Can short-term memory loss, paresthesia in the lower legs and feet, and burning pain in the arms be caused by a brain tumor in a patient with normal serum vitamin B12 levels?

Can This Be a Brain Tumor?

While brain tumors can cause memory impairment, the combination of short-term memory loss with bilateral lower extremity paresthesias and burning arm pain—despite normal B12 levels—is more consistent with other neurological conditions, particularly Guillain-Barré syndrome or functional B12 deficiency with falsely normal serum levels, rather than a primary brain tumor.

Why Brain Tumors Are Less Likely

Brain tumors typically do not cause diffuse peripheral symptoms like bilateral leg paresthesias and arm burning pain unless there is spinal involvement through leptomeningeal spread. 1 Isolated brain parenchymal tumors cause focal neurological deficits corresponding to their anatomical location, not the diffuse peripheral pattern described here. 1

Memory Impairment in Brain Tumors

• Cognitive impairment, including memory deficits, is present in 90% of patients with primary brain tumors and 91% of patients with brain metastases before treatment. 2
• Memory and executive functioning are the most frequently impaired cognitive domains in brain tumor patients. 2
• However, brain tumors causing isolated memory problems would not typically produce the bilateral peripheral sensory symptoms described. 1

When Brain Tumors Could Cause This Pattern

Leptomeningeal metastasis is the primary mechanism to consider when brain tumors cause tingling in multiple body regions simultaneously. 1 This occurs when:

• Tumor cells disseminate along meningeal and ependymal surfaces or with CSF flow. 1
• Radicular signs including sensory deficits, weakness, and cauda equina syndrome develop when tumor cells involve nerve roots. 1
• The multifocal nature reflects involvement of multiple CNS levels simultaneously. 1

More Likely Alternative Diagnoses

Guillain-Barré Syndrome

This presentation is highly consistent with Guillain-Barré syndrome, which characteristically presents with distal paresthesias preceding or accompanying bilateral ascending weakness. 2, 3

Key features matching this case:

• Distal paresthesias or sensory loss that precede or accompany weakness. 2, 3
• Pain (muscular, radicular, or neuropathic) is frequently reported and can be an early symptom. 2, 3
• Bilateral symptoms typically starting in the legs and progressing to the arms. 2, 3
• About two-thirds of patients report symptoms of infection in the 6 weeks preceding disease onset. 3

Functional B12 Deficiency Despite Normal Serum Levels

Normal serum B12 levels do not exclude functional B12 deficiency, as anti-intrinsic factor antibodies can cause falsely normal or elevated serum vitamin B12 levels. 4

Critical diagnostic considerations:

• Paresthesia is a common presenting complaint in vitamin B12 deficiency and may be central (myelopathic) or peripheral (neuropathic) in origin. 5
• Neurological symptoms can occur without anemia or macrocytosis. 6
• When patients report numbness even without decreased serum vitamin B12 levels, pernicious anemia and subacute combined degeneration should be suspected. 4
• Measurements of serum homocysteine and anti-intrinsic factor antibodies should be obtained. 4

Recommended Diagnostic Approach

Immediate Workup

Obtain cerebrospinal MRI with contrast to evaluate for leptomeningeal spread if brain tumor is suspected. 1 The American Academy of Neurology recommends this in patients with known or suspected brain tumors presenting with tingling in legs, back, and arms. 1

Characteristic MRI findings of leptomeningeal disease include:

• Sulcal enhancement, linear ependymal enhancement. 1
• Cranial nerve root enhancement. 1
• Leptomeningeal enhancing nodules of the cauda equina. 1
• Sensitivity ranges from 66-98% for detecting leptomeningeal metastases. 1

Additional Testing to Exclude Alternatives

Perform detailed neurological examination documenting reflexes, sensory distribution, and motor strength. 2

• Decreased or absent reflexes suggest Guillain-Barré syndrome. 2, 3
• Electromyography can confirm peripheral neuropathy patterns. 7
• Spinal MRI may show T2-weighted hyperintense lesions in subacute combined degeneration. 4

Obtain serum homocysteine and anti-intrinsic factor antibodies even with normal B12 levels. 4

• Elevated homocysteine with positive anti-intrinsic factor antibody confirms functional B12 deficiency. 4
• This testing is essential because anti-intrinsic factor antibody can cause falsely normal or elevated serum vitamin B12 levels. 4

Common Pitfalls to Avoid

• Do not rely solely on serum B12 levels to exclude B12 deficiency. Neurological symptoms can occur with normal or even elevated B12 levels when anti-intrinsic factor antibodies are present. 4
• Do not assume diffuse peripheral symptoms indicate brain pathology. Brain tumors cause focal deficits unless there is leptomeningeal or spinal involvement. 1
• Do not delay workup if symptoms progress rapidly. Guillain-Barré syndrome reaches maximum disability within 2 weeks and requires urgent treatment. 2, 3