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1

Virginia. General Assembly. Joint Legislative Audit & Review Commission. Evaluation of House Bill 2156: mandated coverage of second opinions for primary malignant brain tumor patients at NCI Comprehensive Cancer Center. Richmond, Va: Commonwealth of Virginia, 2007.

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2

Fields, William S., ed. Primary Brain Tumors. New York, NY: Springer New York, 1989. http://dx.doi.org/10.1007/978-1-4612-3676-4.

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3

Primary central nervous system tumors: Pathogenesis and therapy. New York: Humana Press, 2011.

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4

Ibegbu, Chinazom, and Nimish A. Mohile. Brain Tumors in Pregnancy. Edited by Emma Ciafaloni, Cheryl Bushnell, and Loralei L. Thornburg. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190667351.003.0018.

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Approximately 79,000 people are diagnosed with a central nervous system (CNS) tumor each year, but only a few of these patients are pregnant women. There is no evidence that pregnancy confers an increased risk of developing a brain tumor and incidence during child-bearing years is estimated to be 12.24 per 100,000 women. The care and management of all patients with primary brain tumors can be challenging and requires a multidisciplinary team that includes neurologists, medical neuro-oncologists, neurosurgeons, radiation-oncologists, and palliative care physicians. In a pregnant patient, this multidisciplinary team should also include a high-risk obstetrician. This chapter provides a detailed care map for pregnant patients with brain tumors. All management decisions regarding the neoplasm must consider the health of the expectant mother, the health of the fetus, the neurological and medical complications due to the brain tumor, and the potential effect that the brain tumor has on the patient’s survival.
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5

Theeler, Brett J., and Mark R. Gilbert. Primary Central Nervous System Tumors. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199937837.003.0129.

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Ependymomas are rare primary central nervous system (CNS) tumors that are thought to arise from ependymal cells lining the ventricular system located throughout the CNS. Ependymomas occur in all age groups but are more common in the pediatric population. Ependymomas typically present as mass lesions within the ventricular system, brain or spinal cord parenchyma. As with most central nervous system tumors, pathologic evaluation is required for definitive diagnosis. Ependymomas are typically treated with a combination of surgery and radiotherapy although this varies depending on tumor location, tumor grade, patient age, extent of tumor resection, and other pretreatment factors. Recent molecular studies demonstrate molecularly defined tumor heterogeneity that appears to have a region-specific pattern. Translating the emerging molecular profiles of ependymomas into improved treatment strategies is the primary goal of ongoing research efforts.
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6

Eseonu, Chikezie I., Jordina Rincon-Torroella, and Alfredo Quiñones-Hinojosa. Unusual Gliomas. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190696696.003.0002.

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Patients with intra-axial brain tumors often present with neurologic symptoms based on the anatomic location of their tumor. Workup for a brain tumor includes cranial imaging such as magnetic resonance imaging and computed tomography, as well as systemic imaging to assess for primary tumor if metastasis is suspected. Maximal safe resection optimizes outcomes including overall survival. Surgical decisions are based on variables such as medical comorbidities and anatomic location of the tumor. Gliomas in eloquent areas may require intraoperative cortical and subcortical mapping of motor and/or language areas to optimize safety and help maximize resection. Adjuvant chemotherapy and radiation lead to a median survival of 14.6 months for patients with glioblastoma. Rapidly recurring glioblastoma after surgery has a poor prognosis.
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7

Kaley, Thomas J. Oligodendrogliomas. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199937837.003.0128.

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Gliomas represent the most common symptomatic primary brain tumors, of which oligodendrogliomas are the least common subtype of glioma.1 The traditional thinking is that although the rarest, they also offer patients the best prognosis and they are deemed to be the most sensitive to treatment. However, although they may have a longer average survival than most other gliomas, nearly all patients with an oligodendroglioma will ultimately succumb to their illness due to either progressive and recurrent tumor or malignant transformation into a higher grade tumor. Optimal treatment of oligodendroglial tumors, especially those harboring a 1P/19Q codeletion, remains controversial.
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8

Huntoon, Kristin, and J. Bradley Elder. High-Grade Gliomas. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190696696.003.0001.

