MNJ (Malang Neurology Journal) Vol. 9, No.

2, July 2023

http://mnj.ub.ac.id/
DOI: 10.21776/ub.mnj.2023.009.02.13
eISSN: 2442-5001 pISSN: 2407-6724
Accredited by DIKTI Decree No: 21/E/KPT/2018

REVIEW OPEN ACCESS

SLEEP DISTURBANCE AFTER TRAUMATIC BRAIN

INJURY: NEW INSIGHT
Desak Ketut Indrasari Utami1, Faldi Yaputra1

Correspondence: indrasari@unud.ac.id
1Department of Neurology, Faculty of Medicine, Universitas Udayana, Sanglah Hospital, Bali, Indonesia.

Article History: ABSTRACT

Received: April 16, 2023
Accepted: February 24, 2023
Published: July 1, 2023
Cite this as:
Utami DKI, Yaputra F. Sleep
disturbance after traumatic brain
injury: New insight. Malang
Neurology Journal; 2023.9:145-
148. DOI:
http://dx.doi.org/10.21776/ub.mnj
.2023.009.02.13
Disruptions in sleep-wake cycles are particularly prevalent after a Traumatic Brain Injury (TBI). Sleep
disruptions may occur as a main impact of brain damage or as a result of other neuropsychiatric sequelae
of TBI, such as anxiety disorder, depressive disorders, substance abuse, chronic pain, and/or medication
consumption. Chronic discomfort (headache and broad pain, presumably of central origin) and/or sleep
difficulties (insomnia, disturbed breathing, periodic limb movements) occur in about one in five people
with TBI. Disruptions in sleep-wake cycles linked with TBI need therapy. Although data specific to
individuals with TBI is currently limited, cognitive-behavioral treatment and medication may be
beneficial in alleviating sleep-wake problems in people who have sustained a TBI. This article aims to
raise awareness of sleep disturbance after TBI to enhance diagnosis, assessment, and therapy and
disclose new research opportunities.
Keywords: Sleep disturbance, traumatic brain injury, hypersomnia, insomnia

Introduction prevalent sleep problem shortly after injury, and it is

Fatigue and sleep problems are two typical debilitating
symptoms that impair healing and interfere with
rehabilitation in individuals who have survived traumatic
brain injury (TBI). Despite their prevalence, reliable data on
their occurrence, etiology, and therapy in the TBI literature
are sparse. Sleep is poorly understood in the initial postacute
phase following brain damage, despite the fact that
interrupted sleep is frequently seen by clinicians. After
traumatic brain injury, sleep disruption has a poor correlation
with the first Glasgow Coma Scale (GCS). However,
patients spent substantially longer in hospital, indicating that
sleep disruption may be an indicator for more serious
injuries.1
Sleep disturbances are frequently experienced following a
TBI, and they may contribute to or exacerbate a range of co-
morbid conditions, including depression, anxiety, irritability,
exhaustion, cognitive deficiencies, pain, and functional
impairments. After a TBI, 50% of patients experienced some
sort of sleep disruption and 25%–29% had a documented
sleep disorder (insomnia, hypersomnia, or apnea) much
higher rates than those observed in the general population.
Additionally, they were two to four times as likely to have
difficulty maintaining sleep quality and efficiency,
nightmares, excessive drowsiness, early awakenings, and
sleep walking.2
Sleep and TBI
Sleep is thought to be crucial for TBI rehabilitation. Sleep
deprivation may result in cognitive impairments and
decreased general function.3 Sleep fragmentation is the most
associated with an increase in night terrors at later time
periods. Additionally, although it has long been established
that TBI may result in sleep-wake disruptions and increased
daytime drowsiness, the particular processes behind these
alterations remain unknown.4
Sleep disruption following TBI is objectively defined as
frequent overnight awakenings, increased proportions of
stage 1 and stage 2 sleep, reduced percentage of rapid eye
movement (REM) sleep, and shorter REM sleep latencies.5
It is shown that 7–10% of people who initially experience
insomnia have a disruption in their circadian rhythm;
nevertheless, this disruption may go unrecognized by both
patients and physicians. Periodic interruptions of daily
physiological cycles are related with changes in the patterns
of melatonin secretion as well as body temperature, which
are known as circadian rhythm sleep disorders. TBI patients
have been shown to have abnormal circadian rhythms,
including alterations in heart rate, body temperature, blood
pressure, sleep-wake cycles, and hormone cycles.
Additionally, circadian disruptions might impair
neurogenesis, a vital component of TBI recovery.6
Insomnia is more prevalent in mild TBI patients than in
severe TBI patients. Repeated mild TBI significantly
increases the risk.7
Pathophysiology of Sleep Disturbance
after TBI
TBI-related neuropsychiatric problems such as depression,
anxiety, drug abuse, chronic pain, and/or medication use may

