What is the management approach for patients presenting with Peripheral Nervous System (PNS) symptoms, such as neuropathy?

Management Approach for Peripheral Nervous System Symptoms

The management of peripheral nervous system symptoms, particularly neuropathy, requires a systematic approach focusing on identifying underlying causes, implementing appropriate screening, and utilizing evidence-based pharmacological and non-pharmacological interventions to reduce morbidity, mortality, and improve quality of life.

Diagnosis and Screening

• All patients with type 2 diabetes should be screened for diabetic peripheral neuropathy (DPN) starting at diagnosis, while those with type 1 diabetes should be screened 5 years after diagnosis and annually thereafter using simple clinical tests such as a 10-g monofilament 1
• Clinical assessment should follow the typical DPN pattern, starting distally (dorsal aspect of the hallux) on both sides and moving proximally until threshold is detected 1
• Screening tests should include assessment of pinprick sensation, vibration threshold using a 128-Hz tuning fork, light touch perception using a 10-g monofilament, and ankle reflexes 1
• In patients with severe or atypical neuropathy, consider causes other than diabetes such as neurotoxic medications, heavy metal poisoning, alcohol abuse, vitamin B12 deficiency, renal disease, chronic inflammatory demyelinating neuropathy, inherited neuropathies, and vasculitis 1, 2
• Electrodiagnostic testing or referral to a neurologist is rarely needed except when clinical features are atypical or the diagnosis is unclear 1

Treatment of Underlying Causes

• Tight glycemic control is the only strategy convincingly shown to prevent or delay the development of DPN and cardiovascular autonomic neuropathy (CAN) in type 1 diabetes and slow progression in some patients with type 2 diabetes 1
• Address cardiovascular risk factors (hypertension, hyperlipidemia) as these are common in DPN 1
• Correct vitamin B12 deficiency if present, as this is a common treatable cause of peripheral neuropathy 1, 2
• Manage other potential underlying causes including thyroid disorders, renal disease, and alcohol abuse 2, 3

Pharmacological Management of Neuropathic Pain

First-Line Medications

• Duloxetine (60-120 mg daily) and pregabalin (300-600 mg daily) are FDA-approved for the treatment of painful diabetic peripheral neuropathy and should be considered first-line options 1, 4
• Tricyclic antidepressants (TCAs) such as amitriptyline (10-75 mg at bedtime), nortriptyline (25-75 mg at bedtime), or imipramine (25-75 mg at bedtime) are effective with a number needed to treat of 1.5-3.5 1
• When using TCAs, start at a low dose (10 mg/day), especially in older patients, and titrate as needed up to 75 mg/day; doses >100 mg/day are associated with increased risk of sudden cardiac death 1
• Gabapentin (900-3600 mg/day in divided doses) is also considered a first-line option 1, 5

Second-Line Medications

• Venlafaxine (150-225 mg/day) can be considered if first-line agents are ineffective or not tolerated 1
• Carbamazepine (200-800 mg/day) or topiramate (25-100 mg/day) may be used in patients who fail to respond to first-line treatments 1
• Capsaicin cream (0.025-0.075%) applied 3-4 times daily can provide topical relief 1

Opioid Medications

• Tramadol (200-400 mg/day) may be considered for short-term use when other medications fail 1
• Opioids should generally be avoided due to risk of dependence and other adverse effects 5

Management of Autonomic Neuropathy

• Screen for signs and symptoms of cardiovascular autonomic neuropathy (e.g., orthostatic hypotension, resting tachycardia) in patients with more advanced disease 1
• For orthostatic hypotension, consider increased salt/fluid intake, salt tablets, fludrocortisone, midodrine, droxidopa, or pyridostigmine 1
• For gastroparesis, evaluate with solid-phase gastric emptying using double-isotope scintigraphy if symptoms are suggestive 1
• Manage constipation, which is the most common lower-gastrointestinal symptom but can alternate with episodes of diarrhea 1

Foot Care for Patients with Neuropathy

• Perform annual comprehensive foot examinations for all patients with diabetes to identify risk factors for ulcers and amputations 1
• Examine feet at every visit for patients with insensate feet, foot deformities, or ulcers 1
• Provide general foot self-care education to all patients with diabetes 1
• Use a multidisciplinary approach for individuals with foot ulcers and high-risk feet 1
• Refer patients who smoke, have loss of protective sensation, structural abnormalities, or prior lower-extremity complications to foot care specialists 1

Non-Pharmacological Approaches

• Exercise has shown low to moderate quality evidence for benefit in diabetic peripheral neuropathy 5
• Consider neuromodulation with spinal cord stimulation or transcutaneous electrical nerve stimulation (TENS) for pain management 5
• Peripheral TENS is well-tolerated and inexpensive, though benefits are modest 5

Monitoring and Follow-up

• Regularly assess pain and quality of life using validated tools 1
• Monitor medication response objectively as patients may not obtain desired pain reduction, adverse effects are common, and serious adverse effects can occur 5
• Adjust treatment based on response, with consideration of combination therapy if partial response to single agents 1