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Glioblastoma is the most common primary malignant brain tumor. This chapter discusses the clinical presentation and initial workup for a patient with a suspected glioblastoma, as well as the optimal treatment strategy and prognosis. Diagnosis is typically made using magnetic resonance imaging. Optimal treatment involves maximal safe surgical resection followed by adjuvant chemotherapy and radiation therapy. Surgical adjuncts including intraoperative imaging modalities and brain mapping techniques help improve neurologic morbidity associated with surgery. Despite maximal treatment, virtually all patients with glioblastoma will experience recurrence of their tumor and may be considered for clinical trials or second-line therapy. This chapter highlights important pearls associated with management of patients with glioblastoma and written for those who are interested in neuro-oncology, neurosurgery, and the field of brain tumors.
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9

Primary Brain Tumors. Springer My Copy UK, 1989.

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10

Primary Brain Tumors. Springer Verlag, 1989.

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11

Sanai, Nader. Low-Grade Gliomas. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190696696.003.0027.

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Low grade gliomas encompass multiple histologic diagnoses of primary brain tumors, most commonly grade 2 oligodendroglioma and grade 2 astrocytoma. This chapter presents a case of a patient with a left temporal low grade glioma who presented with seizures, which are a common presenting symptom for this tumor type. Management of patients with a newly diagnosed low grade glioma typically begins with maximal safe surgical resection for surgically accessible tumors. Surgical planning may involve functional imaging such as with fMRI. Genetic and molecular markers help distinguish subtypes of low grade gliomas, and this subtyping has implications for the type and timing of adjuvant therapy.
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12

Taylor, Jennie, and Patrick Y. Wen. Meningomas. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199937837.003.0130.

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Meningiomas are the most common primary brain tumor diagnosed in adults. Arising from the arachnoid (meningothelial) cells of the inner layer of the dura, they are often slow growing, but can lead to significant morbidity. They can invade through the outer layer of dura into overlying bone or skin, or into critical bordering structures such as the cavernous sinus or orbits, or encase cerebral blood vessels. These limitations can make surgical resection difficult if not impossible in some circumstance. However, they rarely metastasize outside the central nervous system (CNS), with the lungs being the most common site seen with higher-grade tumors.
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13

Brain Metastases from Primary Tumors. Elsevier, 2014. http://dx.doi.org/10.1016/c2013-0-18945-3.

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14

Brain Metastases from Primary Tumors. Elsevier, 2015. http://dx.doi.org/10.1016/c2013-0-23234-7.

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15

Rajan, Shobana, and Vibha Mahendra. Awake Craniotomy. Edited by David E. Traul and Irene P. Osborn. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190850036.003.0003.

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Awake craniotomies are performed when the site of surgical instrumentation or resection directly involves or abuts eloquent areas of the brain and require a cooperative patient, a tailored neuroanesthetic technique, and good teamwork. Eloquent cortex refers to any cortical region in which injury produces a symptomatic cognitive or motor deficit and includes the primary sensorimotor cortex, essential speech areas, occipital visual areas, and mesial temporal regions crucial for episodic memory. An awake patient allows for intraoperative testing of motor, speech, or sensation function while removing or manipulating brain tissue. The two principal aims of resection of a brain tumor or an epileptic focus are to maximize excision of the offending lesion for better prognosis while minimizing or avoiding damage to surrounding brain tissue. Damage to adjacent brain tissue can be catastrophic, especially if the tumor or epileptogenic areas are located close to the eloquent regions of the brain.
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16

T, Thomas D. G., ed. Neuro-oncology: Primary malignant brain tumors. Baltimore: Johns Hopkins University Press, 1990.

