Neuropathic pain (NP) is defined as pain initiated by a primary lesion or dysfunction of the nervous system. NP may be an idiopathic process reflecting abnormal sensory processing in the peripheral or central nervous system but with no clearly associated pathologic lesion. Secondary NP appears after physical insult or disease that affects the peripheral or central nervous system. Although secondary NP may be due to ongoing disease, healed injury may leave the nervous system in a pathologic state as in painful posttraumatic neuropathies. NP in the orofacial region (neuropathic orofacial pain [NOP]) includes a number of entities.
DIAGNOSIS OF NEUROPATHIC PAIN
The diagnosis of any disease relies on the appearance of a specific combination of signs and symptoms that have been previously recognized and classified as a precise entity. Often the initial diagnosis is confirmed by response to treatment. There are various classifications of NOP, but none is comprehensive and we therefore rely on a number of classification systems in daily practice.
Certain features are characteristically associated with NP syndromes. Symptomatology of NP may include touch-evoked or stimulus-dependent pain that may be constant or intermittent. In addition, there may be spontaneous or stimulusindependent pain. However, these are often observed in inflammatory pain, so they are not pathognomonic. More specific to NOP is the combination of positive sensory signs or symptoms (e.g., pain or hyperalgesia) with negative signs or symptoms (e.g., numbness). Some of these signs and symptoms (thermal and mechanical allodynia) are especially associated with NP. Quantitative sensory testing (QST) provides accurate and reproducible data that are extremely valuable for patient assessment, treatment, and research, particularly in traumatic neuropathies. This technique is briefly described in the next section. When advanced QST apparatus is unavailable, a simple pin, blunt instruments, warmed and cooled implements, and cotton wool may be employed to test sensory modalities. The mapping of affected areas and photographic documentation add information as to the dermatomal distribution of the sensory changes and should form part of patient evaluation and follow-up.
QUANTITATIVE SENSORY TESTING
QST uses noninvasive assessment and quantification of sensory nerve function in patients with suspected neurologic damage or disease. The common concepts in QST methods are that the assessment of normal and nonnormal responses to various stimuli provides information about the functioning of the peripheral and central nervous system and that these responses can be quantified by the amount of physical stimuli required to evoke specific levels of sensory perception. External stimuli are usually mechanical, thermal, or electrical, and each selectively activates different sensory nerve fibers. Heat stimuli activate the thin, slow, nonmyelinated C-fibers (0.3 to 1.5 μm diameter, conduction velocity 0.4 to 2 m/sec) that comprise 60-90% of the cutaneous nerve fibers. In addition to the prevalent heat-activated C fibers, an important subset of C fibers is the polymodal nociceptors that respond to chemical, mechanical, and thermal nociceptive stimuli. Aδ fibers possess a thin myelin sheath (1 to 5 μm diameter, conduction velocity 4 to 30 m/sec) and are activated mainly by cold stimuli, fast-onset contact, radiant (including laser) heat, and punctuate mechanical stimulation such as from a pin. Aβ fibers have a thicker myelin coat (6 to 12 μm diameter, conduction velocity 35 to 70 m/sec) and mediate touch and vibratory sensations. Aβ fibers are preferentially activated by pulsed electrical stimuli at the threshold for detection.
Clinical Relevance
Mechanical nerve damage or total nerve transection is characterized by myelinated and unmyelinated nerve fiber hyposensitivity that clinically can be translated to elevated detection thresholds to heat, electrical, and mechanical stimulation. Partial damage may be followed by either hyposensitivity or hypersensitivity accompanied by ongoing NP. In contrast to the neuropathic process of mechanical nerve damage, other specific nociceptive processes may provide a different, identifiable sensory signature. For example, early perineural inflammation produces short-lasting large myelinated nerve-fiber hypersensitivity that is characterized by reduced detection of electrical and mechanical stimuli. This increased sensitivity has been demonstrated in clinical models.
