Neuro-oncology

Roger J. Packer, David Schiff, Roger J. Packer, David Schiff

• Publisher: Wiley-Blackwell
• Year: 2012
• Print ISBN: 9780470655757
• eBook ISBN: 9781118321447
• Edition: 1
• Topic: Medicine
• Subtopic: Neurology

Cancer imposes daunting effects on the nervous system

Brain cancer is one of the most devastating diagnoses a physician can deliver. Cancer of the nervous system can take many different forms. Treatment is specific to the type of malignancy, its location in the nervous system and, increasingly, its molecular characteristics. The challenges manifest further when management choices need to be made, and multidisciplinary approaches are required. Additional complexities arise in children, where the developing neurological system requires more sensitive treatment.

Neuro-oncology unmasks the complexities to provide a straightforward guide to cancers of the nervous system. Following a general approach to diagnosis and treatment, the clinical aspects of specific cancer types in adults and children are explained in practical terms. A final section considers the effect of system cancer on the nervous system and the side effects of treatment.

Clinical in approach, practical in execution, Neuro-oncology will help you diagnose and manage your patients more effectively.

Neurology in Practice

Series Editors
Robert A Gross , MD, PhD, Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA
Jonathan W Mink, MD, PhD, Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA

The Neurology in Practice series provides clinical 'in the office' or 'at the bedside' guides to effective patient care for neurologists. The tone is practical, not academic, with authors offering guidance on what might be done and what should be avoided. The books are informed by evidence-based practice and feature:

• Algorithms and guidelines where they are appropriate
• 'Tips and Tricks' boxes – hints on improving outcomes
• 'Caution' warning boxes – hints on avoiding complications
• 'Science Revisited' – quick reminder of the basic science principles
• Summaries of key evidence and suggestions for further reading

Part I: Overview and General Aspects of Therapy

1

Diagnosis of Brain Tumors: Clinical and Radiographic

Isabel C. Arrillaga-Romany Eudocia Quant Lee and Patrick Y. Wen

Center for Neuro-Oncology, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA, USA

Introduction

Recent epidemiologic studies by the Central Brain Tumor Registry of the United States report the rate of symptomatic brain tumors at 19 per 100,000 person-years. An estimated 64,500 new cases of primary central nervous system (CNS) tumors and 150,000 cases of brain metastases are expected to be diagnosed in the United States in 2011. Surgery, chemotherapy, and radiation are the mainstays of therapy, and early diagnosis may produce better outcomes.

This chapter focuses on the diagnosis of tumors of the CNS and reviews both presenting clinical and neuroimaging features. Clinical recognition and imaging are essential early steps in identification of CNS tumors, although pathologic evaluation of tissue samples remains the gold standard for diagnosis. Rarely, when a biopsy is not feasible (for example with pediatric brainstem tumors), imaging has an even more valuable role. Our goal is to familiarize clinicians with general principles that are useful in the clinical recognition of potential brain tumors and to review imaging modalities that help differentiate brain tumors from other mass lesions.

Clinical Diagnosis of Brain Tumors

History

Diagnosis of CNS neoplasms begins with a good clinical history and examination. Both nonspecific and focal neurologic complaints and symptoms can alert the primary care physician or neurologist to the possibility of an underlying mass lesion and indicate the need for further work-up. Key aspects of the history that help differentiate neoplastic lesions from other diagnoses include timing of symptom onset, tempo of progression, and severity of symptoms. Systemic symptoms and the presence of other diseases or hereditary syndromes are additional valuable pieces of information that can help narrow the diagnosis by their association with specific CNS tumors.

Symptoms produced by brain tumors may be either nonspecific or focal, and in general tend to be subacute in onset. The presentation varies widely and neither a normal neurologic exam nor presentation with acute onset of symptoms rules out a brain tumor. At the outset many brain tumors produce minimal or no symptoms. In contrast, brain tumors can also present with acute onset stroke-like symptoms. This type of acute presentation is usually the result of a focal seizure or hemorrhage into the tumor bed. Less common causes include infarction or intraparenchymal hemorrhage resulting from stroke or venous sinus thrombosis, two conditions to which brain tumor patients are predisposed given their inherent hypercoagulable state.

