Intracranial mass lesions may come to clinical attention by producing headaches, seizures, or other focal neurological findings. Some mass lesions are life-threatening, placing the patient at risk for increased intracranial pressure or recurrent seizures. Others are “incidentalomas,” which grow slowly and bear watching, but have a more benign prognosis. The important factors in diagnosing a mass lesion are its location, the patient’s immune status, and their geographic background. This chapter reviews common intracranial mass lesions in adults. Many pediatric tumors or less common masses are not discussed, and the reader is instead referred to a more comprehensive neuro-oncology text.1
Supratentorial, brainstem, and cerebellar masses
Metastatic tumors are the most common intracranial tumors in adults. Their diagnosis is usually fairly straightforward in patients with a known primary tumor, but metastatic lesions may also be the first presentation of cancer. Three radiological features help to differentiate metastatic lesions from other intracranial masses: they tend to be multiple, they are located at the gray–white junction, and they are associated with large amounts of surrounding vasogenic edema (Figure 23.1).2
The first steps in evaluating a patient with cerebral metastasis are to control the surrounding edema and address or prevent increased intracranial pressure (Chapter 2). Treat patients with vasogenic edema with a 10 mg loading dose of dexamethasone followed by 4 mg qid. When prescribing dexamethasone, be sure to provide ulcer prophylaxis with an agent such as ranitidine (150 mg bid).
Cerebral metastases also pose an increased risk for seizures (Chapter 20). Unless the patient presents with a seizure, however, anticonvulsant prophylaxis is not indicated, as it does not prevent seizures and has the potential to interact with chemotherapy.3
The next step in managing a patient with cerebral metastasis is to define the origin of the tumor. Common tumors that metastasize to the brain include carcinomas of the lung, breast, kidney, and colorectal region, and melanoma. Evaluation for a primary tumor should therefore include a CT scan of the torso with and without contrast and careful dermatological assessment. Women should undergo mammography. Although tumors of the prostate and testicular region are less frequent sources of metastases, men require directed testicular examination, scrotal ultrasound, and prostate-specific antigen measurement if no other primary source is found. In some patients, a thorough medical evaluation does not disclose the source of the metastasis, and the primary tumor is defined only after brain biopsy.
Definitive management of newly discovered cerebral metastasis depends on patient age and the status of the primary cancer. As might be expected, younger patients and those with a lower burden of systemic disease have better prognoses and are better candidates for more aggressive management. Patients with surgically accessible lesions and otherwise favorable prognosis should undergo tumor resection followed by whole-brain radiation therapy. Those with inaccessible lesions but otherwise good prognosis should undergo stereotactic radiosurgery. Patients with poor prognosis should receive palliative whole brain radiotherapy. Unfortunately, most patients with cerebral metastasis have a poor overall prognosis, with most surviving for just a few months.
Primary brain tumors
Glial tumors are the most common primary intracranial neoplasms. High-grade gliomas, including glioblastoma multiforme and high-grade oligodendrogliomas,
Figure 23.1 Axial fluid attenuation inversion recovery (FLAIR) MRI showing metastasis (arrow) with large amounts of surrounding cerebral edema.
are typically hypodense on T1-weighted images and enhance heterogeneously (Figure 23.2). Common presentations include headache and seizures. The diagnosis must be made by examining tissue, either by stereotactic biopsy or at the time of resection. Unfortunately, high-grade gliomas have a poor prognosis. Patients who choose aggressive therapy should be treated with a combination of maximal resection, adjuvant radiation therapy, and temozolomide.
Low-grade gliomas are unlike many other brain tumors in that they often exert minimal mass effect. They have a propensity to produce refractory seizures, which often brings them to clinical attention (Chapter 20). Optimal management of low-grade gliomas is not entirely clear. Because they may transform into higher-grade tumors, aggressive treatment including surgical resection and radiotherapy would seem to be the most reasonable approach. However, some low-grade gliomas follow a fairly benign course and may be followed with serial MRI every 3 months, with surgery being reserved for patients with tumor growth or transformation.