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17

T, Thomas David G., ed. Neuro-oncology: Primary malignant brain tumours. London: Edward Arnold, 1990.

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18

Roy Morgan, Lee, and Feyzi Birol Sarica, eds. Brain and Spinal Tumors - Primary and Secondary. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.77682.

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19

Brain Metastases from Primary Tumors, Volume 3. Elsevier, 2016. http://dx.doi.org/10.1016/c2014-0-05005-8.

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20

Clifford, Schold S., ed. Primary tumors of the brain and spinal cord. Boston: Butterworth-Heinemann, 1997.

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21

1913-, Fields William S., ed. Primary brain tumors: A review of histologic classification. New York: Springer-Verlag, 1989.

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22

Fields, William S. Primary Brain Tumors: A Review of Histologic Classification. Springer-Verlag Telos, 1989.

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23

Brain Metastases from Primary Tumors Vol. 1: Epidemiology, Biology, and Therapy. Elsevier Science & Technology Books, 2014.

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24

Hayat, M. A. Brain Metastases from Primary Tumors: Epidemiology, Biology, and Therapy. Elsevier Science & Technology Books, 2015.

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25

P, Rock Jack, ed. The practical management of low-grade primary brain tumors. Philadelphia: Lippincott Williams & Wilkins, 1999.

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26

Norden, Andrew D., David A. Reardon, and Patrick C. Y. Wen. Primary Central Nervous System Tumors: Pathogenesis and Therapy. Humana Press, 2011.

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27

1948-, Csécsei G., ed. Primary and secondary brain stem lesions. Wien: Springer-Verlag, 1987.

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28

De Braganca, Kevin C., and Roger J. Packer. Medulloblastoma. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199937837.003.0139.

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Medulloblastoma is the most common malignant brain tumor in pediatric patients. Patients are presently stratified to either standard or high-risk groups based on clinical and pathologic criteria. Approximately 80% of patients with standard risk disease are cured of their primary disease. High-risk and recurrent disease groups have a poorer outcome; 5-year progression-free survival is only 65% with high-risk disease. Disease control after recurrence is very poor. Treatment is multimodal and also aims to limit short- and long-term toxicities. Recent identification of four molecular subtypes of medulloblastoma may change risk assignment and therapy. Addressing the medical and psychosocial issues of survivors continues to improve the quality of life for these patients beyond the disease’s treatment.
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29

McDonald, Elizabeth S., Azadeh Elmi, and David A. Mankoff. Breast Cancer Metastatic Imaging. Edited by Christoph I. Lee, Constance D. Lehman, and Lawrence W. Bassett. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190270261.003.0010.

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This chapter reviews appropriate indications for advanced imaging, such as PET/CT, in the evaluation of breast cancer. An informed imaging approach is based on primary tumor size and pathological characteristics, as well as patient symptoms that may indicate a higher likelihood of metastatic disease. When evaluation for metastatic disease is indicated, survey imaging with CT, bone scintigraphy, abdominal MRI, brain MRI, and/or PET/CT can be used to establish disease burden, and to identify a biopsy target for pathological confirmation. We emphasize the evolving role of FDG PET/CT in this chapter, including basic principles of PET imaging, followed by a short section on image interpretation. Finally, the concept of using imaging as a response biomarker is introduced.
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30

Sara, Booth, and Bruera Eduardo, eds. Palliative care consultations in primary and metastatic brain tumours. Oxford: Oxford University Press, 2004.

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31

Kaplan, Tamara, and Tracey Milligan. Neoplasms of the CNS (DRAFT). Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190650261.003.0016.

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The video in this chapter discusses neoplasms of the central nervous system (CNS), including metastatic tumors, common primary brain tumors (pediatric astrocytoma, pediatric medulloblastoma, adult meningioma, and adult glioblastoma), as well as pituitary adenoma, and pineal tumors, which can present with Parinaud syndrome.
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32

Amirian, E. Susan, Quinn T. Ostrom, Yanhong Liu, Jill Barnholtz-Sloan, and Melissa L. Bondy. Nervous System. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780190238667.003.0056.