QST can add a further dimension to NP evaluation. Hyperalgesia to heat stimulus suggests thin unmyelinated nerve-fiber pathology, whereas tactile hyperalgesia or allodynia suggests involvement of myelinated fibers. Severe mechanical nerve damage and total nerve transection are characterized by elevated detection thresholds to all modalities: heat, electrical, and mechanical stimulation. In contrast to mechanical nerve damage, neuritis (perineural inflammation), with no frank axonal nerve damage, mainly during its early phase is characterized by a reduced detection threshold or hypersensitivity in large myelinated Aβ nerve fibers. Furthermore, applying QST methodology can support the diagnosis of centrally mediated NP. A measurable reduction in the interval between detection and pain thresholds, or detection to pain ratio, has been shown to have a clinical relevance in centrally mediated pain conditions. This feature may add information vital to the treatment decision (e.g., the use of centrally acting drugs).
TRIGEMINAL NEURALGIA
Trigeminal neuralgia (TN) is an excruciating short-lasting, unilateral facial pain ( Table 54-1 ). The diagnostic criteria published by the International Headache Society (IHS) recognize a classic (previously idiopathic or primary) TN. The use of the term classic is in line with recent evidence suggesting that many cases of classic TN (CTN) result from compression of the trigeminal nerve root by a vascular malformation. A symptomatic (or secondary) form is related to a variety of clear pathologies ( Table 54-2 ). The vast majority (>85%) of TN patients are diagnosed as having CTN. Lifetime prevalence figures suggest that approximately 70 TN cases occur per 100,000 population, and TN is therefore a rare condition. TN is extremely rare in children; peak incidence begins at 50 to 60 years and increases with age.
| Feature | Notes |
|---|---|
| Paroxysmal attacks of pain lasting from a fraction of a second to 2 minutes |
|
| May affect one or more divisions of the trigeminal nerve |
|
Pain characteristics:
|
|
| Stereotyped attacks | Attack duration, distribution, and so on may vary among patients but are highly consistent within cases. |
| Usually no clinically evident neurologic deficit | Particularly in longstanding cases, sensory testing may reveal mild deficits in the distribution of the trigeminal nerve. |
| Pathology that may mimic trigeminal neuralgia (TN) must be ruled out by history, physical examination, and special investigations. All patients with TN should undergo brain imaging. | |
| Compression of the nerve root by a vascular malformation (tortuous or aberrant vessels) is considered “classic.” | |
| Feature | Notes |
|---|---|
Features are very similar to those of classic trigeminal neuralgia (TN):
|
|
| Pain characteristics | No refractory period occurs as in classic TN. |
|
Pain quality may also differ. |
|
|
| Sensory dysfunction is usually present but may be undetectable in a small number of patients | Usually accompanied by other cranial nerve dysfunction |
| Initially stereotyped attacks | A progressive pattern in duration, spread, associated neurologic deficits, and intensity may be evident. |
| A causative lesion or systemic disease, other than vascular compression, is diagnosed by special investigative imaging and/or posterior fossa exploration | |
CLINICAL FEATURES OF TRIGEMINAL NEURALGIA
TN (see Table 54-1 ) may mimic dental pain, and a quarter of affected patients will initially consult a dentist. Unfortunately TN is often misdiagnosed, and many patients may undergo unwarranted dental interventions; some eventually may be rendered edentulous. Thorough clinical and radiographic dental examinations are essential. Invasive dental treatment must not be performed when no positive anamnestic, clinical, and radiographic signs indicate it.
The location, intensity, and triggers of TN may vary among patients. However, within individual TN patients, pain attacks are highly stereotyped—that is, all attacks are similar. TN is a unilateral facial pain syndrome. Bilateral pain has been reported in 1-4% of cases. Pain location is most commonly (35%) described in the maxillary and mandibular dermatomes together. In just under two fifths of patients the maxillary or the mandibular branch is affected singly, whereas the ophthalmic is affected singly in only about 2% of cases. All three branches are involved in 14% of patients. The jaws are therefore involved in most cases, explaining why CTN patients so often seek help from dentists. Pain radiation is generally within the dermatome of origin.
