Mild-to-Moderate Traumatic Brain Injury: A Review with Focus on the Visual System

Abstract

Traumatic Brain Injury (TBI) is a major global public health problem. Neurological damage from TBI may be mild, moderate, or severe and occurs both immediately at the time of impact (primary injury) and continues to evolve afterwards (secondary injury). In mild (m)TBI, common symptoms are headaches, dizziness and fatigue. Visual impairment is especially prevalent. Insomnia, attentional deficits and memory problems often occur. Neuroimaging methods for the management of TBI include computed tomography and magnetic resonance imaging. The location and the extent of injuries determine the motor and/or sensory deficits that result. Parietal lobe damage can lead to deficits in sensorimotor function, memory, and attention span. The processing of visual information may be disrupted, with consequences such as poor hand-eye coordination and balance. TBI may cause lesions in the occipital or parietal lobe that leave the TBI patient with incomplete homonymous hemianopia. Overall, TBI can interfere with everyday life by compromising the ability to work, sleep, drive, read, communicate and perform numerous activities previously taken for granted. Treatment and rehabilitation options available to TBI sufferers are inadequate and there is a pressing need for new ways to help these patients to optimize their functioning and maintain productivity and participation in life activities, family and community.

Full text

Citation: Rauchman, S.H.; Albert, J.;
Pinkhasov, A.; Reiss, A.B.
Mild-to-Moderate Traumatic Brain
Injury: A Review with Focus on the
Visual System. Neurol. Int. 2022,14,
453–470. https://doi.org/10.3390/
neurolint14020038
Academic Editors: Thomas Müller
and Tissa Wijeratne
Received: 18 April 2022
Accepted: 25 May 2022
Published: 30 May 2022
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4.0/).
Review
Mild-to-Moderate Traumatic Brain Injury: A Review with Focus
on the Visual System
Steven H. Rauchman 1, * , Jacqueline Albert 2, Aaron Pinkhasov 3and Allison B. Reiss 2
1The Fresno Institute of Neuroscience, Fresno, CA 93730, USA
2Department of Medicine, Biomedical Research Institute, NYU Long Island School of Medicine,
Mineola, NY 11501, USA; jacqueline.albert@duke.edu (J.A.); allison.reiss@nyulangone.org (A.B.R.)
3Department of Psychiatry, NYU Long Island School of Medicine, Mineola, NY 11501, USA;
aron.pinkhasov@nyulangone.org
*Correspondence: dr.rauchman@yahoo.com
Abstract:
Traumatic Brain Injury (TBI) is a major global public health problem. Neurological damage
from TBI may be mild, moderate, or severe and occurs both immediately at the time of impact
(primary injury) and continues to evolve afterwards (secondary injury). In mild (m)TBI, common
symptoms are headaches, dizziness and fatigue. Visual impairment is especially prevalent. Insomnia,
attentional deficits and memory problems often occur. Neuroimaging methods for the management
of TBI include computed tomography and magnetic resonance imaging. The location and the extent
of injuries determine the motor and/or sensory deficits that result. Parietal lobe damage can lead to
deficits in sensorimotor function, memory, and attention span. The processing of visual information
may be disrupted, with consequences such as poor hand-eye coordination and balance. TBI may
cause lesions in the occipital or parietal lobe that leave the TBI patient with incomplete homonymous
hemianopia. Overall, TBI can interfere with everyday life by compromising the ability to work, sleep,
drive, read, communicate and perform numerous activities previously taken for granted. Treatment
and rehabilitation options available to TBI sufferers are inadequate and there is a pressing need
for new ways to help these patients to optimize their functioning and maintain productivity and
participation in life activities, family and community.
Keywords: head injury; prognosis; traumatic brain injury; vision; retina
1. Introduction
Traumatic brain injury (TBI) is an imminent global health challenge and the primary
cause of trauma-related long-term or permanent disability worldwide [
1
]. In 2019, the CDC
reported 61,000 deaths related to TBI [
2
]. With incidence rates of 50 million cases per year,
TBI may be categorized as mild, moderate or severe [
3
]. Mild-to-moderate TBI accounts
for about 90% of all TBIs while approximately 80% of TBI cases in the United States are
classified as mild (mTBI) [
4
,
5
]. Severity and morbidity are disproportionately high among
lower- and middle-income countries and the estimated global economic cost is 400 billion
USD annually [6–8].
The assumption that mTBI has little consequence has been debunked as it may result
in neurological symptoms and cognitive impairment with tangible impacts on quality of
life and substantial demands on health services [9,10].
2. Methods
An extensive literature review was performed using PubMed and Google with regard
to the topics “mild or moderate traumatic brain injury”, “concussion” and “traumatic brain
injury, eye, and vision”. The search terms included “traumatic brain injury”, “concussion”,
“visual pathways AND traumatic brain injury”, “parietal lobe AND traumatic brain injury”,
Neurol. Int. 2022,14, 453–470. https://doi.org/10.3390/neurolint14020038 https://www.mdpi.com/journal/neurolint

Neurol. Int. 2022,14 454
“traumatic brain injury AND treatment”, “traumatic brain injury AND medications”, “trau-
matic brain injury AND rehabilitation”, “traumatic brain injury AND quadrantanopia”,
and “traumatic brain injury AND imaging”. Studies available in English from 1989 onward
were included. This yielded approximately 1000 manuscripts from which we narrowed
the scope by looking at human studies (observational, randomized, prospective and retro-
spective) as well as meta-analysis papers and reviews of each key topic area. We excluded
studies that focused primarily on severe TBI and hospitalization. The final number of
papers reviewed after applying these selection criteria was 200.
3. Basics of TBI
3.1. Detemining Severity
Manifestations of TBI occur after an external mechanical force is sustained by the
patient in the area of the head, neck and/or face leading to a primary injury characterized
by neuronal impairment [
11
]. The most commonly observed clinical features of mTBI are
headache, dizziness, nausea and poor concentration [
12
]. More severe injuries can lead
to aphasia, seizures, amnesia, behavioral abnormalities and, in the worst cases, coma [
13
].
These may manifest within seconds to minutes following TBI. The most widely used clinical
assessment of TBI is the Glasgow Coma Scale (GCS) which classifies TBI as mild (14–15),
moderate (9–13), or severe (3–8) [
14
,
15
]. The GCS is comprised of the eye opening, verbal,
and motor subscales, which are combined to give a total GCS score. The GCS system
has several shortcomings due to its ambiguity in diagnosing mild and moderate TBI. For
instance, there is still persistent disagreement on whether a GCS of 13 should be treated as
mild or moderate TBI [
16
]. Other notable challenges to the accurate diagnosis of TBI stem
from inter-rater variability and a plurality of etiologies as well as a general disagreement in
the literature over which of the many possible TBI symptoms should be used to determine
disease severity [
17
]. Even after an accurate diagnosis, different patients with similar
diagnoses on the GCS can present a multitude of outcomes due to underlying genetic
factors, the type of injury, and the severity of the secondary injury that occurs due to the
initiation of damaging biochemical cascades by the primary injury [18].
3.2. Initial Treatment
A large concern of TBI treatment relies on immediate therapeutic intervention to
prevent secondary injury, as the primary injury cannot be undone. Secondary injury can
present minutes to days after the initial insult due to neuro-inflammation, changes in cranial
blood pressure, and the disruption of neurological homeostasis resulting in neuronal cell
damage, apoptosis and death [
19
]. There is no pharmacological medication with proven
efficacy for human TBI. Current treatments aim to prevent hypoxia, hypercapnia and
hypotension and regulate cerebral perfusion pressure (CPP), ensuring that euvolemia is
maintained and secondary injury is avoided [20,21].
3.3. Diagnostic Issues in mTBI
There is a lack of attention paid to mTBI since it is not regarded as an imminent medical
emergency. This can result in the dismissal of patients from serious medical care and the
failure to adequately characterize the severity of underlying neurological impairment.
Additionally, many patients who have sustained mTBI injuries do not seek medical care,
or are treated by healthcare providers lacking specific experience in this area. This is a
pressing issue, since there exist a multitude of significant and persistent complications for
mTBI patients such as impairments in cognition and motor function, psychiatric problems,
and impaired neurological development in children [
22
]. Given that approximately 80–90%
of TBIs are classified as mild, this neglects the lasting neurological implications of injuries
for a large majority of TBI patients [23,24].
Public awareness surrounding the high incidence of mTBI has increased in recent years
due to the publication of data surrounding high levels of mTBI complications in athletes
and veterans, in particular [
25
]. Another subgroup with high rates of mTBI includes victims

Neurol. Int. 2022,14 455
of abuse, who are a vulnerable and oftentimes neglected population. A greater emphasis
on the treatment of mTBI and the management of its prolonged neurological consequences
would have significant implications on quality of life for affected individuals [26,27].
4. Focal and Diffuse Injury
Traumatic brain injury results from either a blunt force directly striking the head in
a closed or penetrating strike, or due to non-impact force. This initial strike results in a
primary injury, which encompasses both direct brain damage caused by the sustained
impact and the subsequent damage caused by the impairment of cerebral blood flow and
alterations to homeostatic metabolism [
28
]. The type of primary injury sustained from the
blunt or non-impact force usually fits into one of two broad categories: focal and diffuse
injuries. Focal brain injury, often affecting the frontal and temporal lobes, results from
the compression of brain tissue specifically at the site of impact due to collision forces
acting on the skull and has clinical manifestations such as subdural and epidural hematoma
and hemorrhagic contusions [
29
,
30
]. The temporal lobes are particularly vulnerable to
the physical compression and vascular disruption that accompanies focal brain injury,
perhaps because the bony covering is thinner relative to the bone over the frontal lobes. The
frontal lobes also receive some cushioning from the air-filled sinuses. Since the temporal
lobes harbor important memory-related structures, even mild contusions can lead to
significant and enduring impairment [
31
]. Impacts to the frontal cortex can manifest
as poor judgement and problem-solving abilities [
32
]. Focal TBI can disrupt the blood
brain barrier (BBB), leading to cellular fluid extravasation into the extracellular space [33].
The cerebral blood flow may be altered, leading to hypo- or hyper-perfusion [
28
]. These
homeostatic disruptions can cause brain tissue destruction, neuronal necrosis, and the
formation of brain cavities due to glial cell reactivity [
34
]. Damage to the BBB is implicated
in chronic inflammation after TBI, likely a result of microvasculopathy, which can lead to
post-injury development of epilepsy and other neurological disorders [35].
Contrecoup brain injury is a specific subset of focal traumatic brain injury in which
the major cerebral contusions occur on the side opposite from the site of blunt force impact.
Mechanistically, this phenomenon can be explained by visualizing the brain, which at rest
is encased in the skull and floating in the cerebrospinal fluid (CSF). When the head rapidly
accelerates, and then suddenly decelerates, the brain is displaced in the denser CSF in
relation to the skull and collides with the internal skull in the contrecoup location [
36
,
37
].
This is seen when the brain collides with the skull and then rebounds in the opposite
direction (coup-contrecoup), causing additional brain injury across from the location of
blunt force impact (Figure 1). Coup-contrecoup injuries can lead to widespread damage
due to the additional site of injured tissue at a remote location in the brain, resulting
in a broadened array of symptoms in patients. This has a particularly strong effect on
visual symptoms of TBI, as accommodatively-based visual symptoms such as trouble
focusing eyes, visual fatigue, and blurred vision are highly correlated with coup-contrecoup
injury [38].
Diffuse brain damage generally occurs after rapid acceleration-deceleration of the
head, and is associated with disorders of consciousness related to axonal and vascular
injury as well as brain swelling [14]. Diffuse damage is often detected via CT scans, and a
recent influx of magnetic resonance imaging (MRI) data due to advancements in imaging
technology have suggested a relationship between the presence of diffuse axonal injury
(DAI) and worse outcomes of TBI [
39
]. The location of axonal shearing or sustained focal
lesions in DAI heavily affects patient outcome, with common locations including the corona
radiata, corpus callosum, internal capsule, brainstem, and thalamus [
40
]. Many cases of
fatal DAI contain three specific hallmark structural features: focal lesions in the corpus
callosum, focal lesions in the rostral brain stem and diffuse axonal damage [
41
]. These
features are difficult to identify in living patients, complicating not only the diagnosis of
DAI but also the ease of studying less severe cases of DAI that do not result in death.

