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Neuralgia Trigemino PDF
Neuralgia Trigemino PDF
Review Article
Trigeminal Neuralgia
Giorgio Cruccu, M.D., Giulia Di Stefano, M.D., Ph.D.,
and Andrea Truini, M.D., Ph.D.
T
From the Department of Human Neuro rigeminal neuralgia, traditionally called tic douloureux, is a
science, Sapienza University of Rome, chronic neuropathic pain disorder characterized by spontaneous and elic-
Rome. Address reprint requests to Prof.
Cruccu at Dipartimento Neuroscienze ited paroxysms of electric shock–like or stabbing pain in a region of the
Umane, Università Sapienza di Roma, face. A poor quality of life and suicide in severe cases have been attributed to the
Viale Università 30, 00185 Rome, Italy, or disorder.1,2 A classification of trigeminal neuralgia has been adopted by several
at giorgio.cruccu@uniroma1.it.
professional societies and forms the basis of its description in the International
N Engl J Med 2020;383:754-62. Classification of Diseases, 11th Revision (ICD-11).3
DOI: 10.1056/NEJMra1914484
Copyright © 2020 Massachusetts Medical Society.
Ophthalmic
Maxillary
Mandibular
Extraoral
territories
Intraoral
territories
tribution of trigger zones that elicit pain are the physician may notice a blink or a small
shown in Figure 1. Few patients report no triggers. mouth movement of which the patient is un-
Examination for trigeminal neuralgia includes aware.4 Less often, during a paroxysmal attack,
observation of the face while the patient is forceful contraction of the facial muscles, called
seated and remains completely still. With a “tic convulsif,” may occur. Sensory examination
spontaneous paroxysm of trigeminal neuralgia, of the face is generally unrevealing in cases of
Table 1. Trigger Maneuvers in 120 Patients with Classical for approximately 15% of cases, is attributable to
Trigeminal Neuralgia.* an identifiable neurologic disease such as mul-
tiple sclerosis or a tumor in the cerebellopontine
No. of angle, which alters the root entry zone of the
Triggers Patients (%)
trigeminal nerve or otherwise compresses the
Activities of daily living nerve in its extracranial course. Idiopathic tri-
Talking 71 (59) geminal neuralgia, in which no apparent cause
Washing face 52 (43) of nerve disturbance can be found, accounts for
Chewing 49 (41) approximately 10% of cases.
Brushing teeth 43 (36) The clinical features of classical and second-
ary trigeminal neuralgia are similar, although
Drying face 43 (36)
patients with secondary trigeminal neuralgia are
Eating 23 (19)
usually younger, more likely to have sensory loss
Drinking 17 (14) on a portion of the face, and are more likely to
Shaving 16 (13) have bilateral pain.8 Since the three forms of
Applying makeup 7 (6) trigeminal neuralgia may be clinically indistin-
Combing hair 2 (2) guishable, magnetic resonance imaging (MRI)
Washing hair 2 (2)
with gadolinium to rule out multiple sclerosis
and cerebellopontine masses is advisable at the
Specific movements
time of the initial diagnosis. A recent study
Swallowing 13 (11) showed rare variants in genes encoding voltage-
Blowing nose 11 (9) gated ion channels in patients with a family
Gently touching face 106 (88) history of classical or idiopathic trigeminal neu-
Jaw movement 7 (6) ralgia, but the frequency and clinical importance
Head movement 7 (6) of this finding are not known.9
Yawning 7 (6)
Flexing the trunk forward 5 (4) Neurova scul a r C ompr e ssion in
Cl a ssic a l T r igemina l Neur a l gi a
Pronouncing labial letters 5 (4)
Raising voice 5 (4) Over the past several decades, the classical form
Laughing 3 (3) of trigeminal neuralgia has been revealed through
Eye movement 2 (2) the work of Peter Jannetta and others, and the
Tongue movement 2 (2)
potential for cure by means of intracranial mi-
crovascular surgery has been studied. The patho-
* Data are from 120 patients seen at the Center for Neuro physiology is considered to be compression of
pathic Pain at Sapienza University in Rome between the sensory portion of the trigeminal nerve,
January 2015 and December 2019.
