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Jurnal Reading Cedera Kepala Traumatik

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JURNAL
Neuropsychiatric Disease and Treatment 2016:12 339–348
Cedera Kepala Traumatik Pencetus Gangguan Tidur
Mari Viola-Saltzman dan Camelia Musleh
Abstrak : Gangguan tidur sering dijumpai pada kasus pasca cedera otak traumatis,
yang mempengaruhi 30% -70% orang, dan sering terjadi setelah cedera kepala ringan.
Insomnia, kelelahan, dan mengantuk adalah keluhan tidur yang paling sering
ditemukan setelah cedera otak traumatis. Sleep apnea, narkolepsi, gangguan gerakan
anggota badan periodik, dan parasomnia juga dapat terjadi setelah cedera kepala.
Selain itu, depresi, Gangguan Cemas, dan nyeri adalah komorbiditas cedera otak yang
umum dengan pengaruh signifikan pada kualitas tidur. Dua jenis cedera otak
traumatis yang berdampak negatif pada tidur adalah cedera akselerasi / deselerasi
yang menyebabkan kerusakan otak dan cedera kontak yang menyebabkan kerusakan
otak fokal. Polysomnography, multiple latency testing, dan / atau actigraphy dapat
digunakan untuk mendiagnosis gangguan tidur setelah cedera kepala. Bergantung
pada gangguan tersebut, pengobatan mungkin mencakup penggunaan obat-obatan,
positive airway pressure, dan / atau modifikasi perilaku. Sayangnya, penanganan
gangguan tidur yang terkait dengan cedera otak traumatis mungkin tidak
memperbaiki fungsi neuropsikologis atau kantuk.
Kata kunci: Cedera otak traumatis, insomnia, hipersomnia, sleep apnea, gangguan
gerakan anggota badan periodik, kelelahan.
Pendahuluan
Gangguan tidur sering dijumpai pada kasus pasca cedera otak traumatis, yang
memengaruhi 30% -70% orang, dan sering terjadi setelah cedera kepala ringan.1-3
Cedera otak traumatis adalah penyebab kecacatan dan kematian yang signifikan di
seluruh dunia. Glasgow Coma Scale mengklasifikasikan cedera otak traumatis
menjadi ringan, sedang, atau berat (ringan = 13-15, sedang = 9-12, berat = 8 dari 15).4
Cedera otak dapat menyebabkan gangguan sensori, motor, kognitif, dan emosional.
Bahkan cedera otak traumatik ringan pun bisa dikaitkan dengan pusing, sakit kepala,
mual / muntah, gangguan keseimbangan dan koordinasi, perubahan penglihatan,
tinitus, perubahan mood dan ingatan, kesulitan dengan memori dan perhatian,
kelelahan, dan / atau gangguan tidur. Hubungan antara cedera kepala dan perubahan
kesadaran dan perubahan kognitif telah dijelaskan dengan baik, namun hubungan
antara trauma kepala dan gangguan tidur belum diteliti secara luas.5
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Epidemiologi dan faktor risiko
Cedera otak traumatis paling sering disebabkan oleh terjatuh (28%),
kecelakaan kendaraan bermotor (20%), hantaman ke benda keras (19%), dan tindakan
kekerasan (11%).6 Luka ini sering terkait dengan cedera saat berolahraga, kecelakaan
konstruksi atau industri, dan kekerasan dalam rumah tangga. Ada kecemasan yang
muncul akan cedera otak traumatis di dalam kalangan militer yang dikerahkan di
medan pertempuran. Di antara militer AS yang bertugas di luar negeri, 11% -23%
menderita cedera otak traumatis ringan, seringkali dari ledakan Improvised Explosive
Device (IED).7
Angka prevalensi yang tepat dari gangguan tidur post-traumatic spesifik tidak
diketahui dengan baik. Baumann et al menemukan bahwa tiga dari empat pasien yang
awalnya dirawat di rumah sakit karena cedera otak traumatik mengalami gangguan
tidur pada 6 bulan pasca-operasi. Mayoritas pasien ini memiliki gejala hipersomnia
atau kelelahan, sementara insomnia hanya ada sekitar 5% dari total pasien tersebut.8
Namun, penulis lain telah mengidentifikasi prevalensi insomnia yang lebih tinggi
setelah cedera kepala. Dalam sebuah penelitian yang meneliti 60 pasien dengan
keluhan terkait tidur 3-24 bulan setelah cedera otak traumatis (tingkat keparahan
cedera otak traumatis adalah 40% ringan, 20% sedang, dan 40% berat), 25% peserta
mengeluhkan insomnia.9
Pada anak-anak juga dilaporkan terdapat masalah tidur setelah mengalami
cedera otak traumatis. Seratus enam belas anak yang dirawat di rumah sakit karena
cedera otak traumatis ringan segera dievaluasi, dan 39% - 67% populasi melaporkan
kelelahan, masalah dengan onset tidur, kantuk, dan / atau tidur lebih atau kurang dari
biasanya. Pada kunjungan tindak lanjut (2-3 minggu setelah cedera), gejala yang
berhubungan dengan tidur meningkat namun bertahan 22% -38%.10 Dalam sebuah
penelitian besar terhadap 681 anak-anak yang menderita cedera otak ringan sampai
berat, 14,7% melaporkan masalah tidur pada follow-up 1 bulan. Persentase ini
berkurang menjadi 10,7% pada masa follow-up 4 bulan dan tidak ada pasien yang
melaporkan masalah tidur pada follow-up 10 bulan.11 Akhirnya, dalam penelitian
besar lain terhadap 729 anak-anak dengan cedera otak ringan sampai berat
dibandingkan dengan 197 pasien Dengan cedera ortopedi, kelompok cedera otak
traumatis mengalami durasi yang lebih lama dan tingkat keparahan gangguan tidur
yang lebih tinggi pada usia 3, 12, dan 24 bulan.12
Hou et al mempelajari 98 pasien cedera otak post-traumatic untuk
menyelidiki faktor risiko yang terkait dengan perkembangan gangguan tidur. Faktor
risiko gangguan tidur setelah cedera otak traumatis termasuk tingkat keparahan
cedera kepala (yang diukur dengan Glasgow Coma Scale), tahun-tahun pendidikan
yang lebih rendah, dan adanya gejala residual (yaitu, sakit kepala dan / atau pusing).
Baik hilangnya kesadaran maupun penyebab luka berkorelasi dengan perkembangan
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gangguan tidur. Kehadiran sakit kepala residual, pusing, cemas, dan / atau depresi
secara independen terkait dengan perkembangan insomnia. Nilai Glasgow Coma
Scale secara independen terkait dengan hipersomnia.13
Patofisiologi
Cedera otak traumatis ditandai sebagai cedera otak primer atau sekunder.
Cedera otak primer mengacu pada kerusakan struktural yang tercipta pada saat
dampak dari kontak, percepatan-perlambatan, dan / atau gaya rotasi. Cedera otak
sekunder mengacu pada kerusakan yang diderita dari proses seluler berikutnya yang
terjadi akibat cedera primer (yaitu hipoksia dan / atau tekanan intrakranial yang
meningkat).14
Kekuatan tumbukan yang terjadi di lokasi cedera dapat menyebabkan cedera
fokal atau difus. Cedera fokal meliputi kontusi kontak, perdarahan subdural, epidural,
dan / atau intraparenkimal. Cedera yang difus seringkali disebabkan oleh percepatan
atau peralambatan yang dapat menyebabkan pergeseran dan cedera aksonal yang
meluas di otak.14 Lokasi cedera di daerah otak yang mengatur tidur menyebabkan
gejala tidur tertentu. Hanya sedikit studi yang membuktikan korelasi tersebut secara
klinis; Namun, pada sejumlah penelitan yang ada menunjukkan beberapa korelasi.
Misalnya, hipersomnia dapat terjadi bila area yang melibatkan penggala kesadaran
terluka. Daerah ini termasuk pons rostral, bagian caudal dari otak tengah, dan
thalamus.15 Faktanya, cedera kepala tertutup diketahui dapat menyebabkan gaya
"geser" sepanjang jalur serat utama yang menyebabkan perdarahan - perdarahan kecil
di daerah ini.16 Rasa kantuk dan serangan tidur juga sering dikaitkan dengan lesi pada
saraf spinal cervical, yang mungkin diakibatkan gangguan pernafasan saat tidur.17
Menariknya, dalam sebuah penelitian yang meneliti pasien trauma kepala dengan
hipersomnia, pernapasan yang tidak teratur ditemukan pada semua pasien whiplash
dan diperkirakan telah terjadi pasca trauma.18 Dalam cedera kepala, ada luka coup di
lokasi otak yang terkena dampak dan cedera contrecoup di area otak yang berlawanan
dengan lokasi awal cedera. Sebuah cedera contrecoup biasanya terjadi di dasar
tengkorak.19,20 Jenis cedera ini terjadi di daerah tulang yang tidak rata (terutama di
penonjolan os sphenoid), dengan kerusakan selanjutnya pada daerah anterior
temporal dan frontal inferior,19,20 termasuk daerah basal otak depan, yang terlibat
dalam inisiasi tidur. Oleh karena itu, luka di daerah ini dapat menyebabkan gejala
insomnia.21 Gangguan tidur-bangun setelah cedera otak traumatik ringan dikaitkan
dengan panjang tentorial yang lebih panjang dan sudut tentorial yang lebih datar
(sudut yang terbentuk antara tentorium dan garis melintang melalui foramen
magnum) dibandingkan dengan pasien dengan cedera otak traumatik ringan tanpa
gangguan tidur-bangun. Lama waktu untuk pemulihan berkorelasi langsung dengan
panjang tentorial dan secara tidak langsung berkorelasi dengan sudut tentorial.
