Trigeminal Neuralgia: Types, Symptoms and Anatomy

Trigeminal Neuralgia (TN) Overview

• TN is a chronic neuropathic disorder causing sudden, severe, unilateral facial pain along the trigeminal nerve distribution.
• TN Types:
  • Classic TN: Neurovascular compression.
  • Secondary TN: Tumors, multiple sclerosis (MS), or trauma.
  • Idiopathic TN: Unknown cause.
• Symptoms: Brief, electric shock-like episodes triggered by innocuous stimuli.
• Early Diagnosis & Treatment: Critical for reducing morbidity and improving life quality.
• Also known as Tic Douloureux (French for facial spasm).
• Usually limited to one side of the face.

Trigeminal Nerve Anatomy

• The trigeminal (fifth cranial) nerve provides sensation to:
  • Skin of the face
  • Anterior half of the head
  • Nasal and oral mucosa
• The motor part innervates muscles involved in chewing (masseters, pterygoids) and others.
• Largest of the cranial nerves.
• Exits in the lateral midpons, traverses the middle cranial fossa to the semilunar ganglion in Meckel's cave.
• Divides into three branches:
  • Ophthalmic (V1)
  • Maxillary (V2)
  • Mandibular (V3)
• V1 and V2 traverse the cavernous sinus and exit via the superior orbital fissure and foramen rotundum.
• V3 exits through the foramen ovale.
• Predominantly sensory, with motor innervation exclusively in V3.
• The cornea is primarily innervated by V1, with possible inferior crescent V2 innervation.
• Pain and temperature fibers descend ipsilaterally to the upper cervical spinal cord as the spinal tract of V before synapsing with the spinal nucleus of V.
• Accounts for facial numbness with spinal cord lesions above C2.
• Located adjacent to crossed ascending fibers of the spinothalamic tract in the brainstem.
• Produces a "crossed" sensory loss for pain and temperature with lateral lower brainstem lesions.
• Ensheathed by oligodendrocyte-derived myelin for up to 7 mm after leaving the brainstem.
• High frequency of trigeminal neuralgia in multiple sclerosis (MS), a disorder of oligodendrocyte myelin.

Etiology of TN

• Classic TN: Primarily caused by vascular compression of the trigeminal nerve root, leading to demyelination and aberrant signaling.
• Secondary TN: Arises from structural lesions or nerve damage from trauma/surgery.
• Genetic predisposition and autoimmune mechanisms may contribute.
• Idiopathic TN: Lacks identifiable pathology.
• Ophthalmic branch carries sensory information from the scalp, forehead, upper eyelid, conjunctiva, cornea, nose, nasal mucosa, frontal sinuses, and parts of meninges.
• Maxillary branch carries sensory information from lower eyelid, cheek, upper lip, upper teeth/gums, nasal mucosa, palate, roof of pharynx, and sinuses.
• Mandibular branch carries sensory information from the lower lip, lower teeth, gums, chin, jaw, parts of the external ear, and other parts of the meninges.
• Vascular compression (artery or vein) comes into contact with the trigeminal nerve at the base of the brain in Primary Trigeminal Neuralgia.
• Secondary TN caused by Trauma, Multiple Sclerosis, Vestibular Schwannoma, Meningioma, Cyst, Saccular Aneurysm, Arterio-venous malformation.
• Demyelination, vascular and degenerative changes in the sensory ganglion lead to ectopic impulse generation, causing ephaptic transmission.
• Symptoms result from ectopic generation of action potentials in pain-sensitive afferent fibers of the fifth cranial nerve root.
• Compression or pathology leads to demyelination of large myelinated fibers, causing them to become hyperexcitable and electrically coupled with smaller unmyelinated fibers.
• Tactile stimuli, conveyed via large myelinated fibers, can stimulate paroxysms of pain.
• Compression of the trigeminal nerve root by a blood vessel, often the superior cerebellar artery, is believed to be the source of trigeminal neuralgia in most patients.
• Age-related brain sagging and increased vascular thickness and tortuosity explain the prevalence of trigeminal neuralgia in later life.

Incidence and Risk Factors

• Annual incidence: 5.5-12.6 cases per 100,000.
• Higher incidence in women (2:1 ratio) and adults >50 years
• Lifetime prevalence: 0.3%, peaking at ages 60–70.
• Risk Factors:
  • Female sex: Hormonal and anatomical factors increase susceptibility.
  • Age >50: Degenerative vascular changes elevate neurovascular compression risk.
  • Comorbidities: MS, hypertension, or autoimmune disorders.