Pain in TN is severe, paroxysmal, shooting, sharp, piercing, stabbing, or electrical in nature (70-95%). Up to one third of TN patients may describe paroxysmal attacks of short sharp pain superimposed on a background pain of varying duration that is dull, throbbing, and burning. Pain in TN may be precipitated by innocuous stimuli (light touch, wind) in trigger areas or initiated by trigger factors. A short gap between stimulation of a trigger area and pain onset may be observed and is termed latency . However, TN attacks are often spontaneous, and trigger areas are not always clinically identifiable. Trigger areas are usually in the distribution of the affected trigeminal branch, particularly around the lips. Trigger factors are distinct from trigger areas and include noise, lights, and stress. Individual attacks last from 10 sec up to 2 min. This is followed by a refractory period during which it is impossible or extremely difficult to trigger a TN attack. Accompanying the pain of TN is a classic contraction of the facial musculature, hence the terms tic douloureux and tic convulsif .
Long-term follow-up of TN patients reveals that there are well-defined periods of remission that may last from weeks to years. However, about 90% of TN patients report increased attack frequency and severity. A progressive and increasing resistance to pharmacologic and surgical treatment is common; TN therefore is a progressive disease with a poor prognosis.
Sensory disturbances such as hypoesthesia are rare but occur in some patients with TN. These may be more readily detected when sophisticated examination techniques such as QST are employed but may go unnoticed in gross examination. After successful microvascular decompression (MVD), nerve conduction properties return to normal.
A thorough cranial nerve examination should be routine. Imaging techniques such as magnetic resonance tomographic angiography (MRTA) may indicate neurovascular compression. More sophisticated techniques such as three-dimensional magnetic resonance imaging (MRI) with constructive interference in steady state (CISS) sequence has shown superiority over MRTA in detecting venular compressions. Published evidence suggests that all TN patients should undergo imaging (computed tomography [CT] or MRI) at least once during diagnosis and therapy. A thorough clinical and radiographic evaluation of oral structures is essential to rule out pathology. All patients treated with anticonvulsants need baseline and follow-up of hematologic, biochemical (renal, hepatic), and physical parameters. The presence of hypertension has been found to increase the risk of TN.
TN significantly interferes with daily functioning and reduces health status directly in relation to pain severity. Patients with TN are often depressed and anxious with a reduced quality of life; this is as much a result of pain as it is of side effects of the drugs employed.
UNUSUAL TRIGEMINAL NEURALGIA PRESENTATIONS
Up to 30% of TN patients report atypical features such as a constant background pain. Atypical TN is unrecognized by any classification system but is clinically significant in that it carries a reduced prognosis. An early form of TN termed pretrigeminal neuralgia (PTN) has been described. PTN has been reported in 18% of TN patients and is characterized by a dull continuous pain in one of the jaws, at times with a throbbing quality, that lasts from days to years. Thermal stimuli may cause triggering at a relatively higher rate and may result in diagnostic confusion with dental pathology. PTN is responsive to anticonvulsant therapy, and careful dental assessment should help differentiate it. PTN is usually diagnosed when all other possibilities are exhausted or in retrospect once CTN develops.
TN most often occurs as a single pain syndrome. However it has been reported rarely to occur with cluster headache and with paroxysmal hemicrania; these are termed cluster-tic and chronic paroxysmal hemicrania-tic syndromes , respectively. Concurrence of TN with glossopharyngeal neuralgia is higher than expected, suggesting some pathophysiologic association.
SYMPTOMATIC TRIGEMINAL NEURALGIA
See Table 54-2 .
MULTIPLE SCLEROSIS
Multiple sclerosis (MS) is a common disabling disease affecting individuals between the ages of 20 and 40. MS increases the risk of developing TN by a factor of 20. Clinical signs predictive of MS in TN patients are bilateral pain (14% in MS) and young age. Very rarely (0.3%) does TN herald the onset of MS. Usually TN develops in a diagnosed case of MS, on average about 12 years after the onset of MS, and occurs in 1.5-4.9% of MS cases.
