What is the diagnosis and treatment for an older adult patient presenting with short-term memory loss, paresthesia (tingling) in the lower legs and feet, and burning pain in the arms?

Suspected Vitamin B12 Deficiency with Peripheral Neuropathy and Cognitive Impairment

This presentation of short-term memory loss combined with distal paresthesias (tingling in legs/feet) and burning pain in the arms strongly suggests vitamin B12 deficiency until proven otherwise, and you should immediately order serum B12, methylmalonic acid, homocysteine, and complete blood count before initiating empiric B12 replacement therapy. 1, 2

Immediate Diagnostic Workup

Essential Laboratory Tests

• Vitamin B12 level is the single most important test, as deficiency commonly presents with this exact triad of cognitive impairment, distal sensory neuropathy, and burning dysesthesias 1, 2
• Methylmalonic acid and homocysteine should be ordered simultaneously, as they are elevated even when B12 levels are borderline-low and increase diagnostic sensitivity 1
• Complete blood count to assess for macrocytic anemia, though neurologic symptoms often precede hematologic changes 2
• Thyroid function tests (TSH, free T4) as hypothyroidism can mimic this presentation 1, 2
• Comprehensive metabolic panel to exclude renal dysfunction and electrolyte abnormalities 3, 2
• Hemoglobin A1c or fasting glucose since diabetic neuropathy is the most common cause of peripheral neuropathy with burning pain and paresthesias 4

Cognitive Assessment

• Administer Montreal Cognitive Assessment (MoCA) as it is more sensitive than MMSE for detecting mild cognitive impairment, particularly in memory domains 1, 3
• Obtain collateral history from a reliable family member using the AD8 or IQCODE to corroborate the degree of memory impairment and assess whether instrumental activities of daily living are affected 3, 2

Neuroimaging

• Order brain MRI to exclude structural causes including stroke, tumor, or normal pressure hydrocephalus, particularly given the cognitive symptoms 1, 2
• MRI may also reveal white matter changes suggesting vascular cognitive impairment or medial temporal lobe atrophy suggesting neurodegenerative disease 1

Peripheral Neuropathy Evaluation

Clinical Examination

• Perform thorough neurologic examination focusing on distal sensory loss, vibration sense, proprioception, and ankle reflexes 4
• The combination of burning pain in arms and tingling in lower extremities suggests a length-dependent sensory polyneuropathy, most commonly from B12 deficiency or diabetes 4

Electrodiagnostic Testing

• Consider electromyography with nerve conduction studies if the diagnosis remains uncertain after initial laboratory workup, as this can distinguish between peripheral neuropathy, radiculopathy, and other causes 4

Additional Neuropathy Workup

• Serum ferritin should be checked if restless legs symptoms are present, as values less than 50 ng/mL are consistent with RLS and suggest need for iron supplementation 4

Differential Diagnosis Considerations

Most Likely: Vitamin B12 Deficiency

• This is the unifying diagnosis that explains both cognitive and peripheral nerve symptoms in older adults 1, 2
• B12 deficiency causes subacute combined degeneration affecting both the peripheral nerves (causing paresthesias and burning pain) and the central nervous system (causing memory impairment) 4

Alternative Diagnoses to Exclude

• Diabetic peripheral neuropathy typically presents with burning feet, tingling, and paresthesias in a stocking-glove distribution 4
• Hepatitis C-related peripheral neuropathy can cause distal sensory symptoms and cognitive impairment, but is less common 4
• Paraneoplastic syndrome should be considered if symptoms are rapidly progressive, particularly with smoking history, as small cell lung cancer can present with peripheral neuropathy and cognitive changes 5
• Early dementia (Alzheimer's or vascular) could explain memory loss, but would not typically cause the prominent peripheral neuropathy symptoms 1, 3

Treatment Approach

If B12 Deficiency Confirmed

• Initiate vitamin B12 replacement immediately with intramuscular cyanocobalamin 1000 mcg daily for one week, then weekly for one month, then monthly maintenance 1
• Oral high-dose B12 (1000-2000 mcg daily) is an alternative for patients without severe neurologic symptoms or malabsorption 1

If Diabetic Neuropathy Confirmed

• First-line pharmacologic therapy includes tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs), or anticonvulsants (gabapentin, pregabalin) for painful symptoms 4
• Optimize glycemic control as the primary disease-modifying intervention 4

Symptomatic Management

• For burning pain and dysesthesias, consider gabapentin starting at 300 mg at bedtime, titrating up to 900-3600 mg daily in divided doses, or pregabalin 75-300 mg twice daily 4
• Avoid opioids as first-line therapy given addiction risk and limited long-term efficacy data 4

Critical Pitfalls to Avoid

• Do not delay B12 replacement while waiting for test results if clinical suspicion is high, as neurologic damage can become irreversible 1
• Do not attribute all symptoms to "normal aging" without proper workup, as this presentation demands investigation for reversible causes 4, 2
• Do not start cholinesterase inhibitors for memory symptoms until reversible causes like B12 deficiency, hypothyroidism, and medication effects are excluded 3, 2
• Review all medications immediately for anticholinergics, benzodiazepines, or opioids that could contribute to cognitive impairment 3, 2

Follow-Up Protocol

• Reassess in 4-6 weeks after initiating B12 replacement to evaluate response in both cognitive and neuropathic symptoms 1
• If no improvement occurs, proceed with more extensive evaluation including referral to neurology for consideration of other causes of peripheral neuropathy and cognitive impairment 4, 2
• Schedule comprehensive cognitive reassessment in 3-6 months if memory symptoms persist despite treatment of reversible causes 1, 2