Abstract
Trigeminal neuralgia (tic douloureux) is a potentially disabling cause of head and facial pain. The majority of patients with painful cranial neuralgias present with unilateral facial pain, headache, or both. Many headaches with facial pain present with overlapping symptoms, making a specific diagnosis challenging. Onset of symptoms is usually after age 50 years and more common in women. Oral antiepileptics are typically the first-line pharmacologic agents. Botulinum toxin injections have shown a favorable response in some studies. Surgical interventions and neuromodulation have been found to be effective in resistant cases. Headache and facial pain significantly affect physical, cognitive, and psychosocial functioning. More effective diagnostic markers are important in both clinical practice and research to improve patient outcomes and overall quality of life.
Keywords
Facial pain, Headache, Migraine headache, Tic douloureux, Trigeminal neuralgia
Introduction
Cranial neuralgias and trigeminal autonomic cephalalgias are potentially disabling neurologic disorders. Trigeminal neuralgia (TN) is also called tic douloureux (Tic) . Trigeminal neuropathies are defined as “head and/or facial pain in the distribution of one or more branches of the trigeminal nerve caused by another disorder and indicative of neural damage. The pain is highly variable in quality and intensity according to the cause.”
The International Classification of Headache Disorders (ICHD) defines headache as “pain located above the orbitomeatal line.” Primary headache, such as migraine and tension-type headache, is a disorder unto itself; no underlying disease process is present. Secondary headache is a manifestation of an underlying disease process. A variety of headaches are frequently associated with facial pain. The ICHD-3 β, the most updated edition, defines facial pain as “pain below the orbitomeatal line, above the neck and anterior to the pinna.”
Trigeminal autonomic cephalalgias (TACs) characteristically feature unilateral pain and “share the clinical features of headache, which is usually lateralized, and often prominent cranial parasympathetic autonomic features, which again are lateralized and ipsilateral to the headache.” The majority of patients with painful cranial neuralgias present with unilateral facial pain, headache, or both. However, for many headache and facial pain disorders, pain patterns can cross these so-called boundaries. Classification of these disorders often overlaps significantly, leading to misdiagnosis or a prolonged treatment regimen involving trial and error of various pharmacologic and nonpharmacologic therapies. It has been questioned if these overlapping disorders are distinct entities or a continuum of the same disorder.
Epidemiology and Disease Burden
Epidemiologic evidence shows the prevalence of TN to be approximately 4–28.9/100,000 persons worldwide. Onset is usually after age 50 years and increases with advancing age. Women are affected 1.7 times more than men. A large retrospective cohort study demonstrated an increased risk of having comorbid depression or anxiety disorders in patients with TN. Activities of daily living, work productivity, and quality of sleep all may be affected.
Epidemiologic data show a strong association of TN in multiple sclerosis (a 20-fold increased risk of developing TN compared with the general population), as well as in cases of hypertension and stroke.
Another epidemiologic evaluation was completed to evaluate the diagnostic approaches for patients presenting to a tertiary neurology outpatient clinic with a complaint of side-locked headache and facial pain. Strictly unilateral headaches accounted for 19.2% of total headaches. Patients who present with secondary headaches and cranial neuralgias are more prevalent as age increases. Classical TN and persistent idiopathic facial pain (PIFP) were the most common painful cranial neuropathies.
Diagnostic Criteria
The ICHD is a detailed hierarchical classification of all headache-related disorders and facial pain published by the International Headache Society. The ICHD third β edition (ICHD 3-β) helps to further clarify the terminology used to classify these challenging neuropathic pain syndromes. This schematic classification is divided into three parts containing 14 sections. The first part identifies the primary headache disorders, including the TACs. The second part describes headaches attributed to an underlying (secondary) condition. The third part characterizes painful cranial neuropathies, other facial pains, and other headaches. Section 13 in the ICHD 3-β is further subdivided into other painful cranial neuropathies.