Prevention and Clinical Manifestations

• Manage hypertension and autoimmune conditions.
• Avoid triggers (e.g., cold wind, chewing hard foods).
• Use stress reduction techniques to minimize attacks.
• Paroxysmal pain: Sudden, unilateral, electric shock-like episodes lasting seconds to minutes.
• Trigger zones: Light touch to the face, chewing, or talking precipitates pain.
• Autonomic symptoms: Lacrimation or flushing rarely accompany attacks.
• Remission periods: Pain-free intervals between attacks.
• Psychological impact: Anxiety or depression due to unpredictable pain.
• Trigeminal neuralgia may sometimes be attributed to dental pain:
  • Classic trigeminal neuralgia typically presents as intermittent, sharp pain.
• Recurrent paroxysms of pain in one or more branches of the CN V unilaterally: burning, stabbing, sharp, penetrating, like an electric shock.
• Severe pain may last seconds to up to 15 minutes.
• Trigger zones may be present where light contact with the area initiates an attack.
• Described as the most excruciating pain in humanity.
• Usually unilateral; suspect MS if bilateral.

Characteristics of TN

• Excruciating paroxysms of pain in the lips, gums, cheek, or chin.
• Rarely, in the distribution of the ophthalmic division of the fifth nerve.
• The pain seldom lasts more than a few seconds or a minute or two but may be so intense that the patient winces, hence the term tic.
• The paroxysms, experienced as single jabs or clusters, tend to recur frequently, both day and night, for several weeks.
• May occur spontaneously or be brought on with movements of affected areas by speaking, chewing, or smiling.
• Trigger zones, typically on the face, lips, or tongue, provoke attacks.
• Tactile stimuli generate excruciating pain.
• Objective signs of sensory loss cannot be demonstrated on examination.
• Relatively common, with an estimated annual incidence of 4-8 per 100,000 individuals.
• Middle-aged and elderly persons are affected primarily, and ~60% of cases occur in women.
• Onset is typically sudden, and bouts tend to persist for weeks or months before remitting spontaneously.
• Remissions may be long-lasting, but the disorder ultimately recurs.

Review of Systems & Assessment

• Neurological: Facial pain, numbness (rare in classic TN).
• Dermatological: Trigger points in V1-V3 distributions.
• Psychiatric: Anxiety, sleep disturbances.
• Otolaryngological: Jaw stiffness, difficulty eating.
• Physical Assessment Findings:
  • Trigger point activation: Light palpation of the cheek/lip induces pain.
  • Normal sensory exam: No objective sensory loss in classic TN.
• Cranial nerve exam: Excludes cerebellopontine angle tumors.
• MS signs: Nystagmus or limb weakness in secondary TN.
• Hypertensive retinopathy: If comorbid hypertension.
• Barrow Neurological Institute Pain Scale: Quantifies pain severity and treatment response.
• MRI Severity Grading: Assesses neurovascular compression.

High Yield Questions to Ask Patient

• Describe the pain quality (electric, burning, throbbing)?
• Does pain occur in specific zones (e.g., cheek, jaw)?
• What triggers the pain (e.g., brushing teeth, wind)?
• Any history of MS, hypertension, or facial trauma?
• Have you tried medications? If so, which ones?
• Any numbness or weakness between attacks?
• Does pain disrupt sleep or eating?
• Family history of TN or autoimmune disorders?
• Recent weight loss or neurological symptoms?
• Do you experience anxiety about pain recurrence?

Differential Diagnoses

• Classic TN: Trigger-induced pain, normal neuro exam; use MRI with FIESTA sequence for diagnosis.
• Dental Pain: Localized to tooth, worse with percussion; use Dental X-ray for diagnosis.
• Migraine: Throbbing pain, photophobia, aura; diagnosis via Clinical history.
• Ramsay Hunt Syndrome: Vesicular rash, hearing loss; use VZV PCR for diagnosis.
• Temporomandibular Disorder: Jaw clicking, limited range; Physical exam, CT jaw.
• Trigeminal neuralgia needs to be distinguished from other causes of face and head pain, pain arising from diseases of the jaw, teeth, or sinuses.
• Pain from a migraine or cluster headache tends to be deep-seated and steady with the superficial stabbing quality of trigeminal neuralgia.
• In temporal arteritis, superficial facial pain is present but is not typically shocklike.
• Elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) are suggestive of Temporal Arteritis.
• When trigeminal neuralgia develops in a young adult or is bilateral, MS is a key consideration.
• Cases that are secondary to mass lesions usually produce objective signs of sensory loss in the trigeminal nerve distribution.

Diagnostic Studies and Criteria

• Diagnosis is typically made from history and presentation.
• Pain caused by TN lasts > 15 min without radiation.
• Pain is characterized by at least 3 events of intense, sharp, burning, superficial, or stabbing precipitated by a trigger event.
• Absence of neurological deficits.
• No other attributable cause.
• MRI Brain with Contrast: Identifies neurovascular compression (90% sensitivity) or MS plaques.
• CT Angiography: Detects vascular anomalies (e.g., aneurysms).
• Serum Studies: Elevated ESR/CRP if autoimmune, Lyme titers in endemic areas.
• EMG/NCS: Normal in classic TN, abnormal in MS-related TN.
• Trigeminal Reflex Testing: Differentiates classic vs. secondary TN.
• An ESR or CRP is indicated if temporal arteritis is suspected.
• Neuroimaging studies are unnecessary but valuable in patients younger than 40 years or when symptoms are bilateral and MS is a consideration.

