Trigeminal and Glossopharyngeal Neuralgia

Definition

The International Association for the Study of Pain (IASP) has defined TN as “sudden, usually unilateral, severe, brief, stabbing, recurrent pains in the distribution of one of more branches of the fifth cranial nerve” ( ). TN can be either idiopathic or secondary to lesions such as tumors, cysts, or multiple sclerosis (also called symptomatic TN). Atypical or type 2 TN is the terminology used when constant pain remains after the initial sharp pain resolves.

Epidemiology

TN is a rare disease, and scant high-quality epidemiological data on it exist. One systematic review of the epidemiology of TN has been performed ( ). The crude annual incidence in women and men based on U.S. data between the years 1945 and 1984 was 5.7 and 2.5 per 100,000/yr, respectively, and incidence rates increased with age ( ). More recently, electronic primary care databases have been searched, and these have shown a higher incidence rate and a younger age group. U.K. ( ) and Dutch studies ( ) reported an overall yearly incidence of 26.8 and 28.9 per 100,000 patient-years, respectively. However, it is likely that some of these cases were misdiagnosed as dental pain, sinusitis, or even temporomandibular disorders. showed that the rate of misdiagnosis in general practitioners was as high as 48%. After diagnosis by experts, the overall incidence rate was 12.6 per 100,000 person-years with a mean age of 51.5 years and a 66% female preponderance ( ). Multiple sclerosis, increasing age, and possibly hypertension are associated risk factors.

Etiology and Pathophysiology

It is widely but not universally accepted that the most common cause of typical TN is arterial compression of the trigeminal nerve in the posterior fossa ( ). The theory of neurovascular compression is based on three concepts: (1) a normal blood vessel compresses the nerve in its course through the basal cisterns; (2) the nerve is compressed in the root entry zone, the area of transition from central to peripheral myelin, which is particularly sensitive to pressure; and (3) compression results in demyelination and ephaptic (i.e., extrasynaptic) transmission of impulses from touch fibers to pain fibers, which results in the paroxysms of pain. The root entry zone of the trigeminal nerve is conical in shape and extends to within 3–5 mm of the brain stem, as seen in Figure 66-1 .

The ignition hypothesis elegantly combines the known role of ion channels in neuropathic pain with previously described intraoperative and cadaveric anatomical observations ( ). According to this hypothesis, injury to afferent trigeminal neurons renders them hyperexcitable, presumably via changes in the regulation and trafficking of channel proteins, and prone to synchronized afterdischarge activity. From the results of electron microscopy it would appear that the central event in the genesis of TN is axonal swelling and subsequent focal demyelination. Similar ultrastructural changes have been seen in biopsy samples from patients with both TN and GPN ( ). In assessing TN in multiple sclerosis patients with trigeminal reflex testing and magnetic resonance imaging (MRI), found evidence of pontine plaque causing damage to primary trigeminal afferent fibers. Although neurovascular compression does not appear to be the universal cause of TN, it is reasonable to accept that it plays a substantial role in patients in whom the nerve is noted to be thinned at the site of compression, both by visual inspection and by MRI ( ). Recent studies also suggest that etiological differences exist between classic TN and other forms of the disease. Investigations using nociceptive blink reflexes and pain-related evoked potentials indicate that atypical forms of TN exhibit a higher degree of central sensory transmission and over-activation than typical TN does ( ), with a deficit in descending inhibition being found only in patients with atypical TN ( ).

Clinical Features

The clinical manifestations of TN have not all been validated by evidence-based methodologies. This task is made more difficult by the absence of a “gold standard” diagnostic study with high sensitivity and specificity ( ). The classification system of the lists the following clinical criteria for the diagnosis of typical TN, which were determined by a small expert committee:

• A.

  Paroxysmal attacks of pain lasting from a fraction of a second to 2 minutes that affect one or more divisions of the trigeminal nerve and fulfill criteria B and C.

• B.

  The pain has at least one of the following characteristics:

  • Intense, sharp, superficial, or stabbing

  • Precipitated at trigger areas or by trigger factors

• C.

  Attacks are stereotyped in individual patients.

• D.

  No neurological deficits are clinically evident.

• E.

  No other disorder can explain the symptoms.

At present, the diagnosis of TN is made principally by patient history, which must be taken with the utmost care. demonstrated that the key diagnostic features of TN, summarized in Figure 66-2 , have high sensitivity. Patients should be encouraged to “tell their own story” because the words that they use to describe the quality of their pain (i.e., shock-like, lightning, shooting, or electric current), its severity, and its periodicity are often pathognomonic for the condition. The clinical history can be supplemented with the McGill Pain Questionnaire, which discriminates well between typical TN and atypical facial pain syndromes ( ). The most frequently used words to describe typical TN are sharp, shooting, and cutting (70–95%); other common descriptors include unbearable, stabbing, exhausting, tender, vicious, terrifying, and torturing ( ). Some patients have an additional dull, aching, burning component of their pain. This pain, labeled as atypical, lingers for a considerable time after the main sharp, severe pain or may even be present continuously. No studies have been performed to determine whether atypical features are part of the initial constellation of TN symptoms or develop over time, possibly as a result of progressive changes in the trigeminal nerve.