Penulis mendalilkan bahwa pada cedera otak ringan, dampak langsung yang
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melibatkan tentorium dan kelenjar pineal dapat menyebabkan terganggunya
homeostasis melatonin dan gangguan bangun tidur.22
Cedera otak traumatis dapat mengganggu nukleus suprachiasmatika. Hal ini dapat
menyebabkan gangguan ritme sirkadian dan, selanjutnya dapat menyebabkan
gangguan kombinasi antara hipersomnia dan insomnia. Sebuah pembalikan total dari
ritme sirkadian telah ditemukan dan diteliti.23 Dalam satu kasus, seorang pria berusia
20 tahun menderita cedera otak ringan sampai sedang dan luka di mata yang tembus
setelah ledakan IED. Dia ditemukan memiliki ritme sirkadian yang berjalan kacau
dan berhasil diobati dengan melatonin malam.24 Studi lain tentang 23 pasien cedera
otak traumatis ditemukan tingkat produksi melatonin malam yang lebih rendah
dibandingkan dengan kontrol yang sesuai dengan usia dan jenis kelamin.25 Cedera
Kepala traumatis juga telah terbukti dikaitkan dengan perubahan pada irama sirkadian
yang berhubungan dengan axis hipotalamus-hipofisis-adrenal.
Tingkat cairan serebro spinal hipokretin-1 yang rendah dapat dihubungkan
dengan narkolepsi dengan cataplexi tetapi tidak dengan jenis hipersomnia sentral
lainnya.27 Misalnya, kadar hypocretin-1 biasanya normal pada hipersomnia idiopatik.
Tingkat hipokretin-1 rendah (110 pg / mL) atau menengah (110-200 pg / mL)
ditemukan pada sejumlah orang dengan lesi neurologis atau penyakit yang
mempengaruhi hipotalamus; beberapa pasien ini menunjukkan rasa kantuk dan
cataplexy.28 Pasien cedera otak traumatis sedang-sampai-berat biasanya ditemukan
memiliki tingkat hipokretin-1 rendah atau sedang pada fase akut cedera, namun
tingkat ini cenderung menormalkan (menjadi .200 pg / mL) 6 bulan pasca trauma.8
Rodrigues dan Silva menerbitkan sebuah kasus pasien yang mengalami
pergerakan tubuh agresif selama fase REM (Rapid Eye Movement) dan gerakan
ekstremitas periodik menyusul cedera otak traumatis yang dialami. Latensi tidur
pendek terlihat pada beberapa uji latensi tidur. Penulis mendalilkan bahwa cedera
kepala pasien ini dikaitkan dengan perubahan jalur dopaminergik dan menyarankan
kemungkinan keterlibatan hipotalamus hipokretin dalam patofisiologinya.29
Gambaran klinis dan diagnosis
Trauma kepala dapat menyebabkan gangguan tidur yang signifikan, lebih
sering pada mereka yang menderita cedera kepala ringan dibandingkan dengan cedera
kepala yang lebih parah. Mahmood et al meneliti 87 pasien dengan cedera otak
traumatik ringan sampai berat dan menemukan bahwa orang dengan cedera ringan
memenuhi kriteria gangguan tidur lebih sering daripada mereka yang cedera sedang
atau berat. Salah satu alasannya adalah bahwa pasien dengan cedera otak traumatis
yang lebih parah mungkin melaporkan lebih sedikit gangguan tidur karena mereka
kurang menyadari masalah tidur mereka. Selanjutnya, pasien dengan cedera otak
traumatis ringan kemungkinan akan menyelesaikan proses rehabilitasi lebih cepat
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daripada mereka yang menderita cedera otak traumatis yang lebih parah dan dengan
demikian menghadapi tekanan yang lebih dekat untuk bergabung kembali ke dalam
masyarakat. Faktor psikososial ini dapat menyebabkan peningkatan pelaporan
gangguan tidur pada populasi ini. Akhirnya, perbedaan organik dalam kerusakan
neurologis yang terlihat pada cedera otak traumatis ringan dan parah dapat
menyebabkan gangguan tidur yang berbeda.30,31 Lebih dari itu, umum bagi pasien
post-traumatic untuk mengeluh sakit kepala awal yang dapat menyebabkan rasa sakit
terus-menerus dan meluas atau nyeri terpusat. yang dapat memiliki efek pada kualitas
tidur.32 Aktivitas beta dan gamma Electroencephalogram (EEG) ditemukan dominan
pada semua tahap tidur di daerah frontal, sentral, dan oksipital pada pasien posttraumatic dengan rasa sakit.33
Insomnia
Salah satu pola umum yang mengikuti cedera kepala biasanya melibatkan
masalah saat memulai dan mempertahankan tidur, dengan atau tanpa rasa kantuk
pada siang hari. Dalam sebuah penelitian terhadap 452 pasien dengan cedera otak
traumatis, 50% menunjukkan gejala insomnia.34 Pada beberapa pasien, insomnia
adalah manifestasi dari gangguan tidur irama sirkadian, biasanya gangguan
penundaan fase bangun-tidur atau gangguan irama tidur-bangun yang tidak teratur.35
Di antara personil militer laki-laki, beberapa cedera otak ditemukan menyebabkan
peningkatan risiko insomnia.36 Veteran dengan gangguan PTSD (Post Traumatic
Stress Disorder) dan cedera otak ringan mungkin terganggu oleh mimpi buruk.37
Mantan pasukan AS yang terlibat dalam Operasi Enduring Freedom (Afghanistan)
dan Operasi Iraqi Freedom (Irak), mengeluhkan insomnia yang terkait dengan cedera
otak traumatik ringan dan PTSD, secara subjektif ditemukan lebih mengantuk
dibandingkan veteran dengan insomnia karena PTSD saja.38 Namun, resolusi dari
sakit kepala dan defisit neurologis lainnya pada veteran berkorelasi dengan perbaikan
gejala PTSD dan rasa kantuk di siang hari.39
Hipersomnia
Hipersomnia dapat terjadi setelah cedera kepala. Jika hipersomnia hadir
paling tidak selama 3 bulan, multiple latency sleep test membuktikan latensi tidur
rata-rata 8 menit atau kurang, dan tidak ada penyebab lain yang jelas (yaitu, gangguan
tidur, gangguan kejiwaan, dan / atau pengobatan lainnya), maka International
Classification of Sleep Disorders (edisi ketiga) yang diterbitkan oleh American
Academy of Sleep Medicine mengklasifikasikan kondisi ini sebagai "hipersomnia
karena gangguan medis".40 Jika hipersomnia post-traumatic dikaitkan dengan dua
atau lebih onset tidur yang cepat di fase REM pada multiple latency sleep test,
diagnosisnya adalah "narkolepsi tipe 1 atau tipe 2 karena kondisi medis".
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Kelainan tidur lainnya juga terlihat pada pasien yang telah mengalami cedera
kepala dan mengeluhkan hipersomnia. Masel et al meneliti total 71 pasien cedera
kepala dalam program perawatan residensial, semua tanpa riwayat gangguan tidur
atau hipersomnia sebelumnya.41 Di antara 33 pasien hipersomnolent (46,5%), empat
pasien memiliki obstructive sleep apnea, tujuh pasien memiliki gangguan gerak
ekstremitas secara periodik, dan satu pasien menderita narkolepsi (selain gangguan
gerak ekstremitas secara periodik). Pasien yang tersisa diberi diagnosis "posttraumatic hipersomnia". Guilleminault et al mempelajari 184 pasien cedera otak
traumatis dan menemukan bahwa mayoritas pasien memiliki rasa kantuk yang
obyektif dan hanya 17% pasien memiliki latensi tidur rata-rata normal (lebih dari 10
menit) pada multiple latency sleep test. Pernapasan yang tidak teratur (terutama
obstructive sleep apnea) ditemukan pada 32% pasien dan 16 pasien whiplash
didiagnosis dengan pernapasan yang tidak teratur. Selain itu, rasa sakit merupakan
penyebab gangguan tidur nokturnal yang signifikan dan gangguan pada siang hari.18
Castriotta et al secara prospektif mengikuti 87 orang dewasa setidaknya selama 3
bulan setelah cedera otak traumatis. Semua subjek diperiksa dengan
polysomnography dan multiple latency testing. Empat puluh enam persen pasien
memiliki hasil penelitian yang abnormal. Obstructive sleep apnea didiagnosis pada
23% pasien, 11% ditemukan menderita hipersomnia post-traumatic, 7% memiliki
pergerakan anggota tubuh secara periodik dalam tidur, dan 6% memenuhi kriteria
narkolepsi.42
Meskipun jarang terjadi, cedera otak traumatis juga telah dilaporkan memicu
kasus sindrom Kleine-Levin, gangguan yang melibatkan episode berulang
hipersomnia dan sering disertai gangguan kognitif atau perilaku, hiperseksual, dan /
atau makan kompulsif.43
Parasomnia, Kelelahan, dan Gangguan Mood.
