Trigeminal Neuralgia

Introduction and History

Trigeminal neuralgia, first described in detail by Dr. James Fothergill in the 18th century, is an affliction of such severe facial pain that it has previously been dubbed the “suicide disease.” Early treatments primarily focused on peripheral neuroablative procedures. Carnochan documented the first successful surgical treatment of the disease in 1856, which used a transantral approach to follow the maxillary nerve back to the gasserian ganglion, which was subsequently excised. In the 1890s Victor Horsley developed a subtemporal approach to the gasserian ganglion where he sectioned the preganglionic nerve fibers. Also in the 1890s Hartley and Krause independently described the extradural approach for gasserian ganglionectomy. In the late 1890s Cushing developed a modification of this extradural ganglionectomy that utilized a more basal trajectory to avoid bleeding from the middle meningeal artery. Dandy was the first to perform a lateral suboccipital approach (“cerebellar route” ) to the trigeminal nerve for treatment of trigeminal neuralgia in the 1920s. Similar to other techniques, his involved sectioning of the preganglionic trigeminal nerve. As a result of his intracranial approach through the posterior fossa, he was the first to note the frequent incidence of vascular compression on the trigeminal nerve in its cisternal segment and postulate that sensory root compression may be an important factor in the pathogenesis of trigeminal neuralgia. Gardner furthered this theory in the 1960s and published successful results from vascular decompression of the nerve root. With the advent of the surgical microscope, Jannetta solidified the theory of vascular compression as the underlying etiology for trigeminal neuralgia and demonstrated the excellent response rate and surgical safety for microvascular decompression (MVD) of the trigeminal nerve in a large series of patients.

Percutaneous techniques also evolved in parallel to open surgical treatments for trigeminal neuralgia. As early as 1910, Harris documented the percutaneous injection of alcohol into the gasserian ganglion in the treatment of a patient with trigeminal neuralgia. In 1914 Härtel described the landmarks and trajectory for accessing the gasserian ganglion through an anterior trajectory. Sweet further established the methods of radiofrequency rhizotomy (RFR), and Mullan developed the balloon compression technique. The application of the radiation to achieve lesioning of the trigeminal nerve was the first clinical application of stereotactic radiosurgery (SRS) by Leksell in the 1950s. Taken together, these techniques—MVD, RFR, balloon compression, glycerol rhizotomy, and SRS—continue to represent the current interventional armamentarium for treating trigeminal neuralgia.

Pathogenesis

One important hypothesis regarding the mechanism for trigeminal neuralgia attributes causation to demyelination of the trigeminal sensory fibers (typically in the nerve root, but occasionally in the brainstem). In most cases demyelination involves the proximal part of the nerve root that is technically within the central nervous system (CNS) and myelinated by oligodendroglial cells rather than Schwann cells (the Obersteiner-Redlich zone). Demyelination is commonly caused by arterial compression. Less common causes of demyelination are venous compression, demyelination from multiple sclerosis (MS), or compressive lesions in the posterior fossa. These focal areas of demyelination enable direct apposition of the axons from larger Aα and Aβ sensory fibers with neighboring axons of unmyelinated small Aδ and C fibers transmitting pain signals. This anatomic configuration enables both ephaptic conduction between these apposed fibers as well as ectopic generation of spontaneous nerve impulses. This spontaneous activity is further exacerbated by the deformity associated with vascular indentation. Surgical decompression of the nerve root provides rapid relief of pain by releasing the focal pulsatile distortion of the nerve rootlets and causing separation of the demyelinated rootlets, thus preventing both ectopic nerve signals and the ephaptic spread of these signals. The impact of remyelination over time may play a role in preventing recurrence of the neuralgia over the long term.

An alternative hypothesis, first suggested by Devor in 1994, states that a cluster of damaged neurons in the gasserian ganglion becomes hyperexcitable, forming an “ignition focus” and subsequent autonomous firing within the ganglion that ceases once the neural refractory period is reached. This may explain the not infrequent (up to 17% of cases) instance of trigeminal neuralgia that occurs in the absence of mass lesions, demyelinating diseases, or neurovascular compression.

