What is the differential diagnosis (Dx) for left-sided paresthesia?

Differential Diagnosis for Left-Sided Paresthesia

Left-sided paresthesia most critically suggests right hemisphere cerebrovascular disease (stroke or TIA) until proven otherwise, requiring urgent evaluation to prevent permanent disability or death. 1

Immediate Life-Threatening Causes (Evaluate First)

Cerebrovascular Disease

• Right hemisphere ischemia or infarction (right internal carotid or middle cerebral artery distribution) classically presents with left-sided paresthesia, left-sided weakness, left-sided neglect, and abnormal visual-spatial ability 1
• Symptoms lasting <24 hours (typically 15 minutes) suggest TIA, while symptoms >24 hours indicate completed stroke 1
• Cerebral venous thrombosis involving the superior sagittal sinus can cause bilateral or unilateral paresthesias with motor signs 1, 2
• Brainstem stroke should be suspected when paresthesias accompany cranial nerve findings or crossed sensory/motor deficits 2

Spinal Cord Pathology

• Acute spinal cord ischemia presents with acute onset paraparesis and sensory changes, particularly following thoracic aortic procedures (2-6% incidence) 3, 2
• Epidural abscess or hematoma presents with localized back pain, fever (only one-third of abscess cases), radiculopathy, and progressive spinal cord syndromes 3
• A sharp sensory level indicates spinal cord injury requiring emergent MRI 3, 2

Central Nervous System Causes

Demyelinating Disease

• Multiple sclerosis presents with multifocal paresthesias affecting different body regions at different times 3, 2
• MRI shows periventricular white matter lesions that are sharply demarcated, round or flame-shaped, may enhance with gadolinium, spare U-fibers initially, and involve the corpus callosum 3, 2
• Symptoms evolve over hours to days, typically stabilize, and may resolve spontaneously 2

Inflammatory/Infectious CNS Disease

• Lyme disease encephalomyelitis presents with multifocal white matter involvement, CSF lymphocytic pleocytosis, and positive two-tier serology with intrathecal antibody production 3, 2
• Brainstem or spinal cord inflammation from sarcoidosis, Sjögren syndrome, neuromyelitis optica, or transverse myelitis can cause intermittent or progressive paresthesias 2

Peripheral Nervous System Causes

Acute Inflammatory Neuropathy

• Guillain-Barré syndrome progresses over days to 4 weeks with bilateral paresthesias, weakness, absent/decreased reflexes, elevated CSF protein without pleocytosis, and electrodiagnostic evidence of neuropathy 3, 2
• Progressive symptoms >4 weeks without respiratory involvement suggests alternative diagnosis 2
• Miller-Fisher syndrome (5-25% of GBS cases) presents with ataxia, areflexia, and ophthalmoplegia, though incomplete forms occur 2

Entrapment Neuropathy

• Carpal tunnel syndrome remains the most common cause of acroparesthesia, typically affecting the hand rather than entire left side 4
• Meralgia paresthetica affects the lateral femoral cutaneous nerve, causing thigh paresthesia (not typically described as "left-sided" globally) 5

Metabolic/Nutritional Neuropathy

• Vitamin B12 deficiency causes subacute combined degeneration with both central (myelopathic) and peripheral (neuropathic) manifestations, presenting as paresthesias 3, 2
• Late Lyme disease peripheral neuropathy manifests as mild, diffuse "stocking-glove" paresthesias with reduced vibratory sensation 2

Metabolic/Electrolyte Disturbances

• Hypocalcemia from hypoparathyroidism causes paresthesias, particularly perioral and acral 2
• Hypokalemia, hypomagnesemia, and hypophosphataemia trigger intermittent paresthesias through altered nerve excitability 2
• Hyperthyroidism can precipitate paroxysmal symptoms including paresthesias 2

Critical Red Flags Requiring Urgent Evaluation

• Acute onset with fever suggests infection or inflammatory process requiring immediate CSF analysis 2
• Sharp sensory level indicates spinal cord injury requiring emergent imaging 3, 2
• Bladder/bowel dysfunction suggests cauda equina syndrome or spinal cord compression 3, 2
• Altered consciousness (except in Bickerstaff brainstem encephalitis) suggests CNS pathology beyond typical peripheral neuropathy 2
• Asymmetric, proximal, multifocal paresthesias or those associated with predominant motor signs require urgent evaluation for Guillain-Barré syndrome or vasculitis 4

Diagnostic Approach Algorithm

Initial Assessment

• Document temporal pattern: acute onset (<24 hours) suggests vascular/inflammatory causes; gradual progression suggests neoplastic/metabolic etiologies 3, 6
• Identify accompanying symptoms: weakness, visual changes, speech difficulties, cranial nerve deficits, bladder/bowel dysfunction 1
• Assess for stroke risk factors and vascular disease 1

Laboratory Evaluation

• For suspected vascular causes: complete blood count, chemistry panel, prothrombin time, activated partial thromboplastin time 3, 6
• For metabolic causes: thyroid function, vitamin B12, electrolytes (potassium, magnesium, phosphate, calcium) 3, 2
• For inflammatory/infectious causes: CSF examination showing elevated protein in Guillain-Barré syndrome and lymphocytic pleocytosis in Lyme neuroborreliosis 3, 2

Imaging

• MRI with gadolinium is the preferred imaging modality for suspected CNS pathology, demonstrating plaques of demyelination in MS and characterizing inflammatory lesions 3, 2
• Brain MRI for suspected stroke or demyelinating disease 1
• Spine MRI for suspected spinal cord pathology 3, 6

Neurophysiologic Studies

• Nerve conduction studies and EMG differentiate demyelinating from axonal neuropathies and identify entrapment sites 2
• Somatosensory or motor evoked potentials detect spinal cord ischemia 6

Common Pitfalls to Avoid

• Do not delay imaging if symptoms suggest stroke/TIA, as rapid action limits disability and prevents death 1
• Do not assume peripheral neuropathy when unilateral paresthesias occur; right hemisphere stroke must be excluded first 1
• Do not dismiss symptoms lasting <24 hours as benign; many patients with symptoms briefer than 24 hours have cerebral infarction on imaging 1
• Do not delay investigation of delayed neurological recovery, as prompt evaluation identifies rare but treatable causes like epidural abscess or hematoma 3