TUMORS
Trigeminal nerve dysfunction has been observed in 33% of patients with middle and posterior cranial fossa tumors, but in only 13% was nerve dysfunction the presenting symptom. About 10% of patients with intracranial tumors had TN-like symptomatology. Posterior fossa tumors and meningiomas are most likely to cause TN-like symptoms. Cerebellopontine angle tumors (e.g., acoustic neuromas) may also cause TN, and this diagnosis is more likely when the patient is young and has pain in more than one trigeminal branch. In TN patients under the age of 29 years, the prevalence of intracranial tumor or MS is extremely high (approximately 100%) but subsequently decreases with increasing age. Specifically, 10-13.4% of TN patients may have intracranial tumors, and MRI is the most sensitive diagnostic technique. A reduced corneal reflex and hypesthesia were typical of cranial masses. Most of these patients are younger than expected for cases of TN and develop subtle or frank neurologic deficits, and only a small number have CTN with no significant sensory aberration. The data stress the importance of thorough cranial nerve examination and indicate that all TN patients need imaging studies.
PATHOPHYSIOLOGY
Several lines of evidence point to compression of the trigeminal root at or near the dorsal root entry zone (DREZ) by a blood vessel as a major causative or contributing factor. The compression is often arterial but may be venous or combined. Imaging methods and surgical observations confirm a high rate of vascular compression of the nerve in TN patients. Decompression of the nerve leads to prolonged pain relief and reversal of sensory loss in many patients. According to the ignition hypothesis, injury renders axons and axotomized somata hyperexcitable, resulting in synchronized afterdischarge activity, cross-excitation of nociceptors, and pain paroxysms. Central nervous system neuroplasticity will no doubt occur in the presence of such peripheral changes and will ultimately affect the clinical phenotype and response to therapy.
Of interest, some cases of TN have no vascular contact in the DREZ on operation. Moreover, cadavers with no history of TN demonstrate vascular contacts in up to 14% of cases, albeit with minimal grooving. Pain is reported in some patients who did not appear to have a severe compressive injury at surgical exposure, and it is therefore probable that additional mechanisms are at play.
TREATMENT
Pharmacologic
Based on current evidence, therapy with carbamazepine is initiated and patients are switched at the earliest opportunity to the controlled-release (CR) formulation, which has fewer side effects. Up to 30% of patients may be initially resistant and up to 50% become refractory to carbamazepine therapy. If carbamazepine causes troublesome side effects, reduce the dose and add baclofen. Alternatively oxcarbazepine or add-on therapy either with lamotrigine or with phenytoin may be tried. In refractory cases gabapentin is probably the most promising drug. Pregabalin, topiramate or even the “older” anticonvulsants valproate and phenytoin may be tried in recalcitrant cases ( Table 54-3 ).
| Drug | Initial Dose (mg) | Target or Maximal Dose (mg) * | Dose Increase (Titration) * | Schedule |
|---|---|---|---|---|
| Carbamazepine | 100–200 | 1200 | 100–200 mg/2 days | ×3–4/day |
| Carbamazepine CR | 200–400 | 1200 | Usually switch from regular format at equivalent dose | ×2/day |
| Oxcarbazepine | 300 | 1200–2400 | 300–600 mg/week | ×3/day |
| Baclofen | 5–15 | 30–60 | 5 mg/3 days | ×3/day |
| Gabapentin | 300 | 900–2400 | 300 mg/1–2 days | ×3/day |
| Pregabalin | 150 | 300–600 | 50 mg/2–3 days | ×2–3/day |
| Lamotrigine † | 25 | 400-600 | 25-50 mg/week | ×1-2/day |
* Titrate according to response and side effects.
† Evidence for efficacy based on study using lamotrigine as add-on therapy.
Even in successfully treated patients, exacerbations (breakthrough pain) may occur and require temporary dose adjustment. Medically resistant patients who are physically able to withstand neurosurgery, particularly with typical CTN, are prime candidates for surgery.
