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Introduction
Neurooncology is a part of neuroscience which deals with tumors in the nervous system. To be more specific, neurooncology is a specialty which involves the management of metastatic central and peripheral nervous system neoplasms; neurologic complications of cancer and related disorders; and neurologic complications of therapy utilized in such patients. Seizures play a very important role in the quality of life, particularly in patients with slow-growing primary brain tumors. Tumor-related seizures are often refractory to anti epileptic treatment. Despite the importance of this subject to the fields of neurology, neurosurgery and neurooncology, the pathogenesis of tumor-related epilepsy remains poorly understood. Approximately 30-50% of patients with brain tumors present with seizures as the initial symptom. These seizures often manifest as focal seizures with secondary generalization and are often refractory to anti epileptic treatment. A number of studies have established an association between epileptic seizures at disease onset and a more favorable prognosis.

General Information

 * 1) Primary Tumors of the Central Nervous System

Primary brain tumors can occur at any age, from infancy to late in life. These tumors often afflict people during their prime years. Factors such as age, tumor location, and clinical presentation are helpful in differential diagnosis. Most types of primary brain tumors are more common in men with the exception of meningiomas, which are more common in women.


 * 1) Metastatic Tumors of the Central Nervous System

Cancer spreads to the nervous system by direct invasion, compression, or metastasis. Direct invasion or compression from continuous tissues relates to the proximity of the nervous system to other structures, such as the brachial plexus, lumbosacral plexus, vertebral neuroforamina, base of skull, cranium, and pelvic bones.


 * Intracranial Metastasis

There are three types of intracranial metastasis: brain metastasis, dural metastasis, and leptomeningeal metastasis. Brain metastasis can be single or multiple and involve any portion of the brain. Metastasis to dural structures generally occurs by hematogenous spread or direct invasion from a contiguous bone. Dural metastases can invade the underlying brain and cause focal edema and associated neurologic symptoms. These processes tend to cause seizures early in the course because of their cortical location. Metastasis to the leptomeninges is an uncommon but well-recognized clinical presentation in cancer patients. Leptomeningeal metastasis most commonly is due to breast, lung, or melanoma primary tumors.

initel Metastases to the skull are divided into two categories by general site: calvarium and skull base. Metastases to the calvarium usually are asymptomatic. Metastases to the skull base quickly become symptomatic because of their proximity to cranial nerves and vascular structures.
 * Skull Metastasis


 * Spinal Metastasis

The spine most often is affected by metastatic disease involving the epidural space. This usually occurs as direct tumor spread from a vertebral body (85%) or by invasion of paravertebral masses through a neuroforamin (10-15%).


 * 1) Genetic Syndromes and Risk Factors

There multiple hereditary conditions that increase a person's chance of developing brain tumors.


 * Nongenetic Risk Factors

Few issues in medicine are as potentially contentious as the suspicion of environmental and occupational causes of cancer, including brain tumors. Prior cranial irradiation is the only risk factor that definitely predisposes to brain tumor formation. Some of the risk factors are ionizing radiation, nonionizing radiation, nitrosamines and industrial chemicals.

Tumor Factors

 * 1) Histology

Seizures are common in patients with low-grade tumors such as dysembryoblastic neuroepithelial tumors, gangligliomas, and oligodendrogliomas. The rapid growth of fast-growing high-grade brain tumors may damage the subcortical network essential for electrical transmission, whereas slow-growing tumors have been suggested to induce partial deafferentation of cortical regions, causing denervation hypersensitivity and producing an epileptogenic milieu. Studies strongly suggest that genetic factors may play a role in tumor development and tumor-related epilepsy.


 * 1) Tumor location

The location of tumors is closely related to their histology. The majority of glioneuronal tumors occur in the temporal lobe. Some data have shown that oligodendroglial tumors were more likely to be located in frontal lobe, whereas astrocytomas were more commonly found in temporal locations. It may be postulated that tumor-related seizures have unique characteristics, which may share some common genetic pathways with tumorigenesis.


 * 1) Blood-brain barrier disruption (BBB)

Human and animal studies have suggested that perturbations in neurovascular integrity and breakdown of the BBB lead to neuronal hypersynchronization and epileptiform activity. Relevant molecular changes in brain tumors that affect BBB structure and function include decreased expression of transmembrane junctional proteins and heightened release of vascular endothelial growth factor. Results suggest that pathological disruption of thet BBB in brain tumor patients may contribute to seizure activity.