During the development of proper diagnostic criteria, several debates on terminology were created. The ICHD 3-β adds that “trigeminal and glossopharyngeal neuralgias present a problem of terminology. When pain is found to result from compression of the nerve by a vascular loop at operation, the neuralgia should strictly be regarded as secondary. Since many patients do not come to operation, it remains uncertain as to whether they have primary or secondary neuralgias. For this reason, the term classical (see Box 21.1 ) rather than primary has been applied to those patients with a typical history even though a vascular source of compression may be discovered during its course. The term secondary can then be reserved for those patients in whom a neuroma or similar lesion is demonstrated.” The ICHD 3-β no longer lists secondary or symptomatic TN as separate diagnostic categories.
13.1.1 Classical trigeminal neuralgia
Previously used term:
Tic douloureux
Description:
Trigeminal neuralgia developing without apparent cause other than neurovascular compression
Diagnostic criteria:
- A.
At least three attacks of unilateral facial pain fulfilling criteria B and C
- B.
Occurring in one or more divisions of the trigeminal nerve, with no radiation beyond the trigeminal distribution
- C.
Pain has at least three of the following four characteristics:
- 1.
recurring in paroxysmal attacks lasting from a fraction of a second to 2 min
- 2.
severe intensity
- 3.
electric shock–like, shooting, stabbing, or sharp in quality
- 4.
precipitated by innocuous stimuli to the affected side of the face
- 1.
- D.
No clinically evident neurologic deficit
- E.
Not better accounted for by another ICHD-3 diagnosis.
Notes:
- 1.
Some attacks may be, or appear to be, spontaneous, but there must be at least three that are precipitated in this way to meet this criterion.
- 2.
Hypoesthesia or hypoalgesia in the affected trigeminal region always indicates axonal damage. When either is present, there is trigeminal neuropathy and extensive diagnostic workup is necessary to exclude symptomatic cases. There are some patients with hyperalgesia in the painful region, which should not necessarily lead to a diagnosis of trigeminal neuropathy because it may reflect the patient’s increased attention to the painful side.
ICHD , International Classification of Headache Disorders.
Several grading systems are available, which makes it difficult to classify patients with TN in practice or research. It also hampers the design of clinical guidelines. The International Association for the Study of Pain (IASP) defines TN as “sudden, usually unilateral, severe, brief, stabbing, recurrent episodes of pain in the distribution of one or more branches of the trigeminal nerve.” Treede et al. suggested that the following definition of neuropathic pain be revised as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.” Cruccu et al. stated that “formally classifying trigeminal neuralgia as neuropathic pain based on the grading system of the IASP is complicated by the requirement of objective signs confirming an underlying lesion or disease of the somatosensory system.” Cruccu et al. reported that with endorsements from the Neuropathic Pain Special Interest Group of the IASP and the Scientific Panel of Pain of the European Academy of Neurology, a new diagnostic grading system for TN was proposed, which is in alignment with diagnostic certainty and was first introduced for neuropathic pain (see Fig. 21.1 ). The remainder of this chapter utilizes the ICHD 3-β diagnostic criteria for discussion.
Neuroanatomic Basis and Pathogenesis
Sensory axons at the distal aspect of the Gasserian ganglion form the three major divisions (V 1 , V 2 , and V 3 ). Motor axons travel in the mandibular division (V 3 ). A single neurite, consisting of cell bodies from the trigeminal ganglion, bifurcates and then projects out into the periphery and into the medullary dorsal horn, ultimately forming the major relay center for head and facial pain called the trigeminal nucleus caudalis. The descending root, or spinal tract, extends down through the pons, the medulla, and the upper cervical spinal cord as far down as C2–C4.