Meningiomas are the second most common primary intracranial tumors. They are often asymptomatic,
Figure 23.2 Contrast-enhanced T1-weighted MRI of a high-grade glial tumor showing a hypodense occipital lesion with a ring of surrounding enhancement and scant edema (arrow).
but some come to clinical attention by producing headaches, seizures, or focal neurological findings. Radiologically, meningiomas are typically dural-based masses that enhance homogeneously with contrast (Figure 23.3). Asymptomatic meningiomas may be followed with serial MRI, initially every 6–12 months. When possible, symptomatic meningiomas and those that show evidence of expansion should be removed surgically. Patients with surgically accessible higher-grade lesions should undergo postoperative radiation therapy, while those with inaccessible lesions should be treated with radiotherapy.
Primary CNS lymphoma
Primary CNS lymphoma (PCNSL) usually presents with headaches or focal neurological findings. They are most commonly solitary, invasive, periventricular lesions. A classic but uncommon radiographic finding is crossing of the corpus callosum. Lymphomas are extremely sensitive to steroids, and for this reason, steroids may obscure the diagnosis and should not be administered until PCNSL is confirmed histologically. The mainstay of treatment of PCNSL is chemotherapy with systemic methotrexate. Although adding radiation therapy to methotrexate may improve survival, this combination may be quite toxic and should be considered with extreme caution, especially in older patients.
Figure 23.3 Contrast-enhanced T1-weighted MRI of a meningioma showing a homogeneously enhancing mass (thick arrow). Note the dural tail (thin arrow), a helpful sign in diagnosing meningioma.
Arteriovenous malformations (AVMs) produce a variety of symptoms including hemorrhages, seizures, headaches, and focal neurological signs such as hemiparesis or visual field cuts. They often present for the first time in childhood or young adulthood. The annual risk for hemorrhage from AVMs is approximately 2–3%, and 20% of these hemorrhages will be fatal.4 Beyond imaging studies, little is generally needed to make a diagnosis of an AVM: the vascular flow voids, which resemble a ball of worms on MRI, are pathognomonic (Figure 23.4). Decisions concerning management of AVMs depend on their size, location, and the presence of deep venous drainage (Table 23.1). In general, lesions with a Spetzler–Martin grade of I, II, or III should undergo microvascular surgery, endovascular surgery, or radiosurgery.4Procedures for grade IV and V AVMs are associated with high morbidities, and decisions about intervention should be made very carefully based on the experience and comfort level of the neurosurgeon.
Intracranial abscesses are life-threatening infections, which are usually acquired via direct spread (e.g.
Figure 23.4 T2-weighted axial MRI showing large frontoparietal arteriovenous malformation. The flow voids seen on T2 resemble a “ball of worms.”
head trauma, neurosurgery, or sinus infection) or as a result of hematogenous dissemination of an infection elsewhere. Headache is the most common sign of abscess. Because fever is present inconsistently, the diagnosis is often missed because it is not considered. In more severe cases, abscesses may produce seizures or encephalopathy. The preferred neuroimaging study for evaluating abscesses is MRI with contrast, which characteristically shows a ring-enhancing lesion. The diagnosis is established via brain biopsy, with blood cultures playing a potentially important role prior to tissue confirmation. Common causes of abscesses in immunocompetent patients include Gram-positive cocci, Gram-negative rods, and anaerobic bacteria. Empiric therapy should be designed with the assistance of an infectious disease specialist, and usually includes a combination of vancomycin, ceftriaxone or cefotaxime, and metronidazole. Surgical drainage of the abscess is definitive.