Peri-tumoral factors
Contemporary imaging techniques provide testimony to the remarkable differences between the peri-tumoral brain and normal tissue.


 * 1) Morphological changes

Certain morphological changes in the peri-tumoral brain tissue, such as persistent neurons in the white matter, inefficient neuronal migration, and changes in synaptic vesicles, are also believed to contribute to seizure generation.


 * 1) Hypoxia, acidosis and metabolic changes

Tumors with insufficient blood supply often cause interstitial hypoxia, which subsequently contributes to acidosis. The intratumoral hypoxia and acidosis may extend to the surrounding tissue. Furthermore, hypoxia causes acidosis as a consequence of both heightened metabolic requirements of the proliferating tissue and impaired oxidative energy metabolism.


 * 1) Ionic changes

Ionic changes in the peri-tumoral zone may influence neuronal activity. An interesting hypothesis was proposed by Sontheimer, who suggested that glioma invasion into the peri-tumoral zone is in part mediated by chloride channel overexpression, allowing cells to traverse the extracellular space through rapid changes in cell shape.


 * Glutamate neurotransmission

Recent work has demonstrated a close link between seizure activity and high extracellular glutamate in tumor-related epilepsy. Glutamate activation of ionotropic receptors leads to a rapid excitatory signal based on cation influx that can cause release of calcium from intracellular stores. GABA levels appeared to be higher in human tumor-inflicted tissues than in control tissue. Immune-mediated neuronal damage of the peri-tumoral brain area, coupled with changes in the balance between stimulatory and inhibitory cytokines, may contribute to the development of tumor-related epilepsy.

Initial Patient Evaluation and Care

 * 1) Brain Tumor Presentations
 * 2) Spinal Cord Tumor Presentations
 * 3) Approach to the Evaluation of New Patients
 * 4) Practical Strategies for Providing Appropriate Patient Care

Diagnostic Procedures

 * 1) Diagnostic Imaging of the Brain and Spinal Cord
 * 2) Lumbar Puncture and Cerebrospinal Fluid Analysis
 * 3) Pathologic Diagnosis

Commonly Used Treatments in Neuro-Oncology

 * 1) Radiotherapy
 * 2) Chemotherapy
 * 3) Corticosteroids
 * 4) Neurosurgical Interventions

Primary Tumors

 * 1) Malignant Astrocytomas
 * 2) Other Astrocytomas
 * 3) Oligodendrogliomas
 * 4) Brain Stem Gliomas
 * 5) Pituitary Region Tumors
 * 6) Germ Cell and Pineal Region Tumors
 * 7) Medulloblastoma and Other Primitive Neuroectodermal Tumors
 * 8) Meningiomas and Other Meningeal Tumors
 * 9) Tumors of the Optic Nerve and Chiasm
 * 10) Primary Central Nervous System Lymphoma
 * 11) Primary Spinal Cord Tumors

Metastatic Tumors

 * 1) Spinal Cord Metastasis
 * 2) Brain Metastasis
 * 3) Leptomeningeal Metastasis

Approach to Clinical Problems in Neuro-Oncology

 * 1) Anorexia and Weight Loss
 * 2) Brain Tumors in Women of Childbearing Age
 * 3) Central Nervous System Infections
 * 4) Constipation
 * 5) Cranial Nerve Syndromes
 * 6) Deep Venous Thrombosis and Pulmonary Embolus
 * 7) Depression and Anxiety
 * 8) Differential Diagnosis of Brain Tumor Progression
 * 9) Fatigue and Weakness
 * 10) Fever and Neutropenia
 * 11) Gait Disturbances
 * 12) Headaches
 * 13) Hiccups
 * 14) Increased Intracranial Pressure, Herniation Syndromes, and Coma
 * 15) Insomnia
 * 16) Mental Status Changes
 * 17) Nausea and Vomiting
 * 18) Paraneoplastic Syndromes
 * 19) Peripheral Nerve Problems: Plexopathies and Neuropathies
 * 20) Seizures and Other Spells
 * 21) Stroke and Other Cerebrovascular Complications
 * 22) Urinary Problems
 * 23) Visual Symptoms

Pain and Terminal Care

 * 1) Palliative and Terminal Care
 * 2) Cancer Pain Management

Treatment implications for tumor-related epilepsy
Studies on adult patients demonstrated that gross total resection or even extended lesionectomy could greatly improve seizure prognosis. The fact that both tumoral and peri-tumoral factors contribute to the pathogenesis of tumor-related epilepsy suggests that VPA should be considered as a first line therapy in treating tumor-related epilepsy.