What could be causing a patient with a history of chemotherapy for brain tumors to experience feelings of disorientation, memory issues, heaviness in the head, and paresthesia (tingling) in their limbs?

Chemotherapy-Induced Cognitive Impairment and Peripheral Neuropathy in Brain Tumor Survivors

This patient is experiencing chemotherapy-induced cognitive impairment ("chemobrain") combined with peripheral neuropathy—both well-documented sequelae of chemotherapy for brain tumors that require systematic evaluation to exclude tumor progression and management of reversible contributing factors. 1

Understanding the Clinical Picture

The constellation of symptoms—disorientation, memory problems, head heaviness, and limb paresthesias—reflects two distinct but commonly co-occurring neurotoxic effects of chemotherapy:

Cognitive Dysfunction ("Chemobrain")

• Cognitive impairment is already present in 90% of patients with primary brain tumors before treatment and can be worsened by chemotherapy, radiation, or both. 1
• The symptoms described (feeling "out of it," memory issues, head heaviness) align with the most commonly affected cognitive domains: memory, attention, executive functioning, and processing speed. 1, 2
• These deficits can persist for years after treatment completion, with documented impairments up to 10 years post-chemotherapy. 2
• The underlying mechanisms include white matter damage from neurotoxicity, elevated cytokines causing blood-brain barrier disruption, and structural changes in gray matter volumes. 1, 2

Peripheral Neuropathy

• Tingling in the limbs represents chemotherapy-induced peripheral neuropathy, which is among the most common neurotoxic side effects of chemotherapy. 3
• Vinca-alkaloids, cisplatin, and taxanes are the primary culprits for peripheral neurotoxicity and are widely used for various malignancies. 3
• This neuropathy is clearly related to cumulative dose or dose-intensities. 3

Critical First Step: Rule Out Tumor Progression

Before attributing symptoms solely to treatment effects, imaging is mandatory to exclude CNS disease progression or new complications. 1

• For patients presenting with concomitant focal neurologic deficits or evolving symptoms, imaging is indicated to rule out brain or CNS disease. 1
• Worsening of pre-existing neurological symptoms in brain tumor patients often heralds tumor progression, and repeat MRI should be considered. 1
• This is particularly important because progressive disease causes 33% of acute neurologic dysfunction in the early post-treatment period and 55% beyond 100 days from treatment. 4

Systematic Assessment Approach

Screen for Reversible Contributing Factors

Patients presenting with cognitive impairment should be screened for potentially reversible factors including depression, pain, fatigue, and sleep disturbance. 1

• Review all current medications, including over-the-counter medications and supplements, as some can contribute to cognitive impairment. 1
• Fatigue and depression are common in cancer survivors and may negatively influence cognitive function. 1
• Address any potentially contributing factor identified. 1

Evaluate for Metabolic and Iatrogenic Causes

• Dysmetabolic states and iatrogenic factors cause 45% of acute neurologic dysfunction in the first 100 days following treatment. 4
• Check for electrolyte abnormalities, hepatic or renal dysfunction, and medication side effects. 4
• Dexamethasone use is significantly associated with acute neurologic dysfunction (p < 0.004). 4

Consider Leptomeningeal Disease

The combination of mental changes and sensorimotor deficits of extremities should raise suspicion for leptomeningeal metastasis in patients with known cancer. 5

• Key features include cognitive fog, radicular signs (weakness, voiding problems), and gait difficulties. 5
• Cerebrospinal MRI without and with contrast is the gold standard for diagnosing leptomeningeal metastasis, with sensitivity 66-98%. 5

Management Strategy

Nonpharmacologic Interventions (First-Line)

The NCCN Guidelines recommend nonpharmacologic interventions as first-line management, with pharmacologic interventions only as a last resort when other interventions fail. 1, 2

• Instruction in coping strategies to help patients adapt to cognitive changes. 1, 2
• Management of contributing factors: Aggressively treat distress, pain, sleep disturbances, and fatigue, as these can significantly worsen cognitive symptoms. 1, 2
• Occupational therapy to help patients develop adaptive strategies for daily function. 1, 2
• Cognitive rehabilitation and computerized cognitive exercise are options for managing cognitive problems in an individualized manner. 6

Pharmacologic Options (When Nonpharmacologic Measures Insufficient)

Pharmacotherapy should be tailored to the individual's cognitive profile and used only when other interventions have been insufficient. 1, 6

• Stimulant medications (borrowed from attention-deficit/hyperactivity disorder management) have shown benefits for patients with brain tumors. 6
• Acetylcholinesterase inhibitors have demonstrated benefits when tailored to cognitive profiles. 6
• Memantine may provide neuroprotection, particularly if further radiation therapy is planned. 6

Peripheral Neuropathy Management

Management mainly consists of cumulative dose-reduction or lower dose-intensities, especially in patients at higher risk for neurotoxic side effects. 3

• None of the neuroprotective agents can be recommended for standard use in daily practice at this time, and further studies are needed. 3
• Symptomatic management with gabapentinoids or duloxetine may provide relief, though evidence specific to chemotherapy-induced neuropathy in brain tumor patients is limited. 3

Important Caveats

Discordance Between Subjective and Objective Testing

• The correlation between patient reports of cognitive decline and results of neuropsychological testing has not been consistently demonstrated. 1
• A disparity often exists between self-reported cognitive complaints and objective neurocognitive testing results, suggesting current testing may be inadequate for detecting subtle changes. 2
• This means that normal neuropsychological testing does not invalidate the patient's experience—their symptoms are real and warrant intervention. 1, 2

Long-Term Perspective

• Cognitive deficits can persist long-term, with studies showing impairments in breast cancer survivors an average of 21 years post-diagnosis. 1
• Currently, no established management strategies or clinical guidelines are available for chemotherapy-induced cognitive impairment. 2
• The focus should be on quality of life optimization through the nonpharmacologic interventions described above. 1, 2

Monitoring for Progression

• Since worsening symptoms often herald tumor progression, maintain a low threshold for repeat imaging if symptoms evolve or worsen. 1
• Regular clinical follow-up to assess response to interventions and detect any new neurological signs is essential. 1