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all have an influence on sleep, whether as a direct result of
brain injury or as a secondary consequence (figure 1).8
Primary and secondary brain damage are two types of
traumatic brain injury. The term primary injury refers to the
irreversible structural damage that occurs following a
trauma. Secondary damage is a term that refers to a
reversible cascade of cellular events that occur after initial
brain injury. These mechanisms include glutamate release,
glial activation, the formation of free radicals, and brain
ischemia, all of which result in structural, chemical, and
genetic alterations that disturb sleep.9
Figure 1. TBI and Sleep disturbance (private property).
Traumatic brain injury is most often caused by coup–
countercoup, which frequently happens towards the base of
the skull in regions with bony prominences, frequently
injured the inferior frontal regions, anterior temporal and, as
well as the base of forebrain. Due to the fact that the basal
forebrain is involved in sleep initiation, damage to this area
may result in insomnia symptoms.10 As a result, sleep
disruption is common following TBI, as the sleep-wake
cycle related to some areas in the brain, including the
brainstem, basal forebrain, frontal-subcortical system and
hypothalamus.
Table 1. Acute and Chronic Sleep Disturbances After TBI11
Time Diagnosis
Insomnia
Insomnia related to post traumatic mood
disturbance
Acute
Insomnia related to post traumatic headache
disorder
Hypersomnia
Insomnia
Circadian rhythm disorder
Chronic Obstructive sleep apnea
Narcolepsy
Chronic traumatic encephalopathy
Some of the frequent sleep disorders that occur with TBI
include insomnia, hypersomnia, sleep-wake cycle
irregularities, and parasomnia. Sleep disturbance may arise
as a distinct characteristic or as a sign of various mental,
medical, or neurological disorders. It is possible for TBI
patients to suffer a wide range of sleep disruptions at various
times after the injury.It is possible for TBI patients to suffer
a wide range of sleep disruptions at various times after the
injury (Table 1).
MNJ (Malang Neurology Journal) Vol. 9, No. 2, July 2023
Insomnia
Insomnia is defined as troubles sleeping and/or staying
asleep. Patients usually complains of difficulties falling
asleep, fragmentation of sleep, and/or waking up too early in
the morning, resulting in exhaustion, sleepiness, and poor
mood and low performance throughout the day. Insomnia
affects between 30% and 60% of patients who have had a
TBI, irrespectively of severity; however, it appears to be
more frequent in mild TBIs. Frequent TBIs may raise the risk
of acquiring insomnia, as well as cognitive impairment in
general.12
Acute traumatic brain injury (TBI) causes insomnia as a
result of damage to the frontobasal and anterior temporal
areas of the brain, as well as generalized anxiety,
psychological consequences of the event, and increased
sensitivity to light and noise. A detailed history, the use of
sleep diaries, and actigraphy may all aid in the determination
of the diagnosis. There are many treatments available,
including cognitive behavioral therapy, sleep hygiene,
treatment of psychiatric comorbidities, and medication, such
as non-benzodiazepine hypnotics, trazodone, suvorexant,
and melatonin.9
Hypersomnia
Hypersomnia, often known as excessive daytime sleepiness
(EDD), is a sleep disorder characterized by recurrent bouts
of excessive daytime sleepiness or involuntary sleepiness at
unexpected times. Drowsiness during sedentary activity is
what distinguishes hypersomnia from tiredness, which is
more typically seen while exerting physical effort. TBI
patients tend to underestimate their symptoms of daytime
sleepiness in the same way as they underestimate their
symptoms of insomnia. A decrease of hypocretin-1 levels in
CNS might be a cause. In the initial days after TBI,
hypocretin-1 levels in the CSF were found to be low in 25 of
27 individuals.13,14
MSLT has showed that almost half of individuals with severe
TBI exhibit pathological sleepiness with latency periods of
at least 10 minutes. The pathogenesis of posttraumatic
hypersomnia is most likely connected to direct injury to the
tuberomammillary histaminergic wakefulness neurons,
which drop by around 40% after a severe traumatic brain
injury.15
In order to properly diagnose hypersomnia, objective sleep
tests must be done to demonstrate the presence of
pathological sleepiness throughout the night. The test is
referred to as the multiple sleep latency test (MSLT).
Treatment for this disorder may include the use of stimulant
medications such as modafinil, methylphenidate, or
amphetamines.12
Circadian Rhythm Disorder
Disturbances of the circadian rhythm after a traumatic brain
injury are sometimes confused for insomnia. TBI-induced
hypothalamic and suprachiasmatic nucleus damage is
thought to be the primary cause of circadian rhythm
disruption. In addition, the normal 24-hour cycle of
biological cycles, such as body temperature and melatonin
release is disrupted.9

