What is the differential diagnosis (ddx) of widespread paroxysmal nerve pain?

Differential Diagnosis of Widespread Paroxysmal Nerve Pain

The differential diagnosis of widespread paroxysmal nerve pain must distinguish between primary neuralgic conditions, metabolic neuropathies, movement disorders with sensory features, and central demyelinating diseases, with the key discriminating features being pain distribution (focal vs. widespread), temporal pattern (seconds vs. minutes), presence of autonomic features, and associated neurological deficits.

Primary Neuralgic Conditions

Trigeminal Neuralgia

• Paroxysmal attacks lasting seconds to minutes with mandatory refractory periods between attacks, characterized by sharp, shooting, electric shock-like pain 1, 2
• Pain is unilateral and follows specific trigeminal nerve divisions, most commonly V2 and V3 1, 3
• Triggered by light touch, washing face, cold wind, eating, or brushing teeth 3
• Bilateral symptoms are atypical and warrant expanded differential diagnosis 1
• MRI with high-resolution thin-cut sequences is the gold standard to evaluate for neurovascular compression and exclude secondary causes 1

Glossopharyngeal Neuralgia

• Unilateral deep ear and/or back of tongue, tonsils, neck pain with sharp, shooting, electric shock-like quality 2
• Triggered by swallowing, coughing, or touching the ear 2
• May be associated with syncope 2
• Pain distribution is not in the V2/V3 distribution of trigeminal neuralgia 2

Metabolic and Toxic Neuropathies

Painful Diabetic Peripheral Neuropathy

• Symptoms are distal, symmetrical, and associated with nocturnal exacerbation 4
• Pain descriptors include burning, pressing (ongoing pain), electric shock-like sensations (paroxysmal pain), and allodynia 5
• Paroxysmal pain (electric shock-like sensations) occurs in 37-42% of diabetic peripheral neuropathy patients 5
• Diagnosis is clinical, relying on patient description of pain with blunting of sensation on examination 4
• Painful diabetic neuropathy is invariably symmetrical; asymmetrical symptoms require assessment for other etiologies 4
• Nerve conduction studies are important to exclude entrapment syndromes 4

Acute Painful Diabetic Neuropathy ("Insulin Neuritis")

• Precipitated by sudden improvement of glycemic control 4
• Symptoms may be present in the absence of signs 4
• Prognosis is good with complete resolution usually occurring within one year 4

Movement Disorders with Sensory Features

Paroxysmal Kinesigenic Dyskinesia (PKD)

• Recurrent and transient episodes of involuntary movements precipitated by sudden voluntary action 4
• Involuntary movements manifested as dystonia, chorea, ballism, or combinations 4
• Approximately 78-82% of PKD patients experience aura described as numbness, tingling, and muscle weakness 4
• Age of onset generally ranges from several months to 20 years, with high incidence among 7-15 year-old children and adolescents 4
• Triggered by sudden standing, starting to run, getting on/off a car, or encountering traffic lights 4
• PRRT2 gene mutations account for the majority of cases worldwide 4

Trigeminal Autonomic Cephalgias

SUNCT/SUNA Syndromes

• Rapid attacks lasting seconds to several minutes with up to 200 attacks daily and no refractory period between attacks 2
• Prominent autonomic symptoms including tearing, conjunctival injection, rhinorrhea, nasal blockage, facial redness, and ear fullness 2
• Mainly distributed in the first and second trigeminal divisions 2
• Distinguished from trigeminal neuralgia by presence of autonomic features 2

Post-Infectious Neuropathies

Post-Herpetic Neuralgia

• Continuous burning pain at the site of previous herpes zoster eruption, not paroxysmal 2
• Associated with allodynia and hyperalgesia in the affected dermatome 2
• Clear history of herpes zoster rash preceding pain by at least 3 months 6

Central Demyelinating Diseases

Multiple Sclerosis with Trigeminal Involvement

• Demyelinating plaques affecting the trigeminal nerve pathway can cause secondary trigeminal neuralgia 1
• Sensory deficits in trigeminal distribution require urgent MRI to rule out secondary causes 3
• May present as trigeminal autonomic cephalgia-trigeminal neuralgia overlap 7

Neuromyelitis Optica Spectrum Disorder (NMOSD)

• Can present with acute paroxysmal facial pain in V1-V2 distribution with features of both trigeminal autonomic cephalgia and trigeminal neuralgia 7
• Involvement of somatotopically arranged spinal trigeminal nucleus explains the unique presentation 7
• AQP4-seropositive diagnosis with brainstem involvement 7

Critical Diagnostic Algorithm

Step 1: Characterize Pain Temporal Pattern

• Paroxysmal attacks lasting seconds with refractory periods suggest classical neuralgia 1, 2, 3
• Continuous burning pain suggests post-herpetic neuralgia, post-traumatic neuropathy, or atypical odontalgia 2
• Paroxysmal attacks without refractory periods (up to 200 daily) suggest SUNCT/SUNA 2

Step 2: Assess Distribution Pattern

• Unilateral facial pain in trigeminal distribution suggests trigeminal neuralgia or SUNCT/SUNA 1, 2
• Bilateral distal symmetrical pain suggests diabetic peripheral neuropathy 4
• Widespread involuntary movements with sensory aura suggest paroxysmal kinesigenic dyskinesia 4

Step 3: Identify Autonomic Features

• Presence of tearing, conjunctival injection, or rhinorrhea indicates trigeminal autonomic cephalgias, not true neuralgia 2
• Absence of autonomic features supports classical trigeminal neuralgia or diabetic neuropathy 1, 2

Step 4: Evaluate for Red Flags

• Sensory deficits in nerve distribution require urgent MRI to rule out tumors or multiple sclerosis 3
• Bilateral trigeminal symptoms are atypical and warrant expanded differential diagnosis 1
• Continuous pain from onset should prompt MRI evaluation to exclude secondary causes 3
• Asymmetrical symptoms in suspected diabetic neuropathy require assessment for other etiologies 4

Step 5: Order Appropriate Investigations

• MRI with high-resolution thin-cut sequences through the trigeminal nerve course for suspected trigeminal neuralgia 1
• Nerve conduction studies for suspected diabetic peripheral neuropathy to exclude entrapment syndromes 4
• Genetic testing for PRRT2 mutations in suspected paroxysmal kinesigenic dyskinesia 4
• AQP4 antibody testing if brainstem symptoms or area postrema syndrome precede facial pain 7

Common Pitfalls to Avoid

• Do not diagnose trigeminal neuralgia if patient describes continuous pain or can trigger attacks repeatedly without pain-free intervals 2
• Do not attribute widespread paroxysmal pain to trigeminal neuralgia, which is characteristically unilateral 1
• Do not overlook paroxysmal kinesigenic dyskinesia in younger patients with movement-triggered episodes and sensory aura 4
• Do not miss secondary causes of trigeminal neuralgia such as multiple sclerosis or NMOSD in patients with additional neurological deficits 1, 7
• Do not confuse the sensory aura of paroxysmal kinesigenic dyskinesia (numbness, tingling, muscle weakness) with true neuropathic pain 4