Brainstem Tumors

Foreword 1
Foreword 2
Preface
Acknowledgments
Contents
Contributors
Chapter 1: History of Brainstem Glioma Surgery
	1.1 Introduction
	1.2 Classical Era
	1.3 Fifteenth Through Seventeenth Centuries
	1.4 Eighteenth Century
	1.5 Nineteenth Century
	1.6 Early Twentieth Century
	1.7 Mid-to-Late Twentieth Century
	1.8 Conclusion
	References
Chapter 2: Anatomy of the Brainstem
	2.1 Introduction
	2.2 Developmental Anatomy: Phylogeny and Ontogeny
	2.3 Anatomical Features of the Brainstem
		2.3.1 Mesencephalon (Midbrain)
		2.3.2 Pons (Bridge)
		2.3.3 Medulla Oblongata
	2.4 Vascular Anatomy of the Brainstem
		2.4.1 Arterial Supply [7, 8]
			2.4.1.1 Midbrain
			2.4.1.2 Pons
			2.4.1.3 Medulla
		2.4.2 Venous Anatomy [9]
			2.4.2.1 Midbrain
			2.4.2.2 Pons
			2.4.2.3 Medulla
		2.4.3 Vascular Relationships and the Rule of Three [8]
	2.5 Special Microsurgical Regions and Surgical Safe Entry Zones
		2.5.1 Interpeduncular Fossa and Cerebral Peduncles [15, 16]
		2.5.2 Quadrigeminal and Ambient Cisterns
		2.5.3 Floor of Fourth Ventricle [4, 19]
		2.5.4 Cerebellopontine Angle and Related Cisterns
	2.6 Conclusion
	References
Chapter 3: Imaging of Brainstem Lesions
	3.1 Introduction
	3.2 Imaging Techniques
		3.2.1 Magnetic Resonance Imaging (MRI)
		3.2.2 Computed Tomography (CT)
		3.2.3 Positron Emission Tomography (PET)
		3.2.4 Ultrasound
	3.3 Intra-Axial Lesions: Neoplastic
		3.3.1 Brainstem Glioma
			3.3.1.1 Imaging
		3.3.2 Lymphoma
			3.3.2.1 Imaging
		3.3.3 Metastatic Disease
			3.3.3.1 Imaging
	3.4 Intra-Axial Lesions: Non-Neoplastic
		3.4.1 Cavernous Malformation
			3.4.1.1 Imaging
		3.4.2 Capillary Telangiectasia
			3.4.2.1 Imaging
		3.4.3 Hemorrhage/Hematoma
			3.4.3.1 Imaging
		3.4.4 Infarction
			3.4.4.1 Imaging
		3.4.5 Hypertrophic Olivary Degeneration
			3.4.5.1 Imaging
		3.4.6 Demyelination
			3.4.6.1 Imaging
		3.4.7 Infection
			3.4.7.1 Imaging
	3.5 Extra-Axial Lesions
		3.5.1 Schwannoma
			3.5.1.1 Imaging
		3.5.2 Meningioma
			3.5.2.1 Imaging
		3.5.3 Epidermoid Cyst
			3.5.3.1 Imaging
	3.6 Conclusion
	References
Chapter 4: Clinical Presentation and Assessment for Brainstem Tumors
	4.1 Introduction
	4.2 Patient History
	4.3 Neurological Examination
		4.3.1 Cranial Nerve Palsies
			4.3.1.1 Trochlear Nerve Palsy
			4.3.1.2 Trigeminal Nerve Palsy
			4.3.1.3 Abducens Nerve Palsy
			4.3.1.4 Facial Nerve Palsy
			4.3.1.5 Lower Cranial Nerves Palsy
		4.3.2 Pyramidal Tract Signs
		4.3.3 Truncal Ataxia
		4.3.4 Fundoscopic Changes
		4.3.5 Nystagmus
	4.4 Brainstem Syndromes Associated with Tumors
