What causes paresthesia?

Causes of Paresthesia

Paresthesia is primarily caused by damage or dysfunction to peripheral nerves or central nervous system pathways, with the most common etiologies being peripheral neuropathies, nerve compression, and systemic diseases that affect nerve function. 1, 2

Peripheral Causes

Neuropathies and Nerve Damage

• Peripheral sensory, motor, or sensorimotor polyneuropathies commonly present with paresthesias, numbness, cramps, burning feet, and tingling 1
• Medication-induced neuropathy, particularly from chemotherapeutic agents like bortezomib and thalidomide, which can cause dose-dependent peripheral neuropathy 1
• Small fiber sensory polyneuropathy can manifest as paresthesias and is often associated with conditions like restless legs syndrome 1

Compression Syndromes

• Nerve entrapment syndromes such as carpal tunnel syndrome, which presents with bilateral paresthesias in a characteristic distribution 1, 2
• Compression from tumors or inflammatory processes affecting peripheral nerves 3
• Nerve compression from trauma or structural abnormalities 2

Infection-Related Causes

• Viral infections can lead to post-viral neuropathies with paresthesias 1
• Bacterial infections causing inflammatory processes near nerve pathways 4
• HCV-related extrahepatic manifestations frequently involve peripheral nervous system, causing paresthesias in up to 50% of infected patients 1

Central Nervous System Causes

Structural and Vascular Disorders

• Ischemic events affecting the central nervous system, including stroke, transient ischemic attacks, and lacunar infarctions 1
• Space-occupying lesions such as brain tumors that compress neural pathways 1, 2
• Demyelinating diseases like multiple sclerosis can cause paresthesias as part of their neurological manifestations 1

Inflammatory and Autoimmune Conditions

• Guillain-Barré syndrome presents with distal paresthesias that may progress to weakness 1
• Immune-mediated nervous tissue injury in conditions like encephalopathy syndromes or myelitis 1
• Vasculitic or vasculopathic ischemic damage to neural tissue 1

Systemic and Metabolic Causes

Metabolic Disorders

• Diabetes mellitus is a common cause of peripheral neuropathy with paresthesias 2
• Uremic neuropathy in renal failure 2
• Nutritional deficiencies, particularly B vitamins 2

Toxic Exposures

• Chemical toxins affecting peripheral nerves 3
• Alcohol-related neuropathy 2
• Medication side effects beyond chemotherapeutics 2

Vascular and Ischemic Mechanisms

• Ischemia can induce paresthesias through membrane depolarization affecting sodium channels 5
• Post-ischemic paresthesias occur when hyperpolarization is prevented by elevated extracellular potassium 5
• Vasculopathic conditions like hypertension can contribute to nerve dysfunction 1

Physiological Mechanisms

• Paresthesias arise from ectopic impulse activity in cutaneous afferents or their central projections 5
• Cutaneous afferents are more excitable than motor axons due to differences in biophysical properties 5
• Ectopic discharges can be induced in normal afferents by hyperventilation, ischemia, release of ischemia, and prolonged tetanization 5

Diagnostic Approach

• Thorough neurological examination to determine if the paresthesia is central or peripheral in origin 2
• Electromyography with peripheral nerve neurophysiological tests for suspected peripheral nerve involvement 1
• Neuroimaging (MRI, CT) when central causes are suspected 1
• Laboratory testing for metabolic, infectious, or inflammatory causes 2

Special Considerations

• Bilateral paresthesias often suggest systemic disease or central pathology 2
• Asymmetric or focal paresthesias more commonly indicate localized nerve compression or injury 2
• Paresthesias accompanied by weakness, autonomic symptoms, or other neurological findings warrant more urgent evaluation 1

Understanding the specific pattern, distribution, and associated symptoms of paresthesia is crucial for determining the underlying cause and guiding appropriate treatment.