close to its root entry zone in the pons, by an
adjacent small branch of the basilar artery, most
trigeminal neuralgia, although some patients often the superior cerebellar artery. However,
report areas of mild hypoesthesia. simple contact between the nerve and a vascular
structure does not appear to be adequate to
cause or explain the disorder. To attribute the
T y pe s a nd C ause s
disorder to neurovascular compression, the
Three types of trigeminal neuralgia have been anomalous vessel should ideally be shown to
delineated: classical, secondary, and idiopathic. induce anatomical alterations in the trigeminal
The classical type, which is the most common, root, such as distortion or atrophy.5,10 The most
is caused by intracranial vascular compression characteristic finding at operation is a small,
of the trigeminal nerve root, as described below. tortuous artery or arterial loop impinging on the
The responsible vessel is usually the superior medial aspect of the trigeminal root at its entry
cerebellar artery, which induces morphologic zone, causing lateral dislocation, distortion, flat-
changes in the adjacent trigeminal nerve root. tening, or atrophy of the trigeminal root (Fig. 2).
Secondary trigeminal neuralgia, which accounts Neurovascular compression can be seen with
for control of paroxysmal pain in patients with tients, this type of surgery is generally under-
trigeminal neuralgia, regardless of the cause.8 taken only if standard doses of medications are
Although these treatments are not supported by not sufficient to control symptoms or if side ef-
data from randomized, controlled trials, clini- fects prevent continued use.
cians consider the drugs to be highly effective, One group of surgical interventions, now
with meaningful pain control in almost 90% of used infrequently, involves peripheral blockade
patients.8 The treatment effect is proposed to be of trigeminal nerve branches at their emergence
related to blockade of voltage-gated sodium from the facial bones by means of neurectomy,
channels, resulting in stabilization of hyperex- alcohol injections, or induction of radiofrequency
cited neuronal membranes and inhibition of re- lesions or cryolesions. The purpose of these pro-
petitive firing.16 However, clinical improvement cedures is to produce an area of anesthesia on the
is often offset by side effects, including dizzi- face that corresponds to the distribution of the
ness, diplopia, ataxia, and elevated aminotrans- damaged nerve. However, the benefit of such
ferase levels, one or more of which may lead to treatments has not been adequately supported by
treatment withdrawal in 23% of patients.42 Ox- trials,8 and the procedures often led to anesthe-
carbazepine may have fewer side effects and a sia dolorosa (intense pain in the area of sen-
lower potential for drug–drug interaction than sory loss).
carbamazepine,43 though it may be discontinued A second group of interventions seeks to per-
because of excessive central nervous system de- cutaneously damage the trigeminal ganglion in
pression or dose-related hyponatremia.10 Other, Meckel’s cave or exiting branches of the ganglion
more selective sodium-channel blockers are un- at the base of the skull by means of radiofre-
der development. Contraindications to the use of quency thermocoagulation,45 chemical destruction
sodium-channel blockers include cardiac conduc- through injection of glycerol,46 or mechanical
tion problems and allergic reactions, with a high compression through balloon inflation.47 Radio-
degree of cross-reactivity (40 to 80%) with aro- frequency thermocoagulation preferentially dam-
matic antiepileptic drugs.44 Carbamazepine and ages small-diameter pain fibers. To prevent
oxcarbazepine reduce the high-frequency dis- corneal deafferentation and resultant keratitis,
charges that characterize the electric shock–like the electrode is aimed so as to avoid damaging
paroxysms, but the effect of these drugs on con- the first division of the trigeminal nerve. Balloon
comitant continuous pain is usually limited.22,37 compression and glycerol injection preferentially
Gabapentin, pregabalin, and antidepressant damage large myelinated fibers. Pain relief is
agents, which have been shown to be effective in immediate with these techniques and has been
the treatment of other neuropathic conditions reported in the following percentages of cases:
characterized by continuous pain, may be tried 68% (range, 55 to 80) with balloon compression
as additional agents along with oxcarbazepine or (follow-up, 4.2 to 10.7 years), 58% (range, 26 to
carbamazepine. Clinical experience suggests that 82) with radiofrequency thermocoagulation (fol-
gabapentin may have a lesser effect on trigeminal low-up, 3.0 to 9.3 years), and 28% (range, 19 to
neuralgia than carbamazepine and oxcarbaze- 58) with glycerol rhizolysis (follow-up, 4.5 to
pine but is associated with a lower incidence of 8.0 years).8 Trigeminal sensory deficits are usually
adverse events and can be attempted either as transient with balloon compression and glycerol
monotherapy or as add-on therapy, if it is associ-injection and are more severe and longer lasting
ated with an acceptable side-effect profile, in- after radiofrequency thermocoagulation.