Tumefactive multiple sclerosis
Multiple sclerosis (MS) may produce demyelinating lesions that resemble gliomas both clinically and radiographically. This so-called tumefactive MS leads to symptoms that are otherwise unusual in MS, including
Table 23.1 Spetzler–Martin arteriovenous malformation grading scale5
The Spetzler–Martin grade is obtained by adding the numbers in the second column.
seizures and headache. Although there are no radiological features that reliably distinguish between glioma and tumefactive MS, findings that are more consistent with MS include young age of onset, the presence of multiple lesions, and minimal perilesional edema.6 In patients with known MS, it may be appropriate to perform magnetic resonance spectroscopy to differentiate between tumefactive MS and glioma.7 Unfortunately, brain biopsy is the only definitive way to make the diagnosis.
Sellar region masses
Masses in the sellar region are often noted as incidental findings in patients with nonspecific headache. In other patients, sellar masses are first detected when ocular motor abnormalities, visual field cuts, or hypothalamic–pituitary dysfunction develop. Approximately 90% of pituitary masses in adults are adenomas.8 Less common masses include craniopharyngioma, meningioma, metastases, abscesses, and cysts. Unfortunately, it is often difficult to distinguish among these masses radiographically. Although biopsy is the definitive way to diagnose a sellar region mass, the first step in the evaluation is to classify the mass by size, prolactin level, and whether it is causing any neuro-ophthalmologic abnormalities9:
• Masses that secrete prolactin are prolactinomas, and should be treated with dopamine agonists.
• Masses that secrete hormones other than prolactin are functional adenomas, and should undergo excision.
• Masses that produce neuro-ophthalmologic abnormalities should undergo excision.
• Masses that are smaller than 10 mm and that do not produce neuro-ophthalmologic abnormalities should be re-evaluated with MRI at 1 year. If there is no growth, repeat imaging studies only if neuro-ophthalmologic or endocrine symptoms develop.
• Tumors larger than 10 mm that do not produce neuro-ophthalmologic abnormalities should be evaluated with MRI at 6 months and then yearly if no growth is observed.
The assistance of an endocrinologist should be obtained in all but the most straightforward of cases.
Cerebellopontine angle masses
The most common presentation of a cerebellopontine angle (CPA) mass is hearing loss due to compression of the vestibulocochlear nerve. Because most CPA lesions grow slowly, compression of the vestibular portion of this nerve does not usually produce frank vertigo, but patients may complain of a mild sensation of feeling off balance. Other structures in the CPA that may be compressed include the trigeminal nerve, facial nerve, cerebellum, and brainstem.
Vestibular schwannomas (acoustic neuromas) account for the majority of CPA tumors. In patients with neurofibromatosis type 2, these tumors are bilateral. Meningiomas represent a small but important minority, and other masses such as cholesteatomas, gliomas, and metastases are uncommon. Decisions concerning treatment of a CPA tumor depend on the size of the tumor, its histology, and the symptom burden it produces. Surgical resection is the best approach for patients with large, symptomatic tumors. Because vestibular schwannomas and meningiomas grow slowly, patients with smaller, minimally symptomatic tumors may be followed with serial MRI scans every 6–12 months, or sooner if symptoms progress.
Masses in immunocompromised patients
AIDS patients, bone marrow transplant recipients, and other immunocompromised patients are susceptible to intracranial mass lesions that do not affect immunocompetent people. The two most important of these are toxoplasmosis and PCNSL. Fungal abscesses are also relatively specific to immunocompromised patients. Obviously, when evaluating an immunosuppressed patient with an intracranial mass lesion, it is
Figure 23.5 Multiple contrast-enhancing T1 lesions, some of which are ring-enhancing, in a patient with HIV infection and a CD4 count of 90 cells/µl, consistent with toxoplasmosis.
important to not neglect the possibility of masses that affect immunocompetent patients including primary and metastatic tumors.
