Low-Grade Astrocytoma Clinical Presentation

No historical factors are pathognomonic for low-grade glioma. The history, however, should alert the clinician to the presence of a neurologic disorder and the need for an imaging study. Putting together the information from the history, the physical examination, and the imaging data will lead to a tentative diagnosis of low-grade glioma. The histories of patients with low-grade glioma are strangely similar. With low-grade astrocytomas, the most common complaints in the history are seizure and headache. Infiltrating low-grade astrocytomas can cause focal neurologic deficits (ie, weakness or numbness). Generally, these symptoms have a gradual onset.

• Pilocytic astrocytomas tend to be midline and may cause symptoms related to this location. A large cerebellar tumor can cause obstructive hydrocephalus, and the patient may present with headache and lethargy. These patients may also have a history of imbalance, falling, or incoordination. Pilocytic tumors in the brain stem cause neurologic deficits secondary to the involvement of brainstem nuclei, while hypothalamic tumors cause a variety of endocrine problems (eg, hypernatremia). Brainstem symptoms may include double vision or facial weakness. Persons with optic nerve tumors may present with visual deficits.
• Subependymal giant-cell astrocytomas frequently cause obstructive hydrocephalus in patients with tuberous sclerosis. Headache is then secondary to hydrocephalus and elevated intracranial pressure.
• Patients with pleomorphic xanthoastrocytoma frequently have long-standing histories of seizures in addition to the more general complaints already noted.
• A small percentage of low-grade astrocytomas present in the spinal cord of both children and adults. The history is characterized by a slow onset of back pain and neurologic deficits. The pain usually is localized over the region of the tumor, which is most common in the cervicothoracic area. Neurologic symptoms include paresthesias in the arms or legs. Weakness, objective numbness, and bowel or bladder symptoms also may be present.

A thorough neurologic examination is mandatory. Level of consciousness should be noted first. Lethargy is an important sign of elevated intracranial pressure. Examination of the cranial nerves may indicate involvement of the brain stem. Nystagmus is an important sign. Papilledema can be seen if intracranial pressure is elevated. The motor and sensory examination may show weakness or impairment of sensory discrimination if the motor or sensory pathways are involved with tumor, edema, or mass effect. Hemiparesis may be accompanied by increased deep tendon reflexes or an extensor plantar response (Babinski sign). Examining for cerebellar signs (eg, ataxia) is important if a tumor in that location is suspected.

• Since low-grade astrocytomas are associated with some genetic disorders, examining patients for these diseases is important. Patients with tuberous sclerosis have decreased intelligence and a characteristic skin lesion on the face (around the nose) called adenoma sebaceum, which is actually angiofibroma. Other cutaneous manifestations also may be present (eg, ash-leaf spots). Patients with NF-1 may have obvious cutaneous neurofibromas and/or café-au-lait spots.
• Low-grade astrocytomas that affect the spinal cord may result in various degrees of weakness and/or sensory change in the arms, legs, or sacral area. Myelopathy with increased deep tendon reflexes and/or positive Babinski sign may be present.

The etiology of low-grade gliomas is poorly understood. High-grade gliomas, which are much more common, have been studied in greater detail regarding possible environmental factors. Environmental factors that are linked with a higher incidence of high-grade gliomas include exposure to radiation or N- nitroso compounds. These factors have been verified in experimental models; however, the degree to which these factors play a role in the incidence of human tumors is unclear.

Neoplastic transformation is thought to be a genetic process, and deletions and mutations in certain genes are thought to play a role in the change of normal glial precursor cells to gliomas. For example, p53 mutations have been found in some, but not all, low-grade gliomas. Chromosomal analysis also has shown gain or loss of genetic material in certain low-grade gliomas, although as yet no consistent pattern has been appreciated. Patients with NF-1 are known to have an abnormality on chromosome 17, while the exact genetic defect in tuberous sclerosis still is being investigated.

In summary, the environmental or genetic factors that are involved in the generation of low-grade gliomas are unknown. As mentioned already, however, patients with NF-1 or tuberous sclerosis are at much higher risk of developing these tumors and should undergo surveillance imaging by MRI.