Neurol. Int. 2022,14 456
Neurol. Int. 2022, 14, FOR PEER REVIEW 4
Figure 1. Coup contrecoup traumatic brain injury. The coup portion of the injury occurs when the
movement of the head stops abruptly and the brain continues to move in the forward direction so
that it hits the skull. The contrecoup portion further compounds the damage as the brain bounces
off the skull and hits the side of the skull opposite the side of initial impact.
Diffuse brain damage generally occurs after rapid acceleration-deceleration of the
head, and is associated with disorders of consciousness related to axonal and vascular
injury as well as brain swelling [14]. Diffuse damage is often detected via CT scans, and a
recent influx of magnetic resonance imaging (MRI) data due to advancements in imaging
technology have suggested a relationship between the presence of diffuse axonal injury
(DAI) and worse outcomes of TBI [39]. The location of axonal shearing or sustained focal
lesions in DAI heavily affects patient outcome, with common locations including the co-
rona radiata, corpus callosum, internal capsule, brainstem, and thalamus [40]. Many cases
of fatal DAI contain three specific hallmark structural features: focal lesions in the corpus
Figure 1.
Coup contrecoup traumatic brain injury. The coup portion of the injury occurs when the
movement of the head stops abruptly and the brain continues to move in the forward direction so
that it hits the skull. The contrecoup portion further compounds the damage as the brain bounces off
the skull and hits the side of the skull opposite the side of initial impact.
5. Brain Imaging Techniques in TBI
The most widely used brain imaging technologies for the diagnosis of TBI include
standard CT and MRI scans. Standard noncontrast CT scans are preferentially employed for
rapid and comparatively low-cost imaging results, especially in cases of critical moderate
and severe TBI where immediate medical intervention may be required [
42
]. Repeated
CT imaging is controversial, but has shown promise in improving patient outcome in
several studies [
43
,
44
]. However, CT scans present several concerns pertaining to ionizing
radiation exposure in vulnerable age groups, such as children and pregnant women [
45
–
47
].
Performing noncontrast CT scans also has significant limitations in TBI prognosis, including
inaccurately displaying the severity of early traumatic contusions, limitations for detecting

Neurol. Int. 2022,14 457
changes in intracranial pressure and cerebral edema, and difficulty in identifying diffuse
traumatic injury [48].
The predictive value in determining prognosis is comparable for MRI and CT scans,
with the added advantage of MRI of an increased sensitivity in detecting small contusions
and hemorrhagic injury to axons [
49
,
50
]. The drawbacks of MRI in comparison to standard
CT imaging include high cost, lower accessibility of MRI machinery, and longer duration
of time to obtain results. CT is also superior in detecting skull fractures and CSF leak [
51
].
The most common acute and chronic finding on CT or MRI of the brain is a normal exam.
Thus, the routine neuroradiological investigation of head trauma often performed in the
emergency department is insensitive to the structural abnormalities that suggest a patient
has undergone TBI. CT imaging usually appears normal when investigating subacute TBI
(more than 7 days and less than 3 months after the primary injury) or chronic TBI (3 or
more months after the primary injury) [52].
Several classifications centering on CT readings have been developed for risk strat-
ification and prediction of mortality of TBI patients. These include Marshall, Rotter-
dam, Stockholm, Helsinki and NeuroImaging Radiological Interpretation System (NIRIS)
scores [53–58] (Table 1).
Table 1.
Summary of classifications systems based on imaging for risk stratification and prediction of
mortality in TBI.
Classification Scoring Key Features
Marshall (1992) [53]Diffuse Injury I to
Diffuse Injury VI
Diffuse injury I—No visible intracranial pathology on CT.
Progresses up to Diffuse Injury VI with high or mixed
density lesion > 25 mL not surgically evacuated. Evaluates
perimesencephalic cisterns, midline shift, and presence of a
mass lesion.
Rotterdam (2006) [54] 1 to 6
4 scored elements: basal cistern compression status;
degree of midline shift; epidural hematomas,
intraventricular and/or subarachnoid hemorrhage.
Differentiates between types of mass lesions, recognizes more
favorable prognosis for epidural hematomas.
Stockholm (2010) [55]
Traumatic subarachnoid
hemorrhage score
Range: (0 to 6)
Builds on Marshall and Rotterdam. Adds separate
scoring for traumatic subarachnoid hemorrhage.
Magnitude of midline shift used as a continuous variable (not
dichotomous) for prediction of favorable or
unfavorable outcome. Incorporates diffuse axonal injury.
Helsinki (2014) [56]−3 to 14
Refined to include type of mass lesion (subdural,
intracerebral or epidural hematoma. Intraventricular hemorrhage
as a predictor of outcome. Includes
suprasellar cisterns status (normal, compressed,
obliterated).
NeuroImaging Radiological
Interpretation System (NIRIS)
(2018) [57]
NIRIS 0
to NIRIS 4
Score gives management guidance: NIRIS 0—patients typically
discharged, NIRIS 1—follow-up neuroimaging and/or hospital
admission, NIRIS 2—admission to an advanced care unit, NIRIS
3—neurosurgical intervention, NIRIS 4—high likelihood of fatal
outcome from TBI.
The use of single photon emission computed tomography (SPECT) to detect abnormal-
ities in regional cerebral blood perfusion (rCBF) allows for high resolution and detection of
small perfusion differences that may aid in predicting the likelihood of recovery [
59
,
60
].
SPECT is a functional brain imaging tool that uses a gamma-emitting radionuclide that
can cross the BBB to show regions of abnormal blood flow [
61
,
62
]. Performing a SPECT
scan is a minimally invasive method of assessing regional cerebral blood flow, therefore
providing useful information on the relative activity levels of different regions of the brain
to help detect pathologically significant brain perfusion patterns [
63
–
65
]. The utility of

Neurol. Int. 2022,14 458
SPECT comes into play particularly in cases where structural abnormalities are not found
on CT. Irregularities in brain perfusion can be seen immediately after mTBI and can identify
regions of both hypoperfusion and hyperemia as well as other tissue dysfunction local to
sites of brain lesions, indicating BBB disruption [66].
Abnormalities in rCBF are most easily detected in moderate and severe cases. The
detected abnormalities in rCBF are most commonly located in the frontal or parietal lobe
for patients with traumatic brain disorder [
67
]. In approximately 50% of SPECT scans
of TBI patients, abnormalities in the occipital lobe (the visual cortex) are also detected.
Abnormalities in rCBF that are localized in the visual cortex manifest clinically in cortical
visual impairment. Therefore, it is relevant to consider the visual findings in TBI for patients
with mTBI [68].
Sequential SPECT scans can be used to track the clinical evolution of a TBI patient
throughout the duration of treatment [
67
,
69
]. SPECT can be used as a marker for improve-
ment. Normalizing blood flow over time (studies months or years apart) usually indicates
clinical improvement. If a new drug is developed that may improve the long-term outcome
of TBI patients, it would be very useful to have serial SPECT scans to help prove the drug is
actually working. Imaging of the brain is critical in making a correct neurologic diagnosis.
The limitations of the immediate head CT in the emergency room have been previously
described. SPECT is not indicated in every case, but merits addition to the arsenal of tests
as a companion to CT for evaluation of TBI patients.
6. Visual Symptoms of TBI
A significant percentage of patients with mTBI report visual symptoms. Among the
most common of these is photophobia, a form of light sensitivity in which light exposure
causes eye and head pain [
70
–
72
]. Photophobia and its associated migraine-like symptoms
are major sources of functional impairment in TBI [
73
]. Other commonly reported visual
symptoms of mTBI include disorders of extraocular movements, affecting saccadic move-
ments and smooth pursuits. Patients that have experienced TBI exhibit latencies such as
lagged smooth pursuit movements as well as position errors and reduced acceleration in
saccadic movements [
74
]. Difficulties with reading in TBI patients are noteworthy, with
documented abnormalities including increased fixations and regressions per 100 words,
reduced reading rates, and lower comprehension and sophistication in reading level [75].
7. Visual Pathway, Parietal Lobes and Vision
Optic nerves from each eye transport visual impulses from retinal ganglion cells in the
retina to the optic chiasm and then to higher visual processing centers in the brain. As a
result of partial decussation at the optic chiasm, each optic tract contains the fibers from
the ipsilateral temporal and contralateral nasal retina (Figure 2).
The optic nerve and tracts can be damaged from transmitted forces during TBI, even
when the impact is minor, and can result from either the primary or secondary injury. The
mechanism of traumatic optic neuropathy is not fully understood, but may result from ten-
sion on the nerve or nerve compression and involve damage to the axons and/or reduction
of the blood supply to the nerve [
76
–
78
]. The visual impairment from optic nerve damage
in TBI generally occurs at the time of injury and may vary from a deficit in color vision to
loss of visual acuity to sudden, complete visual loss [
79
,
80
]. Treatment is difficult and may
be medical, with high dose systemic corticosteroids or surgical, with decompression of the
optic canal, or a combination of surgery and corticosteroids. Observation is also a valid
approach because spontaneous visual recovery is well-documented [81–83].
When evaluating the consequences of TBI on ophthalmologic function, a critical
region of the brain to consider is the parietal cortex. The posterior parietal cortex is a
central associative region of the brain and is located in the center of the brain behind the
frontal lobes of the brain and in front of the occipital lobes [
84
]. This structural proximity
lends itself to functional connections among the parietal cortex and the temporal visual
area, the occipital visual area, and the prefrontal cortex [
85
]. The parietal lobes have great