The nerve fiber peptidergic content plays an integral role in the modulation of pain transmission in the trigeminovascular system. Calcitonin-gene-related peptide, substance P, and neurokinin A are found in meningeal sensory fibers. Sympathetic fibers (containing neuropeptide Y) arise from the ipsilateral superior cervical ganglion, whereas parasympathetic fibers (containing vasoactive intestinal polypeptide) arise from the sphenopalatine and otic ganglia. Vascular loops can compress sensory roots, thus causing TN. Mechanical, thermal, or chemical stimuli activate sensory fibers and can create central sensitization of meningeal nociceptors ( Fig. 21.2 ).
The classic studies of Ray and Wolff demonstrated that “the brain itself is largely insensitive to pain, but the dura mater, the intracranial segments of the trigeminal, vagus, and glossopharyngeal nerves, and the proximal portions of the large intracranial vessels including the basilar, vertebral, and carotid branches, are pain-sensitive.” The dura mater consists of a large plexus of unmyelinated fibers, arising from the ophthalmic division of the trigeminal nerve and the upper cervical dorsal roots. Sympathetic and parasympathetic sensory nerve fibers innervate the dura.
There are several hypotheses to describe the relationship of vascular compression and TN. Classical TN usually occurs when there is vascular compression of the trigeminal nerve in the cerebellopontine angle. This theoretical model is still not well defined but is accepted in the literature. Neuroimaging may reveal a vascular anomaly (most commonly the superior cerebellar artery) or a cerebellopontine angle mass; then a diagnosis of secondary TN is given.
Some believe TN occurs as a result of focal demyelination of the nerve root entry zone due to pulsatile indentation at the impingement site, which often is a result of a tortuous vascular loop (most often the superior cerebellar artery). The establishment of central sensitization is a plausible mechanism to explain nociception and chronic pain. Other theories suggest a neurobiological mechanism with an underlying predisposing genetic basis.
Clinical Approach to Diagnosis
It is important to obtain a detailed clinical history and identify the location of pain—side-locked unilateral, bilateral, side-switching unilateral (before, during, or after attacks), or unilateral spreading to become bilateral. The pain described needs to be localized as central or peripherally based. The duration of the pain attack needs to be well characterized, lasting a fraction of second to minutes to hours or days. The frequency of attacks in TN can be as few as 1 to over 50 per day. An attack is an individual episode of pain, whereas remission is defined as a pain-free period in between attacks, with episodes occurring 1–50 times per day. One needs to establish if the pain attack consists of headache, facial pain, or both. The quality of the pain as well as associated symptoms, premonitory symptoms (warning signs), radiation pattern, and any medications taken need to be elicited from the patient. Often, pain questionnaires are utilized to obtain more detailed information.
In addition to routine review of past medical history, a thorough neurologic history should include history of orofacial, head, or neck trauma; comorbid psychiatric disorders; quality of sleep; family or personal history of migraine, stroke, multiple sclerosis, or other neurodegenerative disorders; history of skin disorder of the face or scalp; dental disorder or dental procedures; and history of infection or inflammatory disorder of the head and neck. A functional history must be taken.
Physical examination includes inspection of the skin (rash, vesicles etc.) and assessment of range of motion of the cervical spine and temporomandibular joint. Neurologic examination is often normal, but it is important to carefully test cranial nerves, sensation (sometimes a subtle sensory deficit is present, other times allodynia is present), temperature sense, and trigeminal reflexes.
Neuroimaging is utilized to rule out red flags. Gadolinium-enhanced magnetic resonance imaging (MRI) of the brain and fine cuts through the trigeminal nerves should be ordered for patients with acute or newly diagnosed TN. Conventional brain MRI may not always detect symptomatic neurovascular contact. High-resolution “constructive interference in steady state” (CISS) coronal imaging may better visualize neurovascular compression (see Fig. 21.3 ). The CISS protocol is commonly ordered for detecting intracranial lesions to assist with the diagnosis of TN. A multidisciplinary evidence-based review of the published literature by the American Academy of Neurology and the European Federation of Neurological Societies (EFNS) concluded that standard MRI is currently too insensitive for detecting neurovascular compression of the trigeminal nerve to recommend routine use.
