Trigeminal Neuralgia (tic douloureux)

Gregg Goldin, MD

Timothy Miller, MD

9/28/18

Neurology and Neurosurgery Grand Rounds

Disclosures

-None

Objectives

• 1) Epidemiology, pathophysiology, and medical management (GG)

• 2) Surgical options (TM)

• 3) Radiosurgical option (GG)

Debilitating neuropathic condition involving the fifth (trigeminal) cranial nerve

• Chronic facial pain disorder

• Severe/episodic

• Typically unilateral

• Usually affects mandibular and maxillary divisions

• Isolated involvement of the ophthalmic division is much less common

• Early 1500’s: Leonardo da Vinci sketches the cranial nerves

• 1600: Johannes Fehr and Elias Schmidt (secretaries of philosopher John Locke) describe the clinical entity

• 1756: Nicolas Andre coined the term tic douloureux

• 1773: John Fothergill described the first case series

• 1820: Charles Bell first localized the pain to the trigeminal nerve

• 1925: Walter Dandy sectioned the trigeminal nerve

• Late 1960’s: Peter Jannetta introduced the microvascular decompression (MVD)

• 1971, Lars Leksell treated first patient with stereotactic radiosurgery (SRS)

Nicolas Andre John Fothergill

Epidemiology • Prevalence = ~40,000

• Incidence = ~15,000/year

• Condition of elderly

• Slightly more common in Women

• >$100 million spent on procedures alone annually in the US

Harsha KJ, et al. Imaging of vascular causes of trigeminal neuralgia. J Neuroradiol. 2012;39(5):281–9

Mauskop A. Trigeminal neuralgia (tic douloureux). J Pain Symptom Manage. Apr 1993;8(3):148-54

Natural History (Classical TN)

• Misdiagnosed and under treated

• No clear natural history

• Paroxysmal attacks

• Pain tends to occur in cycles

• Pain-free intervals typically grow shorter

• Patients often live in fear and anticipation

Natural History

• Triggers: sensory stimulation • touch, certain head movements, talking, chewing,

swallowing, shaving, brushing teeth, or even a cold draft.

•

• In many, pain is generated spontaneously

• Stabbing electric shocks, burning, sharp, pressing, crushing, exploding or shooting pain

Pathophysiology • Believed to involve loss of the myelin

around the trigeminal nerve

• Etiologies include: • Neurovascular compression (most

commonly accepted) • at TN entrance into the brainstem (pons).

• In one study, 64% of the compressing vessels were identified as an artery, • most commonly the superior cerebellar (81%).

• Multiple Sclerosis

• Tumor

• Arteriovenous Malformation

• Facial Injury

Pamir MN, et al. Microvascular decompression in the surgical management of trigeminal

neuralgia. Neurosurg Rev. 1995;18(3):163–7.

Lummel N, et al. Diffusion tensor imaging of the trigeminal nerve in patients with trigeminal

neuralgia due to multiple sclerosis. Neuroradiology. 2015;57(3):259–67.

Samadian M, et al. Trigeminal Neuralgia Caused by Venous Angioma: A Case Report and

Review of the Literature. World Neurosurg. 2015;84(3):860–4.

Pathophysiology

• Mechanical compression often occurs as the nerve leaves the pons

• Nerve region especially susceptible to pathologic changes from vascular contact is the Redlich-Obersteiner’s zone, also known as the root entry zone (REZ).

• REZ is characterized by nerve axons ensheathed in central myelin, transitioning to peripheral myelin.

Agrawal SM, Kambalimath DH. Trigeminal neuralgia

involving supraorbital and infraorbital nerves. Natl J Maxillofac Surg. 2010;1(2):179–82.

Neurophysiological Mechanism “Ignition Therory”

• Vascular contact leads to instability and atrophy

• Nerves become hyperexcitable and generate abnormal discharges

• Spontaneous firing results in burning and paresthesias

• Cascade propagation to the trigeminal nucleus is perceived as burst of pain.

• Intense flares from synchronization of bursts • “ephaptic crosstalk” • increased ions or neurotransmitters in the

interstitial space Devor M, Amir R, Rappaport ZH. Pathophysiology of

trigeminal neuralgia: the ignition hypothesis. The Clinical

journal of pain. 2002;18(1):4–13.

Diagnosis • Diagnosis of exclusion

• Neuro exam findings are usually normal.

• Rapid spreading of pain, bilateral affliction, or involvement of other cranial nerves suggests a systemic cause • multiple sclerosis

• expanding cranial tumors

• Nerve compression on MRI often not visualized

• Blood work indicated if medical therapy is contemplated or to exclude collagen vascular diseases

Haines SJ, Jannetta PJ, Zorub DS. Microvascular relations of the trigeminal nerve: an anatomical study with clinical correlation. Journal of

neurosurgery. 1980;52(3):381–386.

Hamlyn PJ, King TT. Neurovascular compression in trigeminal neuralgia: a clinical and anatomical study. Journal of

neurosurgery. 1992;76(6):948–954.