Neurol. Int. 2022,14 459
significance due to their involvement in sensorimotor integration, decision making, spatial
navigation, and short term memory [
86
,
87
]. The parietal cortex encodes spatial coordinates
and is engaged during the planning of reaching toward a target [
88
]. Surgery affecting the
parietal lobes is associated with a risk of the loss of language and visual field deficits [
89
].
Neurol. Int. 2022, 14, FOR PEER REVIEW 7
Figure 2. The visual pathway. The optic nerves from each eye partially cross at the optic chiasm so
that fibers from the nasal half of each retina cross over to the contralateral optic tract. Fibers from
the temporal portion of each retina remain ipsilateral. As a result, the left optic tract contains fibers
originating from the left temporal retina, and the right nasal retina while the right optic tract con-
tains fibers originating from the right temporal retina, and the left nasal retina.
The optic nerve and tracts can be damaged from transmitted forces during TBI, even
when the impact is minor, and can result from either the primary or secondary injury. The
mechanism of traumatic optic neuropathy is not fully understood, but may result from
tension on the nerve or nerve compression and involve damage to the axons and/or re-
duction of the blood supply to the nerve [76–78]. The visual impairment from optic nerve
damage in TBI generally occurs at the time of injury and may vary from a deficit in color
vision to loss of visual acuity to sudden, complete visual loss [79,80]. Treatment is difficult
and may be medical, with high dose systemic corticosteroids or surgical, with decompres-
sion of the optic canal, or a combination of surgery and corticosteroids. Observation is
also a valid approach because spontaneous visual recovery is well-documented [81–83].
When evaluating the consequences of TBI on ophthalmologic function, a critical re-
gion of the brain to consider is the parietal cortex. The posterior parietal cortex is a central
associative region of the brain and is located in the center of the brain behind the frontal
lobes of the brain and in front of the occipital lobes [84]. This structural proximity lends
itself to functional connections among the parietal cortex and the temporal visual area, the
occipital visual area, and the prefrontal cortex [85]. The parietal lobes have great signifi-
cance due to their involvement in sensorimotor integration, decision making, spatial nav-
igation, and short term memory [86,87]. The parietal cortex encodes spatial coordinates
Figure 2.
The visual pathway. The optic nerves from each eye partially cross at the optic chiasm so
that fibers from the nasal half of each retina cross over to the contralateral optic tract. Fibers from
the temporal portion of each retina remain ipsilateral. As a result, the left optic tract contains fibers
originating from the left temporal retina, and the right nasal retina while the right optic tract contains
fibers originating from the right temporal retina, and the left nasal retina.
8. TBI Affects the Parietal Lobes, Vestibular System and Visual Perception
8.1. Parietal Lobes
The parietal lobes are frequently injured in head trauma, leading to deficits in sensori-
motor function, memory, and attention span [
90
,
91
]. Given that eyesight is one of the core
senses integrated in the parietal cortex, it is therefore critical to examine the ophthalmologic
manifestations of TBI in the parietal region. The parietal lobes integrate visual data from
rapid eye movements (saccadic movements) to direct the mechanistic reaching movements
of the hand, allowing the individual to place an object in space and reach out to grasp
it [
88
,
92
]. However, when the parietal cortex is impaired, depth perception cannot function
properly, causing loss of the ability to perceive the spatial layout of the objects surrounding
them [
93
]. Another consequence of parietal lobe dysfunction occurs in patients who lose
the ability to shift their spatial attention or distinguish things on their left or their right side,
leading to difficulty navigating even simple tasks such as walking across a room [
90
,
94
].
Banal tasks are further impacted in TBI patients that have sustained damage to the parietal
lobe, as the parietal lobe plays a crucial role in integrating limb movements to produce

Neurol. Int. 2022,14 460
coordinated actions [
84
]. The aforementioned challenges greatly decrease quality of life
and increase the risks faced in high-danger zones such as work sites and this can then
disqualify the TBI sufferer from employment.
Further manifestations of parietal lobe damage in TBI patients can be observed as
functional deficits in speech and language, or as behavioral changes in impulse control
and decision-making situations. As far as risk aversion, one study showed that TBI in
a rat model chronically altered the propensity of the rats to make high-risk decisions,
leading to an increase in risk-taking behavior [
95
]. Humans with TBI-inflicted damage to
the parietal lobes have been observed to experience a decrease in both altruistic behavior
and goal-directed behavior, especially when damage is sustained in the lateral parietal
cortex [
96
] This has grave implications on a patient’s quality of life, as apathetic behavior
increases the difficulty a patient will have completing everyday tasks [97].
As detailed above, the effects of parietal lobe damage on ophthalmologic function
are complex phenomena that are often experienced as confusing by the patient. This
complicates the process of detecting visual abnormalities in TBI patients, since many of the
described deficits are not detectable with standard eye examinations. Detecting parietal
lobe damage via ophthalmologic evaluation includes an exhaustive evaluation of visual
field measurement to detect abnormalities in depth perception [
98
,
99
]. Abnormalities in
depth perception are often difficult for patients to describe. Therefore, evaluation with
specialized equipment is key to diagnosing a patient and providing them with accurate
medical care. This equipment also allows for the assessment of a patient’s peripheral vision,
which is also often affected in patients with parietal lobe damage. Accurately detecting
these visual abnormalities are essential to determining the long-term consequences a patient
will experience after sustaining TBI, as visual dysfunction can alter the ability of a patient
to work or live independently.
Another common ophthalmologic manifestation of TBI is homonymous quadran-
tanopia, a type of incomplete homonymous hemianopia that results from lesions occurring
in the postchiasmal visual pathways in the occipital or parietal lobe [
100
–
102
]. Quadran-
tanopia is loss of a visual field quadrant and homonymous quadrantanopia involves the
loss of the congruent quadrant on the same side in both eyes [
103
]. It is commonly known
as the “pie in the sky” phenomenon and causes difficulty in visual scanning and detection,
leading to complications in everyday life processes such as driving a car or operating
other machinery [
104
,
105
]. Although some spontaneous recovery may occur, rehabilitation
generally involves visual aids and strategies to compensate for the loss [106–108].
Injury to the primary visual pathways through the parietal and temporal lobes should
be understood separately from disorders of higher-level visual processing. Since damage
occurs before transfer to the occipital lobe for primary processing, the homonymous
hemianopsias are very distinct and well-defined on visual field testing [109].
8.2. Vestibular System
Deficits in multisensory processing in TBI patients can also be caused by vestibular
impairment. The vestibular system, located inside the ear, is essential for the integration
of sensory information to produce balanced body and eye movements for posture control
and navigation [
110
]. Visual tracking neurons receive vestibular information in cortical
sites located in the associative parietal and temporal cortex. Parietal regions are involved
in processing vestibular information for the perception of self-motion [
111
]. In cases of
post-concussion or mTBI vestibular dysfunction, vestibular impairment causes a myriad
of symptoms related to imbalance and disorientation, which often manifests as dizzi-
ness/vertigo and/or lightheadedness and may be accompanied by nausea as well [
112
,
113
].
For non-hospitalized TBI patients, vestibular function testing detects abnormalities in some-
where between about 30 to 60% of those tested and symptoms may continue for in excess of
one year in 10 to 15% of patients with a mild concussion [
10
,
114
–
117
]. Vestibular symptoms
make return-to-work difficult and interfere with many normal activities. Symptoms are
most prominent with head movement or when the patient is moving on foot [118].

Neurol. Int. 2022,14 461
Reciprocal interactions occur between visual and vestibular cortical regions. Altered
vestibular function has been hypothesized to cause postconcussive visual motion sensitivity.
Allen et al. found that post-concussion patients with subacute vestibular impairment symp-
toms showed exaggerated activation in the multisensory processing centers involved in
visual-vestibular sensory processing [
119
]. They hypothesize that these patients developed
overreliance on visual stimuli to compensate for vestibular impairment and that this may
lead to difficulty in recovering after TBI. Targeted vestibular rehabilitation may help in
these cases [120].
8.3. Visuospatial Neglect
Visuospatial neglect occurs when spatial awareness is lost on the side opposite the
injured hemisphere. Patients display reduced attention unilaterally and will not explore
spontaneously or respond to stimuli originating in the contralesional hemi-space [
121
].
Visuospatial neglect happens more often when the right parietal lobe is injured resulting in
left hemi-field inattention [
122
]. It is most commonly seen after hemispheric stroke, but
may occur after TBI as well and is associated with poorer recovery. It leads to postural
instability and the risk of falls. Treatment is usually partial visual occlusion via eye-patching
of the non-neglected half of the visual spatial field [
123
]. Prism adaptation, which laterally
displaces the visual field using special lenses, can improve the performance of spatial
tasks [124].
9. TBI, Insomnia, and the Eyes
The incidence of sleep disruption in patients that have experienced significant head
trauma has been reported in the range of 27% to 72.7% in several studies, depending on the
type of sleep disruption and the severity of TBI [
125
,
126
]. Commonly observed sleep dis-
ruptions in TBI patients include hypersomnia, insomnia and daytime
sleepiness [127–129]
.
This heightened prevalence in abnormal sleep patterns in TBI patients is present in both
patients who have a history of sleep issues and patients who have never had sleep difficul-
ties and is very troubling to patients [
130
,
131
]. Sleep problems can exacerbate depression,
stress and pain [132–134]. Lack of sleep also makes sufferers more accident-prone [135].
Disruptions in sleep patterns impede the rehabilitation process, as they result in
lethargy, attentional deficits, and the overall impairment of cognitive function that sig-
nificantly reduces quality of life [
136
,
137
]. Sleep deficits interfere with brain recovery
pathways that occur during healthy sleep cycles. Patients that experience sleep-wake cycle
disturbances display abnormal levels of neurotransmitters, leading to irregular neuronal
activation patterns and the disruption of brain repair mechanisms [137].
The chronic lack of sleep observed in TBI patients has damaging effects on recovering
eye cells [
138
]. The cells in the retina are metabolically active for the entire day as they
process information from the electromagnetic waves they are continuously
receiving [139]
.
Altered circadian rhythmic function has been linked to imbalances in metabolic home-
ostasis, causing abnormal regulation of gene transcription and the dysfunction of glucose
metabolism [
140
]. Therefore, sleep disruption inhibits the ability of retinal cells to replenish
their energy reserves and leads to issues in homeostatic maintenance in cells such as the rods
and cones. This cellular homeostatic imbalance in the rods and cones causes wear down in
the main photoreceptors of the eye, resulting in visual fatigue and hindering recovery.
Another type of sleep disorder that has been found in TBI patients is sleep apnea, in
which a patient experiences irregular breathing patterns during sleep [
141
]. In addition
to the sleep deficits caused by sleep apnea, the repeated cessation of breathing in sleep
apnea patients can amplify the neurological sequelae of TBI, as it causes hypoxemia and is
negatively correlated with cognitive function in TBI patients [142].
10. The Ruptured Globe
The eyeball itself can be harmed directly via blunt or sharp trauma. In cases where
direct damage occurs to the eyeball, it can be difficult to address the injury early in the

