The neurologic disorder in which fatigue has been best evaluated is multiple sclerosis in which at least 78% of these patients suffer from fatigue and is often the most disabling symptom of this disease (55). Similarly, in a study of over 1300 cancer patients, 58% of patients described problems with fatigue, yet less than 52% of those ever reported symptoms to their caregivers, and only 14% had received some type of treatment (56). Perhaps the greatest obstacle to recognizing fatigue is in terms of definition as various health care professionals define fatigue differently based on their area of expertise. The most common complaint heard in our outpatient brain tumor clinic on a daily basis from patients, regardless of stage of treatment, is that they feel fatigue. This may be further defined as tiredness, exhaustion, muscle weakness, lethargy, or depression. Because fatigue can mean different things to physicians and patients it is imperative that the physician obtain a comprehensive history to better define what the patient is describing.

Treatment—General Considerations

• Exercise: this helps stimulate the appetite, maintain muscle mass.

• Nutrition: avoid refined sugars, which can alter blood glucose levels, that can cause fatigue as levels "spike" and then drop. Make sure hydration is adequate.

• Limit caffeine and tobacco: both of these act as CNS stimulants and can interfere with sleep.

• Limit alcohol intake: it is a CNS depressant, can affect other drugs metabolized in the liver and possibly affect seizure threshold.

No drugs have been approved by the Food and Drug Administration (FDA) for treatment of fatigue in brain tumor patients, however various medications have been used clinically over the years. Currently two clinical trials in brain tumor patients are looking at treating fatigue related problems (http://www.clinicaltrials.gov). The first trial is a "Phase III Randomized trial of D-Methylphenidate To Improve Quality of Life in Patients Receiving Radiotherapy for Primary or Metastatic Brain Tumor" This is a placebo controlled trial. The second trial is a "Pilot Randomized Study of Modafanil for Treatment of Fatigue and Neurobehavioral Dysfunction in Patients with Primary Brain Tumors." Meyer et al. (57) evaluated 30 primary brain tumor patients who received either 10, 20, or 30 mg of methylphenidate bid. All patients underwent neuropsychological assessment. They reported significant improvements in cognitive function at the 10 mg bid dose. Functional motor improvement was also noted. No increased seizure activity was noted and these gains were noted despite progression on MRI in at least half of the cases. An abstract was presented at the Society for Neuro-oncology (SNO) meeting in Toronto in November 2004 evaluating the effect of Donepezil in previously irradiated brain tumor patients (58). Patients were given donepezil at 5 mg/d for 6 wk and then 10 mg/d for 18 wk. They reported an improvement in the health-related quality of life and mood as measured by Functional Assessment of Cancer Therapy for Brain (FACT-BR) and Profile of Mood States (POMS). Patients also reported a significant reduction in fatigue. Further clinical trials are required looking for ways to improve patient quality of life and in particular fatigue.

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