Circadian sleep disorder include abnormal sleep-wake cycles
and, more typically, delayed sleep phase syndrome. It is
indeed crucial to know the difference between insomnia and
circadian rhythm disorder since the two conditions need
different approaches to therapy. When individuals with this
disease are able to fall asleep, both the length and pattern of
their sleep are normal.1 It is preferable to use melatonin or
strong light treatment rather than prescribing hypnotics. 9
There are two common abnormalities in the circadian rhythm
of sleep that might be unnoticed following a traumatic brain
injury: delayed sleep phase syndrome and irregular sleep-
wake rhythm. As a result, insomnia may be misdiagnosed
when a patient complains of difficulties getting to sleep,
staying asleep, and problems waking up at their typical
time.16
Treatment
It is critical to establish a diagnosis. Other comorbid
psychological and medical illnesses must be recognized and
treated since they may be contributing to or increasing the
sleep disturbance. Pharmacological therapies are used in
conjunction with a variety of nonpharmacological methods,
including sleep hygiene practices, phototherapy,
chronotherapy, and psychotherapy.
Pharmacological
Benzodiazepine Sedative-Hypnotics
GABA (gamma-aminobutyric acid) receptor activation by
benzodiazepines results in improved sleep, which has been
shown to be both subjective and objectively
effective. Theoretically, benzodiazepines might hinder
neuronal recovery in patients with brain damage, thus they
should be administered with care. Lorazepam (0.5–2.0 mg),
temazepam (7.5–30 mg), and clonazepam (0.25–2.0 mg) are
among the benzodiazepines routinely used at bedtimes as
hypnotics. The most common use is to treat short-term
insomnia or temporary insomnia. As a general rule,
benzodiazepines should not be administered for more than
three or four days, however this may not always be possible
in clinical practice.1
Nonbenzodiazepine Sedative-Hypnotics
Since nonbenzodiazepines operate only on the type 1
benzodiazepine receptor complex, they have a lower risk of
producing cognitive adverse effects. Additionally, they have
short half-lifes and are less prone to produce sleepiness
throughout the day. Nausea anxiety, and dysphoric
responses are all common adverse effects; anterograde
amnesia and rebound insomnia have also been
recorded. Zaleplon (5–10 mg at bedtime) and Zolpidem (5–
10 mg at bedtime) are both nonbenzodiazepines that are
often used to treat temporary insomnia.1
Modafinil and Armodafinil
The American Academy of Sleep Medicine (AASM)
suggests these two medications for the treatment of
hypersomnia related to traumatic brain injury.17 Taking 100-
200 mg/day of modafinil in the morning has been shown to
be both safe and effective for improving sleepiness. Only
half of the recommended dose should be given to patients
with liver disease because there is risk of liver toxicity.18 The
MNJ (Malang Neurology Journal) Vol. 9, No. 2, July 2023
Page 147 of 4
most prevalent complaint from patients was a headache.
Between baseline and final visit, patients receiving 250 mg
armodafinil, the R-enantiomer of modafinil, saw a
substantial reduction in sleep latency compared to
placebo.18,19
Melatonin
The pineal gland produces melatonin, a hormone that
regulates sleep and wake cycles. Melatonin levels are lower
in individuals with TBI compared to their healthy
counterparts, suggesting that TBI interferes with the
melatonin pathway, according to previous study.20
Melatonin has also been shown to lessen symptoms of