The rate of progression of symptoms is also quite variable but tends to be gradual over weeks to months, helping to differentiate neoplasms from other more static disorders such as degenerative disease or more rapidly progressing infectious conditions. By paralleling the growth and spread of CNS neoplasms, the rate of symptomatic progression can serve as a rough clinical estimate to tumor grade. Typically, benign tumors such as meningiomas, or low-grade neoplasms such as oligodendrogliomas, will have a slower progression of symptoms than more malignant tumors such as glioblastomas.

Various other historical factors associated with brain tumors that can be elicited in the history are helpful in the formulation of a differential diagnosis. A careful review of systems, for instance, should identify symptoms such as weight loss, lethargy, and night sweats that are nonspecific but can be associated with many types of cancers. When combined with neurologic symptoms, these symptoms should raise suspicion of primary or metastatic CNS neoplasms, though should not rule out subacute infectious, inflammatory, or autoimmune CNS processes. Likewise, a detailed review of past medical history may identify genetic syndromes or other conditions with a higher than normal incidence of CNS neoplasms. Li–Fraumeni syndrome, resulting from germline mutations in the p53 tumor suppressor gene, is associated with a strong family history of multiple cancers including breast cancer, sarcoma, and leukemia, and associated with glioblastomas. Neurofibromatosis type 1 is associated with gliomas and cutaneous manifestations, neurofibromatosis type 2 is associated with vestibular schwannomas and meningiomas, while von Hippel–Lindau syndrome is associated with hemangioblastomas. Other systemic illnesses increase the risk for specific CNS neoplasm; one of the best examples of this is the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Neurologic symptoms in immunocompromised patients, and in particular those with HIV/AIDS, should raise concern for primary CNS lymphoma (PCNSL). Likewise, focal neurologic symptoms in patients with a prior history of systemic cancers or lymphoma raises suspicion for brain metastases or CNS lymphoma. Lastly, knowledge of prior exposure to ionizing radiation can be helpful. Irradiation of the cranium is the only environmental exposure or behavior that is known unequivocally to increase the risk for intracranial tumors, specifically meningiomas, glial tumors, and schwannomas.

Clinical Presentation and Symptoms

Though classically patients with mass lesions are thought to present with focal or lateralizing symptoms, the reality is that many patients present with impairments reflecting multifocal, global, or nonspecific cerebral dysfunctions. The variety of symptoms and symptom subtypes reflect the diverse actions of tumors, either directly or indirectly, on brain function. Tumors such as gliomas or lymphomas can directly invade and destroy brain parenchyma. Others, such as meningiomas, directly compress and distort brain tissue. Such direct effects can result in a disruption of brain functioning at the cellular or circuit level resulting in focal neurologic signs. Alternatively, compression or invasion of other intracranial structures such as blood vessels, leptomeninges, and CSF outflow tracts is possible, and could lead to infarctions, venous sinus thromboses, elevated intracranial pressure, and hydrocephalus. Disruption of the blood–brain barrier (BBB) is another frequent occurrence that leads to vasogenic edema and thus increases the territory of brain parenchyma that becomes affected. Importantly, other factors inherent to the tumor itself, including location, size, and growth rate, impact the clinical presentation. Tumor size will determine how much of the brain is affected, which can correlate with both the number and severity of symptoms. The rate of tumor growth impacts the brain’s ability to adapt to pathologic changes, and slower growing tumors often produce milder symptoms.

Generalized Non-Focal Symptoms

Generalized tumor-associated symptoms are global and nonlocalizable. Often, patients with intracranial neoplasms have generalized impairments of cerebral function and present with vague complaints, making accurate diagnosis difficult. Headaches, nausea, vomiting, and changes in mental status, cognition, and level of consciousness usually reflect raised intracranial pressure from mass effect or hydrocephalus. Other symptoms and signs, such as global mental status changes, are quite pervasive and include apathy, change in personality, irritability, psychomotor retardation, lethargy, and forgetfulness. Such nonspecific impairments in mental function have been linked to lesions in the frontal and temporal lobes, corpus callosum, thalamocortical fibers, and reticular formation, among others. Occasionally, increased intracranial pressure can present in a similar fashion though usually alongside other indicative signs such as papilledema or with progressive altered levels of consciousness. Still other nonlocalizable presentations are the result of multifocal tumors, often seen in metastatic disease, presenting with a mixture of focal signs and symptoms that can be confused for generalized clinical manifestations.

