What tests can confirm the cause of reduced deep tendon reflexes in the arm, absent reflexes in the legs, inability to sense position or vibration cues of toes and fingers, gait disturbance, forgetfulness, and paresthesia?

Diagnostic Testing for Peripheral Neuropathy with Cognitive Impairment

The clinical presentation of reduced arm reflexes, absent leg reflexes, impaired proprioception and vibration sense in digits, gait disturbance, forgetfulness, and paresthesias requires immediate serum vitamin B12 level measurement, followed by nerve conduction studies and electromyography to confirm the underlying cause. 1

Urgent Life-Threatening Consideration: Guillain-Barré Syndrome

Before pursuing other diagnoses, Guillain-Barré syndrome (GBS) must be urgently excluded given the bilateral ascending pattern with areflexia, as approximately 20% of patients develop life-threatening respiratory failure. 1, 2

Immediate Assessment Required

• Measure vital capacity, negative inspiratory force (NIF), and maximum inspiratory/expiratory pressures immediately using the "20/30/40 rule": patient is at risk of respiratory failure if vital capacity <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 2
• Assess for preceding infection within 6 weeks (Campylobacter jejuni, CMV, Hepatitis E, Mycoplasma, EBV, or Zika), which occurs in approximately two-thirds of GBS patients 1, 2
• Monitor for dysautonomia including blood pressure and heart rate instability, which can be life-threatening 1, 2

Critical Diagnostic Tests for GBS

• MRI of the entire spine without and with contrast is the critical first test to exclude cord compression, transverse myelitis, or nerve root enhancement characteristic of GBS 1
• CSF analysis should be performed to look for albumino-cytological dissociation (elevated protein with normal cell count), though protein may be normal in the first week 1, 2
• Electrodiagnostic studies (nerve conduction studies and EMG) should be conducted to look for sensorimotor polyradiculoneuropathy with reduced conduction velocities, temporal dispersion, or conduction blocks 1, 2
• Look for "sural sparing pattern" where sural sensory nerve action potential is normal while median and ulnar sensory nerve action potentials are abnormal or absent 3, 2

Primary Diagnostic Algorithm After Excluding GBS

First-Line Laboratory Tests

Serum vitamin B12 level is the single most important initial test given the combination of peripheral neuropathy with cognitive impairment (forgetfulness), as B12 deficiency causes both subacute combined degeneration and cognitive dysfunction 1

• Complete blood count to assess for macrocytic anemia suggesting B12 deficiency 2
• Fasting glucose and HbA1c to evaluate for diabetic neuropathy, which commonly presents with distal symmetric polyneuropathy affecting vibration and position sense 3
• Thyroid function tests as hypothyroidism can cause both neuropathy and cognitive impairment 1
• Serum creatine kinase (CK) to assess for muscle involvement 2
• Kidney and liver function tests to exclude uremic or hepatic neuropathy 3

Electrodiagnostic Studies

Nerve conduction studies (NCS) and needle electromyography are essential to confirm neuropathy and differentiate axonal from demyelinating patterns. 3

• NCS can identify mononeuropathies, differentiate multiple mononeuropathy versus polyneuropathy, and distinguish axonal from demyelinating neuropathies 3
• Testing should include motor and sensory conduction velocity in ulnar and peroneal nerves 3
• Electrodiagnostic studies may be normal when performed early in disease course (within 1 week) or in mild disease, requiring repeat testing 2-3 weeks later 3

Neurologic Testing for Diabetic Neuropathy

If diabetes is present or suspected, specific testing includes thermal sensitivity, pinprick sensation, vibration perception (128-Hz tuning fork), pressure sensation (10-g monofilament), and ankle reflexes 3

Secondary Diagnostic Considerations

Cervical Spinal Cord Lesion

Bilateral hand involvement with fine motor dysfunction and gait disturbance suggests a cervical cord lesion at C5-C7 level, which may require urgent surgical decompression 1

• MRI cervical spine is indicated when focal neurological signs, gait disturbance, or increased muscle tone are present 3

Metabolic and Toxic Causes

The diagnosis should exclude other causes of neuropathy including:

• Cervical and lumbar disease (nerve root compression, spinal stenosis) 3
• Neurotoxicity of drugs, especially chemotherapeutic agents 3
• Metabolic toxicants from renal insufficiency 3

Autoimmune Considerations

In patients with systemic symptoms, consider systemic lupus erythematosus with peripheral neuropathy, which occurs in 2-3% of SLE patients and presents with altered sensation, pain, and muscle weakness 3

Critical Pitfalls to Avoid

• Do not dismiss GBS based on normal CSF protein in the first week, as protein elevation may develop later 1, 2
• Do not wait for electrodiagnostic study results to initiate GBS treatment if clinical suspicion is high and imaging excludes structural lesion 1, 2
• Delaying MRI spine can result in permanent paralysis if cord compression is present 1
• Do not attribute absent reflexes solely to age or technical difficulty without proper assessment using alternative elicitation methods 4
• Marked persistent asymmetry, bladder dysfunction at onset, or marked CSF pleocytosis (>50 × 10⁶/l cells) should prompt reconsideration of GBS diagnosis and evaluation for alternative causes 2

Interpretation of Deep Tendon Reflexes

The pattern of reduced arm reflexes with absent leg reflexes suggests a length-dependent polyneuropathy or ascending polyradiculoneuropathy. 3

• Absent or diminished reflexes are a key diagnostic feature of GBS, typically beginning in lower limbs but can affect upper extremities 3, 1
• In diabetic neuropathy, ankle reflexes are commonly absent while other reflexes may be preserved initially 3
• Hyper-reflexia or clonus would suggest upper motor neuron pathology requiring urgent spinal cord imaging 3