What is the diagnosis for a diabetic patient with numbness that started in one foot, spread to one lower extremity, and then one upper extremity?

Diabetic Mononeuropathy Multiplex (Asymmetric Diabetic Neuropathy)

This presentation is most consistent with diabetic mononeuropathy multiplex (also called asymmetric diabetic neuropathy), which manifests as sequential involvement of individual peripheral nerves in an asymmetric pattern, rather than the typical symmetric "glove and stocking" distribution of distal symmetric polyneuropathy. 1

Key Distinguishing Features

The clinical pattern described—numbness starting in one foot, then spreading to one lower extremity, and subsequently affecting one upper extremity—is characteristic of asymmetric neuropathy rather than the more common distal symmetric polyneuropathy (DPN). 1

Why This Is NOT Typical Diabetic Peripheral Neuropathy

• Typical DPN presents bilaterally and symmetrically in a "glove and stocking" distribution, affecting both feet simultaneously before progressing proximally 2, 3
• Asymmetric presentation with sequential limb involvement suggests mononeuropathy multiplex, which results from ischemic infarction of the vasa nervosa (blood vessels supplying peripheral nerves) 1
• This pattern accounts for approximately 25% of diabetic neuropathies, while distal symmetric polyneuropathy accounts for 75% 1

Diagnostic Approach

Immediate Clinical Assessment

• Document the exact distribution and timeline of sensory loss to confirm the asymmetric, sequential pattern 1
• Perform focused neurologic examination including pinprick sensation (small fiber function), vibration perception with 128-Hz tuning fork (large fiber function), and ankle reflexes 4, 5
• Assess for motor weakness in affected limbs, as asymmetric neuropathies often involve both sensory and motor deficits 1

Critical: Rule Out Alternative Diagnoses

Diabetic neuropathy is a diagnosis of exclusion—asymmetric neuropathies in diabetic patients must be investigated for other causes before attributing symptoms solely to diabetes. 4, 5

• Screen for entrapment neuropathies (carpal tunnel syndrome, ulnar neuropathy, peroneal nerve compression), which are more common in diabetes and can mimic mononeuropathy multiplex 1
• Check vitamin B12 levels, especially if the patient takes metformin, as deficiency compounds neuropathy risk and can present asymmetrically 5, 6
• Evaluate thyroid function to exclude hypothyroidism-related neuropathy 5
• Review medications for neurotoxic agents; avoid nitrofurantoin as it significantly increases neuropathy risk 5, 7

Confirmatory Testing

• Nerve conduction studies are particularly valuable in asymmetric neuropathies to localize lesions and differentiate from entrapment 1
• Consider MRI if focal nerve lesions or structural causes are suspected 8

Management Strategy

Disease-Modifying Interventions

• Optimize glycemic control gradually to prevent progression, but avoid rapid HbA1c reduction if severely elevated, as this can paradoxically worsen neuropathic symptoms 5, 7
• Aggressively manage cardiovascular risk factors including blood pressure and lipids, as asymmetric neuropathies result from vascular insufficiency 5, 7, 1

Symptomatic Pain Management (If Present)

• Initiate first-line pharmacotherapy immediately if neuropathic pain develops: pregabalin, duloxetine, or gabapentin 4, 5
• Pregabalin dosing for diabetic neuropathic pain: 100-200 mg three times daily (maximum recommended dose) 9
• Do not delay treatment waiting for electrodiagnostic studies 5

Prognosis and Natural History

• Asymmetric neuropathies typically have acute onset from ischemic nerve infarction and may improve spontaneously over months, unlike progressive distal symmetric polyneuropathy 1
• Monitor for progression to symmetric polyneuropathy, as patients can develop both patterns 1

Critical Preventive Measures

• Educate on daily foot inspection for cuts, blisters, or pressure areas, as sensory loss increases ulceration risk regardless of neuropathy pattern 5, 10
• Perform annual 10-g monofilament testing on all affected limbs to monitor progression and identify areas at risk for ulceration 4, 5, 10
• Arrange podiatry referral for regular foot care and proper footwear assessment 5

Common Pitfall to Avoid

Do not assume all neuropathy in diabetic patients is due to diabetes—the asymmetric presentation mandates thorough evaluation for alternative or coexisting causes, particularly entrapment neuropathies and vitamin B12 deficiency. 5, 1