Cedera otak traumatis kadang-kadang memicu parasomnia, termasuk
sleepwalking, sleep terror, dan gangguan pola tidur pada REM.49 Kadang kala,
kombinasi dari parasomnia pada REM dan non-REM, menghasilkan gangguan
parasomnia yang tumpang tindih. Kelelahan juga terkait dengan cedera otak traumatis
dengan efek buruk pada kualitas hidup. Di antara 119 pasien yang diteliti setidaknya
selama 1 tahun setelah menderita cedera otak traumatis, hingga 53% melaporkan
kelelahan. Hal ini lebih sering dilaporkan pada wanita atau orang dengan gejala
depresi, nyeri, atau gangguan tidur.45 Dalam studi lain terhadap pasien yang
menderita cedera otak traumatik sedang-sampai-berat, 16% -32% dan 21% -34%
(masing-masing pada 1 dan 2 tahun) melaporkan tingkat kelelahan yang signifikan.46
Kelainan mood juga bisa terjadi setelah cedera otak traumatis. Pasien dengan
cedera otak ringan dan keluhan tidur lebih cenderung melaporkan perasaan tertekan
pada 10 hari dan 6 minggu setelah cedera mereka.47 Dalam sebuah studi besar tentang
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personil militer, skrining positif untuk cedera otak traumatis dan masalah tidur
ditemukan sebagai indikator awal risiko untuk mengembangkan gangguan stres dan /
atau depresi post-traumatic.48 Gangguan cemas onset dini setelah cedera otak
traumatis adalah prediktor yang signifikan terhadap gangguan tidur, walaupun
hubungan sebab akibatnya tidak jelas.4
Diagnosa
Riwayat pasien adalah aspek penting dari langkah kerja untuk 1)
mendokumentasikan hubungan trauma dengan gangguan tidur, 2) menyingkirkan
gangguan tidur yang sudah ada sebelumnya, dan 3) menilai perkembangan gejala
setelah cedera kepala. Pemeriksaan fisik juga penting (Gambar 1). Polisomnografi
harus dipertimbangkan jika hipersomnia dan / atau gejala apnea tidur lainnya ada.
Kasus hipersomnia post-traumatic menunjukkan peningkatan durasi tidur dengan
atau tanpa perubahan pada tindakan tidur lainnya.50 Pasien dengan insomnia posttraumatic telah menunjukkan latensi tidur yang lama, efisiensi tidur rendah,
penurunan durasi tidur malam hari, dan peningkatan pada stadium-1 tidur.34,51 Pasien
dengan cedera otak traumatik sedang-ke-parah menunjukkan peningkatan tidur fase
slow-wave, mengurangi tidur fase REM, dan terbangun nokturnal yang lebih sering
dibandingkan dengan kontrol.52 Polysomnography terus-menerus telah
mengkonfirmasi adanya peningkatan total tidur per 24 jam, pada beberapa pasien
dengan hipersomnia post-traumatic.50 Dari perspektif sejarah, menarik untuk dicatat
bahwa polysomnography selama periode koma memiliki nilai prognostik untuk
pengembangan pemulihan penuh tanpa gangguan tidur post-traumatic. Jumlah
normal sleep spindels, kompleks K, dan siklus yang normal antara tidur fase REM
dan non-REM adalah tanda prognostik yang menguntungkan.5,53,54 Baru-baru ini,
Valente et al juga menunjukkan bahwa pola tidur terorganisir, namun bukan skor
Glasgow Coma Scale, diprediksi sebagai prognosis yang lebih baik selama tahap
subakut koma post-traumatic.55 Jika kantuk di siang hari merupakan keluhan utama,
multiple sleep latency test dan polisomnogram dapat membantu menentukan apakah
ada hipersomnia sentral. Pada hipersomnia post-traumatic dengan kantuk di siang
hari, latensi tidur mungkin sangat pendek. Di sisi lain, pasien dengan insomnia posttraumatic menunjukkan latensi tidur yang berkepanjangan pada multiple sleep latency
test, dan juga pada studi tidur semalam.51 Seperti telah disebutkan, kehadiran
gangguan pernafasan saat tidur dan onset tidur saat fase REM tidak menghilangkan
kemungkinan bahwa trauma kepala merupakan faktor pemicu dalam perkembangan
gangguan tidur. Karena kecelakaan saat mengemudi juga dapat terjadi karena kantuk
yang ada sebelumnya, penyelidikan menyeluruh diperlukan untuk mengkompensasi
korban gangguan tidur sekunder dengan tepat, bahkan dengan adanya faktor risiko
yang ada sebelumnya. Pemeriksaan medis harus mencakup penilaian aktivitas
individu sebelum kecelakaan terjadi. Penilaian ini harus mencakup 1) wawancara
dengan pasangan dan rekan kerja; 2) penyelidikan track record selama berkerja,
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riwayat medis, dan riwayat mengemudi sebelumnya; dan 3) riwayat pekerjaan,
termasuk di saat cuti atau tidak masuk kerja. Trauma kepala jelas merupakan pemicu
sindrom pada seseorang dengan kantuk di siang hari yang terkait dengan pernapasan
yang tidak teratur yang sebelumnya memiliki catatan kerja teladan, kerja penuh, dan
catatan mengemudi yang memadai sebelum kecelakaan itu terjadi.
Gambar 1.Kerangka Diagnosis dari Gangguan Tidur
Keterangan : PSG, polysomnogram; MSLT, multiple sleep latency test
Kegemukan dan ciri anatomi kraniofasial kadang-kadang dapat menyebabkan
seseorang mengalami gangguan tidur post-traumatic dan hal ini harus diperhatikan
pada pemeriksaan.18 Laporan perjalanan tidur, yaitu di mana seseorang
mendokumentasikan pada sebuah bagan saat mereka mencoba untuk tidur dan berapa
banyak waktu tidur yang dapat tercapai, merupakan alat yang sangat berguna
Akhirnya, aktigrafi yaitu alat yang dipakai di pergelangan tangan untuk merekam
gerakan, ditemukan sebagai tambahan yang membantu dalam laporan perjalanan tidur
pada mereka yang telah menderita cedera otak.56
Tatalaksana
Mengobati insomnia post-traumatic merupakan sebuah tantangan menantang
(Gambar 2). Benzodiazepin harus dihindari akibat efek samping kognitifnya, yang
mungkin ditemukan pada pasien dengan cedera otak traumatis.57 Lebih jauh lagi,
dokter sering ragu meresepkan benzodiazepin karena risiko ketergantungan dan / atau
penyalahgunaan. Agonis reseptor non-benzodiazepin banyak digunakan, termasuk
zolpidem, eszoplasida yang bekerja lebih lama, dan zaleplon yang pendek. Meskipun
obat ini sering membantu dengan memulai dan / atau mempertahankan tidur, namun
dikaitkan dengan beberapa efek samping, termasuk perilaku tidur yang berhubungan
dengan perilaku aneh kompleks saat tidur (yaitu, berjalan dalam tidur dan gangguan
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makan yang berhubungan dengan tidur). Percobaan secara random crossover dan
double blind, yang melibatkan cedera otak traumatis dan pasien stroke yang diobati
dengan lorazepam (0,5-1 mg) dan zopiclone (3,75-7,5 mg, agonis reseptor nonbenzodiazepin lain yang tersedia di luar AS) pada waktu tidur menemukan bahwa ini
agen sama efektifnya. Tidak ada perbedaan besar dalam karakteristik tidur atau
kinerja kognitif pada hasil tes Mini Mental State Examination (MMSE).58 Sebagai
tambahan, banyak antidepresan penenang digunakan untuk insomnia, terutama saat
terjadi depresi komorbid. Obat-obat ini termasuk trazodone, mirtazapine, dan
doxepin. Suvorexant (Belsomra®; Merck & Co Inc, Kenilworth, NJ, USA) baru-baru
ini disetujui untuk pengobatan insomnia di Amerika Serikat dan memiliki mekanisme
aksi yang unik, yang melibatkan pemblokiran pengikatan neuropeptide pencetus
keadaan bangun (orexin A dan B ) ke reseptor (OX1R dan OX2R). Obat ini harus
digunakan dengan hati-hati karena dapat menyebabkan gangguan koordinasi motorik,
perilaku terkait tidur yang kompleks, perubahan mood / perilaku / kognitif,
kelumpuhan tidur, dan / atau gejala seperti cataplexy. Selanjutnya, pasien sering
diobati dengan obat-obatan seperti gabapentin, quetiapine, atau olanzapine karena
efek samping kantuknya yang terkenal, namun tidak ada bukti efikasi untuk
penggunaannya pada insomnia post-traumatic. Obat over-the-counter, seperti
diphenhydramine, doxylamine, dan hydroxyzine (semua antihistamin generasi
pertama), sering digunakan untuk membantu tidur. Melatonin dan berbagai suplemen
herbal juga sering digunakan, termasuk valerian, gamma-aminobutyric, 5-l-5hydroxytryptophan, kava, dan banyak lainnya. Secara keseluruhan, ada beberapa
studi yang membandingkan keefektifan berbagai agen ini. Dalam percobaan random
crossover, double-blind dan controlled, membandingkan amitriptilin (25 mg) dan
melatonin (5 mg) pada sekelompok kecil pasien cedera otak traumatis dengan
gangguan tidur kronis, tidak ada perbedaan yang ditemukan pada durasi tidur / latensi
/ kualitas atau kondisi terjaga pada siang hari.59 Bila menggunakan obat / suplemen
ini, pemberi resep harus mengingatkan pasien agar tidak mengemudi (atau melakukan
kegiatan lain yang dapat membahayakan diri sendiri atau orang lain) setelah minum
obat. Pasien sebaiknya tidak menggunakan obat ini dengan alkohol dan menggunakan
pengekangan saat meminum obat penenang lain ini.