		4.4.1 Midbrain Syndromes
		4.4.2 Pontine Syndromes
		4.4.3 Medullary Syndromes
	4.5 Conclusion
	References
Chapter 5: Intraoperative Neurophysiological Monitoring During Brainstem Surgery
	5.1 Introduction
	5.2 Surgery of the Midbrain
		5.2.1 Mapping
			5.2.1.1 Identification of the Oculomotor Nerve Nuclei at the Level of the Tectal Plate
			5.2.1.2 Identification of the Corticospinal Tract at the Level of the Cerebral Peduncle
		5.2.2 Monitoring
			5.2.2.1 Monitoring of Motor Evoked Potentials
			5.2.2.2 Monitoring of Brainstem Auditory Evoked Potentials
	5.3 Surgery of the Pons
		5.3.1 Mapping
			5.3.1.1 Mapping of the Facial Colliculus on the Floor of the Fourth Ventricle
		5.3.2 Monitoring
			5.3.2.1 Monitoring of the Facial Nerve
	5.4 Surgery of the Medulla Oblongata
		5.4.1 Mapping
			5.4.1.1 Mapping the IX/X, XI and XII Cranial Nerve Nuclei
		5.4.2 Monitoring
			5.4.2.1 Lower Cranial Nerve Monitoring
	5.5 Other Monitoring Techniques in the Brainstem
	5.6 Conclusion
	References
Chapter 6: Low-Grade Pediatric Brainstem Gliomas
	6.1 Introduction
	6.2 Classification
	6.3 Symptoms
	6.4 Diagnosis and Imaging
	6.5 Pathology
	6.6 Differential Diagnosis
	6.7 Treatment Rationale
	6.8 Biopsy Considerations
	6.9 Surgical Treatment
		6.9.1 Treatment of Hydrocephalus
		6.9.2 Tumor Resection
		6.9.3 Postoperative Complications
	6.10 Adjuvant Oncological Treatments
	6.11 Outcome and Prognostic Factors
	6.12 Follow-Up Modalities
	6.13 Adult Low-Grade Brainstem Tumors
	6.14 Conclusion
	References
Chapter 7: High-Grade Tumors of the Brainstem (Except DIPG)
	7.1 Adult Malignant Brainstem Tumors
		7.1.1 Introduction
		7.1.2 Clinical Presentation
		7.1.3 Imaging and Histopathological Diagnosis
			7.1.3.1 Focal Malignant Brainstem Gliomas
			7.1.3.2 Focal Tectal Gliomas
			7.1.3.3 Other Brainstem Gliomas
		7.1.4 Chemotherapy
		7.1.5 Conclusion
	7.2 Pediatric Malignant Brainstem Tumors, Excluding Diffuse Intrinsic Pontine Gliomas (DIPG)
		7.2.1 Introduction
		7.2.2 Clinical Presentation
		7.2.3 Imaging and Histopathological Diagnosis
			7.2.3.1 High-Grade Gliomas (HGG)
			7.2.3.2 Atypical Teratoid Rhabdoid Tumor (ATRT)
			7.2.3.3 Embryonal Tumor with Multilayered Rosettes (ETMR) and Historical Central Nervous System Primitive Neuroectodermal Tumor (CNS-PNET)
		7.2.4 Treatment and Outcome
			7.2.4.1 Atypical Teratoid Rhabdoid Tumor (ATRT)
			7.2.4.2 Embryonal Tumor with Multilayered Rosettes (ETMR) and Historical Central Nervous System Primitive Neuroectodermal Tumor (CNS-PNET)
