Trigeminal Nerve and Trigeminal Neuralgia

• Trigeminal neuralgia (TN) is a facial neuropathy of the fifth cranial nerve, characterized by sudden, intense, shock-like pain on one side of the face.
• TN most commonly affects the V2 (maxillary) and V3 (mandibular) divisions of the trigeminal nerve.
• TN attacks are brief but recurrent, triggered by activities like talking, chewing, smiling, drinking (hot or cold), shaving, or brushing teeth.
• Physical contact or even a cold wind can also trigger TN attacks.
• TN episodes last seconds but can occur hundreds of times daily and may include facial spasms (tic douloureux).

Diagnostic Criteria

• Recurrent unilateral facial pain along trigeminal nerve divisions.
• Severe pain lasting fractions of a second to 2 minutes, described as electric, shock-like, stabbing, or sharp.
• Triggered by non-noxious stimuli.
• Not better explained by another condition.

Anatomy of the Trigeminal Nerve

• The trigeminal nerve (fifth cranial nerve) has motor and sensory functions.
• It originates in the pons and splits into larger sensory and smaller motor roots.
• The sensory division forms the trigeminal ganglion in the trigeminal cave, lateral to the cavernous sinus.
• The three sensory divisions are ophthalmic (V1), maxillary (V2), and mandibular (V3).
• The ophthalmic division exits through the superior orbital fissure, maxillary through the foramen rotundum, and mandibular through the foramen ovale.
• The motor portion innervates the mandibular division (V3).
• Brainstem reflexes like blink, corneal, and jaw jerk reflexes use sensory and motor portions of the trigeminal nerve.
• The trigeminal nerve is near vital structures like superior cerebellar arteries and parotid glands.

Pathophysiology

• Classical TN involves neurovascular compression seen on MRI or during surgery.
• Secondary TN is caused by a primary disease process.
• Idiopathic TN has no identifiable cause.
• Classical TN is most common (75%), followed by secondary (15%) and idiopathic (10%).
• Demyelination from neurovascular compression, often by the superior cerebellar artery (50%), is thought to cause classical TN.
• Venous compression accounts for approximately 25% of cases.
• Other associated vessels include pontine veins, the anterior inferior cerebellar artery, and basilar artery.
• The trigeminal nerve root entry zone is vulnerable to injury due to the transition from Schwann cell to oligodendroglia myelin fibers.
• Contact between vessels and the trigeminal nerve isn't sufficient for diagnosis, as it can occur without TN history.
• Secondary TN results from tumors (brainstem lesions), arteriovenous malformations, or demyelinating diseases like multiple sclerosis (MS).
• The "ignition hypothesis" suggests damaged sensory neurons become hyperexcitable, generating ectopic pain impulses and cross-excitation.
• Other pain mechanisms involve voltage-gated ion channel mutations (sodium and potassium), neural inflammation, microvascular ischemia, and reduced gray matter volume.
• Dysregulation of sodium channel expression and SCN8A mutations may explain the efficacy of antiseizure medications.

Epidemiology

• TN is rare, occurring in 4 to 13 per 100,000 persons annually.
• It typically presents after age 50 (between 53 and 57 years).
• There is a slight female predominance: 1.15:1 to 1.7:1.
• Secondary TN can present earlier, around age 43 and becomes more common with age
• Earlier presentation is common with MS, where up to 2% of patients have both TN and MS.
• TN in MS may present bilaterally instead of unilaterally.
• Familial or genetic links are suggested by family clusters of TN, possibly with autosomal dominant transmission, and may involve neuropathies similar to glossopharyngeal and Charcot-Marie-Tooth disease.
• Pediatric TN is exceedingly rare.

Clinical Presentation

• Patients experience severe, debilitating, unilateral paroxysmal pain described as burning, sharp, stabbing, or shooting.
• Pain most often occurs in the maxillary (V2) or mandibular (V3) distributions but can affect the ophthalmic (V1) distribution in up to 25% of cases.
• There is a slight predominance for right-sided laterality (60%). Bilateral pain is rare and suggests another condition
• TN does not present with autonomic dysfunction like conjunctival tearing or rhinorrhea.
• Attacks can be accompanied by brief facial spasms
• Up to half of patients, especially later in the disease course, report a continuous background of dull pain in the same area as the spasms, more common in females.
• Attack duration ranges from a fraction of a second to 2 minutes. Longer attacks suggest another condition
• Frequency ranges from a few to hundreds of spasms daily, with maximal pain at onset
• Pain can be induced by stimuli like a breeze, talking, chewing, laughing, light touch, or teeth brushing.
• Patients may have symptom-free periods lasting days to years, and spontaneous remission can occur.
• Patients with TN may have higher rates of anxiety and depression

History

• A thorough history is critical, as physical examination findings are usually normal
• Focus on the characteristics of the pain, including onset, location, and duration, and exclude other conditions
• Onset is sudden and memorable and the pain paroxysmal and pulse-like, lasting no more than 2 minutes.
• Location is unilateral, most often over the maxillary or mandibular tracts, with right-sided predominance (60%). Pain elsewhere should be absent, but hyperalgesia or hypoesthesia may be present in the affected area.
• History-taking should exclude other conditions, including headaches, head trauma, dental issues, TMJ disorders, visual disturbances, rheumatic or autoimmune processes, and infections (particularly herpes zoster).