Hal yang juga cukup penting untuk membimbing pasien untuk pertama kali
mencoba pengobatan pada malam hari ketika mereka tidak perlu melakukan kegiatan
atau aktivitas sehari-hari pada hari berikutnya sehingga mereka dapat memantau
setiap rasa kantuk residual di hari berikutnya.
Selain penatalaksanaan secara farmakoterapi, teknik non-farmakoterapi harus
didiskusikan dan dicoba untuk semua pasien insomnia. Termasuk terapi psikologis
dan perilaku, namun tidak hanya terbatas pada terapi kontrol stimulus, latihan
relaksasi, meditasi kesadaran, dan terapi perilaku kognitif. Satu studi yang meneliti
54 pasien dengan insomnia kronis menunjukkan bahwa intervensi meditasi secara
9
signifikan mengurangi waktu bangun total dan juga indeks keparahan insomnia dari
awal sebelum dibandingkan dengan kontrol pemantauan diri.60 Metode lain yang
mungkin digunakan bersamaan dengan terapi tidur ini adalah terapi pembatasan tidur,
biofeedback, paradoxical intention, dan edukasi sleep hygiene.61 Terapi ini
menghasilkan kualitas tidur nokturnal yang lebih baik dan pengurangan kelelahan
siang hari pada orang-orang dengan insomnia yang berhubungan dengan cedera otak
traumatis.62 Selain itu, akupunktur juga merupakan perawatan yang baik untuk
meningkatkan kualitas tidur setelah cedera otak traumatis.63
Gambar. 2 Tatalaksana Gangguan Tidur Terkait Cedera Kepala Traumatik
Catatan : Diambil dari Neurologic Clinics; 30(4); Viola-Saltzman M, Watson NF; Traumatic Brain Injury and Sleep Disorders;
1299–1312; Copyright 2012, dengan persetujuan dari Elsevier.75 Keterangan : CPAP, continuous positive airway pressure.
10
Pasien dengan narkolepsi atau hipersomnia karena cedera otak traumatis dapat
diuntungkan dengan penggunaan obat-obatan stimulansia. Modafinil bisa menjadi
obat pilihan pertama karena memiliki efek samping lebih sedikit dibandingkan
stimulan lainnya. Modafinil mengaktifkan daerah hipotalamus dan diberikan dalam
dua dosis terbagi (di pagi hari dan sekitar waktu makan siang). Percobaan yang
prospektif, double blind, randomised, terkontrol plasebo menemukan bahwa
modafinil (100-200 mg dosis setiap pagi) secara signifikan meningkatkan kantuk
yang diukur dengan Epworth Sleepiness Scale and the Maintenance of Wakefulness
Test, walaupun modafinil tidak terbukti efektif. untuk kelelahan.64 Namun, penelitian
lain menunjukkan bahwa modafinil memiliki efektivitas kantuk yang terbatas terkait
dengan cedera otak traumatis.65 Armodafinil (Nuvigil®; Teva Pharmaceuticals,
Petha Tikva, Israel), R-enansiomer modafinil, hanya diberi dosis sekali sehari .
Methylphenidate dan amfetamin juga digunakan pada orang dengan narkolepsi (atau
hipersomnia) yang berhubungan dengan cedera kepala. Pasien dengan trauma kepala
parah yang mengeluh kelambatan intelektual bisa mendapat manfaat lebih dari obat
berbasis amfetamin karena ini memiliki efek "pengaktifan" umum yang tidak sematamata ditujukan untuk mengantuk. Ketika cataplexy hadir dalam narkolepsi, oxybate
natrium dapat diresepkan karena tidak hanya efektif dalam pengobatan kantuk, tapi
juga mengkonsolidasikan tidur dan dapat mengurangi frekuensi amfetil cataplexy /
hypnagogic / kelumpuhan tidur.
Jika jenis ini tidak digunakan, maka antidepresan trisiklik, selektif serotonin
reuptake inhibitor, atau venlafaxin diresepkan untuk mengurangi cataplexy, jika
ada.66 Tidak diragukan lagi, pasien harus diedukasi mengenai tidur siang dan
penggunaan kafein yang efektif dan tidak mengemudi jika mengantuk. Terapi nonfarmasi lainnya mungkin termasuk terapi “sinar biru” setiap hari yang baru ditemukan
untuk memperbaiki kelelahan pasca trauma
Sleep apnea akibat cedera otak traumatis ditangani dengan seperti biasa,
biasanya dengan terapi tekanan udara positif yang kontinyu. Kadang-kadang dengan
terapi tipe spontaneous/timed bilevel positive airway pressure atau servoventilasi
adaptif diperlukan untuk sleep apnea sentral maupun obstruktif. Perawatan lain untuk
obstructive sleep apnea dapat mencakup mandibular advancement device. Ini
digunakan saat obstructive sleep apnea ringan maupun sedang dan memiliki tingkat
keberhasilan ~ 50%. Mereka kurang efektif untuk obstructive sleep apnea berat dan
pada mereka yang mengalami obesitas. Nasal expiratory positive airway pressure,
alat yang dimasukkan ke dalam lubang hidung saat tidur, juga telah terbukti efektif
untuk mengobati obstructive sleep apnea. Prosedur pembedahan kadang
dipertimbangkan, terutama pada mereka dengan obstructive sleep apnea parah atau
pada mereka yang memiliki kesulitan untuk menoleransi positive airway pressure.
Prosedur operasi meliputi tonsilektomi, septoplasty, reduksi turbinate,
uvulopalatopharyngoplasty, manipulasi genioglossus dan miotomi hyoid.
11
Trakeostomi jarang digunakan untuk obstructive sleep apnea, dan biasanya dilakukan
pada kasus yang mengancam jiwa. Operasi penurunan berat badan adalah
pertimbangan bedah lain pada pasien obesitas yang tidak sehat dengan obstructive
sleep apnea. Sebagai tambahan, perangkat yang baru disetujui Inspire® (Inspire
Medical Systems Inc, Minneapolis, MN, USA), sistem stimulasi saluran napas bagian
atas, digunakan untuk mengobati obstructive sleep apnea. Akhirnya, perawatan
konservatif untuk obstructive sleep apnea meliputi penurunan berat badan, hindari
posisi telentang saat tidur, dan pertahankan patensi hidung dengan penggunaan
semprotan cairan saline atau semprotan steroid, jika diperlukan. Seseorang juga harus
menghindari alkohol dan obat-obatan yang dapat mengurangi tonus otot atau
mempengaruhipernapasan (misalnya, narkotika dan benzodiazepin) sebelum waktu
tidur.68
Gangguan gerakan anggota tubuh periodik telah dikaitkan dengan cedera otak
traumatis dan diperlakukan dengan cara yang sama seperti restless legs syndrome.