Neurol. Int. 2022,14 462
emergency room assessment, as the eyelids tend to be highly swollen and bruised after
impact. This may result in the failure to identify an injury to the eyes, as doctors may be
hesitant to forcibly separate the upper and lower eyelids of the trauma patient in order to
inspect the eyeball.
A serious eye trauma-related injury not to be overlooked is a ruptured globe. A
ruptured globe or open globe injury is a full-thickness injury to the cornea, sclera or both of
these components of the protective shell of the eyeball [
143
,
144
]. It can be caused by a blunt
or penetrating force and exposes the fragile contents of the interior of the eye, which are
easily perturbed [
145
]. These highly critical tissues are extremely sensitive to any element
of disruption, increasing the probability of vision loss in patients. The ruptured globe must
be recognized immediately as an ophthalmologic emergency and surgical repair should be
undertaken as soon as possible. Ophthalmic examination must be attempted on patients
with a ruptured globe as preoperative visual acuity is an important prognostic indicator
for surgical outcome [
146
]. The presence of any intraocular foreign bodies can be detected
by examination or CT scan [
147
–
149
]. Since time elapsed between injury and surgery is
another predictor of outcome, ruptured globe surgery usually takes place within 12 to 24 h
after trauma to restore and preserve the structural integrity of the eyeball.
The prognosis of ruptured globe depends heavily upon the size and severity of the
rupture [
143
,
144
]. A small laceration to the cornea tends to have a better prognostic outcome
than a deeper rupture, with a higher probability of vision recovery due to the cornea’s
location on the surface of the eye. Larger lacerations or ruptures of the more posterior sclera,
often cause damage to the retina and carry a much poorer prognosis due to the immense
difficulty of correcting deep eye damage. In the most severe of cases, patients may present
with no light perception and the eye may not be salvageable. Surgery on patients with no
light perception often ends in enucleation, or the complete removal of the eye, to prevent
sympathetic ophthalmia, a sight-threatening disorder caused by trauma to the contralateral
eye [150]. However, surgical globe repair may be a preferred alternative [151–153].
Permanent vision loss is a severe complication of head and facial trauma. Prompt
treatment of the ruptured globe is important to avoid permanent loss of vision. The initial
surgical effort in severe cases is to restore the integrity of the globe and prevent leakage
of internal ocular tissues outside the eyeball. This is to prevent secondary damage to the
structural integrity of the eyeball Future surgeries are often required to remove blood,
fix the retina, and remove damaged lenses or traumatic cataracts. If these efforts are
unsuccessful, it may become necessary to remove the eye entirely via enucleation.
11. An Ophthalmologist Clinical Perspective
11.1. Diagnostic Tools for Ophthalmologic Evaluation of TBI
Oculomotor assessment following TBI generally includes an evaluation of smooth
pursuit eye movements and fixation, vergence and accommodation and saccades [
154
].
Poorer oculomotor function is correlated with more symptoms post-TBI and difficulties
with everyday activities [155,156].
Visual field defects are frequently observed after TBI [
157
]. Formal visual field testing
is generally performed in an ophthalmology outpatient setting. The cost of these devices
limits acquisition in more general medical practices [158].
The King Devick test, which can be routinely performed in an ophthalmology office
or on the sideline during sporting events, is a widely used standardized test to assess for
TBI by evaluating cognitive processing speed and rapid shifting of gaze [
159
]. This is a
simple yet sensitive test based on the ability to complete a rapid number-naming task on
an iPad or paper [
160
]. It is not sufficient to use this test alone and it is known to have a
high false-positive rate [161].
The Brain Injury Vision Symptom Survey (BIVSS), a 28-item symptom questionnaire,
is useful in documenting vision complaints and distinguishing between patients with and
without mild-to-moderate TBI [
108
,
160
,
162
]. This test is considered a valid instrument for
vision symptoms that can be administered online, in-person or by healthcare providers.

Neurol. Int. 2022,14 463
11.2. Visual Consequences of TBI in Daily Life
The undesirable consequences of TBI are experienced by in excess of 5 million people
spanning all ages in the United States alone [
8
]. The vast majority of TBI falls into the
mild category and those affected may never be seen by a healthcare provider and never
receive a formal diagnosis [
163
]. Some may enter an emergency department or urgent
care facility immediately after an automobile collision or other type of accident and then
be discharged with no follow-up. Routine CT and MRI scans of the brain are somewhat
insensitive measures of mild TBI and often yield a normal reading. Unfortunately, despite
normal imaging, patients may remain symptomatic months to years after injury [
164
]. Even
if these individuals receive a comprehensive neurologic evaluation, effective interventions
are lacking.
Although visual symptoms and findings are common, they may go unnoticed by
medical providers. The importance of ophthalmologic evaluation of such patients is
underestimated. The enormous role of the brain in visual information processing is not
subsumed within a standard eye exam [
165
,
166
]. There is a need for coordination among
specialists, including ophthalmologists, in order to address TBI-related losses in ability
to gather and process huge amounts of visual data, processing of which is essential for
everyday life [167,168].
Reading text on a computer screen has become one of the single most important tasks
in an ever-evolving technological world and fatigue and eyestrain result from this common
task [
169
,
170
]. For many TBI patients this fatigue becomes burdensome and disabling.
Many individuals rely upon a smart phone, a powerful mini-computer that has become a
necessary tool to multitudes around the globe. The tiny letters and numbers on various
screens are reported to appear blurry or hard to read after TBI [
171
]. Driving is essential
to independence for some and the light sensitivity so often experienced by TBI patients
may interfere with this activity and act as a dangerous distraction [
172
]. Sleep disruption
induced by mild TBI can exacerbate visual disturbances and impair perception [171–174].
The treatment of the visual symptoms and findings of TBI involve the prescription of
eyeglasses with tints and prism combinations, bi-nasal occlusion as well as light-filtering
lenses [
175
–
177
]. Interdisciplinary care is needed to get the best outcomes of rehabilitation
for these patients [178].
12. Conclusions
This review has explored and discussed the pathophysiology and difficulty in the
diagnosis of mild-to-moderate TBI. The various neuroradiological modalities employed
to determine the extent of the damage and their shortcomings have been covered. Nor-
mal MRI, CT, and other test results can be deceptive and conflict with subjective symp-
tomatology. The long-term sequelae of mild-to-moderate TBI are a serious concern with
consequences affecting quality-of-life, productivity and the economic viability of patients.
Common symptoms include confusion, headache, balance problems, nausea, vomiting,
vertigo, visual disturbances, photophobia, fatigue, insomnia, and sound sensitivity. Emo-
tional and behavioral symptoms such as depression, mood swings, agitation and anxiety
are also associated with TBI. Achieving functional recovery is difficult and the available
rehabilitation options offer modest benefits in many cases. Prolonged effects on visual path-
ways and visual processing are often prominent and can affect visuo-motor coordination
and tasks such as driving, reading and the use of computer technology. Preventing future
TBIs is critical because the cumulative number of head injuries suffered negatively impacts
recovery. While novel approaches to the treatment of TBI are urgently needed, head injury
prevention programs and the implementation of education and outreach where possible
can yield tangible results.
Author Contributions:
S.H.R. and A.B.R. conceptualized the topic of the review. The manuscript
was drafted by S.H.R., A.B.R. and J.A.; critically edited by A.P. Figures were designed by A.B.R. and
A.P. All authors have read and agreed to the published version of the manuscript.

Neurol. Int. 2022,14 464
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Data Availability Statement:
All data listed in this manuscript is publically available from manuscripts
found on PubMed.
Acknowledgments:
Original artwork in Figures 1and 2by Samantha M. Steiner. We thank Lynn
Drucker and Edmonds Bafford.
Conflicts of Interest: The authors declare no conflict of interest.
References
1.
Iaccarino, C.; Carretta, A.; Nicolosi, F.; Morselli, C. Epidemiology of severe traumatic brain injury. J. Neurosurg. Sci.
2018
,62,
535–541. [CrossRef] [PubMed]
2.
Centers for Disease Control and Prevention. National Center for Health Statistics: Mortality Data on CDC WONDER. Available
online: https://wonder.cdc.gov/mcd.html (accessed on 20 April 2022).
3.
Savitsky, B.; Givon, A.; Rozenfeld, M.; Radomislensky, I.; Peleg, K. Traumatic brain injury: It is all about definition. Brain Inj.
2016
,
30, 1194–1200. [CrossRef] [PubMed]
4.
Dewan, M.C.; Rattani, A.; Gupta, S.; Baticulon, R.E.; Hung, Y.C.; Punchak, M.; Agrawal, A.; Adeleye, A.O.; Shrime, M.G.;
Rubiano, A.M.; et al.
Estimating the global incidence of traumatic brain injury. J. Neurosurg.
2019
,130, 1080–1097. [CrossRef]
[PubMed]
5.
Taylor, C.A.; Bell, J.M.; Breiding, M.J.; Xu, L. Traumatic brain injury–related emergency department visits, hospitalizations, and
deaths—United States, 2007 and 2013. MMWR Surveill. Summ. 2017,66, 1–16. [CrossRef]
6. Khellaf, A.; Khan, D.Z.; Helmy, A. Recent advances in traumatic brain injury. J. Neurol. 2019,266, 2878–2889. [CrossRef]
7.
Bonow, R.H.; Barber, J.; Temkin, N.R.; Videtta, W.; Rondina, C.; Petroni, G.; Lujan, S.; Alanis, V.; La Fuente, G.; Lavadenz, A.; et al.
The outcome of severe traumatic brain injury in Latin America. World Neurosurg. 2018,111, e82–e90. [CrossRef]
8.
Rubiano, A.M.; Carney, N.; Chesnut, R.; Puyana, J.C. Global neurotrauma research challenges and opportunities. Nature
2015
,
527, S193–S197. [CrossRef]
9.
McAllister, T.W.; Flashman, L.A.; McDonald, B.C.; Saykin, A.J. Mechanisms of working memory dysfunction after mild and
moderate TBI: Evidence from functional MRI and neurogenetics. J. Neurotrauma 2006,23, 1450–1467. [CrossRef]
10.
Cassidy, J.D.; Cancelliere, C.; Carroll, L.J.; Côté, P.; Hincapié, C.A.; Holm, L.W.; Hartvigsen, J.; Donovan, J.; Boussard, C.N.-D.;
Kristman, V.L.; et al. Systematic review of self-reported prognosis in adults after mild traumatic brain injury: Results of the
international collaboration on mild traumatic brain injury prognosis. Arch. Phys. Med. Rehabil. 2014,95, S132–S151. [CrossRef]
11.
Menon, D.K.; Schwab, K.; Wright, D.W.; Maas, A.I. Position statement: Definition of traumatic brain injury. Arch. Phys. Med.
Rehabil. 2010,91, 1637–1640. [CrossRef]
12.
Feddermann-Demont, N.; Echemendia, R.J.; Schneider, K.J.; Solomon, G.S.; Hayden, K.A.; Turner, M.; Dvoˇrák, J.; Straumann, D.;
Tarnutzer, A.A. What domains of clinical function should be assessed after sport-related concussion? A systematic review. Br. J.
Sports Med. 2017,51, 903–918. [CrossRef] [PubMed]
13.
Darshini, J.K.; Afsar, M.; Vandana, V.P.; Shukla, D.; Rajeswaran, J. The Triad of Cognition, Language, and Communication in
Traumatic Brain Injury: A Correlational Study. J. Neurosci. Rural Pract. 2021,12, 666–672. [CrossRef] [PubMed]
14.
Capizzi, A.; Woo, J.; Verduzco-Gutierrez, M. Traumatic Brain Injury: An Overview of Epidemiology, Pathophysiology, and
Medical Management. Med. Clin. N. Am. 2020,104, 213–238. [CrossRef]
15.
Teasdale, G.; Maas, A.; Lecky, F.; Manley, G.; Stocchetti, N.; Murray, G. The Glasgow coma scale at 40 years: Standing the test of
time. Lancet Neurol. 2014,13, 844–854. [CrossRef]
16.
Mena, J.H.; Sanchez, A.I.; Rubiano, A.M.; Peitzman, A.B.; Sperry, J.L.; Gutierrez, M.I.; Puyana, J.C. Effect of the modified Glasgow
Coma Scale score criteria for mild traumatic brain injury on mortality prediction: Comparing classic and modified Glasgow
Coma Scale score model scores of 13. J. Trauma 2011,71, 1185–1193. [CrossRef]
17.
Chung, P.; Khan, F. Traumatic Brain Injury (TBI): Overview of Diagnosis and Treatment. J. Neurol. Neurophysiol.
2013
,5, 1.
[CrossRef]
18.
Davanzo, J.R.; Sieg, E.P.; Timmons, S.D. Management of Traumatic Brain Injury. Surg. Clin. N. Am.
2017
,97, 1237–1253. [CrossRef]
[PubMed]
19.
Abdelmalik, P.A.; Draghic, N.; Ling, G.S.F. Management of moderate and severe traumatic brain injury. Transfusion
2019
,59,
1529–1538. [CrossRef]
20.
Taran, S.; Pelosi, P.; Robba, C. Optimizing oxygen delivery to the injured brain. Curr. Opin. Crit. Care
2022
,28, 145–156. [CrossRef]
21.
Khan, R.; Alromaih, S.; Alshabanat, H.; Alshanqiti, N.; Aldhuwaihy, A.; Almohanna, S.A.; Alqasem, M.; Al-Dorzi, H. The Impact
of Hyperoxia Treatment on Neurological Outcomes and Mortality in Moderate to Severe Traumatic Brain Injured Patients. J. Crit.
Care Med. (Targu Mures) 2021,7, 227–236. [CrossRef]
22.
Laskowski, R.A.; Creed, J.A.; Raghupathi, R. Pathophysiology of Mild TBI: Implications for Altered Signaling Pathways. In Brain
Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects; Kobeissy, F.H., Ed.; CRC Press/Taylor & Francis: Boca Raton,
FL, USA, 2015.