Physical Examination

• The physical examination rules out other causes of facial pain or finds causes for secondary TN.
• Findings are usually normal unless associated with another condition like MS or a space-occupying lesion.
• Other cranial nerve abnormalities or focal neurologic deficits suggest another mimicking condition
• Facial examination is last, as it may trigger an attack.
• Patients may have grimacing and unilateral facial spasms ipsilateral to the pain and should not have other unwanted movements.
• The head and neck should be without erythema, edema, trauma, rash, or lesions, and the oral membranes and dentition without infection.
• A thorough cranial nerve examination rules out other conditions as patients should not have deficits in hearing, vision, balance, extraocular, facial, neck, tongue, or palatal movements. Sensation should be intact, although 30% may experience facial hypoesthesia on the affected side and Reflex testing should be symmetrical
• Palpation of the head and neck should not reveal lymphadenopathy, and the interior of the buccal cavities should be without cavities or abscesses.
• Palpation of the TMJ joint should be without pain, crepitus, or locking.

Diagnostics

• TN is a clinical diagnosis, but diagnostics determine the etiology (classical, secondary, or idiopathic) and rule out other conditions
• MRI, particularly high-resolution 3-Tesla, is standard for clarifying secondary causes.
• MRI with and without contrast should include 3D T2-weighted, 3D time-of-flight, and magnetic resonance angiography with 3D T1-weighted gadolinium sequences. Thin cuts through the trigeminal ganglion should be made
• FIESTA imaging of the pons can elucidate the relationship between the trigeminal nerve and surrounding vascular structures.
• Diffusion tensor imaging with MRI can further elucidate TN caused by vascular compression.
• MRI without contrast and CT scans are alternatives if MRI is not possible, though CT scans provide poor resolution
• Trigeminal reflex testing examines the function of the bilateral ophthalmic, maxillary, and mandibular trigeminal nerve distributions with 87% specificity and 94% sensitivity.
• Additional laboratory studies include CBC, LFTs, and electrolyte panel for antiseizure medication monitoring and ECG testing as several antiseizure medications are contraindicated with atrioventricular blocks.

Red Flags for Further Workup

• Any neurologic findings outside of mild hypoesthesia of the affected side should be investigated further.
• Sudden, severe, or new-onset headache ("worst headache of my life")
• Sudden nausea and vomiting associated with a headache
• Infectious symptoms—fever, nuchal rigidity, elevated WBC count
• Cerebellar findings such as grossly positive Romberg testing, ataxia, dysmetria
• Vision loss or changes, such as diplopia
• Extraocular movements intact (EOMI) palsies, particularly VI or III

Interprofessional Collaborative Management

• Patients with abnormal neurologic findings should be referred to a neurologist as well anyone experiencing initial treatment failure.
• Consultation with a neurosurgeon and pain management specialists is often necessary.

Nonpharmacologic Management

• Avoiding triggers like talking, chewing, hair brushing, teeth brushing, smiling, and palpation of the face or neck is critical.
• Limiting stimulation and activities and promoting a calming environment can help promote relaxation
• Patients with pain refractory to medical management may be candidates for surgical or percutaneous therapy.
• Major surgical interventions include microvascular decompression, ablative treatment (invasive) with mechanical compression, and stereotactic radiosurgery.
• Microvascular decompression is preferred for younger patients with refractory classical TN entailing surgical exploration of the posterior fossa and inserting a soft cushion between the blood vessel and the nerve. It is considered the most effective technique.
• Ablative percutaneous treatments can be used for nonclassical TN and older patients with more comorbidities. These procedures damage the nerve and interrupt pain transmission.
• Stereotactic radiosurgery includes Gamma Knife surgery to cut the trigeminal nerve using focused beams of radiation. Pain relief may take up to 3 months

Pharmacologic Management

• Preventative treatments via sodium channel blockers like carbamazepine and oxcarbazepine are the gold standard
• Oxcarbazepine may have fewer side effects, though both are generally well-tolerated
• Options can be used sequentially or combined with lamotrigine, gabapentin, pregabalin, or baclofen.
• Monitoring of sodium levels is necessary.
• Lamotrigine can be used as monotherapy or as an adjunct but requires slow titration to avoid cutaneous reactions and is associated with lower bone mineral density
• Other adjunctive options include gabapentin, pregabalin, baclofen, tizanidine, clonazepam, phenytoin, topiramate, valproate, tocainide, botulinum toxin, and localized anesthetics.
• Opioids are not effective and should be avoided.
• Hospitalization is considered for patients with pain refractory to several modalities or limitations caused by TN that require concomitant modalities, including lidocaine, valproate and phenytoin infusions, or sphenopalatine ganglionic blocks.

Patient Education

• The comorbidity of depression, anxiety, and insomnia are common.
• Facial twitches can cause social isolation, and medical management side effects can be debilitating.
• Pain can result in loss of sleep and poor nutrition and and misdiagnosis frequently leads to unnecessary dental procedures and treatment delays
• Both TN and concomitant depression may respond to neuropathic medications, including duloxetine.

This quiz covers the divisions and functions of the trigeminal nerve. It also covers the diagnosis, characteristics, and triggers of trigeminal neuralgia. The questions test knowledge of anatomy, diagnostic criteria, and potential complications.