Agonis dopamin (yaitu, ropinirol atau pramipexol) biasanya digunakan untuk
mengatasi gangguan ini. Gabapentin, pregabalin (Lyrica®; Pfizer Inc, New York City,
NY, USA), dan gabapentin encarbil (Horizant®; XenoPort Inc, Santa Clara, CA,
USA) juga sering digunakan dan mungkin memiliki profil efek samping yang lebih
dapat ditolerir. Levodopa telah terbukti efektif namun karena risiko augmentasi,
penggunaannya jarang dilakukan. Narkotika dan benzodiazepin juga efektif, namun
dicadangkan untuk kasus yang lebih signifikan yang tidak merespons pengobatan
lainnya. Khususnya, kadar zat besi harus diperiksa pada pasien ini untuk memastikan
tingkat feritin 50 ng / mL atau lebih. Suplementasi zat besi adalah pengobatan pilihan
jika feritin kurang dari yang diinginkan.69
Saat merawat pasien dengan gangguan tidur otak traumatis, klinisi juga harus
mengatasi rasa sakit, depresi, dan kegelisahan yang mendasarinya karena masalah ini
juga berdampak pada tidur (Gambar 3). Penghindaran (atau minimisasi) narkotika
dan benzodiazepin penting karena obat ini dapat memperburuk apnea tidur yang
berhubungan dengan trauma otak. "Mengobati sendiri" dengan alkohol dapat
menyebabkan gangguan tidur, mimpi buruk, penurunan tidur fase REM, dan apnea
tidur yang memburuk. Selektif Serotonin Reuptake Inhibitor yang diresepkan untuk
depresi atau kegelisahan harus dilakukan di pagi hari karena dapat menyebabkan
insomnia bila dikonsumsi pada waktu tidur. Akhirnya, antidepresan trisiklik sering
diberikan untuk mengobati masalah nyeri kronis dan mungkin juga membantu
insomnia karena efek penenang mereka.
Prognosis
Ada beberapa studi tindak lanjut yang dilakukan secara hati-hati terhadap
pasien dengan gangguan tidur post-traumatic. Kesan klinis umum adalah bahwa
sekali stabil, gangguan tidur yang terkait dengan kerusakan otak organik
12
menunjukkan sedikit perubahan lebih lanjut, selain respons reversibel terhadap
pengobatan. Sebuah studi kohort prospektif meneliti kantuk pada 514 pasien cedera
otak traumatis 1 bulan setelah cedera dan kemudian pada 1 tahun. Kuesioner
mengenai kondisi mengantuk dibuat dari Sickness Impact Profile (SIP), yang
merupakan kuesioner kualitas hidup terkait kesehatan, yang mencakup hal-hal
berikut: 1) Saya tidur atau tertidur sebagian besar waktu siang atau malam; 2) Saya
duduk setengah tertidur; 3) Saya tidur atau tidur siang lebih siang hari; dan 4) Saya
tidur lebih lama di malam hari. Pada 1 bulan, 55% mengaku setidaknya satu item
pada kuesioner mengantuk empat item ini. Pada 1 tahun,
Gangguan
Tidur
Cedera
Kepala
Traumatis
Perubahaan
Mood
Nyeri
Gambar. 3 Relasi antara perubahan terkait gangguan tidur
Catatan : Diambil dari Neurologic Clinics; 30(4); Viola-Saltzman M, Watson NF; Traumatic Brain Injury and Sleep Disorders;
1299–1312; Copyright 2012, dengan persetujuan dari Elsevier.75
hanya 27% yang mendukung satu atau lebih dari item ini. Dua Penelitian prospektif
lain terhadap 51 pasien dengan cedera otak traumatis menunjukkan bahwa pada 3
tahun pasca trauma, 67% pasien terus mengeluhkan gangguan tidur-bangun, terutama
hipersomnia dan kelelahan.70 Tidur nokturnal yang terganggu mungkin merupakan
penanda cedera yang lebih parah pada pasien dengan cedera kepala tertutup.71
Peningkatan efisiensi tidur berkorelasi dengan resolusi amnesia post-traumatic.72
Pada orang dengan cedera otak traumatis, adanya obstructive sleep apnea
dikaitkan dengan lebih banyak penurunan perhatian dan memori yang berkelanjutan
dibandingkan pasien dengan cedera otak traumatis yang parah tanpa obstructive sleep
apnea.73 Pasien cedera otak traumatis dengan hipersomnia siang hari memiliki waktu
reaksi lebih lambat dan kinerja yang buruk pada Tes Kewaspadaan Psikomotor
dibandingkan pasien “nonsleepy”.42
13
Sayangnya, penanganan gangguan tidur yang berhubungan dengan cedera
otak traumatis biasanya tidak memperbaiki kantuk atau fungsi neuropsikologis.
Dalam kelompok yang tidak dipilih dari 57 pasien dengan cedera otak traumatis,
Castriotta et al mendokumentasikan gangguan tidur pada 22 subjek (39%)
menggunakan polysomnogram. Pengobatan tidak menyebabkan perubahan signifikan
dalam kualitas hidup, mood, atau kinerja kognitif. Pengobatan obstructive sleep
apnea (13 subjek, 23%) dengan positive airway pressure terus menerus tidak
menyebabkan peningkatan kantuk, seperti yang diukur oleh Epworth Sleepiness Scale
and Multiple Sleep Latency Test.74
Kesimpulan
Kelainan tidur lazim terjadi pada pasien setelah cedera otak traumatis. Gejala
dan kelainan ini meliputi hipersomnia, insomnia, gangguan irama sirkadian,
parasomnia, kelelahan, dan perubahan mood, yang juga bisa mempengaruhi tidur.
Riwayat perjalanan penyakit menggambarkan trauma kepala sebelum onset
gangguan tidur serta tes diagnostik seperti polysomnogram, Multiple Sleep Latency
Test, dan / atau actigraphy adalah elemen penting untuk membuat diagnosis.
Pengobatan harus dilakukan secara spesifik; Namun, pengobatan gangguan tidur
seperti obstructive sleep apnea mungkin tidak mengarah pada perbaikan kantuk atau
disfungsi neurologis. Hal ini bisa membuat penanganan gangguan tidur posttraumatic dan gejalanya sulit dan kompleks. Diperlukan penelitian lebih lanjut untuk
membantu menetapkan pedoman penanganan gangguan tidur akibat cedera otak
traumatis.
Penutup
Penulis tidak melaporkan adanya konflik kepentingan dalam pekerjaan ini.
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59. Kemp S, Biswas R, Neumann V, Coughlan A. The value of melatonin for
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60. Ong JC, Manber R, Segal Z, Xia Y, Shapiro S, Wyatt JK. A randomized
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62. Ouellet MC, Morin CM. Efficacy of cognitive-behavioral therapy for insomnia
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63. Zollman FS, Larson EB, Wasek-Throm LK, Cyborski CM, Bode RK.
Acupuncture for treatment of insomnia in patients with traumatic brain injury:
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the treatment of fatigue and excessive daytime sleepiness in individuals with
chronic traumatic brain injury. J Head Trauma Rehabil. 2008;23(1):52–63.
66. Morgenthaler TI, Kapur VK, Brown TM, et al. Standards of Practice
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Randomized controlled trial of light therapy for fatigue following traumatic
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2012;30(4):1299–131
19
JOURNAL
Neuropsychiatric Disease and Treatment 2016:12 339–348
Traumatic brain injury-induced sleep disorders
Mari Viola-Saltzman and Camelia Musleh
Abstract: Sleep disturbances are frequently identified following traumatic brain
injury, affecting 30%–70% of persons, and often occur after mild head injury.
Insomnia, fatigue, and sleepiness are the most frequent sleep complaints after
traumatic brain injury. Sleep apnea, narcolepsy, periodic limb movement disorder,
and parasomnias may also occur after a head injury. In addition, depression, anxiety,
and pain are common brain injury comorbidities with significant influence on sleep
quality. Two types of traumatic brain injury that may negatively impact sleep are
acceleration/deceleration injuries causing generalized brain damage and contact
injuries causing focal brain damage. Polysomnography, multiple sleep latency testing,
and/or actigraphy may be utilized to diagnose sleep disorders after a head injury.
Depending on the disorder, treatment may include the use of medications, positive
airway pressure, and/or behavioral modifications. Unfortunately, the treatment of
sleep disorders associated with traumatic brain injury may not improve
neuropsychological function or sleepiness.
Keywords: traumatic brain injury, insomnia, hypersomnia, sleep apnea, periodic limb
movement disorder, fatigue
Introduction
Sleep disturbances are frequently identified following traumatic brain injury,
affecting 30%–70% of persons, and often occur after mild head injury. Traumatic
brain injury is a significant cause of disability and death worldwide. The Glasgow
Coma Scale scores traumatic brain injury as mild, moderate, or severe (mild =13–15,
moderate =9–12, severe = #8 out of 15).4 Brain injury can result in significant
sensory, motor, cognitive, and emotional impairments. Even mild traumatic brain
injury can be associated with dizziness, headache, nausea/vomiting, impaired balance
and coordination, vision changes, tinnitus, mood and memory changes, difficulty with
memory and attention, fatigue, and/or sleep disturbances. The relationship between
head injuries and altered consciousness and cognitive changes has been well
described, but the association between head trauma and sleep disturbance has not
been extensively researched.5
1–3
Epidemiology and risk factors
Traumatic brain injuries are most commonly caused by falls (28%), motor vehicle
accidents (20%), impact from an object (19%), and assaults (11%).6 These injuries
often are related to athletic injuries, construction or industrial accidents, and domestic
(and child) abuse. There is increasing awareness of traumatic brain injury in deployed
20
military. Among the US military serving abroad, 11%–23% have suffered mild traumatic brain injury, often from improvised explosive device blasts.7
The exact prevalence of specific posttraumatic sleep disorders is not well defined.