Surgery
The decision to opt for surgery is based on response to and side effects from medical treatment, the patient’s age and profession, and the surgical facilities and expertise available. The candidate must be in a physical condition that will allow safe general anesthesia and neurosurgery. Patients require concise and clear explanations of the alternative neurosurgical procedures.
Surgery may be aimed peripherally at the affected nerve or centrally at the trigeminal ganglion or the posterior fossa. Any surgical procedure seems to have a better prognosis when carried out as a first procedure, particularly on patients with typical CTN; in MVD best effects are obtained when performed within 7 years of TN onset.
Peripheral Procedures.
Peripheral procedures for the treatment of TN are often requested from oral surgeons or oral medicine specialists. Other than the temporary relief afforded by local anesthetic injections, peripheral procedures all aim at inducing nerve damage and therefore carry the attendant risk of developing dysesthesia. Reported early success rates for neurectomy are conflicting (50-64%) and involve relatively small series with short-term follow-up. Moreover, peripheral neurectomy may lead to NP and is therefore not recommended. Cryotherapy of peripheral branches may give pain relief for 6 months. However, up to one third of patients may develop atypical facial pain (AFP) after cryotherapy, and this technique is therefore also not recommended. Alcohol injections have been used but are painful, and fibrosis makes repeat injections technically difficult. Complications may include full thickness skin or mucosal ulceration, cranial nerve palsies, painful neuropathies, herpes zoster (HZ) reactivation, and bony necrosis. A 60% success rate at 24 months after peripheral glycerol injection has been reported, but others report pain relapse by 7 months, Reinjection is, however, possible, with reportedly good results.
In summary, high recurrence and complication rates in peripheral procedures give no benefit over ganglion-level procedures. Peripheral procedures should be reserved for emergency use or in patients with significant medical problems that make other procedures unsafe.
Central Procedures
Percutaneous Trigeminal Rhizotomy.
Three techniques may be used: radiofrequency rhizolysis, glycerol injection, or balloon compression. The basis of these techniques is that controlled heat (69° to 90° C), a neurotoxin, or ischemic and mechanical damage, respectively, will selectively ablate nociceptors (Aδ and C) while sparing mechanoreceptors (Aβ). The ability of these modalities to selectively damage nociceptive fibers has been questioned, and patients often experience sensory loss of all fibers.
These three modalities give approximately equal initial pain relief (around 90%), but each is associated with different rates of recurrence and complications. Overall, radiofrequency rhizolysis consistently provides the highest rates of pain relief but is associated with high frequencies of facial and corneal numbness.
Microvascular Decompression.
MVD is based on the hypothesis that proximity between the intracerebral arteries and the trigeminal nerve root may allow pulsatile stimulation to cause chronic demyelination, leading to TN. Therefore separating them may offer a permanent cure. Surgical morbidity in MVD has declined to about 0.3-3%, making MVD an attractive option. Long-term follow-up reveals that after 10 years, 30-40% of patients who underwent MVD experience a relapse. Notwithstanding, MVD is at present the most cost-effective surgical approach to CTN. MVD is most efficacious in patients with classic symptoms of CTN, no background pain or sensory loss, and less than 7 years from disease onset.
Gamma Knife.
Gamma knife stereotactic radiosurgery (GKS) is a minimally invasive technique that is becoming common practice for the treatment of TN. The technique precisely delivers radiosurgical doses of 70 to 90 Gray units and relies on accurate MRI sequencing. The isocenter is the trigeminal nerve root at the point of vascular compression as mapped by MRI. Alternatively, if no compressing vessels are identified, the site of exit of the trigeminal nerve from the pons or other preselected position on the trigeminal nerve is treated. GKS showed better long-term pain relief with less treatment-related morbidity than glycerol rhizotomy and may be indicated in patients who are poor candidates for MVD. Although posterior fossa surgery (MVD or partial nerve section) was shown to be superior to GKS over a mean follow-up duration of about 2 years, there are reports that GKS may be a more efficient primary intervention and the procedure of choice for recurrent CTN. Because GKS centers or gamma knife units are rare in most medical centers, the choice of treatment technique is usually restricted to percutaneous and MVD techniques.
