What is the mechanism of action, diagnostic criteria, findings, investigation, management, and treatment of trigeminal neuralgia?

Trigeminal Neuralgia: Comprehensive Clinical Overview

Mechanism of Action

Trigeminal neuralgia results from demyelination of trigeminal nerve fibers, most commonly caused by neurovascular compression at the root entry zone, leading to abnormal depolarization and ectopic impulse generation that produces the characteristic paroxysmal pain attacks. 1, 2

The pathophysiology involves:

• Neurovascular compression (most common in classical TN) causes focal demyelination of primary trigeminal afferents at the root entry zone 1, 3
• Dysregulation of voltage-gated sodium channels in demyelinated nerve membranes creates hyperexcitable neuronal states 4, 3
• Central sensitization develops with widespread neural plasticity changes in pain modulation pathways 3
• Carbamazepine's therapeutic effect works by reducing polysynaptic responses and blocking post-tetanic potentiation, thereby modulating these abnormal sodium channel activities 2

Type 2 TN (with concomitant continuous pain) may originate from more central mechanisms rather than peripheral neurovascular compression 1

Diagnostic Criteria

Diagnose trigeminal neuralgia based on sudden, unilateral, severe, brief stabbing recurrent episodes of pain in one or more trigeminal nerve branches, with mandatory refractory periods between attacks lasting seconds to minutes. 5, 6

Key Clinical Features:

• Pain quality: Electric shock-like, sharp, shooting, stabbing 5, 7
• Duration: Seconds to minutes per attack 6, 7
• Mandatory refractory period: Cannot trigger attacks repeatedly without pain-free intervals 6
• Triggers: Light touch, washing, cold wind, eating, brushing teeth 7
• Distribution: Follows V1, V2, or V3 branches (V2/V3 most common) 1, 4
• Unilateral presentation in >95% of cases 5

Classification by Etiology:

• Classical TN: Neurovascular compression demonstrated on MRI 5, 8
• Secondary TN: Underlying neurological disorder (multiple sclerosis, tumor, post-stroke) 1, 8
• Idiopathic TN: No identifiable cause on imaging 8

Critical pitfall: The presence of continuous pain between attacks suggests Type 2 TN or alternative diagnoses and requires urgent MRI to exclude secondary causes 1, 6

Differential Diagnosis

Trigeminal Autonomic Cephalgias (SUNCT/SUNA)

• Distinguishing features: Prominent autonomic symptoms (tearing, conjunctival injection, rhinorrhea, nasal blockage, facial redness) 1, 5
• Up to 200 attacks daily with no refractory period between attacks 1, 6
• Attacks last seconds to several minutes, mainly in V1/V2 distribution 1

Giant Cell Arteritis (Critical Not-to-Miss)

• Age >50 years is mandatory consideration 1, 7
• Continuous, dull, aching temporal/jaw pain (not paroxysmal) 7
• Associated scalp tenderness, visual disturbances, jaw claudication, elevated ESR/CRP 7
• Requires immediate high-dose corticosteroids to prevent blindness 1, 7

Post-Herpetic Neuralgia

• Continuous burning pain (not paroxysmal) at site of previous herpes zoster eruption 6
• Associated allodynia and hyperalgesia in affected dermatome 6

Glossopharyngeal Neuralgia

• Same paroxysmal characteristics as TN but different distribution: deep ear, posterior tongue, tonsils, neck 1, 6
• Triggered by swallowing, coughing, or touching ear 6
• May be associated with syncope due to vagal proximity 1

Persistent Idiopathic Facial Pain (Atypical Facial Pain)

• Continuous, non-anatomical pain without paroxysmal attacks or characteristic triggers 1, 6
• Often associated with chronic pain history, mood disturbance, poor coping skills 1

Investigation

Obtain MRI with high-resolution thin-cut sequences through the entire trigeminal nerve course in all patients with suspected trigeminal neuralgia to identify neurovascular compression and exclude secondary causes. 1, 5, 8