Baumann et al discovered that three out of four patients who were initially
hospitalized for traumatic brain injury developed sleep–wake disturbances by 6
months postinjury.
The majority of these patients had symptoms of hypersomnia or fatigue, while
insomnia was present in only 5%.8 However, other authors have identified a higher
prevalence of insomnia after head injury. In a study that examined 60 patients with
sleep-related complaints 3–24 months after traumatic brain injury (severity of
traumatic brain injury was 40% mild, 20% moderate, and 40% severe), 25% of the
participants complained of insomnia.9
Children also report sleep issues after suffering traumatic brain injury. One
hundred and sixteen children hospitalized for mild traumatic brain injury were
immediately evaluated, and 39%–67% of the population reported fatigue, trouble
with sleep onset, drowsiness, and/or sleeping more or less than usual. At follow-up
visit (2–3 weeks after injury), the sleep-related symptoms improved but persisted in
22%–38%.10 In a large study of 681 children who suffered from mild-to-severe
traumatic brain injury, 14.7% reported sleep problems at 1-month follow-up. This
percentage reduced to 10.7% at 4-month follow-up and no patients reported sleep
issues at 10-month follow-up.11 Finally, in another large study of 729 children with
mild-to-severe traumatic brain injury compared to 197 patients with orthopedic
injury, the traumatic brain injury group experienced a more prolonged duration and
higher severity of sleep disturbances at 3, 12, and 24 months.12
Hou et al studied 98 posttraumatic brain injury patients to investigate the risk
factors associated with the development of sleep disturbances. Risk factors for sleep
disturbances after traumatic brain injury included severity of the head injury (as
measured by the Glasgow Coma Scale), lower years of education, and the presence of
residual symptoms (ie, headache and/or dizziness). Neither loss of consciousness or
cause of injury was correlated with the development of sleep disturbances. The
presence of residual headache, dizziness, anxiety, and/or depression was
independently associated with the development of insomnia. The Glascow Coma
Scale score was independently associated with hypersomnia.13
Pathophysiology
Traumatic brain injuries are characterized as primary or secondary brain injuries. A
primary brain injury refers to the structural damage created during the time of impact
from contact, acceleration–deceleration, and/or rotational forces. A secondary brain
injury refers to the damage sustained from the subsequent cellular processes that
occur from the primary injury (ie, hypoxia and/or raised intracranial pressure).14
The collision forces that act on the site of injury may lead to focal or diffuse
injury. Focal injuries may include contact contusions, subdurals, epidurals, and/or
intraparenchymal hemorrhages. Diffuse injuries are often caused by acceleration–
21
deceleration forces that can cause shearing forces and widespread axonal injury in the
brain.14 The location of injury within sleep-regulating brain regions leads to a specific
sleep symptom. There is a paucity of clinicopathological correlative studies; however,
those that do exist indicate several correlations. For instance, hypersomnia can result
when areas involving the maintenance of wakefulness are injured. These regions
include the rostral pons, caudal midbrain, and thalamus.15 In fact, closed head injury
is known to lead to “shearing” forces along the direction of main fiber pathways
causing microhemorrhages in these areas.16 Sleepiness and sleep attacks have also
been linked to high cervical cord lesions, possibly by disruption of breathing during
sleep.17 Interestingly, in a study that examined head trauma patients with
hypersomnia, sleep-disordered breathing was found in all whiplash patients and
thought to have occurred postinjury.18
In head injury, a coup injury exists at the brain’s site of impact and a contrecoup
injury involves the area of the brain opposite to the initial site of injury. A contrecoup
injury usually occurs at the base of the skull.19,20 This type of injury occurs in areas of
bony irregularities (especially the sphenoid ridges), with subsequent damage to the
anterior temporal and inferior frontal regions,19,20 including the basal forebrain, which
is involved in sleep initiation. Therefore, an injury in this area can lead to symptoms
of insomnia.21 Sleep–wake disturbances after mild traumatic brain injury are
associated with a longer tentorial length and flatter tentorial angle (the angle formed
between the tentorium and a line through the foramen magnum) compared to patients
with mild traumatic brain injury without sleep–wake disturbances. The length of time
to recovery was directly correlated with tentorial length and indirectly correlated with
tentorial angle. The authors postulated that in mild traumatic brain injury, direct
impact involving the tentorium and pineal gland may result in the disruption of
melatonin homeostasis and sleep–wake disturbances.22
Traumatic brain injury may compromise the nucleus suprachiasmatica and/or its
output. This may cause disturbances in the circadian rhythm and, subsequently, a
combination of hypersomnia and insomnia. A complete reversal of the circadian
rhythmicity has been reported.23 In one case, a 20-year-old man suffered mild-tomoderate traumatic brain injury and penetrating eye injuries after an improvised
explosive device blast. He was found to have a free-running type of circadian rhythm
and was successfully treated with evening melatonin.24 Another study of 23 traumatic
brain injury patients found lower levels of evening melatonin production compared to
age- and sex-matched controls.25 Traumatic head injury has also been shown to be
associated with alterations in the hypothalamic–pituitary–adrenal axis circadian
rhythm.26
Low levels of cerebral spinal fluid hypocretin-1 are associated with narcolepsy
with cataplexy but not with other types of central hypersomnias.27 For example,
hypocretin-1 levels are usually normal in idiopathic hypersomnia. Low (,110 pg/mL)
or intermediate (110–200 pg/mL) levels of hypocretin-1 have been found in a number
of persons with neurologic lesions or diseases affecting the hypothalamus; some of
these patients exhibit both sleepiness and cataplexy.28 Moderate-to-severe traumatic
brain injury patients are usually found to have low or intermediate levels of
22
hypocretin-1 in the acute phase of injury, but these levels tend to normalize (become
.200 pg/mL) by 6 months after the insult.8
Rodrigues and Silva published a case of a patient who suffered from aggressive
body movements during rapid eye movement sleep and periodic limb movements
following a traumatic brain injury. Short sleep latencies were seen on multiple sleep
latency test. The authors postulated that this patient’s head injury was associated with
alterations in the dopaminergic pathways and suggested the possibility of
hypothalamic hypocretin involvement in its pathophysiology.29
Clinical features and diagnosis
Head trauma may result in significant sleep disturbance, more frequently in those
suffering from mild head injury compared to those from more severe head injury.
Mahmood et al examined 87 patients with mild-to-severe traumatic brain injuries and
found that people with mild injury met the criteria for sleep disturbance more often
than those with moderate or severe injury. One reason for this may be that patients
with more severe forms of traumatic brain injury possibly reported less sleep
disturbance because they were less aware of their sleep problems. Furthermore,
patients with mild traumatic brain injuries were likely to complete the rehabilitation
process quicker than those suffering from more severe traumatic brain injuries and
thus face more imminent pressures to reintegrate into society. These psychosocial
factors may lead to increased reporting of sleep disturbances in this population.
Finally, organic differences in the neurological insults seen in mild and severe
traumatic brain injuries may lead to different sleep disturbances.30,31 Moreover, it is
common for posttraumatic patients to complain of initial headaches that may lead to
persistent and widespread pain or centralized pain that can have effects on sleep
quality.32 Beta and gamma electroencephalogram (EEG) activity were found to be
dominant in all sleep stages over the frontal, central, and occipital regions in
posttraumatic patients with pain.33
Insomnia
One of the more common patterns following head injury involves trouble initiating
and maintaining sleep, with or without subjective daytime sleepiness. In a study of
452 patients with traumatic brain injury, 50% endorsed insomnia symptoms.34 In
some patients, insomnia was a manifestation of a circadian rhythm sleep disorder,
typically delayed sleep–wake phase disorder or irregular sleep–wake rhythm
disorder.35 Among male military personnel, multiple brain injuries were found to lead
to an increased risk for insomnia.36 Veterans with posttraumatic stress disorder and
mild traumatic brain injury may be troubled by nightmares.37 Former US forces
involved in Operation Enduring Freedom (Afghanistan) and Operation Iraqi Freedom
(Iraq), who complained of insomnia associated with mild traumatic brain injury and
posttraumatic stress disorder, were subjectively found to be sleepier compared to
veterans with insomnia due to posttraumatic stress disorder alone.38 However,
resolution of headaches and other neurologic deficits in veterans correlated with
improvement of posttraumatic stress disorder symptoms and daytime sleepiness.39
23
Hypersomnia
Hypersomnia may develop after a head injury. If hypersomnia is present for at least 3
months, multiple sleep latency testing proves a mean sleep latency of 8 minutes or
less, and there is no other obvious cause (ie, another sleep disorder, psychiatric
disorder, and/or medication), then the International Classification of Sleep Disorders
(third edition) published by the American Academy of Sleep Medicine classifies this
condition as “hypersomnia due to a medical disorder”.40 If posttraumatic hypersomnia
is associated with two or more sleep onset rapid eye movement periods on multiple
sleep latency testing, the diagnosis is “narcolepsy type 1 or type 2 due to a medical
condition”.