TRIGEMINAL NEURALGIA
Trigeminal neuralgia (TN) is an excruciating short-lasting, unilateral facial pain ( Table 54-1 ). The diagnostic criteria published by the International Headache Society (IHS) recognize a classic (previously idiopathic or primary) TN. The use of the term classic is in line with recent evidence suggesting that many cases of classic TN (CTN) result from compression of the trigeminal nerve root by a vascular malformation. A symptomatic (or secondary) form is related to a variety of clear pathologies ( Table 54-2 ). The vast majority (>85%) of TN patients are diagnosed as having CTN. Lifetime prevalence figures suggest that approximately 70 TN cases occur per 100,000 population, and TN is therefore a rare condition. TN is extremely rare in children; peak incidence begins at 50 to 60 years and increases with age.
| Feature | Notes |
|---|---|
| Paroxysmal attacks of pain lasting from a fraction of a second to 2 minutes |
|
| May affect one or more divisions of the trigeminal nerve |
|
Pain characteristics:
|
|
| Stereotyped attacks | Attack duration, distribution, and so on may vary among patients but are highly consistent within cases. |
| Usually no clinically evident neurologic deficit | Particularly in longstanding cases, sensory testing may reveal mild deficits in the distribution of the trigeminal nerve. |
| Pathology that may mimic trigeminal neuralgia (TN) must be ruled out by history, physical examination, and special investigations. All patients with TN should undergo brain imaging. | |
| Compression of the nerve root by a vascular malformation (tortuous or aberrant vessels) is considered “classic.” | |
| Feature | Notes |
|---|---|
Features are very similar to those of classic trigeminal neuralgia (TN):
|
|
| Pain characteristics | No refractory period occurs as in classic TN. |
|
Pain quality may also differ. |
|
|
| Sensory dysfunction is usually present but may be undetectable in a small number of patients | Usually accompanied by other cranial nerve dysfunction |
| Initially stereotyped attacks | A progressive pattern in duration, spread, associated neurologic deficits, and intensity may be evident. |
| A causative lesion or systemic disease, other than vascular compression, is diagnosed by special investigative imaging and/or posterior fossa exploration | |
CLINICAL FEATURES OF TRIGEMINAL NEURALGIA
TN (see Table 54-1 ) may mimic dental pain, and a quarter of affected patients will initially consult a dentist. Unfortunately TN is often misdiagnosed, and many patients may undergo unwarranted dental interventions; some eventually may be rendered edentulous. Thorough clinical and radiographic dental examinations are essential. Invasive dental treatment must not be performed when no positive anamnestic, clinical, and radiographic signs indicate it.
The location, intensity, and triggers of TN may vary among patients. However, within individual TN patients, pain attacks are highly stereotyped—that is, all attacks are similar. TN is a unilateral facial pain syndrome. Bilateral pain has been reported in 1-4% of cases. Pain location is most commonly (35%) described in the maxillary and mandibular dermatomes together. In just under two fifths of patients the maxillary or the mandibular branch is affected singly, whereas the ophthalmic is affected singly in only about 2% of cases. All three branches are involved in 14% of patients. The jaws are therefore involved in most cases, explaining why CTN patients so often seek help from dentists. Pain radiation is generally within the dermatome of origin.
Pain in TN is severe, paroxysmal, shooting, sharp, piercing, stabbing, or electrical in nature (70-95%). Up to one third of TN patients may describe paroxysmal attacks of short sharp pain superimposed on a background pain of varying duration that is dull, throbbing, and burning. Pain in TN may be precipitated by innocuous stimuli (light touch, wind) in trigger areas or initiated by trigger factors. A short gap between stimulation of a trigger area and pain onset may be observed and is termed latency . However, TN attacks are often spontaneous, and trigger areas are not always clinically identifiable. Trigger areas are usually in the distribution of the affected trigeminal branch, particularly around the lips. Trigger factors are distinct from trigger areas and include noise, lights, and stress. Individual attacks last from 10 sec up to 2 min. This is followed by a refractory period during which it is impossible or extremely difficult to trigger a TN attack. Accompanying the pain of TN is a classic contraction of the facial musculature, hence the terms tic douloureux and tic convulsif .
