have been provided, probably because of lack
of follow-up. In this study, with a median follow-up interval
of 4.5 months, spontaneous resolution of hypertropia and
diplopia was observed in fewer than 50% of patients,
varying widely according to cause (Table 2). If skew devi-
Walter and Trobe: J Neuro-Ophthalmol 2021; 41: 69-76
Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
Original Contribution
ation was of undetermined origin, it had a slightly better
than 50% chance of disappearing. Among all causes of skew
deviation, recovery usually occurred within the first 3
months but was often delayed for longer than 12 months
(Table 3).
The frequently accompanying neurologic signs often
proved to be more debilitating and enduring than the skew
deviation. Improvement was noted in only slightly more
than half of the cohort. When improvement did occur, it
was often delayed 12 months or more. We acknowledge
that follow-up was incomplete and that patients may not
have returned because they had recovered or sought care
elsewhere.
A critical finding in this study was that 62% of the
patients with enduring diplopia could have it relieved with
spectacle prisms. Surprisingly, neither the cause of the skew,
the size of the hypertropia, nor the degree of incomitance
predicted success in relieving diplopia. Surprisingly, diplo-
pia associated with large hypertropia could sometimes be
palliated with spectacle prisms, suggesting that some
patients may be reporting relief of diplopia even when
ocular misalignment persists.
This study further delineates the clinical and imaging
profile of skew deviation. Its strengths are a large patient
cohort with adequate clinical documentation confirmed on
examination by neuro-ophthalmologists, strict exclusion
criteria to avoid inclusion of clinical imitators of skew
deviation, high prevalence of high-definition neuroimaging,
and a search engine capable of detecting any mention of
skew deviation in electronic medical record text.
But there are also weaknesses inherent in such a retro-
spective study. Examination techniques were performed by
3 different neuro-ophthalmologists in a nonstandard fash-
ion, often generating incomplete data. Symptoms of
alteration in the subjective visual vertical were not elicited,
and measurements of postural differences in hypertropia,
ocular torsion, and a disturbed visual vertical were not often
performed.
Acknowledging these study strengths and weaknesses,
the relevant conclusions from this study are as follows:
1) Most patients with skew deviation will report a visual
disturbance—usually diplopia, but if the hypertropia is
less than 3 PD, they may describe blurred vision.
2) The hypertropia of skew deviation will be incomitant in
an important minority of cases; within that subgroup,
the hypertropia often reverses in gaze from side to side
(“alternating skew deviation”).
3) Skew deviation is usually accompanied by other neurologic
manifestations, especially nystagmus, saccadic pursuit, hor-
izontal gaze paresis, internuclear ophthalmoplegia, and
ataxia; such accompanying signs, often subtle, are impor-
tant in distinguishing skew deviation from other causes of
acute hypertropia, especially if visual symptoms are isolated
or most prominent.
75
 Original Contribution
4) An important subgroup, amounting to 11% in this
study, will consist of patients with skew deviation
without other neurologic abnormalities or correlative
imaging abnormalities; perhaps they have had
a stroke too small to show up on current brain
imaging.
5) Stroke accounts for most cases of skew deviation, occur-
ring at any level of the brainstem, including the cerebel-
lum, and especially in the thalamus; other important
causes are posterior fossa tumors, operative injury, brain-
stem demyelination, nontumorous cerebellar disorders,
and traumatic brain injury.
6) Skew deviation may be persistent even among patients
in whom it is the only clinical manifestation.
7) Diplopia associated with persistent skew deviation may
be relieved with spectacle prisms in slightly more than
half of cases, even among patients with incomitance and
large vertical misalignment.
8) The neurologic manifestations accompanying skew devi-
ation, especially ataxia, may be more debilitating and
enduring than the diplopia.
The important management implications of this profile
are the following:
1) Attention must be paid to detection of accompanying
neurologic features, which are common and critical for
diagnosis.
2) In the small proportion of cases where acute hypertropia
is the only clinical abnormality and high-definition brain
imaging is negative, the diagnosis of skew deviation is
viable but must be questioned.
3) Patients should be advised that skew deviation may last
for months or even indefinitely, and that accompanying
neurologic manifestations, especially ataxia, may be
more debilitating.
76
Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
4) Prism spectacles may alleviate diplopia even when the
misalignment is greater than 3 PD and incomitant;
when that intervention fails, eye muscle surgery may
be effective in relieving diplopia.
STATEMENT OF AUTHORSHIP
Category 1: a. conception and design: E. Walter and J. D. Trobe; b.
acquisition of data: E. Walter and J. D. Trobe; c. analysis and
interpretation of data: E. Walter and J. D. Trobe. Category 2: a.
drafting the manuscript: E. Walter and J. D. Trobe; b. revising it for
intellectual content: E. Walter and J. D. Trobe. Category 3: a. final
approval of the completed manuscript: E. Walter and J. D. Trobe.
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