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Although brain and other nervous system tumors are relatively rare, constituting up to 4% of incident primary cancer diagnoses, they are often associated with high morbidity and mortality. Several etiologic factors have been examined in relation to nervous system tumors, with the majority of studies focusing on central nervous system tumors. Despite decades of research, the only established risk factors for brain tumors are family history and moderate to high levels of ionizing radiation exposure. Differences in study designs, case ascertainment, control selection, and accuracy of exposure assessment are challenges associated with studying risk factors for nervous system tumors, and may partly explain why the majority of risk for these tumors remains unexplained. There is now substantial evidence that gliomas are inversely associated with allergies and atopy and positively associated with taller height.
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33

Hovinga, K. E., Y. Esquenazi, and P. H. Gutin. Meningiomas. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190696696.003.0011.

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Meningiomas are the most common primary central nervous system tumors and account for about one third of all primary brain and spinal tumors. They are classified according to the World Health Organization into 3 groups (I–III). Treatment strategies range from observation, surgery, and/or a radiation therapy. Many meningiomas are slow growing and discovered incidentally. Symptoms can vary widely, depending on the location. Patient’s specific factors and the location of the meningioma in relation to critical brain structures are all important factors in determining the optimal treatment. This chapter presents common clinical scenarios of meningioma. Differential diagnosis, perioperative workup, surgical nuances, and postoperative complications are discussed.
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34

Nageshwaran, Sathiji, Heather C. Wilson, Anthony Dickenson, and David Ledingham. Neuro-oncology. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199664368.003.0013.

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This chapter discusses the classification and grading of primary brain tumours and their evidence-based treatment. The management of tumour complications (raised intracranial pressure and seizures) is also reviewed.
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35

Hoskin, Peter. Radiotherapy planning for metastatic disease. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199696567.003.0021.

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Chapter 16 discusses radiotherapy planning for metastatic disease, predominantly for patients with bone metastasis, spinal cord compression, and brain metastasis. The techniques for such treatments are specific to this indication rather than the primary tumour site.
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36

Thomas, David G. T. Neuro-Oncology: Primary Malignant Brain Tumors (Johns Hopkins Series in Contemporary Medicine and Public Health). The Johns Hopkins University Press, 1990.

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37

Hayat, M. A. Brain Metastases from Primary Tumors, Volume 3: Epidemiology, Biology, and Therapy of Melanoma and Other Cancers. Elsevier Science & Technology Books, 2016.

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38

Maldaun, Marcos Vinicius Calfat, Sujit Prabhu, Claudio Tatsui, and Luis Souhami, eds. The Role of Modern Neuro-oncology in the Treatment of Primary CNS Tumors, and Brain and Spinal Metastases. Frontiers Media SA, 2020. http://dx.doi.org/10.3389/978-2-88963-852-9.

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39

Mason, Peggy. Cells of the Nervous System. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190237493.003.0002.

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The nervous system is made up of neurons and glia that derive from neuroectoderm. Since neurons are terminally differentiated and do not divide, primary intracranial tumors do not arise from mature neurons. Tumors outside the nervous system may metastasize inside the brain or may release a substance that negatively affects brain function, termed paraneoplastic disease. Neurons receive information through synaptic inputs onto dendrites and soma and send information to other cells via a synaptic terminal. Most neurons send information to faraway locations and for this, an axon that connects the soma to synaptic terminals is required. Glial cells wrap axons in myelin, which speeds up information transfer. Axonal transport is necessary to maintain neuronal function and health across the long distances separating synaptic terminals and somata. A common mechanism of neurodegeneration arises from impairments in axonal transport that lead to protein aggregation and neuronal death.
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40

Kleihues, Paul, Elisabeth Rushing, and Hiroko Ohgaki. The 2016 revision of the WHO classification of tumours of the central nervous system. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199651870.003.0001.