Other sleep disorders are also seen in patients who have suffered a head injury and
complain of hypersomnia. Masel et al reviewed a total of 71 head injury patients in a
residential treatment program, all without a prior history of sleep disturbances or
hypersomnia.41 Among the 33 (46.5%) hypersomnolent patients, four had obstructive
sleep apnea, seven had periodic limb movement disorder, and one had narcolepsy (in
addition to periodic limb movement disorder). The remaining patients were given a
diagnosis of “posttraumatic hypersomnia”. Guilleminault et al studied 184 traumatic
brain injury patients and found that the majority of patients had objective sleepiness
and only 17% of the patients had a normal mean sleep latency (greater than 10
minutes) on the multiple sleep latency test. Sleep-disordered breathing (primarily
obstructive sleep apnea) was present in 32% of the patients and all 16 whiplash
patients were diagnosed with sleep-disordered breathing. In addition, pain was a
significant cause of nocturnal sleep disruption and daytime impairment.18 Castriotta et
al prospectively followed 87 adults for at least 3 months after traumatic brain injury.
All subjects underwent polysomnography and multiple sleep latency testing. Fortysix percent of the patients had abnormal studies. Obstructive sleep apnea was
diagnosed in 23% of the patients, 11% were found to suffer from posttraumatic
hypersomnia, 7% had periodic limb movements in sleep, and 6% met the criteria for
narcolepsy.42
Although rare in occurrence, traumatic brain injury has also been reported to
trigger cases of Kleine–Levin syndrome, a disorder involving recurrent episodes of
hypersomnia and often accompanied by cognitive or behavioral disturbances,
hypersexuality, and/or compulsive eating.43
Parasomnias, fatigue, and mood disorders
Traumatic brain injury occasionally precipitates parasomnias, including sleepwalking,
sleep terrors, and rapid eye movement sleep behavior disorder.44 At times, a
combination of rapid eye movement and non–rapid eye movement parasomnias
produces a “parasomnia overlap disorder”. Fatigue is also associated with traumatic
brain injury with adverse effects on quality of life. Among the 119 patients studied at
least 1 year after suffering a traumatic brain injury, up to 53% reported fatigue. This
was more frequently reported in women or those with symptoms of depression, pain,
or sleep disturbance.45 In another study of patients who had suffered a moderate-to-
24
severe traumatic brain injury, 16%–32% and 21%–34% (at 1 and 2 years,
respectively) reported significant levels of fatigue.46
Mood disorders may also occur after traumatic brain injury. Patients with mild
traumatic brain injury and sleep complaints were more likely to report feeling
depressed at 10 days and 6 weeks after their injury.47 In a large study of military
personnel, a positive screening for traumatic brain injury and sleep problems was
found to be an early indicator of risk for developing posttraumatic stress disorder
and/or depression.48 New-onset anxiety after a traumatic brain injury was a significant
predictor of sleep disturbance, though the cause–effect relationship is unclear.49
Diagnosis
The patient’s history is a crucial aspect of the workup to 1) document the association
of the trauma with the sleep disorder, 2) rule out a preexisting sleep disorder, and 3)
assess the progression of symptoms after the head injury. Physical examination is also
important (Figure 1). Polysomnography should be considered if hypersomnia and/or
other symptoms of sleep apnea are present. Cases of posttraumatic hypersomnia have
shown an increase in sleep duration with or without changes in other sleep
measures.50 Patients with a posttraumatic insomnia have shown long sleep latencies,
low sleep efficiency, a decrease in nightly sleep duration, and an increase in stage-1
sleep.34,51 Patients with moderate-to-severe traumatic brain injury showed increased
slow-wave sleep, reduced rapid eye movement sleep, and more frequent nocturnal
awakenings compared to controls.52 Continuous polysomnography has confirmed an
increase in total sleep per 24 hours in some patients with posttraumatic
hypersomnia.50 From a historical perspective, it is of interest to note that
polysomnography during the comatose period has prognostic value for the
development of full recovery without posttraumatic sleep disturbance. Normal
amounts of sleep spindles, K-complexes, and normal cycling between non–rapid eye
movement and rapid eye movement sleep are favorable prognostic signs.5,53,54 More
recently, Valente et al also demonstrated that organized sleep patterns, but not
Glasgow Coma Scale scores, were predictive of better prognosis during the subacute
stages of posttraumatic coma.55
If daytime sleepiness is a major complaint, a multiple sleep latency test following
polysomnogram may aid in determining if a central hypersomnia is present. In
posttraumatic hypersomnia with daytime sleepiness, sleep latency may be markedly
shortened.50 On the other hand, patients with posttraumatic insomnia exhibit
prolonged sleep latencies on multiple sleep latency testing, as well as during the overnight sleep studies.51 As already mentioned, the presence of sleep-disordered
breathing and sleep-onset rapid eye movement periods does not eliminate the
possibility that the head trauma was the precipitating factor in the development of the
sleep disorder. Since a driving accident may also occur due to prior existing
sleepiness, a thorough inquiry is needed to appropriately compensate victims of
secondary sleep disorders, even in the presence of preexisting risk factors. The
medical workup should include assessment of the activity of the individual prior to
the accident. This assessment should include 1) interviews of bed partners and
25
coworkers; 2) investigation of employer records and prior health and driving records;
and 3) employment history, including missed work days. Head trauma is obviously a
trigger of the syndrome in an individual with daytime sleepiness associated with
sleep-disordered breathing who previously had an exemplary work record, full
employment, and adequate driving records prior to the accident.
Obesity and craniofacial anatomical features can sometimes predispose a person to
posttraumatic sleep disturbance and these should be noted on exam.18 Sleep diaries, in
which a patient documents on a chart the times they attempted to sleep and how much
sleep was attained, is a very useful tool. Finally, actigraphy, a device worn on the
wrist to record movement, has been found to be a helpful adjunct to a sleep diary in
those who have suffered a brain injury.56
Treatment
Posttraumatic insomnia may be challenging to treat (Figure 2). Benzodiazepines
should be avoided secondary to their cognitive side effects, which may be
compounded in a patient with traumatic brain injury.57 Furthermore, clinicians are
often hesitant to prescribe benzodiazepines due to their risk of dependency and/or
abuse. The non-benzodiazepine receptor agonists are extensively used, including
zolpidem, the longer-acting eszopiclone, and the shorter-acting zaleplon. Although
these medications are often helpful with initiating and/or maintaining sleep, they are
associated with some concerning side effects, including complex sleep-related
behaviors (ie, sleepwalking and sleep-related eating disorder). A randomized, doubleblinded, crossover trial involving traumatic brain injury and stroke patients treated
with lorazepam (0.5–1 mg) and zopiclone (3.75–7.5 mg, another non-benzodiazepine
receptor agonist available outside of the US) at bedtime found that these agents were
equally effective. There were no major differences in sleep characteristics or
cognitive performance on the Mini Mental Status Exam.58 In addition, many sedating
antidepressants are used for insomnia, especially when comorbid depression exists.
These medications include trazodone, mirtazapine, and doxepin. Suvorexant
(Belsomra®; Merck & Co Inc, Kenilworth, NJ, USA) was recently approved for the
treatment of insomnia in the US and has a unique mechanism of action, which
26
involves blocking the binding of wake-promoting neuropeptides (orexin A and B) to
receptors (OX1R and OX2R). This medication should be used with care as it can lead
to
impaired
motor
coordination,
complex
sleep-related
behaviors,
mood/behavioral/cognitive changes, sleep paralysis, and/or cataplexy-like symptoms.
Furthermore, patients are frequently treated with medications such as gabapentin,
quetiapine, or olanzapine due to a well-known side effect of sleepiness, but there is
no evidence of efficacy for their use in posttraumatic insomnia. Over-the-counter
medications, such as diphenhydramine, doxylamine, and
hydroxyzine (all first-generation antihistamines), are often used to aid sleep.
Melatonin and various herbal supplements are also frequently utilized, including
valerian, gamma-aminobutyric, 5-l-5-hydroxytryptophan, kava, and many others.
Overall, there are few studies comparing the effectiveness of these various agents. In
27
a randomized, double-blind, controlled crossover trial comparing amitriptyline (25
mg) and melatonin (5 mg) in a small group of traumatic brain injury patients with
chronic sleep disturbances, no difference was found in sleep duration/latency/quality
or daytime alertness.59 When using any of these medications/supplements, the
prescriber should caution the patient not to drive (or do any other activity that could
be of danger to self or others) after taking the medication. The patient should not use
these medications with alcohol and use restraint when taking these with other
sedating medications. It is also important to guide the patient to first try the
medication on an evening when they do not need to be somewhere early the next day
so that they can monitor for any residual sleepiness the following day.
