What are the different types of peripheral neuropathy?

Types of Peripheral Neuropathy

Peripheral neuropathy can be classified into three main anatomic patterns: mononeuropathies (single nerve), multifocal neuropathies (multiple individual nerves), and polyneuropathies (diffuse, symmetric nerve involvement), with polyneuropathies further subdivided into axonal and demyelinating forms based on electrodiagnostic findings. 1

Classification by Anatomic Distribution

Mononeuropathies

• Single nerve involvement affecting one isolated peripheral nerve, most commonly carpal tunnel syndrome (median nerve compression at the wrist), which has a prevalence of 5% and incidence of 1-2 per 1,000 person-years 1
• Cranial neuropathies can involve the eighth, oculomotor (third, fourth, sixth), fifth, or seventh cranial nerves 2
• Optic neuropathy includes both inflammatory optic neuritis and ischemic/thrombotic variants 2

Multifocal Neuropathies (Mononeuropathy Multiplex)

• Multiple individual nerves affected asymmetrically, often seen in vasculitis or other systemic inflammatory conditions 3
• Can present with patchy, asymmetric sensory loss and weakness in different nerve distributions 2

Polyneuropathies

• Distal symmetric polyneuropathy is the most common pattern, presenting with length-dependent symptoms starting in the toes and progressing proximally in a "stocking and glove" distribution 4, 5
• Accounts for the majority of peripheral neuropathy cases, particularly in diabetic patients 4

Classification by Pathophysiology

Axonal Neuropathies

• Characterized by primary damage to the nerve axon itself, most commonly seen in metabolic, toxic, and nutritional causes 6, 1
• Diabetic neuropathy is predominantly axonal 4
• Slowly progressive axonal polyneuropathies comprise about 20-25% of chronic polyneuropathies where no direct cause is identified 1

Demyelinating Neuropathies

• Characterized by damage to the myelin sheath surrounding nerve axons 6
• Includes acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome) with annual incidence of 1-2 per 100,000 persons 1
• Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) has an incidence of 0.2-0.5 per 100,000 persons annually 1
• Demyelinating neuropathy in IBD patients is proportionally more common in women, presenting with proximal and distal symmetrical weakness 2

Mixed Neuropathies

• Combined axonal and demyelinating features can occur in certain conditions 6

Classification by Fiber Type Involvement

Small-Fiber Neuropathy

• Affects unmyelinated C-fibers and thinly myelinated Aδ-fibers, causing pain, burning sensations, tingling (dysesthesia), and temperature sensation abnormalities 2
• Most common early symptoms in diabetic peripheral neuropathy 2
• Can be diagnosed by skin biopsy demonstrating loss of intraepidermal nerve fibers when electrodiagnostic studies are normal 2

Large-Fiber Neuropathy

• Affects myelinated Aα and Aβ-fibers, causing numbness, loss of vibration sense, loss of proprioception, and loss of protective sensation (LOPS) 2
• Detected by abnormal vibration perception (128-Hz tuning fork) and 10-g monofilament testing 2
• LOPS is a major risk factor for diabetic foot ulceration 2

Sensorimotor Neuropathy

• Involves both sensory and motor fibers, causing combined sensory symptoms and muscle weakness or atrophy 2, 5
• Later stages of diabetic neuropathy may involve proximal numbness and distal weakness 5

Classification by Autonomic Involvement

Cardiac Autonomic Neuropathy (CAN)

• Affects cardiovascular autonomic regulation, presenting with resting tachycardia (>100 bpm), orthostatic hypotension (fall in systolic BP >20 mmHg or diastolic BP >10 mmHg upon standing), and decreased heart rate variability 2
• Associated with mortality independently of other cardiovascular risk factors 2

Gastrointestinal Neuropathies

• Affects any portion of the gastrointestinal tract, manifesting as esophageal dysmotility, gastroparesis, constipation, diarrhea, and fecal incontinence 2

Genitourinary Neuropathies

• Affects urogenital function, causing erectile dysfunction, retrograde ejaculation in men, decreased sexual desire and arousal in women, and bladder dysfunction (urinary incontinence, nocturia, urgency) 2

Common Pitfalls and Caveats

• Up to 50% of diabetic peripheral neuropathy may be asymptomatic, making systematic screening essential to prevent foot ulceration and amputation 2
• Peripheral neuropathy is a diagnosis of exclusion—always evaluate for treatable causes including vitamin B12 deficiency, hypothyroidism, toxins (alcohol, medications like metronidazole), renal disease, malignancies, infections (HIV), chronic inflammatory demyelinating neuropathy, inherited neuropathies, and vasculitis 2, 3, 4
• Electrodiagnostic testing is rarely needed except when clinical features are atypical or diagnosis remains unclear 2
• In IBD patients, peripheral neuropathy is very rare and treatable causes (vitamin/micronutrient deficiencies, metronidazole) must be identified first 2
• Idiopathic neuropathy accounts for 25-46% of cases after comprehensive diagnostic evaluation 5, 1