Could a brain tumor be causing symptoms of persistent anxiety, paresthesias, and cognitive impairment in a patient with a complex medical history and recent discontinuation of multiple medications, including a history of impaired fasting glucose and mild inflammatory markers?

Could This Be a Brain Tumor?

While brain tumors can cause cognitive impairment, anxiety, and paresthesias, these symptoms are nonspecific and more commonly result from medication withdrawal, metabolic derangements, or psychiatric conditions—however, given the persistence and combination of symptoms, neuroimaging with MRI is warranted to definitively exclude intracranial pathology. 1

When to Suspect a Brain Tumor

Brain tumors should be considered in patients presenting with:

• New-onset psychiatric symptoms or personality changes, even without focal neurological deficits 2
• Cognitive impairment with atypical features or progressive course 1
• Persistent symptoms despite addressing reversible causes (medication effects, metabolic issues, depression) 1

The key clinical context here is that 90% of primary brain tumor patients and 91% of brain metastasis patients already have cognitive impairment before any treatment, making cognitive dysfunction a common presenting feature 1

Cognitive Dysfunction Pattern in Brain Tumors

Brain tumors characteristically affect specific cognitive domains:

• Memory and executive functioning are the most frequently impaired domains in brain tumor patients 1
• Tumors cause both local damage and global cognitive dysfunction through disruption of cognitive networks, not just from mass effect 1
• Attention, processing speed, and visuospatial functioning are also commonly affected 1

Critical Distinguishing Features

Favoring Brain Tumor:

• Progressive worsening of cognitive symptoms over time 1
• Focal neurological deficits developing alongside cognitive/psychiatric symptoms 1
• New-onset seizures in a patient without prior epilepsy history (should trigger immediate neuroimaging) 1

Favoring Alternative Diagnosis:

• Recent discontinuation of multiple medications (benzodiazepines, antidepressants, etc.) can cause withdrawal-related anxiety, paresthesias, and cognitive fog 1
• Impaired fasting glucose and inflammatory markers suggest metabolic or systemic inflammatory processes 3
• Symptoms that fluctuate significantly or improve with addressing reversible factors 1

Diagnostic Approach

Obtain brain MRI with contrast as the definitive imaging modality for any patient with: 1, 2

• Persistent cognitive impairment with unclear etiology
• New-onset psychiatric symptoms or personality changes
• Symptoms refractory to treatment of reversible causes

Before imaging, systematically address reversible factors: 1

• Screen for depression, anxiety, pain, fatigue, and sleep disturbance—all can mimic or exacerbate cognitive impairment
• Review all medications including over-the-counter drugs and supplements for cognitive side effects
• Correct metabolic derangements (glucose dysregulation, electrolyte abnormalities)

Important Clinical Pitfalls

• Do not rely on brief screening tools like MMSE—they lack sensitivity for subtle cognitive decline that may indicate early brain tumor 1
• Anxiety alone is not a typical presenting symptom of brain tumors, but when combined with progressive cognitive impairment and paresthesias, warrants investigation 2
• Inflammatory markers (elevated CRP, etc.) in glioma patients correlate with behavioral symptoms including depression and anxiety, but this does not exclude tumor as the primary cause 3
• Medication withdrawal (especially benzodiazepines, SSRIs) can cause a constellation of symptoms mimicking neurological disease—timeline of symptom onset relative to medication changes is crucial 1

Risk Stratification for Imaging

High priority for immediate MRI: 1, 2

• Any focal neurological signs
• Progressive cognitive decline despite addressing reversible factors
• New-onset seizures
• Personality changes or atypical psychiatric presentations

Moderate priority (can address reversible factors first, then image if persistent): 1

• Isolated cognitive complaints with recent medication changes
• Symptoms with clear temporal relationship to medication discontinuation
• Presence of multiple reversible factors (metabolic, psychiatric, medication-related)

The clinical scenario described—persistent anxiety, paresthesias, cognitive impairment with complex medical history—falls into a gray zone where imaging should not be delayed beyond 2-4 weeks of addressing reversible factors, particularly given the nonspecific nature of early brain tumor presentations 1, 2