Toxoplasmosis and primary CNS lymphoma
Toxoplasmosis (caused by reactivation of infection with the protozoan parasite Toxoplasma gondii) and PCNSL are the two intracranial masses that should be considered first in immunosuppressed patients. Both lesions occur in patients with CD4 counts lower than 100 cells/µl. Radiographic features may help to differentiate between the two, but are not entirely reliable: toxoplasma lesions are more likely to be multiple and to have a ring-enhancing pattern (Figure 23.5), while PCNSL is more likely to be a solitary mass and to involve or cross the corpus callosum. The usual protocols to differentiate between toxoplasmosis and PCNSL are:
• In stable patients, treat toxoplasmosis empirically with pyrimethamine (200 mg loading dose followed by 75 mg/day) and sulfadiazine (1.5–2 mg/kg qid) for 2 weeks. If the lesions decrease in size on repeat MRI, the diagnosis is toxoplasmosis, and appropriate treatment should be continued with the guidance of an infectious disease specialist. If the lesions do not decrease in size, arrange for brain biopsy.
• In patients with severe mass effect and impending herniation, initiate dexamethasone (10 mg × 1 followed by 4 mg qid) and arrange for diagnostic brain biopsy and resection of the mass.
In addition to the typical organisms that form intracranial abscesses in immunocompetent patients, immunocompromised patients are also susceptible to abscess formation by fungi such as Aspergillus, Candida albicans, Coccidioides immitis, and Cryptococcus neoformans. Evaluation of a suspected fungal abscess should include fungal blood cultures and spinal fluid analysis, provided that the abscess is not producing substantial mass effect. Treatment should be conducted with the supervision of an infectious disease specialist. Unfortunately, the outcome of fungal abscesses in immunocompromised patients is poor.
Masses in patients from the tropics and developing world
Infection with the pork tapeworm Taenia solium leading to neurocysticercosis is common in Latin America, Africa, and Asia. Although understanding the transmission and entire life cycle of the organism is helpful in managing the disorder, the two stages that are clinically relevant to the neurologist are active cysts and calcified cysts. Active cysts leading to seizures are the best-known neurological manifestation of neurocysticercosis (Chapter 20). Calcified cysts are usually asymptomatic and are noted only incidentally upon neuroimaging for other indications (Figure 23.6). Neurocysticercosis may also lead to ventricular obstruction, which in turn produces headaches and increased intracranial pressure. Both MRI and CT are used to diagnose neurocysticercosis. Active lesions enhance on MRI, and in some
Figure 23.6 Noncontrast head CT showing three calcified cysts (arrows) in a patient with neurocysticercosis.
cases, a scolex of the organism may be visible. CT is better suited for identifying calcified cysts. The diagnosis is confirmed by finding a positive enzyme-linked immunoelectrotransfer blot assay result in the serum. Treat patients with active lesions with albendazole 800 mg for 8 days with close infectious disease consultation; patients with multiple lesions and those that produce ventricular obstruction may require longer courses of treatment.10 When initiating albendazole, be sure to include a rapid prednisone taper, as antiparasitic agents may produce a life-threatening inflammatory response as the organisms die. Supportive care is an important component of treating neurocysticercosis: patients with seizures should be treated with anticonvulsants and those with ventricular obstruction may require neurosurgical intervention.
Hematogenous seeding of Mycobacterium tuberculosis may lead to an accumulation of organisms in the brain known as a tuberculoma. This is particularly common in patients from the Indian subcontinent and East Asia. Tuberculomas are often clinically silent, but may also produce a wide variety of serious neurological problems including seizures, headache, stroke, and meningitis (Chapter 1). The radiographic appearance of tuberculoma is quite variable: the most common appearance is a mass lesion with a T2-hypointense core and hyperintense rim, with approximately two-thirds of patients having more than one and sometimes numerous lesions.11 Treatment of tuberculoma includes a four-drug regimen (isoniazid, pyrazinamide, rifampin, and either ethambutol or streptomycin) supervised by an infectious disease specialist. Lesions that produce severe mass effect may require neurosurgical intervention.
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