MRI Protocol:

• 3D heavily T2-weighted sequences (FIESTA, DRIVE, or CISS) to visualize neurovascular compression 1, 8
• MR angiography to characterize vascular anatomy 1
• Include brainstem imaging to evaluate for multiple sclerosis plaques 1
• 3 Tesla MRI provides superior anatomic resolution when available 1
• Imaging demonstrates 83-100% congruence with surgical findings 6

When to Image Urgently:

• Any sensory deficits in trigeminal distribution 6
• Continuous pain between paroxysmal attacks 6
• Bilateral symptoms 3
• Age <40 years (higher risk of secondary causes) 3

CT Role:

• Complementary for evaluating osseous skull base and neural foramina 1
• Useful for surgical planning but inferior to MRI for soft tissue and neurovascular compression 1

Pharmacological Management

Start carbamazepine as first-line treatment for all patients with trigeminal neuralgia, as it remains the gold standard with FDA approval specifically for this indication. 1, 5, 2

First-Line Agents:

• Carbamazepine: 200-1200 mg/day divided doses 1, 2

  • FDA-approved specifically for TN 2
  • Therapeutic plasma levels: 4-12 mcg/mL 2
  • Autoinduction occurs over 3-5 weeks; half-life decreases from 25-65 hours initially to 12-17 hours with chronic dosing 2

• Oxcarbazepine: Equally effective with fewer side effects 1, 5

  • Preferred alternative when carbamazepine side effects are intolerable 1

Second-Line Agents (when first-line inadequate or not tolerated):

• Lamotrigine 1, 5
• Baclofen 1, 5
• Gabapentin (evidence from RCT combined with ropivacaine) 1, 5
• Pregabalin (evidence from long-term cohort studies) 1, 5

Treatment Monitoring:

• Assess response within 3-5 weeks after autoinduction completes 2
• Monitor for side effects: dizziness, ataxia, diplopia, hyponatremia 2
• Consider plasma level monitoring if response is suboptimal 2

Critical pitfall: Carbamazepine is not a simple analgesic and should not be used for trivial aches or pains 2

Surgical Management

Consider surgical intervention when pain control becomes suboptimal despite medication optimization or when medication side effects become intolerable; obtain neurosurgical consultation at an early stage. 1, 5

Microvascular Decompression (MVD)

MVD is the preferred non-ablative procedure for patients with documented neurovascular compression and acceptable surgical risk. 1, 5

• Indications: Classical TN with neurovascular compression on MRI, younger patients, good surgical candidates 1, 9
• Efficacy: 70% pain-free at 10 years 1, 5
• Complications:
  • Hearing loss: 2-4% 1, 5
  • Mortality: 0.4% 1, 5
  • Rare trigeminal nerve complications (nerve remains intact) 1
• Mechanism: Identifies and removes vascular compression without destroying nerve 1

Ablative Procedures (for elderly, high-risk patients, or failed MVD)

All ablative procedures destroy sensory fibers to varying degrees, resulting in sensory loss 1:

• Radiofrequency thermocoagulation of Gasserian ganglion 1, 5
• Glycerol rhizotomy 1, 5
• Balloon compression of Gasserian ganglion 1, 5
• Gamma Knife radiosurgery 1, 5
  • Median time to pain relief: 1 month (can take up to 6 months) 6
• Peripheral neurectomy 1

Surgical Decision Algorithm:

1. Document neurovascular compression on MRI → Consider MVD if good surgical candidate 1, 9
2. No neurovascular contact on MRI → Consider neuroablative procedures 9
3. Elderly or significant comorbidities → Prefer ablative procedures over MVD 5
4. Patient preference against major surgery → Offer ablative alternatives 9

Important caveat: SUNCT/SUNA may have poorer surgical outcomes than classical TN, possibly due to different etiology 1