Neuro-Oncology is the study of brain and spinal cord neoplasms, many of which are (at least eventually) very dangerous and life-threatening. (astrocytoma, glioma, glioblastoma multiforme, ependymoma, pontine glioma and brain stem tumours are among the many examples of these). Among the malignant brain cancers, gliomas of the brainstem and pons, glioblastoma multiforme, and high-grade (highly anaplastic) astrocytoma are among the worst. In these cases, untreated survival usually amounts to only a few months, and survival with current radiation and chemotherapy treatments may extend that time from around a year to a year and a half, possibly two or more, depending on the patient’s condition, immune function, treatments used, and the specific type of malignant brain neoplasm. Surgery may in some cases be curative, but, as a general rule, malignant brain cancers tend to regenerate and emerge from remission easily, especially highly malignant cases. In such cases, the goal is to excise as much of the mass (tumour cells) and as much of the tumour margin as possible without endangering vital functions or other important cognitive abilities.

Primary Tumours Of The Central Nervous System

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

Metastatic Tumours Of The Central Nervous System

The 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 oedema 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 tumours. 

Skull Metastasis

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. 

Spinal Metastasis

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

Genetic Syndromes And Risk Factors

Multiple hereditary conditions increase a person’s chance of developing brain tumours.

Nongenetic Risk Factors

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

MECHANISM

Tumour Factors

Histology

Seizures are common in patients with low-grade tumours such as embryoblastic neuroepithelial tumours, gangliogliomas and oligodendrogliomas. The rapid growth of fast-growing high-grade brain tumours may damage the subcortical network essential for electrical transmission, whereas slow-growing tumours 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 tumour development and tumour-related epilepsy. 

Tumour Location

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

Blood-Brain Barrier Disruption (BBB) 

Human and animal studies have suggested that perturbations in neurovascular integrity and breakdown of the BBB lead to neuronal hyper synchronization and epileptiform activity. Relevant molecular changes in brain tumours that affect BBB structure and function include decreased expression of transmembrane junctional proteins and heightened release of vascular endothelial growth factors. Results suggest that pathological disruption of the BBB in brain tumour 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.

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.

Hypoxia, Acidosis And Metabolic Changes

Tumours 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.

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 tumour-related epilepsy. Glutamate activation of ionotropic receptors leads to a rapid excitatory signal based on cation influx that can cause the release of calcium from intracellular stores.

Diagnostic Procedures

Diagnostic Imaging Of The Brain And Spinal Cord

The imaging studies commonly used in neurooncology are computed tomography (CT) and magnetic resonance imaging (MRI). Less commonly used are myelography, positron emission tomography  (PET), and diagnostic angiography. 

Lumbar Puncture And Cerebrospinal Fluid Analysis

Lumbar puncture (LP) and cerebrospinal fluid (CSF) analysis are important for the evaluation of some primary tumours, metastatic conditions, and neurologic complications of cancer. 

Pathologic Diagnosis

Accurate histologic diagnosis is critical for treatment planning and patient counselling. Surgically obtained tissue usually is required to make a histologic diagnosis. For certain tumours, a definitive diagnosis can be accomplished by vitreous aspirate, cerebrospinal fluid (CSF) cytology, or suggested by the presence of certain tumour markers in the CSF.

Treatments

  • Radiotherapy
    Radiotherapy is an important treatment for central nervous system tumours and has been demonstrated to extend survival and improve the quality of life for patients with many primary and metastatic brain tumours. 
  • Chemotherapy
    Chemotherapy, or the use of drugs in the treatment of cancer, can lead to the long-term control of many malignancies. Some tumours, such as testicular cancer of Hodgkin’s disease, maybe cured even when they are widespread. As chemotherapy may be associated with severe toxicity, it should be given under the supervision of one skilled in the administration and monitoring of such agents. 
  • Corticosteroids
    Corticosteroids (CS) are commonly used in patients with a variety of neuro-oncologic conditions. CS treatment often is required to control symptoms related to increased intracranial pressure (ICP) or peritumoral oedema. 
  • Neurosurgical Interventions
    Neurosurgical intervention is warranted in almost all cases of primary central nervous system tumours and for many metastatic tumours. A biopsy usually establishes a definitive histologic diagnosis. The role of surgery depends on the nature of the tumour. With modern neurosurgical techniques, most patients with extra-axial brain tumours are cured with minimal residual neurologic deficit