anxiety and tiredness in individuals, as well as boost their
perceptions of their own vitality and cognitive abilities.21
Melatonin is a serotonin metabolite. Melatonin synthesis is
enhanced in the dark, whereas its secretion is suppressed in
the light. It is critical for maintaining the biological rhythm
of the body and for coordinating the sleep-wake cycle with
the surroundings. The suprachiasmatic nucleus, which
regulates circadian rhythm, contains several melatonin
receptors, indicating the hormone's importance in
maintaining the body's internal clock.1
The MT1 and MT2 receptors in suprachiasmatic nucleus, are
activated by the melatonin agonist (Ramelteon). T he Food
and Drug Administration has authorized Ramelteon to
be used in the treatment of insomnia characterized by
problems in falling asleep.5 Ramelteon works by altering
sleep mechanisms in suprachiasmatic nucleus.1
Non-pharmacological
Sleep Hygiene and Behavioural Therapy
Noise and disruptions, particularly in a hospital, should be
taken into consideration. To enable patients to sleep through
the night, it is critical that the number of blood draws and the
timing of vital sign checks be kept to a minimum. Educating
patients about proper sleeping habits is critical while they are
rehabilitating at home. Keeping a sleep diary and
establishing a daily regimen might be helpful. Late afternoon
is the ideal time to avoid caffeinated beverages, such as tea,
coffee, and soda. When it comes to nighttime routines, it's
best to avoid using television, tablets, or smartphones in the
bedroom. If you've been awake for more than 20 minutes, it's
time to get out of bed and do something calming like
listening to music or reading a book. Restriction of the
amount of time spent in bed is a key component of sleep
restriction treatment. The goal of this treatment is to enhance
the desire to sleep, improve the quality of sleep, and reduce
the amount of time spent awake throughout the night. 18
CBT for insomnia (CBTi) is regarded as the first-line
treatment for insomnia management.22 Aims at changing
sleep-related beliefs and attitudes by identifying and
correcting their root causes. It has been shown using
objective sleep measurements such as actigraphy and
polysomnography that it enhances total sleep duration and
lowers sleep–onset latency, and that it is superior to
pharmacological treatment.1
Light therapy
Stimulant and antidepressant effects have both been found in
the utilization of certain wavelengths of ocular light
exposure. Neuroendocrine, neurobehavioral, and circadian
Page 148 of 4
responses have been shown to be stimulated by this therapy.
Non-image forming photoreceptors apart from rods and
cones influence the brain's response to light.
Studies have shown that exposure to blue or blue-enriched
light improves alertness and mood the most. As a
consequence, sleep quality may be improved by increasing
sleep duration and lowering nocturnal awakenings.23
Treatment with blue light 45 minutes/day for four weeks
resulted in decreased daytime sleepiness and fatigue, with a
return to baseline after treatment cessation.24
Conclusion
Insomnia, hypersomnia, sleep-wake cycle irregularities, and
parasomnia are a few of the most common sleep disorders
associated with TBI. Sleep disturbances may manifest as a
unique trait or as a symptom of various mental, medical, or
neurological conditions. Patients with TBI may experience a
variety of sleep disturbances at different points after the
injury.
Acknowledgement
None.
Conflict of Interest
None.
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