Diagnostic Criteria

• Recurrent paroxysms of unilateral facial pain in the distribution(s) of one or more divisions of the trigeminal nerve, with no radiation beyond.
• Pain has all of the following characteristics: lasting from a fraction of 1 second to 2 minutes, severe intensity, electric shock-like, shooting, stabbing, or sharp in quality.
• Precipitated by innocuous stimuli within the affected trigeminal distribution.
• Not better accounted for by another ICHD-3 diagnosis.

Treatment Prioritization

• First-line: Carbamazepine (200-1200 mg/day) or oxcarbazepine (600-1800 mg/day).
• Second-line: Gabapentin (900–3600 mg/day) or lamotrigine (50-400 mg/day).
• Refractory cases: Microvascular decompression or gamma knife radiosurgery.
• Pregnancy: Avoid teratogenic medications (e.g., carbamazepine); consider gabapentin.
• Elderly: Higher risk of medication side effects.
• Start with lower medication doses to avoid toxicity.

Nonpharmacological Interventions

• Trigger avoidance: Modify diet (soft foods), use electric razors.
• Acupuncture: Reduces pain frequency in 30-40% of patients.
• Cognitive behavioral therapy (CBT): Addresses pain-related anxiety.

Additional Treatment Options

• Avoidance of stimulation to trigger area's e.g. breeze, heat, cold
• Surgical decompression involves craniotomy and vascular separation
• Surgical ablation is the lesioning of the trigeminal ganglion by radiofrequency thermoregulation, mechanical balloon compression or chemical injection
• Peripheral Neurectomy or Nerve block involves the risk of muscle weakness, loss of facial sensation, recurrent neuralgia
• If pain is uncontrolled, weight loss, dehydration, poor dental hygiene, and depression need to be considered
• Drug therapy with carbamazepine is effective in ~50–75% of patients, start with a single daily dose of 100 mg taken with food and increased gradually; most patients require a maintenance dose of 200 mg four times daily.
• Doses >1200 mg daily provide no additional benefit.
• Dizziness, imbalance, sedation, and rare cases of agranulocytosis are the most important side effects of carbamazepine
• Add a second agent if symptoms persist or if dose is intolerable: Baclofen, Lamotrigine, Phenytoin, Gabapentin
• If drug treatment fails, surgical therapy should be offered, microvascular decompression is the most widely used method.
• Gamma knife radiosurgery of the trigeminal nerve root is also used for treatment and results in complete pain relief
• Radiofrequency thermal rhizotomy creates a heat lesion of the trigeminal ganglion or nerve; short-term relief is experienced by >95% of patients

Pharmacological Management: Carbamazepine

• Start at 100 mg BID, titrate to 200-400 mg TID; monitor CBC, LFTs, sodium.
• Initial treatment: Anticonvulsants (block nerve firing)
• Carbamazepine 100-200mg PO twice daily- increase dose by 200mg daily- Max dose 1200 mg daily
• MOA: unknown, but in seizures, carbamazepine reduces polysynaptic responses and blocks post-tetanic potentiation, and may reduce pain by stimulating the infraorbital nerve and depressing thalamic potential and bulbar and polysynaptic reflexes.
• FDA indication: treatment of trigeminal neuralgia.
• Side effects: drowsiness, dizziness, ataxia; monitor for Stevens-Johnson syndrome and toxic epidermal necrolysis.
• Test for HLA-B*1502 allele in patients at increased risk of serious cutaneous adverse reactions (Asian ancestry).
• Aplastic anemia and agranulocytosis have been reported with use of carbamazepine.

Initial Diagnosis Patient Guidance

• Educate on medication adherence and side effects.
• Demonstrate trigger avoidance techniques.
• Provide emergency plan for acute attacks.

Follow Up and Surveillance

• 2-4 weeks post-diagnosis: Assess medication efficacy/side effects.
• Annual MRI: Monitor for new lesions in MS-related TN.
• 70% achieve pain control with medications; 50% relapse within 5 years.
• Surgical interventions offer long-term relief in 80-90% of classic TN.

Possible Complications

• Medication toxicity: Stevens-Johnson syndrome (carbamazepine), hyponatremia.
• Corneal abrasions: From reduced blinking due to pain.
• Malnutrition: Due to avoidance of chewing.

Key Points

• Forehead sparing suggests central pathology.
• Carbamazepine remains first-line; MRI is mandatory to rule out secondary causes.
• Early surgical referral improves outcomes in refractory cases.