Neurol. Int. 2022,14 465
23.
Skandsen, T.; Nilsen, T.L.; Einarsen, C.; Normann, I.; McDonagh, D.; Haberg, A.K.; Vik, A. Incidence of Mild Traumatic Brain
Injury: A Prospective Hospital, Emergency Room and General Practitioner-Based Study. Front. Neurol.
2019
,10, 638. [CrossRef]
[PubMed]
24.
Forrest, R.H.; Henry, J.D.; McGarry, P.J.; Marshall, R.N. Mild traumatic brain injury in New Zealand: Factors influencing
post-concussion symptom recovery time in a specialised concussion service. J. Prim. Health Care
2018
,10, 159–166. [CrossRef]
[PubMed]
25.
McCrory, P.; Meeuwisse, W.H.; Aubry, M.; Cantu, R.C.; Dvoˇrák, J.; Echemendia, R.J.; Engebretsen, L.; Johnston, K.M.; Kutcher, J.S.;
Raftery, M.; et al. Consensus statement on concussion in sport—The 4th International Conference on Concussion in Sport held in
Zurich, November 2012. PM R 2013,5, 255–279. [CrossRef] [PubMed]
26.
Pavlovic, D.; Pekic, S.; Stojanovic, M.; Popovic, V. Traumatic brain injury: Neuropathological, neurocognitive and neurobehavioral
sequelae. Pituitary 2019,22, 270–282. [CrossRef]
27.
Shepherd, D.; Landon, J.; Kalloor, M.; Barker-Collo, S.; Starkey, N.; Jones, K.; Ameratunga, S.; Theadom, A.; BIONIC Research
Group. The association between health-related quality of life and noise or light sensitivity in survivors of a mild traumatic brain
injury. Qual. Life Res. 2020,29, 665–672. [CrossRef]
28. Werner, C.; Engelhard, K. Pathophysiology of traumatic brain injury. Br. J. Anaesth. 2007,99, 4–9. [CrossRef]
29.
Andriessen, T.M.; Jacobs, B.; Vos, P.E. Clinical characteristics and pathophysiological mechanisms of focal and diffuse traumatic
brain injury. J. Cell. Mol. Med. 2010,14, 2381–2392. [CrossRef]
30.
McGinn, M.J.; Povlishock, J.T. Pathophysiology of Traumatic Brain Injury. Neurosurg. Clin. N. Am.
2016
,27, 397–407. [CrossRef]
31.
Bigler, E.D. Anterior and middle cranial fossa in traumatic brain injury: Relevant neuroanatomy and neuropathology in the study
of neuropsychological outcome. Neuropsychology 2007,21, 515–531. [CrossRef]
32.
Yue, J.K.; Winkler, E.A.; Puffer, R.C.; Deng, H.; Phelps, R.; Wagle, S.; Morrissey, M.R.; Rivera, E.J.; Runyon, S.J.; Vassar, M.J.; et al.
The Track-Tbi Investigators Temporal lobe contusions on computed tomography are associated with impaired 6-month functional
recovery after mild traumatic brain injury: A TRACK-TBI study. Neurol. Res. 2018,40, 972–981. [CrossRef]
33.
Cipolotti, L.; MacPherson, S.E.; Gharooni, S.; van-Harskamp, N.; Shallice, T.; Chan, E.; Nachev, P. Cognitive estimation:
Performance of patients with focal frontal and posterior lesions. Neuropsychologia 2018,115, 70–77. [CrossRef] [PubMed]
34.
Korn, A.; Golan, H.; Melamed, I.; Pascual-Marqui, R.; Friedman, A. Focal cortical dysfunction and blood-brain barrier disruption
in patients with Postconcussion syndrome. J. Clin. Neurophysiol. 2005,22, 1–9. [CrossRef] [PubMed]
35.
Bar-Klein, G.; Lublinsky, S.; Kamintsky, L.; Noyman, I.; Veksler, R.; Dalipaj, H.; Senatorov, V.V., Jr.; Swissa, E.; Rosenbach, D.;
Elazary, N.; et al. Imaging blood-brain barrier dysfunction as a biomarker for epileptogenesis. Brain
2017
,140, 1692–1705.
[CrossRef] [PubMed]
36.
Drew, L.B.; Drew, W.E. The contrecoup-coup phenomenon: A new understanding of the mechanism of closed head injury.
Neurocrit. Care 2004,1, 385–390. [CrossRef]
37.
Ratnaike, T.E.; Hastie, H.; Gregson, B.; Mitchell, P. The geometry of brain contusion: Relationship between site of contusion and
direction of injury. Br. J. Neurosurg. 2011,25, 410–413. [CrossRef]
38.
Green, W.; Ciuffreda, K.J.; Thiagarajan, P.; Szymanowicz, D.; Ludlam, D.P.; Kapoor, N. Static and dynamic aspects of accommoda-
tion in mild traumatic brain injury: A review. Optometry 2010,81, 129–136. [CrossRef]
39.
Humble, S.S.; Wilson, L.D.; Wang, L.; Long, D.A.; Smith, M.A.; Siktberg, J.C.; Mirhoseini, M.F.; Bhatia, A.; Pruthi, S.;
Day, M.A.; et al.
Prognosis of diffuse axonal injury with traumatic brain injury. J. Trauma Acute Care Surg.
2018
,85, 155–159.
[CrossRef]
40.
Galgano, M.; Toshkezi, G.; Qiu, X.; Russel, T.; Chin, L.; Zhao, L.R. Traumatic Brain Injury: Current Treatment Strategies and
Future Endeavors. Cell Transplant. 2017,26, 1118–1130. [CrossRef]
41.
Adams, J.H.; Graham, D.I.; Murray, L.S.; Scott, G. Diffuse Axonal Injury Due to Nonmissile Head Injury in Humans: An Analysis
of 45 Cases. Ann. Neurol. 1982,12, 557–563. [CrossRef]
42.
Mutch, C.A.; Talbott, J.F.; Gean, A. Imaging Evaluation of Acute Traumatic Brain Injury. Neurosurg. Clin. N. Am.
2016
,27, 409–439.
[CrossRef]
43.
Lobato, R.D.; Alen, J.F.; Perez-Nuñez, A.; Alday, R.; Gómez, P.A.; Pascual, B.; Lagares, A.; Miranda, P.; Arrese, I.; Kaen, A. Utilidad
de la TAC secuencial y la monitorización de la presión intracraneal para detectar nuevo efecto masa intracraneal en pacientes
con traumatismo craneal grave y lesión inicial Tipo I-II [Value of serial CT scanning and intracranial pressure monitoring for
detecting new intracranial mass effect in severe head injury patients showing lesions type I-II in the initial CT scan]. Neurocirugia
2005,16, 217–234. [PubMed]
44.
Brown, C.V.; Zada, G.; Salim, A.; Inaba, K.; Kasotakis, G.; Hadjizacharia, P.; Demetriades, D.; Rhee, P. Indications for routine
repeat head computed tomography (CT) stratified by severity of traumatic brain injury. J. Trauma
2007
,62, 1339–1344; discussion
1344–1345. [CrossRef] [PubMed]
45.
Lindberg, D.M.; Stence, N.V.; Grubenhoff, J.A.; Lewis, T.; Mirsky, D.M.; Miller, A.L.; O’Neill, B.R.; Grice, K.; Mourani, P.M.;
Runyan, D.K. Feasibility and Accuracy of Fast MRI Versus CT for Traumatic Brain Injury in Young Children. Pediatrics
2019
,144,
e20190419. [CrossRef] [PubMed]
46.
Wilson, T.T.; Merck, L.H.; Zonfrillo, M.R.; Movson, J.S.; Merck, D. Efficacy ofComputed Tomography Utilization in the Assessment
of Acute Traumatic Brain Injury in Adult and Pediatric Emergency Department Patients. R. I. Med. J. 2019,102, 33–35.