			7.2.4.3 High-Grade Gliomas (HGG)
		7.2.5 Conclusion
	References
Chapter 8: Diffuse Midline Glioma – Diffuse Intrinsic Pontine Glioma
	8.1 Introduction
	8.2 Clinical Presentation
	8.3 Imaging Characteristics
	8.4 Surgical Options
		8.4.1 To Biopsy or Not to Biopsy a Potential DIPG?
		8.4.2 Tenets for Obtaining a DIPG Biopsy
	8.5 Pathology and Molecular Signatures
	8.6 Management Strategies
		8.6.1 Radiotherapy and Chemotherapy
		8.6.2 Targeted Therapy
	8.7 Conclusion
	References
Chapter 9: Surgery for Vascular Lesions of the Brainstem
	9.1 Introduction
	9.2 Natural History
	9.3 Presentation and Diagnosis
		9.3.1 Clinical Presentation
		9.3.2 Imaging
	9.4 Regional Management Strategies for Brainstem Vascular Lesions
		9.4.1 Midbrain
			9.4.1.1 Aneurysms
			9.4.1.2 Arteriovenous Malformations (AVMs)
			9.4.1.3 Cavernous Malformations (CMs)
		9.4.2 Pons
			9.4.2.1 Aneurysms
			9.4.2.2 Arteriovenous Malformations (AVMs)
			9.4.2.3 Cavernous Malformations (CMs)
		9.4.3 Medulla
			9.4.3.1 Aneurysms
			9.4.3.2 Arteriovenous Malformations (AVMs)
			9.4.3.3 Cavernous Malformations (CMs)
	9.5 Conclusion
	References
Chapter 10: Inflammatory and Infectious Lesions of the Brainstem
	10.1 Introduction
	10.2 Clinical Presentation
	10.3 Diagnostic Approach
	10.4 Etiologies
		10.4.1 Brainstem Infections
			10.4.1.1 Brainstem Abscess
			10.4.1.2 Brainstem Encephalitis
			10.4.1.3 Postinfectious Brainstem Encephalitis
			10.4.1.4 Infectious Brainstem Vasculitis
		10.4.2 Brainstem Inflammatory Lesions
			10.4.2.1 Idiopathic Inflammatory Demyelinating Diseases of the Brainstem
			10.4.2.2 Connective Tissue Diseases (CTDs) and Vasculitis
			10.4.2.3 Paraneoplastic Brainstem Encephalitis
	10.5 Conclusion
	References
Chapter 11: Surgical Approaches to Mesencephalic (Midbrain) Tumors
	11.1 Introduction: Anatomy and Embryology
	11.2 Midbrain Lesions
		11.2.1 Thalamopeduncular Tumors
		11.2.2 Tectal Gliomas
		11.2.3 Aqueductal and Periaqueductal Tumors
	11.3 Surgical Approaches to Midbrain Tumors
		11.3.1 Anterior Midbrain
			11.3.1.1 Transchoroidal and Subchoroidal Approaches
			11.3.1.2 Peritemporal Approaches
		11.3.2 Central Midbrain
		11.3.3 Posterior (Dorsal) Midbrain
	11.4 Surgical Decision-Making
	11.5 Prognosis
	11.6 Conclusion
	References
Chapter 12: Surgical Approaches to Pontine Tumors
	12.1 Introduction
	12.2 Surgical Anatomy of the Pons
	12.3 Safe Entry Zones
		12.3.1 Peritrigeminal
		12.3.2 Supratrigeminal
		12.3.3 Lateral Pontine (Middle Cerebellar Peduncle)
		12.3.4 Suprafacial Collicular (Suprafacial Triangle)
		12.3.5 Infrafacial Collicular (Infrafacial Triangle)
		12.3.6 Superior Foveal (Lateral Sulcus Limitans)
		12.3.7 Fourth Ventricular Median Sulcal (Interfacial)
		12.3.8 Superior Ventral Pontine
	12.4 Anterior (Ventral) Pons
		12.4.1 Orbito-Fronto-Zygomatic Approach
			12.4.1.1 Surgical Setup and Patient Positioning
			12.4.1.2 Surgical Corridor(s) and Approach
		12.4.2 Endoscopic Endonasal Transclival Approach (Fig. 12.8)
			12.4.2.1 Surgical Setup and Patient Positioning
			12.4.2.2 Surgical Corridor(s) and Approach
	12.5 Anterolateral Pons