Clinical Features and Diagnosis

The annual incidence of trigeminal neuralgia is ~4.5 per 100,000. The overall prevalence is up to 27 cases per 100,000 people-years. It is about twice as common in females as in males, and peak incidence occurs between 50 and 60 years of age. The classic description of facial pain associated with trigeminal neuralgia is a unilateral, sharp, lancinating, electric-shock–like pain that is episodic in nature with interval pain-free periods. Frequently, there are trigger areas or activities (eg, eating, dental care) that provoke pain episodes. Though mild hypesthesia may be present, trigeminal nerve function typically does not show impairment on physical exam.

The majority of patients will have an initial response to anticonvulsant medications such as carbamazepine, and about 50% of patients will achieve remission of pain for 6 months or more. However, in nearly four of five patients, pain will recur after the initial diagnosis. The frequency of pain may vary substantially between patients, from occasional paroxysms to incessant twinges of “status trigeminus.” Distribution of pain is most frequently in the V2 and V3 branches of the trigeminal nerve (one-third of patients); configuration of pain in V2 or V3 alone, or in V1 and V2 alone, occurs in about 15% of patients; pain in V1 alone is rare (~4%). In evaluating patients with pain in the trigeminal distribution, it is important to assess for other potential causes of facial pain. These include dental pathology, temporomandibular joint pain, migraines, postherpetic neuralgia, and temporal arteritis. It is also important to realize that trigeminal neuralgia may go unrecognized by other providers less attuned to the diagnosis, and patients with tic pain may undergo numerous dental procedures or other such treatments before the correct diagnosis of trigeminal neuralgia is reached.

The International Headache Society distinguishes neurogenic facial pain in the distribution of the trigeminal nerve as either symptomatic trigeminal neuralgia or “idiopathic” trigeminal neuralgia. Symptomatic trigeminal neuralgia refers to trigeminal nerve pain related to an identifiable pathology, such as CP angle tumors; idiopathic trigeminal neuralgia refers to trigeminal nerve pain without an identifiable pathology. It is important to differentiate between cases of symptomatic tic pain and idiopathic cases, as treatment strategies will differ between the two groups. Symptomatic cases, such as those due to MS, schwannomas, meningiomas, metastatic tumors, epidermoid cysts, arachnoid cysts, or other pathologies, are best addressed by direct treatment of the underlying pathology. In cases of new onset trigeminal neuralgia without additional cranial neuropathies, magnetic resonance imaging (MRI) reveals an underlying pathology (not including vascular compression of the trigeminal nerve) in approximately 15% of cases. Pooled data from MRI studies reveal vascular compression of the symptomatic nerve in 77% (sensitivity) of patients, whereas there is no vascular compression in asymptomatic nerves in 71% (specificity) of cases.

Trigeminal neuralgia in the setting of MS is particularly important to consider. Patients with MS are 20 times more likely to suffer from trigeminal neuralgia than those without MS; about 5% of patients with trigeminal neuralgia also have MS, whereas about 2% of patients with MS will develop trigeminal neuralgia. These patients typically do not tolerate the anticonvulsant medicines as well as non-MS patients and thus more frequently experience medically intractable pain. They also do not respond as well to MVD in comparison to idiopathic cases of trigeminal neuralgia and are more prone to surgical complications. Special consideration should be made in these cases; in many cases the pain may be well controlled with less invasive procedures such as RFR or SRS. Idiopathic trigeminal neuralgia may be further characterized by its clinical manifestations. Typical trigeminal neuralgia (type 1 TN) is pain that is >50% sharp, lancinating, and shocklike with pain-free intervals and atypical trigeminal neuralgia; “atypical” (type 2 TN) is pain for which >50% of symptoms are constant with an aching, throbbing, or burning character. Patients with typical trigeminal neuralgia more frequently are found to have arterial vascular compression at surgery and have both more frequent and more durable responses to microvascular decompression. Although they have a less favorable outcome profile compared to “typical” trigeminal neuralgia, patients with atypical trigeminal neuralgia still demonstrate a meaningful response to treatment and remain surgical candidates. Other forms of trigeminal nerve pain exist—such as deafferentation pain (related to prior rhizotomies), neuropathic pain (related to peripheral trigeminal nerve trauma), and atypical facial pain. These categories and their optimal management, however, are less well defined in the literature.