Differential Diagnosis • Trigeminal neuropathy

• postherpetic neuralgia (PHN)

• Neoplasms

• Granulomatous inflammation

• odontogenic pain, geniculate neuralgia, glossopharyngeal neuralgia, temporomandibular disorders, sinusitis, cluster headache, hemicrania, and SUNCT (short-lasting, unilateral neuralgia from headache attacks with conjunctival injection and tearing) syndrome

MRI Characteristics • MRI (using heavily T2 weighted (FIESTA) sequences) to visualize cranial

nerves and exclude neoplasia

• Anatomical

• Volume: depletion of the trigeminal nerve volume is correlated with TN

• Neurovascular compression

• Functional • Decreased Fractional Anisotropy: indicator of microstructural changes and reduced “connectivity”

• Increased Apparent Diffusion Coefficient: associated with nerve atrophy

World Neurosurg. 2017 Feb;98:89-97. doi: 10.1016/j.wneu.2016.10.104. Epub 2016 Oct 27.

Treatment

• Medical treatment is first line

• Surgical interventions (including SRS) for refractory cases

• up to 50% of patients with classic TN will eventually require surgery

Medical Therapy

• Interrupt the temporal summation of afferent impulses

• After breakthrough on a single agent, a second and even third medication may be required • Anticonvulsant medicines—carbamazepine (most effective), oxcarbazepine, topiramate,

clonazepam, phenytoin, lamotrigine, and valproic acid. • many adverse CNS side effects

• up to 44% relapse or have unsatisfactory relief

• Gabapentin or baclofen

• Tricyclic antidepressants used to treat pain described as constant, burning, or aching

• Opiates are typically not helpful

Dalessio DJ. Trigeminal neuralgia. A practical approach to treatment. Drugs. Sep 1982;24(3):248-55.

Surgical Management of Facial Pain

Classification of Facial Pain

Classification of Facial Pain

Trigeminal Neuralgia Diagnostic Questionnaire

https://neurosurgery.ohsu.edu/tgn.php

Facial Pain Treatment Algorithm

Trigeminal Tract Neuroanatomy

-Semilunar Ganglion -Gasserian Ganglion -Gasser’s Ganglion -Trigeminal Ganglion

Trigeminal Tract Neuroanatomy VPM

Trigeminal Tract Neuroanatomy

Peripheral Trigeminal Nerve Interventions

V3 block V2 block

Peripheral nerve blockade

Peripheral Trigeminal Nerve Interventions

Neurectomy

Infraorbital

Supraorbital

Inferior Alveolar

Peripheral Trigeminal Nerve Interventions

Peripheral Neurostimulation

Interventions at the Ganglion

Percutaneous Radiofrequency Trigeminal Gangliolysis

Interventions at the Ganglion

Balloon Compression and

Glycerol Rhizolysis

Interventions at the Ganglion

Gasserian Stimulation

Dorsal Root Entry Zone

Microvascular Decompression

Dorsal Root Entry Zone

Trigeminal Rhizotomy

Trigeminothalamic Tract

-Trigeminal Tractotomy -Nucleus Caudalis DREZ

Trigeminothalamic Tract

High Cervical Spinal Cord Stimulation

Thalamus

Deep Brain Stimulation

Cortex

Temporary Trials

Stereotactic Radiosurgery • Absence of surgical risk

• Targets focused beams of high dose radiation to the trigeminal nerve at exit from the brainstem

• Axonal degeneration and necrosis disrupt transmission of pain signals

• Single treatment: maximum dose of 70 to 90 Gy

• Average pain-free is about the same as for radiofrequency (RF) rhizotomy, or around 3 years

Delineate the retrogasserian sensory root of the prepontine TN

• 1) anatomy tends to be symmetric.

• 2) Find the trigeminal eminence

• 3) Find Meckel’s cave

• 4) trigeminal sensory root will travel between brainstem and Meckel’s cave

• 5) Reference the coronal and sagittal images

• 6) target volume encompassed by 2 to 3, two mm thick MR slices

Gammaknife

Cyberknife Frameless SRS

• initial pain relief in up to 90% of cases,

• lag time ranging from 1 to 3 months.

• side effects: facial numbness, ranging from 20% to 32%, and less commonly dysesthesias and weakness

• One of the challenges of SRS is the long-term durability of pain relief

• Of 59 studies, 41 reported on SRS (n =5242), 12 reported on MVD (n= 8028), and 5 reported on both SRS (n = 535) and MVD (n =237).

• Efficacy • In the group treated with SRS, the initial success rate was 71.1%. Success rates

at follow-up (2 years, between years 2 and 5, and after 5 years) amounted to 77.8%, 63.1%, and 63.8%, respectively.

• In the group treated with MVD, the initial success rate was 86.9%. At followup, success rates were 91.4% (2 years), 80.6% (between years 2 and 5), and 84% (>5 years), respectively.

• With a median follow-up time of 36 months, the median recurrence rate was 11% for MVD and 25% for SRS, respectively

Complications

• less frequent complications: • MVD: perioperative mortality (0.31%),

cerebrospinal fluid leak (2.73%), and the combined percentage of cerebrovascular, cardiologic, pneumologic, or thromboembolic events (3.92%) in MVD.

• SRS: Keratitis, Anesthesia dolorosa (0.04%), tinnitus (0.15%), brainstem edema (0.06%), and chronic fatigue (0.79%)

Conclusions

• MVD yields more immediate and better long-term relief

• Although surgical complications associated with MVD are not negligible, dysesthesia and other CN effects after SRS may significantly compromise the patient’s quality of life too.

• MVD is a valid first-line treatment option for patients free of comorbidities. SRS would be advised in patients with a high surgical and anesthetic risk.

Questions?