Long-term follow-up of TN patients reveals that there are well-defined periods of remission that may last from weeks to years. However, about 90% of TN patients report increased attack frequency and severity. A progressive and increasing resistance to pharmacologic and surgical treatment is common; TN therefore is a progressive disease with a poor prognosis.
Sensory disturbances such as hypoesthesia are rare but occur in some patients with TN. These may be more readily detected when sophisticated examination techniques such as QST are employed but may go unnoticed in gross examination. After successful microvascular decompression (MVD), nerve conduction properties return to normal.
A thorough cranial nerve examination should be routine. Imaging techniques such as magnetic resonance tomographic angiography (MRTA) may indicate neurovascular compression. More sophisticated techniques such as three-dimensional magnetic resonance imaging (MRI) with constructive interference in steady state (CISS) sequence has shown superiority over MRTA in detecting venular compressions. Published evidence suggests that all TN patients should undergo imaging (computed tomography [CT] or MRI) at least once during diagnosis and therapy. A thorough clinical and radiographic evaluation of oral structures is essential to rule out pathology. All patients treated with anticonvulsants need baseline and follow-up of hematologic, biochemical (renal, hepatic), and physical parameters. The presence of hypertension has been found to increase the risk of TN.
TN significantly interferes with daily functioning and reduces health status directly in relation to pain severity. Patients with TN are often depressed and anxious with a reduced quality of life; this is as much a result of pain as it is of side effects of the drugs employed.
UNUSUAL TRIGEMINAL NEURALGIA PRESENTATIONS
Up to 30% of TN patients report atypical features such as a constant background pain. Atypical TN is unrecognized by any classification system but is clinically significant in that it carries a reduced prognosis. An early form of TN termed pretrigeminal neuralgia (PTN) has been described. PTN has been reported in 18% of TN patients and is characterized by a dull continuous pain in one of the jaws, at times with a throbbing quality, that lasts from days to years. Thermal stimuli may cause triggering at a relatively higher rate and may result in diagnostic confusion with dental pathology. PTN is responsive to anticonvulsant therapy, and careful dental assessment should help differentiate it. PTN is usually diagnosed when all other possibilities are exhausted or in retrospect once CTN develops.
TN most often occurs as a single pain syndrome. However it has been reported rarely to occur with cluster headache and with paroxysmal hemicrania; these are termed cluster-tic and chronic paroxysmal hemicrania-tic syndromes , respectively. Concurrence of TN with glossopharyngeal neuralgia is higher than expected, suggesting some pathophysiologic association.
SYMPTOMATIC TRIGEMINAL NEURALGIA
See Table 54-2 .
MULTIPLE SCLEROSIS
Multiple sclerosis (MS) is a common disabling disease affecting individuals between the ages of 20 and 40. MS increases the risk of developing TN by a factor of 20. Clinical signs predictive of MS in TN patients are bilateral pain (14% in MS) and young age. Very rarely (0.3%) does TN herald the onset of MS. Usually TN develops in a diagnosed case of MS, on average about 12 years after the onset of MS, and occurs in 1.5-4.9% of MS cases.
TUMORS
Trigeminal nerve dysfunction has been observed in 33% of patients with middle and posterior cranial fossa tumors, but in only 13% was nerve dysfunction the presenting symptom. About 10% of patients with intracranial tumors had TN-like symptomatology. Posterior fossa tumors and meningiomas are most likely to cause TN-like symptoms. Cerebellopontine angle tumors (e.g., acoustic neuromas) may also cause TN, and this diagnosis is more likely when the patient is young and has pain in more than one trigeminal branch. In TN patients under the age of 29 years, the prevalence of intracranial tumor or MS is extremely high (approximately 100%) but subsequently decreases with increasing age. Specifically, 10-13.4% of TN patients may have intracranial tumors, and MRI is the most sensitive diagnostic technique. A reduced corneal reflex and hypesthesia were typical of cranial masses. Most of these patients are younger than expected for cases of TN and develop subtle or frank neurologic deficits, and only a small number have CTN with no significant sensory aberration. The data stress the importance of thorough cranial nerve examination and indicate that all TN patients need imaging studies.