In addition to pharmaceutical treatment, nonpharmaceutical techniques should be
discussed and attempted for all insomnia patients. Psychological and behavioral
therapies include, but are not limited to, stimulus control therapy, relaxation training,
mindfulness meditation, and cognitive behavioral therapy. One study that examined
54 patients with chronic insomnia showed that a mindfulness meditation intervention
significantly reduced total wake time as well as the insomnia severity index from
baseline when compared to a self-monitoring control.60 Other modalities likely used
with these are sleep restriction therapy, biofeedback, paradoxical intention, and sleep
hygiene education.61 These therapies lead to improved nocturnal sleep quality and a
reduction in daytime fatigue in those with insomnia related to traumatic brain
injury.62 In addition, acupuncture is also a good treatment for improving sleep quality
following traumatic brain injury.63
Patients with narcolepsy or hypersomnia due to a traumatic brain injury may
benefit from the use of a stimulant medication. Modafinil may be the medication of
first intention since it has fewer side effects than the other stimulants. Modafinil
activates hypothalamic regions and is given in two divided doses (in the morning and
around lunchtime). A prospective, double-blind, randomized, placebo-controlled trial
found that modafinil (100–200 mg dose each morning) significantly improved
sleepiness as measured by the Epworth Sleepiness Scale and the Maintenance of
Wakefulness Test, although modafinil did not prove to be effective for fatigue.64
However, another study showed that modafinil had limited effectiveness for
sleepiness associated with traumatic brain injury.65 Armodafinil (Nuvigil®; Teva
Pharmaceuticals, Petha Tikva, Israel), the R-enantiomer of modafinil, is dosed only
once per day. Methylphenidate and amphetamines are also used in those with
narcolepsy (or hypersomnia) related to a head injury. Patients with severe head
trauma who complain of intellectual slowness may benefit more from amphetaminebased medications since these have a general “activating” effect that is not solely
devoted to sleepiness. When cataplexy is present in narcolepsy, sodium oxybate may
be prescribed since it is not only effective in the treatment of sleepiness, but it also
consolidates sleep and may reduce the frequency of cataplexy/hypnagogic
hallucinations/sleep paralysis. If this is not used, then a tricyclic antidepressant,
selective serotonin reuptake inhibitor, or venlafaxine is prescribed to reduce
cataplexy, if present.66 Undoubtedly, patients should be educated regarding strategic
napping and caffeine use and not to drive if drowsy. Another non-pharmaceutical
28
therapy may include daily blue-light therapy that was found to improve posttraumatic
fatigue.67
Sleep apneas resulting from a traumatic brain injury are treated in the usual
manner, usually with continuous positive airway pressure therapy. Sometimes the
spontaneous/timed mode of bilevel positive airway pressure therapy or adaptive
servoventilation is necessary for central sleep apnea or when both obstructive and
central sleep apneas are present. Other treatments for obstructive sleep apnea may
include mandibular advancement device (or oral appliance). These are used when
mild or moderate obstructive sleep apnea is present and have a success rate of ~50%.
They are less effective for severe obstructive sleep apnea and in those who are obese.
Nasal expiratory positive airway pressure, a device applied to the nostrils during
sleep, has also been proven effective to treat obstructive sleep apnea. Surgical
procedures are considered at times, especially in those with severe obstructive sleep
apnea or in those who have difficulty tolerating positive airway pressure. Surgical
procedures
include
tonsillectomy,
septoplasty,
turbinate
reduction,
uvulopalatopharyngoplasty, genioglossus advancement and hyoid myotomy, and/or
maxillomanibular advancement. Tracheostomy is rarely used for obstructive sleep
apnea, and is usually reserved for life-threatening cases. Weight reduction surgeries
are another surgical consideration in morbidly obese patients with obstructive sleep
apnea. In addition, a newly approved device Inspire® (Inspire Medical Systems Inc,
Minneapolis, MN, USA), an upper airway stimulation system, is used to treat
obstructive sleep apnea. Finally, conservative treatments for obstructive sleep apnea
include weight loss, avoiding supine position during sleep, and maintaining nasal
patency with the use of saline spray or prescribed nasal steroid spray, if needed. One
should also avoid alcohol and medications that may reduce muscle tone or influence
the respiratory drive (eg, narcotics and benzodiazepines) prior to bedtime.68
Periodic limb movement disorder has been associated with traumatic brain injury
and is treated in the same manner as restless legs syndrome. The dopamine agonists
(ie, ropinirole or pramipexole) are commonly used to treat this disorder. Gabapentin,
pregabalin (Lyrica®; Pfizer Inc, New York City, NY, USA), and gabapentin encarbil
(Horizant®; XenoPort Inc, Santa Clara, CA, USA) are also often used and may have a
more tolerable side effect profile. Levodopa has been proven effective but due to the
risk of augmentation, it is utilized less frequently. Narcotics and benzodiazepines are
also effective, but are reserved for more significant cases that do not respond to other
medications. Notably, iron storage levels should be checked in these patients to
ensure a ferritin level of 50 ng/mL or greater. Iron supplementation is the treatment of
choice if ferritin is less than desired.69
When treating a patient with a traumatic brain injury sleep disorder, the clinician
must also address underlying pain, depression, and anxiety as these issues also impact
sleep (Figure 3). Avoidance (or minimization) of narcotics and benzodiazepines is
important as these medications can worsen traumatic brain injury–related sleep apnea.
“Self-medicating” with alcohol may lead to sleep disruption, nightmares, reduction in
rapid eye movement sleep, and worsening sleep apnea. Selective serotonin reuptake
inhibitors prescribed for depression or anxiety should be taken in the morning since
29
they can induce insomnia when taken at bedtime. Finally, tricyclic antidepressants are
often given to treat chronic pain issues and may also be helpful with insomnia due to
their sedating effects.
Prognosis
There are few careful follow-up studies of patients with posttraumatic sleep disorders.
The general clinical impression is that once stabilized, sleep disturbance related to
organic brain damage shows little further change, other than a reversible response to
treatment. A prospective cohort study examined sleepiness in 514 traumatic brain
injury patients 1 month after the injury and then at 1 year. Sleepiness questions were
extracted from sickness impact profile (SIP), a health-related quality-of-life
questionnaire, which included the following: 1) I am sleeping or dozing most of the
time – day or night; 2) I sit around half-asleep; 3) I sleep or nap more during the day;
and 4) I sleep longer during the night. At 1 month, 55% admitted to at least one item
on this four-item sleepiness questionnaire. At 1 year, only 27% endorsed one or more
of these sleepiness items.2 Another prospective study of 51 patients with traumatic
brain injury demonstrated that at 3-years postinjury, 67% of the patients continued to
complain of sleep–wake disturbances, especially hypersomnia and fatigue.70
Disturbed nocturnal sleep may be a marker of more severe injury in patients with
closed head injury.71 Improved sleep efficiency correlated with resolution of posttraumatic amnesia.72
In those with traumatic brain injury, the presence of obstructive sleep apnea was
associated with more impairment of sustained attention and memory compared to
patients with similar severity traumatic brain injury without obstructive sleep apnea.73
Traumatic brain injury patients with daytime hypersomnia had slower reaction times
30
and poorer performance on the Psychomotor Vigilance Test than nonsleepy
patients.42
Unfortunately, treatment of sleep disorders associated with traumatic brain injury
usually does not improve sleepiness or neuropsychological function. In an unselected
group of 57 patients with traumatic brain injury, Castriotta et al documented sleep
disorders in 22 subjects (39%) using polysomnogram. Treatment did not lead to
significant changes in quality of life, mood, or cognitive performance. Treatment of
obstructive sleep apnea (13 subjects, 23%) with continuous positive airway pressure
did not lead to improvement in sleepiness, as measured by the Epworth Sleepiness
Scale and multiple sleep latency test.74
Conclusion
Sleep disorders are prevalent in patients following traumatic brain injury. These
symptoms and disorders include hypersomnia, insomnia, circadian rhythm disruption,
parasomnias, fatigue, and mood alterations, which can also affect sleep. A careful
history delineating head trauma prior to onset of sleep disruption as well as diagnostic
tests such as polysomnogram, Multiple Sleep Latency Test, and/or actigraphy are
important elements of making a diagnosis. Treatment is disorder specific; however,
treatment of a sleep disorder such as obstructive sleep apnea may not lead to
improvement in sleepiness or neurological dysfunction. This can make treatment of
posttraumatic sleep disruption and its symptoms difficult and complex. Further
studies are needed to help establish guidelines for the treatment of sleep disorders
secondary to traumatic brain injuries.
Disclosure
The authors report no conflicts of interest in this work.
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