Neurol. Int. 2022,14 466
47.
Darlan, D.; Prasetya, G.B.; Ismail, A.; Pradana, A.; Fauza, J.; Dariansyah, A.D.; Wardana, G.A.; Apriawan, T.; Bajamal, A.H.
Algorithm of Traumatic Brain Injury in Pregnancy (Perspective on Neurosurgery). Asian J. Neurosurg.
2021
,16, 249–257. [CrossRef]
48.
Smith, L.; Milliron, E.; Ho, M.L.; Hu, H.H.; Rusin, J.; Leonard, J.; Sribnick, E.A. Advanced neuroimaging in traumatic brain injury:
An overview. Neurosurg. Focus 2019,47, E17, Erratum in Neurosurg. Focus 2021,50, E22. [CrossRef]
49.
Chastain, C.A.; Oyoyo, U.E.; Zipperman, M.; Joo, E.; Ashwal, S.; Shutter, L.A.; Tong, K.A. Predicting outcomes of traumatic brain
injury by imaging modality and injury distribution. J. Neurotrauma 2009,26, 1183–1196. [CrossRef]
50.
Audenaert, K.; Jansen, H.M.; Otte, A.; Peremans, K.; Vervaet, M.; Crombez, R.; de Ridder, L.; van Heeringen, C.; Thirot, J.;
Dierckx, R.; et al. Imaging of mild traumatic brain injury using 57Co and 99mTc HMPAO SPECT as compared to other diagnostic
procedures. Med. Sci. Monit. 2003,9, MT112–MT117.
51.
Schweitzer, A.D.; Niogi, S.N.; Whitlow, C.T.; Tsiouris, A.J. Traumatic Brain Injury: Imaging Patterns and Complications.
Radiographics 2019,39, 1571–1595. [CrossRef]
52.
Shetty, V.S.; Reis, M.N.; Aulino, J.M.; Berger, K.L.; Broder, J.; Choudhri, A.F.; Kendi, A.T.; Kessler, M.M.; Kirsch, C.F.;
Luttrull, M.D.; et al. ACR Appropriateness Criteria Head Trauma. J. Am. Coll. Radiol. 2016,13, 668–679. [CrossRef]
53.
Marshall, L.F.; Marshall, S.B.; Klauber, M.R.; Van Berkum Clark, M.; Eisenberg, H.; Jane, J.A.; Luerssen, T.G.; Marmarou, A.;
Foulkes, M.A. The diagnosis of head injury requires a classification based on computed axial tomography. J. Neurotrauma
1992
,9
(Suppl. S1), S287–S292. [PubMed]
54.
Maas, A.I.; Hukkelhoven, C.W.; Marshall, L.F.; Steyerberg, E.W. Prediction of outcome in traumatic brain injury with computed
tomographic characteristics: A comparison between the computed tomographic classification and combinations of computed
tomographic predictors. Neurosurgery 2006,57, 1173–1182. [CrossRef] [PubMed]
55.
Nelson, D.W.; Nyström, H.; MacCallum, R.M.; Thornquist, B.; Lilja, A.; Bellander, B.M.; Rudehill, A.; Wanecek, M.;
Weitzberg, E.
Extended analysis of early computed tomography scans of traumatic brain injured patients and relations to outcome. J.
Neurotrauma 2010,27, 51–64. [CrossRef] [PubMed]
56.
Raj, R.; Siironen, J.; Skrifvars, M.B.; Hernesniemi, J.; Kivisaari, R. Predicting outcome in traumatic brain injury: Development
of a novel computerized tomography classification system (Helsinki computerized tomography score). Neurosurgery
2014
,75,
632–646; discussion 646–647. [CrossRef] [PubMed]
57.
Wintermark, M.; Li, Y.; Ding, V.Y.; Xu, Y.; Jiang, B.; Ball, R.L.; Zeineh, M.; Gean, A.; Sanelli, P. Neuroimaging Radiological
Interpretation System for Acute Traumatic Brain Injury. J. Neurotrauma 2018,35, 2665–2672. [CrossRef] [PubMed]
58.
Khaki, D.; Hietanen, V.; Corell, A.; Hergès, H.O.; Ljungqvist, J. Selection of CT variables and prognostic models for outcome
prediction in patients with traumatic brain injury. Scand. J. Trauma Resusc. Emerg. Med. 2021,29, 94. [CrossRef]
59.
Nedd, K.; Sfakianakis, G.; Ganz, W.; Uricchio, B.; Vernberg, D.; Villanueva, P.; Jabir, A.M.; Bartlett, J.; Keena, J. 99mTc-HMPAO
SPECT of the brain in mild to moderate traumatic brain injury patients: Compared with CT—A prospective study. Brain Inj.
1993
,
7, 469–479. [CrossRef]
60.
Lin, A.P.; Liao, H.J.; Merugumala, S.K.; Prabhu, S.P.; Meehan, W.P., 3rd; Ross, B.D. Metabolic imaging of mild traumatic brain
injury. Brain Imaging Behav. 2012,6, 208–223. [CrossRef]
61.
Raji, C.A.; Henderson, T.A. PET and Single-Photon Emission Computed Tomography in Brain Concussion. Neuroimaging Clin. N.
Am. 2018,28, 67–82. [CrossRef]
62. Goffin, K.; van Laere, K. Single-photon emission tomography. Handb. Clin. Neurol. 2016,135, 241–250. [CrossRef]
63.
Santra, A.; Kumar, R. Brain perfusion single photon emission computed tomography in major psychiatric disorders: From basics
to clinical practice. Indian J. Nucl. Med. 2014,29, 210–221. [CrossRef] [PubMed]
64.
Pavel, D.; Jobe, T.; Devore-Best, S.; Davis, G.; Epstein, P.; Sinha, S.; Kohn, R.; Craita, I.; Liu, P.; Chang, Y. Viewing the functional
consequences of traumatic brain injury by using brain SPECT. Brain Cogn. 2006,60, 211–213. [PubMed]
65.
Gowda, N.K.; Agrawal, D.; Bal, C.; Chandrashekar, N.; Tripati, M.; Bandopadhyaya, G.P.; Malhotra, A.; Mahapatra, A.K.
Technetium Tc-99m ethyl cysteinate dimer brain single-photon emission CT in mild traumatic brain injury: A prospective study.
AJNR Am. J. Neuroradiol. 2006,27, 447–451. [PubMed]
66.
Sakas, D.E.; Bullock, M.R.; Patterson, J.; Hadley, D.; Wyper, D.J.; Teasdale, G.M. Focal cerebral hyperemia after focal head injury
in humans: A benign phenomenon? J. Neurosurg. 1995,83, 277–284. [CrossRef] [PubMed]
67.
Khalili, H.; Rakhsha, A.; Ghaedian, T.; Niakan, A.; Masoudi, N. Application of Brain Perfusion SPECT in the Evaluation of
Response to Zolpidem Therapy in Consciousness Disorder Due to Traumatic Brain Injury. Indian J. Nucl. Med.
2020
,35, 315–320.
[CrossRef]
68.
Silverman, I.E.; Galetta, S.L.; Gray, L.G.; Moster, M.; Atlas, S.W.; Maurer, A.H.; Alavi, A. SPECT in patients with cortical visual
loss. J. Nucl. Med. 1993,34, 1447–1451.
69.
Laatsch, L.; Pavel, D.; Jobe, T.; Lin, Q.; Quintana, J.C. Incorporation of SPECT imaging in a longitudinal cognitive rehabilitation
therapy programme. Brain Inj. 1999,13, 555–570. [CrossRef]
70. Digre, K.B.; Brennan, K.C. Shedding light on photophobia. J. Neuroophthalmol. 2012,32, 68–81. [CrossRef]
71.
Merezhinskaya, N.; Mallia, R.K.; Park, D.; Millian-Morell, L.; Barker, F.M., 2nd. Photophobia Associated with Traumatic Brain
Injury: A Systematic Review and Meta-analysis. Optom. Vis. Sci. 2021,98, 891–900. [CrossRef]
72. Armstrong, R.A. Visual problems associated with traumatic brain injury. Clin. Exp. Optom. 2018,101, 716–726. [CrossRef]
73.
Mares, C.; Dagher, J.H.; Harissi-Dagher, M. Narrative Review of the Pathophysiology of Headaches and Photosensitivity in Mild
Traumatic Brain Injury and Concussion. Can. J. Neurol. Sci. 2019,46, 14–22. [CrossRef] [PubMed]

Neurol. Int. 2022,14 467
74.
DiCesare, C.A.; Kiefer, A.W.; Nalepka, P.; Myer, G.D. Quantification and analysis of saccadic and smooth pursuit eye movements
and fixations to detect oculomotor deficits. Behav. Res. Methods 2017,49, 258–266. [CrossRef] [PubMed]
75.
Reddy, A.; Mani, R.; Selvakumar, A.; Hussaindeen, J.R. Reading eye movements in traumatic brain injury. J. Optom.
2020
,13,
155–162. [CrossRef] [PubMed]
76.
Li, Y.; Singman, E.; McCulley, T.; Wu, C.; Daphalapurkar, N. The Biomechanics of Indirect Traumatic Optic Neuropathy Using a
Computational Head Model with a Biofidelic Orbit. Front. Neurol. 2020,11, 346. [CrossRef] [PubMed]
77.
Jacobs, S.M.; Van Stavern, G.P. Neuro-ophthalmic deficits after head trauma. Curr. Neurol. Neurosci. Rep.
2013
,13, 389. [CrossRef]
[PubMed]
78.
Rasiah, P.K.; Geier, B.; Jha, K.A.; Gangaraju, R. Visual deficits after traumatic brain injury. Histol. Histopathol.
2021
,36, 711–724.
[CrossRef]
79.
Ellis, M.J.; Ritchie, L.; Cordingley, D.; Essig, M.; Mansouri, B. Traumatic Optic Neuropathy: A Potentially Unrecognized Diagnosis
after Sports-Related Concussion. Curr. Sports Med. Rep. 2016,15, 27–32. [CrossRef]
80.
Saliman, N.H.; Belli, A.; Blanch, R.J. Afferent Visual Manifestations of Traumatic Brain Injury. J. Neurotrauma
2021
,38, 2778–2789.
[CrossRef]
81.
Chen, H.H.; Lee, M.C.; Tsai, C.H.; Pan, C.H.; Lin, Y.T.; Chen, C.T. Surgical Decompression or Corticosteroid Treatment of Indirect
Traumatic Optic Neuropathy: A Randomized Controlled Trial. Ann. Plast. Surg. 2020,84, S80–S83. [CrossRef]
82.
Yu-Wai-Man, P. Traumatic optic neuropathy-Clinical features and management issues. Taiwan J. Ophthalmol.
2015
,5, 3–8.
[CrossRef]
83.
Volpe, N.J.; Levin, L.A. How should patients with indirect traumatic optic neuropathy be treated? J. Neuroophthalmol.
2011
,31,
169–174. [CrossRef] [PubMed]
84. Whitlock, J.R. Posterior parietal cortex. Curr. Biol. 2017,27, R691–R695. [CrossRef] [PubMed]
85.
Caminiti, R.; Cafee, M.V.; Battaglia-Mayer, A.; Crowe, D.A.; Georgopoulos, A.P. Understanding the parietal lobe syndrome from a
neurophysiological and evolutionary perspective. Eur. J. Neurosci. 2010,31, 2320–2340. [CrossRef] [PubMed]
86.
Hadjidimitrakis, K.; Bakola, S.; Wong, Y.T.; Hagan, M.A. Mixed Spatial and Movement Representations in the Primate Posterior
Parietal Cortex. Front. Neural Circuits 2019,13, 15. [CrossRef]
87.
Medendorp, W.P.; Heed, T. State estimation in posterior parietal cortex: Distinct poles of environmental and bodily states. Prog.
Neurobiol. 2019,183, 101691. [CrossRef]
88.
Baltaretu, B.R.; Monaco, S.; Velji-Ibrahim, J.; Luabeya, G.N.; Crawford, J.D. Parietal Cortex Integrates Saccade and Object
Orientation Signals to Update Grasp Plans. J. Neurosci. 2020,40, 4525–4535. [CrossRef]
89.
Dziedzic, T.A.; Bala, A.; Marchel, A. Cortical and Subcortical Anatomy of the Parietal Lobe from the Neurosurgical Perspective.
Front. Neurol. 2021,12, 727055. [CrossRef]
90. Husain, M.; Nachev, P. Space and the parietal cortex. Trends Cogn. Sci. 2001,11, 30–36. [CrossRef]
91.
Sours, C.; Raghavan, P.; Medina, A.E.; Roys, S.; Jiang, L.; Zhuo, J.; Gullapalli, R.P. Structural and Functional Integrity of the
Intraparietal Sulcus in Moderate and Severe Traumatic Brain Injury. J. Neurotrauma 2017,34, 1473–1481. [CrossRef]
92.
Gottlieb, J. From thought to action: The parietal cortex as a bridge between perception, action, and cognition. Neuron
2007
,53,
9–16. [CrossRef]
93.
Breveglieri, R.; Bosco, A.; Borgomaneri, S.; Tessari, A.; Galletti, C.; Avenanti, A.; Fattori, P. Transcranial Magnetic Stimulation Over
the Human Medial Posterior Parietal Cortex Disrupts Depth Encoding During Reach Planning. Cereb. Cortex
2021
,31, 267–280.
[CrossRef] [PubMed]
94.
Marchette, S.A.; Vass, L.K.; Ryan, J.; Epstein, R.A. Anchoring the neural compass: Coding of local spatial reference frames in
human medial parietal lobe. Nat. Neurosci. 2014,17, 1598–1606. [CrossRef] [PubMed]
95.
Ozga-Hess, J.E.; Whirtley, C.; O’Hearn, C.; Pechacek, K.; Vonder Haar, C. Unilateral parietal brain injury increases risk-taking on
a rat gambling task. Exp. Neurol. 2020,327, 113217. [CrossRef] [PubMed]
96.
Tumati, S.; Martens, S.; de Jong, B.M.; Aleman, A. Lateral parietal cortex in the generation of behavior: Implications for apathy.
Prog. Neurobiol. 2019,175, 20–34. [CrossRef] [PubMed]
97.
Moretti, R.; Signori, R. Neural Correlates for Apathy: Frontal-Prefrontal and Parietal Cortical- Subcortical Circuits. Front. Aging
Neurosci. 2016,8, 289. [CrossRef]
98.
Suleiman, A.; Lithgow, B.J.; Anssari, N.; Ashiri, M.; Moussavi, Z.; Mansouri, B. Correlation between Ocular and Vestibular
Abnormalities and Convergence Insufficiency in Post-Concussion Syndrome. Neuroophthalmology 2019,44, 157–167. [CrossRef]
99.
Alvarez, T.L.; Kim, E.H.; Vicci, V.R.; Dhar, S.K.; Biswal, B.B.; Barrett, A.M. Concurrent vision dysfunctions in convergence
insufficiency with traumatic brain injury. Optom. Vis. Sci. 2012,89, 1740–1751. [CrossRef]
100. Jacobson, D.M. The Localizing Value of a Quadrantanopia. Arch Neurol. 1997,54, 401–404. [CrossRef]
101.
Suchoff, I.B.; Kapoor, N.; Ciuffreda, K.J.; Rutner, D.; Han, E.; Craig, S. The frequency of occurrence, types, and characteristics of
visual field defects in acquired brain injury: A retrospective analysis. Optometry 2008,79, 259–265. [CrossRef]
102.
Zhang, X.; Kedar, S.; Lynn, M.J.; Newman, N.J.; Biousse, V. Homonymous hemianopias: Clinical-anatomic correlations in 904
cases. Neurology 2006,66, 906–910. [CrossRef]
103. Monserrate, A.E.; De Jesus, O. Homonymous Superior Quadrantanopia; StatPearls Publishing: Treasure Island, FL, USA, 2022.
104.
Bowers, A.R. Driving with homonymous visual field loss: A review of the literature. Clin. Exp. Optom.
2016
,99, 402–418.
[CrossRef] [PubMed]