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The revised fourth edition of the WHO classification of Tumours of the Central Nervous System, published in 2016, comprises several newly recognized tumour entities, and a significant restructuring of the classification, mainly based on genetic profiling. Glioblastomas are now classified into two major types. Isocitrate dehydrogenase (IDH)-wildtype glioblastoma (primary glioblastoma IDH-wildtype) develops rapidly de novo without a recognizable precursor lesion. IDH-mutant glioblastoma (secondary glioblastoma IDH-mutant) develops more slowly through malignant progression from diffuse or anaplastic astrocytoma. Medulloblastomas are now defined by combining histological patterns (classic, desmoplastic/nodular, extensive nodularity, anaplastic) and genetic hallmarks (WNT-activated; SHH-activated, TP53-mutant; SHH-activated, TP53-wildtype; non-WNT/non-SHH). Other newly recognized tumour entities include diffuse midline glioma, H3 K27M-mutant; ependymoma, RELA fusion-positive; and embryonal tumour with multilayered rosettes. The new classification is a significant step forward and will facilitate the development of novel targeted therapies of brain tumours.
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41

Jalali, Rakesih, Patrick Y. Wen, and Takamitsu Fujimaki. Meningiomas. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199651870.003.0011.

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Meningiomas are the most common type of primary brain tumour, comprising approximately one-third of all intracranial neoplasms. It is therefore important for all neuro-oncologists to understand the biology and optimal managements of these tumours. The majority of meningiomas are World Health Organization grade I benign tumours, but grade II (atypical) or grade III (anaplastic) tumours are not uncommon. Total surgical removal is the standard of care but may not be feasible if the tumour involves critical structures such as cranial nerves or important blood vessels. Conventional radiation therapy, stereotactic radiosurgery, or particle irradiation is used for residual or recurrent tumours. To date, medical treatments have had a limited role, except for controlling seizures. However, there are ongoing clinical trials with molecularly targeted drugs and immunotherapies based on improved understanding of the molecular pathogenesis of these tumours. In this chapter, the clinical presentation, biology, and therapy for these tumours are discussed.
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42

Sahota, Pradeep, and Niranjan N. Singh. Sleep in other neurological disorders—headache. Edited by Sudhansu Chokroverty, Luigi Ferini-Strambi, and Christopher Kennard. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199682003.003.0031.

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Headache and sleep disorder are among the most commonly reported problems in clinical practice and often coexist in the same patient. The two are related in several ways, though the relationship is very complex and is still not very well understood. The brainstem and hypothalamic nuclei are hypothesized to regulate both sleep and headache. Differential diagnosis of headache during sleep includes cluster headache, hypnic headache, migraine, sleep apnea headache, exploding head syndrome, tension-type headache, and paroxysmal hemicrania. Management of these headaches depends upon the diagnosis as a primary headache like migraine and cluster headaches versus secondary headaches during sleep seen in the patient with brain tumors, stroke, or meningitis. Management of primary headaches can be divided into nonpharmacological approaches, which predominantly include lifestyle modification, diet and exercise, avoidance of triggers, and sleep hygiene, and pharmacological approaches, including preventive and abortive treatments.
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43

Rossor, Martin. Coma. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780198569381.003.0749.

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Many pathological processes can be responsible for stupor or coma, for example, head injury, tumour, vascular and inflammatory lesions, and most commonly toxic and metabolic states which usually lead to unconsciousness primarily through their effect upon the brainstem. In the series of Plum and Posner (1980) of 500 cases of stupor or coma, initially of unknown aetiology, 101 proved to be due to supratentorial lesions probably producing their effects by indirect action upon the brainstem, 65 to subtentorial lesions, and 326 to diffuse or metabolic brain.
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