Primary Tumours

  • Malignant Astrocytomas: Malignant astrocytomas are the most common primary brain tumours in adults. Malignant astrocytomas generate symptoms and signs by mass effect, local brain infiltration, tissue destruction, cerebral oedema, and increased intracranial pressure. Headaches and seizures are the most frequent initial symptoms. Associated focal neurologic signs and symptoms occur depending on the anatomic location of the tumour. Confusion and mental status difficulties occur in patients with large tumours, those that cross the corpus callosum and those with a lot of associated oedema.
  • Other Astrocytomas: Tumours of presumed or known astrocytic lineage other than the malignant astrocytomas include a variety of tumours categorized by histology, location, age of onset, and natural history.
  • Oligodendrogliomas: The oligodendrogliomas include low-grade oligodendroglioma, anaplastic oligodendroglioma, and oligoastrocytoma (mixed glioma). This group of tumours, although less common than astrocytomas, has received increased attention in the past decade because of reports of chemosensitivity and a favourable survival rate when compared with astrocytomas of similar grade.
  • Brain Stem Gliomas: Brain stem glioma is a distinct category of central nervous system tumours because of its unique location and behaviour. The histology of brain stem gliomas spans the spectrum of gliomas located elsewhere in the central nervous system. The cause of these tumours is still unknown. Researchers have not found any direct genetic link.
  • Pituitary Region Tumors: A wide variety of tumours can occur in and around the sella turcica. The most common tumours in this region are craniopharyngiomas, pituitary adenomas, meningiomas, and optic chiasm gliomas. Visual impairment is a common presenting symptom, due to compression or invasion of the optic chiasma.
  • Germ Cell and Pineal Region Tumors: Most tumours of the pineal region are either germinomas or pineal cell tumours and are tumours of adolescents and young adults. Presentation relates to the location in the nervous system.
  • Medulloblastoma and Other Primitive Neuroectodermal Tumors: Medulloblastoma and other primitive neuroectodermal tumours (PNETs) are a group of highly aggressive central nervous system tumours with a tendency to spread via cerebrospinal fluid pathways. These typically are tumours of childhood and young adulthood.
  • Meningiomas and Other Meningeal Tumors: Meningioma is the most common tumour in the central nervous system. Although most are slow-growing and histologically benign, they can induce significant symptoms depending on location.
  • Tumors of the Optic Nerve and Chiasm: These tumours include the tumours involving the orbit and optic pathways, which include optic nerve gliomas and optic nerve sheath meningiomas.
  • Primary Central Nervous System Lymphoma: Primary central nervous system lymphoma (PCNSL), a rare central nervous system tumour, occurs preferentially in immunocompromised patients; however, it is increasing in incidence in both the HIV and non-HIV populations.
  • Primary Spinal Cord Tumors: Primary spinal cord tumours are uncommon and most are either astrocytomas or ependymomas.

Metastatic Tumours

  • Spinal Cord Metastasis: The management of spinal cord metastasis depends on whether or not the metastasis is causing epidural spinal cord compression as well as the overall status of the patient’s systemic cancer.
  • Brain Metastasis: The occurrence of brain metastases represents a significant challenge in the care of patients with cancer. Symptoms may significantly alter the quality of life of affected patients, and brain metastases generally represent overall treatment failure. Long-term survival is poor.
  • Leptomeningeal Metastasis: Leptomeningeal metastasis (LM) is a rare complication of systemic cancer in which the leptomeninges are infiltrated by cancer cells. The overall incidence is 3–8% but is increasing as more cancer patients survive following initial treatment.

Palliative And Terminal Care

Palliative care is a special type of care provided to improve the quality of life of patients who suffer from a serious or life-threatening disease, such as cancer. The purpose of palliative care is not to cure but to prevent or treat, as early as possible, the symptoms and side effects of the disease and its treatment, in addition to the related psychological, social, and spiritual problems. Palliative care is also called comfort care, supportive care, and symptom management. Palliative care is provided throughout a patient’s experience with cancer. It usually begins at diagnosis and continues through treatment, follow-up care, and the end of life.

Cancer Pain Management 

  • Cancer pain can be managed.
  • Controlling pain is part of a patient’s cancer treatment.
  • Talking openly with the physician and health care team helps them manage one’s pain.
  • The best way to control pain is to stop it from starting or keep it from getting worse.
  • There are many different medicines to control pain. Everyone’s pain control plan is different.
  • Patients keeping a record of their pain helps create the best pain control plan.
  • People who take cancer pain medicines as prescribed rarely become addicted to them.
  • Your body does not become immune to pain medicine. Stronger medicines should not be saved for “later.”

Treatment Implications For Tumour-Related Epilepsy

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