Neurol. Int. 2022,14 468
105.
Papageorgiou, E.; Hardiess, G.; Schaeffel, F.; Wiethoelter, H.; Karnath, H.O.; Mallot, H.; Schoenfisch, B.; Schiefer, U. Assessment of
vision-related quality of life in patients with homonymous visual field defects. Graefes Arch. Clin. Exp. Ophthalmol.
2007
,245,
1749–1758. [CrossRef] [PubMed]
106.
Sahraie, A.; Smania, N.; Zihl, J. Use of NeuroEyeCoach
™
to Improve Eye Movement Efficacy in Patients with Homonymous
Visual Field Loss. Biomed. Res. Int. 2016,2016, 5186461. [CrossRef] [PubMed]
107.
Lane, A.R.; Smith, D.T.; Schenk, T. Clinical treatment options for patients with homonymous visual field defects. Clin. Ophthalmol.
2008,2, 93–102. [CrossRef]
108.
Fox, S.M.; Koons, P.; Dang, S.H. Vision Rehabilitation after Traumatic Brain Injury. Phys. Med. Rehabil. Clin. N. Am.
2019
,30,
171–188. [CrossRef]
109. Gilbert, C.D.; Li, W. Top-down influences on visual processing. Nat. Rev. Neurosci. 2013,14, 350–363. [CrossRef] [PubMed]
110.
Yoder, R.M.; Taube, J.S. The vestibular contribution to the head direction signal and navigation. Front. Integr. Neurosci.
2014
,8, 32.
[CrossRef]
111.
Britton, Z.; Arshad, Q. Vestibular and Multi-Sensory Influences Upon Self-Motion Perception and the Consequences for Human
Behavior. Front. Neurol. 2019,10, 63. [CrossRef]
112.
Trofimova, A.; Smith, J.L.; Ahluwalia, V.; Hurtado, J.; Gore, R.K.; Allen, J.W. Alterations in Resting-State Functional Brain
Connectivity and Correlations with Vestibular/Ocular-Motor Screening Measures in Postconcussion Vestibular Dysfunction. J.
Neuroimaging 2021,31, 277–286. [CrossRef]
113.
Skóra, W.; Sta´nczyk, R.; Pajor, A.; Jozefowicz-Korczy´nska, M. Vestibular system dysfunction in patients after mild traumatic brain
injury. Ann. Agric. Environ. Med. 2018,25, 665–668. [CrossRef]
114.
Davies, R.A.; Luxon, L.M. Dizziness following head injury: A neuro-otological study. J. Neurol.
1995
,242, 222–230. [CrossRef]
[PubMed]
115.
Basford, J.R.; Chou, L.S.; Kaufman, K.R.; Brey, R.H.; Walker, A.; Malec, J.F.; Moessner, A.M.; Brown, A.W. An assessment of gait
and balance deficits after traumatic brain injury. Arch. Phys. Med. Rehabil. 2003,84, 343–349. [CrossRef] [PubMed]
116.
Glendon, K.; Desai, A.; Blenkinsop, G.; Belli, A.; Pain, M. Recovery of symptoms, neurocognitive and vestibular-ocular-motor
function and academic ability after sports-related concussion (SRC) in university-aged student-athletes: A systematic review.
Brain Inj. 2022; ahead of print. [CrossRef]
117.
Chamelian, L.; Feinstein, A. Outcome after mild to moderate traumatic brain injury: The role of dizziness. Arch. Phys. Med.
Rehabil. 2004,85, 1662–1666. [CrossRef] [PubMed]
118.
Leddy, J.J.; Haider, M.N.; Noble, J.M.; Rieger, B.; Flanagan, S.; McPherson, J.I.; Shubin-Stein, K.; Saleem, G.T.; Corsaro, L.; Willer, B.
Clinical Assessment of Concussion and Persistent Post-Concussive Symptoms for Neurologists. Curr. Neurol. Neurosci. Rep.
2021
,
21, 70. [CrossRef] [PubMed]
119.
Allen, J.W.; Trofimova, A.; Ahluwalia, V.; Smith, J.L.; Abidi, S.A.; Peters, M.; Rajananda, S.; Hurtado, J.E.; Gore, R.K. Altered
Processing of Complex Visual Stimuli in Patients with Postconcussive Visual Motion Sensitivity. AJNR Am. J. Neuroradiol.
2021
,
42, 930–937. [CrossRef]
120.
Murray, D.A.; Meldrum, D.; Lennon, O. Can vestibular rehabilitation exercises help patients with concussion? A systematic
review of efficacy, prescription and progression patterns. Br. J. Sports Med. 2017,51, 442–451. [CrossRef]
121. Karnath, H.O.; Rorden, C. The anatomy of spatial neglect. Neuropsychologia 2012,50, 1010–1017. [CrossRef]
122.
Marotta, J.J.; McKeeff, T.J.; Behrmann, M. Hemispatial neglect: Its effects on visual perception and visually guided grasping.
Neuropsychologia 2003,41, 1262–1271. [CrossRef]
123.
Smania, N.; Fonte, C.; Picelli, A.; Gandolfi, M.; Varalta, V. Effect of eye patching in rehabilitation of hemispatial neglect. Front.
Hum. Neurosci. 2013,7, 527. [CrossRef]
124.
Rusconi, M.L.; Carelli, L. Long-term efficacy of prism adaptation on spatial neglect: Preliminary results on different spatial
components. Sci. World J. 2012,2012, 618528. [CrossRef]
125.
Mahmood, O.; Rapport, L.J.; Hanks, R.A.; Fichtenberg, N.L. Neuropsychological performance and sleep disturbance following
traumatic brain injury. J. Head Trauma Rehabil. 2004,19, 378–390. [CrossRef] [PubMed]
126.
Mathias, J.L.; Alvaro, P.K. Prevalence of sleep disturbances, disorders, and problems following traumatic brain injury: A
meta-analysis. Sleep Med. 2012,13, 898–905. [CrossRef] [PubMed]
127.
Crichton, T.; Singh, R.; Abosi-Appeadu, K.; Dennis, G. Excessive daytime sleepiness after traumatic brain injury. Brain Inj.
2020
,
34, 1525–1531. [CrossRef] [PubMed]
128.
Ouellet, M.C.; Beaulieu-Bonneau, S.; Morin, C.M. Sleep-wake disturbances after traumatic brain injury. Lancet Neurol.
2015
,14,
746–757. [CrossRef]
129.
Leng, Y.; Byers, A.L.; Barnes, D.E.; Peltz, C.B.; Li, Y.; Yaffe, K. Traumatic Brain Injury and Incidence Risk of Sleep Disorders in
Nearly 200,000 US Veterans. Neurology 2021,96, e1792–e1799. [CrossRef]
130.
Theadom, A.; Rowland, V.; Levack, W.; Starkey, N.; Wilkinson-Meyers, L.; McPherson, K.; TBI Experiences Group. Exploring
the experience of sleep and fatigue in male and female adults over the 2 years following traumatic brain injury: A qualitative
descriptive study. BMJ Open 2016,6, e010453. [CrossRef]
131.
Agtarap, S.D.; Campbell-Sills, L.; Jain, S.; Sun, X.; Dikmen, S.; Levin, H.; McCrea, M.A.; Mukherjee, P.; Nelson, L.D.; Temkin, N.;
et al. TRACK-TBI Investigators Satisfaction with Life after Mild Traumatic Brain Injury: A TRACK-TBI Study. J. Neurotrauma
2021,38, 546–554. [CrossRef]