It is generally accepted that pain severity increases with time, but no formal studies have validated this assertion. During an attack of severe pain the patient’s face may become distorted or “freeze,” and the hands may be positioned in front of the face as though to protect it. Patients may cry out in pain. Such non-verbal behavior is a useful clue to the severity of the pain.

Another important characteristic is the location of the pain, which is generally unilateral along the trigeminal nerve distribution. Around 4% of patients have bilateral pain, but it rarely occurs simultaneously on both sides of the face. There is a slight right-sided predominance, around 60%, but this does not link to handedness ( ), and the second and third divisions are more commonly affected than the first.

The timing of pain attacks is highly significant. Each single burst of pain usually lasts for seconds, but several bursts may follow in rapid succession before the nerve becomes refractory, thus giving the impression that an attack lasts for minutes. There is no gradual buildup or decrease in pain. Attacks of pain diminish at night. Patients can be free of pain for years (6%), months (36%), weeks (16%), or only days (16%). Diurnal constant pain is present in 4% of patients, and 23% have no recordable pain-free intervals ( ). Patients often have long, spontaneous remission periods, which tend to occur early in the disease process. Major precipitating factors of pain include chewing and talking (76%), touching (65%), and cold (48%) ( ). A trigger zone can be identified in 50% of these patients, and most indicate that it lies within the trigeminal nerve distribution. Apart from avoiding touching and moving their face, patients can do little to gain relief without recourse to drug therapy. Autonomic symptoms are rare.

Many patients will avoid precipitating factors and consequently lose weight, avoid cleaning their teeth on the affected side, and minimize socializing, especially if it involves eating and talking. Patients with TN, especially when experiencing bouts of severe pain, will suffer from anhedonia and even depression. Coping strategies need to be ascertained, fear of severe pain recurrence is ever present, and suicides have been reported ( ).

Examination

Neurological examination rarely detects any abnormalities in patients with idiopathic TN, but the cranial nerves must be tested carefully. It is important to repeat the examination periodically because neurological changes may occur with time. In a small percentage of patients, reported that secondary TN was diagnosed 6.3 years after the initial diagnosis of TN. Instrumental examinations indicate that over half of patients may have at least one abnormal measure of sensation, not only in the trigger zone division but also in adjacent divisions ( ). No evidence currently suggests that these subtle findings reflect disease severity or predict the presence of vascular compression. Patients with neurological abnormalities or progressive pain often have a structural lesion responsible for the symptoms. proposed that patients with atypical TN and trigeminal neuropathy are more likely to have evidence of allodynia as well as sensory loss.

Investigations

Once the clinical diagnosis of TN has been made, radiographic imaging should be performed to rule out symptomatic lesions. MRI is the preferred imaging modality. No imaging studies have thus far proved to be consistently useful in diagnosing idiopathic TN. Particular MRI sequences (i.e., fast imaging employing steady-state acquisition [FIESTA] or constructive interfering steady state [CISS]) are very sensitive in detecting blood vessels in contact with the trigeminal nerve, but they are not helpful in differentiating arteries from veins. Magnetic resonance angiography (MRA) can identify vascular compression of the trigeminal nerve with the added benefit of distinguishing arteries from veins ( ). Combining conventional MRI and MRA resulted in a sensitivity and specificity of 76% and 75%, respectively, for identifying the offending vessel ( ). An evaluation of MRI-based diagnostic methods can be found in recent TN guidelines ( ).

More recently, diffusion tensor imaging (DTI) has been investigated as a potential tool for diagnosing TN. Studies in patients with multiple sclerosis have demonstrated that demyelination is associated with changes in water diffusion that can be detected by DTI ( ). Early evidence suggests that changes in DTI parameters are also found in the affected trigeminal nerve in persons with TN ( ). Although more research is certainly needed, DTI may be an intriguing tool for identifying trigeminal nerve pathology. Besides neuroimaging studies, electrophysiological testing such as laser-evoked potentials and quantitative sensory testing are being evaluated for their ability to differentiate between idiopathic and symptomatic TN ( ).

Differential Diagnosis

The differential diagnosis of unilateral facial pain in the distribution of the trigeminal nerve is extensive. Frequently, the initial clinical setting in which the patient is seen influences the diagnosis. Some disease entities that need to be considered are listed in Table 66-1 ; others can be found in references on oral and dental pain. In the early stages of the disease it can be difficult to differentiate TN from a toothache because the initial symptom in many patients is often intra-oral.