What is the differential diagnosis for a 50-year-old woman with recurring paroxysmal nerve pains in the arms, legs, torso, and generalized areas?

Differential Diagnosis of Recurring Paroxysmal Nerve Pains in Multiple Body Regions

Primary Diagnostic Considerations

The most critical first step is to determine whether this represents a peripheral neuropathy, a central pain syndrome, or a paroxysmal movement disorder, as the paroxysmal nature and generalized distribution are atypical for common peripheral neuropathies. 1

Peripheral Neuropathy (Most Common in This Age Group)

• Diabetic peripheral neuropathy should be the first consideration in a 50-year-old woman, as it affects 1-7% of the general population with higher rates after age 50, though the paroxysmal nature is somewhat atypical 1
• Classic presentation includes distal symmetric "stocking-and-glove" distribution with burning, tingling, or electric shock-like sensations, though your patient's generalized distribution is unusual 2, 1
• The paroxysmal quality could represent superimposed paroxysmal pain on background neuropathy, described as electric shock-like sensations occurring in 22-42% of neuropathy patients 3
• Critical caveat: True peripheral neuropathy is almost always symmetrical and distal-predominant; asymmetric or generalized patterns should raise suspicion for alternative diagnoses 2

Trigeminal Neuralgia and Other Cranial Neuralgias

• Trigeminal neuralgia presents with paroxysmal, unilateral, brief shock-like pain in trigeminal nerve distributions, triggered by light touch 4, 5
• If facial pain is present, this becomes a leading diagnosis; carbamazepine is first-line treatment 4
• Glossopharyngeal neuralgia causes similar paroxysmal pain in the throat, ear, and tongue, sometimes with syncope 2
• These conditions are characterized by brief attacks (seconds to minutes) with refractory periods between episodes 2, 5

Multiple Sclerosis (Secondary Neuropathy)

• Multiple sclerosis can cause paroxysmal neuropathic pain affecting multiple body regions simultaneously through demyelinating lesions 5
• This should be strongly considered given the generalized, non-anatomic distribution and paroxysmal nature 5
• MRI brain and spine with contrast is essential to exclude demyelinating disease 2, 5

Small Fiber Neuropathy

• Small fiber neuropathy presents with burning pain, paresthesias, and allodynia but typically follows a length-dependent pattern (feet first) 2, 1
• Can occur with normal nerve conduction studies; diagnosis requires skin biopsy showing reduced intraepidermal nerve fiber density 2
• Associated with diabetes, autoimmune conditions, and can be idiopathic in 25-46% of cases 1

Paroxysmal Movement Disorders (Less Likely but Important)

• Paroxysmal kinesigenic dyskinesia causes brief episodes triggered by sudden movement, but these are dystonic/choreiform movements rather than pure pain 2
• Duration is typically <1 minute, which may fit if your patient's episodes are very brief 2
• This diagnosis is unlikely if the primary complaint is pain rather than abnormal movements 2

Essential Diagnostic Workup

Mandatory Initial Laboratory Tests

• Fasting blood glucose and HbA1c to exclude diabetes (most common treatable cause) 1
• Vitamin B12 level (deficiency causes peripheral neuropathy) 1
• Thyroid-stimulating hormone (hypothyroidism causes neuropathy) 1
• Complete blood count (to assess for anemia, infection, malignancy) 1
• Comprehensive metabolic panel (renal disease, electrolyte abnormalities) 1
• Serum protein electrophoresis with immunofixation (to exclude multiple myeloma, monoclonal gammopathy) 1
• Erythrocyte sedimentation rate and C-reactive protein (to assess for vasculitis or inflammatory conditions) 6

Imaging Studies

• MRI brain and cervical/thoracic spine with contrast is indicated given the generalized distribution to exclude multiple sclerosis, spinal cord lesions, or structural abnormalities 2, 5
• Plain radiographs are insufficient for this presentation 2
• CT is less sensitive than MRI for nerve root compression and demyelinating disease 2

Specialized Testing (If Initial Workup Negative)

• Nerve conduction studies and electromyography to distinguish axonal from demyelinating neuropathy, though these may be normal in small fiber neuropathy 2, 1
• Quantitative sensory testing can detect early small fiber dysfunction 2
• Skin biopsy for intraepidermal nerve fiber density if small fiber neuropathy suspected with normal nerve conduction studies 2
• Referral to neurology is appropriate if initial evaluation is inconclusive 1

Red Flags Requiring Urgent Evaluation

• Progressive weakness or sensory loss suggests evolving structural lesion or inflammatory process 2
• Bowel or bladder dysfunction indicates spinal cord involvement requiring emergency imaging 2
• Fever, weight loss, or constitutional symptoms raise concern for malignancy, infection, or vasculitis 2, 6
• Asymmetric presentation is atypical for metabolic neuropathy and suggests structural or inflammatory cause 2
• Rapid progression over days to weeks suggests Guillain-Barré syndrome or other acute inflammatory neuropathy requiring hospitalization 1

Critical Clinical Pitfalls

• Do not assume idiopathic neuropathy until comprehensive workup excludes treatable causes; 54-75% of cases have identifiable etiology 1
• Paroxysmal quality does not exclude peripheral neuropathy; 22-42% of neuropathy patients experience paroxysmal electric shock-like pain 3
• Normal nerve conduction studies do not exclude neuropathy; small fiber neuropathy requires skin biopsy for diagnosis 2, 1
• Generalized distribution is unusual for typical peripheral neuropathy and should prompt consideration of central causes (multiple sclerosis) or systemic inflammatory conditions 2, 5
• Pain description matters: burning/pressing suggests ongoing neuropathic pain, while electric shock-like sensations suggest paroxysmal pain, and both can coexist 3