Neurol. Int. 2022,14 469
132.
Manber, R.; Edinger, J.D.; Gress, J.L.; San Pedro-Salcedo, M.G.; Kuo, T.F.; Kalista, T. Cognitive behavioral therapy for insomnia
enhances depression outcome in patients with comorbid major depressive disorder and insomnia. Sleep
2008
,31, 489–495.
[CrossRef]
133.
Smith, M.T.; Haythornthwaite, J.A. How do sleep disturbance and chronic pain inter-relate? Insights from the longitudinal and
cognitive-behavioral clinical trials literature. Sleep. Med. Rev. 2004,8, 119–132. [CrossRef]
134.
Miller, M.; Williams, R.; Pagulayan, K.; Barber, J.; Ehde, D.M.; Hoffman, J. Correlates of sleep disturbance in Veterans with
traumatic brain injury and chronic pain: A cross-sectional study. Disabil. Health J. 2022,15, 101203. [CrossRef]
135.
Goel, N.; Rao, H.; Durmer, J.S.; Dinges, D.F. Neurocognitive consequences of sleep deprivation. Semin. Neurol.
2009
,29, 320–339.
[CrossRef] [PubMed]
136.
Nakase-Richardson, R.; Sherer, M.; Barnett, S.D.; Yablon, S.A.; Evans, C.C.; Kretzmer, T.; Schwartz, D.J.; Modarres, M. Prospective
evaluation of the nature, course, and impact of acute sleep abnormality after traumatic brain injury. Arch. Phys. Med. Rehabil.
2013,94, 875–882. [CrossRef] [PubMed]
137.
Lowe, A.; Neligan, A.; Greenwood, R. Sleep disturbance and recovery during rehabilitation after traumatic brain injury: A
systematic review. Disabil. Rehabil. 2020,42, 1041–1054. [CrossRef] [PubMed]
138.
Li, S.; Tang, L.; Zhou, J.; Anchouche, S.; Li, D.; Yang, Y.; Liu, Z.; Wu, J.; Hu, J.; Zhou, Y.; et al. Sleep deprivation induces corneal
epithelial progenitor cell over-expansion through disruption of redox homeostasis in the tear film. Stem Cell Rep.
2022
,17,
1105–1119. [CrossRef] [PubMed]
139.
Yang, T.T.; Li, H.; Dong, L.J. Role of glycolysis in retinal vascular endothelium, glia, pigment epithelium, and photoreceptor cells
and as therapeutic targets for related retinal diseases. Int. J. Ophthalmol. 2021,14, 1302–1309. [CrossRef]
140.
Malik, D.M.; Paschos, G.K.; Sehgal, A.; Weljie, A.M. Circadian and Sleep Metabolomics Across Species. J. Mol. Biol.
2020
,432,
3578–3610. [CrossRef]
141.
Quan, S.F.; Gillin, J.C. New definitions of sleep disordered breathing—Not yet a mandate in clinical practice. Sleep
1999
,22, 662.
[CrossRef]
142.
O’Hara, R.; Luzon, A.; Hubbard, J.; Zeitzer, J.M. Sleep apnea, apolipoprotein epsilon 4 allele, and TBI: Mechanism for cognitive
dysfunction and development of dementia. J. Rehabil. Res. Dev. 2009,46, 837–850. [CrossRef]
143.
Coelho, J.; Ferreira, A.; Kuhn, F.; Meireles, A. Globe ruptures: Outcomes and prognostic analysis of severe ocular trauma.
Ophthalmologica, 2022; ahead of print. [CrossRef]
144.
Fujikawa, A.; Mohamed, Y.H.; Kinoshita, H.; Matsumoto, M.; Uematsu, M.; Tsuiki, E.; Suzuma, K.; Kitaoka, T. Visual outcomes
and prognostic factors in open-globe injuries. BMC Ophthalmol. 2018,18, 138. [CrossRef]
145.
Schmidt, G.W.; Broman, A.T.; Hindman, H.B.; Grant, M.P. Vision survival after open globe injury predicted by classification and
regression tree analysis. Ophthalmology 2008,115, 202–209. [CrossRef]
146.
Agrawal, R.; Rao, G.; Naigaonkar, R.; Ou, X.; Desai, S. Prognostic factors for vision outcome after surgical repair of open globe
injuries. Indian J. Ophthalmol. 2011,59, 465–470. [CrossRef] [PubMed]
147.
Bi, H.; Cui, Y.; Li, Y.; Wang, X.; Zhang, J. Clinical characteristics and surgical problems of ruptured globe injury. Curr. Ther. Res.
Clin. Exp. 2013,74, 16–21. [CrossRef] [PubMed]
148.
Vingopoulos, F.; Wang, Y.; Grob, S.; Li, C.; Eliott, D.; Kim, L.A.; Vavvas, D.G.; Miller, J.B. Open Globe Injury with Intraocular
Foreign Body. J. Vitreoretin. Dis. 2021,5, 288–294. [CrossRef]
149.
Patel, S.N.; Langer, P.D.; Zarbin, M.A.; Bhagat, N. Diagnostic value of clinical examination and radiographic imaging in
identification of intraocular foreign bodies in open globe injury. Eur. J. Ophthalmol. 2012,22, 259–268. [CrossRef]
150.
Galor, A.; Davis, J.L.; Flynn, H.W., Jr.; Feuer, W.J.; Dubovy, S.R.; Setlur, V.; Kesen, M.R.; Goldstein, D.A.; Tessler, H.H.;
Ganelis, I.B.; et al.
Sympathetic ophthalmia: Incidence of ocular complications and vision loss in the sympathizing eye. Am. J.
Ophthalmol. 2009,148, 704–710. [CrossRef] [PubMed]
151.
Feng, K.; Hu, Y.T.; Ma, Z. Prognostic indicators for no light perception after open-globe injury: Eye injury vitrectomy study. Am. J.
Ophthalmol. 2011,152, 654–662.e2. [CrossRef]
152.
Heidari, E.; Taheri, N. Surgical treatment of severely traumatized eyes with no light perception. Retina
2010
,30, 294–299.
[CrossRef]
153.
Zhao, X.; Zhao, Q.; Meng, L.; Zhang, W.; Chen, Y. Clinical and imaging features of sympathetic ophthalmia and efficacy of the
current therapy. Acta Ophthalmol. 2022; ahead of print. [CrossRef]
154.
Hunt, A.W.; Mah, K.; Reed, N.; Engel, L.; Keightley, M. Oculomotor-Based Vision Assessment in Mild Traumatic Brain Injury: A
Systematic Review. J. Head Trauma Rehabil. 2016,31, 252–261. [CrossRef]
155.
Sussman, E.S.; Ho, A.L.; Pendharkar, A.V.; Ghajar, J. Clinical evaluation of concussion: The evolving role of oculomotor
assessments. Neurosurg. Focus 2016,40, E7. [CrossRef]
156. Cochrane, G.D.; Christy, J.B.; Almutairi, A.; Busettini, C.; Swanson, M.W.; Weise, K.K. Visuo-oculomotor Function and Reaction
Times in Athletes with and without Concussion. Optom. Vis. Sci. 2019,96, 256–265. [CrossRef]
157.
Pillai, C.; Gittinger, J.W., Jr. Vision Testing in the Evaluation of Concussion. Semin. Ophthalmol.
2017
,32, 144–152. [CrossRef]
[PubMed]
158.
Johnson, C.A.; Wall, M.; Thompson, H.S. A history of perimetry and visual field testing. Optom. Vis. Sci.
2011
,88, E8–E15.
[CrossRef] [PubMed]

Neurol. Int. 2022,14 470
159.
Guskiewicz, K.M.; Register-Mihalik, J.; McCrory, P.; McCrea, M.; Johnston, K.; Makdissi, M.; Dvoˇrák, J.; Davis, G.;
Meeuwisse, W.
Evidence-based approach to revising the SCAT2: Introducing the SCAT3. Br. J. Sports Med.
2013
,47, 289–293. [CrossRef]
[PubMed]
160.
Le, R.K.; Ortega, J.D.; Chrisman, S.; Kontos, A.P.; Buckley, T.A.; Kaminski, T.W.; Meyer, B.P.; Clugston, J.R.; Goldman, J.;
McAllister, T.W.; et al.
King-Devick Sensitivity and Specificity to Concussion in Collegiate Athletes. J. Athl. Train. 2021; ahead of
print. [CrossRef]
161.
Kaufman, M.W.; Su, C.A.; Trivedi, N.N.; Lee, M.K.; Nelson, G.B.; Cupp, S.A.; Voos, J.E. The Current Status of Concussion
Assessment Scales: A Critical Analysis Review. JBJS Rev. 2021,9, e20. [CrossRef]
162.
Laukkanen, H.; Scheiman, M.; Hayes, J.R. Brain Injury Vision Symptom Survey (BIVSS) Questionnaire. Optom. Vis. Sci.
2017
,94,
43–50. [CrossRef]
163. Bigler, E.D. Structural neuroimaging in sport-related concussion. Int. J. Psychophysiol. 2018,132, 105–123. [CrossRef]
164.
Smith, K. Traumatic brain injury: CT scan does not predict outcome of mild traumatic brain injury. Nat. Rev. Neurol.
2012
,8, 474.
[CrossRef]
165. Froment Tilikete, C. How to assess eye movements clinically. Neurol. Sci. 2022,43, 2969–2981. [CrossRef]
166. Yadav, S.; Tandon, R. Comprehensive eye examination: What does it mean? Community Eye Health 2019,32, S1–S4.
167.
Schuett, S.; Heywood, C.A.; Kentridge, R.W.; Zihl, J. The significance of visual information processing in reading: Insights from
hemianopic dyslexia. Neuropsychologia 2008,46, 2445–2462. [CrossRef]
168.
Ciuffreda, K.J.; Ludlam, D.; Thiagarajan, P. Oculomotor diagnostic protocol for the mTBI population. Optom. J. Am. Optom. Assoc.
2011,82, 61–63. [CrossRef] [PubMed]
169.
Rosenfield, M. Computer vision syndrome: A review of ocular causes and potential treatments. Ophthalmic Physiol. Opt.
2011
,31,
502–515. [CrossRef] [PubMed]
170.
Porcar, E.; Pons, A.M.; Lorente, A. Visual and ocular effects from the use of flat-panel displays. Int. J. Ophtalmol.
2016
,9, 881–885.
[CrossRef]
171.
Beaton, M.D.; Hadly, G.; Babul, S. Stakeholder Recommendations to Increase the Accessibility of Online Health Information for
Adults Experiencing Concussion Symptoms. Front. Public Health 2021,8, 557814. [CrossRef]
172.
Callahan, M.L.; Lim, M.M. Sensory Sensitivity in TBI: Implications for Chronic Disability. Curr. Neurol. Neurosci. Rep.
2018
,18, 56.
[CrossRef]
173.
Dyakova, O.; Rångtell, F.H.; Tan, X.; Nordström, K.; Benedict, C. Acute sleep loss induces signs of visual discomfort in young
men. J. Sleep Res. 2019,28, e12837. [CrossRef]
174.
Batuk, I.T.; Batuk, M.O.; Aksoy, S. Evaluation of the postural balance and visual perception in young adults with acute sleep
deprivation. J. Vestib. Res. 2020,30, 383–391. [CrossRef]
175.
Ciuffreda, K.J.; Yadav, N.K.; Ludlam, D.P. Binasal Occlusion (BNO), Visual Motion Sensitivity (VMS), and the Visually-Evoked
Potential (VEP) in mild Traumatic Brain Injury and Traumatic Brain Injury (mTBI/TBI). Brain Sci. 2017,7, 98. [CrossRef]
176.
Yadav, N.K.; Ciuffreda, K.J. Effect of binasal occlusion (BNO) and base-in prisms on the visual-evoked potential (VEP) in mild
traumatic brain injury (mTBI). Brain Inj. 2014,28, 1568–1580. [CrossRef]
177.
Padula, W.V.; Capo-Aponte, J.E.; Padula, W.V.; Singman, E.L.; Jenness, J. The consequence of spatial visual processing dysfunction
caused by traumatic brain injury (TBI). Brain Inj. 2017,31, 589–600. [CrossRef]
178.
Rytter, H.M.; Westenbaek, K.; Henriksen, H.; Christiansen, P.; Humle, F. Specialized interdisciplinary rehabilitation reduces
persistent post-concussive symptoms: A randomized clinical trial. Brain Inj. 2019,33, 266–281. [CrossRef] [PubMed]