PATHOPHYSIOLOGY
Several lines of evidence point to compression of the trigeminal root at or near the dorsal root entry zone (DREZ) by a blood vessel as a major causative or contributing factor. The compression is often arterial but may be venous or combined. Imaging methods and surgical observations confirm a high rate of vascular compression of the nerve in TN patients. Decompression of the nerve leads to prolonged pain relief and reversal of sensory loss in many patients. According to the ignition hypothesis, injury renders axons and axotomized somata hyperexcitable, resulting in synchronized afterdischarge activity, cross-excitation of nociceptors, and pain paroxysms. Central nervous system neuroplasticity will no doubt occur in the presence of such peripheral changes and will ultimately affect the clinical phenotype and response to therapy.
Of interest, some cases of TN have no vascular contact in the DREZ on operation. Moreover, cadavers with no history of TN demonstrate vascular contacts in up to 14% of cases, albeit with minimal grooving. Pain is reported in some patients who did not appear to have a severe compressive injury at surgical exposure, and it is therefore probable that additional mechanisms are at play.
TREATMENT
Pharmacologic
Based on current evidence, therapy with carbamazepine is initiated and patients are switched at the earliest opportunity to the controlled-release (CR) formulation, which has fewer side effects. Up to 30% of patients may be initially resistant and up to 50% become refractory to carbamazepine therapy. If carbamazepine causes troublesome side effects, reduce the dose and add baclofen. Alternatively oxcarbazepine or add-on therapy either with lamotrigine or with phenytoin may be tried. In refractory cases gabapentin is probably the most promising drug. Pregabalin, topiramate or even the “older” anticonvulsants valproate and phenytoin may be tried in recalcitrant cases ( Table 54-3 ).
| Drug | Initial Dose (mg) | Target or Maximal Dose (mg) * | Dose Increase (Titration) * | Schedule |
|---|---|---|---|---|
| Carbamazepine | 100–200 | 1200 | 100–200 mg/2 days | ×3–4/day |
| Carbamazepine CR | 200–400 | 1200 | Usually switch from regular format at equivalent dose | ×2/day |
| Oxcarbazepine | 300 | 1200–2400 | 300–600 mg/week | ×3/day |
| Baclofen | 5–15 | 30–60 | 5 mg/3 days | ×3/day |
| Gabapentin | 300 | 900–2400 | 300 mg/1–2 days | ×3/day |
| Pregabalin | 150 | 300–600 | 50 mg/2–3 days | ×2–3/day |
| Lamotrigine † | 25 | 400-600 | 25-50 mg/week | ×1-2/day |
* Titrate according to response and side effects.
† Evidence for efficacy based on study using lamotrigine as add-on therapy.
Even in successfully treated patients, exacerbations (breakthrough pain) may occur and require temporary dose adjustment. Medically resistant patients who are physically able to withstand neurosurgery, particularly with typical CTN, are prime candidates for surgery.
Surgery
The decision to opt for surgery is based on response to and side effects from medical treatment, the patient’s age and profession, and the surgical facilities and expertise available. The candidate must be in a physical condition that will allow safe general anesthesia and neurosurgery. Patients require concise and clear explanations of the alternative neurosurgical procedures.
Surgery may be aimed peripherally at the affected nerve or centrally at the trigeminal ganglion or the posterior fossa. Any surgical procedure seems to have a better prognosis when carried out as a first procedure, particularly on patients with typical CTN; in MVD best effects are obtained when performed within 7 years of TN onset.
Peripheral Procedures.
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