Toxins, Cancers, and CNS infections

Question 1

Benign brain tumors

Answer 1

this is a misnomer, because “benign” tumors are not harmless. They can undergo malignant transformations and given their location (especially around the brain stem) can become lethal. They do not invade neighboring cells. They grow slowly by way of expansion (often compressing other areas); are circumscribed; resemble the cell of origin; and tend to be well differentiated. These include meningiomas, epidermoid tumors, dermoid tumors, hemangioblastomas, colloid cysts, pleomorphic xanthoastrocytomas, craniopharyngiomas, and schwannomas (which can grow on cranial cells).

Meningiomas are the most common, making up 15% of all adult brain tumors (1/3 of the gliomas), reaching peak incidence in middle age, affecting more females than males. The gender difference is an exception to the rule, because tumors of the CNS are overall more common in males.

Question 2

Malignant brain tumors

Answer 2

are anaplastic, meaning they cannot be clearly demarcated from normal tissue); they vary in shape, size, and overall pattern; and usually proliferate rapidly. The proliferation rate is related to the so-called “aggressiveness” of the tumor. They invade and destroy neighboring cells. The term “malignant,” as used here, differs from its common usage with other types of cancer. Because brain tumors rarely metastasize- save medullablastoma and ependymoma- “malignant” in this case refers to its aggressive characteristics and prognostic implications. They are caused by multiple changes in gene expression (predominantly the p53 gene, located on chromosome 17p), which lead to uncontrolled cell proliferation and cell death. Oncogenes and cancer suppressor genes are implicated in tumor growth. Malignant tumors include anaplastic astrocytoma, glioblastoma multiforme, anaplastic oligodendroglioma, medulloblastomas, and pineoblastomas.

-these make up 1.4% of all cancers (2% of cancer-related deaths)

Question 3

Brain tumor epidemiology

Answer 3

Malignant brain tumors: 1.4% of all cancers (2% of cancer-related deaths)

• peak incidence of brain tumors: 74-84 years of age.
• average age of onset (primary brain tumors): 54 years of age
• gender differences: Greater incidence in boys and men
• GLOBOCAN 2002 worldwide annual incidence of CNS tumors:
  
  • 3.7 and 2.6 cases per 100,000 males and females, respectively
  • total is 7.3 cases per 100,000
  • higher rates in more developed nations

-incidence rates of cancer in general is greater in African Americans, but incidence rates of CNS tumors are higher in Caucasians (7.2 per 100,000) than African Americans (3.9 per 100,000)

Question 4

Brain tumor signs and symptoms

Answer 4

varies from essentially asymptomatic to significant cognitive and behavioral impairment.

Rapidly growing tumors can cause increased intracranial pressure, which is then usually responsible for many signs and symptoms observed in patients (e.g., headache, vomiting, and personality and cognitive changes). Increased ICP can also lead to false localizing signs, due to a shift in distal intracranial structures.

Significant tumor growth can cause herniations in the temporal, cerebellar, and subfalcial areas, due to a shift in tissue to compartments where the pressure is low.

Tumors can also release unknown substances causing vasogenic edema, which can further increase intracranial pressure.

Most common symptom is headache for adults and children. Over 50% of adult patients with brain tumors experience headaches, as early or late symptoms, whereas headaches occur in 33% of children. Headaches are described as nonpulsatile and intermittent, and may resemble migraine or tension headaches. With increased ICP, a bifrontal or bioccipital headache, regardless of localization, may occur. If lateralized, headache is often ipsilateral to tumor location.

Partial and/or generalized seizures are a common symptom, particularly if the tumor is slow growing and affects cortical regions. Seizures occur in 40-60% of adult patients at some time, and may be the symptom leading to a diagnosis. Seizures affect 38% of children with brain tumors.

Lateralized or localizing symptoms can occur. Vomiting, loss of appetite, personality and mood changes, vertigo, fatigue, and cognitive problems may present in adults and children. Vomiting and vertigo are common symptoms of tumors affecting the posterior fossa. Compression of the brain stem results in motor and/or sensory signs, cranial nerve impairments, and hydrocephalus. Loss of appetite, personality and mood changes can be associated with frontal lobe tumors, particularly when the orbital frontal area is affected. Contralateral motor weakness, expressive language problems, attention and/or memory problems may also occur. Frontal lobe tumors can, however, be asymptomatic. Cognitive symptoms tend to be focal in nature. Thus, lesions in the left hemisphere may impair language-mediated functions. In contrast, lesions in the right hemisphere may affect visual-perceptual/spatial skills. Thalamic tumors also can cause cognitive impairment, contralateral sensory loss, hemiparesis, and aphasia, among other symptoms. Cerebellar and medial temporal lesions cause ataxic symptoms and memory loss, respectively.