cluding in patients with multiple sclerosis.8,37 If Generating a lesion of the trigeminal root
a course of medical treatment is ineffective or with a gamma knife is a more recently intro-
associated with unacceptable side effects, surgi- duced procedure and is supported by several
cal decompression of the trigeminal nerve may studies. A challenge of this procedure is accurate
be considered. identification of the coordinates of the trigemi-
nal root before their entrance into the pons,
Local Surgical Procedures where the radiation beams must be collimated
Although surgical procedures are effective in to avoid damaging the pons. In contrast to the
reducing the severity and frequency of attacks of immediate pain relief associated with percutane-
trigeminal neuralgia in appropriately chosen pa- ously caused lesions of the trigeminal ganglion,
B Trigeminal
nerve
Basilar
artery
Superior
cerebellar
artery
Sponge
the pain-relieving effect of gamma-knife stereo- rovascular compression5 or finds a mere contact,
tactic radiosurgery takes 6 to 8 weeks to devel- with no apparent nerve compression. In these
op. Approximately 24 to 71% of patients report cases, the surgeon usually inserts the separating
continued pain relief 1 to 2 years after undergo- sponge anyway, even though the rate of failure
ing the procedure, and 33 to 56% report contin- is higher than it is when distortion of the nerve
ued pain relief at 4 to 5 years.8 Facial numbness root is identified. This problem underscores
has been reported in 16% of patients, whereas the advantage of using established MRI criteria
anesthesia dolorosa is virtually absent. A meta- to identify morphologic changes in the trigemi-
analysis showed that approximately 34% of pa- nal root.5
tients do not have pain relief at 1 year and re- Despite the lack of high-level evidence-based
quire repeat procedures.48 data,49,50 meta-analyses have suggested that micro-
vascular decompression is the most efficacious
Microvascular Decompression surgical intervention for classical trigeminal
Microvascular decompression has become the neuralgia. At 1 to 2 years after undergoing the
surgical procedure that is now favored for most procedure, 68 to 88% of patients have pain relief,
cases of trigeminal neuralgia that do not re- and 61 to 80% have pain relief at 4 to 5 years.8
spond to medication. The neurosurgeon identi- The average mortality associated with the sur-
fies the vessel that is compressing the trigemi- gery is 0.3%. Cerebrospinal fluid leaks occur in
nal nerve root, moves it from under the nerve to 2.0% of patients, brain-stem infarctions or hema-
over the nerve if necessary (Fig. 3), and typically tomas in 0.6%, and meningitis in 0.4%. Sensory
inserts a small sponge to keep the pulsating loss in part or all of the trigeminal nerve sen-
artery separated from the nerve root. In about sory distribution on the face occurs in 2.9% of
11% of patients, the surgeon does not find neu- patients. The most troubling long-term compli-
cation, although rare (incidence, 1.8%), is ipsi- many patients have side effects, and those who
lateral hearing loss.8 have concomitant continuous pain are less likely
There is insufficient evidence to support or to have a good response to treatment. Diagnos-
refute the effectiveness of surgical management tic tests, particularly neuroimaging, are useful
of trigeminal neuralgia in patients with multiple for identifying the cause and for identifying pa-
sclerosis, although patients with multiple sclero- tients with trigeminal neuralgia due to major
sis who have drug-resistant trigeminal neuralgia neurologic diseases and patients in whom small
may be offered microvascular decompression.36 branches of the basilar artery compress the
However, both percutaneous ganglion lesions and proximal nerve. The application of standardized
gamma-knife lesions have also been reported to MRI criteria for identifying neurovascular com-
have good outcomes in patients with multiple pression may aid in selecting patients for micro-
sclerosis.39 vascular decompression.
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