What could be causing memory loss and tingling sensations in a patient's lower legs, back, arms, and face?

Differential Diagnosis: Memory Loss with Widespread Tingling

The combination of memory loss and tingling in multiple body regions (lower legs, back, arms, face) strongly suggests vitamin B12 deficiency (pernicious anemia) as the most likely diagnosis, which requires immediate evaluation with serum B12 levels, complete blood count, and consideration of intramuscular B12 replacement. 1

Priority: Rule Out Reversible Causes First

Vitamin B12 Deficiency (Pernicious Anemia)

• This is the most critical diagnosis to exclude because it presents with both cognitive impairment and peripheral neuropathy affecting multiple body regions 1
• Classic presentation includes:
  • Memory impairment and cognitive changes 1
  • Tingling sensations in a "stocking-glove" distribution that can extend proximally 2
  • Bilateral lower extremity weakness, numbness, and hyperreflexia 1
  • Ataxia and coordination problems 1
• Immediate laboratory workup required:
  • Serum vitamin B12 level (expect low values) 3
  • Complete blood count showing low hemoglobin/hematocrit and elevated mean corpuscular volume 1
  • Parietal cell antibodies and intrinsic factor antibodies 1
  • Homocysteine level 3
• Treatment is highly effective: Intramuscular vitamin B12 injections can lead to near-complete resolution of symptoms if initiated early 1
• Critical pitfall: Delayed diagnosis can result in permanent neurologic damage 1

Medication-Induced Neuropathy with Cognitive Effects

• Gabapentin and pregabalin are common culprits that cause both memory impairment and peripheral sensory symptoms 4, 5
• Pregabalin specifically causes:
  • Memory impairment (3-4% of patients) 4
  • Paresthesia and peripheral neuropathy 4
  • Disturbance in attention (4-6% of patients) 4
  • Hypoesthesia and coordination abnormalities 4
• Gabapentin causes:
  • Somnolence and dizziness affecting cognition 5
  • Ataxia and sensory disturbances 5
• Action required: Review all medications including over-the-counter preparations 6

Secondary Considerations

Lyme Disease with Neurologic Involvement

• Late neurologic Lyme disease presents with:
  • Peripheral neuropathy in a "stocking-glove" pattern with limb paresthesias and radicular pain 2
  • Encephalopathy with mild memory and cognitive abnormalities 2
  • Reduced vibratory sensation in distal lower extremities 2
• Diagnostic requirements:
  • Two-tier serology (ELISA and IgG immunoblot) expected to be positive 2
  • Electrophysiologic studies showing confluent mononeuritis multiplex 2
• Geographic exposure history is critical 2

Multiple Sclerosis or Demyelinating Disease

• Can present with:
  • Cognitive impairment and memory deficits 7
  • Sensory symptoms affecting multiple body regions 7
  • Progressive neurologic impairment 7
• Imaging required: Brain MRI to assess for demyelinating lesions 3

Peripheral Neuropathy from Other Causes

• Diabetes, thyroid disease, or other metabolic disorders can cause:
  • Distal sensory neuropathy affecting feet/legs initially 2
  • Cognitive changes from metabolic derangements 2
• Laboratory screening: Complete metabolic panel, TSH, HbA1c, lipid panel 3

Diagnostic Algorithm

Step 1: Immediate Laboratory Evaluation

• Vitamin B12 and homocysteine (highest priority) 3, 1
• Complete blood count with differential 3
• Complete metabolic panel 3
• Thyroid-stimulating hormone 3
• HbA1c 3

Step 2: Medication Review

• Document all prescription and over-the-counter medications 6
• Specifically identify gabapentin, pregabalin, or other neurotoxic agents 4, 5

Step 3: Neuroimaging

• Brain MRI (or CT if contraindicated) to assess for:
  • Structural abnormalities 3
  • Demyelinating lesions 7
  • Vascular disease 3

Step 4: Consider Infectious Workup

• If geographic exposure or systemic symptoms present:
  • Lyme serology (two-tier testing) 2
  • Consider lumbar puncture if encephalitis suspected 2

Step 5: Cognitive Assessment

• Administer validated cognitive screening tool (MoCA or similar) 3
• Obtain collateral history from informant separately 3, 6
• Assess functional impact on instrumental activities of daily living 6

Critical Pitfalls to Avoid

• Do not attribute symptoms to "normal aging" or depression without objective testing and laboratory evaluation 6
• Do not delay B12 testing even if other causes seem more likely—permanent neurologic damage can occur 1
• Do not overlook medication side effects as a reversible cause 4, 5
• Do not assume a single etiology—multiple conditions can coexist (e.g., B12 deficiency with early dementia) 6

Referral Indications

• Immediate hematology referral if pernicious anemia confirmed for B12 replacement protocol 1
• Neurology referral if diagnosis remains unclear after initial workup or if demyelinating disease suspected 3, 6
• Infectious disease consultation if Lyme disease or encephalitis considered 2