		12.5.1 Transpetrosal (See Fig. 12.8)
			12.5.1.1 Surgical Setup and Patient Positioning
			12.5.1.2 Surgical Corridor(s) and Approach
		12.5.2 Retrosigmoid
			12.5.2.1 Surgical Setup and Patient Positioning
			12.5.2.2 Surgical Corridor(s) and Approach
	12.6 Posterior (Dorsal) Pons
		12.6.1 Median Suboccipital Telovelar/Subvermian; Transvermian
			12.6.1.1 Surgical Setup and Patient Positioning
			12.6.1.2 Surgical Corridor(s) and Approach
	12.7 Conclusion
	References
Chapter 13: Surgical Approaches to Medullary Tumors
	13.1 Introduction
	13.2 Clinical Presentation
	13.3 Neuroradiological Evaluation
	13.4 Management Strategies
	13.5 Our Patient Series
		13.5.1 Patient Selection
		13.5.2 Tumor Characteristics
			13.5.2.1 Tumor Location and Extent
			13.5.2.2 Tumor Entities
			13.5.2.3 Molecular Signature
		13.5.3 Surgical Strategies
			13.5.3.1 Goals of Surgery
			13.5.3.2 Timing of Surgery
			13.5.3.3 Preoperative Planning and Tumor Exposure
			13.5.3.4 Microsurgical Dissection Technique
			13.5.3.5 Extent of Tumor Resection
		13.5.4 Clinical Outcome
			13.5.4.1 Pilocytic Astrocytoma
			13.5.4.2 Ganglioglioma
			13.5.4.3 Anaplastic Astrocytoma
			13.5.4.4 Glioblastoma
	13.6 Conclusion
	References
Chapter 14: Radiation and Chemotherapy for Brainstem Tumors
	14.1 Introduction
	14.2 Treatment of Pediatric Diffuse Intrinsic Pontine Glioma (DIPG)
		14.2.1 Radiation Therapy
			14.2.1.1 Hyperfractionated Radiotherapy
			14.2.1.2 Hypofractionated Radiation Therapy
			14.2.1.3 Radiosensitizing Agents
		14.2.2 Chemotherapy
			14.2.2.1 Empiric Therapies
			14.2.2.2 Disease-Specific Targeted Therapy
			14.2.2.3 Biologic Agents
			14.2.2.4 Different Modes of Delivery
	14.3 Treatment of Pediatric Non-DIPG Brainstem Gliomas
		14.3.1 Radiation Therapy
		14.3.2 Chemotherapy
	14.4 Treatment of Adult Brainstem Gliomas
		14.4.1 Radiation Therapy
		14.4.2 Chemotherapy
	14.5 Treatment at Relapse
	14.6 Conclusion
	References
Chapter 15: Future Therapies for Malignant Brainstem Tumors
	15.1 Introduction
	15.2 Obstacles in the Treatment of Malignant Brainstem Tumors
		15.2.1 Maximal Safe Cytoreduction Surgery
		15.2.2 Blood-Brain Barrier
		15.2.3 ATP-Binding Cassette Transporters
		15.2.4 Intratumoral Heterogeneity
		15.2.5 Immune Privilege and Specialization of the Central Nervous System
	15.3 Molecular Characteristics of Malignant Brainstem Tumors
	15.4 Drug Delivery
		15.4.1 Convection-Enhanced Delivery
		15.4.2 Intraarterial Delivery
		15.4.3 Manipulating the Blood-Brain Barrier
			15.4.3.1 Focused Ultrasound
			15.4.3.2 Photodynamic Therapy
			15.4.3.3 Photochemical Internalization
		15.4.4 Inhibition of ATP-Binding Cassette Transporters
		15.4.5 Carriers and Packaging Vehicles
			15.4.5.1 Liposomes
			15.4.5.2 Nanoparticles
	15.5 Signal Transduction Pathway Targeted Therapy
	15.6 Modulating Gene Expression Status: Epigenetic Modulators
	15.7 Immunotherapy
		15.7.1 Therapeutic Antibodies, Radiolabeled Antibodies, and Immunotoxins
		15.7.2 Therapeutic Vaccines
		15.7.3 Immune Checkpoint Inhibitors
		15.7.4 Adoptive Cell Therapies
	15.8 Oncolytic Viruses
	15.9 Conclusion
	References
Index