Headache is one of the most pervasive symptoms in neuro-oncology, occurring in over 50% of this patient population. Pre-existing headache conditions appear to predispose patients to tumor-related headaches, making it difficult to distinguish between tumor and nontumor-related complaints. Some clues, such as change in headache character and increasing frequency or severity of headache, can help with diagnosis and point to the need for further work-up. Importantly, most tumor-related headaches do not appear in isolation. Recent estimates indicate that just 2% of brain tumor patients present with headache as their only clinical manifestation. The association of focal neurologic signs or symptoms with headache is another indication for prompt work-up.

Unfortunately, the character of the headache is not especially helpful in diagnosis. The classical teaching is that headache attributable to an intracranial neoplasm will be progressive, worse in the morning, or wake the patient from sleep, and may be aggravated by coughing, straining, or bending forward. These characteristics were thought to reflect raised intracranial pressures and theoretically to help identify tumor-related headaches. Recent reviews, however, have not corroborated an association between intracranial tumors and headache that is worse in the morning or with cough. Instead, tension-type headaches that are dull, moderate in intensity, and not particularly localizable are found to be the most common headache type in patients with intracranial tumors.

CAUTION!

Patients with headaches that wake them at night or are worse in the morning, or who have focal neurologic deficits, require urgent neuroimaging. However, many patients with brain tumors present with headaches that are indistinguishable from tension headaches.

Nausea and vomiting occur most frequently in association with severe tumor headache, but can also be present in isolation. These symptoms typically manifest first thing in the morning and are only rarely associated with food intake. Usually, tumor-associated vomiting reflects an increase in intracranial pressure or compression of the area postrema, a chemoreceptive trigger zone for vomiting, located in the inferolateral portion of the fourth ventricle. Specific tumor types with a predilection for the fourth ventricle and thus for inducing nausea and vomiting include medulloblastomas and ependymomas. Projectile vomiting without preceding nausea is fairly specific to posterior fossa childhood tumors and is rarely seen in adults. Tumors of the brainstem can also lead to similar symptoms via their effect on the nucleus solitarius.

Dizziness is another frequent complaint in brain tumor patients which can be either vague and ill-described or consistent with frank vertigo. A complaint of classic vertigo should raise suspicion of a tumor in the cerebellopontine angle such as a schwannoma, meningioma, or metastasis, or tumors in the pons or posterior fossa. Posterior fossa tumors sometimes present with vertigo and concomitant headache or dizziness. Concomitant signs of incoordination such as dysmetria or ataxia are highly suggestive of a cerebellar or pontine lesion. Tumors that are supratentorial may at times also present with dizziness, though this is usually of the vague, ill-defined type that is more consistent with a sensation of lightheadedness and can be related to elevations in intracranial pressure.

Seizures are another common clinical manifestation of intracranial tumors. Although they are the result of a focal lesion, their frequent secondary generalization often prevents accurate localization. There may be post-ictal clues, such as Todd paralysis or post-ictal aphasia, which aid in localization of the lesion. If secondary generalization does not occur, or if the seizure semiology prior to generalization is clear, localization may be possible. The frequency of seizures in patients with brain tumors is around 30%, with significant variability by tumor type. Typically, slow-growing low-grade tumors are most epileptogenic and cause seizures that are often difficult to manage clinically. As an example, low-grade gliomas have a seizure frequency of 65–85% whereas the incidence of seizures in glioblastoma is 30–50%, closer to the average across all tumor types. The reason for the higher frequency in lower grade tumors remains elusive but may simply be related to the longer survival times of these patients. About 10–25% of patients with meningiomas or metastasis also develop seizures, with some variation by location. High convexity meningiomas and cortical metastasis are associated with higher seizure frequencies...

Table of contents

• Cover
• Title page
• Copyright page
• Contributors
• Series Foreword
• Preface
• Acknowledgments
• Part I: Overview and General Aspects of Therapy
• Part II: Adult Nervous System Tumors
• Part III: Pediatric Brain Tumors
• Part IV: Effects of Systemic Cancer and Treatment on the Nervous System
• Index
• Color Plates